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Abstract Purpose Targeted therapy development in soft tissue sarcoma (STS) has been burdened by the heterogeneity of this group of rare tumors. B7 homolog 3 protein (B7-H3) is a molecule in the same family as programmed death-ligand 1 (PD-L1). It has limited expression in noncancerous tissues and is overexpressed in many cancers, making it an attractive target for cancer therapy, and clinical trials targeting B7-H3 are actively underway. While available data demonstrate high expression levels of B7-H3 in individual sarcoma subtypes, its expression patterns across STS subtypes are not well described. The purpose of this study was to characterize the expression patterns of B7-H3 in STS. Patients and methods This retrospective analysis evaluated STS tumor specimens from patients with a variety of different subtypes. Specimens were evaluated by immunohistochemistry (IHC) for expression and staining pattern of B7-H3 both in tumors and in associated vasculature. Results Specimens from 153 sarcoma patients included 15 different STS subtypes. B7-H3 was broadly expressed in 97% of samples (95% CI 0.93–0.99) and 69.2% demonstrated high levels of B7-H3 expression (95% CI 0.61–0.76). No significant association between B7-H3 positivity or expression level and prior treatment(s), tumor size, tumor grade, or patient age. B7-H3 positivity in vessels was found in 94.7% (145/153) of samples. In tumors that had been previously assessed for PD-L1 and PD-1, there was no correlation between B7-H3 positivity or expression and the positivity or expression level of PD-L1 or PD-1. Conclusion These data show high levels of B7-H3 positivity across soft tissue sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate whether targeting B7-H3 can provide clinical benefit to help patients with sarcoma.

ObjectiveTo assess the magnitude of racial-ethnic disparities in pandemic-related social stressors and examine frontline work's moderating relationship on these stressors.Data sourcesEmployed Californians' responses to the Institute for Governmental Studies (IGS) poll from April 16-20, 2020, were analyzed. The Pandemic Stressor Scale (PSS) assessed the extent to which respondents experienced or anticipated problems resulting from the inability to pay for basic necessities, job instability, lacking paid sick leave, unavailability of childcare, and reduced wages or work hours due to COVID-19.Study designMixed-effects generalized linear models estimated (1) racial-ethnic disparities in pandemic stressors among workers during the first COVID-19 surge, adjusting for covariates, and (2) tested the interaction between race-ethnicity and frontline worker status, which includes a subset of essential workers who must perform their job on-site, to assess differential associations of frontline work by race-ethnicity.Data collectionThe IGS poll data from employed workers (n = 4795) were linked to the 2018 Centers for Disease Control and Prevention Social Vulnerability Index at the zip code level (N = 1068).Principal findingsThe average PSS score was 37.34 (SD = 30.49). Whites had the lowest PSS score (29.88, SD = 26.52), and Latinxs had the highest (50.74, SD = 32.61). In adjusted analyses, Black frontline workers reported more pandemic-related stressors than White frontline workers (PSS = 47.73 vs. 36.96, p

Background Hypertension affects nearly half of US adults yet remains inadequately controlled in over three‐quarters of these cases. This study aimed to assess the association between adherence to antihypertensive medications and total medical costs, health care use, and productivity‐related outcomes. Methods and Results We conducted cross‐sectional analyses using MarketScan databases, which included individuals aged 18 to 64 years with noncapitated health insurance plans in 2019. Adherence was defined as ≥80% medication possession ratio for prescribed antihypertensive medications. We used a generalized linear model to estimate total medical costs, a negative binomial model to estimate health care use (emergency department visits and inpatient admissions), an exponential hurdle model to estimate productivity‐related outcomes (number of sick absences, short‐term disability, long‐term disability), and a 2‐part model to estimate productivity‐related costs in 2019 US dollars. All models were adjusted for age, sex, urbanicity, census region, and comorbidities. We reported average marginal effects for outcomes related to antihypertensive medication adherence. Among 379 503 individuals with hypertension in 2019, 54.4% adhered to antihypertensives. Per person, antihypertensive medication adherence was associated with $1441 lower total medical costs, $11 lower sick absence costs, $291 lower short‐term disability costs, and $69 lower long‐term disability costs. Per 1000 individuals, medication adherence was associated with lower health care use, including 200 fewer emergency department visits and 90 fewer inpatient admissions, and productivity‐related outcomes, including 20 fewer sick absence days and 442 fewer short‐term disability days. Conclusions Adherence to antihypertensives was consistently associated with lower total medical costs, reduced health care use, and improved productivity‐related outcomes.

