Rates and predictors of 30-day hospital readmissions in adults for drug-induced acute pancreatitis: A retrospective study from the United States National Readmission Database.

BACKGROUND AND AIM: Drug-induced acute pancreatitis (DIAP) linked to several medications is a diagnosis of exclusion and is associated with significant morbidity and mortality, contributing to the US healthcare cost burden. Existing studies on DIAP focus on the drug classes that can cause acute pancreatitis. Hence, our retrospective study aims to determine the rates and predictors for 30-day readmissions (30-DR) in patients with index hospitalization for DIAP. METHODS: From the Nationwide Readmissions Database, we followed adults admitted for DIAP who were discharged alive for 30 days. During 30-DR, we evaluated the rates, predictors, and outcomes of DIAP. RESULTS: Of the 4457 DIAP patients surviving at discharge, 12.5% were readmitted at 30 days. During readmissions, the predictors of 30-DR for DIAP were young age, the Charlson-Deyo Comorbidity Index of 2 and 3, protein-energy malnutrition, and dyslipidemia. During 30-DR, DIAP had a higher mortality rate (2.4% vs. 0.7%; P < 0.020), extended hospital stays (5.6 days vs. 4 days, 0.000), and higher hospital charges ($12 983.6 vs. $8 255.6; P 0.000). CONCLUSIONS: DIAP has high 30-DR rates and poorer outcomes.

Trends of Readmissions for Gastrointestinal Bleeding After Alcoholic Hepatitis: Analysis of the Nationwide Readmission Database.

Background: Alcohol consumption is associated with numerous hepatic manifestations, including alcoholic fatty liver disease, alcoholic hepatitis (AH), and liver cirrhosis. AH is a common and serious complication of alcohol use. Gastrointestinal bleeding (GIB) remains one of the most common causes of death in these patients. In this article, we studied the trends of GIB after AH. Methods: This was a retrospective interrupted trend study. We analyzed the 2010, 2012, 2014, 2016, and 2018 Nationwide Readmission Databases. The first AH hospitalization in the year was marked as index hospitalization. We identified subsequent hospitalizations with GIB within 30 days and marked them as readmissions. A multivariate regression analysis was used to calculate the risk-adjusted odds of trends for GIB readmissions, including esophageal varices bleeding (EVB), upper GIB, lower GIB, and all GIB. Results: The volume of index hospitalizations increased from 10,248 in 2010 to 16,479 in 2018. Similarly, all readmissions increased from 1,838 in 2010 to 3,908 in 2018. Of all readmissions, EVB increased from 3.9% in 2010 to 5.9% in 2018 (odds ratio (OR) trend 1.10; P < 0.001). Readmissions for upper GIB increased from 2.4% in 2010 to 7.8% in 2018 (OR trend 1.22; P < 0.001). On the other hand, lower GIB readmissions decreased from 7.2% in 2010 to 4.7% in 2018 (OR trend 0.95; P = 0.015). There was no statistically significant trend for all GIB readmissions (OR trend 1; P = 0.915). Conclusion: Further studies are needed to evaluate the patterns of lower GIB in patients with liver disease and the recent trends of corticosteroids use in AH patients.

Trends and Outcomes of Alcoholic Liver Cirrhosis Hospitalizations in the Last Two Decades: Analysis of the Nationwide Inpatient Sample.

Background: Liver cirrhosis is a major burden on the health care system. Alcohol is one of the most common etiologies of cirrhosis. The aim of our article is to examine the trends of alcoholic liver cirrhosis (ALC) hospitalizations over the past two decades. Methods: This was a retrospective longitudinal study. Using the International Classification of Diseases, Ninth Revision, Clinical Modification/Procedure Coding System (ICD-9-CM/PCS) and the ICD-10-CM/PCS, the Nationwide Inpatient Sample (NIS) database was analyzed. We included 1998, 2003, 2008, 2013, and 2018 NIS databases. Using multivariate regression analysis, we examined trends of ALC hospitalizations including inpatient mortality, mean length of stay (LOS), and mean total hospital charges (THCs). Results: We included 261,420 hospitalizations with ALC as the primary diagnosis for admission. There was a trend toward increasing hospitalizations over that period; they increased from 46,186 in 1998 to 69,970 in 2018 (P < 0.001). Moreover, there was a 2.1-fold increase in the mean THC in 2018 compared to 1998 (P < 0.001). On the other hand, inpatient mortality decreased from 12.8% in 1998 to 4.7% in 2018 (P < 0.001), and a trend of decreasing mean LOS was observed. The mean LOS decreased from 7.0 days in 1998 to 5.9 days in 2018 (P < 0.001). Conclusions: Over the last two decades, there was a trend of increasing hospitalizations and THC. However, we noticed a trend toward decreasing inpatient mortality and LOS over that period, which might reflect in part an improvement in the medical care provided for these patients.

