Indigo naturalis (Qing dai) for inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Indigo naturalis (Qing dai) is a traditional therapy reported to be useful in inflammatory bowel disease (IBD), especially for ulcerative colitis. We performed a systematic review of its efficacy and safety in IBD. METHODS: Electronic databases (Pubmed, Embase, and Scopus) were searched on 4th March 2023 to identify reports about the use of indigo naturalis in IBD. We extracted data with respect to clinical response, remission, endoscopic and histological responses, and adverse events with the use of indigo naturalis in IBD. Pooled clinical response rates and remission rates were calculated. The quality of studies was assessed using Joanna-Briggs tools. RESULTS: Nine studies reporting on 299 patients were included. The pooled clinical response rate was 0.796 (95 %CI, 0.7465-0.8379, I2=0), and the clinical remission rate in ulcerative colitis was 0.668 (0.488- 0.809, I2=85.2 %). The pooled relative risk of clinical response was higher in the indigo naturalis group as compared to placebo in the two randomized trials [3.82 (2.04; 7.14, I2=0)]. Except for one reversible pulmonary arterial hypertension case, most reported adverse effects were mild. The endoscopic and histological responses, when reported, suggested that indigo naturalis is effective for ulcerative colitis. The limitations of the systematic review included a small number of randomized studies, reports only from East Asia and a relatively small number of patients, especially for Crohn's disease. CONCLUSION: Indigo naturalis is effective in the treatment of ulcerative colitis. Future studies should evaluate the comparative efficacy with other drugs.

Controversies in the management of acute pancreatitis: An update.

This review summarized the current controversies in the management of acute pancreatitis (AP). The controversies in management range from issues involving fluid resuscitation, nutrition, the role of antibiotics and antifungals, which analgesic to use, role of anticoagulation and intervention for complications in AP. The interventions vary from percutaneous drainage, endoscopy or surgery. Active research and emerging data are helping to formulate better guidelines. The available evidence favors crystalloids, although the choice and type of fluid resuscitation is an area of dynamic research. The nutrition aspect does not have controversy as of now as early enteral feeding is preferred most often than not. The empirical use of antibiotics and antifungals are gray zones, and more data is needed for conclusive guidelines. The choice of analgesic is being studied, and the recommendations are still evolving. The position of using anticoagulation is still awaiting consensus. The role of intervention is well established, although the modality is constantly changing and favoring endoscopy or percutaneous drainage rather than surgery. It is evident that more multicenter randomized controlled trials are required for establishing the standard of care in these crucial management issues of AP to improve the morbidity and mortality worldwide.

Endoscopic Ultrasound-guided Trans-esophageal Transmural Drainage of Mediastinal Pseudocysts: A Case Series.

BACKGROUND AND AIMS: Mediastinal pseudocysts (MP) are rare, and surgery is the conventional treatment modality. However, in the last decade, excellent outcomes have been reported with endoscopic transpapillary drainage. Endoscopic ultrasound (EUS) guided trans-esophageal transmural drainage of MP is a minimally invasive and effective non-surgical treatment modality, but the experience is limited. We aimed to report our experience of EUS-guided transmural drainage in 10 patients with MP's. METHODS: A retrospective analysis of patients with pancreatic fluid collections treated with EUS-guided transmural drainage over the last ten years was completed to to identify patients with MP's. RESULTS: Ten patients (8 males, with a mean age of 34.9±9.17 years) with MP treated with EUS-guided transesophageal transmural drainage were identified. Nine patients with MP had concurrent chronic pancreatitis, and only one had MP following acute necrotizing pancreatitis. The mean size of MP was 5.70±1.64 cm, and nine patients (90%) had concurrent abdominal pseudocyst. EUS-guided transesophageal transmural drainage was technically successful in all ten patients. Transmural plastic stents were placed in 9 patients, whereas one patient underwent single-time complete aspiration of the MP. There were no immediate or delayed procedure-related complications. All ten patients had a successful outcome, with the mean resolution time being 2.80±0.79 weeks. There has been no recurrence of PFC or symptoms in nine (90%) successfully treated patients over a mean follow-up period of 43.3 months. CONCLUSIONS: EUS-guided trans-esophageal drainage of MP is safe with a high technical and clinical success rate.