IntroductionThis research investigates what might motivate tech companies and impact-driven investors to adopt a health-promoting strategy in their product development and capital allocation strategies.MethodsParticipants were recruited for semi-structured interviews through purposive and snowball sampling. From 83 outreach attempts, thematic saturation required 19 completed interviews out of the 46 consumer technology executives and impact-focused investors who responded. Interviews were analyzed using grounded theory-based content analysis.ResultsSeven coding categories resulted from inductive coding, with 83 sub-codes. The primary themes were: product-based health impact is magnified when matched to user demographics (making an equity mindset important); stakeholders are eager for reliable health metrics, especially those that hold across industry verticals; when capturing health impact, it is critical to include positive (i.e., economically beneficial) externalities. These results allowed for the creation of a logic model with a recommended theory of change for the private sector to develop health strategy.DiscussionIntentional integration of impact strategy with business priorities will allow teams to design products that promote health, driving buy-in and resource allocation while attracting investment and double returns. For policymakers, it is clear that tech policy and regulation for corporate reporting need to keep pace. These findings are limited by the purposive recruitment of participants, introducing potential bias and risk to generalizability.

Abstract Background Although well-known for their thromboresistance, bileaflet mechanical heart valves (BMHV) require lifelong anti-thrombotic therapy. This must be associated with a certain level of thrombogenicity. Since both thromboresistance and thrombogenicity are explained by the blood-artificial surface or liquid-solid interactions, the aim of the present study was to explore BMHV thromboresistance from new perspectives. The wettability of BMHV pyrolytic carbon (PyC) occluders was investigated in under-liquid conditions. The submerged BMHV wettability clarifies the mechanisms involved in the thromboresistance. Methods The PyC occluders of a SJM Regent™ BMHV were previously laser irradiated, to create a surface hierarchical nano-texture, featuring three nano-configurations. Additionally, four PyC occluders of standard BMHV (Carbomedics, SJM Regent™, Bicarbon™, On-X®), were investigated. All occluders were evaluated in under-liquid configuration, with silicon oil used as the working droplet, while water, simulating blood, was used as the surrounding liquid. The under-liquid droplet-substrate wetting interactions were analyzed using contact angle goniometry. Results All the standard occluders showed very low contact angle, reflecting a pronounced affinity for non-polar molecules. No receding of the contact line could be observed for the untreated occluders. The smallest static contact angle of around 61° could be observed for On-X® valve (the only valve made of full PyC). The laser-treated occluders strongly repelled oil in underwater conditions. A drastic change in their wetting behaviour was observed depending on the surrounding fluid, displaying a hydrophobic behaviour in the presence of air (as the surrounding medium), and showing instead a hydrophilic nature, when surrounded by water. Conclusions BMHV “fear” water and blood. The intrinsic affinity of BMHV for nonpolar fluids can be translated into a tendency to repel polar fluids, such as water and blood. The blood-artificial surface interaction in BMHV is minimized. The contact between blood and BMHV surface is drastically reduced by polar-nonpolar Van der Waals forces. The “hydro/bloodphobia” of BMHV is intrinsically related to their chemical composition and their surface energy, thus their material: PyC indeed. Pertaining to thromboresistance, the surface roughness does not play a significant role. Instead, the thromboresistance of BMHV lies in molecular interactions. BMHV wettability can be tuned by altering the surface interface, by means of nanotechnology.

Abstract Background Play Streets, which are community-based environmental initiatives where public spaces/streets are temporarily closed to create safe, low-cost physical activity opportunities, have demonstrated feasibility and physical activity benefit in rural US areas. Yet, information is needed to identify implementation characteristics that may promote sustainability. This study examined rural Play Streets implementation characteristics that could impact sustainability from local partners’ perspectives. Methods Sixteen Play Streets implementation team members in rural Maryland, North Carolina, Oklahoma, and Texas, USA, participated in interviews. Semi-structured in-person individual and group interviews were conducted in the fall of 2018 (after Play Streets implementation in 2017 and 2018), recorded, and transcribed verbatim. Transcripts were analyzed using iterative, content analyses. Coding frameworks were based on the Public Health Program Capacity for Sustainability Framework, and emergent themes were also identified. Results Interviewees’ perceived characteristics for facilitating Play Streets implementation aligned with the Public Health Program Capacity for Sustainability Framework: funding stability, political support, partnerships, organizational capacity, program adaption, and communication. Interviewees also noted the importance of cultural alignment/support and the reciprocal impact of community connectedness/engagement. Conclusions Future research should examine the reciprocal role of public health impacts, as both outcomes and factors which may influence sustainability.

