Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.

Free CME Credit

This article traces the evolution of estrogen in contraception, with a special focus on the concept of native estrogen with specific actions in tissues, or NEST. Research surrounding estetrols (E4), receptor binding, and target interactions demonstrate that E4 has high selectivity for the estrogen receptors. Clinical trial data are presented that support the view that E4 — a high NEST activity estrogen — is a safe and effective estrogen for use in combined oral contraceptives. This premise was borne out with the approval of an estetrol/drosperinone combined oral contraceptive by the US Food and Drug Administration in April 2021.

Click here to read more

CME CREDITS: .25 CREDIT
To receive CME credit, please read the articles and go to www.omniaeducation.com/estrogen to access the posttest and evaluation.

Authors:

Patricia Geraghty, MSN, FNP-BC, WHNP
Hugh S. Taylor, MD

Free CME Credit

This article traces the evolution of estrogen in contraception, with a special focus on the concept of native estrogen with specific actions in tissues, or NEST. Research surrounding estetrols (E4), receptor binding, and target interactions demonstrate that E4 has high selectivity for the estrogen receptors. Clinical trial data are presented that support the view that E4 — a high NEST activity estrogen — is a safe and effective estrogen for use in combined oral contraceptives. This premise was borne out with the approval of an estetrol/drosperinone combined oral contraceptive by the US Food and Drug Administration in April 2021.

Click here to read more

CME CREDITS: .25 CREDIT
To receive CME credit, please read the articles and go to www.omniaeducation.com/estrogen to access the posttest and evaluation.

Authors:

Patricia Geraghty, MSN, FNP-BC, WHNP
Hugh S. Taylor, MD

Free CME Credit

This article traces the evolution of estrogen in contraception, with a special focus on the concept of native estrogen with specific actions in tissues, or NEST. Research surrounding estetrols (E4), receptor binding, and target interactions demonstrate that E4 has high selectivity for the estrogen receptors. Clinical trial data are presented that support the view that E4 — a high NEST activity estrogen — is a safe and effective estrogen for use in combined oral contraceptives. This premise was borne out with the approval of an estetrol/drosperinone combined oral contraceptive by the US Food and Drug Administration in April 2021.

Click here to read more

CME CREDITS: .25 CREDIT
To receive CME credit, please read the articles and go to www.omniaeducation.com/estrogen to access the posttest and evaluation.

Authors:

Patricia Geraghty, MSN, FNP-BC, WHNP
Hugh S. Taylor, MD

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Cancer surgery is filled with moments of fear, even for doctors. Our cameras follow as an oncologist confronts this anxiety in the second episode of our video series The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Cancer surgery is filled with moments of fear, even for doctors. Our cameras follow as an oncologist confronts this anxiety in the second episode of our video series The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Cancer surgery is filled with moments of fear, even for doctors. Our cameras follow as an oncologist confronts this anxiety in the second episode of our video series The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Among children with sickle cell disease who have not undergone hematopoietic stem cell transplant, Salmonella is now the leading cause of invasive bacterial infection (IBI), according to a new retrospective study (BACT-SPRING) conducted in Europe. Streptococcus pneumoniae was the second most common source of infection, marking a shift from years past, when S. pneumoniae was the most common source. The epidemiology of IBI in Europe has been altered by adoption of prophylaxis and the introduction of the pneumococcal conjugated vaccine (PCV13) in 2009.

Previous studies of IBI have been single center with small sample sizes, and few have been conducted since 2016, said Jean Gaschignard, MD, PhD, during his presentation of the study at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Dr. Gaschignard is head of pediatrics at Groupe Hospitalier Nord Essonne in Longjumeau, France.

The study produced some unexpected results. “We were surprised,” said Dr. Gaschignard, by results indicating that not all children aged under 10 years were undergoing prophylaxis. Instead, the figures were closer to 80% or 90%. Among children over 10, the rate of prophylaxis varies between countries. “Our study is a clue to discuss again the indications for the age limit for prophylaxis against pneumococcus,” said Dr. Gauschignard, during the question-and-answer session following his talk.

