The Population-level Prevalence of Exocrine Pancreas Insufficiency and the Subsequent Risk of Pancreatic Cancer.

OBJECTIVES: To study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk and, pancreas enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching of patients with EPI vs. patients without an EPI diagnosis. Adjusted odds ratio (aOR) and hazard ratios (aHR) with 95% confidence intervals were reported. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years at diagnosis. After propensity score matching, PDAC risk among patients with EPI was twice as high compared to patients without EPI (AHR 1.97, 95% confidence interval [CI] 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (aOR: 4.25, 95% CI 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT with a mean treatment duration of 921 days. No difference was observed in PDAC risk between patients with EPI treated with PERT vs. those that did not receive PERT (AHR 1.10, 95% CI 0.95-1.26, p = 0.17). CONCLUSIONS: Despite a low prevalence, patients with EPI may have a higher risk of PDAC and many of these patients with EPI were not on PERT. PERT did not appear to impact incident PDAC risk after an EPI diagnosis.

Gastrogastric intussusception and acute pancreatitis caused by a large pyloric gland adenoma treated with endoscopic submucosal dissection.

Video 1Gastrogastric intussusception and acute pancreatitis caused by a large pyloric gland adenoma treated with endoscopic submucosal dissection: A 75-year-old woman with a several-week history of intermittent postprandial nausea and vomiting presented to the emergency room after experiencing syncope, following several hours of persistent abdominal pain, nausea, and vomiting. A contrast-enhanced CT scan of the abdomen and pelvis was arranged. Axial images show gastrogastric intussusception with the intussusceptum, indicated by the dashed lines, telescoping into the intussuscipiens indicated by the arrowheads. There is a lobulated mass indicated by the asterisk, serving as the lead point for the intussusception, and there is also a small volume of fluid indicated by the arrow, which delineates the mass from the duodenum. In the coronal images, we can again see a long-segment intussusception indicated by the dashed line with a lobulated mass indicated by the asterisk serving as the lead point and extending into the proximal duodenum. Then the lobulated mass occupying and expanding the duodenal lumen can be seen, indicated by the asterisk. Upon entry into the stomach through endoscopy, the gastrogastric intussusception can be seen. The lobulated mass serving as the lead point can be seen being pulled distally. With air insufflation, the intussusception spontaneously resolved. With continued insufflation, within a few minutes, the native confirmation of the polyp was established. It was located in the proximal body along the greater curve with a lobulated appearance with a Paris 1sp morphology. In addition, there was panatrophy in the background mucosa, which was consistent with autoimmune atrophic gastritis that was subsequently confirmed on histopathology and positive anti-parietal cell antibiotics. An EUS was performed and did not show any evidence of T2 disease. Doppler showed large central feeding vessel. A plan was made for endoscopic submucosal dissection (ESD). The strategy for the ESD was an initial circumferential incision and trimming with subsequent application of multipoint traction. After a circumferential incision, a rich vascular supply is seen. After completion of the incision and trimming, the snare was advanced over the scope and the clip advanced through the instrument channel. Multiple clips were then used to secure the snare to the distal end of the lesion. With traction applied, access to the submucosa became much easier and the ESD proceeded easily. For the final remnant of submucosa, it was more easily dissected in a forward view. Chess is one of the merits of multipoint traction in that traction can be applied both proximally and distally to the lesion. The lesion was resected en bloc. The specimen was retrieved using the attached snare, but unfortunately, some of the friable head was fragmented because of its large size, yet the base remained intact. Final pathology demonstrated PGD+HGD with clear margins vertically and laterally along the base. This case of gastrogastric intussusception, causing gastric outlet obstruction and acute pancreatitis secondary to a large pyloric gland adenoma, highlights several rare clinical entities. First, gastrogastric intussusception in adults is an exceptionally rare phenomenon, with only a few documented cases reported in the literature. Second, in the case of large gastric neoplasms causing intussusception, rarely the neoplasm may extend down into the duodenum and obstruct the ampulla of Vater causing acute pancreatitis. Furthermore, pyloric gland adenomas are rare gastric neoplasms that tend to be polypoid in morphology and are associated with autoimmune gastritis, predominantly occurring in female patients, as in this case. Lastly, the traditional management for lesions causing gastroduodenal intussusception is surgical because of the risk of malignancy. However, in this case, the patient underwent successful curative and therapeutic endoscopic resection with ESD.

The Impact of Patients' Primary Language on Inpatient Gastrointestinal Bleeding Outcomes.

