Tag: nevin manimala

Biometrics. 2026 Apr 9;82(2):ujag098. doi: 10.1093/biomtc/ujag098.

ABSTRACT

Recent advancements in immuno-oncology have significantly improved cancer treatments. Compared with traditional clinical trials, the toxicity of these novel therapies is generally low and tolerable, shifting the focus from solely managing toxicity to improving efficacy. Furthermore, such treatments can be costly, and thus it is crucial to identify a low-dose regimen with a good therapeutic effect for broader drug accessibility. Instead of solely identifying the optimal biological dose (OBD) in a phase I/II trial, we emphasize finding a more economical but effective dose. Current methods typically aim to determine the minimum effective dose (MED) based on a predefined efficacy target, which may not reflect the best balance between efficacy and dosage. This paper introduces the minimum noninferiority dose (MND), derived from the OBD, which eliminates the need for artificially setting an efficacy target. The MND ensures the dose maintains efficacy within a reasonable range below the OBD while keeping the dosage as low as possible. Through leveraging the calibration-free odds (CFO) design to monitor toxicity, we further propose a novel Bayesian two-stage design, called CFO-MND, by incorporating a trade-off between dose and efficacy as well as adaptive randomization. Our model-free approach is versatile and applicable to a wide range of scenarios. Furthermore, we incorporate causal inference into the CFO-MND design by introducing the placebo equivalent dose. This allows for preliminary estimation of the drug’s average treatment effect at the MND, which provides valuable information for subsequent trials.

PMID:42240965 | DOI:10.1093/biomtc/ujag098

Sports Med. 2026 Jun 4. doi: 10.1007/s40279-026-02463-y. Online ahead of print.

ABSTRACT

BACKGROUND: Burnout syndrome in sports is receiving increasing attention in the empirical literature applying psychometric tools. Since 2019, the number of scientific publications has doubled. This growth has increasingly dissociated athletes from their status as workers and burnout is rarely conceived as a phenomenon emerging from a working relationship. This study aims to meta-analyze the empirical measurements of burnout using scales in athletes and occupations related to professional sports during 2014-2023.

RESULTS: The initial search detected 996 studies. After a screening guided by PRISMA principles, we meta-analyzed 113 independent studies comprising 133 burnout measurements from 35,059 athletes, coaches, and referees across 29 countries. The results show a generalized use of the Athlete Burnout Questionnaire (ABQ), a notable heterogeneity in the estimates, signs of publication biases in some specific subscales, higher mean scores in personal accomplishment than other burnout dimensions, a decreasing trend in global scores over time, a higher burnout prevalence in developed countries, and different mean scores according to the scale applied.

CONCLUSIONS: The results highlight the need to continue improving the existing psychometric tools and focus interventions on the perception of accomplishment to reduce burnout incidence.

PMID:42240930 | DOI:10.1007/s40279-026-02463-y

Jpn J Ophthalmol. 2026 Jun 4. doi: 10.1007/s10384-026-01378-5. Online ahead of print.

ABSTRACT

PURPOSE: To compare scleral, iris, and choroidal thickness in central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV) within the pachychoroid disease spectrum, relative to healthy controls.

STUDY DESIGN: Retrospective, case-control METHODS: Subfoveal choroidal thickness was evaluated using enhanced depth imaging (EDI) optical coherence tomography (OCT). Scleral thickness was measured 6 mm posterior to the scleral spur in four quadrants, while iris thickness was assessed at IT2000 (2000 µm from the scleral spur) in the nasal and temporal quadrants using anterior segment OCT (AS-OCT).

RESULTS: A total of 160 individuals participated, including 40 PCV patients, 40 CSC patients, and their respective control groups. Choroidal thickness was significantly greater in the PCV and CSC groups compared to controls (p =.001). Scleral thickness values were higher in both groups; in the CSC group, differences were significant in the superior (p =.007), nasal (p =.003), and temporal (p =.006) quadrants, whereas in the PCV group, although values were higher across all quadrants, these differences did not reach statistical significance (p =.020-.047). Iris thickness was significantly higher in the nasal and temporal quadrants (nasal: p<.001, p=.014, temporal: p=.015, p=.009). In the controls, choroidal and iris thickness decreased with age and were positively correlated, whereas these relationships were not observed in the case groups.

CONCLUSION: Choroidal, scleral, and iris thicknesses are increased in CSC and PCV patients compared to healthy controls. In the spectrum of pachychoroid disease, thick choroid is a known feature, however thick sclera and iris may also play an important role in the pathogenesis.