The data give clinicians an updated picture of the epidemiology in this population following introduction of the PCV13 vaccine. “It was very important to have new data on microbiology after this implementation,” said Marie Rohr, MD, who is a fellow in pediatric infectious diseases at the University Hospitals of Geneva. Dr. Rohr moderated the session where the study was presented.

Dr. Rohr noted the shift from the dominant cause of IBI after the introduction of the PCV10/13 vaccine, from S. pneumoniae to Salmonella. The researchers also found a preponderance of bacteremia and osteoarticular infections. “The mortality and morbidity are still considerable despite infection preventive measures,” said Dr. Rohr.

The results should also prompt a second look at prevention strategies. “Even if the antibiotic prophylaxis is prescribed for a large [proportion of children with sickle cell disease] under 10 years old, the median age of invasive bacterial infection is 7 years old. This calls into question systematic antibiotic prophylaxis and case-control studies are needed to evaluate this and possibly modify antibiotic prophylaxis recommendations in the future,” said Dr. Rohr.

The BACT-SPRING study was conducted between Jan. 1, 2014, and Dec. 31, 2019, using online data. It included 217 IBI episodes from 26 centers in five European countries. Just over half were from France, while about a quarter occurred in Spain. Other countries included Belgium, Portugal, and Great Britain. Participants were younger than 18 and had an IBI confirmed by bacterial culture or PCR from normally sterile fluid.

Thirty-eight episodes occurred in children who had undergone hematopoietic stem cell transplantation (HSCT), and 179 in children who had not undergone HSCT. The presentation focused exclusively on the latter group.

Among episodes in children without HSCT, the mean age was 7. Forty-eight patients had a history of acute chest syndrome, 47 had a history of ICU admission, 29 had a history of IBI, and 27 had a history of acute splenic sequestration. Thirteen underwent a splenectomy. Almost half of children had none of these characteristics, while about one-fourth had two or more.

In the HSCT group, 141 children were on prophylaxis at the time of the infection; 74 were on hydroxyurea, and 36 were currently or previously on a transfusion program. Sixty-eight cases were primary bacteremia and 55 were osteoarticular. Other syndromes included pneumonia empyema (n = 18), and meningitis (n = 17), among others. In 44 cases, the isolated bacteria was Salmonella, followed by S. pneumoniae in 32 cases. Escherichia coli accounted for 22. Haemophilus influenza was identified in six episodes, and group A Streptococcus in three.

The study is the first large European epidemiologic study investigating IBI in children with sickle cell disease, and one of its strengths was the strict inclusion criteria. However, it was limited by its retrospective nature.

Dr. Gaschignard and Dr. Rohr have no relevant financial disclosures.

Among children with sickle cell disease who have not undergone hematopoietic stem cell transplant, Salmonella is now the leading cause of invasive bacterial infection (IBI), according to a new retrospective study (BACT-SPRING) conducted in Europe. Streptococcus pneumoniae was the second most common source of infection, marking a shift from years past, when S. pneumoniae was the most common source. The epidemiology of IBI in Europe has been altered by adoption of prophylaxis and the introduction of the pneumococcal conjugated vaccine (PCV13) in 2009.

Previous studies of IBI have been single center with small sample sizes, and few have been conducted since 2016, said Jean Gaschignard, MD, PhD, during his presentation of the study at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Dr. Gaschignard is head of pediatrics at Groupe Hospitalier Nord Essonne in Longjumeau, France.

The study produced some unexpected results. “We were surprised,” said Dr. Gaschignard, by results indicating that not all children aged under 10 years were undergoing prophylaxis. Instead, the figures were closer to 80% or 90%. Among children over 10, the rate of prophylaxis varies between countries. “Our study is a clue to discuss again the indications for the age limit for prophylaxis against pneumococcus,” said Dr. Gauschignard, during the question-and-answer session following his talk.

The data give clinicians an updated picture of the epidemiology in this population following introduction of the PCV13 vaccine. “It was very important to have new data on microbiology after this implementation,” said Marie Rohr, MD, who is a fellow in pediatric infectious diseases at the University Hospitals of Geneva. Dr. Rohr moderated the session where the study was presented.

