Citations

Purpose: Supervised walking exercise is a critical component of rehabilitation for patients with peripheral artery disease (PAD); however, various barriers could limit participation in such programs, highlighting the need for accessible exercise strategies that may facilitate a gradual transition to more intensive physical activity while improving vascular function and walking performance in this population. We examined the hypothesis that static muscular stretching would improve microvascular function and walking ability in patients with PAD. Methods: Thirty-six PAD patients, classified as Fontaine Stage II or III, were randomized into stretching or non-stretching groups. The stretching group performed daily calf stretching using an ankle dorsiflexion splint for 30 minutes, 5 days a week, for 4 weeks. The six-minute walk test (6MWT) and a vascular occlusion test were used to assess changes in walking ability and calf microvascular function before and after the intervention. Results: Microvascular hyperemic reperfusion significantly increased in the treatment group (4958±1111 to 5749±1459 %*s, p=0.034), with no change observed in the control group (5502±1231 to 5022±1160 %*s, p=0.155). 6MWT total walking distance increased in all participants (260±88 to 285±85 m, p=0.004). A moderate but non-significant correlation was observed between the changes in 6MWT and total walking distance and reperfusion index in the treatment group (r=0.45, p=0.26). Conclusions: Static muscular stretching improves microvascular perfusion in the calf muscles, which may contribute to improvement in walking ability in patients with PAD. This low-cost and time-saving intervention may serve as a gradual transition to traditional supervised walking exercise rehabilitation, especially in patients with severely impaired walking ability.

ABSTRACT Observational studies comparing Impella and venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in cardiogenic shock have reported inconsistent findings. We performed an updated systematic review and meta‐analysis, with exploratory matched‐cohort analyses where directly reportable propensity score–matched event‐level data were available. We searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception through March 2026 for observational studies comparing Impella versus VA‐ECMO in adult patients with cardiogenic shock. The primary outcome was in‐hospital mortality. Secondary outcomes included all‐cause mortality, ICU outcomes, access site bleeding requiring transfusion, peripheral vascular complications, renal outcomes, and stroke. Random‐effects models using restricted maximum likelihood were applied. Fifteen observational studies including 22,618 patients were analyzed. In the primary crude analysis, Impella was not associated with a statistically significant difference in in‐hospital mortality (RR 0.84, 95% CI 0.66−1.07; p = 0.15) with substantial heterogeneity ( I ² = 92.9%). However, leave‐one‐out analysis identified an influential registry study; its exclusion markedly reduced heterogeneity and favored Impella ( p < 0.01). In exploratory propensity score‐matched analysis, Impella was also associated with lower in‐hospital mortality (RR 0.69, 95% CI 0.56−0.85, p < 0.01). Thirty‐day and 6‐month all‐cause mortality were neutral, whereas 12‐month mortality modestly favored Impella ( p = 0.048). Sensitivity analyses similarly resolved heterogeneity and favored Impella for selected secondary outcomes, including 6‐month mortality, acute kidney injury, and ischemic stroke. ICU mortality was neutral, while ICU length of stay was shorter with Impella ( p = 0.01). Impella was also associated with lower access site bleeding requiring transfusion ( p < 0.01), peripheral vascular complications ( p < 0.01), and hemorrhagic stroke ( p < 0.01). In this updated meta‐analysis of observational studies, the primary crude analysis of in‐hospital mortality was neutral overall but highly heterogeneous, whereas sensitivity and exploratory matched‐cohort analyses showed a more consistent association favoring Impella. Impella was also associated with lower bleeding and vascular complications and shorter ICU length of stay, although several outcomes remained sensitive to study‐level influence. These findings should be interpreted cautiously given the observational design, predominance of serious risk of bias, and strong potential for confounding by indication.

Background/Objectives: Accurate detection of pulmonary nodules on chest CT is critical for lung cancer screening, yet training robust detectors remains challenging due to the high cost of reliable annotations. In this work, we present a systematic study of curriculum learning for CT-based lung nodule detection on the enhanced LUNA25 benchmark and propose a hybrid curriculum learning framework for data-efficient optimization. Methods: Our approach estimates sample difficulty by fusing clinically interpretable handcrafted factors such as nodule size and count with model-driven signals such as prediction confidence from a teacher model, and constructs a three-stage progressive training curriculum from easy to hard samples. Using YOLOv11s as a strong baseline, the proposed hybrid curriculum is compared against conventional training without curriculum learning and against single-source curricula. Results: On the held-out LUNA25 test set, hybrid curriculum learning increases mAP50 from 0.672 to 0.696, mAP50–95 from 0.369 to 0.385, recall from 0.588 to 0.634, and precision from 0.725 to 0.764. Extensive data-efficiency experiments with proportional reductions (1/2, 1/5, 1/10) and fixed training samples (5000–40,000 slices) further confirm consistent gains across limited-data regimes. Conclusions: These results demonstrate that jointly leveraging intrinsic image complexity and optimization-aware feedback provides effective sample scheduling for robust and data-efficient lung nodule detection.

