Nevin Manimala

Target Oncol. 2026 Jan 23. doi: 10.1007/s11523-025-01194-w. Online ahead of print.

ABSTRACT

BACKGROUND: Given that immune checkpoint inhibitor-based regimens frequently yield delayed separation and late plateaus, conventional hazard ratio analyses that assume proportional hazards may misstate true benefit.

OBJECTIVE: We aimed to test the validity of the proportional hazards assumption in first-line metastatic clear cell renal cell carcinoma trials and to compare the immune checkpoint inhibitor-based regimens using restricted mean survival time.

METHODS: We performed a systematic review and network meta-analysis of phase III randomized controlled trials of first-line treatment for metastatic clear cell renal cell carcinoma, including immune checkpoint inhibitor-tyrosine kinase inhibitor combinations or dual-immune checkpoint inhibitor regimens. Individual patient data were reconstructed from the Kaplan-Meier curves of overall survival and progression-free survival. The restricted mean survival time differences were estimated.

RESULTS: Five trials (4206 patients; six treatment arms) were examined. Proportional hazards assumption was violated in 60% of both overall survival and progression-free survival comparisons. In the restricted mean survival time-based network meta-analysis of overall survival, immune checkpoint inhibitor-tyrosine kinase inhibitor combinations, especially Nivolumab + Cabozantinib, dominated at 12-48 months, whereas Ipilimumab + Nivolumab ranked highest beyond 48 months. In the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable-risk subgroup, Avelumab + Axitinib showed a favorable long-term profile despite the lack of statistical significance. In IMDC intermediate/poor-risk, patterns mirrored the overall population. For progression-free survival, Pembrolizumab + Lenvatinib ranked best across IMDC subgroups. Limitations included the reliance on reconstructed data and heterogeneity across trials.

CONCLUSIONS: Given the frequent proportional hazards violations, hazard ratio-only syntheses are insufficient for modern immune checkpoint inhibitor-based regimens. In the restricted mean survival time-based network meta-analysis, Pembrolizumab + Lenvatinib delivered rapid disease control, and Ipilimumab + Nivolumab showed the greatest late survival advantage in IMDC intermediate/poor-risk.

PROSPERO REGISTRATION NUMBER: CRD420251143602.

PMID:41575641 | DOI:10.1007/s11523-025-01194-w

Discov Ment Health. 2026 Jan 23. doi: 10.1007/s44192-026-00376-w. Online ahead of print.

ABSTRACT

BACKGROUND: In a post-genocide context, mental health disorders among Rwandan genocide survivors and released perpetrators remain a critical concern. To date, no study has evaluated the effectiveness of the Community Resiliency Model (CRM) skills in addressing the mental health needs of both groups simultaneously. This study assessed the impact of CRM when delivered to a combined group of survivors and perpetrators, compared to groups trained separately.

METHODS: A total of 152 participants were recruited from Nyamagabe district, Rwanda. Participants were assigned into three groups including genocide survivors (n = 51), released genocide perpetrators (n = 51), and a combined group of both survivors and perpetrators (n = 50). Data were collected at three points: pre-intervention, immediately post-intervention, and six months post-intervention using validated psychometric scales for anxiety, depression, posttraumatic stress disorder (PTSD), emotional dysregulation, and anger. Repeated measures ANOVA and Bonferroni post hoc tests were used to analyze changes over time. A statistical significance of p < 0.005 and p < 0.001 was applied.

RESULTS: Our findings showed significant reduction of anxiety (F = 20.17, p < 0.001), depression (F = 37.03, p < 0.001), anger (F = 95.97, p < 0.001), and emotional dysregulation (F = 76.68, p < 0.001) across all groups of participants. These positive changes were sustained at 6 months post-intervention for anxiety, depression, anger, and emotional dysregulation. In contrast, PTSD symptoms only showed a slight, non-significant reduction over time (F = 0.59, p = 0.44). Additionally, there were no significant differences in outcomes between groups that received the intervention separately (survivor-only or perpetrator only) and those that received it in mixed survivor-perpetrator groups.