Dr. Rohr noted the shift from the dominant cause of IBI after the introduction of the PCV10/13 vaccine, from S. pneumoniae to Salmonella. The researchers also found a preponderance of bacteremia and osteoarticular infections. “The mortality and morbidity are still considerable despite infection preventive measures,” said Dr. Rohr.

The results should also prompt a second look at prevention strategies. “Even if the antibiotic prophylaxis is prescribed for a large [proportion of children with sickle cell disease] under 10 years old, the median age of invasive bacterial infection is 7 years old. This calls into question systematic antibiotic prophylaxis and case-control studies are needed to evaluate this and possibly modify antibiotic prophylaxis recommendations in the future,” said Dr. Rohr.

The BACT-SPRING study was conducted between Jan. 1, 2014, and Dec. 31, 2019, using online data. It included 217 IBI episodes from 26 centers in five European countries. Just over half were from France, while about a quarter occurred in Spain. Other countries included Belgium, Portugal, and Great Britain. Participants were younger than 18 and had an IBI confirmed by bacterial culture or PCR from normally sterile fluid.

Thirty-eight episodes occurred in children who had undergone hematopoietic stem cell transplantation (HSCT), and 179 in children who had not undergone HSCT. The presentation focused exclusively on the latter group.

Among episodes in children without HSCT, the mean age was 7. Forty-eight patients had a history of acute chest syndrome, 47 had a history of ICU admission, 29 had a history of IBI, and 27 had a history of acute splenic sequestration. Thirteen underwent a splenectomy. Almost half of children had none of these characteristics, while about one-fourth had two or more.

In the HSCT group, 141 children were on prophylaxis at the time of the infection; 74 were on hydroxyurea, and 36 were currently or previously on a transfusion program. Sixty-eight cases were primary bacteremia and 55 were osteoarticular. Other syndromes included pneumonia empyema (n = 18), and meningitis (n = 17), among others. In 44 cases, the isolated bacteria was Salmonella, followed by S. pneumoniae in 32 cases. Escherichia coli accounted for 22. Haemophilus influenza was identified in six episodes, and group A Streptococcus in three.

The study is the first large European epidemiologic study investigating IBI in children with sickle cell disease, and one of its strengths was the strict inclusion criteria. However, it was limited by its retrospective nature.

Dr. Gaschignard and Dr. Rohr have no relevant financial disclosures.

Among children with sickle cell disease who have not undergone hematopoietic stem cell transplant, Salmonella is now the leading cause of invasive bacterial infection (IBI), according to a new retrospective study (BACT-SPRING) conducted in Europe. Streptococcus pneumoniae was the second most common source of infection, marking a shift from years past, when S. pneumoniae was the most common source. The epidemiology of IBI in Europe has been altered by adoption of prophylaxis and the introduction of the pneumococcal conjugated vaccine (PCV13) in 2009.

Previous studies of IBI have been single center with small sample sizes, and few have been conducted since 2016, said Jean Gaschignard, MD, PhD, during his presentation of the study at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Dr. Gaschignard is head of pediatrics at Groupe Hospitalier Nord Essonne in Longjumeau, France.

The study produced some unexpected results. “We were surprised,” said Dr. Gaschignard, by results indicating that not all children aged under 10 years were undergoing prophylaxis. Instead, the figures were closer to 80% or 90%. Among children over 10, the rate of prophylaxis varies between countries. “Our study is a clue to discuss again the indications for the age limit for prophylaxis against pneumococcus,” said Dr. Gauschignard, during the question-and-answer session following his talk.

The data give clinicians an updated picture of the epidemiology in this population following introduction of the PCV13 vaccine. “It was very important to have new data on microbiology after this implementation,” said Marie Rohr, MD, who is a fellow in pediatric infectious diseases at the University Hospitals of Geneva. Dr. Rohr moderated the session where the study was presented.

