Effects of high bilirubin level in pregnancy in Crigler-Najjar syndrome type 2: An extremely rare but important clinical entity to recognize.

Crigler-Najjar is a rare genetic autosomal recessive disorder caused by deficiency of enzyme Uridine 5-Diphosphate Glucuronosyl Transferase (UDP-GT). We report the case of a 24-year-old female with two consecutive pregnancies with a high level of total bilirubin level of 15.1 mg/dl and a direct bilirubin level of 0.8 mg/dl during the first pregnancy. As she was diagnosed case of Crigler Najjar type 2, she was on phenobarbitone 60 mg daily. With careful monitoring, she continued with the same dose. We concluded that even with high bilirubin level (15.1 mg/dl) in pregnancy, no adverse effects to the baby and mother were seen.

Determinants of Short-term Mortality in Liver Cirrhosis with Acute Kidney Injury: A Prospective Observational Study.

Background: Acute kidney injury (AKI) occurs in 20-50% of patients with cirrhosis and is associated with a poor prognosis. The aim of the study is to identify the baseline factors affecting mortality in these patients at 30 and 90 days. Methods: We enrolled 117 patients with cirrhosis and AKI and followed them up prospectively. Results: Distribution of International club of ascites AKI stages was: 26 (22.03%) stage 1, 59 (50%) stage 2, and 33 (28%) stage 3. Mortalities at 30 and 90 days were 27 (22.8%) and 33 (27.9%) respectively. On multivariate analysis, variables affecting mortality at 30 days were serum creatinine level>2 mg% at 48 hours after AKI development (adjusted OR 7.93, P=0.02) and leukocytosis (total leucocyte count>11000/mm3 ) at admission (adjusted OR 6.54, P=0.002). Only leukocytosis at admission was a predictor of 90 days mortality (adjusted OR 4.76, P=0.01). Though not statistically significant, patients not responding to standard medical treatment had 3 times higher mortality at 30 days, while the maximum AKI stages (2 and 3) had eight times higher mortality at 90 days. Conclusion: In cirrhosis, AKI increases short-term mortality. High serum creatinine at 48 hours affects mortality at 30 days, while leukocytosis at baseline predicts mortality at 30 and 90 days. Progression to a higher AKI stage impacts prognosis.

"The Innate Tail": An Unusual Cause of Rectal Bleeding in an Adult Male.

Retrorectal cystic hamartomas or tailgut cysts are infrequent congenital lesions presenting as presacral masses originating from the embryonic hindgut. They are commonly diagnosed in middle-aged women. Physicians must have a high index of suspicion to diagnose this rare tumor. We report a case of retrorectal hamartoma in a 70-year-old male presenting as rectal bleeding instead of the usual compressive symptoms. The utility of imaging modalities and the paramount importance of histopathology has been described. The treatment modality is surgical excision to prevent the potential malignant transformation.

Hamartomas císticos retrorretais ou "tailgut cysts" sao lesóes congénitas pouco frequentes que se originam do intestino posterior embrionário e que se apresentam como massas pré-sagradas. São comumente diagnosticados em mulheres de meia-idade. Os médicos devem ter um elevado grau de suspeição para diagnosticar este tumor raro. Relatamos um caso de um hamartoma retrorretal num homem com 70 anos de idade que se apresentou com retorragias e não com os sintomas mais comuns de obstrução. A utilidade dos exames de imagem e a grande importância da histopatologia foi demonstrada neste caso. A modalidade terapêutica adoptada foi a excisão cirúrgica para prevenir uma transformação maligna potencial.

Is the Combination of Rectal Diclofenac and Intravenous Ringer Lactate Superior to Individual Therapy for Prophylaxis of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective, Open-Label, Single-Center Randomized Trial.

