Citations

Abstract Purpose: The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings. Experimental Design: In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types. Results: Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P < 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44–0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity. Conclusions: Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.

In this review, we discuss the risks and adverse effects reported for the current Food and Drug Association (FDA)-approved biologics used in the management of asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, and tezepelumab. Our review focuses on the risk of hypersensitivity reactions, infection, and malignancy. Where relevant, we have included information regarding the risk of cardiovascular disease and eosinophilia, and we have included specific information regarding vaccine use among patients receiving the above biologics. We also review currently available data regarding the use of biologics in the context of pregnancy. Our goal is to provide a comprehensive resource for providers utilizing these agents, so that they may adequately counsel patients about the risks of therapy and identify adverse events if they occur.

INTRODUCTION: Evidence-based recommendations for sexual practices regarding anoreceptive intercourse (ARI) do not exist in patients with inflammatory bowel diseases undergoing restorative proctocolectomy with ileal pouch anal anastomosis (IPAA). This study surveys providers on perspectives and attitudes related to sexual practices after IPAA. METHODS: We developed a 23-item survey and distributed it to providers caring for patients with inflammatory bowel diseases. RESULTS: 95% of providers believe that it is important to discuss sexual orientation or practices before IPAA, but only 27% routinely discuss this. 50% did not feel comfortable and 74% did not feel confident discussing ARI recommendations with patients who underwent or will undergo IPAA. DISCUSSION: Future interventions should aim to standardize recommendations regarding feasibility and time line to safe ARI after IPAA.

INTRODUCTION: Immune-modifying therapies in pediatric inflammatory bowel disease (IBD) increase infection risks, including varicella. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, a nationwide US commercial insurance claims database (2007–2022), we conducted a retrospective study of 5,368 patients with IBD aged 21 years or younger matched to a non-IBD cohort. The primary outcome was incidence of varicella. RESULTS: Varicella incidence was low in both groups (IBD: 0.570 vs non-IBD: 0.297 per 1,000 person-years, P = 0.23). At year 4, cumulative varicella incidence was 0.27% for IBD and 0.18% for non-IBD ( P = 0.24). No hospitalizations or deaths occurred. DISCUSSION: Despite immune-modifying therapy, pediatric patients with IBD demonstrate low varicella incidence.

Music is one nonpharmacological intervention to reduce anxiety and stress for mechanically ventilated patients. Efficient delivery of a music listening intervention can be enhanced through digital tools such as a mobile application (app) loaded onto an electronic tablet device. The objective of this study is to describe the iterative development and deployment of a novel app (Soundese) to deliver, record, and retrieve data associated with a two-arm randomized, blinded clinical trial testing music listening intervention compared to control silence condition on delirium severity among critically ill intensive care unit (ICU) older adult patients receiving mechanical ventilatory support. The Soundese mobile app was developed to deliver either experimental music listening intervention or a silence control listening condition to a sample of older adults receiving mechanical ventilatory support in the ICU and retrieve all protocol data. The Soundese app was developed using the Swift software language and is compatible with all iOS devices. The Soundese app consists of two components: (1) a mobile app that delivers the assigned, blinded listening intervention from an iPad through headphones to each subject and automatically logs each listening session, its duration, the randomization arm, and uploads these data to a server, and (2) an analysis app that generates a spreadsheet with summarized data of the respective listening session, music details, and reports for further analyses. A Dropbox application programmer interface enabled the secure storage of files on a designated Dropbox account. After initial field testing and iterative development changes based on research staff feedback, the Soundese app delivers the assigned experimental listening condition or silence control condition when deployed remotely in the field. The app’s mobile nature allows for immediate and automatic data capture, which is summarized for statistical analysis. There is no need for any manual recording of any intervention data by busy ICU staff, including listening time or music selections. The Soundese mobile app efficiently delivers the research protocol with fidelity and collects the necessary data for an ICU-based clinical trial. The app may be useful in other clinical trials testing music listening interventions in various settings or for deploying other audio-based interventions.

Abstract Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdcscid Il2rgtm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+ peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh- like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.