Introduction: Heart disease poses a significant health and economic burden in the U.S., with considerable variations in outcomes across different racial and ethnic groups. The COVID-19 pandemic has further highlighted the disparities in healthcare utilization and costs associated with heart disease. Methods: The authors used the 2021 Merative MarketScan Medicaid claims database to estimate the medical costs and healthcare utilization associated with heart disease by racial and ethnic groups and COVID-19 diagnosis status. This study focused on individuals aged ≥18 years continuously enrolled in a noncapitated insurance plan in 2021. The outcome measures included total medical expenditures and healthcare utilization, including the numbers of emergency department visits and inpatient admissions and length of inpatient stay. The authors employed a generalized linear model with a family of gamma and log links for medical costs, and a negative binomial regression was used for healthcare utilization. Three-way interactions of heart disease, COVID-19 diagnosis, and race and ethnicity categories were implemented after adjusting for age, sex, and comorbidities. The authors reported average marginal effects with 95% CIs. Results: Among 1,008,166 Medicaid beneficiaries, 8% had heart disease in 2021. The cost associated with heart disease was $10,819 per beneficiary in 2021 (95% CI=10,292; 11,347; p

Abstract Background Community health improvement plans (CHIPs) are strategic planning tools that help local communities identify and address their public health needs. Many local health departments have developed a CHIP, yet there is a lack of research on the extent to which these plans address root causes of health disparities such as the social determinants of health. This study aims to inventory the social determinants of health included in 13 CHIPs and examine facilitators and challenges faced by local health departments and partners when trying to include the social determinants of health. Methods We conducted a comparative plan evaluation by scoring 13 CHIPs on their inclusion of equity orientation, inclusive planning processes, and five social determinants of health: health care access and quality, the neighborhood and built environment, economic stability, social and community context, and education access and quality. To supplement the plan evaluation, we conducted 32 in-depth interviews with CHIP leaders and stakeholders to understand the factors contributing to the inclusion and exclusion of the social determinants of health in the planning process. Results CHIPs received an average score of 49/100 for the inclusion of the social determinants of health. Most plans addressed health care access and quality and the neighborhood and built environment, but they often did not address economic stability, the social and community context, and education access and quality. Regarding their overall equity orientation, CHIPs received an average score of 35/100, reflecting a relative lack of attention to equity and inclusive planning processes in the plans. Interviews revealed that challenges engaging partners, making clear connections between CHIPs and social determinants, and a lack of capacity or public and partner support often led to the exclusion of the social determinants of health. Recommendations to improve planning processes include improving data infrastructure, providing resources for dedicated planning staff and community engagement incentives, and centering equity throughout the planning process. Conclusions Although local health departments can leverage CHIPs to improve population health and address health disparities, they face a range of challenges to including the social determinants of health in CHIPs. Additional resourcing and improved data are needed to facilitate broader inclusion of these determinants, and more work is needed to elevate equity throughout these planning processes.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit).Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure.Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment.Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Elevated blood pressure during childhood can lead to hypertension in adulthood and is associated with an increased risk of future cardiovascular disease with early identification as the best option for prevention. This study examines the prevalence of hypertension in Hispanic and White youths and reports the ability of a school-based program to identify hypertension in school-aged children. Approximately 3.5 % of students had hypertension while 7.5 % of students had elevated blood pressure. Elevated body mass index (BMI) was the most common predictor of hypertension in all three grade levels (elementary: 5th grade, middle: 7th grade, and high school: 10th grade). In the elementary school age group, the significant predictors of hypertension were an elevated BMI, sex, and height. In the middle school age group, the factors that were significant predictors of hypertension included ethnicity, an elevated BMI, and height. In high school age students, the only significant predictor of hypertension was elevated BMI; ethnicity alone was not a significant predictor. The only group that ethnicity was a significant predictor of hypertension was the middle school age. Given that at all three grade levels, the Hispanic students had a higher percentage with elevated BMIs compared to White students, they should be considered at higher risk of hypertension.

Abstract Background One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network’s objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis. Methods We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed. Results Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55–9.60]; z = 4.728; P-value

ObjectiveTo assess the single site performance of the Dynamic Criticality Index (CI-D) models developed from a multi-institutional database to predict future care. Secondarily, to assess future care-location predictions in a single institution when CI-D models are re-developed using single-site data with identical variables and modeling methods. Four CI-D models were assessed for predicting care locations >6-12 hours, >12-18 hours, >18-24 hours, and >24-30 hours in the future.DesignPrognostic study comparing multi-institutional CI-D models' performance in a single-site electronic health record dataset to an institution-specific CI-D model developed using identical variables and modelling methods. The institution did not participate in the multi-institutional dataset.ParticipantsAll pediatric inpatients admitted from January 1st 2018 -February 29th 2020 through the emergency department.Main outcome(s) and measure(s)The main outcome was inpatient care in routine or ICU care locations.ResultsA total of 29,037 pediatric hospital admissions were included, with 5,563 (19.2%) admitted directly to the ICU, 869 (3.0%) transferred from routine to ICU care, and 5,023 (17.3%) transferred from ICU to routine care. Patients had a median [IQR] age 68 months (15-157), 47.5% were female and 43.4% were black. The area under the receiver operating characteristic curve (AUROC) for the multi-institutional CI-D models applied to a single-site test dataset was 0.493-0.545 and area under the precision-recall curve (AUPRC) was 0.262-0.299. The single-site CI-D models applied to an independent single-site test dataset had an AUROC 0.906-0.944 and AUPRC range from 0.754-0.824. Accuracy at 0.95 sensitivity for those transferred from routine to ICU care was 72.6%-81.0%. Accuracy at 0.95 specificity was 58.2%-76.4% for patients who transferred from ICU to routine care.Conclusion and relevanceModels developed from multi-institutional datasets and intended for application to individual institutions should be assessed locally and may benefit from re-development with site-specific data prior to deployment.

