Nevin Manimala

Rheumatology (Oxford). 2026 Jul 29:keag391. doi: 10.1093/rheumatology/keag391. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine disease-specific associations of serum vascular cell adhesion molecule-1 (VCAM-1) and associated mortality in systemic sclerosis (SSc).

METHODS: Participants were identified from the Australian Scleroderma Cohort Study. Data were linked with the National Death Index for cause-specific mortality. VCAM-1 was measured using a magnetic Luminex assay. Participant characteristics and information on organ specific manifestations were extracted until February 2024. Participants were stratified into VCAM-1 quartiles.

RESULTS: Of 388 participants, 87.1% were female and 76.8% had limited cutaneous disease. Median age at diagnosis was 45.7 years (IQR 36.4-56.7).Participants with upper quartile VCAM-1 (Q4) had increased mortality compared to others (HR 2.17, 1.54-3.04; p < 0.001). Despite the significant increased mortality in Q4, there were no statistically significant differences in sex, age, disease duration, disease subtype, autoantibody profile or forced vital capacity across the VCAM-1 quartiles.Q4 were more likely to have pulmonary arterial hypertension (PAH; p = 0.028), SSc-attributable myocardial disease (p = 0.009) and digital ulcers (p = 0.003). In cause-specific mortality analysis, Q4 were more likely to have PAH (HR 3.08;1.68-5.65, p < 0.001), SSc-attributable myocardial disease (HR 2.85;1.51-5.38, p = 0.001) and all-cause cardiovascular disease (HR 2.50;1.60-3.89, p < 0.001) listed as a cause or contributor to death. Q4 VCAM-1 level was not associated with interstitial lung disease presence, severity or cause-specific mortality.

CONCLUSION: The increased mortality in participants with SSc and Q4 VCAM-1 levels is attributable to increased frequency of vascular disease manifestations. Q4 participants do not have a disproportionate frequency of other established risk factors for increased mortality, suggesting an independent role for VCAM-1 in disease pathophysiology.

PMID:42525382 | DOI:10.1093/rheumatology/keag391

Ophthalmic Physiol Opt. 2026 Jul 29. doi: 10.1007/s44402-026-00151-y. Online ahead of print.

ABSTRACT

BACKGROUND: Myopia is an ocular condition that commonly develops in childhood and causes blurred distance vision. It poses a lifetime risk of serious ocular complications that can result in irreversible visual impairment. Early detection and implementation of treatment to slow myopia progression are key to managing the increase in prevalence. This study aims to assess the awareness and understanding related to myopia within the Australian community.

METHODS: A cross-sectional nationwide survey was conducted between September and October 2024. The survey was designed using questions drawn from previous myopia awareness studies and tailored for the Australian context. It was administered online and participants were Australian residents, ≥18 years of age. Descriptive statistics and chi-square test of independence were used to evaluate associations between variables of interest.

RESULTS: A total of 1565 responses were analysed, with responses from 68 participants excluded due to their involvement in the eyecare industry. Seventy-nine percent of participants had heard of the term myopia; however, there were aspects relating to risk factors, complications and treatment options that were poorly understood. Only 15% of participants were aware of the existence of treatments to slow myopia progression.

CONCLUSION: While many participants were aware of myopia, significant gaps existed in understanding its symptoms, risk factors and management. Public health initiatives are needed to improve community knowledge and promote early detection, prevention and treatment to reduce the long-term risk of visual impairment for myopic children.

PMID:42525379 | DOI:10.1007/s44402-026-00151-y

Ther Innov Regul Sci. 2026 Jul 29. doi: 10.1007/s43441-026-01026-7. Online ahead of print.

ABSTRACT

BACKGROUND: For slowly progressive ultra-rare diseases, hard clinical endpoints such as mortality or sustained functional decline are often impractical within feasible trial timeframes. Surrogate biomarkers, including fluid and imaging analytes, offer a pathway to accelerate drug development. Achieving cross-jurisdictional regulatory acceptance for these surrogates remains a profound scientific and policy challenge.

