While extreme heat represents an established risk factor for mortality in patients with diabetes mellitus (DM), its synergistic effects with air pollution and green space remain incompletely elucidated. This study aimed to investigate the joint effects of heatwaves, air pollution, and green space on all-cause mortality in older adults aged ≥ 45 years with diabetes mellitus.

We conducted a longitudinal analysis of data from 1,400 adults aged ≥ 45 years with DM, drawn from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). Heatwaves were defined according to six intensity-duration thresholds, based on two temperature thresholds (95th/97.5th percentiles of daily maximum temperature) and three duration criteria (≥ 2/≥3/≥4 consecutive days). Time-varying Cox proportional hazards models were used to estimate hazard ratios (HRs), with adjustments for individual PM₂.₅, NO₂ and greenness exposures as time-varying covariates. Multiplicative and additive interactions were evaluated using product terms and the relative excess risk due to interaction (RERI), complemented by the attributable proportion due to interaction (AP) and the synergy index (S).

Heatwave exposure was significantly associated with increased mortality risk in a graded exposure-response relationship, with HRs increasing from 1.027 (95% CI: 1.013-1.041) to 1.070 (95% CI: 1.048-1.093) as heatwave intensity and duration increased. Additive interaction analyses demonstrated significant synergistic effects between heatwaves and both air pollutants and reduced greenness. These combined effects were more pronounced among older individuals and urban residents.

Heatwaves interact synergistically with air pollution and diminished greenness to elevate mortality risk in diabetic patients. These findings highlight the imperative for integrated public health strategies that concurrently address these coexisting environmental exposures.

Not applicable.

Triglyceride high-density cholesterol-glucose body index (TyHGB) has been identified as a reliable predictor for the risk of metabolic diseases. However, its significance concerning hyperuricemia and gout has not been investigated. Thus, this research aims to examine the link between TyHGB and the risk of hyperuricemia and gout in individuals with T2DM.

In this cross-sectional study, 2527 patients with T2DM admitted to the hospital between 2018 and 2023 were evaluated. Restricted cubic spline (RCS) and logistic regression techniques were utilized, along with further stratified and interaction analyses.

A positive linear association was identified between TyHGB and the prevalence of both hyperuricemia and gout. As TyHGB levels increased, there was a significant rise in the proportion of patients diagnosed with hyperuricemia or gout. Specifically, the prevalence of gout was 2.8%, 3.2%, 4.1%, and 10.4%, while the prevalence of hyperuricemia was 17.4%, 20.8%, 26.4%, and 42.7%, respectively. Multivariable logistic regression analysis revealed that each 1-unit increase in TyHGB was associated with a 15% increasing risk of hyperuricemia (OR = 1.15, 95% CI = 1.10, 1.19) and a 10% increasing risk of gout (OR = 1.10, 95% CI = 1.05, 1.15). Subgroup analyses indicated that this association was more pronounced in females. Furthermore, ROC analysis demonstrated that TyHGB exhibited a superior discriminatory performance compared to either TyG, TG/HDL, BMI, and FPG alone in predicting hyperuricemia (AUC = 0.666) and gout (AUC = 0.693).

TyHGB demonstrates a positive association with the risk of hyperuricemia and gout, highlighting its potential utility as a cost-effective biomarker for stratifying individuals at risk for these conditions.

Not applicable.

Tuberculosis-diabetes mellitus (TB-DM) multimorbidity significantly increases the risk of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Early risk stratification tools for this high-risk population remain lacking.

To develop and validate an interpretable machine learning (ML) model for predicting MDR/RR-TB in patients with TB-DM multimorbidity, and to identify key predictive factors using explainable artificial intelligence.

This dual-center retrospective study enrolled 245 patients with TB-DM multimorbidity from January 2019 to December 2022. Seven machine learning algorithms were constructed and validated with 10-fold cross-validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), accuracy, precision, recall, F1-score, calibration curve, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was applied to identify critical predictive factors.

The random forest (RF) model achieved the optimal performance, with an AUC-ROC of 0.818, accuracy of 0.806, precision of 0.688, recall of 0.611, and F1-score of 0.647; the moderate recall indicates a considerable false-negative rate (FNR) , supporting its use as a triage tool rather than a stand-alone diagnostic test. Calibration and DCA confirmed robust predictive reliability and substantial clinical net benefit within a clinically relevant threshold range of 0.06-0.80. SHAP analysis identified the symptom-to-diagnosis interval, tuberculosis (TB) treatment history, treatment adherence, pulmonary cavitation, and smoking history as the top five critical predictors.

