Timing of endoscopic retrograde cholangiopancreatography in acute biliary pancreatitis without cholangitis: a nationwide inpatient cohort study.

BACKGROUND: The timing of endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute biliary pancreatitis without cholangitis is unclear. We accessed a national database to analyze the outcomes of urgent (<24 h) and early (24-72 h) ERCP in this cohort. METHODS: The cohort was extracted from the Nationwide Inpatient Sample database. Hospital ERCP volumes were generated using unique hospital identifiers. Multivariate regression modeling was used to analyze the predictors of urgent vs. early ERCP use, and to determine various outcome variables between the 2 cohorts. RESULTS: Overall, 105,433 admissions were evaluated. There was a significant rise in urgent ERCP performed over the study period. Older patients, males, patients with comorbidities, African American and Hispanic patient populations were less likely to receive urgent ERCP. High ERCP volume hospitals, teaching hospitals, and hospitals in the Midwest and West were more likely to perform urgent ERCP. There were no differences in mortality rates or complication rates between the 2 cohorts. However, there were significant differences in length of stay and healthcare cost analysis. CONCLUSIONS: The increasing use of urgent ERCP did not result in a clinically significant benefit in terms of mortality, length of stay, or healthcare cost analysis. The use of urgent ERCP is also not uniform across various demographic and hospital cohorts. Urgent ERCP may be over-utilized, and it may be reasonable to perform ERCP in this patient population based on the physician's suspicion about the severity of disease.

Predictors of do-not-resuscitate order utilization in decompensated cirrhosis hospitalized patients: A nationwide inpatient cohort study.

INTRODUCTION AND OBJECTIVES: Decompensated cirrhosis carries high inpatient morbidity and mortality. Consequently, advance care planning is an integral aspect of medical care in this patient population. Our study aims to identify do-not-resuscitate (DNR) order utilization and demographic disparities in decompensated cirrhosis patients. PATIENTS OR MATERIALS AND METHODS: Nationwide Inpatient Sample was used to extract the cohort of patients from January 1st, 2016 to December 31st, 2017, based on the most comprehensive and recent data. The first cohort included hospitalized patients with decompensated cirrhosis. The second cohort included patients with decompensated cirrhosis with at least one contraindication for liver transplantation. RESULTS: A cohort of 585,859 decompensated cirrhosis patients was utilized. DNR orders were present in 14.2% of hospitalized patients. DNR utilization rate among patients with relative contraindication for liver transplantation was 15.0%. After adjusting for co-morbid conditions, disease severity, and inpatient mortality, African-American and Hispanic patient populations had significantly lower DNR utilization rates. There were regional, and hospital-level differences noted. Moreover, advanced age, advanced stage of decompensated cirrhosis, inpatient mortality, and relative contraindications for liver transplantation (metastatic neoplasms, dementia, alcohol misuse, severe cardiopulmonary disease, medical non-adherence) were independently associated with increased DNR utilization rates. CONCLUSIONS: The rate of DNR utilization in patients with relative contraindications for liver transplantation was similar to patients without any relative contraindications. Moreover, there were significant demographic and hospital-level predictors of DNR utilization. This information can guide resource allocation in educating patients and their families regarding prognosis and outcome expectations.

Prevalence and Associations of Avascular Necrosis of the Hip in a Large Well-characterized Cohort of Patients With Inflammatory Bowel Disease.

OBJECTIVES: Avascular necrosis (AVN) is associated with significant morbidity potentially causing severe pain and disability; patients with inflammatory bowel disease (IBD) have a higher prevalence of AVN compared with non-IBD populations. The purpose of our study was to determine the prevalence of AVN in our IBD population and to evaluate these subjects for the presence of clinical characteristics associated with AVN on computed tomography (CT) imaging. METHODS: In 1313 IBD patients with abdomen/pelvis CT scans, we identified 27 patients (2.1%) with CT findings consistent with AVN. Through historical chart review, we confirmed that most patients had prior exposure to steroids, although 2 patients had no documented steroid exposure at all. RESULTS: We found that 59% of the concurrent radiology reports did not comment on the presence of AVN, suggesting that incidental CT findings of AVN among IBD patients are likely underreported. Notably, we found that 63% of these cases had documented complaints of low-back and/or hip pain. Using logistic regression, we found an association between anti-neutrophil cytoplasmic antibody-positive status across IBD (p = 0.007) and a smoking history in Crohn disease (p = 0.03) with the presence of AVN. CONCLUSIONS: We found that a significant proportion of IBD patients with AVN are reported in their records as having hip or low-back pain, and review of CT imaging under dedicated bone windows may identify AVN among this population. Our findings also suggest that additional etiological factors, beyond corticosteroids, contribute to the development of AVN in IBD. Further investigation is warranted regarding the mechanisms associated with AVN in IBD.

Computer versus physician identification of gastrointestinal alarm features.