METHODS: We conducted a narrative synthesis incorporating regulatory guidance documents from the FDA, EMA, and NMPA, alongside PubMed-indexed literature on surrogate endpoint validation, orphan drug approval, and biomarker qualification programs published up to early 2026.

RESULTS: The FDA’s Accelerated Approval pathway and the EMA’s Conditional Marketing Authorization represent the primary regulatory vehicles for surrogate-based approvals. A four-tier validation model is proposed, incorporating mechanistic plausibility, epidemiological association, quantitative surrogacy statistics, and confirmatory post-approval requirements. Case studies from neurology (spinal muscular atrophy) and metabolic disorders (lysosomal storage diseases) illustrate the context-of-use dependency of these surrogates. Cross-jurisdictional divergence in evidentiary standards and the absence of a dedicated ICH guideline for rare disease surrogate endpoints constitute major structural gaps.

CONCLUSIONS: A globally harmonized evidentiary framework for surrogate endpoint qualification in ultra-rare diseases is urgently needed. Validating this framework in the ultra-rare space could serve as a stepping stone for broader rare disease drug development. Bayesian adaptive designs, international consortium registries, and real-world evidence frameworks are key enabling strategies for addressing the inherent sample-size constraints of this research.

PMID:42525369 | DOI:10.1007/s43441-026-01026-7

Target Oncol. 2026 Jul 29. doi: 10.1007/s11523-026-01238-9. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous case series have corroborated the efficacy of the first-line approach of platinum-based chemotherapy and avelumab maintenance followed by enfortumab vedotin monotherapy (PBC-AM-EV) in real-world patients with advanced urothelial carcinoma.

OBJECTIVE: The present investigation aimed to characterize the baseline clinical and pathological characteristics and outcomes of the PBC-AM-EV treatment sequence in the advanced urothelial carcinoma population.

METHODS: ARON-2^EV is a global retrospective study investigating the real-world use of EV in patients with advanced urothelial carcinoma. Two hundred and three patients receiving PBC-AM-EV were analyzed. Primary endpoints were disease response, therapy sequence duration, and overall survival. Secondary objectives included the evaluation of clinical factors associated with outcomes. Patient characteristics were analyzed using descriptive statistics; overall survival and therapy sequence duration were estimated using the Kaplan-Meier method and assessed with log-rank tests and Cox proportional hazards models.

RESULTS: Following a median follow-up of 23.1 months, the median overall survival from PBC initiation was 31.6 months, with a 2-year overall survival rate of 68%. Survival outcomes were consistent across most clinicopathologic subgroups, but were significantly influenced by Eastern Cooperative Oncology Group performance status, prior response to PBC, and cisplatin-based regimens. Median therapy sequence duration was 26.5 months and was prolonged in patients with exclusive nodal metastases and cisplatin exposure. A 43% objective response rate was achieved by EV, including durable disease control, particularly among patients who benefited from prior PBC and avelumab maintenance.

CONCLUSIONS: The PBC-AM-EV sequence demonstrates sustained real-world efficacy, with outcomes driven by baseline characteristics, platinum responsiveness, and preserved EV activity irrespective of prior immunotherapy response.

PMID:42525332 | DOI:10.1007/s11523-026-01238-9

Phys Eng Sci Med. 2026 Jul 29. doi: 10.1007/s13246-026-01768-6. Online ahead of print.

