• [Offloading and immobilization therapy for diabetic foot: Germany experience from theory to clinical practice].
    2 weeks ago
    Diabetic foot is a common condition that imposes a substantial burden on patients and society. Although prolonged activity restriction in traditional management may facilitate ulcer healing, it is detrimental to overall health. Therefore, a balance must be achieved between promoting wound healing and preserving mobility. Offloading and immobilization constitute the core principles of diabetic foot management. Offloading reduces wound stress by redistributing plantar pressure, whereas immobilization promotes local healing by limiting joint motion. To effectively balance these two therapeutic principles, the medical team led by German physicians Dirk Hochlenert and Gerald Engels has accumulated extensive clinical experience through years of clinical practice combining FiF!mobil® felt padding with non-removable offloading orthoses. This article elaborates on the core concepts of pressure offloading and immobilization with targeted clinical examples. The introduced protective devices are structural components designed to redistribute abnormal plantar pressure points without inducing secondary tissue damage, enabling standardized clinical implementation. Given the limited nationwide adoption of this technique in China, our research team co-authored this paper with the aforementioned German specialists to introduce this integrated therapeutic regimen, provide standardized training protocols and practical tools for clinicians, and facilitate continuous improvement in the prevention and management of diabetic foot disease.
    Diabetes
    Cardiovascular diseases
    Care/Management
  • Effects of GLP1-RAs and SGLT2i on liver steatosis and fibrosis in MASLD with type 2 diabetes.
    2 weeks ago
    Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in individuals with type 2 diabetes mellitus (T2DM). MASLD ranges from simple liver steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. New glucose-lowering agents have demonstrated benefits beyond glycemic regulation. This study assesses the effects of receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) on metabolic parameters, hepatic steatosis, and fibrosis in patients with MASLD and T2DM.

    Prospectively, 192 patients were enrolled: 132 added therapy with one novel glucose-lowering drug (GLP-1RA or SGLT2i) or their combination, and 60 patients continued with other glucose-lowering therapies (such as sulfonylureas, PPAR-γ agonists, DPP-4 inhibitors, metformin or insulin). Metabolic parameters, fibrosis indices (APRI, FIB-4, NFS, stiffness), and steatosis assessed by ultrasound-based attenuation imaging (ATT), were evaluated at baseline, 6 and 12 months.

    The four treatment groups had comparable biochemical profiles. At 6 months, significant reductions were observed in the ALT, AST, GGT, and ALP levels (P<0.01). Both GLP-1RA and SGLT2i significantly improve glycemic control at 6 and 12 months; the reduction in HbA1c was associated with a decrease in serum cholesterol (statistically significant in the SGLT2i group). Non-invasive fibrosis scores (FIB-4, APRI, NFS) showed no significant changes; however, NFS showed modest improvement in the SGLT2i group. Liver stiffness values decreased significantly after 12 months in GLP-1RA, SGLT2i, or combination therapy groups. ATT consistently improved hepatic steatosis.

