Citations

Abstract Vertebral metastatic disease results from many types of cancer and can have a devastating impact on patient mobility, psychological health, quality of life, and ultimately overall patient survival. However, the development of radiotherapy and surgical techniques has rapidly surged in conjunction with ongoing advances in basic science and translational studies. In this review, we discuss the paradigm shift in our understanding of the epidemiology and treatment algorithms for spinal oncology, ranging from preoperative optimization strategies, radiation and surgical techniques, the utilization of molecular markers and targeted therapeutics in medical oncology, and prognostication tools that underscore a new multidisciplinary approach to spinal oncology care.

Objective To validate International Bladder Cancer Group (IBCG) definitions of Bacillus Calmette‐Guérin (BCG)‐unresponsive and BCG‐exposed non‐muscle‐invasive bladder cancer (NMIBC) and assess prognostic heterogeneity across various BCG‐failure types. Patients and Methods From a multicentre international cohort of 3806 BCG‐treated patients, 591 who developed high‐grade NMIBC recurrence following BCG between 2003 and 2024 were included. Progression‐free survival (PFS) was the primary endpoint; cancer‐specific (CSM) and overall mortality (OM) were secondary endpoints. Cumulative incidence functions, competing‐risk models and multivariable Cox regression were used. Results Patients with BCG‐unresponsive and BCG‐exposed disease showed similar PFS, CSM, and OM (all P > 0.05). When stratified into five subgroups, prognosis varied: 5‐year progression rates were 29% for BCG‐unresponsive, 32.5% for late relapse (between 6 and 24 months) after adequate BCG, 30% for BCG‐exposed with inadequate BCG (<24 months from induction), 6.2% for BCG‐resistant, and 14% for very late relapse (>24 months since last BCG) ( P < 0.01). In multivariable analysis, BCG‐exposed after inadequate BCG (subdistribution hazard ratio [sHR] 3.42, 95% confidence interval [CI] 1.33–8.84), late relapse (sHR 3.74, 95% CI 1.59–8.78), and BCG‐unresponsive (sHR 2.34, 95% CI 1.00–5.44) were associated with higher progression risks compared to very late relapse. Limitations include retrospective design and treatment heterogeneity. Conclusions Under IBCG definitions, BCG‐unresponsive and BCG‐exposed NMIBC have similarly poor outcomes. A refined classification reveals prognostic heterogeneity, with late relapses after adequate BCG demonstrating outcomes comparable to BCG‐unresponsive, and very late relapses conferring better prognosis.

Background Medication nonadherence has been associated with poor outcomes in transplant recipients yet identifying these behaviors pre-transplant remains challenging. The simplified medication adherence questionnaire (SMAQ) is a brief, reliable instrument to assess medication adherence. The aim of this study was to perform SMAQ testing on thoracic organ candidates and examine correlations between these scores and individual patient factors predicting medication nonadherence. Methods Consenting waitlisted lung, heart, and heart-lung transplant candidates from six thoracic transplant centers were mailed a survey that included demographic information and the Simplified Medication Adherence Questionnaire (SMAQ). Univariate logistic regression analysis was performed to assess association between pre-transplant medication adherence and demographic characteristics, psychosocial factors, and mortality. Results Among 298 participants, 60.7% were medication nonadherent. Nonadherence was associated with some college education (OR: 1.73; CI: 1.06, 2.81), lower positive affect (OR: 0.95; CI: 0.92, 0.99), and higher uncertainty (OR: 1.02; CI: 1.01, 1.04). Higher positivity ratio predicted adherence. Conclusion Identifiable patient-specific characteristics associated with medication nonadherence can be screened for during thoracic transplant evaluation. Interventions aimed at improving these factors during the pre-transplant period may improve clinical post-transplant outcomes, however, larger studies are needed to validate these findings.

Abstract Background Lumbar puncture is a routinely performed procedure, yet it presents significant challenges in patients with abnormal spinal anatomy, such as severe scoliosis or obesity. Conventional ultrasound-assisted neuraxial techniques, while superior to landmark-based methods, are constrained by two fundamental limitations: inaccurate projection of the probe’s geometric center onto the skin when the probe is tilted or rocked, and the difficulty of consistently replicating the exact probe angle during needle insertion. These limitations contribute to multiple needle passes, prolonged procedure time, and increased patient discomfort and complication risk. To address these issues, we developed a novel angle-free ultrasound-assisted technique designed to eliminate the need for replicating probe angulation during needle insertion. Case presentation: This angle-free approach was utilized for serial lumbar punctures in two patients with spinal muscular atrophy requiring repeated intrathecal nusinersen administration. Both patients presented with extreme anatomical complexity, including high body mass index (30 and 35.1 kg/m²) and severe scoliosis (Cobb angles 90° and 83°). The technique follows a three-step protocol: (1) Preprocedural imaging to select the optimal interlaminar space; (2) Ultrasound-guided postural adjustment until the probe could be held perpendicular to the bed edge and parallel to the floor while maintaining target visualization; (3) Needle insertion along this orthogonal trajectory. All 22 procedures (11 per patient) were completed successfully without persistent neurological complications. Procedural outcomes demonstrated a first-attempt success rate of 81.8% (Case 1) and 100% (Case 2), with first-pass success rates of 45.5% and 54.5%, respectively. Longitudinal analysis across sequential procedures revealed a consistent reduction in both the number of needle passes and needling time, reflecting a favorable learning curve. Conclusions The angle-free ultrasound-assisted neuraxial technique offers a valuable alternative for patients with complex spinal anatomy. By using real-time postural adjustments to achieve a needle trajectory, it enhances procedural precision and eliminates the technical hurdle of replicating probe angulation. The structured "4P" framework (Planning, Positioning, Perpendicular, Parallel) offers a practical guide for clinical adoption. The observed learning curve suggests that clinicians can readily acquire and apply this technique to manage such challenging cases.