ABSTRACT

This study evaluated the feasibility of generative adversarial network (GAN)-based postprocessing super-resolution for T2-weighted lumbar spine magnetic resonance imaging (MRI) using both objective resolution metrics and perceptual assessment. Sagittal lumbar spine MRI datasets from healthy volunteers were analyzed. An enhanced super-resolution GAN (ESRGAN) was trained on downsampled images, while zero-filling, bicubic, and bilinear interpolation, as well as enhanced deep residual networks for single image super-resolution (EDSR), were used as comparators. Image quality was assessed by comparing upscaled images from 256 × 256 acquisitions with corresponding 512 × 512 reference images, using full width at half maximum (FWHM) and normalized integrated power spectrum (NIPS), along with similarity metrics including structural similarity index, peak signal-to-noise ratio, and root mean square error. Subjective image quality was evaluated using a ranking method. An additional analysis using 320 × 320 and 640 × 640 image pairs was conducted to assess consistency across resolution settings. Statistical comparisons were performed using the Friedman test with Bonferroni correction. ESRGAN showed no significant differences from the original high-resolution images in FWHM and NIPS, whereas interpolation methods and EDSR demonstrated inferior performance (P < 0.05). Although interpolation methods achieved higher scores in pixel-wise metrics, ESRGAN obtained the highest subjective ratings and interrater agreement. These findings indicate that ESRGAN better restores high-frequency structural information not captured by conventional similarity metrics. GAN-based postprocessing super-resolution may improve image quality in lumbar spine MRI and warrants further investigation of its clinical impact.

PMID:42525326 | DOI:10.1007/s13246-026-01768-6

Gastric Cancer. 2026 Jul 29. doi: 10.1007/s10120-026-01783-2. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical complications after gastrectomy significantly impact recovery and long-term prognosis. While iron status influences outcomes, the conventional 20% transferrin saturation (TSAT) threshold ignores sex-specific physiological differences. We developed a modified TSAT (mTSAT) based on sex and anemia status and evaluated its value in predicting complications.

METHODS: We retrospectively analyzed 243 patients who underwent curative gastrectomy. Optimal TSAT cut-off values for predicting complications classified as Clavien-Dindo grade II or higher were determined using receiver operating characteristic curves stratified by sex and anemia status. Predictive performance was compared between mTSAT and the conventional 20% threshold using the corrected Akaike Information Criterion.

RESULTS: The optimal mTSAT cut-offs were 22.2% for men and 14.2% for women. The mTSAT model demonstrated an improved fit compared with the conventional threshold. The low mTSAT group (mTSAT below the sex-specific cut-off) comprised 78 patients and exhibited a significantly higher incidence of complications than the normal mTSAT group, particularly anastomotic leakage and delayed gastric emptying/ileus. Moreover, postoperative hospital stay was significantly longer in this group. In the primary multivariable analysis, low mTSAT was significantly associated with postoperative complications, whereas the conventional 20% threshold was not. After additional adjustment for clinical stage and surgical approach, the association was attenuated and no longer reached statistical significance.

CONCLUSIONS: Preoperative low mTSAT was associated with an increased risk of postoperative complications. Rather than a standalone predictor, mTSAT functions as a valuable composite clinical indicator reflecting stage-related systemic vulnerability, surgical invasiveness, and underlying malnutrition or iron deficiency.

PMID:42525320 | DOI:10.1007/s10120-026-01783-2

World J Microbiol Biotechnol. 2026 Jul 29;42(8):436. doi: 10.1007/s11274-026-05165-9.