The interpretable RF model accurately and reliably predicts the risk of MDR/RR-TB in patients with TB-DM multimorbidity. The symptom-to-diagnosis interval is the most crucial risk factor. This model can assist clinical triage, early intervention, and personalized management.

Brain abscess remains a serious infection with high morbidity and mortality despite advances in neuroimaging, molecular diagnostics and stereotactic neurosurgical techniques. Most large studies were based on European cohorts. Most Asian studies are single center, with smaller cohorts that consist almost entirely of patients with pyogenic brain abscess (PBA). Here, we present the results of our multi-center, retrospective study, representing the largest cohort of adults with brain abscess in Singapore.

Radiological reports of patients who underwent neuroimaging between 1 Nov 2013 and 31 Dec 2024 at three tertiary hospitals in Singapore were filtered for terms indicating brain abscess. Infectious diseases physicians reviewed the electronic medical records to identify patients who fulfilled pre-determined criteria for "definite" or "probable" diagnosis.

Over the 11-year-old study period, there were 106 patients with brain abscess. The diagnosis of 54 and 52 patients were assessed to be "definite" and "probable", respectively. The median age (interquartile) of the patients was 59 years (49-67), 62.2% (66/106) were male, and 95.3% (101/106) were Singaporeans. 60.4% (64/106) were immunocompromised. PBA (n = 65) accounted for more than half of the cases, followed by tuberculosis (TB) (n = 20), toxoplasmosis (n = 9), Nocardia brain abscess (n = 7), invasive mold infection (n = 3) and cryptococcosis (n = 2), respectively. Most patients with PBA had only one organism identified from microbiological investigations (53/65, 81.5%), among which Klebsiella pneumoniae (n = 21), Streptococcus anginosus (n = 12) and Staphylococcus aureus (n = 8) were most commonly isolated. 28 out of 65 (43.1%) patients had oral cavity bacteria identified from microbiological investigations. Diabetes mellitus was the leading cause of immunosuppression in patients with PBA, while HIV infection was the leading cause in those with TB. In this cohort, 7.5% (8/106) and 14.2% (15/106) died within 30 and 90 days from date of presentation, respectively. On multivariate analysis, having undergone external ventricular drainage was the only clinical parameter found to be associated with increased mortality (OR 6.26, 95% CI: 1.44-27.1, P = 0.0014).

This study has provided valuable insights into the microbiology and clinical characteristics of brain abscesses in adults in Singapore and highlighted challenges in distinguishing between different etiologies. Further study with a larger, multicenter cohort and prospective design may aid to address study limitations.

Diabetes mellitus is recognised as a global health problem and has increasingly been associated with fungal infections, as an independent risk factor. Diabetic patients are predisposed to both superficial as well as invasive fungal disease, and account for substantial morbidity and mortality. Recent pandemic of COVID-19 underlined the global problem of mucormycosis, however, the burden of fungal infections among diabetics has a much broader horizon. This review aims to summarise the spectrum of fungal infections encountered among diabetic patients, along with elucidating immunopathogenesis and clinical challenges encountered in diagnosis and management of such infections.

We conducted a narrative review of all published literature focusing on spectrum of fungal infections, immunopathogenesis and clinical challenges encountered in diagnosis and management, among diabetic patients.

Diabetes mellitus facilitates the acquisition and progression of fungal infections via multiple coordinated mechanisms viz. hyperglycemia, impaired immune (innate and adaptive) response, altered microenvironment and endothelial dysfunction. These changes in the milieu contribute to pervasive clinical presentations, ranging from cutaneous and oral candidiasis to invasive fungal diseases like mucormycosis, aspergillosis and cryptococcosis. Besides predisposing to fungal infections, diabetes also serves as a prognostic factor and has been noted to worsen the outcome. Furthermore, the altered microenvironment affects the pharmacokinetics of antifungal drugs and can also reduce the efficacy of antifungal regime, further convoluting and worsening the progression of disease.

Early diagnosis and management of fungal infections is necessary to mitigate the associated morbidity and mortality among diabetic patients. A multidisciplinary approach is imperative as diabetes hampers the effectiveness of conventional antifungal regimens and facilitates antifungal resistance. Regular monitoring of glycaemic index and compliance for drugs, along with lifestyle modifications desired for optimal levels, is pre-requisite for antifungal therapy to exhibit desired action.