BACKGROUND: The impact of English proficiency on gastrointestinal bleeding (GIB) outcomes remains unclear. In this analysis, we compare inpatient GIB outcomes between patients with English as their primary language (EPL) and those with a primary language other than English (PLOE). METHODS: Using the 2019 State Inpatient Databases for New Jersey, Maryland, and Michigan, we created an analysis cohort of GIB hospitalizations using International Classification of Diseases, 10th Revision codes. Patients were stratified by primary language (EPL vs PLOE) and type of bleeding (variceal upper GI bleeding [VUGIB], nonvariceal upper GI bleeding [NVUGIB], and lower GI bleeding (LGIB)]. Regression analyses were used to compare mortality, 30-day readmissions, and length of stay. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. P < 0.05 was considered statistically significant. RESULTS: In the cohort, 5.5%-10% of the patients spoke a primary language other than English. Endoscopy utilization was lower among patients with PLOE vs EPL for NVUGIB (17.2% vs 21.2%, P < 0.001) and LGIB (26.3% vs 29.2%, P = 0.027). Patients with PLOE had higher odds of dying of VUGIB (aOR 1.45, 95% CI 1.16-2.48) and LGIB (aOR 1.71, 95% CI 1.22-2.12). Patients with PLOE were also more likely to be readmitted after NVUGIB (aOR 1.75, 95% CI 1.64-1.81). However, after controlling for the percentage of patients with PLOE discharged from each hospital, the disparities in mortality and readmissions were no longer detected. DISCUSSION: Disparities exist in GIB outcomes among patients with PLOE, but these gaps narrow at hospitals with higher percentages of patients with PLOE. Cultural and linguistic competence may improve outcomes in this vulnerable group.

A nationwide study of liver disease hospitalizations during the coronavirus pandemic in the United States.

BACKGROUND AND AIM: The impact of the Coronavirus disease-2019 (COVID-19) pandemic on patients with liver disease is not well described at the population level in the United States. We used the largest, nationwide inpatient dataset to describe inpatient liver disease outcomes in the United States during the first year of the pandemic (2020) using 2018 and 2019 as comparator years. METHODS: Using the National Inpatient Sample (2018-2020), we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality for liver-related complications including cirrhosis, alcohol-associated liver disease (ALD) and alcoholic hepatitis using regression modeling. We reported relative change (RC) in the study period. RESULTS: Decompensated cirrhosis hospitalizations decreased in 2020 compared with 2019 (RC: -2.7%, P < 0.001) while all-cause mortality increased by 15.5% (P < 0.001). Hospitalizations for ALD increased compared with pre-pandemic years (RC: 9.2%, P < 0.001) with a corresponding increase in mortality in 2020 (RC 25.2%, P = 0.002). We observed an increase in liver transplant surgery mortality during the peak months of the pandemic. Importantly, mortality from COVID-19 was higher among patients with decompensated cirrhosis (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] [1.53-1.94]), Native Americans (OR 1.76, 95% CI [1.53-2.02]), and patients from lower socioeconomic groups. CONCLUSIONS: Cirrhosis hospitalizations decreased in 2020 compared with pre-pandemic years but were associated with higher all-cause mortality rates particularly in the peak months of the COVID-19 pandemic. In-hospital COVID-19 mortality was higher among Native Americans, patients with decompensated cirrhosis, chronic illnesses, and those from lower socioeconomic groups.

Trends in gastrointestinal disease hospitalizations and outcomes during the first year of the coronavirus pandemic.

BACKGROUND: The impact of the coronavirus on hospitalizations for gastrointestinal (GI) disease, particularly at a population level is understudied. AIM: To investigate trends in hospitalizations, inpatient endoscopy resource utilization, and outcomes during the first year of the coronavirus pandemic and subsequent lockdowns. METHODS: Using the California State Inpatient Database for 2018-2020, we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality (all-cause & viral pneumonia-specific) for common inpatient GI diagnoses including acute pancreatitis, diverticulitis, cholelithiasis, non-infectious gastroenteritis, upper and lower GI bleeding (LGIB), Clostridium difficile, viral gastroenteritis, inflammatory bowel disease, and acute cholangitis. RESULTS: Disease-specific hospitalizations decreased for all included conditions except nonvariceal upper GI bleeding (NVUGIB), LGIB, and ulcerative colitis (UC) (ptrend < 0.0001). All-cause inpatient mortality was higher in 2020 vs 2019, for acute pancreatitis (P = 0.029), diverticulitis (P = 0.04), NVUGIB (P = 0.003), and Crohn's disease (P = 0.004). In 2020, hospitalization rates were lowest in April, November, and December. There was no significant corresponding increase in inpatient mortality except in UC (ptrend = 0.048). Viral pneumonia and viral pneumonia complicated by respiratory failure increased (P < 0.001) among GI hospitalizations. Endoscopy utilization within 24 h of admission was unchanged for GI emergencies except NVUGIB (P < 0.001). CONCLUSION: Our findings suggest that hospitalization rates for common GI conditions significantly declined in California during the COVID pandemic, particularly in April, November and December 2020. All-cause mortality was significantly higher among acute pancreatitis, diverticulitis, NVUGIB, and Crohn's disease hospitalizations. Emergency endoscopy rates were mostly comparable between 2020 and 2019.

