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Study explains link between fatty liver and CRC liver metastasis
according to the authors of new research.
These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.
“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”
To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.
Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.
“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”
One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.
according to the authors of new research.
These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.
“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”
To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.
Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.
“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”
One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.
according to the authors of new research.
These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.
“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”
To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.
Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.
“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”
One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.
FROM CELL METABOLISM
Refined incidence rate of HCC with alcohol-associated cirrhosis encourages surveillance
Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.
“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.
Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.
To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.
“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”
The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.
“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”
The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).
“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.
Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.
Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.
The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.
The association between cirrhosis and hepatocellular carcinoma (HCC) risk is well known and therefore routine surveillance is recommended by the American Association for the Study of Liver Diseases. More recent data has shown alcohol use to be an independent risk factor for HCC along with various other cancers.
Quite frequently, the focus of management in patients with alcohol-associated liver disease is alcohol cessation to prevent further decompensation, with screening often being overlooked. Previous studies have shown, however, that earlier detection is associated with improved survival. Another interesting finding of this study was that those patients who had concomitant smoking use, diabetes, and hepatic decompensation were more likely to develop HCC. When managing patients with alcohol related liver disease, confounding risk factors should be mitigated (that is, encouragement of smoking cessation, enhanced screening for diabetes, and more rigorous screening in decompensated patients).
This study brings to light the need for improved screening and concomitant risk factor mitigation for hepatocellular carcinoma given higher rates of detection in those undergoing surveillance. Larger, prospective studies are needed, however, to validate the findings in this study given the recent overall increase in rates of alcohol-associated liver disease.
Priya Maddur MD, is a visiting clinical associate professor of medicine, University of Arizona, Tucson. Dr. Maddur has no relevant disclosures.
The association between cirrhosis and hepatocellular carcinoma (HCC) risk is well known and therefore routine surveillance is recommended by the American Association for the Study of Liver Diseases. More recent data has shown alcohol use to be an independent risk factor for HCC along with various other cancers.
Quite frequently, the focus of management in patients with alcohol-associated liver disease is alcohol cessation to prevent further decompensation, with screening often being overlooked. Previous studies have shown, however, that earlier detection is associated with improved survival. Another interesting finding of this study was that those patients who had concomitant smoking use, diabetes, and hepatic decompensation were more likely to develop HCC. When managing patients with alcohol related liver disease, confounding risk factors should be mitigated (that is, encouragement of smoking cessation, enhanced screening for diabetes, and more rigorous screening in decompensated patients).
This study brings to light the need for improved screening and concomitant risk factor mitigation for hepatocellular carcinoma given higher rates of detection in those undergoing surveillance. Larger, prospective studies are needed, however, to validate the findings in this study given the recent overall increase in rates of alcohol-associated liver disease.
Priya Maddur MD, is a visiting clinical associate professor of medicine, University of Arizona, Tucson. Dr. Maddur has no relevant disclosures.
The association between cirrhosis and hepatocellular carcinoma (HCC) risk is well known and therefore routine surveillance is recommended by the American Association for the Study of Liver Diseases. More recent data has shown alcohol use to be an independent risk factor for HCC along with various other cancers.
Quite frequently, the focus of management in patients with alcohol-associated liver disease is alcohol cessation to prevent further decompensation, with screening often being overlooked. Previous studies have shown, however, that earlier detection is associated with improved survival. Another interesting finding of this study was that those patients who had concomitant smoking use, diabetes, and hepatic decompensation were more likely to develop HCC. When managing patients with alcohol related liver disease, confounding risk factors should be mitigated (that is, encouragement of smoking cessation, enhanced screening for diabetes, and more rigorous screening in decompensated patients).
This study brings to light the need for improved screening and concomitant risk factor mitigation for hepatocellular carcinoma given higher rates of detection in those undergoing surveillance. Larger, prospective studies are needed, however, to validate the findings in this study given the recent overall increase in rates of alcohol-associated liver disease.
Priya Maddur MD, is a visiting clinical associate professor of medicine, University of Arizona, Tucson. Dr. Maddur has no relevant disclosures.
Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.
“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.
Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.
To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.
“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”
The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.
“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”
The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).
“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.
Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.
Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.
The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.
Incidence rates were higher for cohorts that underwent HCC surveillance versus those that did not undergo surveillance, suggesting that such programs offer significant benefit, lead author Daniel Q. Huang, MBBS, of the University of California, San Diego, and colleagues reported.
“A systematic review of the incidence of HCC among patients with alcohol-associated cirrhosis has not been reported,” the investigators wrote in Clinical Gastroenterology and Hepatology, prompting the present research.
Previous studies have described a broad range of annual incidence findings for HCC in this population, from 0.6% to 5.6%, suggesting that a systematic approach was needed.
To this end, Dr. Huang and colleagues analyzed data from 18 studies that involved 148,333 patients with alcohol-associated cirrhosis. The primary analysis aimed to determine cumulative incidence rates over time, while the secondary analysis characterized the impact of participation in HCC surveillance programs.
“This meta-analysis used reconstructed individual participant data, which is considered to be the gold standard for reporting survival data because it accounts for censoring of events,” the investigators noted. “The current study provides important data that are useful for clinical practice and clinical trial design.”
The cumulative incidence rates of HCC were 1%, 3%, and 9% at 1 year, 5 years, and 10 years, respectively. Among 12 of the risk factors studied, smoking, diabetes, and decompensation were all significantly associated with rate of HCC.
“Therefore, patients with alcohol-associated cirrhosis should be screened for diabetes to identify the patients at high risk for HCC development,” the investigators wrote. “In addition, patients with alcohol-associated cirrhosis should be advised to stop smoking, while patients with hepatic decompensation should be monitored carefully for the development of HCC if clinically appropriate.”
The secondary analysis showed that HCC incidence rates were higher among patients participating in HCC surveillance programs than those who did not participate (18.6 vs. 4.8 per 1,000 person-years; P = .001).
“Patients with alcohol-associated cirrhosis are known to have lower HCC surveillance rates, which may be related to poor disease awareness, clinic time constraints caused by other active medical issues, and provider beliefs regarding the likelihood of adherence,” the investigators noted.
Increased efforts are needed to promote surveillance in this population, they added, suggesting a range of communication pathways, including social media, traditional news outlets, and direct mailing.
Dr. Huang and colleagues also suggested that the findings should be validated in large prospective studies.
The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, and others. Dr. Huang disclosed funding from the Singapore Ministry of Health’s National Medical Research Council.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Clinical Practice Update: Alpha-gal syndrome often causes GI issues without anaphylaxis, skin changes
according to an American Gastroenterological Association clinical practice update.
Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.
“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.
To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.
“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”
Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.
“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.
In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.
Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.
“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.
Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.
The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.
The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.
according to an American Gastroenterological Association clinical practice update.
Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.
“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.
To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.
“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”
Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.
“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.
In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.
Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.
“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.
Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.
The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.
The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.
according to an American Gastroenterological Association clinical practice update.
Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.
“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.
To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.
“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”
Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.
“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.
In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.
Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.
“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.
Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.
The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.
The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA clinical practice update addresses role of endoscopic ultrasound–guided gallbladder drainage in acute cholecystitis
according to a recent clinical practice update by the American Gastroenterological Association.
The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.
“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.
Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.
According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.
Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.
While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.
“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”
Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.
Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”
This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.
according to a recent clinical practice update by the American Gastroenterological Association.
The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.
“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.
Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.
According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.
Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.
While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.
“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”
Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.
Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”
This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.
according to a recent clinical practice update by the American Gastroenterological Association.
The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.
“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.
Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.
According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.
Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.
While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.
“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”
Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.
Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”
This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
PNPLA3 genotype predicts cirrhosis in NAFLD
while those with this genotype who also have diabetes and indeterminate Fibrosis-4 (FIB4) scores may have the same risk of cirrhosis as patients with a high FIB4, according to investigators.
These findings suggest that NAFLD patients with indeterminate FIB4 and metabolic risk factors should routinely undergo PNPLA3 genotyping, lead author Vincent L. Chen, MD, of the University of Michigan, Ann Arbor, and colleagues reported.
“Whether incorporating genetics into risk stratification results in meaningful improvement over clinical predictors, such as FIB4, diabetes, and obesity status, is unknown,” the investigators wrote in Gastroenterology. “Improved understanding of how genetics influences the rate of disease progression and how it interacts with established risk factors for advanced liver disease is crucial for genetic testing to be applicable in clinical practice.”
To evaluate the risk presented by the PNPLA3 p.I148M variant, Dr. Chen and colleagues analyzed data from two independent cohorts with 7,893 patients and 46,880 patients each.
They first characterized the relationship between PNPLA3 genotype and cirrhosis via univariable and multivariable analyses. These efforts revealed that the genotype predicted cirrhosis in both cohorts, with associations also detected for well-documented clinical risk factors, including diabetes, obesity, and high ALT. Of note, PNPLA3 genotype demonstrated an additive effect for cirrhosis when detected in conjunction with these risks.