IntroductionHematopoietic stem cell transplantation (HSCT) is an increasingly utilized therapy for malignant and non-malignant pediatric diseases. HSCT complications, including infection, organ dysfunction, and graft-versus-host-disease (GVHD) often require intensive care unit (ICU) therapies and are associated with mortality. Our aims were to identify the HSCT characteristics, complications and ICU therapies associated with (1) survival, and (2) survival changes over a ten-year period in a national dataset.MethodsA national sample from the Health Facts (Cerner Corporation, Kansas City, MO) database from 2009 to 2018 was utilized. Inclusion criteria were age 30 days to 1 HSCT, the first was analyzed. Data included demographics, hospital length of stay (LOS), hospital outcome, transplant type and indication. HSCT complications included GVHD and infections. ICU therapies were positive pressure ventilation (PPV), vasoactive infusion, and dialysis. Primary outcome was survival to discharge. Statistical methods included bivariate analyses and multivariate logistic regression.Results473 patients underwent HSCT with 93% survival. 62% were allogeneic (89% survival) and 38% were autologous (98% survival). GVHD occurred in 33% of allogeneic HSCT. Infections occurred in 26% of all HSCT. ICU therapies included PPV (11% of patients), vasoactive (25%), and dialysis (3%). Decreased survival was associated with allogeneic HSCT (p

BackgroundHIV disparities continue to be a significant challenge affecting Black sexual minority men in the United States. Inadequate engagement and retention of patients in HIV care has been associated with poor health outcomes. Interventions to improve sustained commitment to HIV care are needed. Mobile health interventions can help facilitate access to and use of HIV health services, particularly among individuals at risk for disengaging with care. ObjectiveWe designed the LetSync app wireframes for a mobile health intervention using a couple-centered design approach to improve HIV engagement and treatment among Black sexual minority men and their partners. The objective of this study was to gauge future app user interest and elicit feedback to improve the design, development, and usability of the LetSync app. MethodsWe conducted in-depth interviews with 24 Black sexual minority men to assess the acceptability of the LetSync app wireframes between May 2020 and January 2021. Participants reviewed the LetSync app wireframes and provided feedback regarding perceived usefulness and interest in future app use and suggestions for improvement. ResultsParticipants indicated interest in the future LetSync app and noted that the wireframes’ features were acceptable and usable. In our study, the future LetSync app was frequently referred to as a potential resource that could help facilitate users’ engagement in HIV care through the following mechanisms: enable scheduling of appointments and timely reminders for clinic visits; help improve HIV medication adherence; encourage and motivate participants to ask questions to their health care provider and stay engaged in conversations during clinic visits; facilitate effective communication by assisting couples with planning, coordination, and management of daily routines; help participants understand their partner’s health needs, including access to and use of health care services; and facilitate participants’ ability to improve their relationship skills, partner support, and self-efficacy in managing conflict. In addition to near-universal interest in potential daily app use, study participants indicted that they would recommend the LetSync app to other family members, friends, and people in their social networks who are living with HIV. ConclusionsOur findings revealed considerable interest in future app use for HIV care management, which could possibly increase the chance of the LetSync app being successfully adopted by Black sexual minority men in couples. Owing to its interactive and couple-centered approach, the LetSync app could help improve communication between Black sexual minority men and their partners and health providers. In addition, the LetSync app could provide an acceptable modality for these men to receive support in accessing HIV care services.

