Invasive non-typhoidal Salmonella (iNTS) infection may cause severe systemic and focal disease, particularly in patients with comorbidities or immunosuppression. Data on the clinical features and antimicrobial resistance patterns of iNTS infections in Türkiye remain limited. This study aimed to evaluate the clinical and microbiological characteristics of adult patients with microbiologically confirmed iNTS infection at a tertiary-care center in Türkiye.

This retrospective, single-center case series included adult patients diagnosed with iNTS infection at a tertiary-care hospital in Türkiye between December 2015 and December 2025. Invasive non-typhoidal Salmonella infection was defined as isolation of non-typhoidal Salmonella from blood or normally sterile body sites. Clinical, microbiological, antimicrobial susceptibility, and outcome data were analyzed.

Nine patients with iNTS infection were identified. The median age was 54 years (IQR, 45-68), and 5 patients (55.6%) were male. Underlying comorbidities were present in 8 patients (88.9%), most commonly hypertension, diabetes mellitus, autoimmune diseases, and HIV infection. Gastrointestinal symptoms were observed in only 2 patients (22.2%), whereas 7 patients (77.8%) presented without typical enteric manifestations. Bacteremia was detected in 7 patients (77.8%), and focal invasive infections were identified in 5 patients (55.6%), including spondylodiscitis, septic arthritis, thyroid abscess, and liver abscess. Salmonella enterica serovar Enteritidis was the predominant serovar, identified in 6 isolates (66.7%), while 3 isolates (33.3%) were classified as Salmonella enterica subsp. enterica without further serovar determination. All isolates remained susceptible to third-generation cephalosporins, whereas resistance to ampicillin and ciprofloxacin was detected in 4 (44.4%) and 3 isolates (33.3%), respectively. The median length of hospitalization was 16 days, and 2 patients (22.2%) died during follow-up.

Invasive non-typhoidal Salmonella infection may present with heterogeneous and frequently non-enteric manifestations, particularly in adults with significant comorbidities or immunosuppression. The high frequency of focal invasive disease and the relatively high rate of ciprofloxacin resistance in this series highlight the importance of early microbiological diagnosis, evaluation for metastatic infectious foci, and appropriate empirical antimicrobial therapy.

Graphical Abstract.

Genetic and lifestyle factors alone cannot explain the rising global burden of type 2 diabetes mellitus (T2DM). Growing evidence implicates endocrine-disrupting chemicals (EDCs) found in plastics, pesticides, food packaging, industrial products, and contaminated water as significant environmental contributors to metabolic dysfunction. EDCs, including bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), and heavy metals, have been associated with insulin resistance, pancreatic β-cell dysfunction, oxidative stress, mitochondrial impairment, chronic inflammation, and epigenetic modifications that collectively promote T2DM pathogenesis. The gut microbiota has emerged as a potential mediator of EDC-associated metabolic disruption, whereby chemical exposures may alter microbial diversity, disturb the Firmicutes/Bacteroidetes ratio, impair short-chain fatty acid production, decrease intestinal barrier integrity, driving metabolic endotoxemia and systemic inflammation. This narrative review examines the major EDCs associated with diabetes, their molecular and metabolic mechanisms of action, and their interactions with the gut microbiota, drawing on current experimental and epidemiological evidence. Special emphasis is placed on probiotic supplementation as an emerging therapeutic strategy targeting the EDC-gut microbiota-metabolic axis. Current evidence for probiotics in EDC-associated metabolic dysfunction is predominantly preclinical, with studies suggesting improvements in microbial homeostasis, pancreatic oxidative damage, and glucose metabolism. However, available evidence remains heterogeneous and human clinical trials specifically examining probiotic intervention in EDC-exposed populations at risk of T2DM remain absent, representing a fundamental translational gap that future research must urgently address. Advancing precision medicine approaches, integrating microbiome profiling, metabolomics, epigenetic analysis, and coordinated efforts across toxicology, clinical medicine, and public health, will be essential to reducing the growing global burden of environmentally driven type 2 diabetes.

Candida esophagitis is the most common fungal infection of the esophagus and typically occurs in patients with impaired immunity or other recognized predisposing conditions. Severe disease in apparently immunocompetent individuals without oral candidiasis is rare and may delay diagnosis.

