Medical Treatment Options for Ulcerative Colitis.

The landscape of management of ulcerative colitis, a type of inflammatory bowel disease, continues to change with advancement in pharmaceutical options as well as clinical treatment targets. Ulcerative colitis primarily involves the superficial layers of the large bowel, and cause active inflammation that can affect the colon from the rectum to the cecum in a relapsing and a remitting course. In this review, we provide evidence-based guidance on the selection of appropriate medical therapies based on individual patient and disease characteristics, with a focus on biologics and small molecules. We also review the role of surgery and management of acute severe ulcerative colitis.

COVID-19 Related Predisposition to Diabetic Ketoacidosis.

Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate hyperglycemia and can cause life-threatening diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM). The objective of this study is to compare the characteristics of diabetic COVID-19 patients with and without DKA and to determine the predictors of mortality in the setting of COVID-19 and DKA. Methods This is a retrospective single-center cohort study including patients admitted to our hospital with COVID-19 and DM from March 2020 to June 2020. Patients with DKA were filtered as per the diagnostic criteria set by the American Diabetes Association (ADA). Patients with hyperosmolar hyperglycemic state (HHS) were excluded. A retrospective analysis was performed, which included those who developed DKA and those with neither DKA nor HHS. The primary outcome measurement was mortality rate and predictors of mortality for DKA. Results Out of 301 patients with COVID-19 and DM, 30 (10%) had DKA and five (1.7%) had HHS. Mortality was significantly higher in the DKA group compared to the non-DKA/HHS group (36.6% vs 19.5%; OR: 2.38; p=0.03). After adjusting for parameters used for multivariate logistic model for mortality, DKA was no longer associated with mortality (OR: 2.08, p=0.35). The independent predictors for mortality were age, platelet count, serum creatinine, C-reactive protein, hypoxic respiratory failure, need for intubation, and need for vasopressors. Conclusion Our study demonstrates higher mortality rate in diabetic COVID-19 patients with DKA. Though direct and independent statistical association of mortality with DKA could not be proven in our multivariate logistic model, physicians must be vigilant in risk-stratifying and managing these patients in a timely manner.

Impact of Obesity on Response to Biologic Therapies in Patients with Inflammatory Bowel Diseases.

Approximately 20-40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is associated with inferior outcomes in patients with IBD, with lower rates of achieving remission, poor quality of life, and higher burden of unplanned healthcare utilization. Multiple cohort studies in patients with immune-mediated inflammatory diseases, including IBD, treated with biologic agents like tumor necrosis factor-α antagonists have suggested that obesity is associated with inferior response to biologic therapy. This may be related to the negative impact of obesity on the pharmacokinetics of biologic agents. Pharmacokinetic studies of multiple biologic agents have demonstrated that high body weight is associated with more rapid clearance and a higher volume of distribution of biologic agents, which leads to low trough concentrations. Randomized trials in patients with psoriasis and psoriatic arthritis treated with biologic agents suggest that diet- or lifestyle-induced weight loss is associated with improved response to therapy. This provides an opportunity to explore intentional weight loss as adjunctive therapy in obese patients with IBD. However, diet and lifestyle interventions for weight loss are hard to implement in patients with IBD; hence, long-term therapy with weight-loss agents (such as with phentermine-topiramate, naltrexone-bupropion) is attractive as adjunctive therapy in obese patients with IBD.

Hematemesis as an Initial Presentation of Enteropathy-Associated T-Cell Lymphoma.

Enteropathy-associated T-cell lymphoma (EATL) is a tumor of intraepithelial T-lymphocytes arising in the small intestine. Based on the genetic profile, immunohistochemistry, and histology, EATL is divided into two subtypes. EATL type I occurs in individuals with celiac disease (CD) while EATL type II is a sporadic form that occurs in individuals without CD. Intensive chemotherapy and surgery are the mainstay treatment. However, despite the currently available treatment options, the five-year survival rate is only 9%. EATL presents as abdominal pain, nausea, or slow gastrointestinal bleeding. Severe bleeding leading to hemodynamic instability is rarely known in EATL. Therefore, we present a unique case of EATL who presented with acute and severe gastrointestinal bleeding with no prior history of CD.

Recurrent Large Bowel Obstruction Caused by Necrotizing Pancreatitis: A Rare Manifestation.

Mechanical obstruction of the colon is rare with necrotizing pancreatitis but is associated with high morbidity and mortality. However, pancreatic ileus, colonic necrosis, and pancreatic colonic fistulae with necrotizing pancreatitis are well known. The anatomic proximity of the pancreas to the transverse colon becomes clinically relevant when a patient with pancreatitis demonstrates a localized ileus of the transverse colon (an old term "the colon cut-off sign"), even when the disease is mild, or lower gastrointestinal bleeding secondary to necrosis of the segment in severe acute pancreatitis. We present the case of a 25-year-old female with choledocholithiasis who presented with severe abdominal pain and was found to have recurrent large bowel obstruction secondary to walled-off pancreatic necrosis. Bowel obstruction is a rare complication of walled-off necrosis, but clinicians should be aware of it due to significantly increased mortality rates. Recurrent bowel obstructions are rarely known in necrotizing pancreatitis and may warrant a bowel resection either electively or acutely. Walled-off necrosis does not respond to typical treatment of symptomatic pseudocysts, which includes endoscopic cystogastrostomy or percutaneous drainage with small-bore catheters. Endoscopic or surgical necrosectomy is necessary for the resolution of walled-off necrosis to evacuate the non-liquefied components.