CONCLUSION: Although the CRM intervention does not replace psychotherapy, it produced lasting and positive effects on mental health symptoms among both genocide survivors and perpetrators, particularly in reducing anxiety, depression, and emotional dysregulation. Importantly, outcomes did not differ whether the intervention was delivered to separate or combined groups. A randomized controlled trial is recommended to further evaluate the long-term effects of CRM on community healing and cohesion.

PMID:41575623 | DOI:10.1007/s44192-026-00376-w

Aesthetic Plast Surg. 2026 Jan 23. doi: 10.1007/s00266-026-05617-5. Online ahead of print.

ABSTRACT

BACKGROUND: Removal of the skin and preseptal orbicularis oculi is the initial step in upper eyelid surgery. Preseptal orbicularis oculi removal has been strongly associated with dry eye symptoms due to sluggish eyelid closure and lagophthalmos. We aimed to investigate the effects of concurrent upper blepharoplasty and external levator advancement (ELA) surgery with or without orbicularis oculi resection on dry eye syndrome and eyelid morphology in Southeast Asian populations.

METHODS: This prospective, single-centre, double-blind, randomised controlled trial involved 20 Thai patients (40 eyes) with aponeurotic blepharoptosis and excess eyelid skin undergoing combined upper blepharoplasty and ELA surgery. Patients were randomised into a skin-muscle excision group (group A) or a skin-only excision group (group B). Dry eye parameters including tear break-up time, Oxford ocular surface staining, Ocular Surface Disease Index, eyelid appearance, and patient satisfaction were evaluated preoperatively and on postoperative days 7, 30, and 90.

RESULTS: Preseptal orbicularis oculi excision had no statistically significant impact on dry eye parameters, eyelid appearance, or patient satisfaction. For both groups, surgery increased the marginal reflex distance 1 without causing significant lagophthalmos, indicating successful ptosis correction irrespective of muscle excision. There were no discernible differences in postoperative appearance between the two groups, and the patients reported high satisfaction with their treatment.

CONCLUSIONS: Combined upper blepharoplasty and ELA surgery, with or without resection of the preseptal orbicularis oculi, may be a safe and potentially effective procedure for patients with aponeurotic blepharoptosis and excess eyelid skin. Our findings demonstrate no evidence of a difference in correlation between either of these techniques and postoperative dry eye parameters or eyelid appearance. Further studies with larger sample sizes and longer follow-up periods are warranted.

LEVEL OF EVIDENCE I: 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:41575571 | DOI:10.1007/s00266-026-05617-5

Eur Radiol. 2026 Jan 23. doi: 10.1007/s00330-025-12172-1. Online ahead of print.

ABSTRACT

OBJECTIVES: As post-mortem (PM) imaging in children becomes more common, there is a need to review the available evidence for its diagnostic yield in suspected child physical abuse. The aim of this review is to synthesise current evidence, assess study quality, and identify ongoing challenges.

MATERIALS AND METHODS: Following PRISMA guidelines, databases were searched until 31 December 2024. Original research articles reporting data on at least ten children with PM imaging in the context of physical abuse were included. Titles and abstracts were screened by two expert reviewers; full texts were assessed by a third, independent reviewer and one of the previous reviewers. Data was extracted by one of 12 experts and independently verified. The study risk of bias was evaluated with the ROBINS-I tool. Study heterogeneity precluded meta-analysis, resulting in descriptive synthesis.

RESULTS: Eighteen out of 1687 potential papers were included. Seven described PM radiography, five post-mortem computed tomography (PMCT), four both PM radiography plus PMCT, and two post-mortem magnetic resonance imaging (PMMR). All but one were retrospective, and most (11/18, 61%) had a moderate-to-high risk of bias. Post-mortem skeletal survey (PMSS) detected subtle fractures, particularly corner metaphyseal fractures. PMCT provided a high-resolution assessment of injuries, particularly rib fractures. PMMR contributed soft-tissue and intracranial detail. All studies emphasised the importance of correlating autopsy findings. Technical variation and potential biases limited direct comparisons between studies.

CONCLUSION: PM imaging can reveal important injury patterns that may be overlooked by autopsy. Nevertheless, standardised imaging methods and larger prospective trials are needed to reduce bias and establish best-practice guidelines.

