Khoruts, Alexander

Abstract Ileostomy creation is common among patients with colorectal cancer, diverticulitis, and inflammatory bowel disease. Surgical removal or diversion of the colon can result in nutrition complications, most notably dehydration—a leading cause of hospital readmission—and increased risk of kidney injury. Existing studies on fluid and electrolyte management after ileostomy largely focus on short bowel syndrome or high‐output stomas, overlooking the physiological implications of ileostomy creation, even in patients with normal output. Given the absence of standardized oral rehydration protocols and limited interventional data, a scoping review was conducted to map the current evidence on oral rehydration solutions for postoperative fluid and electrolyte management in adults without short bowel syndrome or high‐output stoma. Comprehensive searches across five databases identified 5738 articles, of which 6 met inclusion criteria. Eligible studies examined adults with ileostomy for any standard indication in which oral rehydration solution use was a study objective. The included studies were methodologically heterogeneous, encompassing randomized controlled, crossover, double‐blinded comparator, retrospective cohort, and qualitative designs. Collectively, available evidence supports a pivotal role for oral rehydration solutions in both short‐term and long‐term management after ileostomy, improving hydration and reducing complications. This review highlights the need for standardized, evidence‐based oral rehydration regimens and underscores opportunities to reduce postoperative morbidity, kidney injury, and hospital readmissions while optimizing long‐term outcomes in this growing patient population.

Clostridium difficile causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. C. difficile infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against C. difficile’s toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against C. difficile expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans.

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.