Background/Objectives. Decades of research have failed to uncover effective approaches to prevent chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of neurotoxic chemotherapy. Increased interest in placebo response as a potentially under-recognized confounder in CIPN trials was recently sparked by the results of a multisite NCI-funded phase II-III CIPN prevention study of duloxetine, a promising serotonin–norepinephrine reuptake inhibitor that enhances pain-inhibitory mechanisms within the central nervous system. Study findings revealed high and nearly equivalent response rates in three randomized treatment groups—little to no CIPN was reported by 65.2%, 66.0%, and 68.0% of study participants who received duloxetine 30 mg, 60 mg, or placebo treatment, respectively. Methods. We performed a meta-analysis of placebo response rates from seven randomized, double-blinded, placebo-controlled trials conducted over the past 20 years and comprising 191 placebo participants that were specifically testing interventions for oxaliplatin- and paclitaxel-induced peripheral neuropathy and that serially collected patient responses on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-Induced Neuropathy questionnaire. Additionally, we sought to identify trial- and patient-specific factors that predicted higher placebo response rates from a participant-level pooled analysis. Results. The placebo response rate was 10.0% [95% CI: 5.8%, 16.6%] when response was defined more conservatively as patients reporting no neuropathy at all. When the placebo response was defined more broadly based on patients reporting no or a little neuropathy, the placebo response rate was higher (39.6% [95% CI: 27.4%, 53.2%]). Male participants, receipt of oxaliplatin, and a 2:1 randomization ratio favoring the intervention arm were individually associated with a higher placebo response. Conclusions. High placebo response rates can threaten scientific progress toward identifying effective treatments for cancer treatment-associated side effects, like CIPN. Careful attention to study design factors, participant eligibility, and patient and research staff expectations may help to minimize placebo response rates in future CIPN intervention studies.

PURPOSE For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. METHODS NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes. RESULTS Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms. CONCLUSION Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

By 2045, more than three quarters of global cancer deaths are projected to occur in low- and middle-income countries (LMICs); however, the global availability of cancer care remains constrained by high costs and inequitable access. Value-based frameworks that integrate clinical benefit with affordability, feasibility, and equity are essential to better guide research prioritization, resource allocation, and regulatory policies in LMICs. A key component of a value-based approach is the generation of high-quality, locally relevant data to support evidence-based implementation of cancer prevention and control strategies. Herein, we provide three contemporary examples from JCO Global Oncology which demonstrate how economic evaluation in cancer research can address locally relevant, health system–specific questions.

Background: Prosthetic joint infections (PJIs) pose a significant treatment challenge due to biofilm-associated resistance, which limits antibiotic effectiveness. Bacteriophages, naturally occurring viruses that selectively infect and lyse bacteria, can disrupt biofilms, potentially enhancing antibiotic activity. We present the case of a male in his 70s with a history of total hip arthroplasty in 1973 who developed a chronic methicillin-susceptible Staphylococcus aureus (MSSA) PJI. Despite eight surgical interventions and multiple courses of suppressive antibiotics, the infection persisted, necessitating the use of bacteriophage therapy. Methods: The patient's MSSA isolate was sent to a bacteriophage laboratory in Quebec, which identified effective bacteriophages, and a two-bacteriophage cocktail was selected. Following approval by Health Canada and the University of Calgary (REB23-1733), bacteriophages were administered during a planned incision and drainage (I&D). Locally, bacteriophage was applied topically into the hip, followed by 2 weeks of twice-daily intravenous bacteriophage therapy with standard-of-care intravenous antibiotics. Results: Therapy was well tolerated except for initial mild rigors. Now, 24 weeks after bacteriophage administration, there is cessation of pain, normalization of inflammatory markers, and significant improvement in quality of life while continuing on suppressive antibiotics. Conclusions: Bacteriophage therapy was safe in our case, and emerging evidence is promising for its use in PJIs. However, regulatory hurdles, cost, and lack of standardized protocols currently limit its use. Classified as experimental therapy in Canada, bacteriophage use is restricted to clinical trials. This case underscores the potential for broader adoption of bacteriophage therapy in managing PJIs across Canada.

Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.