Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. METHODS: Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. RESULTS: Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. CONCLUSION: Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

WITHDRAWN: Non-Anti-TNF Biologics as Salvage Therapy for Refractory Acute Severe Ulcerative Colitis, A Systematic Review

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Efficacy and safety of biologic therapy in microscopic colitis: systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC). METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs). RESULTS: A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases. CONCLUSION: Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy.

Quality measures in endoscopy: A systematic analysis of the overall scientific level of evidence and conflicts of interest.

Background and study aims Quality measures were established to develop standards to help assess quality of care, yet variation in endoscopy exists. We performed a systematic review to assess the overall quality of evidence cited in formulating quality measures in endoscopy. Methods A systematic search was performed on multiple databases from inception until November 15, 2020, to examine the quality measures proposed by all major societies. Quality measures were assessed for their level of quality evidence and categorized as category A (guideline-based), category B (observational studies) or category C (expert opinion). They were also examined for the type of measure (process, structure, outcome), the quality, measurability, review, existing conflicts of interest (COI), and patient participation of the quality measure. Results An aggregate total of 214 quality measures from nine societies (15 manuscripts) were included and analyzed. Of quality measures in endoscopy, 71.5 %, 23.8 %, and 4.7 % were based on low, moderate, and high quality of evidence, respectively. The proportion of high-quality evidence across societies was significantly different ( P  = 0.028). Of quality measures, 76 % were quantifiable, 18 % contained patient-centric outcomes, and 7 % reported outcome measures. None of the organizations reported on patient involvement or external review, six disclosed existing COI, and 40 % were published more than 5 years ago. Conclusions Quality measures are important to standardize clinical practice. Because over 70 % of quality measures in endoscopy are based on low-quality evidence, further studies are needed to improve the overall quality to effectively set a standard, reduce variation, and improve care in endoscopic practice.

Impact of Cirrhosis on Outcomes in Inflammatory Bowel Disease Hospitalizations.

BACKGROUND: Evidence regarding outcomes in inflammatory bowel disease (IBD) hospitalizations with coexisting cirrhosis is scant. We queried the National Inpatient Sample (NIS) database to evaluate the impact of cirrhosis on hospitalization characteristics and outcomes in patients with Crohn's disease and ulcerative colitis. METHODS: All admissions that listed IBD as a primary diagnosis by ICD-10-CM code (K50.X for Crohn's disease and K51.X for ulcerative colitis) in the NIS for 2016 and 2017 were included. Attributes of admissions with cirrhosis (K74.XX, 70.3, 78.81, and 71.7) were compared with noncirrhosis IBD admissions. The primary outcome was inpatient mortality. Length of stay and total hospital charges comprised secondary outcomes. RESULTS: A total weighted sample of 276,430 IBD admissions were identified, including 4615 with a concomitant diagnosis of cirrhosis. In a multivariate model, after adjusting for comorbidities, age, alimentary surgery during the admission and hospital type (teaching, urban nonteaching or rural), the presence of cirrhosis was associated with a higher inpatient mortality [odds ratio: 1.57; 95% confidence interval (CI): 1.16-2.15] and increased cost of admission (mean difference $11,651; 95% CI: 3830-19,472). No difference was noted in length of stay (difference: 0.44 d; 95% CI: -0.12-1.02) among these groups. Among admission diagnoses, infectious complications were the primary cause of death in 93.3% (95% CI: 87.1%-99.5%) of all inpatient mortality in the IBD with cirrhosis cohort as compared with 80.1% (95% CI: 77.6%-82.7%) of the mortality among IBD patients without cirrhosis ( P =0.01). CONCLUSIONS: This study demonstrates that the presence of cirrhosis has an independent negative impact on outcomes for hospitalized patients with IBD as reflected by increased in-hospital mortality and higher cost of admission. A majority of the mortality was attributable to infections.

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis.

BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC). METHODS: We searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). RESULTS: A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2 : 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2 : 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2 : 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2 : 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2 : 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2 : 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2 : 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2 : 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2 : 0%), respectively. Higher dose was associated with an increased frequency of AEs. CONCLUSIONS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.