Increases in cytoplasmic free Ca²⁺ ions ([Ca²⁺]) are a critical signal in pancreatic islet beta-cells and are usually required for insulin secretion in response to glucose or other secretagogues. Changes in Ca²⁺, monitored using high-speed imaging across individual or multiple planes of the islet, can be used to explore the functional networks of beta-cells required for the precise regulation of insulin secretion. These networks are composed of functionally distinct beta-cell subpopulations: first-responders, highly connected hubs, and leader beta-cells, which initiate, connect, and dictate the pattern of spatially organized Ca²⁺ oscillations, respectively. Alterations in Ca²⁺ coordination among beta-cells contribute to defective insulin secretion, which underlies all forms of diabetes mellitus. Here, we provide a detailed protocol to perform Ca²⁺ imaging in isolated rodent islets, focusing on mouse islets expressing the genetic Ca²⁺ sensor, GCaMP6. We provide a step-by-step guide to evaluate general parameters of islet Ca²⁺dynamics, coordination, connectivity, and identification of specific functional subpopulations. This approach can be applied to investigate the role of Ca²⁺ dynamics and coordination in tissues where coordination is critical for normal function.

Hodgkin Lymphoma (HL) is a heterogeneous malignant disorder in the human body's lymphatic system with distinct clinical and molecular features. The objective of this research was to assess the hematological and molecular status of HL patients in Palestine and explore potential prognostic indicators and potential targets requiring further evaluation. Certain hematological factors, i.e., anemia, increased levels of lactate dehydrogenase, and inflammatory markers, are included in the International Prognostic Score (IPS) for HL. This study highlights the clinical value of accessible hematological biomarkers in resource-limited healthcare settings. A retrospective cohort study was conducted on 557 HL lymph node biopsies (2017-2023) from Palestinian Health Information Center (PHIC) database and hospital medical records. Hematological parameters (hemoglobin, MCV) and biochemical markers (ESR, LDH) were analyzed. Claudin-6 (CLDN6) mRNA expression was quantified in lymph node tissues from HL patients (n = 25) and healthy donors (n = 25) via qRT-PCR, while protein levels were assessed by Western blot. Serum GATA-4 concentrations were measured by ELISA. Nodular Sclerosis was the most common form, which predominantly occurred in young patients with a relatively equal sex distribution. The highest frequency was found in Hebron. Hemoglobin levels differed between subtypes, with the lymphocyte-depleted subtype showing the lowest mean hemoglobin values; the Lymphocyte-Depleted (LD) subtype exhibited the lowest hemoglobin and MCV (74.77 fL), indicating microcytic anemia. ESR was elevated across subtypes, with the highest levels observed in the NOS (63.5 mm/h), reflecting aggressive disease. Male mortality was highest in Mixed Cellularity (87.5%) and NS (75%), while LD and Lymphocyte-Predominant subtypes showed no male deaths. Molecularly, CLDN6 mRNA and GATA-4 levels were significantly elevated in HL tissues (P < 0.001), though Claudin-6 protein expression remained unchanged, suggesting post-transcriptional regulation. This study represents the first combined hematological and molecular characterization of Hodgkin lymphoma in Palestine and provides preliminary evidence for CLDN6-GATA4 regulatory involvement in HL pathogenesis. The hematological changes in Palestinian HL patients are unique. The roles of CLDN6 and GATA-4 as potential markers remain preliminary and require further validation in the context of Hodgkin lymphoma.

Total Neoadjuvant treatment (TNT) has now become the standard of care in locally advanced rectal cancer(LARC) and has shown promising results. However, use and outcome of different TNT regimens in real-world practice is largely unknown.Here we report the feasibility and efficacy of RAPIDO regimen which we adopted since 2021 for LARC.

A retrospective review of prospectively collected data, conducted at Tata Medical Center, Kolkata between January 2021 to June 2024. 95 consecutive patients with localized rectal adenocarcinoma, treated with short course radiotherapy 25 Gy/5frs/1week followed by CAPOX based chemotherapy with or without surgery were analysed. Data was collected in the Redcap Database.

