A Machine Learning Algorithm Avoids Unnecessary Paracentesis for Exclusion of SBP in Cirrhosis in Resource-Limited Settings.

BACKGROUND AND AIMS: Despite the poor prognosis associated with missed or delayed spontaneous bacterial peritonitis (SBP) diagnosis, <15% get timely paracentesis, which persists despite guidelines/education in the US. Measures to exclude SBP non-invasively where timely paracentesis cannot be performed could streamline this burden. METHODS: Using Veterans Health Administration Corporate Data Warehouse (VHA-CDW) we included cirrhosis patients between 2009-2019 who underwent timely paracentesis and collected relevant clinical information (demographics, cirrhosis severity, medications, vitals, and comorbidities). XGBoost-models were trained on 75% of the primary cohort, with 25% reserved for testing. The final model was further validated in two cohorts: Validation cohort #1: In VHA-CDW, those without prior SBP who received 2nd early paracentesis, and Validation cohort #2: Prospective data from 276 non-electively admitted University hospital patients. RESULTS: Negative predictive values (NPV) at 5,10 & 15% probability cutoffs were examined. Primary cohort: n=9,643 (mean age 63.1±8.7 years, 97.2% men, SBP:15.0%) received first early paracentesis. Testing-set NPVs for SBP were 96.5%, 93.0% and 91.6% at the 5%, 10% and 15% probability thresholds respectively. In Validation cohort #1: n=2844 (mean age 63.14±8.37 years, 97.1% male, SBP: 9.7%) with NPVs were 98.8%, 95.3% and 94.5%. In Validation cohort #2: n=276 (mean age 56.08±9.09, 59.6% male, SBP: 7.6%) with NPVs were 100%, 98.9% and 98.0% The final ML model showed the greatest net benefit on decision-curve analyses. CONCLUSIONS: A machine learning model generated using routinely collected variables excluded SBP with high negative predictive value. Applying this model could ease the need to provide paracentesis in resource-limited settings by excluding those unlikely to have SBP.

A specialized HE testing clinic improves rational decision-making for therapy in cirrhosis.

BACKGROUND: Cognitive complaints in cirrhosis are often attributed to HE with reflexive therapy if specialized tests are not performed. The aim was to determine the utility of a specialized HE clinic for management decisions. METHODS: Cirrhosis patients with cognitive complaints were referred through a dedicated consult pathway to a specialized clinic and followed for 6 months. This clinic included detailed history, medication review, standardized tests [Mini-Mental Status Exam (MMSE), Psychometric HE Score, and others], and obstructive sleep apnea screening. Results were communicated with patients and referring providers. A subset was offered repeat testing. RESULTS: A total of 286 patients were tested between 2012 and 2022. Of the 286 patients, 4 patients who showed a Mini-Mental State Exam <25 were referred to neurology. Thirty-nine percent had normal Psychometric HE Score (higher in younger patients, without prior HE, depression, and lower Model for End-Stage Liver Disease-Sodium), while 172 (61%) patients had cognitive impairment. Of the 172 patients, 51 did not want management change, 84 were started on HE therapy, and 37 were considered impaired due to other causes. In 51 without management change, 32 refused lactulose, while the remaining were counseled regarding lactulose titration. Of the 84 patients with HE-therapy initiation, lactulose was initiated in 56 and rifaximin in 28; most therapies continued over 6 months. The ones who were retested improved their Psychometric HE Score. The 37 with other causes (obstructive sleep apnea, mood disorders, substance use, and mild cognitive impairment) led to specialized referrals. No overt HE was found over 6 months in those without HE-related impairment. The clinic was billed for. CONCLUSIONS: A specialized HE clinic for patients with cirrhosis and cognitive complaints established through a dedicated consult pathway showed that 39% of referred patients had normal cognitive performance, while the results guided management changes, including for HE and other causes in the remaining patients.

Bilateral adrenal histoplasmosis presenting as adrenal mass mimicking malignancy in an immunocompetent patient.

We report a case of a 78-year-old immunocompetent man who presented with worsening fatigue and lethargy for one month. He had also been complaining of cough and SOB for two months which had been attributed to his underlying COPD and possible pneumonia. CT showed bilateral pleural effusions, ground-glass opacities, cirrhosis, splenomegaly and bilateral adrenal masses which was highly suspicious for malignancy. After pheochromocytoma was ruled out, EUS-FNA guided biopsy was performed on the left adrenal gland. Histology was positive for yeast cells, with fungal staining (PAS) revealing narrow-based budding compatible with Histoplasma. The patient was treated with amphotericin and itraconazole. Our case is unique as he presented with hepatosplenomegaly, which is reported in less than a quarter of cases. Although typically a diagnosis in immunocompromised patients, a high index of clinical suspicion is required to diagnose disseminated histoplasmosis in an immunocompetent patient. The gold standard for diagnosis is fungal tissue culture. However results may take up to weeks. EUS-FNA guided biopsy of adrenal glands can aid in early definitive diagnosis and management.

