Citations

ABSTRACT Aims This study aimed to describe how emergency nurses (ENs) experience secondary traumatic stress (STS) within their practice environments, focusing on the strategies they use to cope and the supportive resources they draw upon to manage its impact on their lives. Design This paper presents the qualitative findings from a larger mixed‐methods survey study on STS among ENs. Methods A geographically diverse U.S. sample of ENs was recruited through social media to participate in an online survey. All participants ( n = 275) were asked to respond to open‐ended survey questions, and 118 of these participants provided answers to at least one open‐ended question. A self‐selected sample of 20 ENs completed semi‐structured interviews. Inductive content analysis was used to analyse open‐ended survey responses and interview transcripts. Results Three themes reflected ENs' experiences with STS: STS Is Real—It's Going to Affect Your Life; Something Must Be Wrong With Me: A Culture of Disconnection; and It's a Systems Issue, but We're in It Together. Participants described individual, unit, and organizational factors that influenced their experiences of STS and their access to and use of coping strategies and supportive resources. Conclusion ENs and nurse leaders acknowledged the impact of STS on their personal and professional lives and emphasized how the practice environment shaped their experiences. They perceived the accessibility of organizational resources, leadership behaviours, and team culture as influencing the individual strategies ENs use to manage the effects of repeated exposure to others' traumatic experiences. STS is a predictable occupational hazard for ENs; thus, healthcare organizations must invest in nurse‐identified supports to preserve workforce well‐being and clinical expertise. Implications for the Profession Assessing organizational readiness to address STS is recommended to ensure ENs receive effective, timely support. In response to these assessments, healthcare organizations should develop and implement policies that prioritize the mental health and well‐being of ENs, including proactive support systems and accessible mental health resources. Impact This study identifies participant‐perceived individual, team, leadership, and organizational conditions that may hinder or support ENs' management of STS. These findings identify potential targets for organizational assessment and support strategies intended to foster healthier practice environments and promote safe, high‐quality care. Reporting Method Consolidated Criteria for Reporting Qualitative Research (COREQ). Patient or Public Contribution This study did not include patient or public involvement in its design, conduct, or reporting.

Abstract The paradigm in the field of oncolytic virotherapy proposes that tumor cell killing by an oncolytic virus (OV) culminates in the priming of antitumor CD8+ T cells. However, this ignores the impact a highly immunodominant antiviral response against the OV has on the subdominant antitumor response, particularly with regard to the naturally low affinity of tumor antigens to their cognate T-cell receptors. To investigate this experimentally, we first studied the interaction between the two responses in B16 and MC38 tumor models, both expressing ovalbumin (OVA). Contrary to the accepted paradigm, the inflammatory vesicular stomatitis virus (VSV) failed to expand OVA-specific T cells in vivo unless armed with tumor-associated antigen (TAA). In fact, treatment with the control VSV led to the ablation of antitumor T cells and a shift toward dysfunction as determined by the upregulation of markers, including LAG3 and CD39, correlating with lower rates of survival. Combination with anti–PD-1 immune checkpoint blockade therapy significantly improved survival only when VSV expressed TAA. VSV-expressing altered peptide ligand variants of tumor antigens, which evade mechanisms of central tolerance, expanded near self-antigen–specific T cells with the ability to cross-react with tolerized tumor antigens, thus providing an antitumor effector population capable of proliferating in the presence of a potent antiviral response. Taken together, these findings offer a rational approach to OV design which preserves acute antitumor therapy provided by antiviral innate and T-cell responses while promoting the induction of tumor-specific T cells. Significance: Oncolytic viruses can induce an antiviral T-cell response that occludes an antitumor response, challenging the paradigm in the field and elucidating strategies to optimize the efficacy of oncolytic viroimmunotherapy.

Introduction: Laryngopharyngeal symptoms (LPS) refer to aerodigestive complaints that may result from the retrograde flow of gastric contents into the upper aerodigestive tract. These symptoms may be under-recognised in populations exposed to mechanical or environmental stressors. Divers may be at increased risk due to factors such as pressure changes and body positioning. This study characterised the prevalence and severity of LPS among divers and identified associated risk factors. Methods: A cross-sectional, anonymous survey was distributed to members of the Divers Alert Network (DAN). Collected data included demographics, diving-related behaviours, medical history, and LPS burden measured using the Reflux Symptom Index (RSI). Results: Of the 309 survey responses analysed, 47.2% were male with a median age of 50.0 years (IQR: 40.0−60.0). Among 291 divers with complete RSI data, 26.1% (95% CI, 21.4–31.5%) had abnormal RSI scores, representing a +16.0 percentage-point increase (95% CI, 11.3%−21.4%) over non-diving population estimates (P < 0.001). In multivariable analysis, female sex (adjusted prevalence rate [aPR] 1.59, 95% CI 1.07–2.37) and gastroesophageal reflux disease (GERD) history (aPR 1.75, 95% CI 1.16–2.65) were independent predictors. Recreational divers had a lower risk (aPR 0.59, 95% CI 0.39–0.90). Approximately 5% of respondents described their symptoms as life-threatening. Conclusions: Divers may represent an under-recognised population at elevated risk for LPS. Female sex and GERD history were associated with greater symptom burden, while recreational diving appeared less provocative compared to technical diving. These findings may have implications for risk stratification and symptom management in the diving community.

PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

Abstract. Introduction: Preterm birth drives adverse perinatal maternal and infant health outcomes through heterogeneous symptoms, severity, and etiologies. Delivery prior to reaching 37 weeks of gestation may result from medically indicated intervention for pregnancy complications or spontaneously in the absence of prior symptoms. Placental tissue collected following preterm birth exhibits differential DNA methylation compared to full-term placentas and may indicate pregnancy health during gestation. Placental DNA currently has limited utility for assessing health of ongoing pregnancy, as sampling placental tissue during gestation increases the risk of infection and miscarriage. Risks associated with placental sampling during pregnancy limit the use of DNA methylation in clinical preterm birth prediction. Assessing preterm birth risk during gestation requires non-invasive methods for characterizing placental DNA methylation. Results: We quantified genome-wide DNA methylation patterns of hypermethylated cell-free DNA in pregnant (n = 99) and non-pregnant (n = 93) plasma using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq). In each sample, we assessed DNA methylation status in 300-bp genomic windows, examining both sequencing read counts and calculated absolute molar DNA amount. Known hypermethylated placental regions, including RASSF1, STAT5A, and ERG promoters showed significantly increased odds of detection in pregnant samples, suggesting enrichment of cell-free placental DNA. Of the 536,444 300-bp windows examined, 173,071 (32%) showed significant enrichment in pregnant plasma. Linear modeling identified 107,505 differentially methylated regions (DMRs) associated with pregnancies later diagnosed with intrauterine growth restriction (IUGR) (n = 22). Alu elements showed increased representation in these DMRs than expected, while other repetitive elements exhibited underrepresentation. Discussion: These results demonstrate cfMeDIP-seq's ability to enrich for cell-free placental DNA and characterize cell-free DNA methylation signatures of pregnancies complicated by IUGR. Enrichment of cell-free placental DNA enables non-invasive profiling of placental DNA methylation from maternal plasma. Detectable epigenetic signatures in maternal plasma may identify pregnancies at elevated risk for preterm birth before clinical symptoms appear. Our findings further highlight the potential of cell-free placental DNA for monitoring pregnancy health.

Abstract Objective To evaluate the connection between symptom burden and sexual quality of life in women with idiopathic subglottic stenosis (iSGS). iSGS is a rare fibroinflammatory disorder involving progressive airway narrowing and respiratory distress. While the impact on physical functioning is well‐established, the influence of iSGS on sexual health, a key component of quality of life, remains unexplored. Study Design Anonymized cross‐sectional survey using validated questionnaires. Setting Online international iSGS support group (Living with Idiopathic Subglottic Stenosis). Methods The Dyspnea Index (DI), the Female Sexual Quality of Life (SQOL‐F) questionnaire, and the Medical Outcomes Health Survey (SF‐36) were distributed to an iSGS support group. Only complete responses were analyzed. Associations between DI and sexual quality of life were evaluated using correlation and linear regression. Median‐based symptom burden groupings were used for secondary descriptive comparisons. Results 682 completed all items in the assigned questionnaires and met inclusion criteria. DI scores were inversely correlated with SQOL‐F (Rho = −0.305, P < .001). SQOL‐F was consistently lower among those with high symptom burden across nearly all items; only partner communication showed no difference. Each one‐point increase in DI predicted a 0.61‐point decrease in SQOL‐F ( B = −0.609, P < .001). High‐burden patients also reported significantly lower SF‐36 Physical (PCS) and Mental (MCS) Component Scores. Conclusions Greater airway symptom burden in iSGS is associated with significantly diminished sexual and general health‐related quality of life. These findings reinforce a need for patient‐centered care that considers both physical and psychosocial well‐being.

