Nevin Manimala

Breast Cancer. 2026 Jun 12. doi: 10.1007/s12282-026-01869-w. Online ahead of print.

ABSTRACT

BACKGROUND: Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy.

METHODS: Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs.

RESULTS: Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression.

CONCLUSIONS: Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.

PMID:42286385 | DOI:10.1007/s12282-026-01869-w

Eur Spine J. 2026 Jun 12. doi: 10.1007/s00586-026-10072-6. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to characterize biochemical and microenvironmental changes within the Disc Vertebra Complex (DVC) in non-specific low back pain (NSLBP) patients using non-fat-saturation Multi-slices CEST MRI. By performing intra-group comparisons, we assessed associations between disc degeneration and vertebral biochemical variations.

METHODS: Ninety-nine NSLBP patients (62 males, 37 females; median age 45) underwent lumbar spine MRI. Non-fat-saturation Multi-slices CEST imaging was used to assess fat fraction (FF), fat /water content and magnetization transfer contrast in vertebrates, and water content, glycosaminoglycan (GAG), amide proton transfer (APT), nuclear overhauser enhancement (NOE) and magnetization transfer contrast in discs. Metabolic and microenvironmental changes across vertebrae (L2-S1) and intervertebral discs (L2/3-L5/S1) were analyzed. Statistical comparisons were conducted across disc grades, weight categories, and disc abnormalities.

RESULTS: Significant biochemical variations were observed across vertebral levels, with decreasing water content and increasing FF from L2 to S1. The pH-sensitive markers (APT) showed caudal trends, indicating relative changes in proton environment. Protruding discs and discs with high-intensity zones (HIZ) showed reduced pH and hydration, alongside altered macromolecular structures. Adjacent vertebrae of protruding discs exhibited decreased water content, indicative of early bone marrow edema.

CONCLUSIONS: Non-fat-saturation Multi-slices CEST MRI enables holistic profiling of the disc-vertebra complex (DVC) and detects localized, grade-dependent biochemical heterogeneity. Notably, differences emerged between vertebrae and discs with and without protrusion / HIZ, alongside grade-dependent variations.

PMID:42286353 | DOI:10.1007/s00586-026-10072-6

Eur Spine J. 2026 Jun 12. doi: 10.1007/s00586-026-10079-z. Online ahead of print.

ABSTRACT

PURPOSE: Postoperative pain after lumbar microdiscectomy (MD) can be significant. While both the lumbar erector spinae plane block (L-ESPB) and the posterior quadratus lumborum block (P-QLB) are used for analgesia, they have not been directly compared. We hypothesized that L-ESPB and P-QLB would provide different levels of analgesia after MD.

METHODS: This single-center, prospective, randomized controlled trial included 60 adult patients (ASA I-II) undergoing unilateral single-level lumbar MD. Patients were randomized to receive a bilateral, postoperative L-ESPB (n = 30) or P-QLB (n = 30) with 30 mL of 0.25% bupivacaine per side. The primary outcome was the Numerical Rating Scale (NRS) pain score at 2 h postoperatively. Secondary outcomes included NRS pain scores over 24 h, rescue analgesia requirements, and adverse events.

RESULTS: Patients in the L-ESPB group had statistically lower static and dynamic NRS pain scores at all measured time points (1, 2, 4, 8, 16, and 24 h) compared to the P-QLB group (p = 0.001). The number of patients requiring rescue analgesia was lower in the L-ESPB group (1 vs. 9 patients, p = 0.012), and the total tramadol consumption was also lower (p = 0.005). The incidence of nausea and itching was significantly lower in the L-ESPB group. One patient in the L-ESPB group experienced a temporary motor block.

CONCLUSION: In patients undergoing lumbar MD, L-ESPB provided superior analgesia and resulted in lower opioid consumption and fewer opioid-related side effects compared to P-QLB over the first 24 postoperative hours.

PMID:42286352 | DOI:10.1007/s00586-026-10079-z

Am J Respir Crit Care Med. 2026 Jun 12:aamag276. doi: 10.1093/ajrccm/aamag276. Online ahead of print.

