Evaluation of Plasma Amyloid Peptides Aß1-40 and Aß1-42 as Diagnostic Biomarker of Alzheimer's Disease, its Association with Different Grades of Clinical Severity and 18F-Fluorodeoxyglucose Positron Emission Tomography Z score in the Indian Population: A Case-Control Study.

BACKGROUND: We estimated plasma amyloid-peptides levels (Aß1-42 and Aß1-40) as diagnostic biomarker of Alzheimer's disease (AD) and evaluated its association with clinical severity and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) Z score of the different brain regions in the Indian population. PATIENTS AND METHODS: A case-control study was conducted. Diagnostic and statistical manual-IV, Dubois, and NIA-AA criteria were used for the diagnosis of AD. The plasma Aß1-42 and Aß1-40 concentration and 18F-FDG PET Z score were estimated for different brain regions. RESULTS: Forty-seven cognitive impairment patients (AD = 29, mild cognitive impairment = 18) and 33 age-matched controls were enrolled. Plasma Aß1-42 level was significantly higher in the AD group compared to controls (P = 0.046) and a cut-off >5.7 ng/mL has a specificity of 96.9%, sensitivity of 27.6%, positive predictive value 88.9%, and negative predictive value 60.4% for differentiating AD patients from controls. Significant correlation was seen between Aß1-40/Aß1-42 ratio and 18F-FDG PET Z score in the bilateral-parietal, temporal, frontal-association area, and posterior-cingulate areas. CONCLUSION: As a diagnostic biomarker of AD, plasma Aß1-42 level showed good specificity but low sensitivity in the Indian population.

Diagnostic accuracy of the Xpert MTB/RIF assay for abdominal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: We performed a meta-analysis to determine diagnostic accuracy of Xpert MTB/RIF for diagnosis of abdominal (intestinal or peritoneal) tuberculosis (TB) in various tissues (intestinal, omental/peritoneal tissue or ascitic fluid). METHODS: Electronic databases were searched for observational studies on use of Xpert MTB/RIF in ascitic fluid, peritoneal, or omental tissue for diagnosis of peritoneal and intestinal TB. We calculated the pooled sensitivity, specificity and diagnostic odds ratio of Xpert MTB/RIF for diagnosis of peritoneal TB in comparison to composite reference standard (CRS) and culture, and in comparison to CRS for intestinal TB. RESULTS: Twenty-five observational studies were included. The pooled sensitivity and specificity as assessed with peritoneal culture from ascites as an Index test was 64% (95% Confidence Interval [C.I.] 49-76%) and 97% (95% C.I., 95-99%) respectively and with peritoneal CRS was 30% (95% C.I., 22-40%) and 100% (95% C.I., 98-100%) respectively. In the intestinal group, the pooled sensitivity and specificity of Xpert MTB/RIF was 23% (95% C.I., 16-32%) and 100% (95% C.I., 52-100%). The AUC of peritoneal culture and intestinal tissue was 0.935 and 0.499. CONCLUSION: Xpert MTB/RIF has modest sensitivity for diagnosis of peritoneal and intestinal tuberculosis but has a good specificity. PROSPERO REGISTRATION: CRD42020140545.

Impact of plaque burden and composition on coronary slow flow in ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: intravascular ultrasound and virtual histology analysis.

AIM: Coronary slow flow (SF) is an important complication of percutaneous coronary intervention (PCI) associated with poor prognosis. The aim was to assess grey-scale intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) characteristics of culprit lesion in ST-elevation myocardial infarction (STEMI). METHODS: A total of 295 consecutive patients with STEMI underwent coronary angiogram and IVUS. Following PCI, patients divided into two groups; SF (thrombolysis in myocardial infarction [TIMI] flow ≤ 2, n = 74) and normal flow (NF) (TIMI flow >2, n = 221). Coronary plaque burden and its composition in relation to SF were evaluated. RESULTS: On grey-scale IVUS, the plaque area (12.3 mm2 vs. 11.5 mm2, p = .01), plaque volume (110.7 mm3 vs. 99.8 mm3, p < .001), lesion external elastic membrane (EEM) cross-sectional area (14.9 mm2 vs. 14.0 mm2, p = .011) and remodelling index (1.3 vs. 1.2, p = .043) were significantly higher in SF group. On VH-IVUS, absolute fibrous volume (48.1 mm3 vs. 41.5 mm3, p ≤ .001), fibrofatty volume (23.8 mm3 vs. 18.6 mm3, p = .015), necrotic core volume (8.3 mm3 vs. 5.5 mm3, p < .001), dense calcium volume (1.2 mm3 vs. 0.6 mm3, p = .003) and thin cap fibroatheroma either single (30.1% vs. 16.1%, p < .001) or multiple (9.6% vs. 1.8%, p < .001) were higher in SF arm. In multivariable analysis, absolute necrotic core volume (odds ratio = 1.159; 95% CI 1.030-1.305, p = .015) was the only independent predictor of SF. CONCLUSIONS: Higher necrotic core volume as detected by VH-IVUS may be a potential risk factor for the development of coronary SF phenomenon in patients with STEMI after PCI.