The effects of liraglutide on liver enzymes and metabolic factors in patients with nonalcoholic steatohepatitis: a meta-analysis of randomized controlled trials.

Introduction: Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease, but no drug therapies have been approved to date. While glucagon-like peptide-1 (GLP-1) analogues may help in the management, the existing evidence remains conflicting. Aim: This meta-analysis aims to elucidate the efficacy of liraglutide in patients with NASH. Material and methods: We searched 4 databases for randomized controlled trials assessing the efficacy of liraglutide in patients with NASH. We analysed continuous outcomes using the mean difference (MD) and relative 95% confidence interval (CI), while dichotomous outcomes were analysed using the risk ratio (RR) and relative 95% CI. Primary endpoints included alanine aminotransferase (ALT) (IU/l), aspartate aminotransferase (AST) (IU/l), alkaline phosphatase (ALP) (IU/l), and γ-glutamyl transferase (GGT) (IU/l). Secondary outcomes were body mass index (BMI) (kg/m2), waist circumference (cm), total cholesterol (TC) (mmol/l), triglyceride (TG) (mmoll), high-density lipoprotein (HDL) (mmol/l), low-density lipoprotein (LDL) (mmol/l), and glycated hemoglobin (HbA1c) (%). Results: A total of 5 clinical trials were included. The analysis showed that liraglutide is effective in increasing HDL (MD = +0.10 (-0.18, -0.02), p = 0.02) and reducing LDL levels in blood (MD = -0.29 (-0.56, -0.02), p = 0.04). No significant difference was noted in levels of ALT (MD = 2.66 (-1.56, 6.87), p = 0.22), AST (MD = -1.99 (-5.70, 1.72), p = 0.29), GGT (MD = 5.02 (-0.86, 10.90), p = 0.09), ALP (MD = -5.16 (-11.90, 1.59), p = 0.13), TC (MD = -0.31 (-0.65, 0.03), p = 0.07), or TG (MD = -0.14 (-0.53, 0.25), p = 0.48). The HbA1c (%) level was found to be significantly reduced in the liraglutide arm (MD = -0.62 (-0.88, -0.36), p < 0.01). Conclusions: Liraglutide effectively improves the lipid profile in patients with NASH.

Effects of Aramchol in patients with nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis.

Introduction: Nonalcoholic fatty liver disease (NAFLD) comprises a wide range of related liver disorders affecting mainly people who drink no or very little alcohol. Aramchol is a new synthetic molecule that has been shown to reduce liver fat content. There is little evidence supporting its efficacy in humans. Aim: To evaluate the efficacy of Aramchol in patients with NAFLD according to different randomized clinical trials. Material and methods: We searched PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of Aramchol in patients with NAFLD. Risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), glycated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), HOMA-IR, and insulin level. Results: We included 3 clinical trials. We found that the Aramchol group did not show any significant difference from the control group regarding ALT (MD = 3.92 (-21.20, 29.04), p = 0.76), AP (MD = -0.59 (-8.85, 7.67), p = 0.89), HbA1c (MD = -0.11 (-0.32, 0.10), p = 0.29), TC (MD = 14.25 (-626, 34.77), p = 0.17), TG (MD = 2.29 (-39.30, 43.87), p = 0.91), HOMA-IR (MD = -0.11 (-1.58, 1.37), p = 0.89), and insulin levels (MD = -0.88 (-5.82, 4.06), p = 0.73). AST levels were significantly higher in the Aramchol group (MD =11.04 (4.91, 17.16), p = 0.04). Conclusions: Aramchol was a safe and tolerable drug to be used in patients with NAFLD. However, it was not superior to placebo in reducing the biochemical liver markers.

Factors Associated with Difficulty Maintaining Insufflation of the Colon During Endoscopy.

