Risk stratification before esophageal and gastric endoscopic submucosal dissection (ESD) in older adults often relies on age and comorbidity; however, these measures may not capture vulnerability reflected in routinely collected claims data. We aimed to evaluate the claims-based frailty and short-term adverse events association after esophageal and gastric endoscopic submucosal dissection. We used a nationwide Japanese administrative database to identify patients aged ≥ 75 years who underwent first esophageal or gastric ESD. Frailty was defined using the Hospital Frailty Risk Score (HFRS), calculated from diagnoses during a 2 year lookback period. After 1:1 propensity score matching, frail and non-frail patients were compared. The primary outcome was binary composite of short-term adverse events, including in-hospital perforation/peritonitis, delayed bleeding, thromboembolism, aspiration pneumonia, and 30 day all-cause mortality. Component outcomes, survival, length of stay, costs, and readmission were also evaluated. Among 15,184 eligible patients, 4,970 matched pairs were included. Frailty was associated with the composite adverse outcome (adjusted odds ratio 1.35; 95
Diverting loop ileostomy is commonly used to mitigate the consequences of anastomotic leakage after rectal cancer surgery. However, some patients do not undergo stoma closure, resulting in a permanent stoma that may impair quality of life. This study evaluated the closure rate, reasons for non-closure, and associated preoperative factors using multicenter prospective data. This study was a subanalysis of a multicenter prospective study conducted at 24 institutions. Patients with rectal adenocarcinoma who underwent laparoscopic or robotic low anterior resection or intersphincteric resection with planned diverting loop ileostomy between July 2015 and April 2021 were included. Stomas not closed within 1 year were classified as non-closed. Preoperative characteristics were compared between the stoma closure and non-closure groups using univariable analyses. Among 320 patients, 298 (93.1
The gut microbiome influences epithelial barrier integrity, metabolite availability, mucosal immune tone, and vaccine responsiveness, all of which are relevant to enterically transmitted viral infection. Norovirus and rotavirus primarily replicate in the intestinal mucosa and cause acute gastroenteritis, whereas poliovirus replicates in the gut and may disseminate systemically. Hepatitis A virus and hepatitis E virus are acquired through the intestine and shed fecally, but their dominant clinical manifestation is hepatitis. This review synthesizes evidence linking the bacteriome, phageome/virome, and mycobiome with these viruses, while explicitly distinguishing direct enteric virus mechanisms from broader microbiome-immune or metabolite pathways and from cross-kingdom evidence extrapolated from intestinal inflammation or pathobiont studies. The strongest evidence supports selected virus–bacterium and virus–metabolite mechanisms, including bacterial glycan interactions in norovirus, bacterial LPS-mediated poliovirus stabilization, bile acid-dependent human norovirus replication in enteroids, and rotavirus-associated barrier disruption. Human studies remain dominated by stool-based associations that are difficult to separate from inflammation, diet, antibiotic exposure, diarrhea, and sampling time. We therefore rank evidence across experimental, organoid, animal, human observational, and clinical-translational levels, and highlight concrete applications for severe gastroenteritis risk prediction, prolonged shedding, impaired barrier recovery, and oral vaccine nonresponse. Future progress will require longitudinal, spatially resolved, multi-kingdom, and multi-omics studies linked to human-relevant experimental systems.
To reassess the clinico-epidemiological characteristics of chronic pancreatitis (CP) in Japan, we conducted a nationwide epidemiological survey. A two-stage nationwide survey was performed targeting patients with CP treated at participating hospitals in 2021. The first-stage survey estimated the number of patients, and the second-stage survey collected detailed clinical information. The estimated number of patients with definite or probable CP in 2021 was 73,590 (prevalence, 58.6 per 100,000 population), representing a 30
The therapeutic potential of oncolytic adenoviruses (ADVs) in colorectal cancer is constrained by a counterproductive host response: virus-triggered hyperactivation of the pro-survival AKT pathway, which fosters an immunosuppressive tumor microenvironment. We engineered a novel oncolytic adenovirus, ADV-PRK, designed to co-express the AKT-inhibitory peptide PRK. Its antitumor efficacy and mechanisms were evaluated in syngeneic (MC38, CT26) and humanized mouse models. Molecular analyses (Western blot, immunofluorescence, and qPCR) elucidated signaling pathways. Immunological outcomes were assessed via flow cytometry and in vitro co-culture assays. Combination therapies with anti-PD-1 or CAR-T cells were tested in vivo. We demonstrate that ADV-PRK abrogates phosphorylation of both AKT and its downstream effector, the ER calcium channel IP3R3. This suppression drives ER calcium efflux, inducing calreticulin (CRT) translocation to the cell surface. Surface-exposed CRT acts as a potent “eat-me” signal, licensing dendritic cells to prime and activate tumor-specific CD8⁺ T cells, which are essential for efficacy. In vivo, ADV-PRK monotherapy achieved superior tumor control. It demonstrated potent synergy with both anti-PD-1 and CAR-T cell therapy, by remodeling the immune landscape to expand activatable T cells and support adoptive cellular therapy. Its activity in a humanized model confirms translational relevance. Our work delineates a distinct immunomodulatory axis, AKT–IP3R3–Ca2⁺–CRT, to reverse adenovirus-induced immunosuppression. This provides a translatable, mechanism-based strategy to convert immunologically “cold” tumors into environments receptive to immunotherapy, thereby offering a rational combinatorial approach to overcome resistance and significantly broaden the applicability of current immunotherapies. An oncolytic adenovirus delivering the AKT-inhibitory peptide (ADV-PRK) triggers an immunogenic cascade via the AKT–IP3R3–calcium–calreticulin axis. By inducing calreticulin exposure, it arms dendritic cells to prime tumor-specific CD8⁺ T cells, ultimately synergizing with anti-PD-1 or CAR-T therapy against colorectal cancer.
