Ischemic events are a recognized complication of flow diversion stents (FDS) in middle cerebral artery (MCA) aneurysms, often related to branch or perforator coverage. However, the clinical significance of isolated lenticulostriate artery territory infarcts following FDS remains incompletely understood.

We retrospectively reviewed consecutive patients treated with FDS for MCA aneurysms between January 2013 and December 2024. Baseline demographics, vascular risk factors, aneurysm and procedural characteristics were collected. Functional outcomes were assessed by the modified Rankin Scale (mRS) at discharge and at 6 months. All patients underwent magnetic resonance imaging (MRI) within 24-48 hours after treatment.

Forty-two patients were included (69% women; mean age 55.1 years). Diffusion-weighted imaging identified ischemic lesions in 6 patients (14.2%), exclusively within the lenticulostriate artery territory; 4 were clinically silent, and 2 patients (4.8%) had an mRS ≥ 2 at discharge. Ischemic lesions were significantly associated with diabetes mellitus (χ² = 19.385, p < 0.001) and dyslipidemia (χ² = 5.933, p = 0.015). No significant associations were observed with hypertension, smoking status, antiplatelet regimen, device type, or device size. Higher stent-to-vessel diameter ratios showed a non-significant trend toward lower odds of perforator territory ischemia.

In this single-center study, flow diversion for MCA aneurysms was associated with a measurable rate of lenticulostriate territory ischemia, most of which was clinically silent. The strong associations with metabolic comorbidities and the observed influence of device-vessel relationships highlight the importance of patient selection and vascular risk factor optimization. Prospective studies with standardized imaging and neurocognitive follow-up are warranted to clarify the long-term significance of asymptomatic ischemic lesions.

Nocardiosis remains diagnostically challenging in immunocompromised patients. We report disseminated nocardiosis due to Nocardia brasiliensis, supporting the role of repeat deep sampling and specimen concentration by cytocentrifugation in enhancing diagnostic yield. An 80-year-old man with myelodysplastic syndrome with low blasts and ring sideroblasts and type 2 diabetes mellitus presented with a three-week history of progressive pain and swelling of the right thigh and left lower leg. One week before symptom onset, the patient received a five-day course of oral levofloxacin for urinary frequency. Contrast-enhanced computed tomography (CT) demonstrated abscesses in the right thigh musculature, the subcutaneous tissue of the left lower leg, and the prostate. An initial smear from the left subcutaneous lesion was negative. Repeat aspiration of the intramuscular abscess in the right thigh, followed by cytocentrifugation, showed beaded, branching, Gram-positive filamentous bacilli, consistent with Nocardia. 16S ribosomal RNA gene sequencing subsequently identified N. brasiliensis. Antimicrobial susceptibility testing supported treatment with oral trimethoprim-sulfamethoxazole, which led to clinical improvement and a decrease in the size of the abscesses on follow-up contrast-enhanced CT. The patient was discharged on hospital day 23. In immunocompromised patients, nocardiosis may involve atypical anatomic sites. When the initial smear is negative, especially after prior antibiotic exposure, prompt repeat sampling with adequate volume from a deeper or alternative site, combined with cytocentrifugation, is essential to avoid delays in diagnosis and treatment.

Type 2 diabetes mellitus (T2DM) is a global health challenge associated with significant morbidity and mortality. Previous studies have indicated that the traditional Chinese medicine formula Tangzhiwan pills (TG) exhibits therapeutic potential against T2DM. However, the precise molecular mechanisms underlying its therapeutic efficacy, particularly at the systemic multiomics level, remain largely unexplored.

The main components of TG pills were analyzed by LC‒MS. RNA-seq and metabolomics were used to analyze the potential mechanism. A rat model of T2DM was established, and integrated metabolomics and transcriptomics analyses were conducted on liver tissue before and after TG treatment. Network pharmacology was deployed to identify bioactive metabolites and underlying targets of TG for improving T2DM.

