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Background. Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus. Methods. Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths. Results. Gastroenteritis mortality averaged 39/1 000 000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains. Conclusions. Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.

Background. Mortality among patients with Clostridium difficile infection (CDI) is high. Because of high age and multiple underlying diseases, CDI-related mortality is difficult to estimate. We estimated CDI-related mortality in an endemic situation, not influenced by outbreaks and consequently certain patients and C. difficile strains. Methods. Between 2006 and 2009, 13 Dutch hospitals included all hospitalized CDI patients. Nine hospitals individually matched each CDI patient to 2 control patients, based on ward and time of CDI hospitalization. Survival status was obtained via the Dutch Civil Registration System. Kaplan-Meier and Cox regression were used for survival analysis. Results. We identified 1366 patients with CDI (1.33 per 1000 admissions). All-cause mortality risk was 13% after 30 days and 37% after 1 year. The highest mortality was seen among elderly patients and patients with polymerase chain reaction ribotype 027. Three hundred seventeen CDI patients were matched to 317 patients without diarrhea and 232 patients with diarrhea, with a 30-day mortality risk of 5.4% and 8.6%, respectively. CDI patients had a 2.5-fold increased 30-day mortality rate compared to controls without diarrhea (hazard ratio 2.5 [95% confidence interval, 1.4–4.3]) when adjusted for age, sex, and underlying diseases. CDI-related death occurred mainly within 30 days after diagnosis. Conclusions. Mortality among CDI patients is high, even in an endemic situation. Our results show that CDI is associated with to a 2.5-fold increase in 30-day mortality. This highlights the considerable disease burden and clinical impact of CDI, even in absence of an outbreak.

Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15–1.36; P  = 1.8 × 10 −7 ), including sepsis (HR 2.68; 95% CI = 2.25–3.19; P  = 3.1 × 10 −28 ), pneumonia (HR 1.76; 95% CI = 1.53–2.03; P  = 2.3 × 10 −15 ), digestive system infections (HR 1.51; 95% CI = 1.32–1.73; P  = 2.2 × 10 −9 ) and genitourinary infections (HR 1.25; 95% CI = 1.11–1.41; P  = 3.7 × 10 −4 ). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections. The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

Background. The implementation of treated municipal water systems in the 20th century led to a dramatic decrease in waterborne disease in the United States. However, communities with deficient water systems still experience waterborne outbreaks. In August 2004, we investigated an outbreak of gastroenteritis on South Bass Island, Ohio, an island of 900 residents that is visited by>500,000 persons each year. Methods. To identify the source of illness, we conducted a case-control study and an environmental investigation. A case was defined as diarrhea in a person who traveled to the island during the period from May 1 through 30 September 2004 and became ill within 2 weeks after the visit. Healthy travel companions served as matched control subjects. We also performed an environmental assessment and extensive testing of island water sources. Results. Among the 1450 persons reporting illness, Campylobacter jejuni, norovirus, Giardia intestinalis, and Salmonella enterica serotype Typhimurium were identified in 16, 9, 3, and 1 persons, respectively. We interviewed 100 case patients and 117 matched control subjects. Case patients were more likely to drink water on the island than control subjects (68% vs. 35%; matched odds ratio, 4.3; 95% confidence interval, 2.2–9.3). Sampling of ground water wells indicated contamination with multiple fecal microbes, including Escherichia coli, C. jejuni, Salmonella species, and Giardia species. Irregularities in sewage disposal practices that could have contaminated the underground aquifer were noted. Conclusions. The combined epidemiological and environmental investigation indicated that sewage-contaminated ground water was the likely source of this large outbreak. Long-term changes to the island's water supply and sewage management infrastructure are needed.

Microplastics (MPs) and nanoplastics (NPs), formed as a result of plastic product degradation, pose a global environmental threat by penetrating biological systems and inducing systemic pathological changes. This systematic review, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, aims to analyze the molecular and cellular mechanisms of the toxic effects of MPs and NPs on the human cardiovascular, nervous, reproductive, urinary, and digestive systems. The primary mechanisms include oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, autophagy, ferroptosis, and impaired barrier functions. In the cardiovascular system, MPs and NPs contribute to endothelial dysfunction, disorders of lipid metabolism, and fibrosis; in the nervous system, they promote neuroinflammation, pathological protein aggregation, and psychiatric disorders; in the reproductive system, they lead to hormonal imbalance and reduced fertility; in the kidneys, they cause inflammation, and fibrosis and lead to deterioration of kidney function; and in the gastrointestinal tract, they contribute to dysbiosis and metabolic disorders. The literature search was conducted in the PubMed, Web of Science, and Scopus databases without limitations on date, language, or access. Studies were selected based on criteria of transparency, statistical validity, sample representativeness, and correctness of data interpretation. The review emphasizes the necessity of an interdisciplinary approach to developing prevention and treatment strategies, including reduction in exposure, antioxidant and immunomodulatory therapy, and restoration of barrier functions and microbiota. The data obtained reveal research gaps and identify directions for further study.