Acute Pancreatitis as a First Presentation of Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare necrotizing antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation in small-sized arteries. Gastrointestinal involvement is exceedingly rare in GPA. Here, we present a case of recurrent acute pancreatitis as the initial presentation of GPA. The diagnosis was made based on radiological and pathological findings of acute pancreatitis in conjunction with positive anti-PR3 antibody which is strongly associated with GPA. Systemic vasculitides are rare but important to consider in cases of idiopathic acute pancreatitis. Early diagnosis and therapy allow for high rates of remission and improved survival rates.

Healthcare Disparities Among Homeless Patients Hospitalized With Gastrointestinal Bleeding: A Propensity-Matched, State-Level Analysis.

GOALS: Examine outcomes among homeless patients admitted with gastrointestinal (GI) bleeding, including all-cause mortality and endoscopic intervention rates. BACKGROUND: Hospitalizations among homeless individuals have increased steadily since at least 2007 but little is known about GI outcomes in these patients. STUDY: The 2010-2014 Healthcare Utilization Project (HCUP) State Inpatient Databases from New York and Florida were used to identify adults admitted with a primary diagnosis of acute upper or lower GI bleed. Homeless patients were 1:3 matched with nonhomeless patients using a propensity-score greedy-matched algorithm. The primary outcome (all-cause in-hospital mortality) and secondary outcomes (30-day readmission rates, endoscopy utilization, length of stay, and total hospitalization costs) were compared. RESULTS: We matched 4074 homeless patients with 12,222 nonhomeless patients. Most hospitalizations for homeless individuals were concentrated in 113 (26.4%) of 428 hospitals. Homeless adults were more likely to be younger, male, African American or Hispanic, and on Medicaid. They experienced significantly higher odds of all-cause inpatient mortality compared with nonhomeless patients admitted with GI bleeding (OR 1.37, 95% CI 1.11-1.69). Endoscopy utilization rates were also lower for both upper (OR 0.62, 95% CI 0.55-0.71) and lower (OR 0.76, 95% CI 0.68-0.85) GI bleeding, though upper endoscopy rates within the first 24 hours were comparable (OR 1.11, 95% CI 1.00-1.23). Total hospitalization costs were lower ($9,715 vs. $12,173, P <0.001) while 30-day all-cause readmission rates were significantly higher in the homeless group (14.9% vs. 18.4%, P <0.001). CONCLUSIONS: Homeless patients hospitalized for GI bleeding face disparities, including higher mortality rates and lower endoscopy utilization.

Refractory Hyperlactatemia and Hypoglycemia in an Adult with Non-Hodgkin's Lymphoma: A Case Report and Review of the Warburg Effect.

Lactate is a byproduct of anaerobic glycolysis, and hyperlactatemia is commonly seen in critically ill patients. We report a case of an elderly male presenting with undifferentiated constitutional symptoms, anemia, thrombocytopenia, severe lactic acidosis, refractory hypoglycemia, and a newly detected abdominal mass. A dedicated workup ruled out infectious etiologies and revealed metastatic non-Hodgkin's lymphoma. This study explores etiologies of type B lactic acidosis in oncology patients, with a focus on Warburg's effect, and its potential for prognostication.

The fragility of randomized placebo-controlled trials for irritable bowel syndrome.