Evidence-based approach to diagnosis and management of abdominal tuberculosis.

Abdominal tuberculosis is an ancient problem with modern nuances in diagnosis and management. The two major forms are tuberculous peritonitis and gastrointestinal tuberculosis (GITB), while the less frequent forms are esophageal, gastroduodenal, pancreatic, hepatic, gallbladder and biliary tuberculosis. The clinicians need to discriminate the disease from the close mimics: peritoneal carcinomatosis closely mimics peritoneal tuberculosis, while Crohn's disease closely mimics intestinal tuberculosis. Imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and occasionally positron emission tomography) guide the line of evaluation. Research in diagnostics (imaging and endoscopy) has helped in the better acquisition of tissue for histological and microbiological tests. Although point-of-care polymerase chain reaction-based tests (e.g. Xpert Mtb/Rif) may provide a quick diagnosis, these have low sensitivity. In such situations, ancillary investigations such as ascitic adenosine deaminase and histological clues (granulomas, caseating necrosis, ulcers lined by histiocytes) may provide some specificity to the diagnosis. A diagnostic trial of antitubercular therapy (ATT) may be considered if all diagnostic armamentaria fail to clinch the diagnosis, especially in TB-endemic regions. Objective evaluation with clear endpoints of response is mandatory in such situations. Early mucosal response (healing of ulcers at two months) and resolution of ascites are objective criteria for early response assessment and should be sought at two months. Biomarkers, especially fecal calprotectin for intestinal tuberculosis, have also shown promise. For most forms of abdominal tuberculosis, six months of ATT is sufficient. Sequelae of GITB may require endoscopic balloon dilatation for intestinal strictures or surgical intervention for recurrent intestinal obstruction, perforation or massive bleeding.

Randomized crossover trial of 'Roll-over' technique of abdominal paracentesis versus standard technique in suspected malignant ascites.

BACKGROUND: The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis (PC) varies from 40-70%. We hypothesized that rolling-over the patient before paracentesis might improve the cytological yield. RESEARCH DESIGN AND METHODS: This was a single center pilot study with a randomized cross-over design. We compared the cytological yield of fluid obtained by roll-over technique (ROG) with standard paracentesis (SPG) in suspected PC. In the ROG group, patients were rolled side-to-side thrice, and the paracentesis was done within 1 minute. Each patient served as their own control, and the outcome assessor (cytopathologist) was blinded. The primary objective was to compare the tumor cell positivity between SPG and ROG groups. RESULTS: Of 71 patients, 62 were analyzed. Of 53 patients with malignancy-related ascites, 39 had PC. Most of the tumor cells were adenocarcinoma (30, 94%) with one patient each having suspicious cytology and one having lymphoma. The sensitivity for diagnosis of PC was (31/39) 79.49% in SPG group and (32/39) 82.05% in ROG group (p = 1.00). The cellularity was similar between both the groups (good cellularity in 58% of SPG and 60% of ROG, p = 1.00). CONCLUSIONS: Rollover paracentesis did not improve the cytological yield of abdominal paracentesis. TRIAL REGISTRATION: CTRI/2020/06/025887 and NCT04232384.

Clinical presentation of COVID-19 in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND/AIMS: Coronavirus disease 2019 (COVID-19) is recognized to have variable clinical manifestations. The clinical presentation of patients with inflammatory bowel disease (IBD) having COVID-19 is unclear. METHODS: We identified articles reporting about the clinical presentation of COVID-19 in those with underlying IBD from PubMed and Embase. The studies, irrespective of design or language, were included. The overall pooled frequency of various symptoms was estimated. Joanna Briggs Institute Critical appraisal checklist was used to assess the quality of studies. RESULTS: Eleven studies, including 1,325 patients, were included in the pooled analysis. The pooled estimates for clinical presentation were; fever: 67.53% (95% confidence interval [CI], 45.38-83.88), cough: 59.58% (95% CI, 45.01-72.63), diarrhea: 27.26% (95% CI, 19.51-36.69), running nose: 27% (95% CI, 15.26-43.19) and dyspnea: 25.29% (95% CI, 18.52-33.52). The pooled prevalence rates for abdominal pain, nausea and vomiting were 13.08% (95% CI, 9.24-18.19), 10.08% (95% CI, 5.84-16.85) and 8.80% (95% CI, 4.43-16.70) per 100 population, respectively. CONCLUSIONS: The clinical presentation of COVID-19 in IBD patients is similar to the general population.