METHODS: This was single-center, open-label, randomized trial. Patients who were undergoing ERCP and who were at high risk for the development of PEP were selected for the study. Patients were randomized into 3 treatment groups: diclofenac suppository group, RL group, and a combination group. RESULTS: Eight of 57 patients (14.03%) in the diclofenac group, 9 of 57 patients (15.78%) in the RL group, and 6 of 57 patients (10.52%) in the combination group developed PEP. The incidence of PEP between the three groups was not statistically significant (P = 0.70). Serum amylase level of >252 U/L had 91.3% sensitivity and 92.6% specificity for the diagnosis of PEP. CONCLUSIONS: Post-ERCP pancreatitis is usually mild to moderate 95% times. Female sex, age younger than 50 years, a benign indication of ERCP, and low bilirubin levels have higher chances of PEP. A combination of rectal diclofenac and hydration with RL does not offer better protection for PEP, as compared with individual prophylaxis.

Effect of moderate aerobic exercises on symptoms of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a commonly encountered entity worldwide and is difficult to treat. Most of the treatment modalities have low-quality evidence for use, except for proton pump inhibitors. Aerobic exercise has been shown to improve the symptoms, but its direct effect on symptoms has never been studied. The objective was to study the effects of moderate aerobic exercise on symptoms of FD and to compare the effect of conventional treatment alone vs. exercise plus conventional treatment. METHODS: Out of 112 patients, 72 were randomly divided into controls (conventional treatment; n=36) and experimental (aerobic exercise for 30 min per session, 5 times a week for 6 weeks with conventional treatment; n=36) groups. Both the groups were assessed on day 1 and at the end of 6 weeks, using Glasgow Dyspepsia Severity Score (GDSS), Depression Anxiety Stress Scales-42 (DASS-42), and visual analogue scale (VAS). RESULTS: Pre-treatment GDSS, DASS-42, and VAS in the experimental group were significantly different as compared to the post-treatment scores (p=0.00019, p=0.0002, p=0.00019, respectively). Even in the control group, pre- and post-treatment GDSS, DASS-42, and VAS scores were significantly different (p=0.00019, p=0.0002, p=0.00019, respectively). However, on the head-to-head comparison of the 2 groups, scores at the end of 6 weeks were significantly different (p< 0.05), in favor of the experimental group. CONCLUSION: Aerobic exercise as an auxiliary therapy to conventional treatment has better outcomes in the functional well-being of dyspepsia.

Vedolizumab in Inflammatory Bowel Disease: West versus East.

BACKGROUND: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody, which binds to α4ß7 integrin on T lymphocytes, thus disturbing the interaction with mucosal vascular addressin cell adhesion molecule 1 on the intestinal endothelial cells to interfere with lymphocyte trafficking to the gut. SUMMARY: Vedolizumab is a safe and effective drug to induce and maintain clinical remission in patients with Crohn's disease (CD) and ulcerative colitis (UC) in both clinical trials and real-world data. Various guidelines recommend vedolizumab as a first- or second-line treatment regimen for steroid-dependent, steroid, or immunomodulator refractory cases of UC and CD; however, it is more effective in anti-TNF-naive patients. The first head-to-head trial (VARSITY trial) comparing the efficacy of vedolizumab to adalimumab has shown better clinical remission and mucosal healing with vedolizumab. KEY MESSAGES: In this review, we have discussed guidelines recommendation of vedolizumab use, as well as its safety data, use in special population, in presence of extraintestinal complications, therapeutic drug monitoring, data from Asian patients, along with other evolving concepts. Because of its excellent safety data and low immunogenicity, vedolizumab is an impressive option for patients with prior malignancy and less chance of reactivation of tuberculosis; however, cost remains an issue.

Thiopurine-induced Myelosuppression with Severe Sepsis in a Patient with Crohn's Disease: A Case Report.

