UNASSIGNED: Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses.
UNASSIGNED: Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy.
UNASSIGNED: Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis.
UNASSIGNED: This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

UNASSIGNED: The incidence of severe infections (SIs) in patients with autoimmune nephropathy after rituximab (RTX) treatment varies significantly. Our study aims to identify high-risk populations, specifically by comparing the differences in the risk of SIs between patients with primary nephropathy and those with nephropathy in the context of systemic autoimmune diseases (referred to as secondary nephropathy).
UNASSIGNED: This retrospective cohort study investigated the occurrence of SIs in adult patients with immune-related kidney disease who received RTX treatment at our institution from 2017 to 2022. Multivariable COX regression models were used to analyze the association between the type of nephropathy (primary or secondary) and SIs. Propensity score analyses, subgroup analyses, and E-value calculations were performed to ensure the reliability of the results.
UNASSIGNED: Out of 123 patients, 32 (26%) developed 39 cases of SIs during a mean follow-up period of 19.7 ± 14.6 months post-RTX treatment, resulting in an incidence rate of 18.9/100 patient-years. The multivariable COX regression analysis indicated that patients with secondary nephropathy had a significantly higher risk of SIs compared to those with primary nephropathy (HR = 5.86, 95% CI: 1.05-32.63, P = 0.044), even after accounting for confounding variables including gender, age, BMI, history of prior SIs, baseline eGFR, lymphocyte counts, IgG levels, and the utilization of other immunosuppressive therapies. Various sensitivity analyses consistently supported these findings, with an E-value of 5.99. Furthermore, advanced age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.023), low baseline IgG levels (HR: 0.75; 95% CI: 0.64-0.89; P < 0.001), and recent history of SIs (HR: 5.68; 95% CI: 2.2-14.66; P < 0.001) were identified as independent risk factors.
UNASSIGNED: The incidence of SIs following RTX administration in patients with autoimmune nephropathy is significant. It is crucial to note that there are distinct differences between the subgroups of primary and secondary nephropathy. Patients with secondary nephropathy, particularly those who are elderly, have low baseline IgG levels, and have a recent history of SI, are more susceptible to SIs.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited.
OBJECTIVE: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association.
METHODS: This study included 19,851 participants with T2D from UK Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders.
RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-years. Compared to those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall <0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall <0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction >0.050).
CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

UNASSIGNED: Preterm birth is a heterogeneous condition with multiple underlying causes, and periodontal diseases are one of them. Approximately 900000 preterm births are reported in Pakistan each year. Oral infections such as periodontitis during pregnancy are associated with adverse pregnancy outcomes such as low birth weight and preterm births. However, different studies have reported contradictory findings. We conducted a cross-sectional study to assess the association of preterm birth with oral infection in pregnancy.
UNASSIGNED: We conducted a cross-sectional analytical study on 400 postpartum pregnant women in Khyber Teaching Hospital, Peshawar. Only women within the age bracket of 18‒40 years were recruited. Data were collected by an interview-based structured questionnaire. The extent and severity index were used to assess the periodontal health of participants. Frequency tables were generated, and the chi-squared test was used to determine associations between different categorical variables.
UNASSIGNED: The mean age of the participants was 25.8±4.9 years. Approximately 87.5% of the women had generalized periodontitis. Approximately 68% of mothers had moderate severity of periodontitis. The extent index showed no notable difference between the preterm and full-term birth groups. In contrast, the severity index displayed a statistically significant difference between the preterm and full-term birth groups.
UNASSIGNED: The majority of women had generalized periodontitis. The severity index demonstrated a significant association between maternal periodontitis and preterm births. There was no association between the age of mothers and preterm births. Complications in pregnancy were not associated with preterm births.

BACKGROUND: This study compared the progression of experimental peri-implantitis between alveolar ridge preservation (ARP) and spontaneous healing (SH) sites in infected (IT) and noninfected tooth (NIT).
METHODS: Bilateral mandibular third or fourth premolars of six beagle dogs were randomly assigned to IT and NIT groups. Before extraction, chronic dehiscence defects were created at the mesial root of mid-buccal area in IT group. Four weeks later, the mesial roots of the third and fourth premolars were extracted in all groups.ARP procedure was randomly conducted on one side of the extraction sockets using collagenated bovine bone substitutes and resorbable collagen membrane, and contralateral side was allowded spontaneous healing. After 12 weeks of healing, bone-level implants (ϕ 3.6 × 8.0 mm) were placed at the extraction sockets. Three months of ligature induced peri-implantitis and three months of spontaneous progression were allowed, with radiographs taken at each phase. Biopsies were retrieved at the implant site for histomorphometric, immunohistochemical, and polarized light-microscopic analyses.
RESULTS: Radiography demonstrated that the changes in the marginal bone level during the spontaneous progression period showed no significant differences between ARP and SH sites. Only small and/or nonsignificant differences in the progression of peri-implantitis were observed between ARP and SH sites in histomorphometric, immunohistochemical, and polarized light microscopic analyses. Additionally, the IT and NIT groups exhibited similar outcomes for most parameters.
CONCLUSIONS: ARP with xenogenic bone substitutes might provide similarly robust results as SH sites regarding the progression of experimental peri-implantitis, irrespective of the infected or noninfected nature of the site before tooth extraction.

