Womack Army Medical Center (WAMC) is a United States Army-run military hospital that is located on Fort Bragg near Fayetteville, North Carolina. The facility is named for Medal of Honor recipient Bryant H. Womack. It contains 138 beds with about 66,000 patients visiting the hospital's emergency department and a total of more than 11,000 patients are admitted yearly. Its physicians perform about 2,700 inpatient and 7,400 outpatient surgeries each year. The Medical Center serves more than 160,000 eligible beneficiaries in the region, the largest beneficiary population in the Army.
BACKGROUND:The interim analysis of the JUPITER-06 study reveals significantly longer progression-free survival (PFS) and overall survival (OS) in advanced esophageal squamous-cell carcinoma (ESCC) patients treated with toripalimab in combination with paclitaxel (Taxol) plus cisplatin (TP). Prior work proposed copy number alteration-corrected tumor mutational burden (ccTMB) and an esophageal cancer genome-based immuno-oncology classification (EGIC) scheme as prespecified biomarkers to predict treatment efficacy. Here, we present the final analysis of the JUPITER-06 study and further explore potential biomarkers associated with OS. PATIENTS AND METHODS:A total of 514 patients with treatment-naïve advanced ESCC were randomly assigned 1: 1 to receive toripalimab or placebo in combination with paclitaxel plus cisplatin every 3 weeks for up to six cycles, followed by toripalimab or placebo maintenance. The coprimary endpoints were OS and PFS assessed by blinded independent central review. Whole exome sequencing of 486 tumors enabled biomarker analyses. RESULT:As of 23 February 2023, toripalimab plus TP significantly improved OS versus placebo plus TP [17.7 months, 95% confidence interval (CI) 14.6-20.8 months versus 12.9 months, 95% CI 11.6-14.1 months; hazard ratio (HR) 0.72, 95% CI 0.58-0.88, P = 0.002). The 3-year OS rates were 29.7% and 19.9% in the two groups, respectively. Neither programmed death-ligand 1 (PD-L1) expression nor TMB significantly correlated with OS benefit. In contrast, prespecified biomarkers, ccTMB, and EGIC scheme robustly stratified patients with different long-term OS benefits from immunochemotherapy. Further exploratory analysis discovered that loss-of-function alterations in the SWI/SNF chromatin remodeling complex were associated with improved OS, whereas gain-of-function alterations in cell cycle and WNT signaling pathways correlated with reduced survival benefits. Importantly, CDK4/6 and PORCN inhibitors were identified as potential partners to overcome resistance and enhance the efficacy of immunochemotherapy. CONCLUSION:This final OS analysis of JUPITER-06 confirms the sustained survival benefit of toripalimab plus chemotherapy in advanced ESCC. ccTMB and EGIC enable consistently precise patient stratification, while pathway-specific vulnerabilities highlight actionable targets for exploratory combination strategies.
INTRODUCTION:Sacroiliac joint (SIJ) pain comprises up to 30% of cases of mechanical low back pain (LBP), the leading cause of disability worldwide. Despite sacral lateral branch cooled radiofrequency ablation (CRFA) showing efficacy in clinical trials, there is a lack of comparative-effectiveness long-term follow-up. METHODS:In this randomized, multicenter, comparative-effectiveness study, 210 patients with injection-confirmed SIJ pain who responded to prognostic lateral branch blocks were randomly assigned to receive CRFA of the L5 dorsal ramus and S1-S3/4 lateral branches or standard medical management (SMM) consisting of pharmacotherapy, physical therapy, injections, and integrative therapies. Patients were followed up at 1, 3, 6, 9, and 12 months, with participants reporting unsatisfactory SMM outcomes being allowed to crossover (XO) and receive CRFA at 3 months. The primary outcome measure was the mean change in average LBP score on a 0-10 Numeric Rating Scale (NRS), with secondary outcomes including measures of quality of life (QoL) and function. A responder was defined as a participant who experienced a ≥30% or ≥2-point decrease in average daily NRS pain score coupled with a score ≥5 out of 7 (moderately better) on the Patient Global Impression of Change scale. RESULTS:At 12 months, the mean NRS pain score declined from a baseline of 6.4±1.4 to 3.5±2.6, with 57.4% (35/61) of participants in the randomized CRFA cohort experiencing a ≥2-point or 30% decrease in average LBP from baseline. In the crossover cohort, 35/63 (55.6%) subjects had the same experience 12 months following the XO procedure; in the XO group, the mean LBP decreased from 6.1±1.5 to 3.4±2.5. Patients also experienced clinically meaningful improvements in QoL via EuroQoL-5D-5L at 12 months (mean change of +0.22±0.27 in the originally-treated CRFA group and +0.21±0.33 in the XO group). Oswestry Disability Index (ODI) scores also improved by 12.4%±14.7 (CRFA) and 13.7%±17.1 (XO) from baseline at study-end. No serious adverse events related to the CRFA procedure were reported. CONCLUSION:CRFA in patients with SIJ pain provided clinically significant and sustained improvements for 12 months following a single CRFA treatment, regardless of previous SMM treatment. TRIAL REGISTRATION NUMBER:NCT03601949.