ABSTRACT

RATIONALE: Physician Orders for Life-Sustaining Treatment (POLST) and Advance Directives (AD) aim to honor patient autonomy. However, the impact of the signatory’s identity-whether the patient or a surrogate-on clinical trajectories in the intensive care unit (ICU) remains poorly characterized.

OBJECTIVES: To evaluate the association between signatory identity and terminal care intensity and hospitalization costs among adult patients in the ICU.

METHODS: This nationwide population-based cohort study utilized the South Korean National Health Insurance Service database, including 1,189,042 adult ICU admissions between 2020 and 2023. Statistical analyses employed high-dimensional fixed-effects models to account for institutional variability across 417 hospitals.

RESULTS: Among 1,189,042 patients, surrogate-determined POLST (SD-POLST) was more than three times as prevalent as patient-determined POLST (PD-POLST). Among 90-day decedents, PD-POLST was associated with significantly reduced odds of invasive terminal care (OR, 0.43; 95% CI, 0.43-0.54). Conversely, SD-POLST more than doubled the odds (OR, 2.16; 95% CI, 1.98-2.35). Notably, even patients with proactive ADs experienced increased care intensity once a surrogate signed the final order (OR, 1.69; 95% CI, 1.51-1.89), indicating a phenomenon of “AD erosion.” SD-POLST was also associated with significantly higher daily hospitalization costs (cost ratio, 1.04; 95% CI, 1.02-1.06) compared with no documentation.

CONCLUSION: The clinical efficacy of POLST in limiting non-beneficial care depends fundamentally on the signatory. Surrogate-led decisions were associated with paradoxically higher care intensity and costs, potentially overriding prior patient wishes. These findings highlight the critical importance of early, patient-led discussions to ensure goal-concordant end-of-life care in the ICU.

PMID:42286341 | DOI:10.1093/ajrccm/aamag276

Aesthetic Plast Surg. 2026 Jun 12. doi: 10.1007/s00266-026-06052-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to comprehensively evaluate the short-term changes in ocular surface parameters and meibomian gland function following Full-incision double-eyelid blepharoplast.

METHODS: In this observational self-controlled study, 50 patients (100 eyes) undergoing full-incision double-eyelid blepharoplasty were enrolled. Assessments were conducted preoperatively and at 1 week, 1 month, and 3 months postoperatively. These included the Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (FBUT), corneal fluorescein staining (CFS), Schirmer I test, meibum quality, meibomian gland expressibility, meibomian gland dropout (excluding 1-week), lipid layer thickness (LLT), and incomplete blinking rate (IBR). Statistical comparisons were performed using ANOVA with post-hoc analysis.

RESULTS: Compared to baseline, OSDI scores, meibum quality, meibomian gland expressibility, and IBR showed statistically significant deterioration at both 1 week and 1 month post-surgery (all p < 0.001). In contrast, no significant changes were observed in FBUT, CFS, Schirmer I test, LLT, or meibomian gland dropout at any time point. By the 3-month follow-up, all significantly altered parameters-OSDI, meibum quality, expressibility, and IBR-had recovered to levels that were not statistically different from preoperative baseline values.

CONCLUSIONS: Full-incision double-eyelid blepharoplasty induces a transient but significant dysfunction of the ocular surface and meibomian glands in the early postoperative period, which is closely associated with a sharp increase in incomplete blinking. These findings underscore the importance of proactive postoperative management, including dry eye counseling, artificial tears, and blink training, to enhance patient comfort during the recovery phase.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42286332 | DOI:10.1007/s00266-026-06052-2

Aesthetic Plast Surg. 2026 Jun 12. doi: 10.1007/s00266-026-06123-4. Online ahead of print.

ABSTRACT

This letter to the editor offers a constructive commentary on a recently published multivariate analysis of predictors of complications in abdominoplasty. The authors commend the original study for its rigorous surgical standardization, consecutive patient enrollment, and single‑surgeon design, and agree that high body mass index and active smoking are independent risk factors, while preservation of Scarpa’s fascia appears protective. However, three methodological limitations are identified. First, the sample size and number of events barely meet the minimum recommended events‑per‑variable ratio for multivariate regression. Second, treating seroma, necrosis, and dehiscence as independent outcomes ignores competing risks among these complications, which may bias risk estimates. Third, the single‑center, single‑surgeon design limits external validity, and the finding that diabetes is not a risk factor contradicts some existing literature. The letter suggests that future analyses adopt competing‑risk models and include multicenter external validation. It also notes that no new patient data are provided, so the proposed statistical refinements await empirical verification.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42286329 | DOI:10.1007/s00266-026-06123-4

Surg Endosc. 2026 Jun 12. doi: 10.1007/s00464-026-12951-x. Online ahead of print.