ABSTRACTBackground and AimsWe aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti‐TNF therapy.MethodsWe included patients treated with their first anti‐TNF therapy for PFCD after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centres. Our exposure was one or more setons at the time of anti‐TNF therapy. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalisation, or faecal diversion for PFCD, and our secondary outcome was fistula remission defined clinically. We used 1:1 cardinality matching and propensity score weighting to control for fistula severity based on centrally read MRIs, luminal characteristics, and concomitant therapies.ResultsOur analysis included 221 patients: 81 with setons and 140 without setons. After cardinality matching, our cohorts were balanced (standardised difference < 0.1 for all covariates). Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons. Our results remained stable when analysed by propensity score weighting and in a sensitivity analysis of patients who underwent an exam under anaesthesia. In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons.ConclusionsIn this multicentre, setons were not associated with improved fistula outcomes. Future prospective controlled studies are warranted.

Background: Patients who experience homelessness manifest poor cancer outcomes, often because of treatment delays. Few studies have used mixed methods to learn what happens at the patient and health care staff level to explain these delays. Methods: This single-institution, multi-site study interrogated the entire medical record system (thousands of patients annually) for homelessness and cancer diagnoses from January 1, 2019, through October 10, 2023. Records were abstracted for relevant quantitative and qualitative data; rigorous methods were used to analyze, integrate, and report findings. Results: Forty-three patients with a median age of 58 years (range: 32, 73 years) and 34 (79%) assigned male sex at birth are the focus of this report. The most common cancers include hematologic (n = 8), gastrointestinal (n = 8), and genitourinary (n = 8). Thirty-five patients (81%) initiated cancer therapy, and 27 (63%) manifested treatment delay (>4 weeks post-diagnosis). The median time to cancer therapy was 9 weeks (95% confidence interval: 4.6, 12 weeks). Qualitative themes that explain delays are as follows: (1) logistical challenges in communication between the patient and health care team (“lack of a cell phone”); (2) patient reluctance to receive care (“patient elected to leave Against Medical Advice”); and (3) medical challenges in providing care (“he was hospitalized after being found down and hypotensive”). Conclusions: This study confirms that initiation of cancer therapy is often delayed in patients who experience homelessness. It sheds light on reasons for delay – for example, lack of phone access, an observation which suggests that perhaps provision of a burner phone might help some patients.

Abstract Context Research and scholarship are core drivers of medicine in the modern era. Evidence-based practice continues to replace expert opinion and long-held practice beliefs. Involvement in the development and writing of these guidelines is critical for Doctors of Osteopathic Medicine (DOs) to maintain a seat at the academic table. According to the American Osteopathic Association (AOA), 11 % of practicing physicians in the US are DOs. This number is growing, as nearly 25 % of current medical students attend an osteopathic medical school. Without involvement in guideline development, DOs risk giving up control of their own practice of medicine. Objectives To quantify the contribution of DOs to the body of literature guiding practice, author information was extracted from all US-based guidelines published in the years 2021, 2022, and 2023 listed in the Emergency Care Research Institute (ECRI) Guidelines Trust database. Methods Authors of US-based guidelines listed in the ECRI Trust database from the years 2021–2023 were counted and categorized into one of three groups based on terminal degree: MD holders, DO holders, and Other-degree holders. Authors whose degrees could not be identified were counted as “Unidentifiable.” Additional data including sponsoring organization, organization type, and specialty were collected. Results A total of 674 guidelines were published by US organizations in 2021, 2022, and 2023, with 604 reporting author information. A total of 9,376 authors were counted. Of that, 7,253 held an MD (77 %), 110 held a DO (1.2 %), and 1,848 held another terminal degree (19.7 %); meanwhile, 1.66 % of counted authors did not have an identifiable degree. A total of 604 guidelines published by US organizations were identified. Of these, 88 (14.6 %) contained at least one DO author in their author list. Sixty-two unique specialties were identified, along with 130 unique sponsoring organizations. Of those specialties, 28 (44.4 %) had at least one DO author of at least one guideline. Of 130 sponsoring organizations, 44 (33.8 %) developed at least one guideline with at least one DO author. No osteopathic sponsoring organizations were identified. Conclusions Based on these results, we conclude that DOs are underrepresented in the development of guidelines.