TG treatment effectively ameliorated key pathological features of T2DM, including hyperglycemia, impaired glucose tolerance, dyslipidemia, and hepatic inflammatory cell infiltration. Integrated multiomics analyses identified dysregulated hepatic glycolysis/gluconeogenesis as a central metabolic perturbation in T2DM, which was effectively normalized by TG treatment. This restoration was mechanistically linked to the concurrent modulation of the PPAR and p53 signaling pathways. These interactions target the p53 and PPAR signaling pathways, thereby inhibiting the expression of associated genes.

Collectively, our study delineates a novel multitarget mechanism whereby TG, via its bioactive components (e.g., 6-demethoxytangeretin and naringin), concurrently modulates the PPAR and p53 signaling axes to restore hepatic glucose metabolic homeostasis, offering a mechanistic rationale for its clinical application in T2DM management.

Orforglipron is a novel non-peptide (GLP-1) receptor agonist designed for daily oral administration without food or water restrictions. This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.

In this 52-week, randomised, open-label, active-controlled, multicentre, multinational, phase 3 study, we enrolled adults (≥18 years) with type 2 diabetes inadequately controlled with metformin (≥1500 mg per day), glycated haemoglobin (HbA_1c) between 7·0% and 10·5% (53-91 mmol/mol), and BMI at least 25 kg/m² from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico, and the USA. Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day. The primary objective of the study was to assess non-inferiority of orforglipron 36 mg versus semaglutide 14 mg and orforglipron 12 mg versus semaglutide 7 mg for mean change at week 52 from baseline in HbA_1c (with a non-inferiority margin of 0·3%) in the intention-to-treat population. Hierarchical analysis for superiority was prespecified after attainment of non-inferiority. The treatment regimen estimand, based on data from all randomly assigned participants regardless of intercurrent events, was the primary estimand; the efficacy estimand was considered supportive. The safety endpoints used data from all participants who received at least one dose of the study drug. This trial was registered on ClinicalTrials.gov (NCT06045221) and is completed.

From Sept 22, 2023, to Aug 22, 2025, 1698 participants were recruited and randomly assigned to orforglipron (n=424 on 12 mg and n=423 on 36 mg) or semaglutide (n=426 on 7 mg and n=425 on 14 mg). For the treatment regimen estimand, mean changes at week 52 from a baseline HbA_1c of 8·3% were -1·71% (SE 0·07) with orforglipron 12 mg, -1·91% (0·08) with orforglipron 36 mg, -1·23% (0·05) with semaglutide 7 mg, and -1·47% (0·06) with semaglutide 14 mg. Estimated treatment differences were -0·48% (95% CI -0·65 to -0·31; p<0·0001) for orforglipron 12 mg versus semaglutide 7 mg; -0·44% (-0·62 to -0·26; p<0·0001) for orforglipron 36 mg versus semaglutide 14 mg; -0·24% (95% CI -0·41 to -0·072; p=0·0050) for orforglipron 12 mg versus semaglutide 14 mg; and -0·68% (-0·85 to -0·50; p<0·0001) for orforglipron 36 mg versus semaglutide 7 mg. The primary objective of non-inferiority was met and both orforglipron doses showed superiority to both semaglutide doses, including orforglipron 12 mg versus semaglutide 14 mg. The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity. More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg), and mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm). Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group.

In individuals with type 2 diabetes inadequately controlled with metformin, orforglipron 12 mg and 36 mg was non-inferior and superior to semaglutide 7 mg and 14 mg with respect to the mean change in HbA_1c from baseline to 52 weeks. Although the safety profiles of both orforglipron and semaglutide were generally consistent with the GLP-1 receptor agonist class, the incidence of gastrointestinal events, discontinuations due to adverse events, and mean increase in pulse rate were higher with orforglipron than oral semaglutide.

Eli Lilly.