BACKGROUND: Insufflation of the colon allows for adequate visualization of the mucosal tissue and advancement of the endoscope during colonoscopy. Most colonoscopies are performed with sedation to mitigate discomfort and enhance the colonoscopy experience for both the patient and the endoscopist. AIM: We aimed to evaluate factors associated with difficulty maintaining insufflation. METHODS: A cross-sectional study of individuals undergoing colonoscopy at the Oklahoma City Veterans Affairs Medical Center was performed. Experiencing difficulty maintaining air insufflation during colonoscopy was assessed with a questionnaire completed by the performing endoscopist at the end of procedure. Information regarding procedure times, sedation used, demographics, comorbidities, surgical history, and medications used was extracted from the medical record. A multivariate regression analysis was performed to identify factors associated with difficulty maintaining air insufflation. A P value < 0.05 was considered significant. RESULTS: 996 Patients were included for the analysis. Difficulty with insufflation was reported in 240 (24%) colonoscopies; mean age of 63.8 ± 10.4 years old and 13% were female. Fellow trainees were involved in 669 (67%) colonoscopies. Older age (OR 1.02, P 0.03, CI [1.00-1.04]), diabetes (OR 1.5, 95% CI [1.03, 2.05]), fellow's involvement (OR 2.6. (95% CI [1.68, 4.09]), total procedure time (OR 1.02, 95% CI [1.00, 1.03]), mean number of adenomas (OR 1.05, 95% CI [1.00, 1.09]), and MAC use (OR 2.6, 95% CI [1.80, 3.85]) were independent predictors for difficulty in maintaining air insufflation. CONCLUSION: Our findings suggest that endoscopists should be cognizant of colon insufflation issues in older, diabetic patients undergoing colonoscopies under deep sedation, particularly if prolonged procedure is anticipated or encountered.

Does Finding Cecal Adenoma Increase the Risk of Discovering More and Advanced Adenomas in the Remainder of the Colon?

OBJECTIVES: Adenomatous polyps are common, occurring in up to 25% of the population older than 50 years of age in the United States. Conflicting data are present in the literature about the impact of specific adenoma locations and the prediction on the number and advanced histology of adenomas elsewhere. With this study we aimed to review the association between cecal adenoma and the risk of discovering more and advanced adenomas in the remainder of the colon. METHODS: We performed a retrospective study of 1880 patients who received outpatient colonoscopies between June 2012 and December 2014 at the Veterans Affairs Medical Center in Oklahoma City. The data collected included patient demographics, indications for colonoscopy, smoking history, alcohol use, family history of colon cancer, quality of bowel preparation, number of adenomas, location, size of adenomas, and the histology of adenomas and colon cancer. RESULTS: The mean age of the study population was 61.6 ± 9.4 year, with 95% of the population being men. Cecal adenomas were found in 243 (12.9%) of patients. Patients with cecal adenoma tended to be older (65 ± 7 vs 61 ± 10, P < 0.0001), more likely to be men (97% vs 94%, P = 0.06) and less likely to have a colonoscopy done for screening indication (11% vs. 13%., P = 0.03). After adjusting for age, sex, indication, and quality of bowel preparation, patients with cecal adenoma were found to have a sixfold increase in finding ≥10 other adenomas elsewhere (4.5% vs 0.8% P = 0.0009) and a threefold increase in finding advanced adenomas (17.7% vs 9.9% P = 0.002) in the remainder of the colon. Stratifying by location, the increased risk was more pronounced in the right side (24.7% vs 8.9% P ≤ 0.0001) compared with the left side. CONCLUSIONS: Cecal adenoma is associated with an increased risk of finding more and advanced adenomas in the remainder of the colon, especially on the right side; therefore, the discovery of a cecal adenoma should prompt a more thorough evaluation of the entire colon, particularly the right colon.

Estimating the optimum number of colon biopsies for diagnosing microscopic colitis: a systematic review.

Microscopic colitis (MC) is an inflammatory disease of the colon characterized by persistent watery, nonbloody diarrhea. Subtypes of MC include collagenous and lymphocytic MC. Microscopic examination of colon tissue is crucial to confirming the diagnosis because the colonic mucosa often appears normal during flexible sigmoidoscopy or colonoscopy. We aim to determine the optimal sites and minimum number of colon biopsies required to diagnose MC from published studies. We systematically searched PubMed, Web of Science, Scopus, and Cochrane databases from inception until October 2020 using the following keywords: microscopic, lymphocytic, collagenous, colitis, biopsy, and biopsies. We screened the search results for eligibility and extracted data from the included studies. We pooled the numbers of biopsies provided by each study to calculate the mean number of biopsies, SD, and SEM. We included three retrospective cohort studies with 356 patients (148 collagenous, 192 lymphocytic, and 16 mixed), and the total number of biopsies were 1854. The mean number of biopsies that were recommended by the included studies are 4, 4, and 9, respectively. The pooled mean ± SD is 5.67 ± 2.89. The included studies reported that biopsies from the ascending colon (AC) and descending colon (DC) had the highest diagnostic rates. To ensure a high level of certainty in diagnosing MC, a total of six biopsies should be taken from the AC and DC (3 AC and 3 DC). However, special care should be directed toward differentiating MC from other forms of colitis. In addition, detailed and comparative studies are needed to provide stronger recommendations to diagnose MC.

Efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis: a systematic review and meta-analysis.