PMID:42240920 | DOI:10.1007/s10384-026-01378-5

J Orthop Traumatol. 2026 Jun 4. doi: 10.1186/s10195-026-00936-4. Online ahead of print.

ABSTRACT

BACKGROUND: Different alignment philosophies and balancing methods may alter femoral and tibial component rotation in distinct ways within the same knee. This study aimed to (1) determine which of three surgical techniques-measured resection (MR), gap balancing with computer-assisted surgery (GB-CAS), or a force-sensor soft-tissue balancing device (FS-STB)-most closely reproduces native femoral, tibial, and combined rotational alignment in mechanically aligned total knee arthroplasty (TKA), and (2) assess whether differences in rotational alignment affect outcomes at 5 years postoperatively.

MATERIAL AND METHODS: A total of 60 patients undergoing primary mechanical alignment TKA were randomly assigned to one of three surgical approaches (n = 20 per group): MR, GB-CAS, or FS-STB. Blinded observers assessed the Knee Society Score (KSS), Western Ontario MacMaster Universities Osteoarthritis Index (WOMAC) score, and hip-knee-ankle angle preoperatively and at the 5-year follow-up visit. Pre- and postoperative two-dimensional (2D)-computed tomography scans were used to measure femoral rotation (BFA), tibial rotation, and combined femur-tibia rotation (TE_PTCA and BC_PTCA). Statistical analyses included paired t-tests, one-way analysis of variance, and effect size calculations.

RESULTS: Femoral rotation remained unchanged in the MR and GB-CAS groups, but decreased slightly (1° external rotation) in the FS-STB group (P = 0.010). Tibial rotation increased significantly in internal rotation in the GB-CAS and FS-STB groups (P < 0.001), but not in the MR group (P = 0.061). The combined TE-PTCA rotation decreased slightly across all groups (P < 0.05), with no significant intergroup differences. Combined BCPTCA rotation increased only with GB-CAS (P = 0.006), but again without significant differences between the techniques. At 5 years, functional KSS and WOMAC scores improved in the FS-STB group compared with that in the MR group, although this difference was not statistically significant (P = 0.058 and P = 0.056, respectively).

CONCLUSIONS: Measured resection best preserved native knee rotation in mechanically aligned TKA. Although the individual component rotations varied by technique, the overall combined rotational alignment and functional outcomes did not differ significantly. Prosthesis design may govern the kinematics, and soft tissue adaptation may mitigate the impact of minor rotational differences in TKA procedures. More technologically assisted balancing methods may not provide meaningful functional advantages in terms of rotational alignment.

LEVEL OF EVIDENCE: Level I, therapeutic study. Trial registration Retrospectively registered on the UK’s Clinical Study Registry platform.

REGISTRATION NUMBER: ISRCTN66642689). Date of registration: 25/10/2025.

PMID:42240919 | DOI:10.1186/s10195-026-00936-4

Surg Today. 2026 Jun 4. doi: 10.1007/s00595-026-03351-8. Online ahead of print.

ABSTRACT

Chewing gum may stimulate gut motility through a “sham feeding” mechanism, but evidence in children is limited. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing chewing gum plus usual care versus usual care alone in patients younger than 18 years undergoing any surgery. We searched five databases through June 2025. Primary outcomes were the time to first flatus, time to first defecation, and postoperative length of stay (LOS). Certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Ten studies (n = 649) were included: abdominal surgery (5), spinal fusion (3), and tonsillectomy (2). Chewing gum may result in little to no difference in the time to first flatus (MD – 3.58 h, 95% CI – 8.08 to 0.91) or first defecation (MD – 3.23 h, 95% CI – 6.63 to 0.18), both with low certainty. LOS evidence was very uncertain (MD – 0.18 days, 95% CI – 0.70 to 0.33). Subgroup analyses suggested shorter LOS after abdominal surgery (MD – 0.60 days, 95% CI – 1.99 to 0.79) but not after spinal fusion (MD 0.10 days, 95% CI – 0.29 to 0.50; p for interaction = 0.0362). The benefits of postoperative chewing gum in children remain uncertain, with potential surgery-specific differences in LOS warranting investigation.

PMID:42240887 | DOI:10.1007/s00595-026-03351-8

Acta Neurochir (Wien). 2026 Jun 4. doi: 10.1007/s00701-026-06927-y. Online ahead of print.