Through an integrated approach combining synthetic chemistry, in vitro enzymatic assays, and advanced computational methods including molecular docking, and DFT calculations, we identified several compounds with superior inhibitory activity compared to the clinical standard acarbose. Compound 17 emerged as the most promising candidate, exhibiting exceptional potency (IC₅₀ = 4.89 ± 1.25 µM for α-amylase and 5.98 ± 1.67 µM for α-glucosidase) alongside favorable drug-like properties. DFT analyses revealed optimal frontier molecular orbital distributions and electrostatic potential patterns that correlate strongly with biological activity, while the molecular docking studies demonstrated specific interactions with key catalytic residues. These findings establish PHQ derivatives as promising leads for developing next-generation antidiabetic agents, with compound 17 representing an excellent candidate for further preclinical evaluation.

Chronic plantar lesions in patients with diabetes mellitus present a significant therapeutic challenge due to microangiopathy, peripheral neuropathy, and delayed wound healing. Unilateral plantar lesions originating from follicular infection may rapidly progress into chronic non-healing ulcers with hyperkeratosis, often mimicking diabetic foot ulcers rather than classical bilateral dermatoses.

To document the integrative Ayurveda management of a chronic unilateral plantar lesion in a patient with long-standing diabetes mellitus and to correlate the clinical presentation with Ayurveda diagnostic concepts.

A 68-year-old male with type 2 diabetes mellitus for 25 years presented with a unilateral fissured plantar lesion that began as a pimple and worsened following irritant topical applications (gentian violet and potassium permanganate). Clinically, the lesion resembled an infected diabetic foot ulcer (Wagner grade 1-2). From an Ayurveda perspective, the condition was interpreted as Dushta Vrana occurring in the background of Prameha with associated Vata-Pitta aggravation. The patient was treated with a structured four-month Ayurveda regimen including Vata-Pitta pacification, metabolic regulation, wound cleansing (Vrana Shodhana), and tissue-healing (Ropana) therapies.

The Ayurveda intervention resulted in complete healing of the chronic unilateral plantar lesion without recurrence or adverse effects. This case suggests that an individualized, physiology-oriented Ayurveda wound-care approach may serve as a supportive integrative strategy in the management of chronic diabetic plantar lesions and highlights the potential value of integrating traditional wound-care principles with modern clinical monitoring in complex chronic wounds associated with metabolic disease.

People in rural and remote areas often participate less actively in colorectal cancer (CRC) prevention practices, including faecal immunochemical testing (FIT). However, the evidence on this is limited.

The aim of this systematic review and meta-analysis was to summarise geographical disparities in participation and positivity of FIT-based CRC screening.

Six databases were searched for articles published until June 2024. We included studies reporting FIT-based CRC screening among average-risk individuals aged 40-74, examining geographical disparities using location-based or geospatial methods. Two reviewers independently screened, assessed bias, and extracted data. Random-effects models estimated pooled participation, positivity rates, and odds ratios for geographical effects.

Of 8532 articles, 35 were included in the review, with 21 used for meta-analysis. The overall FIT participation rate was 49.9% (95% confidence interval [CI]: 40.6, 59.2). In Europe, individuals in rural areas had higher participation rates compared to urban areas (pooled odds ratio [POR]: 1.20; 95% CI: 1.01, 1.42), while in Australia, remote areas exhibited lower odds of participation than metropolitan areas (POR: 0.75; 95% CI: 0.65, 0.87). The overall FIT positivity rate was 8.70% (95% CI: 6.50, 11.70), with no significant difference between rural and urban areas (p = 0.24).

A notable disparity in the FIT-based CRC screening participation rate was observed using the geographical definition of rurality and remoteness. Further research is needed to identify the sociocultural, healthcare access, and policy factors driving these differences and develop targeted strategies to improve screening and address barriers for underserved populations.

Family history of cancer (FHC) is a recognized proxy of inherited cancer susceptibility. In NSCLC, however, the clinical relevance of FHC remains poorly defined, and standardized approaches to identify patients enriched for pathogenic germline variants (PGVs) are lacking.