Thiopurines by their glucocorticoid-sparing property help in maintaining remission for patients with inflammatory bowel disease (IBD), when glucocorticoids are reduced and withdrawn. However, due to bone marrow suppression, it cannot be used in various conditions where it is indicated. A 17-year-old patient presented with pancytopenia with neutropenic sepsis and alopecia after 3 weeks of starting azathioprine for her underlying Crohn's disease. Thiopurine S-methyltransferase (TPMT;*2, *3A, *3C) analysis resulted in a wild-type genotype, whereas homozygous Nudix hydrolase 15 (NUDT 15 C415T) variant was positive. Azathioprine was stopped immediately, and she was started on broad-spectrum antibiotics that led to some clinical improvements initially, but later on, the patient developed intestinal obstruction along with postoperative complications leading to death. In this report, we highlight a case of serious hematological toxicity associated with azathioprine use in a patient with Crohn's disease with homozygous NUDT 15 variant, thus favoring the implementation of a pharmacogenomic approach before starting azathioprine, particularly in the Asian population. HOW TO CITE THIS ARTICLE: Debnath P, Nair S, Jain S, Udgirkar S, Contractor Q, Rathi P. Thiopurine-induced Myelosuppression with Severe Sepsis in a Patient with Crohn's Disease: A Case Report. Indian J Crit Care Med 2021;25(2):228-230. PRIOR PRESENTATION OF CASE REPORT AT PROFESSIONAL MEETING: The case was presented in abstract form at the American College of Gastroenterology Annual Scientific Meeting, held at San Antonio, TX, USA 2019. INFORMED CONSENT FOR PUBLICATION OF CASE DETAILS: Obtained from patient's relatives.

Complete hemogram: simple and cost-effective in staging and predicting outcome in acute pancreatitis.

BACKGROUND: An important goal in management of acute pancreatitis (AP) is early prediction and recognition of disease severity. Various predictive scoring systems are in clinical use with their own limitations and there is always a quest for simple, practical, quantifiable, dynamic and readily available markers for predicting disease severity and outcome. Complete hemogram is routinely ordered in all patients with AP. In recent years red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and platelet lymphocyte ratio (PLR) have been found to be independent predictors of prognosis in various benign and malignant conditions. This prospective study evaluated complete hemogram based markers in AP. MATERIAL AND METHODS: Complete hemogram analysis was done and NLR, LMR, PLR values were calculated. Development of organ failure, the need for intensive care unit (ICU) admission and interventions, development of complications (local/systemic) and 100-day mortality were assessed. RESULTS: In this study 160 subjects of AP were included. Complete hemogram analysis was performed within 24 h after admission. C­reactive protein, RDW, NLR, PLR and bedside index of severity in acute pancreatitis (BISAP) values were higher in severe AP than moderate AP group than mild AP group, while LMR values were decreased in the corresponding severe, moderate and mild AP groups (p < 0.001). The NLR performed best for prediction of ICU admission, organ failure, interventions and mortality with area under receiver operating curve (AUROC) were 0.943, 0.940, 0.902 and 0.910, respectively. CONCLUSION: Hemogram based markers are simple, objective, dynamic and readily available. They can be considered in addition to conventional multifactorial scoring systems for prediction of outcome and prognosis of AP.

A new model to predict response to direct-acting antiviral therapy in decompensated cirrhotics due to hepatitis C virus.