BACKGROUND: Reports of Cutibacterium acnes isolated in cultures of intervertebral disc samples suggest it as possibly responsible for inflammatory conditions causing Modic changes on spinal magnetic resonance imaging (MRI).
OBJECTIVE: Our objective was to investigate the prevalence of C. acnes in samples of intervertebral disc of patients with lumbar disc herniation; to investigate prognostic factors and the relationship of Modic changes with infection 1 year after microdiscectomy.
METHODS: Prospective cohort study.
METHODS: In this single-center study, patients consecutively operated on for disc herniation had samples of the disc, multifidus muscle and ligamentum flavum (as an indication of contamination) extracted for culture.
METHODS: Age, sex, alcohol and tobacco consumption, body mass index; function, pain, and Modic chances in MRI before surgery and MRI 1 year later; rate of disc, muscle and ligament infection (primary outcome); diabetes and corticoid use (confoundings).
METHODS: The protruded disc, muscle and ligament samples were sent for culture analysis in up to 30 minutes. A subsample of 17 patients underwent next-generation sequencing (NGS) molecular analysis too. We performed descriptive analysis and comparison of groups of patients with and without infection or contamination using Student\'s t, Mann-Whitney, chi-square, or Fisher\'s exact tests as appropriate, and pre- and postsurgical comparisons with the Wilcoxon test.
RESULTS: From January 2018 to September 2019, 112 patients underwent open lumbar microdiscectomy, 67 (59.8%) men. Cultures showed 7 (6.3%) positive cases in the disc (2 with C. acnes), 3 (2.7%) in the ligament, and 12 (10, 7%) in muscle. No evidence of a difference in Modic alterations pre- or postoperatively was found between patients with and without positive culture 1 year after surgery. No association was found between culture positivity and functional or pain differences either. NGS results were all negative for C. acnes.
CONCLUSIONS: We identified infective bacterial presence in the herniated disc in less than 2% of patients with disc herniation. C. acnes was not identified in any disc microbiome analysis. No significant association was observed between positivity for tissue infection and any clinical prognostic factor.

BACKGROUND: Although frailty is associated with a range of adverse health outcomes, its association with the risk of hospital-treated infections is uncertain.
METHODS: A total of 416 220 participants from the UK Biobank were included in this prospective cohort study. Fried phenotype was adopted to evaluate frailty, which included 5 aspects (gait speed, physical activity, grip strength, exhaustion, and weight). More than 800 infectious diseases were identified based on electronic health records. Cox proportional models were used to estimate the associations.
RESULTS: During a median 12.3 years (interquartile range 11.4-13.2) of follow-up (4 747 345 person-years), there occurred 77 988 (18.7%) hospital-treated infections cases. In the fully adjusted model, compared with participants with nonfrail, the hazard ratios (HRs) (95% confidence intervals [CIs]) of those with prefrail and frail for overall hospital-treated infections were 1.22 (1.20, 1.24) and 1.78 (1.72-1.84), respectively. The attributable risk proportion of prefrail and frail were 18.03% and 43.82%. Similarly, compared to those without frailty, the HRs (95% CIs) of those with frailty for bacterial infections were 1.76 (1.70-1.83), for viral infections were 1.62 (1.44-1.82), and for fungal infections were 1.75 (1.47-2.08). No association was found between frailty and parasitic infections (HR: 1.17; 95% CI: 0.62-2.20).
CONCLUSIONS: Frailty was significantly associated with a higher risk of hospital-treated infections, except for parasitic infections. Studies evaluating the effectiveness of implementing frailty assessments are needed to confirm our results.

UNASSIGNED: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear.
UNASSIGNED: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated.
UNASSIGNED: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified.
UNASSIGNED: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

OBJECTIVE: Comorbidity level is a predictor of infection in the first 30 days after hip fracture surgery. However, the roles of individual comorbid diseases as predictors of infection remain unclear. We investigated individual major comorbid diseases as predictors of infection after hip fracture surgery.
METHODS: We obtained Danish population-based medical registry data for patients undergoing hip fracture surgery (2004-2018). Information was obtained on 27 comorbidities, included in various comorbidity indices, 5 years before surgery. The primary outcome was any hospital-treated infection within 30 days after surgery. Cumulative incidence of infection was calculated by considering death as competing risk. We used logistic regression to compute mutually adjusted odds ratios with 95% confidence interval for infection.
RESULTS: Of 92,239 patients with hip fracture, 71% were women, and the median age was 83 years. The most prevalent comorbidities were hypertension (23%), heart arrhythmia (15%), and cerebrovascular disease (14%). The 30-day incidence of infection was 15% and 12% among the total cohort and among patients with no record of comorbidities, respectively. Infection incidence was highest among patients with renal disease (24%), depression/anxiety (23%), and chronic pulmonary disease (23%), and lowest among patients with metastatic solid tumor (15%). Adjusted odds ratios of infection ranged from 0.94 [0.80-1.10] for metastatic solid tumor to 1.77 [1.63-1.92] for renal disease.
CONCLUSIONS: Most comorbid diseases were predictors of infection after surgery for hip fracture. Awareness of patients\' comorbidity profiles might help clinicians initiate preventive measures or inform patients of their expected risk.