ABSTRACT

Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), threatens global rice production while growing bactericide resistance and environmental concerns necessitate sustainable disease management alternatives. We employed a microbiome-guided, habitat-specific isolation strategy targeting naturally recovered plants from BLB-endemic hotspots across ten districts of Punjab, Pakistan operating on the ecological premise that plants under pathogen pressure selectively enrich protective microbial taxa, making disease-affected hosts the most coherent source of adapted biocontrol agents. Screening of 1,036 bacterial isolates from rice rhizosphere and phyllosphere using dual-culture antagonism assays yielded six elite strains: Bacillus velezensis, B. amyloliquefaciens, B. subtilis, Pseudomonas fluorescens, and two P. aeruginosa isolates, confirmed by 16 S rRNA and rpoD gene sequencing (> 99% sequence identity). Biochemical profiling revealed multifunctional plant growth-promoting traits including siderophore production, biological nitrogen fixation, indole-3-acetic acid biosynthesis, phosphate solubilization, and hydrogen cyanide production, indicating the potential capacity of selected strains for integrated disease suppression and plant growth promotion. Greenhouse trials across six rice varieties with contrasting genetic resistance backgrounds demonstrated significant reductions in BLB incidence (25-67%) and severity (31-55%) relative to uninoculated controls. Field validation under natural pathogen pressure across two consecutive growing seasons confirmed robust performance, with incidence suppression of 33-65% and severity reduction of 46-67% compared to controls. B. velezensis fsdls3 emerged as the most effective individual agent, achieving 114.5% mean yield protection relative to diseased controls and approaching streptomycin sulfate performance with no statistically significant overall yield difference while outperforming the chemical standard on specific variety-strain combinations. Five of six PGPR agents exceeded the 100% yield protection threshold, delivering agronomic co-benefits including enhanced tillering, increased productive panicles, and elevated total biomass unavailable from chemical bactericide treatment alone. Pronounced cultivar × treatment interactions confirmed that PGPR efficacy is modulated by host genetic background, with resistant varieties carrying pyramided Xa resistance genes showing additive responses to biological treatment. These results establish habitat-adapted, host-recruited PGPR as scientifically credible and ecologically coherent alternatives to chemical bactericides for integrated BLB management in rice.

PMID:42525313 | DOI:10.1007/s11274-026-05165-9

J Neurovirol. 2026 Jul 29;32(4):32. doi: 10.1007/s13365-026-01329-3.

ABSTRACT

To evaluate whether varying degrees of lymphocyte count decline in HIV-positive adults are associated with increased short-term incidence of epilepsy or convulsions. A retrospective cohort study was conducted using the TriNetX global research network. HIV-positive patients with a lymphocyte count ≥ 1.2 × 10³/µL were categorized based on subsequent decline within 3 months: mild (1.01-1.19), moderate (0.81-1.0), or significant (0.61-0.8). Risk analysis and Kaplan-Meier survival analysis were performed and patients with prior diagnosis of epilepsy (G40) or convulsions (R56.9) were excluded. The risk of developing epilepsy or convulsions increased with greater lymphocyte decline. Compared to patients with stable counts, the odds ratios were 1.073 for the mild group, 2.222 for the moderate group, and 3.189 for the significant drop group. Hazard ratios followed a similar trend, reaching 3.24 in the 0.61-0.8 group. Only the mild drop group did not show a statistically significant difference in risk or survival curves. Kaplan-Meier analysis at 1 year showed significant separation between survival curves for all groups except the mild group (p = 0.6973). Among HIV-positive adults, greater short-term lymphocyte count decline is associated with a higher short-term risk of epilepsy or convulsions. These findings suggest that lymphocyte trends may serve as an early signal for neurologic vulnerability. Further investigation is warranted to clarify the underlying mechanisms and clinical implications.

PMID:42525309 | DOI:10.1007/s13365-026-01329-3

Support Care Cancer. 2026 Jul 29;34(8):812. doi: 10.1007/s00520-026-10998-z.

ABSTRACT

BACKGROUND: Patient navigation programs (PNPs) have been increasingly applied in breast cancer (BC) care of underserved clients, as they can significantly assist them with coordinating services across the care continuum. However, existing evidence has produced inconclusive findings regarding the empirical adequacy of BC-related caring interventions developed from PNPs. Hence, the aim of the present systematic review and meta-analysis was to clarify the benefits of PNPs across all phases of the BC care continuum. Primary outcomes comprised care-continuum indicators extracted predominantly from medical records, while secondary outcomes included client-reported healthcare measures.

METHODS: Five electronic data sources were searched for randomized controlled trials (RCTs) that investigated the effectiveness of PNPs across the BC care continuum from 1995 to January 10, 2025, with no restrictions on clients’ sociodemographic characteristics. A random-effects model, using both the DerSimonian-Laird (DL) method and the Hartung-Knapp (HK) adjustment, was applied to estimate standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, with 95% confidence intervals (CIs).