ABSTRACT

PURPOSE: Picture naming is a widely used task for perioperative language assessment and brain mapping in awake surgery for brain tumors. Although there is a consensus on this task between centers performing this type of surgery, the tests used vary from one team to another. The MULTIMAP picture naming task, initially developed in 2021 by the Basque Center on Cognition, Brain and Language, aimed to enhance the perioperative assessment of lexical access of both nouns and verbs in awake surgery patients and to facilitate standardized protocols for international multicenter studies. This study presents the French adaptation, digitization, and standardization of extraoperative MULTIMAP.

METHODS: The tool was standardized on a sample of 416 healthy subjects recruited from the French population, whose performances (score and time) were statistically analyzed. Of the 100 items tested, we retained the 80 (40 objects, 40 actions) that showed the highest naming accuracy and were balanced between nouns and verbs for main psycholinguistic variables.

RESULTS: Gender had no effect on performance, the level of education had a significant effect for the action naming task only, and age for both tasks, allowing to determine percentiles according to these variables. Performances in object and action naming were correlated; however, a significant but minimal difference between the average score and time between tasks was found.

CONCLUSION: The digitized French version of MULTIMAP is a promising tool, that awaits further validation in patients with acquired brain lesions, especially in the context of brain tumor awake surgery.

PMID:42240870 | DOI:10.1007/s00701-026-06927-y

Discov Oncol. 2026 Jun 4. doi: 10.1007/s12672-026-05325-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Lung cancer is currently the leading cause of cancer-related death in men and the second most common cause in women worldwide. In the 9th edition of the TNM classification, N2 lymph node involvement has been divided into two subgroups: N2a and N2b. In this study, we aimed to examine the differences within the N2 group and to identify factors that may affect prognosis.

METHODS: Between 2002 and 2023, patients who underwent preoperative mediastinal staging (EBUS/Mediastinoscopy) and were found to have N2 involvement following lung resection for non-small cell lung cancer across 7 different clinics were included in the study. A total of 149 patients met the inclusion criteria. Of these, 98 had single-station N2 involvement, while 51 had multiple-station N2 involvement. The groups were evaluated in terms of parametric and non-parametric variables using Student’s t-test and Chi-square analysis. Survival analysis was performed using the Kaplan-Meier method and Cox regression analysis. A p-value of < 0.05 was considered statistically significant.

RESULTS: When comparing the groups based on demographic data, the mean age was 61.3 ± 8.2 years in patients with single-station N2 involvement and 59.6 ± 8.3 years in those with multiple-station N2 involvement (p = 0.979). No statistically significant difference was observed between the groups in terms of sex (p = 0.456). There was no significant difference in overall survival between the two groups (p = 0.675). However, adenocarcinoma diagnosis, TNM stage, and receipt of neoadjuvant therapy were identified as statistically significant factors associated with survival (p = 0.024, p = 0.006, and p < 0.001, respectively). In the Cox regression analysis, both pathological diagnosis and neoadjuvant therapy emerged as independent prognostic factors for survival (p = 0.046 and p < 0.001, respectively).

DISCUSSION: Identifying prognostic factors in NSCLC patients with N2 involvement is crucial for determining appropriate treatment and follow-up strategies. In our study, patients with single and multiple N2 involvement exhibited similar demographic characteristics. When the two groups were evaluated in terms of survival, patients diagnosed with adenocarcinoma, those at Stage 3 A, and those who had not received neoadjuvant therapy were found to have significantly better survival outcomes. Our findings also indicated that patients with adenocarcinoma and unexpected N2 involvement had better survival. Independent negative prognostic factors included a non-adenocarcinoma diagnosis and prior neoadjuvant therapy. In cases of NSCLC with multiple N2 involvement, those diagnosed with non-adenocarcinoma type or who had received neoadjuvant therapy should be considered at higher risk for poor prognosis.

PMID:42240869 | DOI:10.1007/s12672-026-05325-1

Clin Oral Investig. 2026 Jun 4;30(6):275. doi: 10.1007/s00784-026-06959-9.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the clinical effectiveness and safety of guided bone regeneration (GBR) using a three-dimensional preformed resorbable Polylactic-co-glycolic acid membrane (3D-PRPM) with simultaneous implant placement.

MATERIALS AND METHODS: Twenty patients (21 sites) with localized ridge defects were treated using implants placed concurrently with GBR using a 3D-PRPM. Cone-beam computed tomography scans were taken preoperatively, immediately postoperatively, and at 5 months. Horizontal bone augmentation (BA), hard tissue gain (HG), bone resorption (BR), and hard tissue gain rate (HGR) were assessed. Changes beyond the original bony envelope were evaluated. Statistical analyses included the Wilcoxon signed-rank and Friedman tests.