KEY POINTS: Question What is the evidence for PM radiologic imaging in suspected physical abuse of children? Findings PM imaging complements autopsy, but diagnostic accuracy varies by modality. Study heterogeneity and bias limit current evidence. Clinical relevance PM imaging can detect injuries missed at autopsy in child abuse cases. Standardised protocols and higher-quality studies are urgently needed.

PMID:41575565 | DOI:10.1007/s00330-025-12172-1

Anaesthesiologie. 2026 Jan 23. doi: 10.1007/s00101-025-01631-5. Online ahead of print.

ABSTRACT

BACKGROUND: A comprehensive transesophageal echocardiography (TEE) examination is nowadays common practice in cardiac surgical procedures. The introduction of 3D technology enables a simultaneous multiplane display of 2D views (X-plane) which can shorten the duration of the TEE examination; however, X‑plane imaging results in a decrease in temporal resolution which can affect the accuracy of routine anatomical linear measurements. The 3D-TEE imaging enables multiplanar reconstruction of 3D datasets and to freely position perpendicular 2D planes to measure anatomical structures more accurately, which has been shown to strongly correlate to computed tomography and magnetic resonance imaging.

OBJECTIVE: Does the integration of multiplane imaging shorten the time of a comprehensive TEE examination without affecting the accuracy of routine 2D anatomical linear measures?

MATERIAL AND METHODS: In a prospective randomized comparative study, patients scheduled for elective cardiac surgery underwent a comprehensive intraoperative TEE examination (Philips CX 50 with X‑72T probe). They were divided into two groups. In the routine protocol (RP) group, the TEE examination was conducted according to the standardized departmental image acquisition protocol, while in the study protocol (SP) group, multiplane views were integrated into the RP to replace the corresponding 2D views. The examinations were conducted by two experienced echocardiographers. At the end of the assigned examination protocol the timer was stopped and the missing views were obtained (2D for the X‑plane and vice versa) as well 3D datasets of the mitral valve, aortic valve and left ventricle. Measurements of mitral and aortic annuli as well as left ventricular length from 2D and X-plane views were subsequently performed offline. Measurements obtained from a multiplanar reconstruction of a full volume (FV) 3D dataset from the same patient were used as the gold standard to compare measurements in RP and SP.

RESULTS: The examination time was significantly shorter in the SP group (SP: 481 ± 60 s; RP 595 ± 60 s; p < 0,001). There was no significant difference for any of the measurements using the SP and RP. The mean percentage error, although not statistically significantly different, was numerically smaller for the X‑plane than for 2D method compared to 3D except for the mitral valve annulus. Overall, X‑plane tended to show lower variability compared to 2D.

CONCLUSION: Integrating multiplane views into a standardized comprehensive TEE image acquisition protocol reduces the examination time. The accuracy of standardized linear measurements in X‑plane mode is comparable to that of conventional 2D imaging.

PMID:41575560 | DOI:10.1007/s00101-025-01631-5

Eur J Nucl Med Mol Imaging. 2026 Jan 23. doi: 10.1007/s00259-026-07772-y. Online ahead of print.

ABSTRACT

INTRODUCTION: We investigated whether prompt changes in prostate-specific-antigen (PSA) levels within two days after the first cycle of prostate-specific-membrane-antigen radioligand therapy (PSMA-RLT) with [¹⁷⁷Lu]Lu-PSMA-617 predicted treatment response and mean survival.

METHODS: In a retrospective study of 76 metastatic castration resistant prostate cancer (mCRPC) patients, we evaluated pretreatment PSA-values and their relative changes in PSA (dPSA) two days later. We tested for correlations between dPSA with long-term biochemical response (BCR) to treatment, using a priori criteria for relevant PSA decrease (dPSA < -10%), stable PSA (-10% ≤ dPSA ≤ + 10%) and relevant PSA increase (dPSA > 10%), along with evaluation of biochemical therapy outcome according to the Prostate-Cancer-Working-Group (PCWG3).

