When a patient's presentation raises suspicions for conditions other than diabetic kidney disease (DKD), such as sudden onset proteinuria <5 years after the onset of type 2 diabetes, proteinuria without retinopathy or neuropathy, acute kidney injury, active urinary sediment, or hematuria, clinically indicated kidney biopsies are typically carried out. Consequently, a high incidence of non-DKD (NDKD) in clinical biopsies from diabetes individuals is not unexpected. The purpose of the study is to investigate the clinical predictors, prevalence and histopathological spectrum of NDKD in patients with type 2 diabetes mellitus.

Dayanand Medical College and Hospital in Ludhiana conducted this cross-sectional observational study. After taking informed consent, 43 patients with diabetes who were suspected of having NDRD had kidney biopsies based on either or both of the following criteria: (1) Hematuria (red blood cell [RBC] casts, RBC >5/hpf). (2) Unexpected elevations in serum creatinine of more than 2 mg/dL. (3) Nephrotic syndrome with sudden onset. (4) Renal failure without diabetic retinopathy (DR). (5) DM duration <5 years. (6) Nephrotic range massive proteinuria with normal renal function. (7) Normal or negligible proteinuria along with severe renal insufficiency (serum creatinine >2 mg/dL) (<500 mg/dL).

(1) Of the 43 patients, 24 (56.0%) had pure NDKD. Four patients (9.3%) had mixed renal disease, while 15 patients (35%) had DKD. (2) The most prevalent NDKD was acute interstitial nephritis (AIN) (12%), which was followed by immunoglobulin A (IgA) nephropathy, localized proliferative glomerulonephritis and crescentic glomerulonephritis (7.0% each). The most prevalent pathology observed in mixed renal disease was DN with AIN. (3) The duration of hypertension was 4.98 ± 2.86 years in the group without DKD and 8.07 ± 4.65 years in the group with DKD, both of which were statistically significant. (4) Compared to the DKD group, more patients in the NDKD group had shorter DM duration (<5 years). A greater proportion of individuals in the DKD group had DM for more than 10 years. (5) Compared to the NDKD group, there were more NPDR patients in the DKD group.

Since several diseases, including MN, IgA nephropathy and AIN, are frequently treatable or even curable, our study demonstrated the need for early suspicion and diagnosis of NDKD.

Diabetic eye disease, the leading microvascular complication of diabetes mellitus (DM), is one of the leading causes of blindness worldwide, whose disease burden and demographics are only expected to grow in the coming decade. Advances in molecular biology techniques have enabled the identification and study of several proteins and transcription factors believed to play key roles in the underlying disease pathogenesis. A majority of these factors work together, contributing to both angiogenic (formation of new blood vessels) and inflammatory processes underlying diabetic retinopathy (DR).As a result, emerging therapies are increasingly targeting specific molecular mechanisms. In parallel, nonpharmacological interventions are being proposed to inform the development of appropriate clinical diagnostic and treatment guidelines. These approaches aim to address the early stages of disease and slow or prevent progression to chronic, later stages that may result in vision loss. This review synthesizes foundational and recent evidence using a qualitative narrative approach, focusing on hypoxia-driven molecular pathways rather than quantitative meta-analysis. Although numerous studies have consistently identified key molecular factors that contribute to the pathogenesis of diabetic eye disease, additional details regarding the specific roles of some factors listed herein, as well as the discovery and involvement of other factors in the pathway, remain to be fully explored and understood.

Our previous studies have demonstrated that the activated pancreatic stellate cell (PSC) could induce islet damage in type 2 diabetes mellitus (T2DM). While tissue-type plasminogen activator (tPA) is significantly reduced in T2DM, its subsequent effects are unclear. The purpose of this experiment was to observe the impact of tPA on PSC activation, with the aim to better understand the potential role of tPA in T2DM.

