Clinician Reviews

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

Isotretinoin use contributed to abnormal lipid lab values in pediatric patients, but no secondary effects were observed, results from a single-center retrospective study demonstrated.

“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”

To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.

Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.

Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.

“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”

She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”

In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”

The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.

[email protected]

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.

The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.

According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.

“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”

Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.

“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.

The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.

Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.

“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”

The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.

“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”

Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.

“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”

Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.

“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”

Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”

To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.

Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”

As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.

To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.

For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.

“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.

The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

People whose immune systems are compromised by therapy or disease may benefit from additional doses of vaccines against SARS-CoV-2, researchers say.

In a study involving 101 people with solid-organ transplants, there was a significant boost in antibodies after the patients received third doses of the Pfizer vaccine, said Nassim Kamar, MD, PhD, professor of nephrology at Toulouse University Hospital, France.

None of the transplant patients had antibodies against the virus before their first dose of the vaccine, and only 4% produced antibodies after the first dose. That proportion rose to 40% after the second dose and to 68% after the third dose.

The effect is so strong that Dr. Kamar and colleagues at Toulouse University Hospital routinely administer three doses of mRNA vaccines to patients with solid-organ transplant without testing them for antibodies.

“When we observed that the second dose was not sufficient to have an immune response, the Francophone Society of Transplantation asked the National Health Authority to allow the third dose,” he told this news organization.

That agency on April 11 approved third doses of mRNA vaccines not only for people with solid-organ transplants but also for those with recent bone marrow transplants, those undergoing dialysis, and those with autoimmune diseases who were receiving strong immunosuppressive treatment, such as anti-CD20 or antimetabolites. Contrary to their procedure for people with solid-organ transplants, clinicians at Toulouse University Hospital test these patients for antibodies and administer third doses of vaccine only to those who test negative or have very low titers.

The researchers’ findings, published on June 23 as a letter to the editor of The New England Journal of Medicine, come as other researchers document more and more categories of patients whose responses to the vaccines typically fall short.

A study at the University of Pittsburgh that was published as a preprint on MedRxiv compared people with various health conditions to healthy health care workers. People with HIV who were taking antivirals against that virus responded almost as well as did the health care workers, said John Mellors, MD, chief of infectious diseases at the university. But people whose immune systems were compromised for other reasons fared less well.

“The areas of concern are hematological malignancy and solid-organ transplants, with the most nonresponsive groups being those who have had lung transplantation,” he said in an interview.

For patients with liver disease, mixed news came from the International Liver Congress (ILC) 2021 annual meeting.

In a study involving patients with liver disease who had received the Pfizer vaccine at Hadassah University Medical Center in Jerusalem, antibody titers were lower in patients who had received liver transplants or who had advanced liver fibrosis, as reported by this news organization.

A multicenter study in China that was presented at the ILC meeting and that was also published in the Journal of Hepatology, provided a more optimistic picture. Among patients with nonalcoholic fatty liver disease who were immunized against SARS-CoV-2 with the Sinopharm vaccine, 95.5% had neutralizing antibodies; the median neutralizing antibody titer was 32.

In the Toulouse University Hospital study, for the 40 patients who were seropositive after the second dose, antibody titers increased from 36 before the third dose to 2,676 a month after the third dose, a statistically significant result (P < .001).

For patients whose immune systems are compromised for reasons other than having received a transplant, clinicians at Toulouse University Hospital use a titer of 14 as the threshold below which they administer a third dose of mRNA vaccines. But Dr. Kamar acknowledged that the threshold is arbitrary and that the assays for antibodies with different vaccines in different populations can’t be compared head to head.

“We can’t tell you simply on the basis of the amount of antibody in your laboratory report how protected you are,” agreed William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., who is a spokesperson for the Infectious Diseases Society of America.

Not enough research has been done to establish that relationship, and results vary from one laboratory to another, he said.