Further analysis revealed that homozygous carriers of PNPLA3 p.I148M with indeterminate FIB4 scores (1.3-2.67) and diabetes had an incidence rate of cirrhosis on par with patients who had high-risk FIB4 (greater than 2.67).
The effects of the risk allele were also made evident by comparing patients with diabetes and indeterminate FIB4 based on presence or absence of the marker – those testing positive for h PNPLA3 p.I148M had 2.9-4.8 times greater risk of cirrhosis. Conversely, patients with FIB4 scores less than 1.3, regardless of other risk factors, had little change in cirrhosis rate regardless of PNPLA3 status.
“We found that PNPLA3 genotyping in conjunction with clinical risk factors may improve risk stratification in patients with NAFLD,” the investigators concluded. “Although it may be possible to develop more complex polygenic risk scores for cirrhosis, these findings suggest that genotyping of PNPLA3 alone, which is less expensive than genomewide genotyping and easier to understand, may have similar clinical applicability for NAFLD.”
Dr. Chen and colleagues therefore recommended that NAFLD patients with metabolic risk factors (particularly diabetes) and indeterminate FIB4 routinely undergo PNPLA3 genotyping, with referral to hepatology if positive for two risk alleles.
The study was supported by the American Association for the Study of Liver Diseases, National Institutes of Health, and the University of Michigan department of internal medicine. The investigators disclosed no conflicts of interest.
Nonalcoholic fatty liver disease (NAFLD) is becoming globally a leading cause of cirrhosis and related complications, namely decompensation and hepatocellular carcinoma. Since NAFLD affects a large fraction of the population, and especially people with obesity, type 2 diabetes and metabolic comorbidities, it is difficult to identify those at risk of cirrhosis and liver-related versus more frequent cardiometabolic events. The first step in risk stratification is based on the calculation of simple liver fibrosis scores, such as the FIB4, but this too often leads to indeterminate results requiring additional testing.
These results will contribute to establish referral pathways to identify persons at high risk of liver disease, even at a young age. This may enable preventive programs based on intensified lifestyle and diabetes management, specific treatments for fibrotic NAFLD once these become available, and close surveillance for complications. What’s more, therapeutic approaches directly targeting liver PNPLA3 p.I148M are already under clinical evaluation to prevent disease progression specifically in this high-risk group.
Luca Valenti, MD, is an associate professor of internal medicine in pathophysiology and transplantation at the Università degli Studi di Milano. He is head of the Precision Lab and Biological Resource Center Unit. Dr. Valenti has no relevant disclosures.
Nonalcoholic fatty liver disease (NAFLD) is becoming globally a leading cause of cirrhosis and related complications, namely decompensation and hepatocellular carcinoma. Since NAFLD affects a large fraction of the population, and especially people with obesity, type 2 diabetes and metabolic comorbidities, it is difficult to identify those at risk of cirrhosis and liver-related versus more frequent cardiometabolic events. The first step in risk stratification is based on the calculation of simple liver fibrosis scores, such as the FIB4, but this too often leads to indeterminate results requiring additional testing.
These results will contribute to establish referral pathways to identify persons at high risk of liver disease, even at a young age. This may enable preventive programs based on intensified lifestyle and diabetes management, specific treatments for fibrotic NAFLD once these become available, and close surveillance for complications. What’s more, therapeutic approaches directly targeting liver PNPLA3 p.I148M are already under clinical evaluation to prevent disease progression specifically in this high-risk group.
Luca Valenti, MD, is an associate professor of internal medicine in pathophysiology and transplantation at the Università degli Studi di Milano. He is head of the Precision Lab and Biological Resource Center Unit. Dr. Valenti has no relevant disclosures.
Nonalcoholic fatty liver disease (NAFLD) is becoming globally a leading cause of cirrhosis and related complications, namely decompensation and hepatocellular carcinoma. Since NAFLD affects a large fraction of the population, and especially people with obesity, type 2 diabetes and metabolic comorbidities, it is difficult to identify those at risk of cirrhosis and liver-related versus more frequent cardiometabolic events. The first step in risk stratification is based on the calculation of simple liver fibrosis scores, such as the FIB4, but this too often leads to indeterminate results requiring additional testing.
These results will contribute to establish referral pathways to identify persons at high risk of liver disease, even at a young age. This may enable preventive programs based on intensified lifestyle and diabetes management, specific treatments for fibrotic NAFLD once these become available, and close surveillance for complications. What’s more, therapeutic approaches directly targeting liver PNPLA3 p.I148M are already under clinical evaluation to prevent disease progression specifically in this high-risk group.
Luca Valenti, MD, is an associate professor of internal medicine in pathophysiology and transplantation at the Università degli Studi di Milano. He is head of the Precision Lab and Biological Resource Center Unit. Dr. Valenti has no relevant disclosures.
while those with this genotype who also have diabetes and indeterminate Fibrosis-4 (FIB4) scores may have the same risk of cirrhosis as patients with a high FIB4, according to investigators.
These findings suggest that NAFLD patients with indeterminate FIB4 and metabolic risk factors should routinely undergo PNPLA3 genotyping, lead author Vincent L. Chen, MD, of the University of Michigan, Ann Arbor, and colleagues reported.
“Whether incorporating genetics into risk stratification results in meaningful improvement over clinical predictors, such as FIB4, diabetes, and obesity status, is unknown,” the investigators wrote in Gastroenterology. “Improved understanding of how genetics influences the rate of disease progression and how it interacts with established risk factors for advanced liver disease is crucial for genetic testing to be applicable in clinical practice.”
To evaluate the risk presented by the PNPLA3 p.I148M variant, Dr. Chen and colleagues analyzed data from two independent cohorts with 7,893 patients and 46,880 patients each.
They first characterized the relationship between PNPLA3 genotype and cirrhosis via univariable and multivariable analyses. These efforts revealed that the genotype predicted cirrhosis in both cohorts, with associations also detected for well-documented clinical risk factors, including diabetes, obesity, and high ALT. Of note, PNPLA3 genotype demonstrated an additive effect for cirrhosis when detected in conjunction with these risks.
Further analysis revealed that homozygous carriers of PNPLA3 p.I148M with indeterminate FIB4 scores (1.3-2.67) and diabetes had an incidence rate of cirrhosis on par with patients who had high-risk FIB4 (greater than 2.67).
The effects of the risk allele were also made evident by comparing patients with diabetes and indeterminate FIB4 based on presence or absence of the marker – those testing positive for h PNPLA3 p.I148M had 2.9-4.8 times greater risk of cirrhosis. Conversely, patients with FIB4 scores less than 1.3, regardless of other risk factors, had little change in cirrhosis rate regardless of PNPLA3 status.
“We found that PNPLA3 genotyping in conjunction with clinical risk factors may improve risk stratification in patients with NAFLD,” the investigators concluded. “Although it may be possible to develop more complex polygenic risk scores for cirrhosis, these findings suggest that genotyping of PNPLA3 alone, which is less expensive than genomewide genotyping and easier to understand, may have similar clinical applicability for NAFLD.”
Dr. Chen and colleagues therefore recommended that NAFLD patients with metabolic risk factors (particularly diabetes) and indeterminate FIB4 routinely undergo PNPLA3 genotyping, with referral to hepatology if positive for two risk alleles.
The study was supported by the American Association for the Study of Liver Diseases, National Institutes of Health, and the University of Michigan department of internal medicine. The investigators disclosed no conflicts of interest.
while those with this genotype who also have diabetes and indeterminate Fibrosis-4 (FIB4) scores may have the same risk of cirrhosis as patients with a high FIB4, according to investigators.
These findings suggest that NAFLD patients with indeterminate FIB4 and metabolic risk factors should routinely undergo PNPLA3 genotyping, lead author Vincent L. Chen, MD, of the University of Michigan, Ann Arbor, and colleagues reported.
“Whether incorporating genetics into risk stratification results in meaningful improvement over clinical predictors, such as FIB4, diabetes, and obesity status, is unknown,” the investigators wrote in Gastroenterology. “Improved understanding of how genetics influences the rate of disease progression and how it interacts with established risk factors for advanced liver disease is crucial for genetic testing to be applicable in clinical practice.”
To evaluate the risk presented by the PNPLA3 p.I148M variant, Dr. Chen and colleagues analyzed data from two independent cohorts with 7,893 patients and 46,880 patients each.
They first characterized the relationship between PNPLA3 genotype and cirrhosis via univariable and multivariable analyses. These efforts revealed that the genotype predicted cirrhosis in both cohorts, with associations also detected for well-documented clinical risk factors, including diabetes, obesity, and high ALT. Of note, PNPLA3 genotype demonstrated an additive effect for cirrhosis when detected in conjunction with these risks.