Abstract Background Thrombotic microangiopathy-induced thrombocytopenia-associated multiple organ failure and hyperinflammatory macrophage activation syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions. Methods We applied consensus, k-means clustering analysis to our extant PHENOtyping sepsis-induced Multiple organ failure Study (PHENOMS) dataset of 404 children. 24-hour computable phenotypes are derived using 25 available bedside variables including C-reactive protein and ferritin. Results Four computable phenotypes (PedSep-A, B, C, and D) are derived. Compared to all other phenotypes, PedSep-A patients (n = 135; 2% mortality) were younger and previously healthy, with the lowest C-reactive protein and ferritin levels, the highest lymphocyte and platelet counts, highest heart rate, and lowest creatinine (p

Perceived safety is recognized throughout the mode choice literature as a key barrier to cycling, yet its constructs are poorly understood. Although commonly understood to relate to crash and injury risk and sometimes vulnerability to crime, health impact assessments identify numerous other pathways through which cycling can negatively impact health. This study leverages a nationally representative survey of U.S. adults in 2022 to assess a set of eleven factors as potential components of perceived cycling safety. We use principal component analysis to identify components of perceived cycling safety and then employ principal component regression to assess these components in relation to predicting unsafe cycling perception. We identify five key dimensions of perceived safety. Specifically, we found that perceived bicycling safety can be encompassed in the following components: (1) contaminant exposure, (2) injurious collision risk, (3) street conditions, (4) weather conditions, and (5) crime risk. In evaluating each identified component, we found that injurious collision risk and street conditions were the most predictive of considering cycling as unsafe. We further develop an understanding of how differences in cycling behavior, such as using cycling for commuting purposes, may contribute to differences in how cycling safety components coalesce into perceived safety.

Objectives: SARS-CoV-2 is a novel and highly infectious virus. An effective response requires rapid training of healthcare workers (HCWs). We measured the change in knowledge related to COVID-19 and associated factors before and after training of HCWs in Vietnam. Methods: A quasi-experimental design was used to evaluate HCW knowledge related to prevention and control of SARS-CoV-2 before and after attending a 2-day training-of-trainers course. Between June and September 2020, 963 HCWs from 194 hospitals in 21 provinces received the training. HCW knowledge was assessed using a 20-item questionnaire consisting of multiple-choice questions at the beginning and closing of the training course. A participant received 1 point for each correct answer. He or she was considered to have improved knowledge the posttest score was higher than the pretest score with a score ≥15 on the posttest. We applied the McNemar test and logistic regression model to test the level of association between demographic factors and change in knowledge of COVID-19. Results: Overall, 100% of HCWs completed both the pretest and posttest. At baseline, only 14.7% scored ≥15. Following the training, 78.4% scored ≥15 and 64.3% had improved knowledge according to the predetermined definition. Questions related to the order of PPE donning and doffing and respiratory specimen collection procedures were identified as having the greatest improvement (44.6% and 60.7%, respectively). Being female (OR, 1.5; 95% CI, 1.1–2.0), having a postgraduate degree (OR, 2.5; 95% CI, 1.4–4.4), working in a nonmanager position (OR, 1.5; 95% CI, 1.1–2.1), previous contact with a COVID-19 patient (OR, 1.5; 95% CI, 1.1–2.0), and working in northern Vietnam (OR, 2.0; 95% CI, 1.4–2.6), were associated with greater knowledge improvement. Conclusions: Most HCWs demonstrated improved knowledge of COVID-19 prevention and control after attending the training. Particular groups may benefit from additional training: those who are male, leaders and managers, those who hold an undergraduate degree, and those who work in the southern provinces.

BackgroundThe Criticality Index-Mortality uses physiology, therapy, and intensity of care to compute mortality risk for pediatric ICU patients. If the frequency of mortality risk computations were increased to every 3 h with model performance that could improve the assessment of severity of illness, it could be utilized to monitor patients for significant mortality risk change.ObjectivesTo assess the performance of a dynamic method of updating mortality risk every 3 h using the Criticality Index-Mortality methodology and identify variables that are significant contributors to mortality risk predictions.PopulationThere were 8,399 pediatric ICU admissions with 312 (3.7%) deaths from January 1, 2018 to February 29, 2020. We randomly selected 75% of patients for training, 13% for validation, and 12% for testing.ModelA neural network was trained to predict hospital survival or death during or following an ICU admission. Variables included age, gender, laboratory tests, vital signs, medications categories, and mechanical ventilation variables. The neural network was calibrated to mortality risk using nonparametric logistic regression.ResultsDiscrimination assessed across all time periods found an AUROC of 0.851 (0.841–0.862) and an AUPRC was 0.443 (0.417–0.467). When assessed for performance every 3 h, the AUROCs had a minimum value of 0.778 (0.689–0.867) and a maximum value of 0.885 (0.841,0.862); the AUPRCs had a minimum value 0.148 (0.058–0.328) and a maximum value of 0.499 (0.229–0.769). The calibration plot had an intercept of 0.011, a slope of 0.956, and the R2 was 0.814. Comparison of observed vs. expected proportion of deaths revealed that 95.8% of the 543 risk intervals were not statistically significantly different. Construct validity assessed by death and survivor risk trajectories analyzed by mortality risk quartiles and 7 high and low risk diseases confirmed a priori clinical expectations about the trajectories of death and survivors.ConclusionsThe Criticality Index-Mortality computing mortality risk every 3 h for pediatric ICU patients has model performance that could enhance the clinical assessment of severity of illness. The overall Criticality Index-Mortality framework was effectively applied to develop an institutionally specific, and clinically relevant model for dynamic risk assessment of pediatric ICU patients.

