Association Between Immunosuppressive Therapy and Outcome of Clostridioides difficile Infection: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.

A Rare Case of Hepatitis C-Associated Cryoglobulinemic Duodenal Vasculitis.

Intestinal involvement of cryoglobulinemia is an uncommon manifestation and marker of severe vasculitis. We describe the case of a woman admitted to our service for management of acute renal failure and progressive gastrointestinal symptoms after initiating hepatitis C virus treatment with ribavirin and sofosbuvir 4 weeks prior. With an undetectable hepatitis C viral load and persistent symptoms despite hepatitis C virus therapy cessation, an upper endoscopy revealed duodenal sloughing, erythema, and bleeding, sparking suspicion for recurrence of cryoglobulinemic vasculitis.

Adverse Effects of Grape Seed Extract Supplement: A Clinical Case and Long-Term Follow-Up.

Grape seed extract (GSE) supplement use is becoming more popular today for its potential chemopreventive and chemotherapeutic role. We report a 49-year-old male who presented with recurrent nausea, vomiting, diarrhea, and acute weakness following GSE use. A thorough medical workup ensued and no causes were identified clinically, procedurally, or with imaging. Symptoms resolved after GSE discontinuation and the patient remained symptom-free 5 years later. This case illustrates the paucity of documented detailed clinical cases and lack of controlled trials detailing a thorough and reproducible adverse effect profile of GSE supplement.

Collagenous colitis with mucosal ulcerations in a patient without nonsteroidal anti-inflammatory drug or lansoprazole use.

Chronic watery diarrhea combined with normal-appearing colonic mucosa at endoscopy with abnormal histopathology is classified as microscopic colitis. Microscopic colitis encompasses both collagenous and lymphocytic colitis. A 42-year-old Caucasian woman presented with severe diarrhea for six weeks with loose watery stools every 1-2 h, approximately 15 episodes per day. She denied any melena or significant abdominal pain. She denied nonsteroidal anti-inflammatory drug or lansoprazole use, and was only taking diphenoxylate/atropine for her symptoms. Colonoscopy revealed superficial ulcerations in the distal ascending and transverse colon and scattered ulcerations in the descending and sigmoid colon, with biopsy confirming collagenous colitis. We report a rare case of collagenous colitis accompanied by mucosal ulcerations in the absence of known culprits of mucosal ulcerations, such as nonsteroidal anti-inflammatory drugs or lansoprazole.

Lyn but not Fyn kinase controls IgG-mediated systemic anaphylaxis.

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to FcγR stimulation by IgG/Ag complexes. We have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). We found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38, and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils, and macrophages resulted in Fyn- and Lyn-regulated mediator release in vitro. FcγR-mediated activation was enhanced in Lyn-deficient (knockout [KO]) cells, but decreased in Fyn KO cells, compared with wild-type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features whereas no change was observed for Fyn KO mice, compared with wild-type littermates. Intriguingly, we establish that mast cells account for most serum histamine in IgG-induced PSA. Taken together, our findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.