'Rollover' abdominal paracentesis versus standard technique: protocol of a crossover randomized comparative trial.

The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis in patients with malignant ascites is 40-70%. Tumor cells shed from the peritoneum settle preferentially in certain recesses of the peritoneum. We aim to compare the standard technique of abdominal paracentesis versus a rollover technique in a randomized crossover study to assess the cytological yield in patients suspected to have peritoneal carcinomatosis. Each patient will serve as their own control and the outcome assessor (cytopathologist) will be blinded to the method of paracentesis performed. The primary objective will be to compare the tumor cell positivity between the standard paracentesis group and the rollover group among enrolled patients. Clinical Trial registration: CTRI/2020/06/025887 and NCT04232384.

Lay abstract Existing methods of diagnosing cancer-related ascites are dependent on microscopic evaluation of fluid obtained from the ascites. However, this may not diagnose all such cases because the fluid may not contain many tumor cells. This may be due to the settling of tumor cells in certain inaccessible locations of the peritoneum (the lining of the abdominal cavity). This trial will look at whether rolling the patient from side to side could be helpful in increasing the chances of finding tumor cells in the ascites.

Hyperbaric oxygen therapy in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Translational data suggest a potential role of hyperbaric oxygen therapy (HBOT) in a subset of patients with inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis for the efficacy and safety of HBOT in IBD. METHODS: We searched Pubmed, Embase and CENTRAL to identify studies reporting the efficacy of HBOT in ulcerative colitis or Crohn's disease. We pooled the response rates for HBOT in ulcerative colitis and Crohn's disease separately. RESULTS: A total 18 studies were included in the systematic review and 16 in the analysis. The overall response rate of HBOT in ulcerative colitis was 83.24% (95% confidence interval: 61.90-93.82), while the response in Crohn's disease was 81.89 (76.72-86.11). The results of randomized trials for HBOT as adjuvant therapy in ulcerative colitis were conflicting. The complete healing of fistula in fistulizing Crohn's disease was noted 47.64% (22.05-74.54), while partial healing was noted in 34.29% (17.33-56.50%). Most of the adverse events were minor. CONCLUSION: Observational studies suggest benefit of use of HBOT in ulcerative colitis flares and Crohn's disease. However, adequately powered randomized trials are needed to draw a definite conclusion.

Antibiotics for induction and maintenance of remission in ulcerative colitis: systematic review and meta-analysis.

Objectives: To ascertain the role of antibiotics in induction and maintenance of remission in ulcerative colitis (UC)Methods: We searched electronic databases for keywords ulcerative colitis or inflammatory bowel disease and antibiotics or antimicrobials. We performed a meta-analysis of randomized trials comparing antibiotics with control/placebo for clinical response, need for second line therapy, colectomy, and adverse effects. Subgroup analysis to clarify the mode of administration, number of antibiotics or the setting of use (acute severe UC or active non-severe UC) were also performed.Results: Thirteen trials with 785 patients were included. The pooled odds ratio of achieving clinical response with antibiotics was 1.74 (95% CI, 1.17-2.58). No differences were noted in relapse rates, need for second line therapy, colectomy or, adverse effects with the use of antibiotics. Subgroup analysis showed no differences with use of single or combination of antibiotics. Analysis of trials only in the setting of acute severe colitis did not demonstrate any benefit.Conclusion: The use of oral antibiotics in the setting of non-severe active UC could have some benefit in clinical response. The use of antibiotics is not of benefit in acute severe colitis, but oral antibiotics need to be evaluated in adult patients.