Abstract Background Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study’s objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. Methods We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. Results The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Conclusions Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

Abstract Background Contained rupture of the ascending aorta is a rare condition, but the severity of this complication enforces strict guidelines for its prevention and a prompt diagnosis, once already occurred. Case presentation A 66-year-old man with a history of type 2 diabetes, longstanding aortic valve stenosis and aortic root aneurysm of 47 mm was hospital admitted for elective surgery. A Bentall-De Bono procedure was performed in order to replace the stenotic bicuspid aortic valve and exclude the dilated portion of the aortic wall. Intraoperatively, a discontinuity of the aortic wall, just above the aortic annulus, at the non-coronary sinus of Valsalva was incidentally observed. The aortic wall discontinuity was none other than a contained aortic rupture. The preoperative CT-scan images were afterwards analyzed by the radiologist, in order to identify the contained aortic rupture. Indeed a false aneurysm of the non-coronary sinus of Valsalva of a maximum diameter of 15 mm was detected, thanks to a 3D reconstruction. Conclusions The diagnosis of contained aortic rupture is certainly demanding, particularly in absence of signs or symptoms of rupture in a chamber of the heart or in the pericardium. Although this case represents a consensus of experts’ opinion, the recognition of these specific cases in which the risk of dissection, rupture or death is at its highest, would allow to operate at the appropriate time, improving the outcomes.

Communities around the world lack safe places for children to play and be physically active. One solution to this issue is Play Streets, which involves the temporary closure of streets for several hours to create a safe space for active play and physical activity. While the benefits of these programs are greater when they are recurring over many years, there is a dearth of literature regarding how to successfully sustain Play Streets. To understand how Play Streets can be sustained in the long term, we conducted semi-structured interviews with 24 Play Streets organizers representing 22 Play Streets programs across the United States. Four recurring sustainability challenges were highlighted from the thematic analysis: 1) securing and sustaining funding, 2) managing community and city resistance to street closures, 3) navigating government bureaucracy, and 4) retaining interest amongst organizers and volunteers. With each challenge, we describe how Play Streets organizers navigated those challenges, with a goal of generating recommendations for those wishing to sustain Play Streets programs in the long term.

Abstract Background Treatments for soft tissue sarcoma (STS) include extensive surgical resection, radiation and chemotherapy, and can necessitate specialized care and excellent social support. Studies have demonstrated that socioeconomic factors, such as income, marital status, urban/rural residence, and educational attainment as well as treatment at high-volume institution may be associated with overall survival (OS) in STS. Methods In order to explore the effect of socio-economic factors on OS in patients treated at a high-volume center, we performed a retrospective analysis of STS patients treated at a single institution. Results Overall, 435 patients were included. Thirty-seven percent had grade 3 tumors and 44% had disease larger than 5 cm. Patients were most commonly privately insured (38%), married (67%) and retired or unemployed (43%). Median distance from the treatment center was 42 miles and median area deprivation index (ADI) was 5 (10 representing most deprived communities). The majority of patients (52%) were treated with neoadjuvant therapy followed by resection. As expected, higher tumor grade (HR 3.1), tumor size > 5 cm (HR 1.3), and involved lymph nodes (HR 3.2) were significantly associated with OS on multivariate analysis. Demographic and socioeconomic factors, including sex, age at diagnosis, marital status, employment status, urban vs. rural location, income, education, distance to the treatment center, and ADI were not associated with OS. Conclusions In contrast to prior studies, we did not identify a significant association between socioeconomic factors and OS of patients with STS when patients were treated at a single high-volume center. Treatment at a high volume institution may mitigate the importance of socio-economic factors in the OS of STS.

Modifying the built environment to make communities more walkable remains one strategy to promote physical activity. These modifications may have the added benefit of reducing the risk of pedestrian injury; however, there is a gap in the physical activity literature regarding how best to measure pedestrian injury. Examining the measures that have been used and related data sources can help inform the use of pedestrian injury data to evaluate whether safety is optimized as walking increases. We conducted a systematic review of the literature to identify studies that evaluated changes to the built environment that support walking and measures impacts on pedestrian injury as a measure of safety. We searched PubMed, PsycInfo, and Web of Science to identify peer-review studies and websites of fifteen organizations to document studies from the grey literature published in English between January 1, 2010 and December 31, 2018. Our search identified twelve studies that met the inclusion criteria. The few studies that measured changes in pedestrian injury used crash data from police reports. Injury frequency was often reported, but not injury severity, and no studies reported injury risk based on walking exposure. We conclude that few studies have measured pedestrian injury in the context of creating more walkable communities. Future research would benefit from using well-characterized measures from existing studies to support consistency in measurement, and from more longitudinal and evaluation research to strengthen the evidence on additional benefits of walkability. Increased collaborations with injury prevention professionals could bolster use of valid and reliable measures.