    GLP-1RA and SGLT2i improve glycemic control and reduce hepatic steatosis and stiffness in patients with MASLD and T2DM.
    Diabetes
    Diabetes type 2
    Policy
  • The Microbiota as a Potential Cause of Disease.
    2 weeks ago
    Background: The human microbiota plays a crucial role in maintaining physiological homeostasis and influencing the development of chronic diseases not only in the gut but in the whole body. Material and Methods: This literature review is based on a comprehensive search of the PubMed database covering the period from 2008 to 2026. Approximately 65 key studies were included in the final analysis. Only articles published in English were included. The search included keywords such as microbiota, inflammaging, eubiosis, diet, gut diseases, cardiovascular diseases, diabetes, and osteoporosis. This narrative review explores the composition, development, and functional significance of the gut microbiota across the human lifespan, highlighting its dynamic interaction with environmental factors. Early-life microbial colonization, shaped by factors including delivery mode and breastfeeding, has long-term implications for immune system maturation and disease susceptibility. Results: A balanced gut microbiota (eubiosis) supports host health through metabolic activities, mainly by the production of short-chain fatty acids (SCFAs), which regulate intestinal barrier integrity, immune responses, and systemic inflammation. Contrarily, dysbiosis-characterized by reduced microbial diversity and an overrepresentation of pro-inflammatory species-is associated with chronic low-grade inflammation (inflammaging) and contributes to the pathogenesis of multiple diseases. Age-related changes in microbial composition are shown to activate inflammatory processes and impair immune regulation, thereby increasing disease risk. Therefore, it is important to recognize the role of microbiota alterations in key pathological conditions, including neurodegenerative diseases, cardiovascular diseases, type 2 diabetes mellitus, and osteoporosis. Conclusions: Finally, the potential of microbiome-targeted interventions, such as probiotics, prebiotics, and dietary modulation-in particular the Mediterranean diet is recognized as the most balanced-is discussed as a promising strategy to restore microbial balance and mitigate inflammaging. Further research is needed to better understand the association between microbiota and host health and to optimize therapeutic approaches for aging populations.
    Diabetes
    Cardiovascular diseases
    Diabetes type 2
    Policy
  • Changes in Expression of Syndecans and Heparan Sulfate Biosynthesis Enzymes in Short-Term Streptozotocin-Induced Diabetic Rat Kidneys.
    2 weeks ago
    The aim of this study was to determine the temporal expression patterns of syndecan family members (SDC1, SDC2, SDC4) and heparan sulfate biosynthesis enzymes (NDST1, NDST2) in kidneys of diabetic rats and age-matched controls.

    Male Sprague-Dawley rats received intraperitoneal streptozotocin (55 mg/kg; DM1 group) or citrate buffer (control group). Kidney samples were harvested after 2 weeks and 2 months and processed for immunofluorescence.

    SDC1 showed significant temporal upregulation in controls that was abolished in diabetic animals. SDC2 exhibited high early expression in the control group with significant decline as the kidneys matured but remained elevated in diabetic kidneys at 2 months compared to controls. SDC4 showed no significant difference between groups, though an age-related decrease was observed in controls. NDST1 was significantly upregulated in diabetic rats at 2 weeks, followed by profound suppression at 2 months (p < 0.0001). NDST2 showed modest but significant early elevation in diabetic animals. Transcript-level analysis of two independent public datasets of streptozotocin-induced diabetic rat renal cortex reproduced the principal directional findings-an early increase in SDC1 and a progressive elevation of SDC2-while indicating post-transcriptional regulation of SDC4 and the early NDST response.

    Diabetes disrupts normal temporal expression of syndecans and heparan sulfate biosynthesis enzymes in rat kidneys. Early compensatory upregulation of NDST1 and NDST2, followed by progressive NDST1 suppression, suggests a deteriorating heparan sulfate biosynthetic capacity, potentially contributing to the progression of diabetic nephropathy.
    Diabetes
    Policy
  • Surveillance vs Standard Surgery and Cost-Effectiveness After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: Secondary Analysis of a Randomized Clinical Trial.
    2 weeks ago
    Active surveillance is noninferior to standard surgery for 2-year survival and improves short-term health-related quality of life among patients with a complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Although active surveillance reduces the upfront costs of surgery and hospital stay, it requires repeated diagnostic tests and, for some patients, delayed surgery and hospitalization during follow-up.

    To assess the cost-effectiveness of active surveillance compared with standard surgery after nCRT.

    This prespecified cost-effectiveness analysis from a health care perspective conducted at 12 hospitals in the Netherlands as a secondary analysis of the Surgery as Needed for Oesophageal Cancer (SANO) trial, a noninferiority, cluster randomized study, enrolled patients with esophageal cancer who achieved a CCR after nCRT between November 8, 2017, and January 17, 2021, with follow-up for up to 5 years. Data were analyzed on June 1, 2025.

    Active surveillance, consisting of repeated response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after nCRT, compared with standard surgery.