Appropriate chemopreventive strategy for anti-tubercular therapy related liver injury is unsettled: Results from a systematic review and network meta-analysis.

BACKGROUND: Role of chemoprophylaxis for prevention of antitubercular therapy-related drug-induced liver injury (ATT-DILI) is uncertain. METHODS: Electronic databases were searched for randomized trials reporting on chemoprophylaxis agents for prevention of ATT-DILI. We included studies evaluating the role of a drug in comparison to controls/placebo. The primary outcome was the occurrence of ATT-DILI. We performed a Bayesian random-effects network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrI) for those arms where at least two studies were available. Additional comparative studies for these arms were also identified. RESULTS: Fourteen studies were identified and seven included in the meta-analysis. The agents used for prevention of ATT-DILI were silymarin/silibinin (4 trials), N-acetylcysteine (NAC) (3 studies), herbal preparations (5 studies) and one study each for cholecalciferol and carnitine. Compared with controls/placebo, the odds of occurrence of hepatotoxicity with NAC was 7 * 10-17 (95% CrI: 2.8 * 10-53, 0.0053) and Silymarin was 0.68 (95% CrI: 0.084, 4.6). NAC had the highest probability of rank 1 (0.99) which was followed by Silymarin (0.004). CONCLUSION: N-acetyl cysteine, but not Silymarin/Silibinin, appears to be beneficial in prevention of ATT-DILI. However, the results were limited by the possible risk of bias in included studies, variable definitions of ATT-DILI and limited number and category of patients.

Antibiotics for prophylaxis of spontaneous bacterial peritonitis: systematic review & Bayesian network meta-analysis.

BACKGROUND: Various antibiotic regimens are used for primary and secondary prevention of spontaneous bacterial peritonitis (SBP). A systematic review and network meta-analysis to compare various antibiotics regimens for primary and secondary prevention of SBP were done. METHODS: We did a comprehensive literature search using various databases (i.e. MEDLINE via Ovid and PubMed, Embase, Cochrane Central Register of Controlled Trials and others) from inception to 26th October 2019 using various keywords. Only randomised studies which evaluated the role of antibiotics in adult cirrhotic patients with ascites for primary or secondary prophylaxis of SBP were included. The primary outcome was occurrence/recurrence of SBP episode and other outcomes assessed were extra-peritoneal infections and reduction in mortality. We did random-effects network meta-analysis using a Bayesian approach, and calculated odds ratios (ORs) and 95% credible intervals (CrI); agents were ranked using rank probabilities. RESULTS: We found total 1701 records in our systematic database search and out of these 17 randomised trials were found eligible for network meta-analysis. For primary prevention of SBP, the odds ratio (95% CrI) for norfloxacin daily was 0.061 (0.0060, 0.33) and for rifaximin daily was 0.037 (0.00085, 0.87) and norfloxacin and rifaximin alternate month was 0.027 (0.00061, 0.61) when compared to placebo or no comparator. For the secondary prevention of SBP, rifaximin daily had odds of 0.022 (0.00011, 0.73). CONCLUSION: Rifaximin is useful for both primary and secondary prevention of SBP whereas norfloxacin daily and alternate norfloxacin and rifaximin are useful for primary prophylaxis.

Risk of hepatitis with various reintroduction regimens of anti-tubercular therapy: a systematic review and network meta-analysis.

Objective: To compare risk of hepatotoxicity between various regimens for reintroduction of antitubercular therapy (ATT) in patients with previous episode of ATT hepatitis.Methods: We searched various databases (PubMed, Embase, CENTRAL, Scopus, WoS and LILACS) for studies comparing ATT reintroduction regimens using terms 'drug-induced liver injury' and 'antitubercular drugs' AND 'reintroduction'. The reintroduction regimens i.e concomitant (all drugs introduced together), sequential (reintroduction of one drug in full dose followed by another) or incremental (one drug in a low dose and then higher dose followed by next drug) were compared using Bayesian approach for network meta-analysis with random-effect model. Cochrane revised tool was used to assess risk of bias in included studies (RoB 2.0).Results: Four randomized studies with 577 patients were eligible for analysis. Compared with concomitant regimen (baseline comparator), incremental regimen appeared to have lower risk of ATT hepatitis (odds ratio [OR] 0.24; 95% CrI 0.017, 1.2) as also the sequential regimen (OR 0.33; 95% CrI 0.033, 1.7). Rifampicin first and isoniazid first reintroduction regimens were similar via-a-vis recurrence of hepatotoxicity.Conclusion: The sequential and incremental regimen may be better than concomitant regimen in reducing risk of ATT hepatitis although the odds did not achieve statistical significance.