That doesn’t mean that antibody tests don’t help, Dr. Schaffner said. On the basis of views of other experts he has consulted, Dr. Schaffner recommends that people who are immunocompromised undergo an antibody test. If the test is positive – meaning they have some antibodies to SARS-CoV-2, however low the titers – patients can take fewer precautions than before they were vaccinated.

But they should still be more cautious than people with healthy immune systems, he said. “Would I be going to large indoor gatherings without a mask? No. Would I be outside without a mask? Yes. Would I gather with three other people who are vaccinated to play a game of bridge? Yes. You have to titrate things a little and use some common sense,” he added.

If the results are negative, such patients may still be protected. Much research remains to be done on T-cell immunity, a second line of defense against the virus. And the current assays often produce false negative results. But to be on the safe side, people with this result should assume that their vaccine is not protecting them, Dr. Schaffner said.

That suggestion contradicts the Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of SARS-CoV-2 vaccination.

The studies so far suggest that vaccines are safe for people whose immune systems are compromised, Dr. Schaffner and Dr. Kamar agreed. Dr. Kamar is aware of only two case reports of transplant patients rejecting their transplants after vaccination. One of these was his own patient, and the rejection occurred after her second dose. She has not needed dialysis, although her kidney function was impaired.

But the FDA has not approved additional doses of SARS-CoV-2 vaccine to treat patients who are immunocompromised, and Dr. Kamar has not heard of any other national regulatory agencies that have.

In the United States, it may be difficult for anyone to obtain a third dose of vaccine outside of a clinical trial, Dr. Schaffner said, because vaccinators are likely to check databases and deny vaccination to anyone who has already received the recommended number.

Dr. Kamar, Dr. Mellors, and Dr. Schaffner have disclosed no relevant financial relationships.

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

Exposure to antibiotics appears to be associated with the development of colon cancer, particularly in younger people, and could be contributing to the increase in early-onset colorectal cancer (CRC) that is being documented, say U.K. researchers.

The team conducted a nested case-control study using data from primary care in Scotland, which involved almost 8,000 cases of CRC and over 30,000 healthy controls.

The analysis suggests that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer (but not rectal) by 49%.

“To our knowledge, this is the first study to link antibiotic use with the growing risk of early onset colon cancer, a disease which has been increasing at a rate of at least 3% per year over the last two decades,” said study presenter Sarah Perrott, a medical student at the University of Aberdeen, Scotland.

“Junk food, sugary drinks, obesity, and alcohol are likely to have played a part in that rise, but our data stress the importance of avoiding unnecessary antibiotics, especially in children and young adults,” Ms. Perrott said in a statement.

“We now want to find out if there is a link between antibiotic use and changes in the microbiome which can make the colon more susceptible to cancer, especially in younger people,” added senior author Leslie Samuel, MD, consultant oncologist at Aberdeen Royal Infirmary.

“It’s a complex situation, as we know that the microbiome can quickly revert to its previous state, even when the bowel has been cleared out for a diagnostic procedure,” Dr. Samuel continued.

The research was presented on July 2 at the European Society for Medical Oncology Congress 2021.

Commenting for ESMO, Alberto Sobrero, MD, PhD, Medical Oncology Unit, Ospedale San Martino, Genoa, Italy, said that younger patients with colon cancer typically have a worse prognosis than older people because they are generally diagnosed later.

“Physicians are less likely to investigate a patient with abdominal discomfort for colon cancer if they are in their 30s than if they are in their 70s, and younger patients are not eligible for bowel cancer screening,” he explained.

However, Dr. Sobrero believes it is “too early to say if excessive use of antibiotics could be a causative factor, and we need to understand more about the possible role of the microbiome in bowel cancer before we consider the impact of antibiotics on the intestinal flora.”

The results, nevertheless, “remind us that antibiotics should not be given unless they are really needed, and we cannot exclude the possibility that unnecessary use of antibiotics may be exposing people to an increased risk of cancer,” he concluded.

Similar comments were made by Thomas Seufferlein, MD, department of internal medicine, Ulm University, Germany, who discussed the findings.