    Incremental cost-effectiveness of active surveillance vs standard surgery and quality-adjusted life-years (QALYs) with 95% CIs up to 5 years were derived with bootstrapping, with 80% of patients (247 of 309) having complete follow-up. Incremental net monetary benefit (iNMB) was calculated at varying willingness-to-pay thresholds. All analyses followed the modified intention-to-treat principle. Costs are given in Euros (currency exchange rate of €1 = US $1.16 as of June 11, 2026).

    Among 309 patients (198 in the active surveillance group; median age, 69 years [IQR, 63-74 years]; 156 men [79%]; and 111 in the standard surgery group; median age, 68 years [IQR, 61-73 years]; 86 men [77%]), those in the active surveillance group had a mean of 2.99 QALYs (95% CI, 2.73-3.26) at 5 years vs 2.88 QALYs (95% CI 2.69-3.06) in the standard surgery group. Mean health care costs per patient at 5 years were €36 733 (95% CI, €33 530-€40 009) in the active surveillance group vs €45 106 (95% CI, €39 449-€51 545) in the standard surgery group. The incremental QALY for active surveillance was 0.11 (95% CI, -0.10 to 0.33) and mean costs were €8374 lower (95% CI, €1792-€15 355) compared with standard surgery. At a willingness-to-pay threshold of €80 000 per QALY, the mean iNMB was €17 568 (95% CI, -€725 to €37 497), indicating that active surveillance is cost-effective. Bootstrap analysis showed that 97% of replications fell in the cost-effective region.

    In this secondary analysis of a randomized clinical trial of patients with esophageal cancer achieving a CCR after nCRT, active surveillance was cost-effective over a 5-year horizon compared with standard surgery. Broader implementation of this strategy among appropriately selected patients would most likely reduce health care costs without compromising health outcomes.

    The Dutch Trial Register: NTR 6803.
    Cancer
    Access
    Care/Management
    Advocacy
  • Intraarterial Dexamethasone for Pain Relief After Uterine Fibroid Embolization: A Randomized Clinical Trial.
    2 weeks ago
    Acute postprocedural pain remains a major barrier to uterine fibroid embolization (UFE).

    To assess whether intraarterial dexamethasone reduces postprocedural pain after UFE.

    This double-blind, placebo-controlled randomized clinical trial was conducted from July 2020 to December 2023, with follow-up through 3 months, at a single tertiary academic medical center. Participants were women, aged 20 to 50 years, undergoing UFE.

    Intraarterial dexamethasone (10 mg) or saline placebo administered during embolization.

    The primary outcome was postprocedural pain through 168 hours. Secondary outcomes included postembolization syndrome symptoms; fibroid-related symptoms and health-related quality of life, assessed using the UFE-Quality of Life questionnaire at baseline and at 1 and 3 months; and percentage reduction in uterine volumes on magnetic resonance imaging.

    Among 42 women randomized (mean [SD] age, 44.7 [4.7] years; 21 per group), 40 women were included in the final analysis (20 randomized to the dexamethasone group and 20 to the placebo group) after excluding 2 participants. In the dexamethasone group, 7 participants (35%) were African American, 6 (30%) were Hispanic, and 7 (35%) were White; in the placebo group, 9 (45%) were African American, 8 (40%) were Hispanic, and 3 (15%) were White. Intraarterial dexamethasone was associated with significantly lower mean (SD) pain scores immediately after the procedure (4.0 [3.3] vs 6.1 [3.1]; mean difference, -2.1 [95% CI, -4.14 to -0.06]; P = .04) and through 96 hours (2.4 [2.4] vs 4.5 [3.2]; mean difference, -2.1 [95% CI, -3.90 to -0.30]; P = .02) compared with placebo. The mean (SE) pain score over 168 hours was significantly lower in the dexamethasone group vs placebo (2.63 [2.28] vs 4.28 [2.27] visual analog scale units; mean difference, -1.64 [95% CI, -3.10 to -0.19]; P = .02). Among participants with paired magnetic resonance imaging follow-up, the mean (SD) uterine volume reduction from baseline to 3 months was 37.4% (17.7%) in the dexamethasone group vs 29.6% (20.2%) in the placebo group (P = .30), and the mean (SD) dominant fibroid volume reduction was 34.4% (22.8%) vs 38.6% (16.7%) (P = .60). No major complications occurred in either group.

