Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study.

BACKGROUND: Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD. METHODS: Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation. RESULTS: The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19). CONCLUSIONS: Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Hydroxychloroquine had neutral effect on long-term risk of malignancy in rheumatoid arthritis patients: A population-based retrospective cohort study.

BACKGROUND: The cancer risk in rheumatoid arthritis (RA) patients has been discussed. Hydroxychloroquine (HCQ) may exert protective effects against malignancy. The study investigated the association between HCQ use and the risk of subsequent malignancy in RA patients. METHODS: Catastrophic illness certificated RA patients were extracted from the National Health Insurance Research Database. The index date was set 180 days after the RA diagnosis date to avoid immortal time bias. Two groups were matched in a 1-to-1 ratio by propensity score regarding age, gender, index date, relevant comorbidities, and comedication. HCQ users prior to the diagnosis of RA were exempted to ensure compliance with the new-user design. Cancers diagnosed before or less than 180 days after the index date were excluded to mitigate protopathic bias. The study adopted the Kaplan-Meier curve and Cox proportional hazards model to examine the association between HCQ use and cancer risk. The assumption of proportional hazard was also tested. RESULTS: Based on strict criteria, we included 492 eligible RA patients and divided them into study and control groups (N = 246 in each group). HCQ users exhibited a neutral risk of cancer relative to the controls (adjusted hazard ratio, 0.99; 95% CI, 0.44-2.21, p > .05). The assumption of proportional hazard was not violated. CONCLUSION: This study does not observe the effect of using HCQ as a primary regimen to prevent cancer in RA patients. We are assured that HCQ is not associated with an increased risk of subsequent malignancy in RA patients. Further mechanistic research is needed.

Association of diverticulitis and potential risk of ischemic stroke: population-based matched cohort study in Taiwan.

BACKGROUND: Previous studies have suggested relationship between diverticular disease and cardiovascular disease. Since cardiovascular disease and cerebrovascular accident share a lot of pathogenesis, diverticulitis could also be a risk factor for stroke. This study tried to establish epidemiological evidence of the relationship between colon diverticulitis and ischemic stroke. METHODS: In this retrospective cohort study, patients with newly diagnosed colon diverticulitis (N = 6238) and patients without colon diverticulitis (control group; N = 24 952) were recruited between January 1, 2000, and December 31, 2017. Both groups were matched by propensity score at a 1:4 ratio by age, sex, comorbidities and medications. Cox proportional hazard regression was applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) of ischemic stroke. We also conducted 4 different regression models and 2 sensitivity analyses to test the robustness of our findings. RESULTS: The diverticulitis group had a higher risk of IS than the control group (adjusted HR, 1.25; 95% CI, 1.12-1.39; P < 0.001). Serial sensitivity analyses yielded consistent positive link between diverticulitis and IS. Further subgroup analysis showed that in the study group, the risk of IS was 2.54-fold higher than the matched controls in 30-39 years. CONCLUSIONS: Our study found that colon diverticulitis was associated with a higher risk of developing subsequent ischemic stroke, especially for patients aged 30-39 years, among Asian population. This result provides us a chance to undertake preventive measures for ischemic stroke in high-risk patients.

Association between blood culture turnaround time and clinical prognosis in emergency department patients with community acquired bloodstream infection: A retrospective study based on electronic medical records.

Importance: Previous investigations have found that time to positive blood culture (TTP) is a prognostic factor for clinical outcomes. In fact, what the emergency physician sees from the medical information system is TAT (turnaround time) defined as time required to post a bacterial culture report. We propose a definition of blood culture TAT that more closely aligns with clinical considerations by measuring the time from starting specimen culture to the release of an official blood culture report.We were curious to know whether the duration of TAT is as intricately linked to the prognosis of bacteremia as TTP. Objectives: To examine the association between TAT and outcomes of adult patients who present to the ED with community acquired bacteremia. Design: Setting, and Participants: This retrospective study utilized electronic medical records from Kaohsiung Veterans General Hospital (KVGH), a 1000-bed tertiary medical center in Taiwan. Patients were adults aged 18 years and older who presented to ED (Emergency department) for initial diagnosis of community acquired bacteremia from January 1, 2016 to March 31, 2021. Data analysis was performed from December 2022 to January 2023.Main outcomes and measures.The primary outcomes included mortality in the ED, all-cause in-hospital mortality, length of hospital stay, and all-cause 30-day mortality in relation to the individual first report of positive blood culture TAT. Results: A total of 4011 eligible patients with bacteremia were evaluated, of which 207 patients had a blood culture TAT of ≤48 h. The overall 30-day all-cause mortality rate was 13%. Contrary to expectation, no statistically significant differences were observed in clinical prognosis between the TAT groups (≤48 versus >48 h). Subgroup analyses indicated that the length of TAT did not have a significant effect on clinical prognosis in patients who underwent lactate level assessment. Furthermore, no difference in clinical outcome was noted between TAT groups (≤48 versus >48 h) in terms of Gram-negative bacilli or Gram-positive cocci bacteremia. However, in patients with delayed antibiotic treatment (>3 h), a shorter TAT was significantly associated with a fatal outcome. Conclusion: In adults with community-acquired bacteremia, this study did not observe a significant association between blood culture TAT and clinical prognosis, except in cases of delayed antibiotic treatment.