He agreed with the authors “that careful use of antibiotics is sensible and paramount” but added that more studies are needed on this suggestion of a link between antibiotic use and the observed increase in early CRC.
 

Study details

Previous studies have demonstrated that, in older adults, significant alterations in the structure and diversity of the gut microbiome induced by antibiotic therapy influence the development of colorectal cancer.

However, Ms. Perrott said that the impact of antibiotic use on early onset colorectal cancer has not been investigated.

The researchers therefore conducted a nested case-control study of primary care records to identify colorectal cancer cases diagnosed in Scotland between 1999 and 2011.

Patients were divided into those diagnosed before 50 years of age and those diagnosed at 50 years and older and matched with up to five healthy controls.

The study included 7,903 CRC cases, of which 5,281 were colon cancer and 2,622 rectal cancer, alongside 30,418 controls.

Among the CRC patients, 445 (5.6%) were under 50 years of age at diagnosis.

The team also analyzed antibiotic use history. Prescriptions for oral antibiotics, stratified by drug class and by anaerobic/nonanaerobic effect, were extracted, and the total antibiotic exposure period was calculated and categorized as 0, 1-15, 16-60, and >60 days.

Overall, 45% of the patients were prescribed antibiotics. Any antibiotic use was associated with a significantly increased risk of colon cancer, but this was most pronounced in patients aged less than 50 years at diagnosis.

Specifically, any antibiotic use was associated with an adjusted odds ratio of colon cancer of 1.49 (P = .018) in patients aged less than 50 years versus 1.09 (P = .029) in those aged 50 years and over.

In younger patients, the largest association between antibiotic use and colon cancer was seen in patients with a total antibiotic exposure of 1-15 days (at an adjusted odds ratio of 1.55), falling to 1.46 with 16-60 days of exposure, and no association for >60 days exposure.

No such relationship was seen in patients with colon cancer aged 50 years and over at diagnosis.

There was also no significant relationship between any antibiotic use and the occurrence of rectal cancer, at an adjusted odds ratio of 1.17 (P = .493) in those aged under 50 years at diagnosis and 1.07 (P = .698) in older patients.

The study was supported by Cancer Research UK. Ms. Perrott, Dr. Sobrero, and Dr. Samuels declared having no conflicts of interest. Dr. Seufferlien has reported relationships with Amgen, Bayer, Merck, Sanofi, Celgene, Shire, Roche, Falk Foundation, AstraZeneca, Lilly, Merck-Serono, Servier, Pierre Fabre, Cantargia, and Boehringer Ingelheim.

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

Exposure to antibiotics appears to be associated with the development of colon cancer, particularly in younger people, and could be contributing to the increase in early-onset colorectal cancer (CRC) that is being documented, say U.K. researchers.

The team conducted a nested case-control study using data from primary care in Scotland, which involved almost 8,000 cases of CRC and over 30,000 healthy controls.

The analysis suggests that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer (but not rectal) by 49%.

“To our knowledge, this is the first study to link antibiotic use with the growing risk of early onset colon cancer, a disease which has been increasing at a rate of at least 3% per year over the last two decades,” said study presenter Sarah Perrott, a medical student at the University of Aberdeen, Scotland.

“Junk food, sugary drinks, obesity, and alcohol are likely to have played a part in that rise, but our data stress the importance of avoiding unnecessary antibiotics, especially in children and young adults,” Ms. Perrott said in a statement.

“We now want to find out if there is a link between antibiotic use and changes in the microbiome which can make the colon more susceptible to cancer, especially in younger people,” added senior author Leslie Samuel, MD, consultant oncologist at Aberdeen Royal Infirmary.

“It’s a complex situation, as we know that the microbiome can quickly revert to its previous state, even when the bowel has been cleared out for a diagnostic procedure,” Dr. Samuel continued.

The research was presented on July 2 at the European Society for Medical Oncology Congress 2021.

Commenting for ESMO, Alberto Sobrero, MD, PhD, Medical Oncology Unit, Ospedale San Martino, Genoa, Italy, said that younger patients with colon cancer typically have a worse prognosis than older people because they are generally diagnosed later.