    In this randomized clinical trial of 40 women undergoing UFE, intraarterial dexamethasone was associated with clinically meaningful reductions in postprocedural pain through 96 hours compared with placebo, without compromising treatment efficacy or increasing adverse events, which may offer a simple, low-cost strategy to reduce analgesic burden in individuals undergoing UFE.

    ClinicalTrials.gov Identifier: NCT04655144.
    Cancer
    Access
    Care/Management
    Advocacy
  • Development and validation of an automated evaluation system for lattice radiotherapy using a commercial treatment planning system scripting API.
    2 weeks ago
    Clinical implementation of lattice radiotherapy (LRT) remains constrained by the absence of standardized, automated tools for comprehensive post-plan dosimetric analysis within commercial treatment planning systems (TPS). Herein, an automated script-based tool was developed using the Eclipse Scripting API (ESAPI) to enable rapid, standardized calculation of key LRT-specific metrics, including peak-to-valley dose ratio (PVDR), equivalent uniform dose (EUD), and ablative dose ratio (ADR).

    A modular computational architecture comprising four functional layers was implemented: (1) user interface for protocol configuration, (2) computation layer integrating multiple PVDR algorithms, (3) data service layer providing direct read-only access to three-dimensional dose and anatomical data via ESAPI, and (4) reporting module. To accommodate ESAPI security restrictions, a dual-script architecture incorporating a preprocessing sphere segmentation module was established. Validation was performed using a retrospective cohort of 12 lung cancer LRT patients, with accuracy assessed against manual TPS measurements and established reference values.

    Concordance between automated and manual TPS measurements was high. Standard dose-volume parameter extraction exhibited perfect agreement. For spatially explicit PVDR analysis, mean absolute error relative to manual profile assessment was 0.034 (absolute VPDR units). EUD calculations deviated less than 3% from published reference data. Evaluation time per plan was reduced from 15.41 ± 3.20 min (manual) to 1.97 ± 0.34 min (automated), representing a 7.8-fold efficiency gain with elimination of inter-operator variability.

    This ESAPI-based tool automates and standardizes dosimetric evaluation of LRT, addressing a practical workflow bottleneck. Integration of multiple calculation methods within a deterministic framework establishes a shareable benchmark for consistent multi-institutional analysis, providing a foundation for future investigations correlating detailed dosimetric parameters with clinical outcomes in spatially fractionated radiotherapy.
    Cancer
    Chronic respiratory disease
    Access
    Care/Management
    Advocacy
  • CT radiomics for noninvasive prediction of histologic differentiation in gastric cancer.
    2 weeks ago
    The histological differentiation grade of gastric cancer critically influences treatment and prognosis. While CT radiomics shows promise for noninvasive prediction, its relationship with gene expression remains unclear.

    This study aimed to develop a clinical-radiomics model for predicting tumor differentiation in gastric cancer patients and to explore the underlying mechanisms.

    We retrospectively analyzed clinical data and CT images from 162 gastric cancer patients, who were randomly assigned to training and validation cohorts. The least absolute shrinkage and selection operator (LASSO) method was used to select features and construct the Rad-score. Subsequently, clinical-radiomics models were built and evaluated for their predictive efficacy and clinical incremental value. Furthermore, hub genes were screened, and their associated pathways were investigated using machine learning, bioinformatics analysis, and experimental validation.

    A clinical-radiomics model based on N stage, M stage and Rad-score was developed. The receiver operating characteristic (ROC) curves indicated that the model had preliminary evidence of predictive potential within this single-center cohort (training AUC = 0.872, validation AUC = 0.935). The calibration curves indicated a reasonable concordance between the observed values and the predicted outcomes in this retrospective sample. The decision curve analysis demonstrated a net benefit that requires further confirmation in external cohorts. The clinical impact curve (CIC) demonstrated the model's potential clinical applicability, which warrants validation in prospective settings. Sequencing data further revealed that the key gene IGHG1 was significantly associated with the Rad-score, with potential mechanisms involving the TGF-beta signaling pathway.