A 35-year-old previously healthy man presented with a two-month history of progressive odynophagia, cough, and unintentional weight loss. He had no history of diabetes mellitus, malignancy, chronic kidney or liver disease, corticosteroid use, broad-spectrum antibiotic exposure, proton pump inhibitor therapy, smoking, or alcohol consumption. Human immunodeficiency virus serology was nonreactive, fasting blood glucose and glycated hemoglobin were within normal limits, and examination revealed no oral candidiasis. Upper gastrointestinal endoscopy demonstrated extensive confluent whitish plaques with marked mucosal friability and luminal narrowing, consistent with severe Kodsi grade IV esophageal candidiasis on endoscopic appearance. Histopathological confirmation, fungal culture, species identification, and immunological investigations were not performed because of mucosal friability, financial limitations, and restricted diagnostic resources. The patient was treated with intravenous fluconazole and experienced rapid clinical improvement, with sustained symptomatic recovery at two-week follow-up.

This case demonstrates that severe Kodsi grade IV Candida esophagitis may occur in apparently immunocompetent individuals without oral candidiasis or identifiable risk factors. Clinicians should maintain a high index of suspicion for esophageal candidiasis in patients with persistent odynophagia despite the absence of classical predisposing conditions. Prompt endoscopic evaluation and early antifungal therapy are critical for timely diagnosis and prevention of complications, particularly in resource-limited settings where histopathological confirmation may not be feasible.

This systematic review aimed to evaluate the differences in root canal microbiota composition and microbial load between diabetic and non-diabetic individuals with apical periodontitis.

Electronic searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, the Cochrane Library and EBSCO up to 9 April 2026.Clinical studies using culture-dependent or molecular methods to identify microbial taxa in infected root canals of diabetic and non-diabetic individuals were included. Data on diabetes status, infection type, microbiological method, identified taxa, and quantitative microbial outcomes were extracted. Methodological quality was assessed using the Joanna Briggs Institute critical appraisal tool.

Sixteen studies were included. Most used molecular methods, while few used culture or combined culture/molecular approaches. The studies varied in infection type, microbiological method, glycemic status reporting, and outcome metrics. Several studies reported differences in the prevalence or relative abundance of selected bacterial taxa in diabetic patients, including Peptostreptococcus spp., Porphyromonas gingivalis, Eubacterium infirmum, Enterococcus faecalis, Olsenella, Pseudoramibacter, and Fannyhessea. Fungal and archaeal findings were also reported in a limited number of studies. However, quantitative microbial findings could not be directly compared because different measures were used, including CFU counts, PCR-based detection, qPCR-derived bacterial counts, and sequencing-based relative abundance data.

Diabetes mellitus may be associated with differences in the reported endodontic microbial profile of teeth with apical periodontitis. However, the evidence is observational, clinically heterogeneous, and limited by small sample sizes, inconsistent glycemic reporting, and inadequate control of confounding factors.

Obesity and type 2 diabetes mellitus are characterized by insulin resistance and progressive impairment of β-cell function. Fat mass and obesity-associated (FTO) protein, an m6A demethylase involved in metabolic regulation, has been linked to obesity. However, the relationship between circulating FTO protein levels and β-cell function among individuals with different metabolic profiles remains unclear. This study aimed to investigate circulating FTO levels and their relationship with β-cell function, assessed by (HOMA-β), in individuals with newly diagnosed T2D, obese individuals without diabetes, and normal-weight individuals without diabetes.

This cross-sectional observational study included 82 participants: 39 individuals newly diagnosed with T2D, 23 obese individuals without diabetes, and 20 normal-weight individuals without diabetes. Anthropometric and biochemical parameters, including fasting blood glucose, glycated hemoglobin, fasting insulin, HOMA-IR, and HOMA-β, were assessed. Serum FTO levels were measured using ELISA. Correlation and multiple linear regression analyses were performed to examine the relationship between circulating FTO levels and (HOMA-β).

Serum FTO protein levels differed significantly among the three groups (P = 0.002), with the highest levels observed in obese individuals without diabetes. In this group, FTO protein levels were positively correlated with body mass index, fasting insulin, and HOMA-β (P = 0.018, P = 0.040, and P = 0.033, respectively). HOMA-β was also positively correlated with FTO, fasting insulin, and HOMA-IR. However, the positive association between FTO levels and HOMA-β was not statistically significant after adjustment for age, sex, and metabolic status.