50 type 2 diabetic patients and 50 healthy persons were included in the diabetic group and the control group, respectively. Fasting blood was collected separately, and the tPA-level was detected by ELISA. Rat PSCs were isolated from pancreatic tissue using standard explant techniques. The PSCs were then characterized by staining them with Oil Red O to visualize lipid droplets and using immunofluorescent markers (α-smooth muscle actin (α-SMA), vimentin, and glial fibrillary acidic protein (GFAP)). After characterization, the PSCs were treated with tPA, then the proliferation of PSCs was measured using the cell counting kit-8 (CCK-8), the apoptosis was observed by the caspase-3 fluorometric assay kit, and the migration ability was assessed using the wound-healing assay and the transwell migration assay. Finally, a Western blot was used to identify the extracellular matrix (ECM) component synthesized by PSCs.

The diabetic patients had significantly lower levels of tPA compared to the controls. Rat PSCs treated with tPA exhibited more lipid droplet accumulation, and their ability of proliferation, migration, and ECM synthesis were significantly inhibited.

This study demonstrated that tPA can play a crucial role in significantly inhibiting the activation, proliferation, migration, and ECM synthesis of PSC. Therefore, we speculate that the significant reduction of tPA in T2DM may exacerbate the detrimental effect of PSC on β-cell function.

Internal carotid artery fenestration is a rare vascular anomaly that may present with transient ischemic attack symptoms due to localized flow disturbances. It is important to report such cases, as they present unique diagnostic challenges and clinical implications, particularly when associated with systemic vascular risk factors such as diabetes and hypertension. Differentiating internal carotid artery fenestration from other conditions, such as internal carotid artery dissection, is crucial for appropriate management and patient outcomes.

A 78-year-old Iranian female patient with a medical history of uncontrolled diabetes mellitus and hypertension presented to the emergency department with sudden-onset double vision, dizziness, and weakness in her left limbs. Symptoms lasted for 15 minutes and fully resolved. Neurological examination revealed mild weakness in the left upper and lower limbs but no sensory deficits. A bruit was detected over the left carotid artery, raising suspicion for carotid artery disease. Blood tests showed elevated blood glucose, and imaging studies, including carotid Doppler ultrasound, revealed irregularities and increased intima-media thickness, suggesting early vascular changes. Brain computed tomography scan was normal, and computed tomographic angiography of the head and neck revealed an incidental finding of internal carotid artery fenestration at the cervical segment. The fenestration appeared as a mild fusiform dilation of internal carotid artery with no signs of dissection or thrombosis. The patient was started on dual antiplatelet therapy (aspirin and clopidogrel) and optimized for blood pressure and lipid control. She was discharged with no residual neurological deficits, and follow-up was arranged for continued management of her cardiovascular risk factors.

This case highlights the diagnostic challenges and clinical relevance of internal carotid artery fenestration, particularly in patients with systemic vascular risk factors. Although internal carotid artery fenestration is often asymptomatic, it can be associated with cerebrovascular complications, such as ischemic events. In this case, the transient symptoms likely resulted from localized hemodynamic disturbances due to the fenestrated artery. While there is no established consensus on the management of asymptomatic internal carotid artery fenestration, dual antiplatelet therapy and risk factor optimization remain key strategies. Further research is needed to better understand the implications of internal carotid artery fenestration and to refine diagnostic and management protocols for these rare vascular anomalies.

Pneumonia is a common infection that leads to frequent hospitalizations and primary healthcare visits. Previous smaller studies have indicated high prevalence of undiagnosed diabetes mellitus (DM) and increased subsequent risk of coronary heart disease (CHD) among patients with pneumonia. However, previous studies have not used nationwide data that include diagnoses from primary healthcare settings, where most pneumonias are treated. The aim of this study was to examine whether pneumonia is associated with subsequent DM and CHD.

This was an open nationwide cohort study of adults 35–75 years of age in Sweden 2007–2018, including national registers and population-based primary healthcare data. The outcomes were DM and CHD, and individuals with outcomes diagnosed before the index date (including 2002–2005) were excluded. The index date was set as the first pneumonia diagnosis or the first healthcare contact (in those without pneumonia) during the study period. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) while adjusting for potential confounders.