“Physicians are less likely to investigate a patient with abdominal discomfort for colon cancer if they are in their 30s than if they are in their 70s, and younger patients are not eligible for bowel cancer screening,” he explained.

However, Dr. Sobrero believes it is “too early to say if excessive use of antibiotics could be a causative factor, and we need to understand more about the possible role of the microbiome in bowel cancer before we consider the impact of antibiotics on the intestinal flora.”

The results, nevertheless, “remind us that antibiotics should not be given unless they are really needed, and we cannot exclude the possibility that unnecessary use of antibiotics may be exposing people to an increased risk of cancer,” he concluded.

Similar comments were made by Thomas Seufferlein, MD, department of internal medicine, Ulm University, Germany, who discussed the findings.

He agreed with the authors “that careful use of antibiotics is sensible and paramount” but added that more studies are needed on this suggestion of a link between antibiotic use and the observed increase in early CRC.
 

Study details

Previous studies have demonstrated that, in older adults, significant alterations in the structure and diversity of the gut microbiome induced by antibiotic therapy influence the development of colorectal cancer.

However, Ms. Perrott said that the impact of antibiotic use on early onset colorectal cancer has not been investigated.

The researchers therefore conducted a nested case-control study of primary care records to identify colorectal cancer cases diagnosed in Scotland between 1999 and 2011.

Patients were divided into those diagnosed before 50 years of age and those diagnosed at 50 years and older and matched with up to five healthy controls.

The study included 7,903 CRC cases, of which 5,281 were colon cancer and 2,622 rectal cancer, alongside 30,418 controls.

Among the CRC patients, 445 (5.6%) were under 50 years of age at diagnosis.

The team also analyzed antibiotic use history. Prescriptions for oral antibiotics, stratified by drug class and by anaerobic/nonanaerobic effect, were extracted, and the total antibiotic exposure period was calculated and categorized as 0, 1-15, 16-60, and >60 days.

Overall, 45% of the patients were prescribed antibiotics. Any antibiotic use was associated with a significantly increased risk of colon cancer, but this was most pronounced in patients aged less than 50 years at diagnosis.

Specifically, any antibiotic use was associated with an adjusted odds ratio of colon cancer of 1.49 (P = .018) in patients aged less than 50 years versus 1.09 (P = .029) in those aged 50 years and over.

In younger patients, the largest association between antibiotic use and colon cancer was seen in patients with a total antibiotic exposure of 1-15 days (at an adjusted odds ratio of 1.55), falling to 1.46 with 16-60 days of exposure, and no association for >60 days exposure.

No such relationship was seen in patients with colon cancer aged 50 years and over at diagnosis.

There was also no significant relationship between any antibiotic use and the occurrence of rectal cancer, at an adjusted odds ratio of 1.17 (P = .493) in those aged under 50 years at diagnosis and 1.07 (P = .698) in older patients.

The study was supported by Cancer Research UK. Ms. Perrott, Dr. Sobrero, and Dr. Samuels declared having no conflicts of interest. Dr. Seufferlien has reported relationships with Amgen, Bayer, Merck, Sanofi, Celgene, Shire, Roche, Falk Foundation, AstraZeneca, Lilly, Merck-Serono, Servier, Pierre Fabre, Cantargia, and Boehringer Ingelheim.

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

Exposure to antibiotics appears to be associated with the development of colon cancer, particularly in younger people, and could be contributing to the increase in early-onset colorectal cancer (CRC) that is being documented, say U.K. researchers.

The team conducted a nested case-control study using data from primary care in Scotland, which involved almost 8,000 cases of CRC and over 30,000 healthy controls.

The analysis suggests that a history of antibiotic use among individuals younger than 50 appeared to increase the risk of developing colon cancer (but not rectal) by 49%.

“To our knowledge, this is the first study to link antibiotic use with the growing risk of early onset colon cancer, a disease which has been increasing at a rate of at least 3% per year over the last two decades,” said study presenter Sarah Perrott, a medical student at the University of Aberdeen, Scotland.