BACKGROUND: Dyslipidemia is a very common medical disorder affecting nearly 33.5% of US adults over 20 years of age. It represents the major risk factor for non-alcoholic fatty liver (NAFLD) and cardiovascular diseases, which is the most common cause of death worldwide. Elafibranor is a peroxisome proliferator-activated receptor (PPAR) alpha and delta dual agonist. A novel dual peroxisome proliferator-activated receptor alpha/delta (PPAR-α/δ), elafibranor, the agonist is an emerging therapy with promising hepatoprotective results. OBJECTIVES: To estimate the efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis (NASH). METHODS: We searched the following databases: PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of silymarin in patients with NAFLD. Risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), HOMA-IR, total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C). RESULTS: We included four clinical trials. We found that elafibranor significantly reduced the levels of ALT {MD = - 4.60 [- 8.17, - 1.04], (P = 0.01)}, GGT {MD = - 16.57 [- 26.59, - 6.56], (P < 0.01)}, TC {MD = - 0.37 [- 0.66, - 0.08], (P = 0.01)}, TG {MD = - 0.37 [- 0.51, - 0.24], (P < 0.01)}, ALP {(MD = - 14.45 [- 18.99, - 9.91], (P < 0.01)}, and LDL {MD = - 0.20 [- 0.33, - 0.07], (P = 0.003)}. There was no significant difference regarding HOMA-IR {MD = - 0.32 [- 0.88, 0.24], (P = 0.26) and AST (P = 0.53). CONCLUSION: PPAR-alpha/delta dual agonist, elafibranor, is a promising drug that improves most metabolic parameters in dyslipidemic patients.

The association of D-dimers with mortality, intensive care unit admission or acute respiratory distress syndrome in patients hospitalized with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

AIM: To determine if D-dimers are elevated in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who have adverse clinical outcomes including all-cause mortality, intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). METHODS: We conducted a systematic review and meta-analysis of the published literature in PubMed, Embase and Cochrane databases through April 9, 2020 for studies evaluating D-dimer levels in SARS-COV-2 infected patients with and without a composite clinical endpoint, defined as the presence of all-cause of mortality, Intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). A total of six studies were included in the meta-analysis. RESULTS: D-dimers were significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41 ug/ml). CONCLUSION: We conclude that SARS-CoV-2 infected patients with elevated D-dimers have worse clinical outcomes (all-cause mortality, ICU admission or ARDS) and thus measurement of D-dimers can guide in clinical decision making.

Most Common Pathway of Metastasis of Rectal Signet Ring Cell Carcinoma to the Skin: Hematogenous.

Liver represents the most common site of metastasis in patients with advanced colorectal cancer (CRC). Cutaneous metastasis is uncommon and has been documented only in 3% of patients. Most cutaneous metastases demonstrate typical histological features of adenocarcinoma, such as glandular formation and mucin production. We present the case of a 66-year-old male with Crohn's disease (CD) and stage IV rectal signet ring cell carcinoma arising in his rectal stump who presented with a painful papular bilateral groin rash. Biopsy revealed metastatic signet ring cell carcinoma. Since cutaneous metastasis in patients with advanced CRC can be easily confused with infection, especially fungal infection, physicians should be vigilant of the possibility of cutaneous metastasis. Our literature review suggests hematogenous spread as the dissemination pathway of this histological subtype of rectal adenocarcinoma to the skin. We present the first case of cutaneous metastatic signet ring cell carcinoma from a rectal stump of a patient with CD.

Clostridium tertium Bacteremia in a Non-neutropenic Patient with Liver Cirrhosis.

Clostridium tertium bacteremia is a rare condition that predominantly occurs in neutropenic patients. Clostridium tertium bacteremia, although extremely rare in non-neutropenic patients, represents the second-most common cause of bacteremia among Clostridium species. Infection with this bacteria can present variably and is usually managed with broad-spectrum antibiotics.

Laparoscopic Sleeve Gastrectomy: To Suture or not to Suture Staple Line?

Objective To assess the outcome and safety of staple line over-sewing for patients undergoing laparoscopic sleeve gastrectomy (LSG). Study design and location Retrospective descriptive analysis conducted at Shifa International Hospital Islamabad. Materials and methods Consecutive patients undergoing LSG as a treatment for morbid obesity from October 2013 to December 2016 were included in the study after approval from the ethical review board. Patients were divided into two groups: group A who underwent reinforcement using Vicryl 2.0 and group B where no reinforcement was done. Results A total of 225 patients underwent LSG between October 2013 and December 2016, including 147 females (65.4%) and 78 males (34.6%). Both groups were comparable in terms of age, body mass index (BMI) and gender distribution (p-value more than 0.05). There was one leak in group A (1.36%), none in group B. The bleeding rate was 4.3% in group A and 2.7% in group B. Conclusion This was a retrospective analysis of all the patients who underwent LSG, and it was observed that there was no added benefit of sewing the staple line in terms of rate of bleeding and leak.