The median age of the cohort was 53 years. Lower rectal disease, T4,N2,EMVI(Extramural Vascular Invasion) Grade 3/4, MRF (Mesorectal fascia) involvement were seen in 51(54%), 21(22.1%), 86(90.5%), 58(61%) and 70 (73.7%)patients respectively.62 patients (65.2%) underwent surgery. Pathological complete response (pCR) was achieved in 27.4%(17/62) cases. At a median follow-up of 2.4 years,43 patients (45.3%) underwent TNT and surgery and are disease free on follow up. Local failure was seen in 2 patients after surgery(3.2%)0.17 of 62 patients (27.4%) who underwent surgery developed distant metastasis with lung being the most common site (16.1%). The estimated 3 year overall survival of all patients was 83% and for patients who underwent surgery 3-year OS was 92% and 3-year disease free survival(DFS) was 63% Maximum grade≥ 3 diarrhoea and febrile neutropenia during chemotherapy were observed in 17 (17.9%) and 14 (14.7%) patients respectively.

RAPIDO protocol in real world settings shows excellent response rates in LARC. It is a safe and feasible approach, however implementing a prolonged neoadjuvant treatment in the real world remains a challenge because of suboptimal compliance.

Pediatric primary diffuse leptomeningeal melanomatosis (PDLM) is a rare, aggressive malignancy with no established standard of care. We performed an integrated survival analysis to characterize disease course and identify treatment factors associated with overall survival (OS).

A systematic literature search of PubMed, Embase, and Scopus (2000-2025) was conducted in accordance with PRISMA guidelines. Eligible studies included patients < 18 years with histopathologically confirmed PDLM per 2021 World Health Organization and Expert Care for Rare Adult Solid Cancers criteria and reported OS and treatment data. Survival was assessed using Kaplan-Meier analyses, with univariable and multivariable Cox proportional hazards regression.

Thirty-three pediatric PDLM cases were identified (57.6% male; median age 10 [IQR 3-14] years). Diagnosis was established via tissue sampling in 72.7%, cerebrospinal fluid cytology in 21.2%, and both in 6.1%. Among 13 patients with molecular testing, 69.2% harbored NRAS mutations. Twenty-four patients (72.7%) received treatment: chemotherapy (70.7%), radiation therapy (41.7%), and immunotherapy (62.5%). Median OS was 5.0 [3.5-7.0] months. On Kaplan-Meier analysis, immunotherapy was associated with improved OS (p < 0.001), including when combined with radiation (p = 0.038), chemotherapy (p = 0.006), or both (p = 0.048). Univariable Cox regression showed immunotherapy to be significantly associated with reduced hazard of death (HR 0.23 [0.10-0.51], p < 0.001). On multivariable analysis, immunotherapy (HR 0.22 [0.10-0.49], p < 0.001) and chemotherapy (HR 0.44 [0.21-0.94], p = 0.035) were independently associated with improved OS.

Pediatric PDLM carries a uniformly poor prognosis. Immunotherapy and chemotherapy were the only treatments independently associated with improved survival, highlighting their central role in management of this rare disease.

Functional and nutritional impairments adversely affect outcomes in hematologic malignancies; however, the comparative prognostic value of widely available screening instruments remains insufficiently explored. The present study aimed to examine the association between nutritional and functional screening instruments and 12-month mortality in hospitalized patients with hematologic malignancies.

In this prospective cohort of 91 patients (median age 53 years [IQR, 35-61]), nutritional screening and assessment tools (PG-SGA, GLIM criteria) and functional screening instruments (SARC-F, SARC-CalF, and Geriatric 8 [G8]) were applied within 72 h of admission. The G8 was pragmatically used as a multidimensional vulnerability screening instrument. Discriminative ability for mortality was evaluated using ROC curve analysis, and Cox regression models (unadjusted and adjusted) were used to examine associations with mortality.

During follow-up, 29.7% of patients died. The G8 and SARC-CalF were associated with mortality in adjusted models (HR 4.83, 95% CI 1.13-20.68; HR 2.37, 95% CI 1.08-5.17, respectively). PG-SGA Global showed acceptable discriminative performance in ROC analyses (AUC 0.71) but was not associated with mortality after adjustment. GLIM criteria were not associated with mortality in adjusted models.

The G8 and SARC-CalF scores have demonstrated prognostic utility as simple and low-cost screening tools associated with mortality in these patients with hematological malignancies hospitalized in a resource-limited service.