“Junk food, sugary drinks, obesity, and alcohol are likely to have played a part in that rise, but our data stress the importance of avoiding unnecessary antibiotics, especially in children and young adults,” Ms. Perrott said in a statement.

“We now want to find out if there is a link between antibiotic use and changes in the microbiome which can make the colon more susceptible to cancer, especially in younger people,” added senior author Leslie Samuel, MD, consultant oncologist at Aberdeen Royal Infirmary.

“It’s a complex situation, as we know that the microbiome can quickly revert to its previous state, even when the bowel has been cleared out for a diagnostic procedure,” Dr. Samuel continued.

The research was presented on July 2 at the European Society for Medical Oncology Congress 2021.

Commenting for ESMO, Alberto Sobrero, MD, PhD, Medical Oncology Unit, Ospedale San Martino, Genoa, Italy, said that younger patients with colon cancer typically have a worse prognosis than older people because they are generally diagnosed later.

“Physicians are less likely to investigate a patient with abdominal discomfort for colon cancer if they are in their 30s than if they are in their 70s, and younger patients are not eligible for bowel cancer screening,” he explained.

However, Dr. Sobrero believes it is “too early to say if excessive use of antibiotics could be a causative factor, and we need to understand more about the possible role of the microbiome in bowel cancer before we consider the impact of antibiotics on the intestinal flora.”

The results, nevertheless, “remind us that antibiotics should not be given unless they are really needed, and we cannot exclude the possibility that unnecessary use of antibiotics may be exposing people to an increased risk of cancer,” he concluded.

Similar comments were made by Thomas Seufferlein, MD, department of internal medicine, Ulm University, Germany, who discussed the findings.

He agreed with the authors “that careful use of antibiotics is sensible and paramount” but added that more studies are needed on this suggestion of a link between antibiotic use and the observed increase in early CRC.
 

Study details

Previous studies have demonstrated that, in older adults, significant alterations in the structure and diversity of the gut microbiome induced by antibiotic therapy influence the development of colorectal cancer.

However, Ms. Perrott said that the impact of antibiotic use on early onset colorectal cancer has not been investigated.

The researchers therefore conducted a nested case-control study of primary care records to identify colorectal cancer cases diagnosed in Scotland between 1999 and 2011.

Patients were divided into those diagnosed before 50 years of age and those diagnosed at 50 years and older and matched with up to five healthy controls.

The study included 7,903 CRC cases, of which 5,281 were colon cancer and 2,622 rectal cancer, alongside 30,418 controls.

Among the CRC patients, 445 (5.6%) were under 50 years of age at diagnosis.

The team also analyzed antibiotic use history. Prescriptions for oral antibiotics, stratified by drug class and by anaerobic/nonanaerobic effect, were extracted, and the total antibiotic exposure period was calculated and categorized as 0, 1-15, 16-60, and >60 days.

Overall, 45% of the patients were prescribed antibiotics. Any antibiotic use was associated with a significantly increased risk of colon cancer, but this was most pronounced in patients aged less than 50 years at diagnosis.

Specifically, any antibiotic use was associated with an adjusted odds ratio of colon cancer of 1.49 (P = .018) in patients aged less than 50 years versus 1.09 (P = .029) in those aged 50 years and over.

In younger patients, the largest association between antibiotic use and colon cancer was seen in patients with a total antibiotic exposure of 1-15 days (at an adjusted odds ratio of 1.55), falling to 1.46 with 16-60 days of exposure, and no association for >60 days exposure.

No such relationship was seen in patients with colon cancer aged 50 years and over at diagnosis.

There was also no significant relationship between any antibiotic use and the occurrence of rectal cancer, at an adjusted odds ratio of 1.17 (P = .493) in those aged under 50 years at diagnosis and 1.07 (P = .698) in older patients.