AIM: of the study: Decompensated hepatitis C virus (HCV) cirrhosis is a difficult to treat cohort, and there is no gold standard predictor of response to direct-acting antiviral (DAA) therapy. We conducted this study to look for factors responsible for improvement in post-therapy status, i.e. attainment of Child-Turcotte-Pugh (CTP) class A from B or C, and devise a new model to predict post-therapy response. MATERIAL: and methods: Prospective analysis of data from decompensated HCV cirrhotics was done and association of each parameter with patient outcomes at 36 weeks after treatment was assessed. RESULTS: 34 patients (54.8%) attained CTP class A after treatment. Factors that were independently associated with disease outcome included albumin (odds ratio [OR] = 4.84, 95% confidence interval [CI]: 1.43-20.15, p = 0.018), alanine transaminase (ALT) (OR = 1.02, 95% CI: 1-1.04, p = 0.049), bilirubin (OR = 0.41, 95% CI: 0.2-0.75, p = 0.007) and estimated glomerular filtration rate (eGFR) (OR = 1.03, 95% CI: 1.0-1.06, p = 0.045). On multivariate analysis, bilirubin was significantly associated with treatment outcome (OR = 0.28, 95% CI: 0.1-0.64, p = 0.006). A composite model was devised using demographic, biochemical, and clinical features, which has sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 67.86%, 79.41%, 73.08%, 75%, and 73.63% respectively in predicting response to therapy. Only 7.6% of patients with a Model for End-Stage Liver Disease (MELD) score > 15 and none of the patients with CTP class C met the primary end-point of our study. CONCLUSIONS: 55% of our cohort met the primary end-point at 36 weeks. Patients with CTP class C and a MELD score > 15 should be referred for liver transplantation followed by DAA therapy. Our model was good at predicting improvement in post-therapy liver function.

Esophageal Mucosal Bridge of Unknown Etiology Causing Dysphagia in an Elderly Female: Endoscopic Management and Literature Review.

Esophageal mucosal bridge is an elastic stretchable structure, connecting across the lumen, extending either obliquely or horizontally, more commonly seen in the mid or lower esophagus. It can be either congenital or secondary (acquired). Acquired ones are secondary to reflux esophagitis, corrosive esophageal injury, drug-induced esophagitis, radiation esophagitis, Crohn's disease, Mallory-Weiss syndrome, malignant tumors, and infections like candidiasis, HSV, CMV, or tuberculosis. We present a case of an elderly female, who presented with progressive dysphagia for 3 months, more commonly to solids without any history of anorexia or weight loss. No history of corrosive ingestion, radiation exposure, or prior history of any surgical or endoscopic intervention was present. Upper gastrointestinal endoscopy revealed esophageal mucosal bridge at 20 and 25 cm from incisors and mucosal tag. Endoscopic resection was carried out successfully with hot biopsy forceps and needle knife after prophylactic application of hemoclips at two ends of each bridge, without any adverse event. Esophageal mucosal bridge, though rarely reported, should be kept in the differential diagnosis of patients presenting with dysphagia. Endoscopic resection with hot biopsy forceps or needle knife seems to be effective.

Uma ponte mucosa esofágica é uma estrutura elástica que se estende obliquamente ou horizontal mente através do lúmen esofágico, sendo a sua posição mais comum no esófago médio ou distal. Pode ser congénita ou secundária (adquirida). Estas geralmente são secundárias a esofagite de refluxo, lesão corrosiva, medicamentosa, rádica, doença de Crohn, síndroma de Mallory-Weiss, tumores malignos ou por infeções como candidiase, HSV, CMV ou tuberculose. Apresentamos um caso de uma mulher idosa com disfagia progressiva com 3 meses duração, mais para sólidos, sem história de anorexia ou emagrecimento, sem história de ingestáo de caústicos, radioterapia, cirurgia ou qualquer intervenção endoscópica prévia. A endoscopia digestiva alta revelou uma ponte mucosa aos 20 e 25 cm dos incisivos e uma prega mucosa. Procedeu-se a resseção endoscópica com pinça de hot-biopsy e com needle-knife após colocação profilática de hemoclips em ambas as extremidades de cada ponte, com sucesso e sem qualquer efeito adverso. Apesar de raramente reportadas as pontes mucosa esofágicas devem ser consideradas no diagnóstico diferencial de doentes com disfagia. A resseção endoscópica com pinça de hot-biopsy ou needle-knife parece ser eficaz nestes casos.

COMBINED NS5A & NS5B NUCLEOTIDE INHIBITOR THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS C WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HEMODIALYSIS.

BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.