RESULTS: Two days after the first [177Lu]Lu-PSMA-617 cycle, 32 (42%) of the patientsshowed PSA decrease, of whom 19 (59%) had experienced a partial response according toPCWG3 criteria. Of the 37 patients with stable PSA, 17 (46%) showed partial response totreatment according to PCWG3 criteria. Among the seven patients with PSA increase, three(43%) showed partial response. Pearson correlation analysis showed statistically significantcorrelations between dPSA on day 2 and relative Nadir for the first two treatment cycles.Patients with PSA decrease or stable PSA compared to those with an increase of PSA two daysafter cycle 1 lived longer on average (399, 405 and 225 days, respectively).

CONCLUSION: Compared to those with increased PSA levels, patients with decreased or stable PSA levels two days after the first [¹⁷⁷Lu]Lu-PSMA-617 RLT cycle were more likely to have favorable biochemical response according to PCWG3 criteria and presented with a longer overall survival.

PMID:41575546 | DOI:10.1007/s00259-026-07772-y

Lupus. 2026 Jan 23:9612033261419670. doi: 10.1177/09612033261419670. Online ahead of print.

ABSTRACT

AimsLupus nephritis (LN) is common in systemic lupus erythematosus (SLE) and is associated with adverse renal outcomes and premature mortality. There is limited data examining LN outcomes in Aotearoa New Zealand and none examining outcomes since mycophenolate mofetil (MMF) became subsidised for use in class III/IV LN induction. We describe a cohort of adults with biopsy-confirmed LN over an 18-year period in two regions of Aotearoa New Zealand, including LN characteristics, treatment, and outcomes.MethodsCases were identified from laboratory databases and relevant data extracted from patient records. Response was defined per Kidney Disease, Improving Global Outcomes (KDIGO) with overall renal response (ORR) defined as at least partial response (PR). Outcomes among patients with class III/IV LN were explored by induction treatment and timing of MMF restrictions.ResultsOne hundred cases were identified, including 74 with class III/IV LN. Most (85/100) were women, living in urban areas (78%), with ethnicities including Māori (25%), Pacific (13%) and NZ European (38%). The median age at LN diagnosis was 38 years (range 18-74) and the median time between SLE diagnosis and renal biopsy was 2 years. In the MMF-restricted period, MMF was used for induction in class III/IV LN in 43% (12/28) of cases, and in 72% (33/46) of cases in the MMF-unrestricted period (p = .01). In the MMF-unrestricted period, use of high dose cyclophosphamide stopped (18% to 0%), complete response (CR) rates doubled (14% to 33%, p = .08) whereas rates of ORR did not show statistically significant change (39% to 50%, p = .37). At last-observed follow up (mean 7 years from biopsy) 26/74 (36% cases) had poor outcomes with no renal response.ConclusionIn this LN cohort in Aotearoa New Zealand, half of people with LN class III/IV do not achieve early renal response and over one-third have poor outcomes over less than a decade of follow up. Subsidy of MMF substantively increased its use and patients in this time period had better rates of good LN outcomes. These data suggest considerable unmet need for effective treatments for LN and that funding of effective medicine for LN increases their use and improves LN outcomes.

PMID:41575361 | DOI:10.1177/09612033261419670

Health Phys. 2026 Jan 23. doi: 10.1097/HP.0000000000002037. Online ahead of print.

ABSTRACT

This research explores the application of advanced geostatistical methods to predict the locations of residual radioactive hotspots at the former Zamzow uranium mine site, located near Three Rivers, TX. The site, part of the broader Lamprecht-Zamzow project, has a complex history, having undergone in situ uranium mining and processing, followed by decommissioning activities. The role of this study is not to set or recommend remediation goals, as this responsibility lies with the State of Texas. Rather, the purpose of the statistical analyses in this work is to present the data objectively, predicting potential contamination at unsampled locations and where further actions may be needed. Importantly, the findings of this study aim to inform state regulators regarding the unrestricted release of the site for landowner use, providing critical insights into the effectiveness of previous remediation efforts. By employing rigorous geostatistical techniques on survey data collected by environmental services contractors, this study models the spatial distribution of contamination referred to as “hotspots” with precision. This research marks an important advancement toward a scientifically grounded, objective approach in assessing radioactive site remediation and informing future decisions regarding site decommissioning and land restoration at former uranium sites. Importantly, the statistical analysis in this work demonstrated a clear reduction in the number of hotspots after site remediation, highlighting the effectiveness of the intervention.