Further analysis revealed that homozygous carriers of PNPLA3 p.I148M with indeterminate FIB4 scores (1.3-2.67) and diabetes had an incidence rate of cirrhosis on par with patients who had high-risk FIB4 (greater than 2.67).
The effects of the risk allele were also made evident by comparing patients with diabetes and indeterminate FIB4 based on presence or absence of the marker – those testing positive for h PNPLA3 p.I148M had 2.9-4.8 times greater risk of cirrhosis. Conversely, patients with FIB4 scores less than 1.3, regardless of other risk factors, had little change in cirrhosis rate regardless of PNPLA3 status.
“We found that PNPLA3 genotyping in conjunction with clinical risk factors may improve risk stratification in patients with NAFLD,” the investigators concluded. “Although it may be possible to develop more complex polygenic risk scores for cirrhosis, these findings suggest that genotyping of PNPLA3 alone, which is less expensive than genomewide genotyping and easier to understand, may have similar clinical applicability for NAFLD.”
Dr. Chen and colleagues therefore recommended that NAFLD patients with metabolic risk factors (particularly diabetes) and indeterminate FIB4 routinely undergo PNPLA3 genotyping, with referral to hepatology if positive for two risk alleles.
The study was supported by the American Association for the Study of Liver Diseases, National Institutes of Health, and the University of Michigan department of internal medicine. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Liquid albuterol shortage effects reduced by alternative drugs, similar shortages may be increasingly common
The shortage of 0.5% albuterol sulfate inhalation solution, first reported by the FDA last October, gained increasing attention earlier this month when Akorn Pharmaceuticals – one of just two companies making the product – shut down after years of financial and regulatory troubles.
The other manufacturer, Nephron Pharmaceuticals, is producing 0.5% albuterol “as fast as possible” to overcome the shortage, CEO Lou Kennedy said in a written comment.
Meanwhile, the more commonly used version of liquid albuterol, with a concentration of 0.083%, remains in “good supply from several manufacturers,” according to an FDA spokesperson.
Still, headlines concerning the shortage have caused “a bit of a panic” for patients with asthma and parents with asthmatic children, according to David R. Stukus, MD, professor of clinical pediatrics in the division of allergy and immunology at Nationwide Children’s, Columbus, Ohio.
Much of the media coverage has lacked context, causing unnecessary worry, he said, as the shortage only affects one type of albuterol generally reserved for inpatient and emergency use.
“The shortage has not impacted our albuterol inhalers thus far,” Dr. Stukus said in an interview. “So I certainly don’t want people with asthma to panic that they’re going to run out of their inhaler anytime soon.”
Even infants and toddlers can use inhalers
Although Dr. Stukus noted that certain patients do require nebulizers, such as those with conditions that physically limit their breathing, like muscular dystrophy, most patients can use inhalers just fine. He said it’s a “pretty common misconception, even among medical professionals,” that infants and toddlers need nebulizers instead.
“In our institution, for example, we rarely ever start babies on a nebulizer when we diagnose them with asthma,” Dr. Stukus said. “We often just start right away with an inhaler with a spacer and a face mask.”
The shortage of liquid albuterol may therefore have a silver lining, he suggested, as it prompts clinicians to reconsider their routine practice.
“When situations like this arise, it’s a great opportunity for all of us to just take a step back and reevaluate the way we do things,” Dr. Stukus said. “Sometimes we just get caught up with inertia and we continue to do things the same way even though new options are available, or evidence has changed to the contrary.”
Nathan Rabinovitch, MD, professor of pediatrics in the division of pediatric allergy and clinical immunology at National Jewish Health, Denver, said that his center had trouble obtaining liquid albuterol about 2 weeks ago, so they pivoted to the more expensive levalbuterol for about a week and a half, until their albuterol supply was restored.
While Dr. Rabinovitch agreed that most children don’t need a nebulizer, he said about 5%-10% of kids with severe asthma should have one on hand in case their inhaler fails to control an exacerbation.
Personal preferences may also considered, he added.
“If [a parent] says, ‘I like to use the nebulizer. The kid likes it,’ I’m fine if they just use a nebulizer.”
One possible downside of relying on a nebulizer, however, is portability, according to Kelly O’Shea, MD, assistant professor in the division of allergy and clinical immunology at the University of Michigan, Ann Arbor.
“If you’re out at the park or out at a soccer game with your kids, and they are having trouble breathing ... and they need their albuterol, you don’t have that ability if you are tied to a nebulizer,” Dr. O’Shea said in an interview. “As long as a parent feels comfortable – they feel like [their child] can get deep breaths in, I agree that you can use [an inhaler] in the infant and toddler population.”
She also agreed that a nebulizer may serve as a kind of second step if an inhaler isn’t controlling an exacerbation; however, she emphasized that a nebulizer should not be considered a replacement for professional care, and should not give a false sense of security.
“I caution parents to make sure that when they need it, they also take the next step and head over to the emergency room,” Dr. O’Shea said.
Generic drug shortages becoming more common
While the present scarcity of liquid albuterol appears relatively mild in terms of clinical impact, it brings up broader concerns about generic drug supply, and why shortages like this are becoming more common, according to Katie J. Suda, PharmD, MS, professor of medicine and pharmacy, and associate director, center for pharmaceutical policy and prescribing at the University of Pittsburgh.
“Drug shortages continue to increase in frequency, and the duration and severity of the shortages are also getting worse,” Dr. Suda said in an interview.
The reasons for these shortages can be elusive, according to 2022 report by the American Society of Health-System Pharmacists, which found that more than half of shortages came with no explanation from manufacturers.
The same report showed that only 5% of shortages were due to a “business decision,” but this factor is likely more central than publicly stated.
A recent FDA analysis on drug shortages, for instance, lists “lack of incentives to produce less profitable drugs,” as the first “root cause,” and Dr. Suda agrees.
“It’s important that we have generic medicines to decrease costs to our health systems, as well as for our patients,” Dr. Suda said. “But frequently, with those generic products, the price is driven so low that it increases the risk of a shortage.”
The drive to maintain profit margins may motivate companies to cut corners in production, Dr. Suda explained. She emphasized that this connection is speculative, because motivations are effectively unknowable, but the rationale is supported by past and present shortages.
Akorn Pharmaceuticals, for example, received a warning letter from the FDA in 2019 because of a variety of manufacturing issues, including defective bottles, questionable data, and metal shavings on aseptic filling equipment.
When a manufacturer like Akorn fails, the effects can be far-reaching, Dr. Suda said, noting their broad catalog of agents. Beyond liquid albuterol, Akorn was producing cardiac drugs, antibiotics, vitamins, local anesthetics, eye products, and others.
Drug shortages cause “a significant strain on our health care system,” Dr. Suda said, and substituting other medications increases risk of medical errors.
Fortunately, the increasing number of drug shortages is not going unnoticed, according to Dr. Suda. The FDA and multiple other organizations, including the ASHP, American Medical Association, and National Academies of Sciences, Engineering, and Medicine, are all taking steps to ensure that essential medicines are in steady supply, including moves to gather more data from manufacturers.
“I hope that a lot of the efforts that are moving forward ... will help us decrease the impact of shortages on our patients,” Dr. Suda said.
Lou Kennedy is the CEO of Nephron Pharmaceuticals, which commercially produces liquid albuterol. The other interviewees disclosed no relevant conflicts of interest.
The shortage of 0.5% albuterol sulfate inhalation solution, first reported by the FDA last October, gained increasing attention earlier this month when Akorn Pharmaceuticals – one of just two companies making the product – shut down after years of financial and regulatory troubles.
The other manufacturer, Nephron Pharmaceuticals, is producing 0.5% albuterol “as fast as possible” to overcome the shortage, CEO Lou Kennedy said in a written comment.
Meanwhile, the more commonly used version of liquid albuterol, with a concentration of 0.083%, remains in “good supply from several manufacturers,” according to an FDA spokesperson.
Still, headlines concerning the shortage have caused “a bit of a panic” for patients with asthma and parents with asthmatic children, according to David R. Stukus, MD, professor of clinical pediatrics in the division of allergy and immunology at Nationwide Children’s, Columbus, Ohio.
Much of the media coverage has lacked context, causing unnecessary worry, he said, as the shortage only affects one type of albuterol generally reserved for inpatient and emergency use.
“The shortage has not impacted our albuterol inhalers thus far,” Dr. Stukus said in an interview. “So I certainly don’t want people with asthma to panic that they’re going to run out of their inhaler anytime soon.”
Even infants and toddlers can use inhalers
Although Dr. Stukus noted that certain patients do require nebulizers, such as those with conditions that physically limit their breathing, like muscular dystrophy, most patients can use inhalers just fine. He said it’s a “pretty common misconception, even among medical professionals,” that infants and toddlers need nebulizers instead.
“In our institution, for example, we rarely ever start babies on a nebulizer when we diagnose them with asthma,” Dr. Stukus said. “We often just start right away with an inhaler with a spacer and a face mask.”
