Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

A version of this article first appeared on Medscape.com.

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

A version of this article first appeared on Medscape.com.

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

A version of this article first appeared on Medscape.com.

Vaccination strategies for people with rheumatic diseases have received significant scrutiny in regard to COVID-19 vaccines. People with rheumatoid arthritis (RA) are at higher risk for adverse outcomes related to COVID-19 but also may have reduced immunogenicity to COVID-19 vaccines; thus, temporary withdrawal of medications has been suggested. Renner Araujo and colleagues report the results of a single-center randomized study from Brazil looking at the immune response to two doses of the Sinovac-CoronaVac vaccine in 129 patients with RA. They found that those who stopped methotrexate for 2 weeks after both doses had a higher rate of seroconversion, based on immunoglobulin (Ig) G positivity (78% vs. 54%), than those who remained on methotrexate. Antibody titers were also higher in the "methotrexate-hold" group. Flare rates were higher, based on the Clinical Disease Activity Index (CDAI) — though not on the Disease Activity Scale-28 (DAS-28) — in patients who withdrew from methotrexate. This information is interesting with respect to the use of future inactivated virus vaccines, though its applicability to mRNA vaccines, other than predicting the possibility of flare, is less clear. However, the results could be useful in informed discussions and decision-making regarding withdrawing immunosuppressive drugs.

Some people with rheumatic diseases have been concerned about flares of disease activity related to COVID-19 vaccination. Tedeschi and colleagues conducted a prospective observational study of 71 patients with RA who were previously inoculated against COVID-19 with two mRNA vaccine doses or one adenovirus vector vaccine dose. Using the patient-reported Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), they measured disease activity weekly from study enrollment through 4 weeks after an additional dose. They did not find any change in mean RADAI-5 score between pre- and post additional dose, nor was disease activity different in patients who stopped disease-modifying antirheumatic drugs (DMARD) compared with those who did not. The study also examined flow cytometry of lymphocyte populations among a subset of these patients (n = 27) and found no significant differences in T peripheral helper cells, T follicular helper cells, age-associated B cells, and plasmablasts among patients before and after the additional vaccine dose. Though the flow cytometry data are difficult to generalize, given the presumed heterogeneity and small number of patients, the lack of change in RA disease activity after the additional vaccine dose is reassuring.

Achievement of remission in patients with RA is also an area of continued interest, especially because of the difficulty of reaching this target under real-world conditions. Larid and colleagues report the prognostic factors of remission and characteristics of 215 patients with RA over 7 years of follow-up at an academic hospital in France. Notably, 33% of patients were in remission at 1 year, of whom 76% remained in remission at 7 years. However, 48% of patients who were not in remission at 1 year achieved remission at 7 years; 58% of study participants were in remission in total at 7 years of follow-up. Those in remission were more frequently being prescribed both conventional synthetic DMARD (csDMARD) and biologic DMARD (bDMARD), while those not in remission at 7 years were receiving corticosteroids at higher doses. Owing to the lack of more precise treatment information, as well as the large number of patients who did not complete the 7-year follow-up visit, drawing conclusions is difficult. While we cannot say, based on these results, that use of certain medication regimens or strategies is more likely to lead to remission, the data at least lend support to the possibility of achieving remission in the long term.

Finally, Ahmad and colleagues performed a post-hoc analysis of the phase 3b AVERT trial of abatacept vs. methotrexate; 172 patients in remission were evaluated at 6 and 12 months after withdrawal of abatacept + methotrexate, abatacept monotherapy, or methotrexate monotherapy. Similar proportions of patients in all three treatment groups experienced a flare (about 58% at 6 months and 66% at 12 months). Patients with higher Health Assessment Questionnaire Disability Index (HAQ-DI) scores and evidence of erosions on MRI at withdrawal were more likely to experience a flare, consistent with prior studies. This highlights potential predictors of withdrawal from therapy. Given the lack of significant difference between the treatment groups, however, it does raise the question of why combination therapy with abatacept and methotrexate is more likely to lead to patients achieving remission in studies without as big an effect on drug-free remission after withdrawal. A more stringent definition of remission rather than DAS-28 C-reactive protein may be desirable.

Vaccination strategies for people with rheumatic diseases have received significant scrutiny in regard to COVID-19 vaccines. People with rheumatoid arthritis (RA) are at higher risk for adverse outcomes related to COVID-19 but also may have reduced immunogenicity to COVID-19 vaccines; thus, temporary withdrawal of medications has been suggested. Renner Araujo and colleagues report the results of a single-center randomized study from Brazil looking at the immune response to two doses of the Sinovac-CoronaVac vaccine in 129 patients with RA. They found that those who stopped methotrexate for 2 weeks after both doses had a higher rate of seroconversion, based on immunoglobulin (Ig) G positivity (78% vs. 54%), than those who remained on methotrexate. Antibody titers were also higher in the "methotrexate-hold" group. Flare rates were higher, based on the Clinical Disease Activity Index (CDAI) — though not on the Disease Activity Scale-28 (DAS-28) — in patients who withdrew from methotrexate. This information is interesting with respect to the use of future inactivated virus vaccines, though its applicability to mRNA vaccines, other than predicting the possibility of flare, is less clear. However, the results could be useful in informed discussions and decision-making regarding withdrawing immunosuppressive drugs.