Prevalence of polymorphisms in thiopurine metabolism and association with adverse outcomes: a South Asian region-specific systematic review and meta-analysis.

Background: Prevalence and impact of thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) minor allele frequencies in South Asian population is unclear.Methods: We searched PubMed and Embase with keywords-TPMT and NUDT15 combined with South Asian countries. We included studies reporting frequency of TPMT and NUDT15 polymorphisms. We estimated the pooled prevalence of TPMT and NUDT15 polymorphisms and their impact on pooled odds ratio of adverse events with thiopurines.Results: We included 26 studies in our analysis. The pooled prevalence of NUDT15 and TPMT polymorphisms was 16.5% (95% CI: 13.09-20.58) and 4.57% (95% CI: 3.66-5.68), respectively. In patients with adverse effects, the pooled prevalence of NUDT15 and TPMT polymorphism was 49.51% (95% C.I. 21.69-77.64) and 9.47% (95% C.I. 5.39-16.11), respectively. The odds ratio (OR) of adverse events with presence of TPMT polymorphisms was 3.65 (95% C.I., 1.43-9.28). The pooled OR for adverse events in presence of NUDT15 polymorphism was 12.63 (95% C.I., 3.68-43.26).Conclusion: NUDT15 were reported more frequently than the TPMT polymorphisms in South Asian population and were more frequently associated with adverse events. These findings may have implications for preemptive testing amongst South Asian population and immigrants prior to starting thiopurines.

Coronavirus disease (COVID-19) and the liver: a comprehensive systematic review and meta-analysis.

BACKGROUND: Liver function derangements have been reported in coronavirus disease (COVID-19), but reported rates are variable. METHODS: We searched PubMed and Embase with terms COVID and SARS-COV-2 from December 1, 2019 till April 5, 2020. We estimated overall prevalence, stratified prevalence based on severity, estimated risk ratio (RR), and estimated standardized mean difference (SMD) of liver function parameters in severe as compared to non-severe COVID. Random effect method utilizing inverse variance approach was used for pooling the data. RESULTS: In all, 128 studies were included. The most frequent abnormalities were hypoalbuminemia [61.27% (48.24-72.87)], elevations of gamma-glutamyl transferase (GGT) [27.94% (18.22-40.27)], alanine aminotransferase (ALT) [23.28% (19.92-27.01)], and aspartate aminotransferase (AST) [23.41% (18.84-28.70)]. Furthermore, the relative risk of these abnormalities was higher in the patients with severe COVID-19 when compared to non-severe disease [Hypoalbuminemia-2.65 (1.38-5.07); GGT-2.31 (1.6-3.33); ALT-1.76 (1.44-2.15); AST-2.30 (1.82-2.90)]. The SMD of hypoalbuminemia, GGT, ALT, and AST elevation in severe as compared to non-severe were - 1.05 (- 1.27 to - 0.83), 0.76 (0.40-1.12), 0.42 (0.27-0.56), and 0.69 (0.52-0.86), respectively. The pooled prevalence and RR of chronic liver disease as a comorbidity was 2.64% (1.73-4) and 1.69 (1.05-2.73) respectively. CONCLUSION: The most frequent abnormality in liver functions was hypoalbuminemia followed by derangements in gamma-glutamyl transferase and aminotransferases, and these abnormalities were more frequent in severe disease. The systematic review was, however, limited by heterogeneity in definitions of severity and liver function derangements. Graphical depiction of the summary of meta-analytic findings a) pooled prevalence of abnormalities b) Risk ratio of abnormality in severe versus non-severe COVID-19 c) standardized mean difference (SMD) between severe and non-severe group and d) pooled prevalence for parameters based on severity stratification for bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), albumin, globulin and acute hepatic injury (AHI) . Also estimates for overall/total liver disease (TLD) and chronic liver disease (CLD) amongst COVID-19 patients are depicted in a, b, d. For d) In addition to severity stratification, Overall (all studies for a particular estimate) and combined (only those studies which reported severity) estimates are provided.