Circulating FTO levels were highest in obese individuals without diabetes and were positively correlated with HOMA-β in this group. However, this relationship was not independently significant after adjustment for potential confounders. These findings provide preliminary evidence of a relationship between circulating FTO and β-cell function in the context of obesity, while the cross-sectional design precludes causal or temporal inferences.

Diagnostic follow-up times after abnormal screening mammography vary widely across facilities. However, whether the use of digital breast tomosynthesis (DBT) is associated with follow-up timeliness, independent of facility context factors, remains unclear.

To evaluate the extent to which facility mammography volume accounts for the association between facility-level DBT use proportion and recall delay after abnormal screening mammography in Appalachia.

We linked 2016-2018 Medicare fee-for-service claims to facility survey data from screening facilities in five Appalachian states (KY, OH, PA, VA, and WV). Recall delay was modeled using linear mixed-effects models with random intercepts for facility and beneficiary. The models adjusted for DBT use proportion, capacity score, age, race, dual Medicare-Medicaid eligibility, deprivation, rurality, and stand-alone status. To assess whether facility mammography volume accounted for the association between DBT use proportion and recall delay, we compared two models fitted to the same analytic sample with the same covariates. The models differed only in whether facility mammography volume was included. We estimated 95% confidence intervals for the difference in the DBT coefficient using 5000 bootstrap resamples. Facility-level models and exploratory mediation analyses were conducted as complementary analyses.

DBT use proportion was associated with higher facility mammography volume after adjustment for capacity score and facility covariates (β = 0.614, 95% CI [0.170, 1.058], p = 0.007). After adjustment for capacity score, a 1-SD higher facility mammography volume was associated with shorter recall delay (β = -1.103 days, 95% CI [-2.074, -0.132], p = 0.028). The DBT coefficient changed from -0.970 days before adding facility volume to -0.402 days after volume adjustment, corresponding to a raw coefficient change of 0.568 days (95% bootstrap CI [0.130, 1.088]). The complementary facility-level model estimated a corresponding raw coefficient change of 0.620 days (95% bootstrap CI [0.149, 1.143]). An exploratory mediation analysis adjusted for capacity score and facility covariates estimated an indirect estimate through facility mammography volume of -0.620 days (95% CI [-1.111, -0.146], p = 0.004). The direct and total estimates were not statistically significant.

Facility-level DBT use proportion was positively associated with facility mammography volume, and higher facility mammography volume was associated with shorter recall delay after adjustment for the capacity score. The association between DBT use proportion and recall delay was not statistically significant either before or after volume adjustment, although the estimated DBT coefficient decreased in magnitude after facility mammography volume was added. These findings suggest that differences in follow-up timeliness may reflect the facility context in which DBT is implemented and support further study of facility-level determinants of diagnostic follow-up.

Methotrexate is a key chemotherapeutic agent for treating pediatric acute lymphoblastic leukemia (ALL); however, its pharmacokinetics exhibit substantial inter-individual variability. Population pharmacokinetic (PPK) models have identified body weight and renal function as major determinants of methotrexate clearance. Nonetheless, the optimal PPK model for Japanese pediatric patients, considering hydration status, has not yet been established. This study aimed to develop a PPK model of high-dose methotrexate specifically for Japanese pediatric patients with ALL. A retrospective PPK analysis was performed in pediatric patients with ALL, who were treated with high-dose methotrexate at the Tokyo Medical and Dental University Hospital. Data from 38 patients (504 methotrexate concentrations; 27 for model development and 11 for validation) were analyzed using a two-compartment model in NONMEM. Predictive performances of the newly developed and previously published models were assessed using the validation dataset. In the final model, clearance was described as a function of body surface area and hydration volume rate per body surface area (HYDR), whereas intercompartmental clearance was associated with age and HYDR. Evaluation using the validation dataset showed that the developed model had the best predictive performance among the evaluated models (median prediction error, 1.79%; median absolute prediction error, 13.3%; percentage of predictions with an absolute prediction error ≤20%, 70.3%; percentage of predictions with an absolute prediction error ≤30%, 82.9%). Simulation revealed modestly improved target-attainment rates at relatively high hydration rates. These findings highlight the importance of fluid management and support the incorporation of hydration parameters into individualized high-dose methotrexate therapy.