Some people with rheumatic diseases have been concerned about flares of disease activity related to COVID-19 vaccination. Tedeschi and colleagues conducted a prospective observational study of 71 patients with RA who were previously inoculated against COVID-19 with two mRNA vaccine doses or one adenovirus vector vaccine dose. Using the patient-reported Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), they measured disease activity weekly from study enrollment through 4 weeks after an additional dose. They did not find any change in mean RADAI-5 score between pre- and post additional dose, nor was disease activity different in patients who stopped disease-modifying antirheumatic drugs (DMARD) compared with those who did not. The study also examined flow cytometry of lymphocyte populations among a subset of these patients (n = 27) and found no significant differences in T peripheral helper cells, T follicular helper cells, age-associated B cells, and plasmablasts among patients before and after the additional vaccine dose. Though the flow cytometry data are difficult to generalize, given the presumed heterogeneity and small number of patients, the lack of change in RA disease activity after the additional vaccine dose is reassuring.

Achievement of remission in patients with RA is also an area of continued interest, especially because of the difficulty of reaching this target under real-world conditions. Larid and colleagues report the prognostic factors of remission and characteristics of 215 patients with RA over 7 years of follow-up at an academic hospital in France. Notably, 33% of patients were in remission at 1 year, of whom 76% remained in remission at 7 years. However, 48% of patients who were not in remission at 1 year achieved remission at 7 years; 58% of study participants were in remission in total at 7 years of follow-up. Those in remission were more frequently being prescribed both conventional synthetic DMARD (csDMARD) and biologic DMARD (bDMARD), while those not in remission at 7 years were receiving corticosteroids at higher doses. Owing to the lack of more precise treatment information, as well as the large number of patients who did not complete the 7-year follow-up visit, drawing conclusions is difficult. While we cannot say, based on these results, that use of certain medication regimens or strategies is more likely to lead to remission, the data at least lend support to the possibility of achieving remission in the long term.

Finally, Ahmad and colleagues performed a post-hoc analysis of the phase 3b AVERT trial of abatacept vs. methotrexate; 172 patients in remission were evaluated at 6 and 12 months after withdrawal of abatacept + methotrexate, abatacept monotherapy, or methotrexate monotherapy. Similar proportions of patients in all three treatment groups experienced a flare (about 58% at 6 months and 66% at 12 months). Patients with higher Health Assessment Questionnaire Disability Index (HAQ-DI) scores and evidence of erosions on MRI at withdrawal were more likely to experience a flare, consistent with prior studies. This highlights potential predictors of withdrawal from therapy. Given the lack of significant difference between the treatment groups, however, it does raise the question of why combination therapy with abatacept and methotrexate is more likely to lead to patients achieving remission in studies without as big an effect on drug-free remission after withdrawal. A more stringent definition of remission rather than DAS-28 C-reactive protein may be desirable.

Vaccination strategies for people with rheumatic diseases have received significant scrutiny in regard to COVID-19 vaccines. People with rheumatoid arthritis (RA) are at higher risk for adverse outcomes related to COVID-19 but also may have reduced immunogenicity to COVID-19 vaccines; thus, temporary withdrawal of medications has been suggested. Renner Araujo and colleagues report the results of a single-center randomized study from Brazil looking at the immune response to two doses of the Sinovac-CoronaVac vaccine in 129 patients with RA. They found that those who stopped methotrexate for 2 weeks after both doses had a higher rate of seroconversion, based on immunoglobulin (Ig) G positivity (78% vs. 54%), than those who remained on methotrexate. Antibody titers were also higher in the "methotrexate-hold" group. Flare rates were higher, based on the Clinical Disease Activity Index (CDAI) — though not on the Disease Activity Scale-28 (DAS-28) — in patients who withdrew from methotrexate. This information is interesting with respect to the use of future inactivated virus vaccines, though its applicability to mRNA vaccines, other than predicting the possibility of flare, is less clear. However, the results could be useful in informed discussions and decision-making regarding withdrawing immunosuppressive drugs.

Some people with rheumatic diseases have been concerned about flares of disease activity related to COVID-19 vaccination. Tedeschi and colleagues conducted a prospective observational study of 71 patients with RA who were previously inoculated against COVID-19 with two mRNA vaccine doses or one adenovirus vector vaccine dose. Using the patient-reported Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), they measured disease activity weekly from study enrollment through 4 weeks after an additional dose. They did not find any change in mean RADAI-5 score between pre- and post additional dose, nor was disease activity different in patients who stopped disease-modifying antirheumatic drugs (DMARD) compared with those who did not. The study also examined flow cytometry of lymphocyte populations among a subset of these patients (n = 27) and found no significant differences in T peripheral helper cells, T follicular helper cells, age-associated B cells, and plasmablasts among patients before and after the additional vaccine dose. Though the flow cytometry data are difficult to generalize, given the presumed heterogeneity and small number of patients, the lack of change in RA disease activity after the additional vaccine dose is reassuring.