The study was supported by Cancer Research UK. Ms. Perrott, Dr. Sobrero, and Dr. Samuels declared having no conflicts of interest. Dr. Seufferlien has reported relationships with Amgen, Bayer, Merck, Sanofi, Celgene, Shire, Roche, Falk Foundation, AstraZeneca, Lilly, Merck-Serono, Servier, Pierre Fabre, Cantargia, and Boehringer Ingelheim.

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

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

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

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

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

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or fail to uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs – which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors – were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time: Beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, and University of Trieste, Italy, told this news organization.

But the current analysis was adjusted for about 80 variables “that in our interpretation may be main reasons for not introducing drugs and using them in the older patients,” he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an “intrinsic reason” not to abide by HFrEF medical therapy recommendations, said Dr. Stolfo, who presented the analysis at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but “the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs,” Dr. Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older – the average age was 76 – and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, “we could question the need to achieve full dose of an evidence-based drug, but we shouldn’t question the use of these drugs.”

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Dr. Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Dr. Stolfo said.

“We should provide to all patients the best strategy they can tolerate,” he said. “If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital.”

The analysis was supported by Boehringer Ingelheim. Dr. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

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

The U.S. Food and Drug Administration has declined to approve the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals, despite narrow endorsement in a 10-7 vote in favor of approval by one of its advisory panels in May.

According to the company, the FDA did not cite any clinical deficiencies related to the efficacy and safety data packages submitted as part of the biologics license application for teplizumab.

Rather, the sticking point appears to be a study in healthy volunteers that had been raised as an issue with Provention Bio in April.

That study was designed to compare the planned commercial product with the product originally manufactured for clinical trials, but the former was not pharmacologically comparable to the latter, the FDA said in its complete response letter, issued on July 2.

The company expects, later this quarter, to obtain data from a substudy in patients receiving 12 days of therapy in the ongoing PROTECT trial of newly diagnosed patients with type 1 diabetes, which it hopes will help alleviate the FDA’s concerns.

“Upon review of the results from this substudy, the company will determine whether to submit these data to the FDA for its review ... to support pharmacokinetic comparability or otherwise justify why pharmacokinetic comparability is not necessary,” it said in its statement.

The FDA’s complete response letter had also mentioned additional issues related to product quality that Provention believes it has or will be able to address in the short term.

Teplizumab delays type 1 diabetes onset by years

Phase 2 data showing that a 14-day teplizumab infusion delayed the onset of type 1 diabetes by 2 years in high-risk relatives of people with the condition were called “game-changing” when presented at the American Diabetes Association 2019 Scientific Sessions and simultaneously published in the New England Journal of Medicine. These were the data considered by the FDA advisory panel in May.

In response to the FDA decision, the type 1 diabetes research and advocacy organization JDRF said: “It is unfortunate that the FDA has not approved teplizumab at this time and instead has requested additional information from the sponsor. We look forward to Provention Bio addressing the issues outlined in the Complete Response Letter and working with the FDA to bring this option to market safely.”

Teplizumab is one of several potential disease-modifying therapies being studied for type 1 diabetes administered either soon after diagnosis or to asymptomatic individuals with high-risk autoantibodies.

“Disease-modifying therapies such as teplizumab will help address the unmet needs of people with type 1 diabetes and those at risk for developing the disease. In the meantime, our organization will continue to support the research of other disease-modifying therapies that put us on the critical pathway to preventing and ultimately curing type 1 diabetes,” JDRF said in a statement.

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

The U.S. Food and Drug Administration has declined to approve the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals, despite narrow endorsement in a 10-7 vote in favor of approval by one of its advisory panels in May.

According to the company, the FDA did not cite any clinical deficiencies related to the efficacy and safety data packages submitted as part of the biologics license application for teplizumab.

Rather, the sticking point appears to be a study in healthy volunteers that had been raised as an issue with Provention Bio in April.

That study was designed to compare the planned commercial product with the product originally manufactured for clinical trials, but the former was not pharmacologically comparable to the latter, the FDA said in its complete response letter, issued on July 2.