Lung adenocarcinoma exhibits diverse pathological features, some of which for example, histological grading and tumor spread through air spaces (STAS), can be used for prognosis. Extra-alveolar invasion (EX) is a unique pathological factor focused on depth of invasion, and is defined as tumor infiltration into periarterial, peribronchiolar, or interlobular septal stroma. We recently suggested EX as a prognostic indicator, but its significance in sublobar resection remains unclear. We investigated the prognostic impact of EX in 116 patients with pT1mi-pT2a non-mucinous lung adenocarcinoma treated by segmentectomy or wedge resection. EX was evaluated using elastic fiber staining. Among 10 recurrent cases, 8 were EX-positive, and 2 were EX-negative and STAS-positive. The EX(-)/STAS(+) cases had local recurrence, while the EX(+) cases exhibited metastatic recurrence. The pT1abc EX(+) group showed significantly shorter recurrence-free survival (RFS) than the pT1abc EX(-) group, but no significant differences were observed when compared with the pT2 group. EX(+ )/STAS(-) and EX(+ )/STAS(+) groups showed significantly shorter RFS than EX(-)/STAS(-) group, but EX(-)/STAS(+) group did not. In conclusion, EX was associated with poor prognosis after sublobar resection of lung adenocarcinoma. Combined evaluation of EX and STAS may improve postoperative risk stratification.

Bouveret syndrome is a rare complication of cholelithiasis in which a gallstone enters the duodenum via a cholecystoenteric fistula, causing gastric outlet obstruction. Because of chronic inflammation and nonspecific symptoms, the condition can easily be misdiagnosed as a gastrointestinal malignancy. An 85-year-old woman presented with severe weight loss (10 kg), night sweats, and non-bloody vomiting. CT imaging revealed massive aerobilia, a thickened gallbladder wall, and an ill-defined mass at the gastroduodenal junction. These findings raised strong suspicion for a malignant process in the gallbladder or pancreatic head with gastroduodenal infiltration. However, subsequent upper endoscopy revealed the mass to be a huge impacted gallstone obstructing the duodenal bulb. The calculus was successfully fragmented and removed using intracorporeal electrohydraulic lithotripsy, which generates shock waves, resulting in complete resolution of the obstruction without high-risk surgery. Bouveret syndrome can closely mimic the clinical and radiological presentation of gastrointestinal malignancies. Physicians must maintain a high index of suspicion for this syndrome in elderly patients presenting with gastric outlet obstruction with features suggestive of malignancy and aerobilia, as prompt endoscopic evaluation can spare them from unnecessary oncologic interventions.

Hepatocellular carcinoma (HCC) is characterized by high heterogeneity, a complex tumor microenvironment, and multiple physiological barriers that limit conventional therapies and cause significant toxicity. Drug delivery systems (DDS), particularly nanoscale delivery systems, offer promising opportunities to overcome these obstacles through passive targeting, active targeting, and stimuli-responsive drug release. Nevertheless, despite substantial progress in preclinical research, the clinical translation of most DDS remains challenging. This review systematically outlines the pathophysiological rationale underpinning DDS design for HCC, including the aberrant vasculature, hypoxia, low pH, overexpressed enzymes and immunosuppressive features of the TME, as well as liver-specific barriers. Subsequently, we comprehensively evaluate the progress and limitations of passive targeting, active targeting, stimuli-responsive, and locoregional delivery systems. Furthermore, we dissect the core bottlenecks currently impeding clinical translation: tumor heterogeneity, the "interlocking chain" effect of multiple biological barriers, uncertainty of the EPR effect, multidrug resistance mechanisms, poorly defined long-term safety of nanocarriers, and the "valley of death" caused by discrepancies between preclinical models and human disease. Finally, we envision future directions: next-generation targeting strategies should focus on CSCs and metastasis; DDS must be deeply integrated with immunotherapy to remodel the immune microenvironment; biomimetic and bio-derived delivery systems may circumvent inherent limitations of synthetic carriers; multifunctional theranostic platforms enable real-time monitoring and personalized treatment; and establishing more clinically relevant animal models alongside personalized DDS design paradigms is key to accelerating translation. Our central argument is that the future success of DDS for HCC will no longer rely on the "showmanship" of individual technologies, but rather on a "systems engineering" approach grounded in a profound understanding of HCC biological heterogeneity, with the core objectives being precise spatiotemporal control of drug distribution and beneficial interactions with the host immune system.