Introduction Allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) entails prolonged recovery, serious complications, functional limitations, psychological distress, and extended isolation to prevent infection. During the peak of the COVID-19 pandemic, treatment disruptions, restricted caregiver access, and intensified isolation compounded these transplant-specific burdens. The longer-term influence of the pandemic experience on HCT recovery and survivorship remains poorly understood. Methods In this qualitative descriptive study, adults with AML who underwent allogeneic HCT from March through September 2020 participated in virtual semi-structured interviews from July 2022 through April 2023, approximately two years post-transplant. Participants were identified through the Center for International Blood and Marrow Transplant Research registry. Zoom or phone interviews were recorded, transcribed verbatim, and analyzed using inductive qualitative content analysis to describe survivorship experiences and opportunities to improve supportive care. Results A total of 25 AML survivors (ages 24-78, 56% male) were interviewed approximately two years post-transplant. Three themes were found: (1) Transplant is an arduous journey; (2) The COVID-19 pandemic shaped the transplant experience in complex and far-reaching ways; (3) Transplant demands sustained personal and relational investment throughout the transplant journey. Conclusions This study enhances our understanding of the stressors associated with transplantation during periods of heightened adversity, while also identifying opportunities to strengthen healthcare systems and supportive care services for this population. Situating these experiences within the context of a global health emergency offers a rare lens into how external stressors can exacerbate the already demanding nature of HCT survivorship. By understanding survivors’ experiences, healthcare systems can better anticipate and address the evolving needs of transplant survivors.

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.

Recent data suggest that sodium–glucose cotransporter 2 inhibitors have cardioprotective benefits. This effect may extend towards cardioprotection in cancer therapy-related cardiac dysfunction, with proposed mechanisms extending beyond glycemic control to include anti-inflammatory effects, oxidative stress reduction, and metabolic reprogramming. This review synthesizes potential mechanisms, observational data, and emerging trial evidence to support sodium–glucose cotransporter 2 inhibitors as a primary prevention strategy for cancer therapy-related cardiac dysfunction, particularly in anthracycline-exposed populations.

Importance Although adding immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes in high-risk early-stage breast cancer, opportunities remain to further enhance response. Dual checkpoint blockade offers a potential strategy to further enhance efficacy. Objective To evaluate the combination of anti−programmed cell death 1 protein (PD-1) cemiplimab and anti−lymphocyte activation gene 3 (LAG-3) added to neoadjuvant therapy in ERBB2 -negative early-stage, high-risk breast cancer. Design, Setting, and Participants The I-SPY2 (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2) is an ongoing randomized clinical platform trial being conducted at multiple US clinical sites including patients with early-stage (II or III) ERBB2 -negative, high-risk breast cancer. Participants, continuously enrolled since 2010, were adaptively randomized from February 2, 2020, to December 9, 2021, to one of several experimental neoadjuvant therapies or control groups based on receptor subtypes defined by hormone receptor (HR), ERBB2 status, and MammaPrint (Agendia Inc) molecular risk, categorized as high (MP1) or ultrahigh (MP2). Data were analyzed from January 1, 2022, to August 5, 2025. Interventions Both groups received weekly paclitaxel for 12 weeks, then doxorubicin and cyclophosphamide followed by surgery; concomitant with paclitaxel, the intervention group also received 4 doses of cemiplimab and fianlimab (PCF) every 3 weeks. Main Outcomes and Measures Pathologic complete response (pCR). Treatments graduated when they achieved 85% bayesian probability of success in a subtype-specific phase 3 trial. Pathway-specific biomarkers were assessed for response prediction. Results A total of 78 participants (mean [SD] age, 47 [39-54] years) were randomized to the intervention group, with 350 participants (mean [SD] age, 48 [39-57] years) randomized to the historical control population. PCF graduated in all clinical signatures, with pCR rates vs control of 44% (95% CI, 34%-53%) vs 21% (95% CI, 17%-25%) in all ERBB2 , 53% (95% CI, 39%-67%) vs 29% (95% CI, 22%-36%) in triple-negative, and 36% (95% CI, 23%-49%) vs 14% (95% CI, 9%-19%) in HR-positive and ERBB2 -negative disease. Among the total participants, 16 (21%) experienced adrenal insufficiency, including hypophysitis (11% grade 3 or 4), mostly occurring after immunotherapy completion. PCF was found to be highly effective in the subset of patients with immune signature positive status (ImPrint positive). Conclusions and Relevance In this randomized clinical trial, the combination of PD-1 and anti−LAG-3 inhibition with standard NAC was effective in early-stage ERBB2 -negative breast cancer, particularly in patients displaying a positive ImPrint immune signature. These results warrant further definitive trials. Trial Registration ClinicalTrials.gov Identifier: NCT01042379