The shortage of liquid albuterol may therefore have a silver lining, he suggested, as it prompts clinicians to reconsider their routine practice.
“When situations like this arise, it’s a great opportunity for all of us to just take a step back and reevaluate the way we do things,” Dr. Stukus said. “Sometimes we just get caught up with inertia and we continue to do things the same way even though new options are available, or evidence has changed to the contrary.”
Nathan Rabinovitch, MD, professor of pediatrics in the division of pediatric allergy and clinical immunology at National Jewish Health, Denver, said that his center had trouble obtaining liquid albuterol about 2 weeks ago, so they pivoted to the more expensive levalbuterol for about a week and a half, until their albuterol supply was restored.
While Dr. Rabinovitch agreed that most children don’t need a nebulizer, he said about 5%-10% of kids with severe asthma should have one on hand in case their inhaler fails to control an exacerbation.
Personal preferences may also considered, he added.
“If [a parent] says, ‘I like to use the nebulizer. The kid likes it,’ I’m fine if they just use a nebulizer.”
One possible downside of relying on a nebulizer, however, is portability, according to Kelly O’Shea, MD, assistant professor in the division of allergy and clinical immunology at the University of Michigan, Ann Arbor.
“If you’re out at the park or out at a soccer game with your kids, and they are having trouble breathing ... and they need their albuterol, you don’t have that ability if you are tied to a nebulizer,” Dr. O’Shea said in an interview. “As long as a parent feels comfortable – they feel like [their child] can get deep breaths in, I agree that you can use [an inhaler] in the infant and toddler population.”
She also agreed that a nebulizer may serve as a kind of second step if an inhaler isn’t controlling an exacerbation; however, she emphasized that a nebulizer should not be considered a replacement for professional care, and should not give a false sense of security.
“I caution parents to make sure that when they need it, they also take the next step and head over to the emergency room,” Dr. O’Shea said.
Generic drug shortages becoming more common
While the present scarcity of liquid albuterol appears relatively mild in terms of clinical impact, it brings up broader concerns about generic drug supply, and why shortages like this are becoming more common, according to Katie J. Suda, PharmD, MS, professor of medicine and pharmacy, and associate director, center for pharmaceutical policy and prescribing at the University of Pittsburgh.
“Drug shortages continue to increase in frequency, and the duration and severity of the shortages are also getting worse,” Dr. Suda said in an interview.
The reasons for these shortages can be elusive, according to 2022 report by the American Society of Health-System Pharmacists, which found that more than half of shortages came with no explanation from manufacturers.
The same report showed that only 5% of shortages were due to a “business decision,” but this factor is likely more central than publicly stated.
A recent FDA analysis on drug shortages, for instance, lists “lack of incentives to produce less profitable drugs,” as the first “root cause,” and Dr. Suda agrees.
“It’s important that we have generic medicines to decrease costs to our health systems, as well as for our patients,” Dr. Suda said. “But frequently, with those generic products, the price is driven so low that it increases the risk of a shortage.”
The drive to maintain profit margins may motivate companies to cut corners in production, Dr. Suda explained. She emphasized that this connection is speculative, because motivations are effectively unknowable, but the rationale is supported by past and present shortages.
Akorn Pharmaceuticals, for example, received a warning letter from the FDA in 2019 because of a variety of manufacturing issues, including defective bottles, questionable data, and metal shavings on aseptic filling equipment.
When a manufacturer like Akorn fails, the effects can be far-reaching, Dr. Suda said, noting their broad catalog of agents. Beyond liquid albuterol, Akorn was producing cardiac drugs, antibiotics, vitamins, local anesthetics, eye products, and others.
Drug shortages cause “a significant strain on our health care system,” Dr. Suda said, and substituting other medications increases risk of medical errors.
Fortunately, the increasing number of drug shortages is not going unnoticed, according to Dr. Suda. The FDA and multiple other organizations, including the ASHP, American Medical Association, and National Academies of Sciences, Engineering, and Medicine, are all taking steps to ensure that essential medicines are in steady supply, including moves to gather more data from manufacturers.
“I hope that a lot of the efforts that are moving forward ... will help us decrease the impact of shortages on our patients,” Dr. Suda said.
Lou Kennedy is the CEO of Nephron Pharmaceuticals, which commercially produces liquid albuterol. The other interviewees disclosed no relevant conflicts of interest.
The shortage of 0.5% albuterol sulfate inhalation solution, first reported by the FDA last October, gained increasing attention earlier this month when Akorn Pharmaceuticals – one of just two companies making the product – shut down after years of financial and regulatory troubles.
The other manufacturer, Nephron Pharmaceuticals, is producing 0.5% albuterol “as fast as possible” to overcome the shortage, CEO Lou Kennedy said in a written comment.
Meanwhile, the more commonly used version of liquid albuterol, with a concentration of 0.083%, remains in “good supply from several manufacturers,” according to an FDA spokesperson.
Still, headlines concerning the shortage have caused “a bit of a panic” for patients with asthma and parents with asthmatic children, according to David R. Stukus, MD, professor of clinical pediatrics in the division of allergy and immunology at Nationwide Children’s, Columbus, Ohio.
Much of the media coverage has lacked context, causing unnecessary worry, he said, as the shortage only affects one type of albuterol generally reserved for inpatient and emergency use.
“The shortage has not impacted our albuterol inhalers thus far,” Dr. Stukus said in an interview. “So I certainly don’t want people with asthma to panic that they’re going to run out of their inhaler anytime soon.”
Even infants and toddlers can use inhalers
Although Dr. Stukus noted that certain patients do require nebulizers, such as those with conditions that physically limit their breathing, like muscular dystrophy, most patients can use inhalers just fine. He said it’s a “pretty common misconception, even among medical professionals,” that infants and toddlers need nebulizers instead.
“In our institution, for example, we rarely ever start babies on a nebulizer when we diagnose them with asthma,” Dr. Stukus said. “We often just start right away with an inhaler with a spacer and a face mask.”
The shortage of liquid albuterol may therefore have a silver lining, he suggested, as it prompts clinicians to reconsider their routine practice.
“When situations like this arise, it’s a great opportunity for all of us to just take a step back and reevaluate the way we do things,” Dr. Stukus said. “Sometimes we just get caught up with inertia and we continue to do things the same way even though new options are available, or evidence has changed to the contrary.”
Nathan Rabinovitch, MD, professor of pediatrics in the division of pediatric allergy and clinical immunology at National Jewish Health, Denver, said that his center had trouble obtaining liquid albuterol about 2 weeks ago, so they pivoted to the more expensive levalbuterol for about a week and a half, until their albuterol supply was restored.
While Dr. Rabinovitch agreed that most children don’t need a nebulizer, he said about 5%-10% of kids with severe asthma should have one on hand in case their inhaler fails to control an exacerbation.
Personal preferences may also considered, he added.
“If [a parent] says, ‘I like to use the nebulizer. The kid likes it,’ I’m fine if they just use a nebulizer.”
One possible downside of relying on a nebulizer, however, is portability, according to Kelly O’Shea, MD, assistant professor in the division of allergy and clinical immunology at the University of Michigan, Ann Arbor.
“If you’re out at the park or out at a soccer game with your kids, and they are having trouble breathing ... and they need their albuterol, you don’t have that ability if you are tied to a nebulizer,” Dr. O’Shea said in an interview. “As long as a parent feels comfortable – they feel like [their child] can get deep breaths in, I agree that you can use [an inhaler] in the infant and toddler population.”
She also agreed that a nebulizer may serve as a kind of second step if an inhaler isn’t controlling an exacerbation; however, she emphasized that a nebulizer should not be considered a replacement for professional care, and should not give a false sense of security.
“I caution parents to make sure that when they need it, they also take the next step and head over to the emergency room,” Dr. O’Shea said.
Generic drug shortages becoming more common
While the present scarcity of liquid albuterol appears relatively mild in terms of clinical impact, it brings up broader concerns about generic drug supply, and why shortages like this are becoming more common, according to Katie J. Suda, PharmD, MS, professor of medicine and pharmacy, and associate director, center for pharmaceutical policy and prescribing at the University of Pittsburgh.
“Drug shortages continue to increase in frequency, and the duration and severity of the shortages are also getting worse,” Dr. Suda said in an interview.
The reasons for these shortages can be elusive, according to 2022 report by the American Society of Health-System Pharmacists, which found that more than half of shortages came with no explanation from manufacturers.
The same report showed that only 5% of shortages were due to a “business decision,” but this factor is likely more central than publicly stated.
A recent FDA analysis on drug shortages, for instance, lists “lack of incentives to produce less profitable drugs,” as the first “root cause,” and Dr. Suda agrees.
“It’s important that we have generic medicines to decrease costs to our health systems, as well as for our patients,” Dr. Suda said. “But frequently, with those generic products, the price is driven so low that it increases the risk of a shortage.”