Patient Perspective on Safety of Elective Gastrointestinal Endoscopy During the COVID-19 Pandemic.

BACKGROUND: Patients' perception regarding the risks of COVID-19 infection with gastrointestinal (GI) and the preventive measures taken in GI endoscopy units to mitigate infection risk remains unclear. We aimed to assess patients' perception regarding risks of COVID-19 with GI endoscopy and the changes in the endoscopy unit as a result of the ongoing pandemic. METHODS: Outpatients undergoing GI endoscopy at our institution were categorized into those scheduled to undergo GI endoscopy (preprocedure) and those who had recently undergone GI endoscopy during the pandemic (postprocedure). Two separate but similar survey instruments were designed. Patients were asked to respond on a 5-point Likert scale. Responses were stratified as "low," "neutral," and "high" for analysis. RESULTS: A total of 150 and 355 respondents completed the preprocedure and postprocedure surveys, with a combined response rate of 82.5%. Non-white ethnicity was associated with reporting a "high" level of concern for endoscopy related COVID-19 exposure in both the preprocedure (OR 4.09, 95% CI 1.54-10.82) and postprocedure cohorts (OR 2.11, 95% CI 1.04-4.29). 42% of patients in the preprocedure cohort and 11.8% in the postprocedure cohort reported their level of concern for COVID exposure as "high." Among the postprocedure cohort, 88% of the patients were likely to undergo repeat endoscopy during the pandemic if recommended. CONCLUSION: Patients are willing to undergo GI endoscopy during the COVID-19 pandemic. Non-white and older patients, and those undergoing screening examinations were more concerned with the GI endoscopy related COVID-19 transmission risk.

Severe hyperammonemia from intense skeletal muscle activity: A rare case report and literature review.

RATIONALE: Adult hyperammonemia is most often the result of hepatic dysfunction. Hyperammonemia in the setting of normal hepatic function is a much less common phenomenon and has usually been associated with medications and certain disease states. Here, we present an unusual case of severe hyperammonemia caused physiologically by intense muscle activity in a patient lacking any evidence of liver disease. PATIENT CONCERNS: A 36-year-old woman was brought to the emergency department for a suicide attempt after being found covered in Lysol and Clorox germicidal bleach. She was noted to be in a state of violent psychosis with extreme agitation and had to be sedated and intubated for airway protection. DIAGNOSIS AND INTERVENTIONS: Initial labs revealed hyperammonemia, lactic acidosis, and anion gap metabolic acidosis. Aminotransferases, bilirubin, and creatine kinase (CK) were normal. Renal function, prothrombin time, activated partial thromboplastin time, and international normalized ratio were also unremarkable and remained so at 24 hours. Ethyl alcohol, acetaminophen, salicylate, and valproic acid were all undetectable in blood. She received 2 doses of lactulose overnight, with a subsequent bowel movement. Next day, her mentation, serum ammonia level, and lactic acid level were back to normal, and she was extubated. Aminotransferases and CK levels were elevated but improved with supportive care. A detailed history and relevant biochemical investigations were unremarkable for any other etiology of hyperammonemia including the common inborn errors of metabolism (IEM). The combination of clinical findings of extreme skeletal muscle activity along with hyperammonemia and lactic acidosis, and subsequently rhabdomyolysis in the setting of unremarkable history and otherwise normal hepatic function strongly suggest the myokinetic origin of hyperammonemia in the patient. OUTCOME: The patient recovered well with supportive care and was discharged on day 5. LESSONS: This unique case illustrates the important role of skeletal muscle in the human metabolism of ammonia. In our discussion, we also elucidate the underlying pathophysiology, with the objective of improving clinician understanding of various differential diagnoses.

Coccidioidomycosis masquerading as malignancy.

