Publications by Year: 2026

BACKGROUND: Evidence supporting prehabilitation before cardiac procedures is growing, but the efficacy of different components remains unclear.

OBJECTIVES: The primary aim was to assess the efficacy of prehabilitation on clinical outcomes based on recent randomized controlled trials (RCTs). The secondary aim was to identify effective intervention and which patient subgroups benefit most.

METHODS: We searched Medline, Web of Science, PsycINFO, Embase, Scopus, and Cochrane Central Register of Controlled Trials Library for RCTs comparing prehabilitation with standard care in cardiac patients up to August 2024. Trials were screened by 2 reviewers and meta-analyses were performed using random-effects models.

RESULTS: Forty-four RCTs including 3,925 patients were identified. Prehabilitation improved preprocedural functional capacity (6-minute walk distance) and recovery (in-hospital length of stay, intensive care unit stay, and occurrence of postprocedural pneumonia). Six trials (n = 600) showed improved 6-minute walk distance (mean difference [MD] 68.87 m; 95% CI: 12.76-124.98 m; P = 0.020). In 18 studies (n = 1,568), length of stay was shorter (MD -0.95 days; 95% CI: -1.77 to -0.13 days; P = 0.026) and meta-regression showed greater effect in studies including more women (P = 0.015). In 16 trials (n = 1,149), intensive care unit stay was reduced (MD -6.03 hours; 95% CI: -12.01 to -0.06 hours; P = 0.048). In 5 studies (n = 729), postprocedural pneumonia occurred less frequently (OR: 0.33; 95% CI: 0.15-0.72; P = 0.017). The analysis revealed substantial heterogeneity and risk of bias. Analysis of specific components showed no consistent effects.

CONCLUSIONS: Prehabilitation before cardiac procedures may enhance preprocedural functional capacity and postprocedural recovery, particularly in women. Further multicenter studies are needed.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based regimens can be associated with prolonged survival and disease control after treatment discontinuation without further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time both on/off treatment and with/without toxicity. Previous analysis of first-line (1L) nivolumab+ipilimumab for advanced renal cell carcinoma (aRCC) in CheckMate 214 showed treatment-free survival (TFS; time between 1L and second-line (2L) therapies) was twice as long versus sunitinib. TFS and survival states for ICI plus vascular endothelial growth factor receptor-tyrosine kinase inhibitor are of interest.

METHODS: In CheckMate 9ER, 651 randomized patients with aRCC received 1L nivolumab+cabozantinib or sunitinib. Minimum follow-up was 4 years. We partitioned area under the Kaplan-Meier OS curve into three survival states defined from randomization: time on 1L protocol therapy, TFS, and survival after 2L subsequent systemic therapy initiation. TFS and protocol therapy were subdivided into mean times with/without grade 2+ treatment-related adverse events. Areas under and between Kaplan-Meier curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported.

RESULTS: At 4 years post-randomization, Kaplan-Meier OS estimates were 49.2% versus 40.2% with nivolumab+cabozantinib and sunitinib, respectively; 17.6% versus 4.7% of patients were in TFS; 15.8% versus 8.2% remained on 1L protocol therapy. The 48-month mean time on protocol therapy for nivolumab+cabozantinib versus sunitinib was 22.6 and 14.1 months; 48-month mean TFS was 7.0 and 4.6 months (difference, 2.4 (95% CI 0.8 to 3.9)); 48-month mean survival after 2L therapy initiation was 5.5 and 12.0 months, respectively. The nivolumab+cabozantinib group spent 8.5 (95% CI 6.2 to 10.8) months more mean survival time on 1L protocol therapy, whereas the sunitinib group had 6.5 (95% CI 4.4 to 8.6) months more mean survival time after 2L therapy initiation. Both treatment groups spent at least half of TFS with grade 2+toxicity, resulting in a difference in mean TFS without toxicity of 0.7 (95% CI -0.4 to 1.8) months.

CONCLUSIONS: Partitioned survival analysis over 4 years after initiation of 1L therapy for aRCC indicated that longer OS with nivolumab+cabozantinib versus sunitinib involved more time on 1L therapy and in TFS, and less survival time after 2L therapy initiation.

TRIAL REGISTRATION NUMBER: NCT03141177.

BACKGROUND: Over 3.5 million US men are living with prostate cancer (Pica), many with underlying cardiovascular disease (CVD). Fine particulate matter (PM2.5) contributes to higher CVD mortality through inflammation and other mechanisms, and so may increase non-cancer mortality in men with PCa.