Summary: Background: Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children. Methods: We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI. Findings: Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p

Abstract Background Prior to the COVID-19 pandemic, 44% of all reported injuries in U.S. households occurred in the home. Spending more time at home due to the pandemic may increase the number of home injuries. Methods A nationally representative sample of 2011 U.S. adults were surveyed online between June 17 – June 29, 2020. Propensity score weighting and T-tests were used. Results Twenty-eight percent (28%) of households reported a home injury or ingestion during the pandemic; 13% reported experiencing both. Injuries were most often due to falls (32%). Medication ingestions were reported by 6%; household product ingestions were reported by 4%. Relative to households that experienced no injuries or ingestions, those that reported either or both were more likely to: be in urban areas, have household incomes > $100,000, and have children living in them. Among households reporting more time spent at home, those with children were significantly more likely than those without to report an injury or ingestion. Conclusions Results help target prevention messages while U.S. families are continuing to work and learn remotely. During this pandemic and future stay-at-home orders, there is a need for public health efforts to prevent home injuries and ingestions.

Abstract Background Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials. Methods In this multi‐center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first‐line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression‐free survival (PFS) were evaluated using the Kaplan‐Meier method and Cox regression. Results At start of first‐line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first‐line therapy for SS was 24.7 months (95% CI, 20.9‐29.4) and 7.5 months, respectively (95% CI, 6.4‐8.4). Median OS and median PFS from start of first‐line therapy for MRCL was 29.9 months (95% CI, 27‐44.6) and 8.9 months (95% CI 4.5‐12.0). Conclusions To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real‐world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature.

Abstract Background Olaratumab, a fully human monoclonal antibody, selectively binds to human platelet‐derived growth factor receptor alpha and blocks ligand binding. This study assessed the effect of olaratumab on the pharmacokinetics (PK) of doxorubicin and the safety of olaratumab alone and in combination with doxorubicin. Methods This open‐label randomized phase 1 trial enrolled 49 patients ages 27 to 83 with metastatic or locally advanced soft tissue sarcoma (STS). Patients participated in 21‐day treatment cycles (up to 8) until they met discontinuation criteria. In cycles 1 and 2, patients received olaratumab (15 mg/kg in Part A, 20 mg/kg in Part B) and doxorubicin (75 mg/m2). In cycles 3 through 8, patients continued combination treatment (15 mg/kg olaratumab + doxorubicin). Effect of olaratumab on PK of doxorubicin was determined in patients who received all doses in cycles 1 and 2. Results PK properties of doxorubicin administered alone or in combination with olaratumab (15 or 20 mg/kg) were similar for AUC(0‐tlast), AUC(0‐∞), and Cmax. PK properties of olaratumab (15 or 20 mg/kg) were also similar when administered alone or in combination with doxorubicin. Three patients died (2 of disease progression and 1 of neutropenic enterocolitis). Fatigue and nausea (>75% of patients) were the most common treatment‐emergent adverse events (TEAEs). Other common TEAEs included musculoskeletal pain, mucositis, constipation, and diarrhea. Conclusions Olaratumab at 15 or 20 mg/kg before doxorubicin infusion had no clinically relevant effect on systemic exposure to doxorubicin compared with doxorubicin alone in patients with metastatic or locally advanced STS.

Introduction HIV care engagement is lower among black sexual-minority men relative to other racial/ethnic groups of sexual-minority men. Being in a primary relationship is generally associated with more successful HIV care engagement across various populations. However, among black sexual-minority men, the association between primary relationship status and HIV-related outcomes is inconsistent across the HIV care continuum. Given the ubiquity of mobile technology access and use among racial/ethnic minority communities, leveraging mobile technology for HIV care engagement appears a promising intervention strategy. This paper outlines the protocol of the LetSync study, a pilot randomised controlled trial of a mobile health app intervention developed using the Framework of Dyadic HIV Care Engagement to improve care-engagement outcomes among black sexual-minority male couples living with HIV.Methods and analysis Eighty black sexual-minority men in couples (n=160) will be enrolled to pilot test the LetSync app. At least one member of each dyad must be both HIV-positive and self-identify as black/African-American. Couples will be randomised to either a waitlist-control arm or an intervention that uses relationship-based approach to improve HIV care engagement. We will assess feasibility and acceptability of trial procedures and intervention protocols based on predefined metrics of feasibility and acceptability. Execution of the study will yield the opportunity to conduct analyses to test the measurement and analysis protocol on antiretroviral therapy adherence by comparing the intervention and waitlist-control arms on self-reported and biological (hair sample) measures of adherence.Ethics and dissemination Study staff will obtain electronic consent from all participants. This study has been approved by the University of California (UCSF) Institutional Review Board. Study staff will work with the Community Advisory Board at the UCSF Center for AIDS Prevention Studies Board to disseminate results to participants and the community via open discussions, presentations, journal publications and/or social media.Trial registration number NCT04951544.