Metastatic Prostate Adenocarcinoma: A Rare Presentation.

Prostate cancer is the third most diagnosed cancer in men around the world, and it typically metastasizes to bone, lung, and liver. Gastrointestinal (GI) involvement by prostate cancer is rare, as patients tend to present with upper and lower GI bleed among other symptoms not related to prostate cancer, which commonly include lower urinary tract symptoms such as urinary frequency, dribbling of urine, or urinary retention. In cases of patients with prostate cancer and symptoms from the GI system, colonoscopy and biopsy of lesions should be performed to allow physicians to make an accurate and prompt diagnosis in patients with metastatic prostate cancer with rectal involvement. We present a case of a patient who initially complained of melena and was found to have a rectal nodule with biopsy-proven metastatic prostate cancer.

Association of Glucagon-like Peptide 1 Analogs and Agonists Administered for Obesity with Weight Loss and Adverse Events: A Systematic Review and Network Meta-analysis.

BACKGROUND: Comparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown. METHODS: We performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of ≥12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE). FINDINGS: 64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m2; trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide ≥1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide ≤1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I2 >50%) in WL and AEs reflected magnitude, not direction of effect.

Outcomes of Non-Variceal Upper Gastrointestinal Bleed Stratified by Hospital Teaching Status: Insights From the National Inpatient Sample.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a significant cause of mortality and morbidity in the USA. Currently, there are limited data on the inpatient outcomes of patients admitted with a diagnosis of NVUGIB stratified according to teaching hospital status. We analyzed data from the National Inpatient Sample (NIS) intending to evaluate these outcomes. METHODS: We queried the NIS 2016 and 2017 databases for NVUGIB hospitalizations by teaching hospital status. The primary outcome was inpatient mortality while secondary outcomes were rate of endoscopy for hemostasis, rate of early endoscopy (endoscopy in 1 day or less), mean time to endoscopy, rate of complications including acute kidney injury (AKI), acute respiratory failure (ARF), need for blood transfusion, development of sepsis, need for endotracheal intubation and mechanical ventilation as well as healthcare utilization. RESULTS: There were over 71 million weighted discharges in the combined 2016 and 2017 NIS database. A total of 94,900 NVUGIB cases were identified with 63.4% admitted in teaching hospitals. The in-hospital mortality for patients admitted with an NVUGIB in teaching hospitals was 1.98% compared to 1.5% in non-teaching hospitals (adjusted odds ratio (aOR): 1.38, 95% confidence interval (CI): 1.08 - 1.77, P = 0.010) when adjusted for biodemographic and hospital characteristics as well as comorbidities. Patients admitted with a diagnosis of NVUGIB in teaching hospitals had a 10% adjusted increased odds of getting endoscopy for hemostasis (27.0% vs. 24.5%, aOR: 1.10, 95% CI: 1.02 - 1.19, P = 0.016) compared to patients in non-teaching hospitals. There was, however, no difference in early endoscopy between the two groups. CONCLUSION: Patients admitted at teaching hospitals for an NVUGIB had worse outcomes during hospitalizations including mortality, median length of stay, and total hospital charges when compared to NVUGIB patients managed at non-teaching hospitals.

Cohort Study in Parkinsonism: Delayed Transit, Accelerated Gastric Emptying, and Prodromal Dysmotility.

OBJECTIVE: To evaluate gastric emptying (GE) and colonic transit in a cohort of patients with Parkinson disease and other parkinsonism disorders and to determine whether abnormal gut transit precedes motor onset of parkinsonism. METHODS: Medical record review of 84 patients with parkinsonism who underwent clinically indicated transit studies at Mayo Clinic (2001-2019) and 11 patients with transit studies who subsequently developed parkinsonism. Data are summarized as median (interquartile range). RESULTS: The 84 patients (52% female) with parkinsonism were aged 72 (66-76) years with a disease duration of 5 (2-8) years: Parkinson disease = 70, multiple system atrophy = 7, dementia with Lewy bodies = 4, progressive supranuclear palsy = 2, and parkinsonian syndrome = 1. Ten had delayed GE, 10 slow colonic transit, 16 accelerated GE (14 Parkinson disease, 1 multiple system atrophy, and 1 parkinsonian syndrome), and 49 normal transit. One patient with parkinsonian syndrome had both slow colonic and accelerated gastric transit. Longer disease duration and higher levodopa equivalent daily dose were observed for Parkinson disease compared with other parkinsonisms and with slow compared with normal colonic transit. Of 11 patients (5 female) with transit studies who later developed motor parkinsonism after 4 (3-5) years, 1 had accelerated GE, 1 had delayed GE, and 1 had both delayed GE and colonic transit. CONCLUSIONS: Accelerated GE was newly identified in patients with parkinsonism, in addition to delayed GE or colonic transit. Furthermore, gut dysmotility was objectively identified to precede the motor onset of parkinsonism.

Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS: The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Hepatorenal syndrome: a Nationwide Trend Analysis from 2008 to 2018.

OBJECTIVE: This study was designed to assess the epidemiological trends and outcomes associated with Hepatorenal Syndrome (HRS). METHODS: This retrospective interrupted trend study used the Nationwide Inpatient Sample (NIS) database for the years 2008, 2012, 2014, 20z16 and 2018 to identify adult (≥18 years) hospitalizations with a primary diagnosis of HRS. We determined epidemiological characteristics and trends for HRS hospitalizations. Additionally, we also calculated the inpatient mortality, mean length of stay (LOS) and mean total hospital charge (THC) using a multivariate regression trend analysis. RESULTS: There was an increase in the total number of HRS hospitalizations from 22,864 in 2008 to 42,985 in 2018 with a trend towards increasing hospitalizations (p-trend <.001). The mean age for these hospitalizations ranged from 57.4-59.0 years with a significantly rising trend (p-trend <.001). Although the majority of HRS hospitalizations were men, we observed a trend towards increasing hospitalizations for women with an increase from 35.7% in 2008 to 39% in 2018 (p-trend <.001). Additionally, Whites made up a majority of the sample size (Table 1). After a multivariate regression trend analysis, we found a statistically significant trend towards declining inpatient mortality from 36.2% in 2008 to 25.7% in 2018 (p-trend <.001) for HRS hospitalizations (Table 2). We did not find a statistically significant trend for LOS and THC.[Table: see text][Table: see text]. CONCLUSION: Total hospitalizations, hospitalizations for women and the mean age for HRS hospitalizations were on the rise between 2008 and 2018. However, the inpatient mortality declined.KEY MESSAGESIn the United States, there was a trend towards increasing hospitalizations and mean age for HRS.Although a male predominance was noted, HRS hospitalizations for women were on the rise.The inpatient mortality for HRS hospitalizations was on a decline and may indicate significant improvements in management.

Development of a Score to Predict Positive Colonic Histology in Chronic Diarrhea Assessed in Open-access Colonoscopy.

GOALS: To evaluate the diagnostic yield of colonoscopy and esophagogastroduodenoscopy with biopsies and to identify predictors of positive colonic histology in patients with chronic diarrhea. BACKGROUND: Colonoscopy with biopsies is performed in chronic diarrhea with negative initial work-up. STUDY: We reviewed electronic medical records of 1022 consecutive patients with chronic diarrhea referred for a first colonoscopy (including 25% open-access referrals). Predictors of positive colonic histology were investigated using logistic regression. RESULTS: Four hundred thirteen patients with macroscopically normal colon were divided into derivation (n=275) and validation (n=138) cohorts. All patients underwent colonoscopy; 369 had ileoscopy (biopsies in 43%), and 289 underwent esophagogastroduodenoscopy (duodenal biopsies in 93%). In patients with endoscopically normal colon, histology was positive in 13.3%: 10.6% microscopic colitis; 1.5% other colitides. Among 358 patients with negative histology, the recorded diagnoses were: 48% unexplained, 25% irritable bowel syndrome, 5.6% small intestinal bacterial overgrowth, and 4.7% bile acid diarrhea. The rates of diagnoses based on positive histologies were 4% for ileal and 5% for duodenal biopsies. Older age [odds ratio (OR)=1.05] was a positive predictor, whereas body mass index (OR=0.93) and duration of diarrhea (OR=0.98) were negative predictors of positive histology. A clinical diagnostic scoring system could correctly predict 41% to 54% of patients with normal colonic histology, with a false-negative rate of 0.8% to 2.6% and a negative predictive value of 95% to 98%. CONCLUSIONS: Positive colonic biopsies were detected in <15% of patients with chronic diarrhea with normal colonoscopy; a clinical score correctly predicts likelihood of normal histology in about half the patients.

Effects of dietary components on intestinal permeability in health and disease.

