Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Impact of tertiary lymphoid structures on prognosis and therapeutic response in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known to have a heterogeneous desmoplastic tumour microenvironment (TME) with a large number of immunosuppressive cells. Recently, high B-cell infiltration in PDAC has received growing interest as a potential therapeutic target. METHODS: Our literature review summarises the characteristics of tumour-associated tertiary lymphoid structures (TLSs) and highlight the key studies exploring the clinical outcomes of TLSs in PDAC patients and the direct effect on the TME. RESULTS: The location, density and maturity stages of TLSs within tumours play a key role in determining the prognosis and is a new emerging target in cancer immunotherapy. DISCUSSION: TLS development is imperative to improve the prognosis of PDAC patients. In the future, studying the genetics and immune characteristics of tumour infiltrating B cells and TLSs may lead towards enhancing adaptive immunity in PDAC and designing personalised therapies.

Gastrointestinal Permeability After Bariatric Surgery: A Systematic Review.

Gastrointestinal permeability refers to the movement of substances across the gut wall. This is mediated by endotoxemia (bacterial products entering the systemic circulation), and is associated with metabolic disease. The effect of bariatric surgery on permeability remains uncertain; the associated dietary, metabolic and weight changes are suggested to influence, or trigger, altered permeability. The primary aim of this study is to synthesize evidence and analyze the effect of bariatric surgery on permeability. A systematic review was performed, searching MEDLINE, EMBASE, and Scopus until February 2023, using MESH terms "intestinal permeability", "bariatric", for studies reporting in vivo assessment of permeability. Three cohort studies and two case series were identified (n=96). Data was heterogeneous; methodology and controls preclude meta-analysis. Gastroduodenal permeability reduced post-sleeve gastrectomy (SG). Two studies showed an increase in small intestinal permeability after biliopancreatic diversion. Two studies revealed a decrease in post-Roux-en-Y gastric bypass. One study identified increased colonic permeability six months post-SG. Evidence regarding permeability change after bariatric surgery is conflicting, notably for the small intestine. Impaired colonic permeability post-SG raises concerns regarding colonic protein fermentation and harmful dietary sequelae. There are multiple interacting variables confounding gastrointestinal permeability change; procedure type, altered microbiota and metabolic response to surgery. Further understanding of this important aspect of obesity is required, both before and after bariatric surgery.

Gallstone Ileus Caused by Cholecystocolonic Fistula and Gallstone Impaction in the Sigmoid Colon: Review of the Literature and Novel Surgical Treatment with Trephine Loop Colostomy.

Gallstone ileus is an uncommon cause of intestinal obstruction and occurs following the formation of a cholecystoenteric fistula, permitting passage of gallstones into the gastrointestinal tract. Impaction of a gallstone in the sigmoid colon is rare and is usually at sites of previous colonic disease. Definitive management can be challenging due to the advanced age and co-morbidity usually seen in this group of patients. We describe a patient successfully managed with on-table endoscopy and, under local anaesthetic, the formation of a left iliac fossa trephine loop colostomy, permitting an enterolithotomy to deliver the stone whilst accommodating for severe pre-existing distal sigmoid diverticular disease. A review of the literature identified various endoscopic and surgical treatments that, depending on local expertise and patient characteristics, can be considered on a case-by-case basis. We advocate the management described in this case for patients presenting with large bowel obstruction due to gallstone ileus, with a background of diverticular disease and who are not fit for general anaesthetic or formal bowel resection, as an alternative to medical palliation alone.