The company expects, later this quarter, to obtain data from a substudy in patients receiving 12 days of therapy in the ongoing PROTECT trial of newly diagnosed patients with type 1 diabetes, which it hopes will help alleviate the FDA’s concerns.

“Upon review of the results from this substudy, the company will determine whether to submit these data to the FDA for its review ... to support pharmacokinetic comparability or otherwise justify why pharmacokinetic comparability is not necessary,” it said in its statement.

The FDA’s complete response letter had also mentioned additional issues related to product quality that Provention believes it has or will be able to address in the short term.

Teplizumab delays type 1 diabetes onset by years

Phase 2 data showing that a 14-day teplizumab infusion delayed the onset of type 1 diabetes by 2 years in high-risk relatives of people with the condition were called “game-changing” when presented at the American Diabetes Association 2019 Scientific Sessions and simultaneously published in the New England Journal of Medicine. These were the data considered by the FDA advisory panel in May.

In response to the FDA decision, the type 1 diabetes research and advocacy organization JDRF said: “It is unfortunate that the FDA has not approved teplizumab at this time and instead has requested additional information from the sponsor. We look forward to Provention Bio addressing the issues outlined in the Complete Response Letter and working with the FDA to bring this option to market safely.”

Teplizumab is one of several potential disease-modifying therapies being studied for type 1 diabetes administered either soon after diagnosis or to asymptomatic individuals with high-risk autoantibodies.

“Disease-modifying therapies such as teplizumab will help address the unmet needs of people with type 1 diabetes and those at risk for developing the disease. In the meantime, our organization will continue to support the research of other disease-modifying therapies that put us on the critical pathway to preventing and ultimately curing type 1 diabetes,” JDRF said in a statement.

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

The U.S. Food and Drug Administration has declined to approve the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals, despite narrow endorsement in a 10-7 vote in favor of approval by one of its advisory panels in May.

According to the company, the FDA did not cite any clinical deficiencies related to the efficacy and safety data packages submitted as part of the biologics license application for teplizumab.

Rather, the sticking point appears to be a study in healthy volunteers that had been raised as an issue with Provention Bio in April.

That study was designed to compare the planned commercial product with the product originally manufactured for clinical trials, but the former was not pharmacologically comparable to the latter, the FDA said in its complete response letter, issued on July 2.

The company expects, later this quarter, to obtain data from a substudy in patients receiving 12 days of therapy in the ongoing PROTECT trial of newly diagnosed patients with type 1 diabetes, which it hopes will help alleviate the FDA’s concerns.

“Upon review of the results from this substudy, the company will determine whether to submit these data to the FDA for its review ... to support pharmacokinetic comparability or otherwise justify why pharmacokinetic comparability is not necessary,” it said in its statement.

The FDA’s complete response letter had also mentioned additional issues related to product quality that Provention believes it has or will be able to address in the short term.

Teplizumab delays type 1 diabetes onset by years

Phase 2 data showing that a 14-day teplizumab infusion delayed the onset of type 1 diabetes by 2 years in high-risk relatives of people with the condition were called “game-changing” when presented at the American Diabetes Association 2019 Scientific Sessions and simultaneously published in the New England Journal of Medicine. These were the data considered by the FDA advisory panel in May.

In response to the FDA decision, the type 1 diabetes research and advocacy organization JDRF said: “It is unfortunate that the FDA has not approved teplizumab at this time and instead has requested additional information from the sponsor. We look forward to Provention Bio addressing the issues outlined in the Complete Response Letter and working with the FDA to bring this option to market safely.”

Teplizumab is one of several potential disease-modifying therapies being studied for type 1 diabetes administered either soon after diagnosis or to asymptomatic individuals with high-risk autoantibodies.

“Disease-modifying therapies such as teplizumab will help address the unmet needs of people with type 1 diabetes and those at risk for developing the disease. In the meantime, our organization will continue to support the research of other disease-modifying therapies that put us on the critical pathway to preventing and ultimately curing type 1 diabetes,” JDRF said in a statement.

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