Dr. Rohr noted the shift from the dominant cause of IBI after the introduction of the PCV10/13 vaccine, from S. pneumoniae to Salmonella. The researchers also found a preponderance of bacteremia and osteoarticular infections. “The mortality and morbidity are still considerable despite infection preventive measures,” said Dr. Rohr.

The results should also prompt a second look at prevention strategies. “Even if the antibiotic prophylaxis is prescribed for a large [proportion of children with sickle cell disease] under 10 years old, the median age of invasive bacterial infection is 7 years old. This calls into question systematic antibiotic prophylaxis and case-control studies are needed to evaluate this and possibly modify antibiotic prophylaxis recommendations in the future,” said Dr. Rohr.

The BACT-SPRING study was conducted between Jan. 1, 2014, and Dec. 31, 2019, using online data. It included 217 IBI episodes from 26 centers in five European countries. Just over half were from France, while about a quarter occurred in Spain. Other countries included Belgium, Portugal, and Great Britain. Participants were younger than 18 and had an IBI confirmed by bacterial culture or PCR from normally sterile fluid.

Thirty-eight episodes occurred in children who had undergone hematopoietic stem cell transplantation (HSCT), and 179 in children who had not undergone HSCT. The presentation focused exclusively on the latter group.

Among episodes in children without HSCT, the mean age was 7. Forty-eight patients had a history of acute chest syndrome, 47 had a history of ICU admission, 29 had a history of IBI, and 27 had a history of acute splenic sequestration. Thirteen underwent a splenectomy. Almost half of children had none of these characteristics, while about one-fourth had two or more.

In the HSCT group, 141 children were on prophylaxis at the time of the infection; 74 were on hydroxyurea, and 36 were currently or previously on a transfusion program. Sixty-eight cases were primary bacteremia and 55 were osteoarticular. Other syndromes included pneumonia empyema (n = 18), and meningitis (n = 17), among others. In 44 cases, the isolated bacteria was Salmonella, followed by S. pneumoniae in 32 cases. Escherichia coli accounted for 22. Haemophilus influenza was identified in six episodes, and group A Streptococcus in three.

The study is the first large European epidemiologic study investigating IBI in children with sickle cell disease, and one of its strengths was the strict inclusion criteria. However, it was limited by its retrospective nature.

Dr. Gaschignard and Dr. Rohr have no relevant financial disclosures.

Infants with isolated sensorineural hearing loss as a result of congenital cytomegalovirus (cCMV) infection may benefit from treatment with valganciclovir, according to results from the CONCERT nonrandomized trial.

Subjects were found through the Newborn Hearing Screening program, using dried blood spot screening to confirm cCMV Infection. As a result of 6 weeks of therapy, more patients in the treatment group had improvements in hearing at age 20 months, and fewer had deterioration compared with untreated controls.

There is a general consensus that symptomatic cCMV should be treated with valganciclovir for 6 weeks or 6 months, but treatment of patients with only hearing loss is still under debate. The average age of participants was 8 weeks.

The study was presented by Pui Khi Chung, MD, a clinical microbiologist at the Leiden University Medical Center, the Netherlands, at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Out of 1,377 NHS-referred infants, 59 were diagnosed with cCMV (4.3%), and 35 were included in the study. Twenty-five patients received 6 weeks of valganciclovir, while 10 patients received placebo. The control group was expanded to 12 when two additional subjects were identified retrospectively and were successfully followed up at 20 months. Subjects in the treatment group were an average of 8 weeks old when treatment began. Both groups had similar neurodevelopmental outcomes at 20 months, as measured by the Bayley Scales of Infant and Toddler Development (BSID-III) and the Child Development Inventory (CDI). There were no serious adverse events associated with treatment.

To measure efficacy, the researchers used a random intercept, random slope model that accounted for repeated measurements. The differences in slopes for analyses of the best ear were significantly different between the treatment and control groups (estimated difference in slopes, –0.93; P = .0071). Further analyses of total hearing found that improvement was more common in the treatment group, and deterioration/no change was more common in the nontreatment group (P = .044). In another analysis that excluded the most profoundly impaired ears (> 70 db hearing loss), none in the control group experienced improvement and almost half deteriorated. In the treatment group, most were unchanged and a small number improved, with almost none deteriorating (P = .006).