    The clinical-radiomics model, incorporating N stage, M stage, and Rad-score, serves as a preliminary research tool for assessing tumor differentiation in gastric cancer patients within a single-center setting. External validation is required before any consideration of clinical generalization. Radiomics enables noninvasive evaluation of differentiation status while generating hypotheses regarding its underlying mechanisms.
    Cancer
    Access
    Care/Management
    Advocacy
  • Effect of Ultra Processed Foods on Cancer Risk and Strategies for Risk Mitigation.
    2 weeks ago
    This review examines the relationship between ultra-processed foods (UPFs) and cancer risk, covering UPF classification systems, epidemiological evidence, food additive regulatory frameworks, biological mechanisms of carcinogenesis, and dietary strategies to reduce risk.

    A randomized crossover study linked UPF consumption to higher caloric intake and weight gain, implicating metabolic dysfunction in cancer pathogenesis. A 2023 meta-analysis found a 13% increase in overall cancer risk per 10% increment UPF consumption, supporting landmark NutriNet-Santé cohort findings. Recent analysis identified substantial microplastic contamination in protein-based UPFs. UPFs may augment cancer risk through excess caloric intake, obesity, metabolic dysregulation, insulin resistance, chronic inflammation, and exposure to potentially harmful additives and microplastics. Large cohort studies confirm elevated overall cancer risk, with colorectal cancer showing the strongest site-specific association. UPF consumption may displace minimally processed foods, which demonstrate potentially protective effects. Further research and regulatory action are needed to clarify the cumulative effects of multiple food additives.
    Cancer
    Access
    Advocacy
  • Effects of Malnutrition on In-Hospital and Discharge Outcomes Among Young Adults Hospitalized with Gastrointestinal Cancers: National Estimates from the United States.
    2 weeks ago
    Protein-energy malnutrition (PEM) is common in gastrointestinal (GI) cancers and may worsen inpatient outcomes. Contemporary national data describing the impact of PEM among young adults with GI malignancies are limited.

    We conducted a retrospective cohort study using HCUP NIS data from 2018 to 2021. We identified hospitalizations of adults aged 18 to 39 years with GI cancers using ICD 10 CM codes C15 to C26. We defined PEM using ICD-10-CM diagnosis codes recorded during the index hospitalization; therefore, PEM reflects clinically documented/coded malnutrition rather than the full burden of nutritional risk or clinically undiagnosed malnutrition. Primary outcomes were in hospital mortality and discharge disposition. Secondary outcomes were LOS and total hospital charges. We used survey weighted multivariable logistic and linear regression to estimate adjusted associations, accounting for age, sex, race or ethnicity, payer, income quartile, admission type, calendar year, and age adjusted CCI.

    Among 58,910 weighted hospitalizations of young adults with gastrointestinal cancers, 11,915 (20.2%) had protein-energy malnutrition (PEM). Compared with those without PEM, hospitalizations with PEM had a higher burden of advanced disease and acute illness, including a greater prevalence of metastatic disease (71.8% vs. 53.1%), and experienced worse unadjusted outcomes, including higher in-hospital mortality (8.4% vs. 3.2%), longer length of stay (10.43 vs. 5.63 days), and higher total hospital charges ($133,790 vs. $83,702). In adjusted analyses, PEM was independently associated with increased odds of in-hospital mortality (aOR 2.13, 95% CI 1.72-2.56; p < 0.001) and higher odds of non-home discharge (aOR 1.67, 95% CI 1.47-1.89; p < 0.001). PEM was also associated with substantially greater resource utilization, including an adjusted increase of 4.49 hospital days (β + 4.492; SE 0.248; p < 0.001) and $53,513 higher total hospital charges (β +$53,512.6; SE $5,527.6; p < 0.001).

    PEM affected one in five hospitalizations among young adults with GI cancers and was independently associated with increased mortality, non-home discharge, LOS, and hospital charges. These findings support routine inpatient nutritional assessment and early intervention in this high risk population.
    Cancer
    Access
    Care/Management
    Advocacy