RESULTS: Thirty-seven RCTs met the inclusion criteria, including four cluster RCTs and 33 individual RCTs. Quantitative synthesis was not feasible for time-to-resolution, adherence to adjuvant or post-treatment follow-up care, timely treatment initiation, treatment completion, satisfaction with care, or psychological distress; therefore, the effectiveness of PNPs for these outcomes remains uncertain. Meta-analyses of individual RCTs, all conducted using a DL random-effects model, indicated that PNPs significantly improved diagnostic follow-up compliance (OR, 2.42; 95% CI, 1.64, 3.59; P < 0.001); screening mammogram adherence (OR, 2.18; 95% CI, 1.71, 2.77; P < 0.001); and timely diagnostic resolution (OR, 2.51; 95% CI, 1.21, 5.24; P = 0.014). Using the same DL model, PNPs also improved quality of life (SMD, 0.44; 95% CI, 0.09, 0.79; P = 0.014) and reduced anxiety (SMD, -0.94; 95% CI, -1.66, -0.22; P = 0.010). However, no statistically significant effects were observed under the DL model for depression (SMD, -0.34; 95% CI, -0.71, 0.04; P = 0.076) or BC knowledge (SMD, 0.27; 95% CI, -0.19, 0.73; P = 0.247). Substantial heterogeneity was observed across most pooled outcomes (I² = 63.9%-93.0%), accompanied by wide prediction intervals that included the null value. After applying the HK adjustment, the previously observed beneficial effects of PNPs on timely diagnostic resolution, quality of life, and anxiety were no longer statistically significant.

CONCLUSION: Although initial analyses suggested that PNPs may improve several BC-related outcomes, these observed benefits were reduced in magnitude and, in some cases, no longer statistically significant after applying more conservative adjustment methods. Moreover, substantial heterogeneity across studies and the overall low methodological quality limit the certainty of the evidence. Therefore, the current findings should be interpreted cautiously, and further high-quality RCTs are needed to draw more definitive conclusions about the effectiveness of PNPs across the BC care continuum.

PROSPERO REGISTRATION: CRD42023487495.

PMID:42525303 | DOI:10.1007/s00520-026-10998-z

Hernia. 2026 Jul 29;30(1):304. doi: 10.1007/s10029-026-03798-1.

ABSTRACT

PURPOSE: Mesh suture is a suture device designed to distribute pressure at the suture-tissue interface to decrease suture pull-through. The primary aim of this study was to evaluate the feasibility and short-term clinical outcomes in isolated umbilical hernia repairs.

METHODS: A retrospective cohort of patients undergoing umbilical hernia repair using mesh suture was analyzed between January 2023-2025. Patients were identified through institutional implant logs. Outcomes evaluated included surgical site infection (SSI), surgical site events (SSE), hernia recurrence, readmissions, and reoperations.

RESULTS: Fifty-eight isolated umbilical hernia repairs with mesh suture were performed by twenty-four surgeons. The mean hernia width was 1.7 cm (± 0.7). The 90-day SSI rate was 5.2% (n = 3), consisting of two superficial infections and one organ space infection. The 90-day SSE rate was 5.2% (n = 1 fascial dehiscence, n = 2 hematomas). There were seven readmissions (12.1%) within 90 days, of which only one was related to the abdominal wall closure. There were three reoperations within 90 days (5.2%): two hematoma washouts and one fascial dehiscence repair. The mean length of follow up was 594 days (± 284). There were no cases of hernia recurrence.

CONCLUSIONS: Mesh suture provides the simplicity of suture repair with increased force distribution properties of mesh. In this initial multicenter experience, mesh suture demonstrated feasibility and acceptable short-term clinical outcomes for isolated umbilical hernia repair. Future randomized controlled trials comparing mesh suture versus planar mesh and standard suture are needed to compare techniques most effectively.

PMID:42525301 | DOI:10.1007/s10029-026-03798-1