PMID:41575359 | DOI:10.1097/HP.0000000000002037

J Gastroenterol Hepatol. 2026 Jan 23. doi: 10.1111/jgh.70249. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: The effectiveness of standard endoscopic treatment (SET) for non-variceal upper gastrointestinal bleeding (NVUGIB) may vary, particularly depending on the bleeding site, lesion size, and etiology. Recent studies suggest that hemostatic powder (HP) may effectively control bleeding secondary to malignant upper gastrointestinal lesions, but its efficacy in benign etiology for NVUGIB remains uncertain. This systematic review and meta-analysis aimed to compare the effectiveness of HP versus SET as first-line therapy for patients with non-malignant causes of NVUGIB.

METHODS: We systematically searched PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) from inception to January 2025. We used risk ratios (RR) for binary outcomes and mean differences (MD) for continuous outcomes with their corresponding 95% confidence intervals (CIs).

RESULTS: We included 5 RCTs (708 patients). Compared to SET, HP was associated with marginally lower risk of further bleeding during esophagogastroduodenoscopy (EGD) (RR 1.04; 95% CI [1.001, 1.084]; p = 0.04) and similar rebleeding rate within 1, 3, 7, 15, and 30 days. The need for a second endoscopic treatment and the mean procedure time were similar between the groups. Subgroup analyses showed that HP has a lower risk of further bleeding during EGD only when analyzing Forrest IIa lesions, but not in active bleeding.

CONCLUSIONS: In patients with non-malignant NVUGIB, HP demonstrated lower risk of further bleeding during EGD in cases with non-bleeding visible vessels. There was no statistically significant difference in further bleeding during EGD for active bleeding, nor in rebleeding risk at 1, 3, 7, 15, or 30 days.

PMID:41575324 | DOI:10.1111/jgh.70249

J Int Med Res. 2026 Jan;54(1):3000605251411752. doi: 10.1177/03000605251411752. Epub 2026 Jan 23.

ABSTRACT

ObjectiveEsophageal cancer is among the most rapidly spreading malignancies worldwide. Early detection of esophageal cancer is critical for disease prevention and for improving overall population health. Most studies have used statistical methodologies to assess the esophageal cancer risk, and only a few studies have used prediction models.MethodsThe esophageal cancer dataset, comprising 3985 patient records with 85 demographic, pathological, and follow-up features, was obtained from Kaggle. A comprehensive data-engineering pipeline was implemented, including the removal of null and low-variance features, elimination of identifier variables to prevent data leakage, mode-based imputation, label encoding, and data standardization. Feature relevance was assessed using Mutual Information, and the top 31 clinically meaningful features were retained for model development. Six machine learning classifiers-Support Vector Machine, Gaussian Naïve Bayes, k-nearest neighbors, AdaBoost, Multilayer Perceptron, and LightGBM (Gradient Boosting Machine)-were trained and evaluated. A stratified 10-fold cross-validation was applied to maintain class balance, and GridSearchCV was used for hyperparameter optimization. Model interpretability was assessed using Shapley Additive Explanations (SHAP) for global and local feature attribution and Local Interpretable Model-Agnostic Explanations (LIME) for instance-level explanations. Furthermore, the top features identified by SHAP and LIME were used to retrain the LightGBM model to evaluate performance under reduced dimensionality.ResultsAmong all evaluated classifiers, LightGBM exhibited the highest and most stable performance, achieving an accuracy of 99.87% prior to hyperparameter tuning and 99.74% following stratified cross-validated tuning, with near-perfect precision, recall, F1-score, and area under the curve values. Explainability analyses indicated that clinically relevant variables, including tumor staging, smoking-related factors, and follow-up indicators, played a significant role in model predictions. The SHAP-selected top-20 feature model maintained high predictive performance (99.76%), demonstrating that the classifier remained robust despite dimensionality reduction.ConclusionsThe proposed LightGBM-based model demonstrates exceptional predictive accuracy and strong interpretability, suggesting its potential utility for the early detection of esophageal cancer using machine learning approaches.

PMID:41575322 | DOI:10.1177/03000605251411752