Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial.

PURPOSE: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26-43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. CONCLUSIONS: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Neuroleptic malignant syndrome in a case of extra-pontine myelinolysis: On the horns of dilemma.

Osmotic demyelination syndrome (ODS) and neuroleptic malignant syndrome (NMS) lead to severe neurological sequalae. Though currently thought to be different syndromes, literature suggests a relation between the two. We present the case of a 45-year-old male who was found to have chronic severe hyponatremia and underwent rapid correction of sodium and developed parkinsonism features. Magnetic resonance imaging (MRI) confirmed extrapontine myelinolysis (a type of ODS). The patient received haloperidol for agitated behavior and developed new features of rigidity, fever, tachycardia and elevated creatine phosphokinase (CPK) levels and thus neuroleptic malignant syndrome was suspected to overlap with ODS. We report this case highlighting the difficulty in differentiating the between ODS and NMS and their relationship.

Prognostic utility of biomarker levels and clinical severity scoring in sepsis: a comparative study.

Procalcitonin (PCT) is one of the best validated biomarkers in the management of sepsis. However, its prognostic utility remains poorly studied. The present study sought to assess the prognostic utility of serial PCT assessments in patients with sepsis, and to compare the prognostic predictive capability of serial measurements of PCT with conventional markers of inflammation and validated intensive care unit (ICU) severity scoring systems. We recruited consecutive patients admitted to the medical units of a tertiary care center with suspected or proven bacterial infection and sepsis. Measurement of serum PCT levels, inflammatory markers, and ICU severity scores were performed at admission and repeated every 48 hours subsequently for the duration of hospital stay. 99 patients with bacterial infection and sepsis were recruited and followed until death or discharge. Median serum PCT level was similar between survivors and non-survivors on day 1, but was significantly lower at days 3, 5 and 7 in the survivors. The analysis found Acute Physiology and Chronic Health Evaluation (APACHE IV) score on all days (1, 3, 5, and 7), PCT on days 5 and 7, and Sequential Organ Failure Assessment score at 24 hours to have good predictive accuracy for adverse patient outcome. PCT clearance on days 3 and 5 of admission was measured and demonstrated predictive accuracy comparable to day-matched APACHE IV scores. While serial levels of serum PCT in patients with sepsis are accurate in the prediction of adverse patient outcome, they do not offer any additional clinical benefit over existing severity of illness scores and may be cost prohibitive in resource-limited settings. While serial levels of serum PCT in patients with sepsis are accurate in the prediction of adverse patient outcome, they do not offer any additional clinical benefit over existing severity of illness scores and may be cost prohibitive in resource-limited settings.

Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

BACKGROUND: The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. METHODS: This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. RESULTS: Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. CONCLUSION: Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

Effect of oral tobacco use and smoking on outcomes of Crohn's disease in India.

BACKGROUND AND AIM: Smoking has been linked with adverse outcomes in Crohn's disease (CD); however, it is not known whether oral tobacco (OT) use affects disease outcomes in these patients. The study aimed to assess the association between smoking or OT and outcomes in CD. METHODS: Retrospective analysis was performed on prospectively maintained records of CD patients from 2004 to 2016. The parameters assessed included disease characteristics at baseline (location, behavior, age at onset, perianal disease, and extraintestinal manifestations), course pattern, and outcomes (surgery, hospitalizations, immunomodulator or biologics use, and steroid requirement). RESULTS: A total of 426 patients were included (mean age: 39.9 years; 59.9% men; median follow up: 71 months). Forty patients were ever-OT users, and 59 were ever-smokers, ever-use being defined as daily use for at least 2 years. OT use was associated with male sex and smoking. Both OT use and smoking had no effect on baseline characteristics, but upper gastrointestinal disease was less common in ever-smokers. Both OT use and smoking did not have any effect on surgery, immunomodulator, and biologic use. Similarly, no association was found between these outcomes and duration, daily, and cumulative exposure to tobacco. Current but not former tobacco use in both smoked (adjusted odds ratio = 2.59 [1.22-5.49]) and OT (adjusted odds ratio = 2.97 [1.03-8.6]) forms increased risk of hospitalizations. CONCLUSION: Oral tobacco use and smoking had no significant detrimental effect on disease phenotype or medical and surgical requirements in CD in Indian patients, affirming other non-Caucasian studies that found lack of effect of smoking. However, current tobacco use in any form was associated with hospitalization during follow up.