Skeletal coccidioidomycosis is extremely rare and in the non-endemic areas, diagnosis is often delayed or missed resulting in extensive and unnecessary medical investigation for other diseases. The authors report a case of disseminated skeletal coccidioidomycosis in a previously healthy person living in a non-endemic area, who was initially thought to have a malignancy. Due to the presence of multiple expansile lytic bone lesions on x-rays and CT scan, an extensive investigation for malignancy was done. Diagnosis of coccidioidomycosis was made when H&E and Gomori's methenamine silver staining of a bone biopsy sample revealed multiple fungal spherules, which were confirmed to be Coccidioides immitis by culture and PCR. On questioning, the patient admitted to have spent 2 weeks in Arizona (an endemic area) few months ago. He was discharged home on long-term fluconazole. At 1 month clinical follow-up, a significant improvement in his lesions was noticed.

Voriconazole in newborns.

Voriconazole is a newer systemic antifungal agent effective against Candida and Aspergillus. There are few reports of its safe use in newborns. We report the first case series of safe Voriconazole use in critically ill newborns with cardiac disease along with several other cardiac drugs without any significant drug interaction or side-effect.

Play in orphanages.

OBJECTIVES: This paper attempts to validate the programme of structured play lasting 90 minutes a day, for use in orphanages, to check if it can be replicated in other orphanages, with similar results. METHODS: A 2-week workshop on the structured play scheme was conducted at the Missionaries of Charity Orphanage in Delhi, the venue of the original project. 15 MOC sisters from 6 centers attended the workshop. The authors selected the MOC orphanage at Chandigarh to track the benefits of the programme. The development quotient of all the residents between the ages of 6 months - 3 years was assessed by a pediatric-clinical-psychologist using the Development Assessment Scale for Indian Infants (DAS II) scale. A reassessment of all these children was done again 3 months after initiating the programme of structured play here. RESULTS: The mean motor and mental scores at the orphanage in Chandigarh before the start of the intervention were 57.9 and 58.2 respectively. Post intervention assessments showed a rise of 23 points in both the scores. CONCLUSION: The development of children in orphanages rises dramatically after initiating a programme of play. The pre-intervention development scores is similar to that in a pilot study and the benefits after play was also similar. The play programme can be easily replicated in other orphanages with similar results.

Poisoned child: emergency room management.

Poisoning is one of the commonest pediatric emergencies. Most of poisonings in children below 5 years of age, are accidental and fortunately trivial, related to their exploratory nature. However a poisoned child may present as an acute emergency with or without multisystem involvement. The initial phase of management focuses on support of airways, breathing and cardiac function (ABCD of Resuscitation). The second phase includes Evaluation and Detoxification phase. The Evaluation phase involves identification and severity of toxic exposure. Recognizing a Toxidrome (constellation of the signs and symptoms seen with the ingestion of a particular poison) is particularly very helpful when the child presents with an unknown poisoning. Detoxification should proceed simultaneously. The current literature suggests that activated charcoal is the mainstay of GI decontarmination. Whole bowel Irrigation is a new addition to the armamentarium of GI decontamination. At present antidotes are available for few toxins only so the management remains supportive for most poisons.

The clinical risk index of babies (CRIB) score in India.

OBJECTIVE: To assess the usefulness of clinical risk index of babies (CRIB score) in predicting neonatal mortality in extremely preterm neonates, compared to birth weight and gestation. METHODS: 97 preterm neonates with gestational age less than 31 weeks or birth weight less than or equal to 1500 g were enrolled for the prospective longitudinal study. Relevant neonatal data was recorded. Blood gas analysis results and the maximum and the minimum FiO2 required by babies in first 12 hours of life were noted. Mortality was taken as death while the baby was in nursery. The prediction of mortality by birth weight, gestational age and CRIB score was done using the Logistic model, and expressed as area under the ROC curve. RESULTS: The area under the ROC curve for birth weight, gestational age and CRIB score was almost the same, the areas being 0.829, 0.819 and 0.823 respectively. Hence CRIB score did not fare better than birth weight and gestational age in predicting neonatal mortality. CONCLUSION: The CRIB score did not improve on the ability of birth weight and gestational age to predict neonatal mortality in the study.