A total of 4,580,606 individuals without previously diagnosed DM and 4,661,052 individuals without previously diagnosed CHD were included; of these, 348,024 individuals were diagnosed with DM and 295,592 with CHD during follow-up, respectively. Pneumonia preceded DM in 104,598 (30.1%) and CHD in 94,087 (31.8%) individuals. Compared with no diagnosis, pneumonia was associated with an age-adjusted HR of 1.12 (95% CI 1.11–1.13) for DM and 1.18 (95% CI 1.17–1.19) for CHD. In the full model, pneumonia was associated with a HR of 1.11 (95% CI 1.10–1.12) for both outcomes. Several complementary analyses were conducted, showing significant associations across most age-groups, in both sexes, across different follow-up periods (e.g. <1 year and ≥ 10 years), and in patients diagnosed with pneumonia in primary healthcare settings.

This nationwide study found that pneumonia is associated with subsequent DM and CHD. The findings indicate that pneumonia has a potential role as a clinical predictor of DM or CHD, including in primary healthcare settings, which warrants further clinical studies.

The online version contains supplementary material available at 10.1186/s41479-026-00199-x.

Circadian rhythms affect immunity, which could affect the effectiveness of immune checkpoint inhibitor (ICI). Whether the time of ICI administration is associated with clinical outcomes in advanced cancers remains unclear.

To evaluate the association between time of day of ICI administration and oncologic outcomes in patients with advanced solid tumors.

MEDLINE (via PubMed), Embase, and Web of Science Core Collection were searched in February 2026 to identify eligible studies.

Randomized clinical trials and prospective or retrospective cohort studies were included that compared early vs late time-of-day ICI administration and reported overall survival (OS) and progression-free survival (PFS).

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Two authors independently extracted data and assessed risk of bias. Random effects meta-analyses with inverse-variance method were performed.

The primary outcomes were OS and PFS. These outcomes were reported as hazard ratios (HRs) with 95% CIs for early vs late ICI administration.

Of the 7892 records screened, 29 studies with 6129 patients were included. Among these studies, 1 was a randomized clinical trial in non-small cell lung cancer (NSCLC; 210 patients), 1 was a prospective cohort study in head and neck squamous cell carcinoma (62 patients), and 27 were retrospective cohort studies (5857 patients) across NSCLC, melanoma, gastric cancer, head and neck squamous cell carcinoma, renal cell carcinoma (RCC), esophageal cancer, small cell lung cancer, urothelial carcinoma, biliary tract cancer, hepatocellular carcinoma, and other cancers. Earlier ICI administration was associated with increased OS (HR, 0.60; 95% CI, 0.51-0.70) and PFS (HR, 0.62; 95% CI, 0.54-0.71). Subset analyses by cancer type confirmed significantly increased OS and PFS in NSCLC (OS: HR, 0.58 [95% CI, 0.46-0.74]; PFS: HR, 0.60 [95% CI, 0.46-0.76]), gastric cancer (OS: HR, 0.61 [95% CI, 0.49-0.77]; PFS: HR, 0.62 [95% CI, 0.43-0.89]), RCC (OS: HR, 0.60 [95% CI, 0.40-0.90]; PFS: HR, 0.70 [95% CI, 0.50-0.98]), small cell lung cancer (OS: HR, 0.37 [95% CI, 0.26-0.53]; PFS: HR, 0.48 [95% CI, 0.36-0.65]), and biliary tract cancer (OS: HR, 0.62 [95% CI, 0.41-0.93]; PFS: HR, 0.55 [95% CI, 0.38-0.79]).

In this systematic review and meta-analysis of studies including patients with advanced cancers, early immunotherapy administration was associated with improved outcomes. These findings suggest that treatment timing may have clinical relevance and warrant prospective evaluation to establish standardized timing strategies across cancer settings.