ABSTRACT

BACKGROUND: Despite required simulation training and Fundamentals of Endoscopic Surgery certification, concerns remain about endoscopic competency among graduating general surgery residents. No prior study has directly evaluated resident endoscopic performance in clinical practice. Using the Society for Improving Medical Professional Learning (SIMPL) database, this study assesses general surgery resident competency and autonomy in colonoscopy, upper endoscopy, and sigmoidoscopy/proctoscopy.

METHODS: A retrospective analysis of the SIMPL database was conducted for general surgery residents completing endoscopic procedures between January 2015 and August 2025. Faculty-rated performance was dichotomized as competent (practice-ready/exceptional) versus not competent (unprepared/inexperienced/intermediate performance) and resident autonomy was dichotomized as meaningful (passive help/supervision only) versus not meaningful (show and tell/active help). Descriptive statistics on performance and autonomy were evaluated, including agreement between resident and faculty evaluations. Logistic regression was used to assess resident performance and autonomy according to training year, with case complexity as a covariate.

RESULTS: A total of 3,325 cases were evaluated, consisting of 2,696 colonoscopies, 364 upper endoscopies, and 265 sigmoidoscopies/proctoscopies. Faculty observed competent performance in 35.3% of colonoscopies, 50.0% of upper endoscopies, and 42.3% of sigmoidoscopies/proctoscopies. Faculty observed meaningful autonomy in 60.7% of colonoscopies, 68.9% of upper endoscopies, and 59.2% of sigmoidoscopies/proctoscopies. The likelihoods of achieving competency and meaningful autonomy in the most complex colonoscopies were 23.6% and 40.8%, respectively. At the chief resident level, faculty observed competency in 70.6% of colonoscopies, 89.5% of upper endoscopies, and 87.3% of sigmoidoscopies/proctoscopies.

CONCLUSIONS: Nearly one-third of colonoscopies performed by chief residents did not meet practice-ready competency standards, representing the most concerning finding of this study. Performance was even lower for complex cases, with fewer than one-quarter achieving competency and less than half demonstrating meaningful autonomy. Together, these findings highlight gaps in current training pathways and underscore the need to strengthen endoscopy education.

PMID:42286181 | DOI:10.1007/s00464-026-12951-x

Eur Radiol. 2026 Jun 12. doi: 10.1007/s00330-026-12652-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Though subgroup performance reporting helps ensure the safety of artificial intelligence (AI) products, the extent of this reporting remains unclear. This scoping review identifies studies validating commercially available AI-based products and reports the trends in performance reporting across sex, age, and race/ethnicity demographic subgroups.

MATERIALS AND METHODS: Peer-reviewed validation studies of commercially available products published after 2010 were collected from the Health AI Register and PubMed on 29 November 2024. Study trends in the reporting of sex, age, and race/ethnicity were mapped with regression analysis. We apply the Wilson confidence interval equation to estimate which tuberculosis detection studies are underpowered for subgroup meta-analysis.

RESULTS: Three hundred ninety-two of 545 studies validating 252 products reported subgroup demographic data for any of the three groups. Only 77 of these presented subgroup performance results. Skeletal (20/88) and lung (30/139) studies, and those utilizing chest (24/79) or bone (19/63) radiographs, most often presented subgroup performance data. We found no evidence that more recent studies (OR: 1.039 [95% CI: 0.959-1.127]) or company sponsorship (OR: 1.010 [95% CI: 0.492-1.920]) led to increased subgroup reporting. We show that 14/21 tuberculosis datasets may be underpowered for post-hoc subgroup meta-analysis.

CONCLUSION: This scoping review quantifies how fragmented the commercial validation landscape is, showing that reporting for both the demographics and per-subgroup performance is inadequate for estimating subgroup bias. This systemic problem requires effort from all stakeholders, from researchers to regulatory agencies, encouraging thorough reporting and commercial product validation to support physician and patient trust in medical AI products.