FAHIC-Lung (NCT06196424) is a multicenter, cross-sectional/prospective observational study conducted in Italy. Consecutive patients with NSCLC were enrolled, detailed FHC data were collected using a dedicated questionnaire covering cancer type, age at diagnosis, degree of relatedness, smoking exposure, and other risk factors among relatives. A weighted FHC score integrating cancer burden across first-, second-, and third-degree relatives and accounting for family structure and degree of genetic relatedness was developed. Percentile-based thresholds (≥90th percentile, or ≥ 75th percentile with additional risk factors) were used to identify patients with enriched familial cancer profiles.

Among 336 evaluable patients, median age at diagnosis was 67 years, 49.7% were female, and 25.9% were never smokers. Cancer in at least one parent was reported in 63.1% of cases, while 27.7% of patients had a personal history of multiple primary malignancies. The median total FHC score was 0.40 (interquartile range 0.12-0.67). Thirty-three patients (9.5%) exceeded the 90th percentile threshold, and 22 patients (6.5%) met the 75th percentile threshold in association with clinical enrichment criteria. Overall, 55 patients (16.4%) were identified as having enriched familial cancer risk and were selected as a target population for systematic genetic counseling and planned germline testing.

In this prospective observational study, a standardized and weighted assessment of family history identified a clinically meaningful subset of patients with NSCLC enriched for familial cancer patterns. This framework provides a pragmatic approach to optimize referral to genetic counseling and supports targeted germline screening strategies beyond traditional smoking-based risk models. Prospective validation in the planned translational phase will clarify the clinical utility of this approach.

To assess interobserver agreement of computed tomography (CT) features in colon cancer, their association with pathological staging, and the influence of baseline characteristics on clinical-pathological agreement.

CT scans of patients with locally advanced colon cancer treated between 2011 and 2020 at two Dutch hospitals were analyzed. Eleven radiologists independently reviewed the scans in pairs using a structured template. Interobserver agreement was evaluated using Krippendorff's alpha (α) and intraclass correlation coefficients (ICC). Associations between CT features and pathological stages, and the impact of baseline characteristics on clinical-pathological agreement, were assessed using mixed-effects logistic regression.

Interobserver agreement was α = 0.55 (95% CI: 0.51-0.60) for T stage, α = 0.57 (95% CI: 0.52-0.61) for N stage, α = 0.44 (95% CI: 0.36-0.51) for retroperitoneal surgical margin, α = 0.59 (95% CI: 0.52-0.65) for bowel obstruction, α = 0.27 (95% CI: 0.22-0.33) for extramural vascular invasion, α = 0.22 (95% CI: 0.14-0.31) for tumor deposits, ICC = 0.72 (95% CI: 0.70-0.75) for tumor length, and ICC = 0.62 (95% CI: 0.58-0.65) for largest node diameter. Significant associations (P < 0.05) were observed between clinical cT, cN, tumor length, and cEMVI with pT, and between cN, node diameter, and node heterogeneity with pN. Age, tumor location, and differentiation grade significantly influenced agreement.

Several CT features were significantly associated with pathological stage, but their inconsistent interpretation across observers, indicates limited reliability for individualized treatment decisions. Interpretation should therefore focus on features with proven reproducibility, namely tumor length and largest node diameter, applied within standardized protocols, and integrated with the broader clinical and pathological context.

Primary epithelial ovarian malignancies in adolescents are extremely rare (<1%). Mucinous cystadenocarcinoma (MCAC), especially bilateral disease, is exceptional and often mimics benign ovarian cysts, delaying the diagnosis.

We report a 16-year-old girl with hypothyroidism who presented with abdominal distension, pain, and 20-kg weight gain. Imaging showed bilateral ovarian masses with omental nodularity despite normal tumor markers. Surgery confirmed FIGO IIIC bilateral MCAC, and she completed six cycles of paclitaxel-carboplatin.

At three‑ year follow‑ up, the patient continues to be disease‑ free. This case highlights the limitations of tumor markers in adolescent ovarian malignancy, emphasizes the importance of cross‑ sectional imaging and clinical correlation, and demonstrates the challenges of management including considerations of future fertility.