Percutaneous Intervention for Myocardial Infarction After Noncardiac Surgery: Patient Characteristics and Outcomes.

BACKGROUND: Few studies have explored percutaneous coronary intervention (PCI) in perioperative myocardial infarction (PMI), even though PMI is a major cause of mortality in patients undergoing urgent/emergent noncardiac surgery. OBJECTIVES: This study sought to describe the angiographic characteristics and outcomes in patients presenting to the cardiac catheterization laboratory for myocardial infarction sustained after undergoing noncardiac surgery, with a detailed analysis of those undergoing PCI. METHODS: We included all patients presenting to the catheterization laboratory at our institution after PMI from 2003 to 2012, who had noncardiac surgery within the previous 7 days. Data from patients who underwent PCI were analyzed using both standard regression and time-to-event survival analysis. RESULTS: From 2003 to 2012, 1,093 patients with 3,832 person-years of follow-up underwent diagnostic coronary angiography, of whom 281 (40 ST-segment elevation myocardial infarction [STEMI] and 241 non-ST-segment elevation myocardial infarction [NSTEMI] cases) underwent PCI. Using Kaplan-Meier survival analysis, we found 30-day mortality was 5.2% and 1-year mortality was 15% in the overall population. In the PCI subpopulation, we estimated 30-day mortality to be 11.3%. The 30-day death rate in the STEMI cohort was 31.2% and 8.5% in the NSTEMI cohort of the PCI subpopulation. Stepwise logistic regression revealed the following factors as strong predictors of 30-day mortality after PCI: bleeding event after PCI (odds ratio [OR]: 4.33; 95% confidence limits (CL): 1.52 to 12.30), peak troponin T level (OR: 1.20; 95% CL: 1.08 to 1.34), and underlying peripheral vascular disease (OR: 4.86; 95% CL: 1.66 to 14.22). Cox proportional hazard analysis of survival data showed that increasing age (hazard ratio [HR]: 1.03; 95% CL: 1.01 to 1.04), bleeding after PCI (HR: 2.31; 95% CL: 1.61 to 3.32), renal insufficiency (HR: 2.26; 95% CL: 1.51 to 3.39]), and vascular surgery (HR: 1.48; 95% CL: 1.02 to 2.15]) were all significant predictors of long-term mortality after PCI. CONCLUSIONS: Perioperative MI has a markedly high mortality rate, despite PCI. Bleeding event, peak troponin T level, and peripheral vascular disease predict mortality within 30 days of PCI in this patient population. Similarly, older age, vascular surgery, bleeding event, and renal dysfunction strongly predict long-term mortality after PCI in the setting of PMI.

Transforming growth factor ß and insulin signal changes in stromal fibroblasts of individual keratoconus patients.

Keratoconus (KC) is a complex thinning disease of the cornea that often requires transplantation. The underlying pathogenic molecular changes in this disease are poorly understood. Earlier studies reported oxidative stress, metabolic dysfunctions and accelerated death of stromal keratocytes in keratoconus (KC) patients. Utilizing mass spectrometry we found reduced stromal extracellular matrix (ECM) proteins in KC, suggesting ECM-regulatory changes that may be due to altered TGFß signals. Here we investigated properties of stromal cells from donor (DN) and KC corneas grown as fibroblasts in serum containing DMEM: F12 or in serum-free medium containing insulin, transferrin, selenium (ITS). Phosphorylation of SMAD2/3 of the canonical TGFß pathway, was high in serum-starved DN and KC fibroblast protein extracts, but pSMAD1/5/8 low at base line, was induced within 30 minutes of TGFß1 stimulation, more so in KC than DN, suggesting a novel TGFß1-SMAD1/5/8 axis in the cornea, that may be altered in KC. The serine/threonine kinases AKT, known to regulate proliferation, survival and biosynthetic activities of cells, were poorly activated in KC fibroblasts in high glucose media. Concordantly, alcohol dehydrogenase 1 (ADH1), an indicator of increased glucose uptake and metabolism, was reduced in KC compared to DN fibroblasts. By contrast, in low glucose (5.5 mM, normoglycemic) serum-free DMEM and ITS, cell survival and pAKT levels were comparable in KC and DN cells. Therefore, high glucose combined with serum-deprivation presents some cellular stress difficult to overcome by the KC stromal cells. Our study provides molecular insights into AKT and TGFß signal changes in KC, and a mechanism for functional studies of stromal cells from KC corneas.