BACKGROUND: The fragility index (FI) represents the number of participants whose status in a trial would have to change from a non-event (not experiencing the primary endpoint) to an event (experiencing the primary endpoint) in order to turn a statistically significant result into a non-significant result. We sought to evaluate the fragility indices of irritable bowel syndrome [IBS-mixed (IBS-M), IBS-constipation (IBS-C), & IBS-diarrhea (IBS-D)] trials. METHODS: Irritable bowel syndrome trials published in high-impact journals were identified from Medline. Trials had to be in adults, randomized, parallel-armed, with at least one statistically significant binary outcome, and an achieved primary endpoint of therapeutic efficacy. FI and correlation coefficients were calculated, and regression modeling used to identify predictors of a high FI. KEY RESULTS: Twelve trials were analyzed with a median FI of 6 (range: 0-38). Median sample size in all trials was 366 (range: 44-856). Trial publication year (p = 0.71), journal impact factor (p = 0.52), duration of study (p = 0.12), and number need to treat [NNT] (p = 0.29) were not predictive of a high FI. While a lower p-value correlated with a higher FI (p = 0.039), no correlation was noted between FI and impact factor (R = -0.20, p = 0.52), trial publication year (R = 0.12, p = 0.71), duration of trial (R = -0.46, p = 0.13), NNT (R = -0.34, p = 0.29), and sample size (R = 0.23, p = 0.5). The highest FI was in a Ramosetron trial (FI = 30) for IBS-D. CONCLUSION & INFERENCES: A median of six participants is needed to nullify results in the included IBS trials suggesting how easily statistical significance based on a threshold p-value may be overturned.

Third Cranial Nerve Palsy Due to COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is known to be primarily a viral infection affecting the pulmonary system leading to severe pneumonia and acute respiratory distress syndrome. COVID-19 has also been found to affect the neurological system causing various nerve palsies. While some studies have suggested these neurological manifestations may indicate severe disease, cranial nerve palsies in the setting of COVID-19 infection have been linked to improved patient outcomes and mild viral symptoms. We present a case of a 55-year-old male with confirmed COVID-19 infection presenting with third cranial nerve palsy. Since his hospital course remained unremarkable, he was treated supportively for his COVID-19 infection and remained stable on room air during his hospitalization. No causative factors other than COVID-19 were identified as a cause for his cranial three nerve palsy which resolved spontaneously during outpatient follow-up. Although different cranial nerve palsies associated with COVID-19 infection have been identified in the literature, the pathogenesis and prognosis of cranial nerve palsy is still unclear. This case emphasizes the need for continued symptom monitoring and identification in patients diagnosed with COVID-19.

Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission.

Collective migration of epithelial cells is an integral part of embryonic development, wound healing, tissue renewal and carcinoma invasion. While previous studies have focused on cell-extracellular matrix adhesion as a site of migration-driving, traction force-transmission, cadherin mediated cell-cell adhesion is also capable of force-transmission. Using a soft elastomer coated with purified N-cadherin as a substrate and a Hepatocyte Growth Factor-treated, transformed MDCK epithelial cell line as a model system, we quantified traction transmitted by N-cadherin-mediated contacts. On a substrate coated with purified extracellular domain of N-cadherin, cell surface N-cadherin proteins arranged into puncta. N-cadherin mutants (either the cytoplasmic deletion or actin-binding domain chimera), however, failed to assemble into puncta, suggesting the assembly of focal adhesion like puncta requires the cytoplasmic domain of N-cadherin. Furthermore, the cytoplasmic domain deleted N-cadherin expressing cells exerted lower traction stress than the full-length or the actin binding domain chimeric N-cadherin. Our data demonstrate that N-cadherin junctions exert significant traction stress that requires the cytoplasmic domain of N-cadherin, but the loss of the cytoplasmic domain does not completely eliminate traction force transmission.

Calpains mediate p53 activation and neuronal death evoked by DNA damage.

DNA damage is an initiator of neuronal death implicated in neuropathological conditions such as stroke. Previous evidence has shown that apoptotic death of embryonic cortical neurons treated with the DNA damaging agent camptothecin is dependent upon the tumor suppressor p53, an upstream death mediator, and more distal death effectors such as caspases. We show here that the calcium-regulated cysteine proteases, calpains, are activated during DNA damage induced by camptothecin treatment. Moreover, calpain deficiency, calpastatin expression, or pharmacological calpain inhibitors prevent the death of embryonic cortical neurons, indicating the important role of calpain in DNA damage-induced death. Calpain inhibition also significantly reduced and delayed the induction of p53. Consistent with the actions of calpains upstream of p53 and the proximal nature of p53 death signaling, calpain inhibition inhibited cytochrome c release and DEVD-AFC cleavage activity. Taken together, our results indicate that calpains are a key mediator of p53 induction and consequent caspase-dependent neuronal death due to DNA damage.