The drive to maintain profit margins may motivate companies to cut corners in production, Dr. Suda explained. She emphasized that this connection is speculative, because motivations are effectively unknowable, but the rationale is supported by past and present shortages.
Akorn Pharmaceuticals, for example, received a warning letter from the FDA in 2019 because of a variety of manufacturing issues, including defective bottles, questionable data, and metal shavings on aseptic filling equipment.
When a manufacturer like Akorn fails, the effects can be far-reaching, Dr. Suda said, noting their broad catalog of agents. Beyond liquid albuterol, Akorn was producing cardiac drugs, antibiotics, vitamins, local anesthetics, eye products, and others.
Drug shortages cause “a significant strain on our health care system,” Dr. Suda said, and substituting other medications increases risk of medical errors.
Fortunately, the increasing number of drug shortages is not going unnoticed, according to Dr. Suda. The FDA and multiple other organizations, including the ASHP, American Medical Association, and National Academies of Sciences, Engineering, and Medicine, are all taking steps to ensure that essential medicines are in steady supply, including moves to gather more data from manufacturers.
“I hope that a lot of the efforts that are moving forward ... will help us decrease the impact of shortages on our patients,” Dr. Suda said.
Lou Kennedy is the CEO of Nephron Pharmaceuticals, which commercially produces liquid albuterol. The other interviewees disclosed no relevant conflicts of interest.
Review explores the boundaries of endoscopic resection for esophageal adenocarcinoma
A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.
“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”
The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.
Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.
“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.
While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.
“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.
“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”
To truly find the limits of endoscopic resection for EAC, however, more research is needed.
“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.
The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma, a cancer with rising incidence and stage-dependent survival. Early detection of BE-related neoplasia provides the opportunity to intervene through endoscopic eradication therapy and avoid the morbidity associated with esophagectomy. Verheji and colleagues, a group from a robust BE expert center in the Netherlands, provide a comprehensive and detailed overview of the role of endoscopic therapy for superficial esophageal adenocarcinoma (EAC), which is gaining popularity. In this review, they nicely highlight the benefits of this approach as a minimally invasive, organ-preserving, safe, and effective treatment option.
Jennifer M. Kolb, MD, MS, is assistant professor of medicine, Vatche and Tamar Manoukian Division of Digestive Diseases University of California, Los Angeles. She also is affiliated with VA Greater Los Angeles Health Care System. She has no relevant conflicts of interest.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma, a cancer with rising incidence and stage-dependent survival. Early detection of BE-related neoplasia provides the opportunity to intervene through endoscopic eradication therapy and avoid the morbidity associated with esophagectomy. Verheji and colleagues, a group from a robust BE expert center in the Netherlands, provide a comprehensive and detailed overview of the role of endoscopic therapy for superficial esophageal adenocarcinoma (EAC), which is gaining popularity. In this review, they nicely highlight the benefits of this approach as a minimally invasive, organ-preserving, safe, and effective treatment option.
Jennifer M. Kolb, MD, MS, is assistant professor of medicine, Vatche and Tamar Manoukian Division of Digestive Diseases University of California, Los Angeles. She also is affiliated with VA Greater Los Angeles Health Care System. She has no relevant conflicts of interest.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma, a cancer with rising incidence and stage-dependent survival. Early detection of BE-related neoplasia provides the opportunity to intervene through endoscopic eradication therapy and avoid the morbidity associated with esophagectomy. Verheji and colleagues, a group from a robust BE expert center in the Netherlands, provide a comprehensive and detailed overview of the role of endoscopic therapy for superficial esophageal adenocarcinoma (EAC), which is gaining popularity. In this review, they nicely highlight the benefits of this approach as a minimally invasive, organ-preserving, safe, and effective treatment option.
Jennifer M. Kolb, MD, MS, is assistant professor of medicine, Vatche and Tamar Manoukian Division of Digestive Diseases University of California, Los Angeles. She also is affiliated with VA Greater Los Angeles Health Care System. She has no relevant conflicts of interest.
A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.
“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”
The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.
Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.
“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.
While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.
“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.
“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”
To truly find the limits of endoscopic resection for EAC, however, more research is needed.
“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.
The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.
A growing body of evidence shows that deeper and larger tumors can be safely removed with endoscopy instead of surgery when individual patient risk is taken into account, according to a review by Eva P.D. Verheij, a doctoral candidate at Amsterdam University Medical Center, and colleagues.
“Management of patients with superficial esophageal adenocarcinoma (EAC) is becoming less invasive and more patient-tailored,” the researchers wrote in Techniques and Innovations in Gastrointestinal Endoscopy. “In the future, watchful waiting may be a valid alternative to surgery in selected cases.”
The investigators examined new advances that have been made in the management of superficial esophageal adenocarcinomas by endoscopy, and they address how guidelines may be falling short in light of newly published evidence.
Surgery is usually the first choice for the management of advanced esophageal adenocarcinoma. “Endoscopic treatment has become the cornerstone for early cancer confined to the mucosa,” the authors wrote.
“For low-risk submucosal EAC, which only invades the superficial submucosa (sm1, i.e. less than 500 mcm) without any other risk factors, endoscopic treatment as an alternative to surgery is gaining acceptance because multiple studies have demonstrated a very low risk of lymph node metastases (less than 2% for these lesions),” the investigators wrote. Although surgical resection with lymphadenectomy is currently the recommended treatment for cases with deep submucosal invasion, poor differentiation, or lymphovascular invasion, the investigators suggested that even these tumors may be within an endoscopist’s reach.
While the rate of lymph node metastasis for such patients has been reported to be as high as 46%, more recent endoscopic studies show a metastasis rate range of up to 20% after 23-63 months of follow-up.
“One possible explanation for the discrepancy in lymph node metastases rates between surgical and endoscopic studies could be the different preparation of slides for histopathological assessment,” the investigators wrote. “In general, the cuts in surgical specimen are made with wider intervals (±5 mm) than the cuts in endoscopic resection specimens (2-3 mm), with additional cuts in case of submucosal invasion. The hypothesis is that this wider interval may result in missing the area with the deepest tumor infiltration. This could result in an underdiagnosis of the actual invasion depth, and therefore an overestimation of the associated lymph node metastases risk.” A study published in August 2022 in Gastrointestinal Endoscopy found an annual metastases risk of 6.9% in patients with high-risk T1a EAC.
“Given its invasiveness and associated morbidity and mortality, esophagectomy may be overtreatment in those patients who will not develop lymph node metastases,” the investigators wrote. “Given the technical advances in endoscopy that enable us to radically remove large EACs, and to perform more meticulous follow-up, it might be time to swing the pendulum and only send those patients for surgery who have an indisputable indication for surgery, instead of performing esophagectomy as a prophylactic treatment.”
To truly find the limits of endoscopic resection for EAC, however, more research is needed.
“Ongoing studies are necessary to evaluate the lymph node metastases risk on an individual basis, using presence of histological risk factors. By predicting the risk of lymph node metastases, and considering patients’ wishes and condition, one might decide to perform esophagectomy or watchful waiting with strict endoscopic follow-up. In high-risk cases, we may use sentinel node navigated surgery in the future as an extra safety check before deciding on optimal management,” the authors wrote.
The investigators disclosed relationships Medtronic, C2 Therapeutics/Pentax Medical, MicroTech, and Aqua Medical.
FROM TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY
Daily socialization may extend lifespan in elderly
Sometimes more is more.
Correlations between socializing and survival were detected regardless of baseline health status, suggesting that physicians should be recommending daily socialization for all elderly patients, lead author Ziqiong Wang, MD, of Sichuan University West China Hospital, Chengdu, China, and colleagues reported.
These findings align with an array of prior studies reporting physical and mental health benefits from socialization, and negative impacts from isolation, the investigators wrote in the Journal of Epidemiology & Community Health. Not all studies have yielded the same picture, however, and most research has been conducted in Western countries, leading to uncertainty about whether different outcomes would be seen in populations in other parts of the world. Furthermore, the authors added that few studies have explored the amount of socialization needed to derive a positive benefit.
To address this knowledge gap, the investigators analyzed survival data from 28,563 participants in the Chinese Longitudinal Healthy Longevity Survey with a median age of 89 years at baseline.
“[This analysis] is from a highly respected ongoing longitudinal study of aging in China, which includes a large number of subjects and employs very strong research design and statistical analytical methods, so it has credibility,” John W. Rowe, MD, Julius B. Richmond Professor of Health Policy and Aging at Columbia University, New York, said in a written comment.
The investigators stratified frequency of socialization into five tiers: never, not monthly but sometimes, not weekly but at least once per month, not daily but at least once per week, and almost every day.
Survival proportions were calculated using the Kaplan-Meier method after accounting for a range of individual characteristics, including age, sex, household income, smoking status, diabetes, self-rated health, and others. Comparative findings were described in terms of time ratios using multivariable parametric accelerated failure time (AFT) models.