Altered intestinal permeability plays a role in many pathological conditions. Intestinal permeability is a component of the intestinal barrier. This barrier is a dynamic interface between the body and the food and pathogens that enter the gastrointestinal tract. Therefore, dietary components can directly affect this interface, and many metabolites produced by the host enzymes or the gut microbiota can act as signaling molecules or exert direct effects on this barrier. Our aim was to examine the effects of diet components on the intestinal barrier in health and disease states. Herein, we conducted an in-depth PubMed search based on specific key words (diet, permeability, barrier, health, disease, and disorder), as well as cross references from those articles. The normal intestinal barrier consists of multiple components in the lumen, epithelial cell layer and the lamina propria. Diverse methods are available to measure intestinal permeability. We focus predominantly on human in vivo studies, and the literature is reviewed to identify dietary factors that decrease (e.g., emulsifiers, surfactants, and alcohol) or increase (e.g., fiber, short-chain fatty acids, glutamine, and vitamin D) barrier integrity. Effects of these dietary items in disease states, such as metabolic syndrome, liver disease, or colitis are documented as examples of barrier dysfunction in the multifactorial diseases. Effects of diet on intestinal barrier function are associated with precise mechanisms in some instances; further research of those mechanisms has potential to clarify the role of dietary interventions in treating diverse pathologic states.

Expanding criteria for slow colonic transit in patients being evaluated for chronic constipation by scintigraphy.

BACKGROUND: Colonic transit measurement [geometric center (GC) at 24 and 48 hours] identifies slow transit constipation (STC) in patients with chronic constipation. AIM: To evaluate the utility of the difference between GC24 and GC48 (Δ48-24 ) to identify STC in adults with chronic constipation. METHODS: We reviewed medical records of 250 patients, aged 18-75 years, who underwent colonic transit by scintigraphy during 1994-2019 for investigation of chronic constipation. Data collected included demographics, medical and surgical histories, and anorectal manometry. We used colonic transit from 220 healthy controls to identify the 5th percentile for diagnosing STC: 1.3 at 24 hours, and 1.9 at 48 hours. In addition, the 5th percentile for Δ48-24 was 0.38 for females and 0.29 for males. Data are reported as median and IQR [Q1, Q3]). KEY RESULTS: Among the 250 patients [median age 42.5 years (IQR 30.75, 56), 84% female], based on GC24 < 1.3, 52 (20.8%) had STC (3 males, 49 females); and based on GC48 < 1.9, 28(11.2%) had STC (3 males, 25 females). Colonic transit was normal in 74.8%. In the groups with normal GC24 and GC48, Δ48-24 identified an additional 32(15.1%) of 212 female patients and 4 (10.5%) of 38 male patients with slow progression of colonic transit between 24 and 48 hours. Among these 36 patients with abnormal Δ48-24 , 13(36.1%) had evidence of rectal evacuation disorder. CONCLUSIONS & INFERENCES: Δ48-24 measurement on scintigraphic colonic transit can identify an additional 9.2% of STC in patients with constipation without rectal evacuation disorder and can help individualize treatment of chronic constipation.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Current insights into pathogenesis of Parkinson's disease: Approach to mevalonate pathway and protective role of statins.

Although Parkinson's disease (PD) is considered as the second most common life threatening age-related neurodegenerative disorder, but the underlying mechanisms for pathogenesis of PD are remained to be fully found. However, a complex relationship between genetic and environmental predisposing factors are involved in progression of PD. Dopaminergic neuronal cell death caused by mutations and accumulation of α-synuclein in Lewy bodies and neurites was suggested as the main strategy for PD, but current studies have paid attention to the role of mevalonate pathway in incidence of neurodegenerative diseases including PD. The discovery may change the therapeutic protocols from symptomatic treatment by dopamine precursors and agonists to neurodegenerative process halting drugs. Moreover, the downstream metabolites of mevalonate pathway may be used as diagnostic biomarkers for early diagnosis of PD. Statins, as cholesterol lowering drugs, may ameliorate the enzyme complex dysfunction, a key step in the progression of the neurodegenerative disorders, oxidative stress-induced damage and neuro-inflammation. Statins exert the neuroprotective effects on striatal dopaminergic neurons through blocking the mevalonate pathway. In the present review, we have focused on the new approaches to pathogenesis of PD regarding to mevalonate pathway, in addition to the previous understood mechanisms for the disease. It tries to elucidate the novel findings about PD for the development of future diagnostic and therapeutic strategies. Moreover, we explain the controversial role of statins in improvement or progression of PD and the position of these drugs in neuroprotection in PD patients.