Achievement of remission in patients with RA is also an area of continued interest, especially because of the difficulty of reaching this target under real-world conditions. Larid and colleagues report the prognostic factors of remission and characteristics of 215 patients with RA over 7 years of follow-up at an academic hospital in France. Notably, 33% of patients were in remission at 1 year, of whom 76% remained in remission at 7 years. However, 48% of patients who were not in remission at 1 year achieved remission at 7 years; 58% of study participants were in remission in total at 7 years of follow-up. Those in remission were more frequently being prescribed both conventional synthetic DMARD (csDMARD) and biologic DMARD (bDMARD), while those not in remission at 7 years were receiving corticosteroids at higher doses. Owing to the lack of more precise treatment information, as well as the large number of patients who did not complete the 7-year follow-up visit, drawing conclusions is difficult. While we cannot say, based on these results, that use of certain medication regimens or strategies is more likely to lead to remission, the data at least lend support to the possibility of achieving remission in the long term.

Finally, Ahmad and colleagues performed a post-hoc analysis of the phase 3b AVERT trial of abatacept vs. methotrexate; 172 patients in remission were evaluated at 6 and 12 months after withdrawal of abatacept + methotrexate, abatacept monotherapy, or methotrexate monotherapy. Similar proportions of patients in all three treatment groups experienced a flare (about 58% at 6 months and 66% at 12 months). Patients with higher Health Assessment Questionnaire Disability Index (HAQ-DI) scores and evidence of erosions on MRI at withdrawal were more likely to experience a flare, consistent with prior studies. This highlights potential predictors of withdrawal from therapy. Given the lack of significant difference between the treatment groups, however, it does raise the question of why combination therapy with abatacept and methotrexate is more likely to lead to patients achieving remission in studies without as big an effect on drug-free remission after withdrawal. A more stringent definition of remission rather than DAS-28 C-reactive protein may be desirable.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.

Yao and colleagues confirmed that there are well-known risk factors for recurrence of HCC after surgical resection. They retrospectively analyzed 1424 patients who underwent resection with curative intent for Barcelona Clinical Liver Cancer (BCLC) stage 0/A HCC in several centers in China. Of those patients, 679 (47.7%) developed recurrence at a median follow-up of 54.8 months, including 408 (60.1%) with an early recurrence (≤ 2 years after surgery) and 271 (39.9%) with a late recurrence (> 2 years). Cirrhosis (adjusted hazard ratio [aHR] 1.49; P < .001), preoperative alpha-fetoprotein (AFP) level > 400 µg/L (aHR 1.28; P = .004), tumor size > 5 cm (aHR 1.74; P < .001), the presence of satellite nodules (aHR 1.35; P = .040), multiple tumors (aHR 1.63; P = .015), microvascular invasion (aHR 1.51; P < .001), and intraoperative blood transfusion (aHR 1.50; P = .013) were identified as independent risk factors associated with postoperative HCC recurrence. The authors concluded that those patients with risk factors for recurrence would benefit from more intensive surveillance and potentially additional liver-directed therapy with curative intent.

Not all patients with hepatitis C virus (HCV) infection and HCC are offered antiviral therapy. Takaura and colleagues confirmed that active HCV infection worsens the prognosis of patients with very early-stage HCC who undergo treatment with radiofrequency ablation (RFA). In this single-center retrospective study, 302 patients with BCLC stage 0 HCC who underwent RFA were analyzed. Of those patients, 195 had evidence of HCV, and 132 had an active infection. The authors concluded that active HCV infection was a significant risk factor for shorter overall survival (aHR 2.17; P = .003) and early recurrence of HCC (aHR 1.47; P = .022). Patients with active HCV infection had a shorter median overall survival (66 months vs 145 months) and recurrence-free survival (20 months vs 31 months) (both P < .001). Therefore, treatment of active HCV should be offered to patients even after the development of HCC.

Kuroda and colleagues retrospectively analyzed a multicenter cohort of 247 patients with unresectable HCC treated with lenvatinib between 2018 and 2020. Out of those, 63 patients who received lenvatinib and transarterial chemoembolization (TACE) sequential therapy were propensity-score matched to those receiving lenvatinib monotherapy. The overall survival and progression-free survival in the sequential group were significantly higher than those in the lenvatinib monotherapy group, 31.2 (26.4-34.3) vs 15.7 (13.1-19.4) months and 12.2 (8.5-17.3) vs 6.7 (5.3-10.2) months (P = .002 and P = .037), respectively. Multivariate analysis showed that the deep response was independently associated with the initial response to levatinib; the partial response showed an odds ratio of 13.75 (95% CI 0.41-1.32; P < .001). The authors concluded that sequential therapy might provide more clinical benefits than lenvatinib monotherapy in patients who responded to initial lenvatinib treatment, with objective response to initial lenvatinib being an independent factor predicting sequential therapy deep response.