“The AFT model estimates the time ratio (TR), which is interpreted as the expected time to events in one category relative to the reference group,” the investigators wrote. “Unlike the interpretation of proportional hazard model results where hazard ratios larger than 1 are equal to higher risk, a TR of greater than 1 is considered to have a longer time to events, compared with the reference group.”
From baseline to 5 years, each socialization tier was significantly associated with prolonged survival, suggesting a general benefit. Compared with no socialization, socializing sometimes but not monthly was associated with 42% longer survival, at least monthly socialization was associated with 48% longer survival, at least weekly was associated with 110% longer survival, and socializing almost every day was associated with 87% longer survival.
The outsized benefit of daily socialization became clear in a long-term survival analysis, which spanned 5 years through the end of follow-up. Compared with no socialization, daily socialization tripled survival (TR, 3.04; P < .001), compared with prolongations ranging from 5% to 64% for less socialization, with just one of these lower tiers achieving statistical significance (P = .046).
Of note, the benefit of daily socialization was detected regardless of a person’s health status at baseline.
“No matter if elderly participants had chronic diseases or not, [and] no matter if older people had good self-rated health or not, the survival benefits of frequently participating in social activity were the same,” said principal author Sen He, MD, of Sichuan University, in a written comment.
“Socializing almost every day seems to be the most beneficial for a long life,” Dr. Sen added, noting that more research is needed to determine if there is an optimal type of social activity.
Dr. Rowe pointed out two key findings from the study. The first was that it confirmed “prior studies that have identified a beneficial effect of social activity on life expectancy.
“We have known that engagement is essential for successful aging and that isolation is toxic. While this finding is not novel, it is nice to see this confirmation of what we thought we knew,” he wrote.
Secondly, the study has identified “a threshold effect”, which is that “the long-term benefit on life expectancy was only seen in the presence of fairly intense social interactions, essentially daily,” he said.
According to Preeti Malani, MD, professor of medicine and geriatrician at the University of Michigan, Ann Arbor, the findings are also helpful because they offer data from another part of the world, adding confidence in findings from Western countries.
“This [study] happens to focus on older adults in China, which is helpful since aging is not the same everywhere in the world,” Dr. Malani said. “While the numbers here may not be precise, it’s fair to say that socialization is good for your health – for everyone but especially for older adults.”
Considering the body of evidence now spanning a range of populations, Dr. Malani said physicians should be screening for, and recommending, socialization for all elderly patients, particularly because many aren’t getting enough of it.
“Work that my colleagues and I have done (with the National Poll on Healthy Aging) suggests that there is a portion of older adults that have very little to no social contact,” Dr. Malani said. “A physician may not know this unless they are asking routinely about socialization the way we might ask about diet and exercise. How much is enough? No one knows, but anything is better than nothing and likely more is better.”
She also suggested that personalization is key.
“Physical and emotional health may limit the ability to socialize, so not everyone can engage all the time,” Dr. Malani said. “Also, socialization can look different for different people. Technology allows for socialization even if an individual has trouble leaving their home. I especially worry about this issue for older adults that are also caregivers. Those individuals also need time for themselves” and on way to fulfill that need is by socializing with others.
The study was supported by Sichuan (China) Science and Technology Program, the National Key R&D Program of China, and the National Natural Science Foundation of China. The investigators, Dr. Rowe, and Dr. Malani disclosed no relevant conflicts of interest.
Sometimes more is more.
Correlations between socializing and survival were detected regardless of baseline health status, suggesting that physicians should be recommending daily socialization for all elderly patients, lead author Ziqiong Wang, MD, of Sichuan University West China Hospital, Chengdu, China, and colleagues reported.
These findings align with an array of prior studies reporting physical and mental health benefits from socialization, and negative impacts from isolation, the investigators wrote in the Journal of Epidemiology & Community Health. Not all studies have yielded the same picture, however, and most research has been conducted in Western countries, leading to uncertainty about whether different outcomes would be seen in populations in other parts of the world. Furthermore, the authors added that few studies have explored the amount of socialization needed to derive a positive benefit.
To address this knowledge gap, the investigators analyzed survival data from 28,563 participants in the Chinese Longitudinal Healthy Longevity Survey with a median age of 89 years at baseline.
“[This analysis] is from a highly respected ongoing longitudinal study of aging in China, which includes a large number of subjects and employs very strong research design and statistical analytical methods, so it has credibility,” John W. Rowe, MD, Julius B. Richmond Professor of Health Policy and Aging at Columbia University, New York, said in a written comment.
The investigators stratified frequency of socialization into five tiers: never, not monthly but sometimes, not weekly but at least once per month, not daily but at least once per week, and almost every day.
Survival proportions were calculated using the Kaplan-Meier method after accounting for a range of individual characteristics, including age, sex, household income, smoking status, diabetes, self-rated health, and others. Comparative findings were described in terms of time ratios using multivariable parametric accelerated failure time (AFT) models.
“The AFT model estimates the time ratio (TR), which is interpreted as the expected time to events in one category relative to the reference group,” the investigators wrote. “Unlike the interpretation of proportional hazard model results where hazard ratios larger than 1 are equal to higher risk, a TR of greater than 1 is considered to have a longer time to events, compared with the reference group.”
From baseline to 5 years, each socialization tier was significantly associated with prolonged survival, suggesting a general benefit. Compared with no socialization, socializing sometimes but not monthly was associated with 42% longer survival, at least monthly socialization was associated with 48% longer survival, at least weekly was associated with 110% longer survival, and socializing almost every day was associated with 87% longer survival.
The outsized benefit of daily socialization became clear in a long-term survival analysis, which spanned 5 years through the end of follow-up. Compared with no socialization, daily socialization tripled survival (TR, 3.04; P < .001), compared with prolongations ranging from 5% to 64% for less socialization, with just one of these lower tiers achieving statistical significance (P = .046).
Of note, the benefit of daily socialization was detected regardless of a person’s health status at baseline.
“No matter if elderly participants had chronic diseases or not, [and] no matter if older people had good self-rated health or not, the survival benefits of frequently participating in social activity were the same,” said principal author Sen He, MD, of Sichuan University, in a written comment.
“Socializing almost every day seems to be the most beneficial for a long life,” Dr. Sen added, noting that more research is needed to determine if there is an optimal type of social activity.
Dr. Rowe pointed out two key findings from the study. The first was that it confirmed “prior studies that have identified a beneficial effect of social activity on life expectancy.
“We have known that engagement is essential for successful aging and that isolation is toxic. While this finding is not novel, it is nice to see this confirmation of what we thought we knew,” he wrote.
Secondly, the study has identified “a threshold effect”, which is that “the long-term benefit on life expectancy was only seen in the presence of fairly intense social interactions, essentially daily,” he said.
According to Preeti Malani, MD, professor of medicine and geriatrician at the University of Michigan, Ann Arbor, the findings are also helpful because they offer data from another part of the world, adding confidence in findings from Western countries.
“This [study] happens to focus on older adults in China, which is helpful since aging is not the same everywhere in the world,” Dr. Malani said. “While the numbers here may not be precise, it’s fair to say that socialization is good for your health – for everyone but especially for older adults.”
Considering the body of evidence now spanning a range of populations, Dr. Malani said physicians should be screening for, and recommending, socialization for all elderly patients, particularly because many aren’t getting enough of it.
“Work that my colleagues and I have done (with the National Poll on Healthy Aging) suggests that there is a portion of older adults that have very little to no social contact,” Dr. Malani said. “A physician may not know this unless they are asking routinely about socialization the way we might ask about diet and exercise. How much is enough? No one knows, but anything is better than nothing and likely more is better.”
She also suggested that personalization is key.
“Physical and emotional health may limit the ability to socialize, so not everyone can engage all the time,” Dr. Malani said. “Also, socialization can look different for different people. Technology allows for socialization even if an individual has trouble leaving their home. I especially worry about this issue for older adults that are also caregivers. Those individuals also need time for themselves” and on way to fulfill that need is by socializing with others.
The study was supported by Sichuan (China) Science and Technology Program, the National Key R&D Program of China, and the National Natural Science Foundation of China. The investigators, Dr. Rowe, and Dr. Malani disclosed no relevant conflicts of interest.
Sometimes more is more.
Correlations between socializing and survival were detected regardless of baseline health status, suggesting that physicians should be recommending daily socialization for all elderly patients, lead author Ziqiong Wang, MD, of Sichuan University West China Hospital, Chengdu, China, and colleagues reported.
These findings align with an array of prior studies reporting physical and mental health benefits from socialization, and negative impacts from isolation, the investigators wrote in the Journal of Epidemiology & Community Health. Not all studies have yielded the same picture, however, and most research has been conducted in Western countries, leading to uncertainty about whether different outcomes would be seen in populations in other parts of the world. Furthermore, the authors added that few studies have explored the amount of socialization needed to derive a positive benefit.