METHODS: We conducted a retrospective cohort study of 886,876 men diagnosed with PCa between 2000 and 2015 and followed through 2018 across eight state cancer registries. Annual average predictions of five residential PM2.5 component exposures (elemental carbon (EC), organic carbon (OC), nitrate, ammonium (NH4+), sulfate (SO42-)) were obtained from an ensemble-based machine learning model and assigned to geomasked addresses at diagnosis within 50 m (urban) or 1 km (rural). Adjusted hazard ratios (aHR) for associations of components separately and as a mixture with all-cause, PCa, and CVD mortality were estimated from covariate adjusted Cox models.

RESULTS: There were 233,898 deaths over 5,836,741 person-years. Per interquartile range (IQR) increase, OC (aHR 1.03 [95 % CI: 1.02-1.04]), NH4+ (aHR 1.02 [1.01-1.03]), and SO42- (aHR 1.11 [1.09-1.13]) were associated with all-cause mortality. CVD mortality was associated with higher EC (aHR: 1.04 [1.02-1.06]), OC (aHR 1.05 [1.03, 1.07]), NH4+ (aHR 1.09 [1.06-1.12]) and SO42- (aHR 1.19 [1.15-1.24]). There were no associations with nitrates or PCa mortality. Per IQR, PM2.5 components mixtures were associated with higher all-cause (aHR 1.03 [1.02-1.04]), PCa (aHR 1.02 [0.99, 1.05]), and CVD mortality (aHR 1.08 [1.05, 1.11]).

DISCUSSION: Certain PM2.5 components were associated with higher all-cause and CVD mortality in men with PCa. Studies of air pollution in cancer survivors should consider impacts on non-cancer mortality.

Patients who receive hematopoietic stem cell transplantation (HSCT) undergo complex treatment regimens often accompanied by significant physical and psychological symptom burdens. However, patient access to psychosocial care is limited, likely in the context of persistent shortages of supportive care clinicians and services. Clinicians can offer valuable insights into psychosocial needs, barriers to accessing psychosocial support, and recommendations to improve psychosocial care for the HSCT population. This qualitative study aimed to explore the perspectives of HSCT clinicians to better understand the challenges HSCT recipients face accessing psychosocial support and how these barriers can inform strategies to enhance psychosocial care. Unlike existing literature that largely focuses on unmet needs in the HSCT population from patient perspectives and patient-reported outcomes, this study delves into the unique insights of HSCT clinicians. A purposive sampling strategy was employed to recruit clinicians across specialties in the United States, including mental health and oncology, involved in HSCT care. Semistructured individual interviews were conducted to explore psychosocial care within HSCT programs. Using a framework-guided rapid analysis, 2 coders analyzed the interviews for emergent themes. Participants (N = 21) shared perspectives on multiple emerging themes, including (1) patient psychosocial challenges (eg, isolation, psychological distress); (2) barriers to psychosocial care (eg, workforce shortage, gaps in integration and continuity of care); and (3) recommendations to improve care delivery (eg, adopting a holistic, team-based model that is proactive and tailored to the needs of HSCT patients throughout their treatment and recovery). Findings highlight critical gaps in psychosocial care for HSCT recipients and offer actionable clinician recommendations to improve psychosocial care delivery for the HSCT population.

Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome most commonly associated with Alzheimer's disease, characterized by progressive visuospatial and visuoperceptual decline. Although voxel-based morphometry studies have described gray matter loss in PCA, a comprehensive and updated coordinate-based meta-analysis is still missing, and associated structural connectivity alterations remain unclear. We conducted a systematic review and meta-analysis of whole-brain voxel-based morphometry studies comparing patients with PCA and healthy controls (PROSPERO ID: CRD420251010673). Analyses were performed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) with family-wise error correction, and meta-regressions assessed the impact of demographic and clinical variables. To investigate structural connectivity, deterministic tractography was carried out on a normative diffusion MRI template, using meta-analytic gray matter clusters as seeds. Eighteen studies were included (339 PCA; 577 healthy controls). The meta-analysis revealed consistent bilateral gray matter atrophy in the lateral occipital cortex, inferior parietal lobule, precuneus, and ventral occipitotemporal regions. Meta-regression highlighted an interaction between age and disease duration, associated with atrophy in the left superior temporal gyrus and right thalamus. Tractography demonstrated that affected clusters were embedded within major long-range pathways, including the superior and inferior longitudinal fasciculi, vertical occipital fasciculi, and parietal aslant tract. Regression-derived clusters additionally mapped onto the arcuate fasciculus, frontal aslant tract, and superior thalamic radiations. This is the first systematic review and voxel-based meta-analysis of PCA conducted after the establishment of consensus diagnostic criteria, providing a statistically robust characterization of gray and white matter alterations and identifying potential imaging biomarkers for diagnosis and treatment.