INTRODUCTION:Musculoskeletal injuries may require specialty care to maximize return to duty (RTD) for active-duty service members (ADSM). An Investigator General's report revealed specialty care shortages may challenge RTD in ADSM. About half of US military bases reside in federally designated healthcare deserts. This study examines how extremity fractures sustained within healthcare deserts affect rehabilitation, impacting readiness and retention. MATERIALS AND METHODS:This retrospective observational study analyzed de-identified data from the Medical Assessment and Readiness System (MARS). We identified ADSM with fractures, mapped military installations against healthcare deserts, and compared outcomes against rehabilitation services utilization. We assessed the impact of social and community factors, including the social deprivation index (SDI), on fitness outcomes, including physical fitness scores (Army Physical Fitness Test [APFT]), using survival analysis. Key metrics included time to treatment appointments and retention outcomes. RESULTS:From 2011 to 2021, 138,649 ADSM experienced fractures (10.8%). Three-quarters received physical therapy (PT) within 6 months of diagnosis. Among those, 12,828 (9.3%) failed their postinjury APFT. Postfracture APFT failure risk increased nearly 15% when time to first PT session exceeded 3 months (4-6 months: AHR = 1.18; 95% CI: 1.09-1.27; P < .001). Increased clinic SDI associated with a slight increase failure risk (Clinic SDI 26-50: AHR = 1.04; 95% CI: 1.00-1.09; P = .047). However, high clinic SDI unexpectedly correlated with decreased APFT failure (Clinic SDI 76-100: AHR = 0.87; 95% CI: 0.77-0.98; P = .024). Highest APFT failure risk occurred after wrist or hand fractures (AHR = 1.30; P < .001). Demographic risk factors included female sex, younger age, lower rank, non-White race, and higher BMI. CONCLUSIONS:Delayed PT increased postfracture APFT failure risk. Concomitant stress fractures correlated with increased postinjury APFT failure, as did fracture occurrence in low-income locations. Early access to rehabilitation was associated with approximately 30% decreased risk of postfracture APFT failure. Treatment effects estimates demonstrated that PT/rehabilitation services afforded 11 months of additional active service time postinjury.
When critical illness is further complicated by severe respiratory failure, such as in cases of acute respiratory distress syndrome (ARDS) requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), patients may be at an even greater risk for nutritional deficits, immobility, and persistent metabolic stress. Although highly efficacious for cardiopulmonary failure, VV-ECMO introduces the potential for additional metabolic complexities, including altered thermoregulation, increased inflammatory burden, and, traditionally, impaired physical activity from increased lengths of intensive care unit (ICU) stays and prolonged periods of bedrest. Emerging data suggest that comprehensive metabolic and rehabilitative strategies can attenuate muscle loss, reduce ICU-acquired weakness, and improve post-discharge outcomes. This narrative review will discuss the metabolic demands faced by VV-ECMO patients and current strategies to address them. We characterize the catabolic state during VV-ECMO while highlighting the metabolic demand placed on patients. We then examine nutritional support on VV-ECMO, including the assessment of energy expenditure and its limitations, optimal calorie-protein requirements, timing and route of nutritional support, and outcomes associated with nutritional adequacy based on current evidence and guidelines. Next, we explore the potential of pharmacologic agents to possibly reduce hypermetabolism and reverse catabolism. Finally, we discuss the role of physical rehabilitation in VV-ECMO patients by focusing on physical therapy, mobilization, and strategies such as awake ECMO to facilitate activity. Throughout this review, we integrate findings from recent studies and guidelines, with the goal of providing a comprehensive narrative of how to support the metabolic needs of critically ill patients on VV-ECMO.
Introduction Intimate partner violence (IPV) is an important public health concern among military-connected populations, but help-seeking, disclosure, and safety planning may be shaped by military-specific factors, including command structure, relocation, housing dependence, and privacy concerns. This exploratory study described self-reported IPV experiences, resource awareness, and perceptions of a hypothetical military-specific decision-making and safety-planning smartphone application among women recruited from a primary care medical clinic at Fort Bragg, North Carolina. Materials and Methods Using a single-site convenience sample, 18 female service members and civilians completed a 106-item online survey adapted from selected National Intimate Partner and Sexual Violence Survey domains and supplemented with study-specific questions. Analyses were descriptive only. The study was not designed to estimate population prevalence, compare subgroups, evaluate app effectiveness, or assess implementation feasibility. Results Within this small clinical sample, 9 of 18 participants reported IPV-related experiences during the previous 24 months. Emotional abuse and coercive control were the most commonly reported experiences. Reported health and social concerns included difficulty sleeping, chronic pain, financial stress, and resource needs related to housing, legal, community, and advocacy services. Awareness and prior use of IPV-related apps were low; however, 13 of 17 respondents expressed interest in a confidential, military-relevant IPV prevention or safety-support app. Conclusion These findings should be interpreted as descriptive and hypothesis-generating. They suggest low awareness of existing digital IPV resources and preliminary interest in a military-specific safety-support tool within this small convenience sample. Larger studies are needed to evaluate recruitment feasibility, acceptability, sustained use, safety, help-seeking outcomes, and implementation considerations in military-connected populations.