Utility of tissue Xpert-Mtb/Rif for the diagnosis of intestinal tuberculosis in patients with ileocolonic ulcers.

INTRODUCTION: Data on the use of Xpert Mtb/Rif for the diagnosis of intestinal tuberculosis is sparse. We report on the utility of Xpert Mtb/Rif testing for diagnosis of intestinal tuberculosis (ITB) in patients with ileocecal ulcers. METHODOLOGY: We performed a retrospective analysis of patients with ileocecal ulcers and suspected to have ITB and in whom testing of intestinal tissue for Xpert Mtb/Rif was performed. The patients were divided into two groups: those with a final diagnosis of intestinal tuberculosis and those with other diagnosis. These patients were compared for clinical features and presentation. The sensitivity, specificity, positive predictive value, and negative predictive value of Xpert Mtb/Rif for the diagnosis of ITB were calculated. RESULTS: Of the 40 patients studied, 23 were women and the mean age was 32.92 ±â€„12.78 years. Abdominal pain was present in 33 (88.5%) patients and diarrhea in 12 (30%). A total of 25 patients had underlying ITB whereas 15 patients had other diagnoses (Crohn's disease, amebiasis, nonspecific ileitis, etc.). The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of GeneXpert-Mtb/Rif was 32% (CI: 14.95-53.50%), 100% (78.2-100), 46.88% (40.27-53.59%), 100 & 57.50 (40.89-72.89%) respectively. CONCLUSION: A positive GeneXpert-Mtb/Rif helps in the diagnosis of ITB, but the sensitivity is low.

Use of steroids for abdominal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: The role of adjunctive steroids in abdominal tuberculosis is unclear. OBJECTIVE: To evaluate effect of adjunctive use of steroids for abdominal tuberculosis in reducing/preventing complications. METHODS: We searched electronic databases (Medline, Embase, CENTRAL, Scopus, Web of Science, CINAHL) from inception to 25th June 2018 using the terms "abdominal tuberculosis" OR "intestinal tuberculosis" OR "peritoneal tuberculosis" OR "tuberculous peritonitis" AND steroids OR methylprednisolone OR prednisolone. Bibliography of potential articles was also searched. We included studies comparing adjunctive steroids to antitubercular therapy (ATT) alone. We excluded non-English articles, case reports, reviews and unrelated papers. The primary outcome was a comprehensive clinical outcome including need for surgery or the presence of symptomatic stricture (abdominal pain or intestinal obstruction). Quality assessment of included studies was done using ROBINS-I tool. Random-effects model was used to calculate the summary effect for all the outcomes. RESULTS: Of total 633 records, three studies on peritoneal tuberculosis were included in meta-analysis. These papers were of poor quality (one quasi-randomised study and two retrospective cohort studies). Meta-analyses showed adjunctive steroids, with ATT is more effective than ATT alone in tuberculous peritonitis patients for the prevention of composite end point (RR 0.15 [0.04, 0.62], p = 0.008), symptomatic stricture(RR 0.15 [0.04-0.62] p = 0.008) and intestinal obstruction (RR 0.18 [0.03-0.99] p = 0.05). CONCLUSION: The data on use of steroids for abdominal tuberculosis are limited to peritoneal tuberculosis. Although steroids seem to have some benefit in patients of tubercular peritonitis, the poor quality of studies limits the generalisability of the findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016047347.

Are your capsules vegetarian or nonvegetarian: An ethical and scientific justification.

Capsules are important component of day to day health management. But recently an issue came up whether the capsule you are using is of vegetarian or non-vegetarian origin. Capsule shell can be divided into vegetarian and non-vegetarian origin on the basis of their origin. Gelatin capsule shell are typically of animal origin and HPMC or starch based shells are of vegetarian origin. CDSCO received one proposal to replace all non veg capsule with capsule of vegetarian origin. CDSCO has invited comments from different stakeholders regarding this. So, in this editorial, we are addressing different issues lying behind veg and non-veg capsules and scientific justification of the same.