KEY POINTS: Question The number of studies validating the performance of each commercially available radiology AI product for minority subgroup bias is unclear. Findings The currently available commercial AI validation studies often neglect to describe demographic subgroup data, and fewer provide performance results per subgroup, prohibiting algorithmic bias meta-analysis. Clinical relevance Physician and patient trust in the medical AI already used clinically must be built on peer-reviewed literature and meta-analysis. The current literature is insufficient for determining the safety and performance of these products for demographic minorities.

PMID:42286177 | DOI:10.1007/s00330-026-12652-y

Genomics Proteomics Bioinformatics. 2026 Jun 12:qzag046. doi: 10.1093/gpbjnl/qzag046. Online ahead of print.

ABSTRACT

Population admixture is a pivotal evolutionary process that has profoundly shaped genetic diversity and population structure in modern human populations. However, most existing methods for inferring admixture history rely on simplified assumptions, such as strictly sequential contributions from ancestral populations, thereby limiting their applicability to realistic scenarios. Here, we introduce HiMWA, a computational framework based on a hierarchical multiple-wave admixture model for reconstructing complex admixture histories involving multiple ancestral populations. HiMWA characterizes both hierarchical admixture, in which ancestral populations first admix to form intermediate populations, and subsequent multiple-wave admixture that shapes the final admixed population. The framework integrates model selection based on ancestry switch counts with parameter estimation using the length distribution of ancestral tracts. Extensive simulations demonstrate that HiMWA is accurate and robust across diverse admixture scenarios, including those affected by genetic drift and local ancestry inference errors. Applying HiMWA to Kazakhs and Uyghurs revealed a shared hierarchical admixture structure. In both populations, West European and South Asian ancestries first admixed to form a West Eurasian intermediate population, while East Asian and Siberian ancestries formed an East Eurasian intermediate population. These two intermediates subsequently contributed to present-day populations through multiple waves of admixture. Our results highlight the prevalence of hierarchical multiple-wave admixture in Central Asia and provide insights into the region’s complex demographic history. HiMWA offers a powerful and flexible framework for disentangling complex admixture histories and reconstructing realistic population genetic histories from genomic data. The HiMWA software, documentation, and example datasets are publicly available at https://github.com/Shuhua-Group/HiMWA and https://ngdc.cncb.ac.cn/biocode/tool/BT008069.

PMID:42286175 | DOI:10.1093/gpbjnl/qzag046

Commun Psychol. 2026 Jun 12;4(1):95. doi: 10.1038/s44271-026-00487-8.

ABSTRACT

As technology-based learning environments increasingly employ automated feedback, understanding how learners process feedback in real time is essential. This study examined how automated cognitive and metacognitive failure feedback delivered by a humanoid robot affected performance and how effects were moderated by feedback characteristics and learner characteristics. Ninety adults (18-59 years, M_age = 29.53, 61 female, 27 male, 2 diverse) completed a learning task in three conditions: (1) fixed guidance condition with fixed-frequency and content-generic feedback, (2) basic-adaptive condition with frequency-adaptive but content-generic feedback, or (3) personalized-adaptive condition with frequency-adaptive and content-personalized feedback adjusting content to learners specific errors and prior steps. A three-level generalized path model (trials nested within time blocks within learners) was estimated to investigate effects of failure feedback on immediate task performance and cross-level moderation effects. Results showed that cognitive and metacognitive failure feedback increased the likelihood of a correct subsequent response across conditions. Relative to fixed guidance (condition 1), the implemented form of frequency-adaptive feedback (condition 2) did not show statistically significant moderation to these effects. Content-personalized feedback (condition 3) reduced effectiveness of cognitive failure feedback on immediate performance but improved overall performance as compared to content-generic feedback (condition 2). Across conditions, learners with higher cognitive ability benefited less, while those reporting higher momentary on-task boredom benefited more from cognitive feedback. These findings highlight that the effectiveness of automated failure feedback depends on both its design and learners’ situational cognitive and emotional states, illustrating how a situational, temporally sensitive approach can help open the “black box” of feedback effectiveness.

PMID:42286158 | DOI:10.1038/s44271-026-00487-8