Asked whether the treatment has any effect on the most profoundly impaired ears, Dr. Chung said she had not yet completed that analysis, but the hypothesis is that the treatment is unlikely to lead to any improvement. “When you take out the severely impaired ears, you can see a greater [treatment] effect, so it does suggest that it doesn’t do anything for those ears,” Dr. Chung said during the Q&A session following her talk.

She was also asked why the treatment period was 6 weeks, rather than 6 months – a period of treatment that has shown a better effect on long-term hearing and developmental outcomes than 6 weeks of treatment in symptomatic patients. Dr. Chung replied that she wasn’t involved in the study design, but said that at her center, the 6-month regimen is not standard.

There were two key weaknesses in the study. One was the small sample size, and the other was its nonrandomized nature, which could have led to bias in the treated versus untreated group. “Although we don’t see any baseline differences between the groups, we have to be wary in analyses. Unfortunately, an RCT proved impossible in our setting. The CONCERT Trial started as randomized but this was amended to nonrandomized, as both parents and pediatricians had a clear preference for treatment,” said Dr. Chung.

The study could provide useful information about the timing of oral antiviral medication, according to Vana Spoulou, MD, who moderated the session where the research was presented. “The earliest you can give it is best, but sometimes it’s not easy to get them diagnosed immediately after birth. What they showed us is that even giving it so late, there was some improvement,” Dr. Spoulou said in an interview.

Dr. Spoulou isn’t ready to change practice based on the results, because she noted that some other studies have shown no benefit of treatment at 3 months. “But this was a hint that maybe even in these later diagnosed cases there could be some benefit,” she said.

Dr. Chung and Dr. Spoulou have no relevant financial disclosures.

Infants with isolated sensorineural hearing loss as a result of congenital cytomegalovirus (cCMV) infection may benefit from treatment with valganciclovir, according to results from the CONCERT nonrandomized trial.

Subjects were found through the Newborn Hearing Screening program, using dried blood spot screening to confirm cCMV Infection. As a result of 6 weeks of therapy, more patients in the treatment group had improvements in hearing at age 20 months, and fewer had deterioration compared with untreated controls.

There is a general consensus that symptomatic cCMV should be treated with valganciclovir for 6 weeks or 6 months, but treatment of patients with only hearing loss is still under debate. The average age of participants was 8 weeks.

The study was presented by Pui Khi Chung, MD, a clinical microbiologist at the Leiden University Medical Center, the Netherlands, at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Out of 1,377 NHS-referred infants, 59 were diagnosed with cCMV (4.3%), and 35 were included in the study. Twenty-five patients received 6 weeks of valganciclovir, while 10 patients received placebo. The control group was expanded to 12 when two additional subjects were identified retrospectively and were successfully followed up at 20 months. Subjects in the treatment group were an average of 8 weeks old when treatment began. Both groups had similar neurodevelopmental outcomes at 20 months, as measured by the Bayley Scales of Infant and Toddler Development (BSID-III) and the Child Development Inventory (CDI). There were no serious adverse events associated with treatment.

To measure efficacy, the researchers used a random intercept, random slope model that accounted for repeated measurements. The differences in slopes for analyses of the best ear were significantly different between the treatment and control groups (estimated difference in slopes, –0.93; P = .0071). Further analyses of total hearing found that improvement was more common in the treatment group, and deterioration/no change was more common in the nontreatment group (P = .044). In another analysis that excluded the most profoundly impaired ears (> 70 db hearing loss), none in the control group experienced improvement and almost half deteriorated. In the treatment group, most were unchanged and a small number improved, with almost none deteriorating (P = .006).

Asked whether the treatment has any effect on the most profoundly impaired ears, Dr. Chung said she had not yet completed that analysis, but the hypothesis is that the treatment is unlikely to lead to any improvement. “When you take out the severely impaired ears, you can see a greater [treatment] effect, so it does suggest that it doesn’t do anything for those ears,” Dr. Chung said during the Q&A session following her talk.