To address this knowledge gap, the investigators analyzed survival data from 28,563 participants in the Chinese Longitudinal Healthy Longevity Survey with a median age of 89 years at baseline.
“[This analysis] is from a highly respected ongoing longitudinal study of aging in China, which includes a large number of subjects and employs very strong research design and statistical analytical methods, so it has credibility,” John W. Rowe, MD, Julius B. Richmond Professor of Health Policy and Aging at Columbia University, New York, said in a written comment.
The investigators stratified frequency of socialization into five tiers: never, not monthly but sometimes, not weekly but at least once per month, not daily but at least once per week, and almost every day.
Survival proportions were calculated using the Kaplan-Meier method after accounting for a range of individual characteristics, including age, sex, household income, smoking status, diabetes, self-rated health, and others. Comparative findings were described in terms of time ratios using multivariable parametric accelerated failure time (AFT) models.
“The AFT model estimates the time ratio (TR), which is interpreted as the expected time to events in one category relative to the reference group,” the investigators wrote. “Unlike the interpretation of proportional hazard model results where hazard ratios larger than 1 are equal to higher risk, a TR of greater than 1 is considered to have a longer time to events, compared with the reference group.”
From baseline to 5 years, each socialization tier was significantly associated with prolonged survival, suggesting a general benefit. Compared with no socialization, socializing sometimes but not monthly was associated with 42% longer survival, at least monthly socialization was associated with 48% longer survival, at least weekly was associated with 110% longer survival, and socializing almost every day was associated with 87% longer survival.
The outsized benefit of daily socialization became clear in a long-term survival analysis, which spanned 5 years through the end of follow-up. Compared with no socialization, daily socialization tripled survival (TR, 3.04; P < .001), compared with prolongations ranging from 5% to 64% for less socialization, with just one of these lower tiers achieving statistical significance (P = .046).
Of note, the benefit of daily socialization was detected regardless of a person’s health status at baseline.
“No matter if elderly participants had chronic diseases or not, [and] no matter if older people had good self-rated health or not, the survival benefits of frequently participating in social activity were the same,” said principal author Sen He, MD, of Sichuan University, in a written comment.
“Socializing almost every day seems to be the most beneficial for a long life,” Dr. Sen added, noting that more research is needed to determine if there is an optimal type of social activity.
Dr. Rowe pointed out two key findings from the study. The first was that it confirmed “prior studies that have identified a beneficial effect of social activity on life expectancy.
“We have known that engagement is essential for successful aging and that isolation is toxic. While this finding is not novel, it is nice to see this confirmation of what we thought we knew,” he wrote.
Secondly, the study has identified “a threshold effect”, which is that “the long-term benefit on life expectancy was only seen in the presence of fairly intense social interactions, essentially daily,” he said.
According to Preeti Malani, MD, professor of medicine and geriatrician at the University of Michigan, Ann Arbor, the findings are also helpful because they offer data from another part of the world, adding confidence in findings from Western countries.
“This [study] happens to focus on older adults in China, which is helpful since aging is not the same everywhere in the world,” Dr. Malani said. “While the numbers here may not be precise, it’s fair to say that socialization is good for your health – for everyone but especially for older adults.”
Considering the body of evidence now spanning a range of populations, Dr. Malani said physicians should be screening for, and recommending, socialization for all elderly patients, particularly because many aren’t getting enough of it.
“Work that my colleagues and I have done (with the National Poll on Healthy Aging) suggests that there is a portion of older adults that have very little to no social contact,” Dr. Malani said. “A physician may not know this unless they are asking routinely about socialization the way we might ask about diet and exercise. How much is enough? No one knows, but anything is better than nothing and likely more is better.”
She also suggested that personalization is key.
“Physical and emotional health may limit the ability to socialize, so not everyone can engage all the time,” Dr. Malani said. “Also, socialization can look different for different people. Technology allows for socialization even if an individual has trouble leaving their home. I especially worry about this issue for older adults that are also caregivers. Those individuals also need time for themselves” and on way to fulfill that need is by socializing with others.
The study was supported by Sichuan (China) Science and Technology Program, the National Key R&D Program of China, and the National Natural Science Foundation of China. The investigators, Dr. Rowe, and Dr. Malani disclosed no relevant conflicts of interest.
FROM THE JOURNAL OF EPIDEMIOLOGY & COMMUNITY HEALTH
AGA guideline defines role of biomarkers in ulcerative colitis
The American Gastroenterological Association (AGA) has released a new clinical practice guideline defining the role of biomarkers in monitoring and managing ulcerative colitis (UC).
, reported lead guideline panelist Siddharth Singh, MD, of University of California San Diego, La Jolla, Calif., and colleagues.
“[I]n routine clinical practice, repeated endoscopic assessment is invasive, expensive, and may be impractical,” the panelists wrote. Their report is in Gastroenterology. “There is an important need for understanding how noninvasive biomarkers may serve as accurate and reliable surrogates for endoscopic assessment of inflammation and whether they can be more readily implemented in a UC care pathway.”
After reviewing relevant randomized controlled trials and observational studies, Dr. Singh and colleagues issued seven conditional recommendations, three of which concern patients in symptomatic remission, and four of which apply to patients with symptomatically active UC.
“The key take-home message is that the routine measurement of noninvasive biomarkers in addition to assessment of patient reported symptoms is critical in evaluating the disease burden of UC,” said Jordan E. Axelrad, MD, MPH, director of clinical and translational research at NYU Langone Health’s Inflammatory Bowel Disease Center, New York. “Many of these recommendations regarding the assessment of disease activity beyond symptoms alone are widely accepted, particularity at tertiary IBD centers; however, this guideline serves to formalize and structure the recommendations, with appropriate test cutoff values, in a simple UC care pathway.”
Recommendations for patients in symptomatic remission
For patients in remission, the guideline advises monitoring both symptoms and biomarkers, with biomarkers measured every 6-12 months.
Asymptomatic patients with normal biomarkers can skip routine endoscopy to evaluate disease activity, according to the guideline, but those with abnormal fecal calprotectin, fecal lactoferrin, or serum C-reactive protein (CRP) are candidates for endoscopic assessment instead of empiric treatment adjustment. Patients may still need periodic colonoscopy for dysplasia surveillance.
“The most important pearl [from the guideline] is that fecal calprotectin less than 150 mcg/g, normal fecal lactoferrin, or normal CRP, can be used to rule out active inflammation in patients in symptomatic remission,” according to Dr. Axelrad.
The guideline suggests that the two fecal biomarkers “may be optimal for monitoring and may be particularly useful in patients where biomarkers have historically correlated with endoscopic disease activity.” In contrast, normal CRP may be insufficient to rule out moderate to severe endoscopic inflammation in patients who recently entered remission following treatment adjustment.
While abnormal biomarkers in asymptomatic patients are sufficient cause for endoscopy, the guideline also suggests that retesting in 3-6 months is a reasonable alternative. If biomarkers are again elevated, then endoscopic evaluation should be considered.
Recommendations for patients with symptomatically active disease
The recommendations for patients with symptomatically active UC follow a similar pathway. The guideline advises an evaluation strategy combining symptoms and biomarkers instead of symptoms alone.
For example, patients with moderate to severe symptoms suggestive of flare and elevated biomarkers are candidates for treatment adjustment without endoscopy.
Still, patient preferences should be considered, Dr. Singh and colleagues noted.
“Patients who place greater value in confirming inflammation, particularly when making significant treatment decisions (such as starting or switching immunosuppressive therapies), and lesser value on the inconvenience of endoscopy, may choose to pursue endoscopic evaluation before treatment adjustment,” they wrote.
For patients with mild symptoms, endoscopy is generally recommended, according to the guideline, unless the patient recently had moderate to severe symptoms and has improved after treatment adjustment; in that case, biomarkers can be used to fine-tune therapy without the need for endoscopy.
Again, providers should engage in shared-decision making, the guideline advises. Patients with mild symptoms but no biomarker results may reasonably elect to undergo endoscopy prior to testing biomarkers, while patients with mild symptoms and normal biomarkers may reasonably elect to retest biomarkers in 3-6 months.
Data remain insufficient to recommend biomarkers over endoscopy
Dr. Singh and colleagues concluded the guideline by highlighting an insufficient level of direct evidence necessary to recommend a biomarker-based treat-to-target strategy over endoscopy-based monitoring strategy, despite indirect evidence suggesting this may be the case.
“[T]here have not been any studies comparing a biomarker-based strategy with an endoscopy-based strategy for assessment and monitoring of endoscopic remission,” they wrote. “This was identified as a knowledge gap by the panel.”
The authors disclosed relationships with Pfizer, AbbVie, Lilly, and others. Dr. Axelrad disclosed relationships with Janssen, AbbVie, Pfizer, and others.