OBJECTIVE: It is important for clinicians to inquire about "alarm features" as it may identify those at risk for organic disease and who require additional diagnostic workup. We developed a computer algorithm called Automated Evaluation of Gastrointestinal Symptoms (AEGIS) that systematically collects patient gastrointestinal (GI) symptoms and alarm features, and then "translates" the information into a history of present illness (HPI). Our study's objective was to compare the number of alarms documented by physicians during usual care vs. that collected by AEGIS. METHODS: We performed a cross-sectional study with a paired sample design among patients visiting adult GI clinics. Participants first received usual care by their physicians and then completed AEGIS. Each individual thus contributed both a physician-documented and computer-generated HPI. Blinded physician reviewers enumerated the positive alarm features (hematochezia, melena, hematemesis, unintentional weight loss, decreased appetite, and fevers) mentioned in each HPI. We compared the number of documented alarms within patient using the Wilcoxon signed-rank test. RESULTS: Seventy-five patients had both physician and AEGIS HPIs. AEGIS identified more patients with positive alarm features compared to physicians (53% vs. 27%; p<.001). AEGIS also documented more positive alarms (median 1, interquartile range [IQR] 0-2) vs. physicians (median 0, IQR 0-1; p<.001). Moreover, clinicians documented only 30% of the positive alarms self-reported by patients through AEGIS. CONCLUSIONS: Physicians documented less than one-third of red flags reported by patients through a computer algorithm. These data indicate that physicians may under report alarm features and that computerized "checklists" could complement standard HPIs to bolster clinical care.

Clinical outcomes following revision anterior shoulder arthroscopic capsulolabral stabilization.

INTRODUCTION: Traditionally surgeons have treated failed shoulder instability with open capsulolabral repair. Despite improved instrumentation, technique and familiarity in shoulder arthroscopy, few studies have reported the outcomes of arthroscopic revision shoulder instability repair. The purpose of this study was to assess clinical outcomes in patients following revision shoulder arthroscopic anterior capsulolabral stabilization. MATERIALS AND METHODS: Sixty-two patients (63 shoulders) with failure of primary instability repairs were treated with revision arthroscopic anterior shoulder stabilization at a mean follow-up of 46.9 ± 16.8 months (range 18-78). Clinical outcomes were evaluated using validated patient-reported outcome questionnaires including the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, visual analog pain scale and Western Ontario Shoulder Instability Index. In addition, patients were queried for recurrent instability events (subluxation or dislocation) or revision surgery. RESULTS: At final follow-up, the mean postoperative Western Ontario Shoulder Instability normalized score was 80.1 ± 18.7 (range 15.0-100). There were clinically significant improvements in American Shoulder and Elbow Surgeons scores, Simple Shoulder Test scores and ten-point visual analog scale for pain (P < 0.001). Recurrent instability occurred in 12 shoulders (19.0 %), with number of prior surgeries and hyperlaxity found to be significant risk factor for failure (P < 0.001 and P = 0.04, respectively). CONCLUSION: Revision arthroscopic anterior stabilization of the shoulder can result in satisfactory outcomes in appropriately selected patients who have failed previous capsulolabral repair. An increased number of prior surgeries and hyperlaxity are predictive of poor outcome. STUDY DESIGN: Case series, LOE IV.

Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease and conditions such as ischemic stroke affect millions of individuals annually and exert an enormous financial burden on society. A hallmark of these conditions is the abnormal loss of neurons. Currently, there are no effective strategies to prevent neuronal death in these pathologies. We report that several 2-arylidine and 2-hetarylidin derivatives of the 1,4-benzoxazines class of compounds are highly protective in tissue culture models of neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that neuroprotection by these compounds does not involve the Raf-MEK-ERK or PI-3 kinase-Akt signaling pathways nor other survival-promoting molecules such as protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone deacetylases (HDACs). We tested one of these compounds, (Z)-6-amino-2-(3',5'-dibromo-4'-hydroxybenzylidene)-2H-benzo[b][1,4]oxazin-3(4H)-one, designated as HSB-13, in the 3-nitropropionic acid (3-NP)-induced mouse model of Huntington's disease. HSB-13 reduced striatal degeneration and improved behavioral performance in mice administered with 3-NP. Furthermore, HSB-13 was protective in a Drosophila model of amyloid precursor protein (APP) toxicity. To understand how HSB-13 and other 1,4-benzoxazines protect neurons, we performed kinase profiling analyses. These analyses showed that HSB-13 inhibits GSK3, p38 MAPK, and cyclin-dependent kinases (CDKs). In comparison, another compound, called ASK-2a, that protects cerebellar granule neurons against low-potassium-induced death inhibits GSK3 and p38 MAPK but not CDKs. Despite its structural similarity to HSB-13, however, ASK-2a is incapable of protecting cortical neurons and HT22 cells against homocysteic acid (HCA)-induced or Abeta toxicity, suggesting that protection against HCA and Abeta depends on CDK inhibition. Compounds described in this study represent a novel therapeutic tool in the treatment of neurodegenerative diseases.

Synthesis and structure-activity relationship studies of 3-substituted indolin-2-ones as effective neuroprotective agents.

Neurodegenerative diseases are a major health problem particularly among the elderly. Drugs to prevent or slow down the death of neurons are urgently needed but are currently unavailable. We previously reported that the c-Raf inhibitor, GW5074 {5-iodo-3-[(3',5'-dibromo-4'-hydroxyphenyl) methylene]-2-indolinone}, is protective in tissue culture and in vivo paradigms of neurodegeneration. However, at doses slightly higher than those at which it is protective, GW5074 displays toxicity when tested in neuronal cultures. We report herein the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of novel 3-substituted indolin-2-one compounds that are highly neuroprotective but lack the toxicity of GW5074. Of the 45 analogs tested in this study, compounds 7, 37, 39, and 45 were found to be the most potent neuroprotective and thus represent promising lead compounds for preclinical development for the treatment of neurodegenerative disorders.