RESULTS: Mean BA was 2.99 ± 1.15 mm, and mean HG at 5 months was 2.64 ± 1.10 mm. Mean BR was 0.35 ± 0.23 mm, and mean HGR was 87.2% ± 8.2%. Envelope analysis confirmed a significant increase after augmentation with partial reduction during healing; however, ridge dimensions at 5 months remained significantly greater than baseline (P < 0.001). No membrane exposure, infection, or wound dehiscence occurred.

CONCLUSION: 3D-PRPM enabled predictable horizontal ridge augmentation with excellent volumetric stability and favorable short-term safety.

CLINICAL RELEVANCE: A 3D-PRPM may provide a stable, fixation-free resorbable barrier for horizontal ridge augmentation, potentially simplifying GBR procedures and reducing the need for secondary removal.

PMID:42240865 | DOI:10.1007/s00784-026-06959-9

Clin Neuroradiol. 2026 Jun 4. doi: 10.1007/s00062-026-01668-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Flow diverters (FD) have transformed complex aneurysm management, but incomplete aneurysm occlusion remains a significant concern, highlighting the need for practical predictors of successful treatment. While local flow dynamics are known to be critically influenced by parent artery-aneurysm (PA-aneurysm) geometry, their quantitative assessment in clinical settings is challenging. This study aimed to identify practical, readily measurable geometric predictors for complete aneurysm occlusion following FD treatment.

METHODS: This retrospective study analyzed 119 intracranial aneurysms treated with FD between 2014 and 2023 at our center. Morphological and geometric parameters-including maximal diameter, PA-aneurysm inlet and outlet angles, and branch artery incorporation-were quantitatively measured from 3D rotational Digital Subtraction Angiography (DSA). Angiographic outcomes, categorized as complete occlusion or persistence, were assessed at a minimum of 18 months of follow-up without additional intervention. Independent predictors were identified using univariable and multivariable logistic regression.

RESULTS: Aneurysm occlusion was achieved in 89 (74.8%) cases during a median angiographic follow-up of 19.8 months (interquartile range [IQR], 12.2-34.7). In multivariable analysis, a lower likelihood of aneurysm occlusion was significantly associated with a larger PA-aneurysm inlet angle (OR, 0.82 per 10° increase; 95% CI, 0.69-0.98; p = 0.045) and the presence of branch artery incorporation (OR, 0.25; 95% CI, 0.10-0.63; p = 0.004). While a larger neck diameter (OR, 0.94; 95% CI, 0.85-1.03) was also associated with a lower occlusion rate, this association did not reach statistical significance (p = 0.175). The developed multivariable model demonstrated acceptable predictive performance (AUC = 0.743; 95% CI, 0.632, 0.855).

CONCLUSIONS: A smaller PA-aneurysm inlet angle and absence of branch artery incorporation are independent predictors of aneurysm occlusion after flow diversion. These readily measurable geometric parameters from diagnostic DSA may serve as practical and useful indicators for predicting FD treatment outcomes.

PMID:42240864 | DOI:10.1007/s00062-026-01668-y

Pflugers Arch. 2026 Jun 4;478(6):53. doi: 10.1007/s00424-026-03184-x.

ABSTRACT

Experimental medicine studies, small, mechanistically focused investigations, have historically driven key discoveries in human physiology and pharmacology. Despite their foundational role, these studies are increasingly marginalised in today’s drug development environment due to economic pressures, regulatory conservatism, and an overemphasis on statistical endpoints from large-scale trials. This article traces the historical roots and enduring value of experimental medicine, distinguishes it from current early phase drug development studies, and explores the structural forces behind its decline. N-of-1 trials are discussed as a systematic extension of these principles, offering precision insights at the individual level. We apply this discussion to chronic kidney disease (CKD), a field where slow progression and heterogeneous pathophysiology make early mechanistic studies especially valuable. We argue that bypassing such studies in favour of speed represents a strategic gamble that may misdirect costly late-phase trials. Integrating mechanistic insights with statistical power is not superfluous, but essential, particularly in complex diseases like CKD where understanding why and how interventions work may matter as much as whether they do. We acknowledge that achieving this vision necessitates overcoming significant structural, economic, and cultural barriers within the current drug development environment; however, the costs of inaction, manifest as trial failures, patient harm, and missed therapeutic opportunities, are potentially much greater.

PMID:42240850 | DOI:10.1007/s00424-026-03184-x