The American Gastroenterological Association (AGA) has released a new clinical practice guideline defining the role of biomarkers in monitoring and managing ulcerative colitis (UC).
, reported lead guideline panelist Siddharth Singh, MD, of University of California San Diego, La Jolla, Calif., and colleagues.
“[I]n routine clinical practice, repeated endoscopic assessment is invasive, expensive, and may be impractical,” the panelists wrote. Their report is in Gastroenterology. “There is an important need for understanding how noninvasive biomarkers may serve as accurate and reliable surrogates for endoscopic assessment of inflammation and whether they can be more readily implemented in a UC care pathway.”
After reviewing relevant randomized controlled trials and observational studies, Dr. Singh and colleagues issued seven conditional recommendations, three of which concern patients in symptomatic remission, and four of which apply to patients with symptomatically active UC.
“The key take-home message is that the routine measurement of noninvasive biomarkers in addition to assessment of patient reported symptoms is critical in evaluating the disease burden of UC,” said Jordan E. Axelrad, MD, MPH, director of clinical and translational research at NYU Langone Health’s Inflammatory Bowel Disease Center, New York. “Many of these recommendations regarding the assessment of disease activity beyond symptoms alone are widely accepted, particularity at tertiary IBD centers; however, this guideline serves to formalize and structure the recommendations, with appropriate test cutoff values, in a simple UC care pathway.”
Recommendations for patients in symptomatic remission
For patients in remission, the guideline advises monitoring both symptoms and biomarkers, with biomarkers measured every 6-12 months.
Asymptomatic patients with normal biomarkers can skip routine endoscopy to evaluate disease activity, according to the guideline, but those with abnormal fecal calprotectin, fecal lactoferrin, or serum C-reactive protein (CRP) are candidates for endoscopic assessment instead of empiric treatment adjustment. Patients may still need periodic colonoscopy for dysplasia surveillance.
“The most important pearl [from the guideline] is that fecal calprotectin less than 150 mcg/g, normal fecal lactoferrin, or normal CRP, can be used to rule out active inflammation in patients in symptomatic remission,” according to Dr. Axelrad.
The guideline suggests that the two fecal biomarkers “may be optimal for monitoring and may be particularly useful in patients where biomarkers have historically correlated with endoscopic disease activity.” In contrast, normal CRP may be insufficient to rule out moderate to severe endoscopic inflammation in patients who recently entered remission following treatment adjustment.
While abnormal biomarkers in asymptomatic patients are sufficient cause for endoscopy, the guideline also suggests that retesting in 3-6 months is a reasonable alternative. If biomarkers are again elevated, then endoscopic evaluation should be considered.
Recommendations for patients with symptomatically active disease
The recommendations for patients with symptomatically active UC follow a similar pathway. The guideline advises an evaluation strategy combining symptoms and biomarkers instead of symptoms alone.
For example, patients with moderate to severe symptoms suggestive of flare and elevated biomarkers are candidates for treatment adjustment without endoscopy.
Still, patient preferences should be considered, Dr. Singh and colleagues noted.
“Patients who place greater value in confirming inflammation, particularly when making significant treatment decisions (such as starting or switching immunosuppressive therapies), and lesser value on the inconvenience of endoscopy, may choose to pursue endoscopic evaluation before treatment adjustment,” they wrote.
For patients with mild symptoms, endoscopy is generally recommended, according to the guideline, unless the patient recently had moderate to severe symptoms and has improved after treatment adjustment; in that case, biomarkers can be used to fine-tune therapy without the need for endoscopy.
Again, providers should engage in shared-decision making, the guideline advises. Patients with mild symptoms but no biomarker results may reasonably elect to undergo endoscopy prior to testing biomarkers, while patients with mild symptoms and normal biomarkers may reasonably elect to retest biomarkers in 3-6 months.
Data remain insufficient to recommend biomarkers over endoscopy
Dr. Singh and colleagues concluded the guideline by highlighting an insufficient level of direct evidence necessary to recommend a biomarker-based treat-to-target strategy over endoscopy-based monitoring strategy, despite indirect evidence suggesting this may be the case.
“[T]here have not been any studies comparing a biomarker-based strategy with an endoscopy-based strategy for assessment and monitoring of endoscopic remission,” they wrote. “This was identified as a knowledge gap by the panel.”
The authors disclosed relationships with Pfizer, AbbVie, Lilly, and others. Dr. Axelrad disclosed relationships with Janssen, AbbVie, Pfizer, and others.
The American Gastroenterological Association (AGA) has released a new clinical practice guideline defining the role of biomarkers in monitoring and managing ulcerative colitis (UC).
, reported lead guideline panelist Siddharth Singh, MD, of University of California San Diego, La Jolla, Calif., and colleagues.
“[I]n routine clinical practice, repeated endoscopic assessment is invasive, expensive, and may be impractical,” the panelists wrote. Their report is in Gastroenterology. “There is an important need for understanding how noninvasive biomarkers may serve as accurate and reliable surrogates for endoscopic assessment of inflammation and whether they can be more readily implemented in a UC care pathway.”
After reviewing relevant randomized controlled trials and observational studies, Dr. Singh and colleagues issued seven conditional recommendations, three of which concern patients in symptomatic remission, and four of which apply to patients with symptomatically active UC.
“The key take-home message is that the routine measurement of noninvasive biomarkers in addition to assessment of patient reported symptoms is critical in evaluating the disease burden of UC,” said Jordan E. Axelrad, MD, MPH, director of clinical and translational research at NYU Langone Health’s Inflammatory Bowel Disease Center, New York. “Many of these recommendations regarding the assessment of disease activity beyond symptoms alone are widely accepted, particularity at tertiary IBD centers; however, this guideline serves to formalize and structure the recommendations, with appropriate test cutoff values, in a simple UC care pathway.”
Recommendations for patients in symptomatic remission
For patients in remission, the guideline advises monitoring both symptoms and biomarkers, with biomarkers measured every 6-12 months.
Asymptomatic patients with normal biomarkers can skip routine endoscopy to evaluate disease activity, according to the guideline, but those with abnormal fecal calprotectin, fecal lactoferrin, or serum C-reactive protein (CRP) are candidates for endoscopic assessment instead of empiric treatment adjustment. Patients may still need periodic colonoscopy for dysplasia surveillance.
“The most important pearl [from the guideline] is that fecal calprotectin less than 150 mcg/g, normal fecal lactoferrin, or normal CRP, can be used to rule out active inflammation in patients in symptomatic remission,” according to Dr. Axelrad.
The guideline suggests that the two fecal biomarkers “may be optimal for monitoring and may be particularly useful in patients where biomarkers have historically correlated with endoscopic disease activity.” In contrast, normal CRP may be insufficient to rule out moderate to severe endoscopic inflammation in patients who recently entered remission following treatment adjustment.
While abnormal biomarkers in asymptomatic patients are sufficient cause for endoscopy, the guideline also suggests that retesting in 3-6 months is a reasonable alternative. If biomarkers are again elevated, then endoscopic evaluation should be considered.
Recommendations for patients with symptomatically active disease
The recommendations for patients with symptomatically active UC follow a similar pathway. The guideline advises an evaluation strategy combining symptoms and biomarkers instead of symptoms alone.
For example, patients with moderate to severe symptoms suggestive of flare and elevated biomarkers are candidates for treatment adjustment without endoscopy.
Still, patient preferences should be considered, Dr. Singh and colleagues noted.
“Patients who place greater value in confirming inflammation, particularly when making significant treatment decisions (such as starting or switching immunosuppressive therapies), and lesser value on the inconvenience of endoscopy, may choose to pursue endoscopic evaluation before treatment adjustment,” they wrote.
For patients with mild symptoms, endoscopy is generally recommended, according to the guideline, unless the patient recently had moderate to severe symptoms and has improved after treatment adjustment; in that case, biomarkers can be used to fine-tune therapy without the need for endoscopy.
Again, providers should engage in shared-decision making, the guideline advises. Patients with mild symptoms but no biomarker results may reasonably elect to undergo endoscopy prior to testing biomarkers, while patients with mild symptoms and normal biomarkers may reasonably elect to retest biomarkers in 3-6 months.
Data remain insufficient to recommend biomarkers over endoscopy
Dr. Singh and colleagues concluded the guideline by highlighting an insufficient level of direct evidence necessary to recommend a biomarker-based treat-to-target strategy over endoscopy-based monitoring strategy, despite indirect evidence suggesting this may be the case.
“[T]here have not been any studies comparing a biomarker-based strategy with an endoscopy-based strategy for assessment and monitoring of endoscopic remission,” they wrote. “This was identified as a knowledge gap by the panel.”
The authors disclosed relationships with Pfizer, AbbVie, Lilly, and others. Dr. Axelrad disclosed relationships with Janssen, AbbVie, Pfizer, and others.
FROM GASTROENTEROLOGY
How to get started with prescribing and advising on CGM
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.