Allogeneic hematopoietic cell transplant (HCT) is curative for hematologic cancers, yet access remains inequitable for racially and ethnically underrepresented and socioeconomically disadvantaged populations, making the goal of having a suitable donor for every patient who needs a transplant challenging. The ACCESS trial broadened access by enrolling patients without matched donors, who instead received an HCT from a mismatched unrelated donor.

To compare baseline characteristics of ACCESS trial participants with participants enrolled in a similar clinical trial and a patient-reported outcome (PRO) protocol cohort.

This cross-sectional study included adult participants (aged ≥18 years) from 3 cohorts-the ACCESS trial (2021-2024), BMT CTN 1703 trial (2019-2021), and Center for International Blood and Marrow Transplant Research (CIBMTR) PRO Protocol observational study (2020-2025)-who completed a baseline PRO survey. The ACCESS and PRO Protocol cohorts were stratified by conditioning intensity (myeloablative [MAC] vs reduced-intensity and nonmyeloablative [RIC/NMA]); all BMT CTN 1703 participants received RIC/NMA.

Hematopoietic cell transplant.

Racial and ethnic diversity, insurance type, education, and income were compared among cohorts using counts and percentages, and socioeconomic and structural disadvantage were measured using the Social Vulnerability Index and Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy.

Baseline surveys were completed by 208 participants in the ACCESS trial (median [range] age at transplant, 62.3 [20.4-78.9] years; 108 male [51.9%]), 122 participants in the PRO Protocol study (median [range] age at transplant, 63.9 [21.1-78.0] years; 67 male [54.9%]), and 342 participants in the BMT CTN 1703 trial (median [range] age at transplant, 66.9 [20.7-78.6] years; 218 male [63.7%]). Participants in ACCESS were more racially and ethnically diverse, with 15 (7.2%), 25 (12.1%), 46 (22.2%), 110 (53.1%), and 11 (5.3%) of Asian, Black or African American, Hispanic or Latino, White, and other race and ethnicity, respectively, compared with 4 (3.3%), 2 (1.6%), 8 (6.6%) 104 (85.2%), and 4 (3.3%), respectively, in the PRO Protocol and 10 (3.0%), 0, 16 (4.8%), 302 (91.0%), and 4 (1.2%), respectively, in the BMT CTN 1703 trial. Participants in ACCESS were more likely to have Medicaid (36 [18.1%]) vs PRO Protocol (8 [6.7%]) and BMT CTN 1703 (16 [5.1%]) participants and reported lower education (some college or an associate's degree: 103 [49.5%] vs 73 [59.8%] in the PRO Protocol; postcollege education: 34 [17.3%] vs 35 [29.2%] in the PRO Protocol) and household income (<$40 000 annually: 25 [24.0%] vs 8 [11.6%] in the PRO Protocol and 7 [38.9%] in the BMT CTN 1703 trial). Median Social Vulnerability Index scores were highest among participants in the ACCESS MAC group (median [range], 0.72 [0.01-0.97] vs 0.61 [0.16-0.78] in the PRO Protocol MAC group), and 16 participants [27.6%] in the ACCESS MAC group reported moderate to severe financial toxicity. The ACCESS participants lived closer to transplant centers, especially in the RIC/NMA group (median [IQR], 28 [14-75] miles vs 47 [16-96] miles for BMT CTN 1703 participants and 49 [21-104] miles for PRO Protocol participants).

This cross-sectional study of clinical trial participants and a clinical cohort found that the ACCESS trial enrolled a more racially and ethnically diverse and socioeconomically disadvantaged population. Trial designs that broaden eligibility could expand access to HCT, highlighting the need for systemic interventions to ensure equity.

Existing quality-of-life assessment tools for chemotherapy-induced alopecia may not adequately serve women of all races. Non-White patients with breast cancer receiving chemotherapy at our institution were approximately six times less likely than White patients to use scalp cooling (SC).