She was also asked why the treatment period was 6 weeks, rather than 6 months – a period of treatment that has shown a better effect on long-term hearing and developmental outcomes than 6 weeks of treatment in symptomatic patients. Dr. Chung replied that she wasn’t involved in the study design, but said that at her center, the 6-month regimen is not standard.

There were two key weaknesses in the study. One was the small sample size, and the other was its nonrandomized nature, which could have led to bias in the treated versus untreated group. “Although we don’t see any baseline differences between the groups, we have to be wary in analyses. Unfortunately, an RCT proved impossible in our setting. The CONCERT Trial started as randomized but this was amended to nonrandomized, as both parents and pediatricians had a clear preference for treatment,” said Dr. Chung.

The study could provide useful information about the timing of oral antiviral medication, according to Vana Spoulou, MD, who moderated the session where the research was presented. “The earliest you can give it is best, but sometimes it’s not easy to get them diagnosed immediately after birth. What they showed us is that even giving it so late, there was some improvement,” Dr. Spoulou said in an interview.

Dr. Spoulou isn’t ready to change practice based on the results, because she noted that some other studies have shown no benefit of treatment at 3 months. “But this was a hint that maybe even in these later diagnosed cases there could be some benefit,” she said.

Dr. Chung and Dr. Spoulou have no relevant financial disclosures.

Infants with isolated sensorineural hearing loss as a result of congenital cytomegalovirus (cCMV) infection may benefit from treatment with valganciclovir, according to results from the CONCERT nonrandomized trial.

Subjects were found through the Newborn Hearing Screening program, using dried blood spot screening to confirm cCMV Infection. As a result of 6 weeks of therapy, more patients in the treatment group had improvements in hearing at age 20 months, and fewer had deterioration compared with untreated controls.

There is a general consensus that symptomatic cCMV should be treated with valganciclovir for 6 weeks or 6 months, but treatment of patients with only hearing loss is still under debate. The average age of participants was 8 weeks.

The study was presented by Pui Khi Chung, MD, a clinical microbiologist at the Leiden University Medical Center, the Netherlands, at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

Out of 1,377 NHS-referred infants, 59 were diagnosed with cCMV (4.3%), and 35 were included in the study. Twenty-five patients received 6 weeks of valganciclovir, while 10 patients received placebo. The control group was expanded to 12 when two additional subjects were identified retrospectively and were successfully followed up at 20 months. Subjects in the treatment group were an average of 8 weeks old when treatment began. Both groups had similar neurodevelopmental outcomes at 20 months, as measured by the Bayley Scales of Infant and Toddler Development (BSID-III) and the Child Development Inventory (CDI). There were no serious adverse events associated with treatment.

To measure efficacy, the researchers used a random intercept, random slope model that accounted for repeated measurements. The differences in slopes for analyses of the best ear were significantly different between the treatment and control groups (estimated difference in slopes, –0.93; P = .0071). Further analyses of total hearing found that improvement was more common in the treatment group, and deterioration/no change was more common in the nontreatment group (P = .044). In another analysis that excluded the most profoundly impaired ears (> 70 db hearing loss), none in the control group experienced improvement and almost half deteriorated. In the treatment group, most were unchanged and a small number improved, with almost none deteriorating (P = .006).

Asked whether the treatment has any effect on the most profoundly impaired ears, Dr. Chung said she had not yet completed that analysis, but the hypothesis is that the treatment is unlikely to lead to any improvement. “When you take out the severely impaired ears, you can see a greater [treatment] effect, so it does suggest that it doesn’t do anything for those ears,” Dr. Chung said during the Q&A session following her talk.

She was also asked why the treatment period was 6 weeks, rather than 6 months – a period of treatment that has shown a better effect on long-term hearing and developmental outcomes than 6 weeks of treatment in symptomatic patients. Dr. Chung replied that she wasn’t involved in the study design, but said that at her center, the 6-month regimen is not standard.