Background. Because of changes in gut physiology, immune system reactivity, and diet, elderly people are more susceptible to gastrointestinal infections than are younger adults. The gut microflora, which provides a natural defense against invading microorganisms, changes in elderly people with the development of potentially damaging bacterial populations, which may lead to alterations in bacterial metabolism and higher levels of infection. Methods. A randomized, double-blind, controlled feeding trial was done with 18 healthy elderly volunteers (age, >62 years) using a synbiotic comprising Bifidobacterium bifidum BB-02 and Bifidobacterium lactis BL-01 (probiotics) together with an inulin-based prebiotic (Synergy 1; Orafti). Real-time PCR was employed to quantitate total bifidobacteria, B. bifidum, and B. lactis in fecal DNA before, during, and after synbiotic consumption. Counting all viable anaerobes, bifidobacteria, and lactobacilli and identification of bacterial isolates to species level was also done. Results. Throughout feeding, both bifidobacteria species were detected in fecal samples obtained from all subjects receiving the synbiotic, with significant increases in the number of copies of the 16S rRNA genes of B. bifidum, B. lactis, and total bifidobacteria, compared with the control week and the placebo group. At least 1 of these species remained detectable in fecal samples 3 weeks after feeding in individuals that had no fecal B. bifidum and/or B. lactis in the control week, indicating that the probiotics persisted in the volunteers. Counting of viable organisms showed significantly higher total numbers of fecal bifidobacteria, total numbers of lactobacilli, and numbers of B. bifidum during synbiotic feeding. Conclusion. Synbiotic consumption increased the size and diversity of protective fecal bifidobacterial populations, which are often very much reduced in older people.

Despite the significant progress that has been made in the diagnosis and treatment of digestive system diseases, these conditions continue to pose a serious public health concern worldwide. There is an ongoing need for strategies that are precise, efficient and minimally invasive. Nanozymes, engineered nanomaterials that exhibit catalytic functions, have attracted considerable interest in this context. However, clinical application of nanozymes remains limited primarily due to their diversity, targetability, biocompatibility and early-stage clinical translation. The present review presented a comprehensive analysis of nanozymes in digestive system diseases. The main enzyme-like activities of nanozymes are summarized to guide further material selection and characteristic exploration. Preclinical applications are highlighted with mechanisms and theranostic effects discussed alongside their potential limitations. Emerging combination therapies, including photodynamic therapy, sonodynamic therapy and biotherapy, are reviewed. Finally, the current challenges of nanozymes and possible future developments are discussed.

Background Anxiety and depression are prevalent among elderly inpatients and may significantly influence clinical outcomes, particularly in patients with chronic diseases. However, limited research has explored these psychological conditions in elderly patients with digestive system diseases in the Southwest China region. Objective This study aimed to evaluate the associations between depression symptoms and clinical outcomes in elderly inpatients with digestive system diseases in Southwest China. Anxiety symptoms were examined as an associated variable and further analyzed in exploratory subgroup assessments. Methods A retrospective cohort study was conducted using data from 1,290 elderly inpatients aged 60 years or older hospitalized with a primary diagnosis of digestive system disease between January 2018 and December 2022 at a tertiary care hospital in Southwest China. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), with a score ≥ 8 indicating clinically relevant symptoms. Clinical outcomes included prolonged hospital stay (≥ 14 days), hospitalization costs, complications during hospitalization, 30-day readmission, and in-hospital mortality. Multivariable logistic regression models were used to examine the associations, and subgroup analyses stratified by gender and age were performed. Results Anxiety symptoms were observed in 33.2% of patients, while 37.4% exhibited depression symptoms. Depression was significantly associated with longer hospital stays (14.2 ± 6.3 vs. 11.3 ± 5.2 days, P  < 0.001), higher hospitalization costs (¥12,300 vs. ¥10,800, P  < 0.001), and increased complication rates, including infections (29.5% vs. 20.8%, P  < 0.001) and gastrointestinal bleeding (19.1% vs. 11.6%, P  < 0.001). Subgroup analyses revealed that anxiety symptoms were strongly associated with prolonged hospital stays, particularly among female patients aged ≥ 70 years (adjusted OR: 2.35, 95% CI: 1.68–3.30, P  < 0.001). Multivariable analysis identified poor sleep quality, cognitive impairment, and digestive system tumors as variables independently associated with anxiety symptoms. Conclusion Anxiety and depression symptoms are prevalent among elderly inpatients with digestive system diseases in Southwest China and are associated with adverse clinical outcomes, including prolonged hospital stay, increased healthcare costs, and higher complication rates. Female patients and those aged ≥ 70 years are particularly vulnerable. Early psychological assessment and targeted interventions may improve clinical outcomes in this population.

A Man with Recurrent Fever and Liver LesionsA 73-year-old man was admitted because of 22 months of recurrent fever and progressive hypodensities in the liver. A liver-biopsy specimen showed nonnecrotizing granulomas. A diagnosis was made.