This study examines factors contributing to this disparity through interviews with Black women undergoing chemotherapy, focusing on alopecia's impact and attitudes toward its prevention and treatment.

Semi-structured, 1-hour Zoom interviews were conducted and transcribed. Content analysis using NVIVO software and a grounded theory approach identified themes.

Three main domains emerged: (1) alopecia's impact, (2) barriers to SC, and (3) improving alopecia management. Key barriers included limited representation of Black women in SC advertising and concerns about SC's effectiveness on textured hair. Solutions included better counseling on SC use, camouflage options, and increased awareness of other treatment options like dermatology referrals.

The study was conducted at a single institution; participation was voluntary leading to possible selection bias and the risk for recall bias in the setting of assessing patients' attitudes retrospectively.

This study highlights barriers to SC use among Black women, providing insights for developing interventions to improve access to alopecia prevention and treatment.

Heparanase uniquely cleaves heparan sulfate, the main component of the outer layer of endothelial cell plasma membranes, promoting tumour invasion and dissemination. However, it can also enhance tumour immune surveillance and clearance. heparanase's versatility extends to pro-thrombotic properties, such as the promotion of tissue factor release. Interestingly, elevated heparanase levels have been found in ovarian cancer (OC), which has a notably high incidence of venous thrombosis. Previously, single-nucleotide polymorphisms (SNPs) of HPSE were shown to modulate mRNA and protein levels, possibly predicting disease outcomes.

Given the potential role of heparanase in OC, the implications of three SNPs - rs11099592, rs4364254 and rs4693608 - were investigated in OC patients. In the discovery cohort, rs11099592 TT genotype and rs4364254 C allele carriers showed lower survival time than their counterparts (log-rank test, p = 0.025 and p = 0.001, respectively). Validation cohort analysis confirmed the worse prognosis associated with the rs11099592 T allele and the rs4364254 C allele in non-serous (log-rank test, p = 0.016) and platinum-resistant (log-rank test, p = 0.044) OC patients, respectively. The rs4364254 C allele was associated with reduced HPSE expression in peripheral blood components (χ² test, p = 0.005), suggesting a protective role for HPSE in OC patients.

HPSE rs11099592 and rs4364254 showed prognostic value, with T and C allele carriers, respectively, displaying worse clinical outcomes. These results indicate that heparanase could enable a tumour microenvironment shift towards a less aggressive cancer behaviour, facilitating leukocyte migration and anti-tumour responses. Further research should explore the dual mechanisms of this protein to improve OC management.

Neoadjuvant chemotherapy (NAC) is commonly used in early-stage breast cancer. A complete pathologic response (pCR) after NAC is associated with improved outcomes. This study investigated differences in pCR and clinical outcomes by race.

A single-institution, retrospective chart review identified patients with early-stage breast cancer who received NAC between January 1, 2010, and December 31, 2017. Associations between race and pathologic and clinical outcomes were evaluated using multivariable logistic regression and Cox proportional hazard models. Kaplan-Meier estimates and log rank tests assessed differences in recurrence-free survival (RFS) and overall survival (OS).

A total of 532 patients with breast cancer of all receptor subtypes were identified; 323 (60.7%) White, 188 (35.3%) Black and 21 (3.9%) other/unknown. The pCR rate was different between the 3 race categories; White 27.2%, Black 19.1% and other/unknown 9.5% (P = 0.03). In multivariate analysis, pCR rates were higher in White versus Black patients (P = 0.02). Patients with triple-negative disease demonstrated the largest difference in pCR (White 44.3% versus Black 27.1%; P = 0.04). Black patients had inferior OS compared to White patients (P = 0.03). There was no difference in RFS by race (P = 0.07).

Black patients demonstrated a lower pCR rate compared to White patients, and this was more pronounced in the triple-negative subgroup. There was no difference in RFS by race, but OS was inferior among Black patients. It is possible that the lower pCR rate in Black patients may contribute to lower OS; however, more investigation is needed to explain these differences.