There were two key weaknesses in the study. One was the small sample size, and the other was its nonrandomized nature, which could have led to bias in the treated versus untreated group. “Although we don’t see any baseline differences between the groups, we have to be wary in analyses. Unfortunately, an RCT proved impossible in our setting. The CONCERT Trial started as randomized but this was amended to nonrandomized, as both parents and pediatricians had a clear preference for treatment,” said Dr. Chung.

The study could provide useful information about the timing of oral antiviral medication, according to Vana Spoulou, MD, who moderated the session where the research was presented. “The earliest you can give it is best, but sometimes it’s not easy to get them diagnosed immediately after birth. What they showed us is that even giving it so late, there was some improvement,” Dr. Spoulou said in an interview.

Dr. Spoulou isn’t ready to change practice based on the results, because she noted that some other studies have shown no benefit of treatment at 3 months. “But this was a hint that maybe even in these later diagnosed cases there could be some benefit,” she said.

Dr. Chung and Dr. Spoulou have no relevant financial disclosures.

Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.

Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.

Data from a small retrospective study suggest that venetoclax-based regimens may have activity against relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) in children and young adults.

Among seven patients with T-ALL treated with venetoclax (Venclexta) in combination with chemotherapy, four had complete remissions and one had a CR with incomplete recovery of blood counts (CRi), and all four patients had undetectable minimal residual disease (MRD), reported pediatric hematology/oncology fellow Amber Gibson, MD, and colleagues from the University of Texas MD Anderson Cancer Center Children’s Cancer Hospital in Houston.

“This single-institution retrospective review found that venetoclax was safe and well tolerated in combination chemotherapy regimens, thrombocytopenia and neutropenia were the most common toxicities identified, [and] venetoclax should be considered for patients with refractory T-cell ALL and investigated as up-front therapy for this patient population,” they wrote in the abstract accompanying a poster presentation at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Children with relapsed T-ALL and T-lymphoblastic lymphoma (T-LL) have a dismal prognosis, with a 3-year event-free survival rate less than 10%, according to the researchers.

To see whether venetoclax, an inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2), could improve outcomes for children with ALL, the investigators conducted a retrospective chart review of the safety and efficacy of venetoclax in young patients with relapsed/refractory ALL/LL who received the drug at their center.

They identified 10 patients aged 6-21 years (median, 18), 5 of whom had T-ALL (1 with early T-cell precursor ALL), 2 with T-LL, and 3 with B-lineage ALL (B-ALL).

The median number of prior lines of therapy was 3.5. Three of the 10 patients had received hematopoietic stem cell transplants, and the 3 patients with B-ALL had all received prior CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. One of these patients received a dual CD19/CD22 CAR T product, one received CD19-directed blinotumumab.

There were no new safety signals with venetoclax, no treatment-related deaths, and no deaths within 30 days of starting venetoclax.

All 10 patients had grade 4 thrombocytopenias, 6 had grade 4 neutropenia, 3 had grade 4 febrile neutropenia, 2 had grade 4 anemia, and 1 each had grade 4 sepsis, pneumonia, or coagulopathy.

As noted, there were three CRs and one CRi, all in patients with T-ALL. All four of these patients were MRD negative by flow cytometry at a median of 22 days. The median duration of response was 17.4 months (range, 2-18 months).

At the most recent follow-up five patients were still alive, three without disease, one was still undergoing treatment, and one was alive following an allogeneic HSCT.
 

Early studies

Shilpa Shahani, MD, a pediatric oncologist and assistant clinical professor of pediatrics at City of Hope in Duarte, Calif., who was not involved in the study, said that there are early studies exploring the use of venetoclax in infants with ALL.

“Venetoclax is a BCL-2 inhibitor that is pretty well tolerated, but you can also have cytopenias with it,” she said.

She noted that it is not typically used in the frontline setting in pediatric populations, but may be considered for patients with difficult-to-treat disease or for whom the relatively good toxicity profile might be appropriate.

The MD Anderson investigators did not report a funding source. The authors and Dr. Shahani reported no relevant conflicts of interest.