Price for waiting: the adverse outcomes of boarding critically ill elderly medical patients in the emergency department.

PURPOSE: Boarding, the period in which a patient spends in the emergency department (ED) before admission, may be hazardous to critically ill patients, particularly the elderly. This study investigated the associations of boarding with hospital course, prognosis, and medical expenditure in older patients. METHODS: From January 2019 to December 2021, the medical records of older patients (age ≥ 65) visiting the ED of a tertiary referral hospital who were admitted to the medical intensive care unit (ICU) were retrospectively reviewed. Eligible patients were categorized into two groups according to boarding time with a cutoff set at 6 h. Primary outcomes were in-hospital mortality, ICU/hospital length of stay, and total/average hospitalization cost. Subgroup analyses considered age and disease type. RESULTS: Among 1318 ICU admissions from the ED, 36% were subjected to boarding for over 6 h. Prolonged boarding had a longer ICU (8.9 ± 8.8 vs. 11.2 ± 12.2 days, P < .001) and hospital (17.8 ± 20.1 vs. 22.8 ± 23.0 days, P < .001) stay, higher treatment cost (10.4 ± 13.9 vs. 13.2 ± 16.5 thousands of USD, P = .001), and hospital mortality (19% vs. 25% P = .020). Multivariate regression analysis showed a longer ICU stay in patients aged 65-79 (8.3 ± 8.4 vs. 11.8 ± 14.2 days, P < .001) and cardiology patients (6.9 ± 8.4 vs. 8.8 ± 9.7 days, P = .001). Besides, the treatment cost was also higher for both groups (10.4 ± 14.6 vs. 13.7 ± 17.7 thousands of USD, P = .004 and 8.4 ± 14.0 vs. 11.7 ± 16.6 thousands of USD, P < .001, respectively). CONCLUSION: Extended ED boarding for critically ill medical patients over 65 years old was associated with negative outcomes, including longer ICU/hospital stays, higher treatment costs, and hospital mortality.

Spatial and single-cell analyses uncover links between ALKBH1 and tumor-associated macrophages in gastric cancer.

BACKGROUND: AlkB homolog 1, histone H2A dioxygenase (ALKBH1), a crucial enzyme involved in RNA demethylation in humans, plays a significant role in various cellular processes. While its role in tumor progression is well-established, its specific contribution to stomach adenocarcinoma (STAD) remains elusive. This study seeks to explore the clinical and pathological relevance of ALKBH1, its impact on the tumor immune microenvironment, and its potential for precision oncology in STAD. METHODS: We adopted a comprehensive multi-omics approach to identify ALKBH1 as an potential diagnostic biomarker for STAD, demonstrating its association with advanced clinical stages and reduced overall survival rates. Our analysis involved the utilization of publicly available datasets from GEO and TCGA. We identified differentially expressed genes in STAD and scrutinized their relationships with immune gene expression, overall survival, tumor stage, gene mutation profiles, and infiltrating immune cells. Moreover, we employed spatial transcriptomics to investigate ALKBH1 expression across distinct regions of STAD. Additionally, we conducted spatial transcriptomic and single-cell RNA-sequencing analyses to elucidate the correlation between ALKBH1 expression and immune cell populations. Our findings were validated through immunohistochemistry and bioinformatics on 60 STAD patient samples. RESULTS: Our study unveiled crucial gene regulators in STAD linked with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators demonstrated a positive association with distinct immune cell populations across six immune datasets, exerting a substantial influence on immune cell infiltration in STAD. Furthermore, we established a connection between elevated ALKBH1 expression and macrophage infiltration in STAD. Pharmacogenomic analysis of gastric cancer cell lines further indicated that ALKBH1 inactivation correlated with heightened sensitivity to specific small-molecule drugs. CONCLUSION: In conclusion, our study highlights the potential role of ALKBH1 alterations in the advancement of STAD, shedding light on novel diagnostic and prognostic applications of ALKBH1 in this context. We underscore the significance of ALKBH1 within the tumor immune microenvironment, suggesting its utility as a precision medicine tool and for drug screening in the management of STAD.

The Cross-Communication of Cuproptosis and Regulated Cell Death in Human Pathophysiology.

Copper (Cu) plays a crucial and diverse function in biological systems, acting as a cofactor at numerous sites of enzymatic activity and participating in various physiological processes, including oxidative stress regulation, lipid metabolism, and energy metabolism. Similar to other micronutrients, the body regulates Cu levels to ensure homeostasis; any disruption in Cu homeostasis may result in various illnesses. Cuproptosis causes proteotoxic stress and ultimately results in cell death by the binding of Cu ions to lipid-acylated proteins during the tricarboxylic acid cycle of mitochondrial respiration. Cu is not only involved in regulatory cell death (RCD), but also in exogenous factors that induce cellular responses and toxic outcomes. Cu imbalances also affect the transmission of several RCD messages. Therefore, this article presents a thorough examination of the mechanisms involved in Cu-induced RCD as well as the role of Cu complexes in its pathophysiology.