General anesthesia induces reversible changes in consciousness through cortical activity and connectivity alterations, yet the functional connectome dynamics underlying propofol-induced unconsciousness remains unclear. We analyze high-density 128-channel electroencephalogram (EEG) from 31 surgical patients using source localization to identify neurobiological connectome signatures of propofol anesthesia. Propofol anesthesia increases delta and theta functional connectivity and decreases alpha, beta, and gamma connectivity. A classification model and dynamic analysis of consciousness loss reveals that alpha-band connectivity between parietal, occipital, and subcortical regions is critical for sustaining consciousness, with its disruption marking a key transition to unconsciousness. EEG from 46 additional patients under mild sedation with low-dose propofol confirms that decreased parietal-related alpha connectivity serves as a stable marker of reduced consciousness, insensitive to subtle fluctuations but sensitive to the transition from consciousness to unconsciousness. These findings suggest that parietal, occipital, and subcortical alpha connectivity serves as a reliable neural correlate of propofol-induced unconsciousness.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and telomere length are both strongly linked to rare and common genetic variants. Shortened telomere length might itself be causal for IPF. We aimed to evaluate whether rare and common variants compete or cooperate to confer genetic risk of IPF uniformly.

METHODS: In this genetic analysis, we used whole-genome sequencing (WGS) data from a discovery case-control cohort sequenced at Columbia University and validated findings using WGS data from Trans-Omics for Precision Medicine (TOPMed) and UK Biobank. In all cohorts, we identified rare damaging variants in disease-associated genes and computed control-normalised non-overlapping polygenic risk scores (PRS) for IPF and telomere length. We assessed the MUC5B rs35705950 single-nucleotide polymorphism (SNP), an IPF common risk variant with a large effect, independently from the polygenic scores. Telomere length in blood leukocytes was measured using a quantitative PCR assay for the discovery cohort and UK Biobank validation cohort. We conducted logistic regression (adjusting for age, sex, and principal components of ancestry) to evaluate the association between IPF risk and the MUC5B SNP, the IPF PRS excluding MUC5B (IPF-PRS-noMUC5B), and the PRS for telomere length in the overall cohort and analysed their effects in patient subgroups for IPF endotypes (carriers and non-carriers of rare variants stratified by telomere length cutoffs). To assess disease prediction, we calculated cross-validated area under the receiver operating receiver operating curve (AUC). We also compared the liability of IPF explained by genetic variables.

FINDINGS: The discovery cohort was recruited between April 23, 2003 and June 19, 2019 and included 777 patients with IPF and 2905 controls. We replicated the analyses in the TOPMed (1148 patients with IPF and 5202 controls) and UK Biobank (2739 patients with IPF and 395 331 controls) cohorts. 23-43% of patients with IPF had damaging rare variants or telomeres shorter than the tenth percentile. Analysis of the association of genetic variables with IPF diagnosis yielded odds ratios of 1·63 (95% CI 1·47-1·81) for telomere length PRS and 1·60 (1·44-1·77) for IPF-PRS-noMUC5B in the discovery cohort, with similar effect sizes for the two variables in the replication cohorts (1·47, 1·36-1·59 vs 1·37, 1·25-1·50 in TOPMed; 1·24, 1·19-1·29 vs 1·25, 1·21-1·30 in UK Biobank). The telomere length PRS had the greatest effect on disease risk in patients with IPF not harbouring rare variants and with telomere length shorter than the tenth percentile in the discovery cohort (2·02, 1·76-2·33) and UK Biobank replication cohort (1·70, 1·56-1·85). Accounting for clinical variables and all genetic variables (rare variants, MUC5B SNP, IPF PRS, and telomere length PRS) led to the best disease prediction in the discovery cohort (combined AUC 0·89), TOPMed cohort (0·89), and UK Biobank cohort (0·77). Rare and common variants contributed jointly to the genetic liability of IPF. The telomere length PRS accounted for 13% of the explained genetic liability of IPF in the discovery cohort and 8% and 13% in the TOPMed and UK Biobank cohorts, respectively.

INTERPRETATION: Common and rare genetic variation confer context-specific genetic risk in patients with IPF both competitively and cooperatively. In contrast to known IPF common risk variants, the telomere length PRS, which includes more than 180 genetic loci not previously associated with IPF, is associated with increased risk of disease in patients with specific IPF endotypes. Polygenic risk from telomere-associated common variants is a key feature of genetic heterogeneity in IPF.

FUNDING: US National Institutes of Health, UK Medical Research Council, and UK National Institute for Health and Care Research.