Abstract Asthma in the elderly (AIE) represents a unique challenge, necessitating better understanding of the mechanisms that drive airway hyperreactivity and remodeling (thickened, fibrotic airways). Normal aging is associated with increased lung stiffness, and thus the influence of mechanical forces on bronchial airways (breathing, sighs, CPAP) likely changes, potentially increasing with AIE and resultant remodeling, overall highlighting the need to understand the importance of mechanobiology in aging and AIE. Here, mechanosensitive Piezo (Pz) channels are highly expressed in the lung, including within airway epithelium and smooth muscle (ASM) but their specific roles particularly with aging remain largely unexplored. In this study, we used human ASM cells from young vs. old (≥65 y) non-asthmatics vs asthmatics to test the hypothesis that normal aging blunts Pz expression and functionality at baseline as well as in response to mechanical stretch, whereas asthma, particularly, AIE ASM leads to enhanced Pz expression promoting fibrosis and remodeling. Both Pz1 and Pz2 were expressed in ASM and increased in AIE. Oscillatory mechanical stretch mimicking breathing with superimposed static stretch increased Pz, especially in AIE: effects exacerbated by Pz activator Yoda1 and blunted by Pz inhibitor GsMTx4. Stretch or Yoda1 increased Wnt3a, β-catenin and GSK3β activation particularly in AIE, while ASM proliferation and extracellular matrix production remained preserved or even heightened in elderly ASM. Conversely, Pz1 inhibition by GsMTx4 potently reduced ECM deposition, particularly in AIE cells, highlighting Pz1's pivotal role in modulating ECM deposition. Overall, our findings indicate Pz1 as a mechanosensitive regulator of airway remodeling in AIE.

Invasive lobular breast carcinoma (ILC), the most common special histological subtype of breast cancer, is characterized by nearly universal expression of estrogen receptor alpha (ER) and unique sites of metastases, neither of which is fully recapitulated by genetically engineered mouse models. Using reporter-labeled ILC mouse xenografts, herein we used mammary fat pad, tail vein and intracardiac orthotopic growth to analyze spontaneous and experimental metastasis and gene expression. We observed ER-positive primary tumors with single-file histology and collagen deposition, and spontaneous metastasis from the mammary fat pad to bones, ovaries, and brain including the leptomeninges, thereby closely mirroring the growth and metastatic spread of human ILC. Brain metastases showed strong ER staining, confirmed by sequencing analyses which identified estrogen signaling as top activated pathway, and the lesions exhibited robust response to endocrine therapy. In summary, we report endocrine responsive mammary fat pad, tail vein and intracardiac xenografts that faithfully demonstrate unique ILC features and can serve as invaluable pre-clinical translational platforms for validating candidate ILC genetic drivers and testing novel therapeutics.

BACKGROUND: The National Cancer Database (NCDB) captures 73.7% of newly diagnosed cancers in the USs and underpins thousands of outcomes studies informing oncologic practice. To remain relevant amid rapid therapeutic and policy changes, the NCDB has undergone substantial structural and variable-level revisions. We characterized major updates during the past decade and their implications for research. STUDY DESIGN: We performed a narrative review of annual NCDB data dictionary revisions, American College of Surgeons bulletins, and internal program updates in collaboration with NCDB leadership. Structural modifications, variable additions, and policy changes affecting data capture, follow-up, staging, and accessibility were systematically summarized. RESULTS: The NCDB now includes data from 1,413 Commission on Cancer–accredited hospitals and more than 55 million records. Since 2020, the Rapid Cancer Reporting System enables near–real-time monthly submissions. Embargo periods were reduced from 5 to 3 years for survival data and 2 years for other variables, increasing analytic timeliness. Follow-up was limited to 15 years beginning January 1, 2022. Variable refinements include continuous tumor size in millimeters (since 2016), separation of tumor grade into clinical, pathologic, and posttherapy fields (since 2018), phased radiation treatment reporting (since 2018), and American Joint Committee on Cancer eighth edition staging implementation in January 2018 with nineth edition rollout ongoing. New data elements include Medicaid expansion status (2020), COVID-19 variables (2020 to 2021; 12.4% reduction in cases in 2020), smoking status (2023), and planned programmed death-ligand 1 reporting for non–small cell lung cancer beginning in 2025. CONCLUSIONS: The NCDB has evolved toward more granular, contemporary, and policy-relevant data capture while maintaining broad national coverage. Investigators must account for staging transitions, variable maturation, follow-up limits, and registry-specific biases to ensure valid interpretation of NCDB-based research.

Failed pediatric endotracheal intubation, prompting surgical airway management via emergency front of neck access (eFONA), is an intrinsically challenging topic. While rare, all emergency airway providers must be equipped to handle these complex clinical scenarios, both through initial training and maintenance of competency. Needle cricothyrotomy is a commonly taught method in cannot intubate cannot oxygenate (CICO) scenarios for children under age eight. However, needle cricothyrotomy is technically difficult, profoundly rare, and maintaining competency is a challenge. From a multidisciplinary perspective, we examine the utility of continuing to teach needle cricothyrotomy and explore alternatives. This project group suggests that pediatric eFONA training across disciplines should focus on surgical tracheotomy rather than needle cricothyrotomy, with consideration given to specialty-specific human performance factors.