Background: Although some pediatric sepsis survivors experience worsening health-related quality of life (HRQL), many return to their pre-illness HRQL. Whether children can improve beyond baseline is not known. We examined a cohort of pediatric sepsis survivors to determine if those with baseline HRQL scores below the population mean could exhibit ≥10% improvement and evaluated factors associated with improvement.Methods: In this secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study, children aged 1 month to 18 years admitted to 12 academic PICUs in the United States with community-acquired septic shock who survived to 3 months and had baseline HRQL scores ≤ 80 (i.e., excluding those with good baseline HRQL to allow for potential improvement) were included. HRQL was measured using the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale.Findings: One hundred and seventeen children were eligible. Sixty-one (52%) had ≥ 10% improvement in HRQL by 3 months. Lower pre-sepsis HRQL was associated with increased odds of improvement at 3 months [aOR = 1.08, 95% CI (1.04–1.11), p < 0.001] and 12 months [OR = 1.05, 95% CI (1.02–1.11), p = 0.005]. Improvement in HRQL was most prevalent at 3 month follow-up; at 12 month follow-up, improvement was more sustained among children without severe developmental delay compared to children with severe developmental delay.Interpretation: More than half of these children with community acquired septic shock experienced at least a 10% improvement in HRQL from baseline to 3 months. Children with severe developmental delay did not sustain this improvement at 12 month follow-up.

OBJECTIVES:. Develop and compare separate prediction models for ICU and non-ICU care for hospitalized children in four future time periods (6–12, 12–18, 18–24, and 24–30 hr) and assess these models in an independent cohort and simulated children’s hospital. DESIGN:. Predictive modeling used cohorts from the Health Facts database (Cerner Corporation, Kansas City, MO). SETTING:. Children hospitalized in ICUs. PATIENTS:. Children with greater than or equal to one ICU admission (n = 20,014) and randomly selected routine care children without ICU admission (n = 20,130) from 2009 to 2016 were used for model development and validation. An independent 2017–2018 cohort consisted of 80,089 children. INTERVENTIONS:. None. MEASUREMENT AND MAIN RESULTS:. Initially, we undersampled non-ICU patients for development and comparison of the models. We randomly assigned 64% of patients for training, 8% for validation, and 28% for testing in both clinical groups. Two additional validation cohorts were tested: a simulated children’s hospitals and the 2017–2018 cohort. The main outcome was ICU care or non-ICU care in four future time periods based on physiology, therapy, and care intensity. Four independent, sequential, and fully connected neural networks were calibrated to risk of ICU care at each time period. Performance for all models in the test sample were comparable including sensitivity greater than or equal to 0.727, specificity greater than or equal to 0.885, accuracy greater than 0.850, area under the receiver operating characteristic curves greater than or equal to 0.917, and all had excellent calibration (all R2s > 0.98). Model performance in the 2017–2018 cohort was sensitivity greater than or equal to 0.545, specificity greater than or equal to 0.972, accuracy greater than or equal to 0.921, area under the receiver operating characteristic curves greater than or equal to 0.946, and R2s greater than or equal to 0.979. Performance metrics were comparable for the simulated children’s hospital and for hospitals stratified by teaching status, bed numbers, and geographic location. CONCLUSIONS:. Machine learning models using physiology, therapy, and care intensity predicting future care needs had promising performance metrics. Notably, performance metrics were similar as the prediction time periods increased from 6–12 hours to 24–30 hours.

Synovial sarcoma (SS) is a rare cancer that disproportionately affects children and young adults. Cancer testis antigens (CTAs) are proteins that are expressed early in embryonic development, but generally not expressed in normal tissue. They are aberrantly expressed in many different cancer types and are an attractive therapeutic target for immunotherapies. CTAs are expressed at high levels in SS. This high level of CTA expression makes SS an ideal cancer for treatment strategies aimed at harnessing the immune system to recognize aberrant CTA expression and fight against the cancer. Pivotal clinical trials are now underway, with the potential to dramatically alter the landscape of SS management and treatment from current standards of care. In this review, we describe the rationale for targeting CTAs in SS with a focus on NY-ESO-1 and MAGE-A4, the current state of vaccine and T-cell receptor-based therapies, and consider emerging opportunities for future development.

Abstract Background As part of efforts to expand Health in All Policies (HiAP) in Washington State in the U.S., the Washington State Board of Health (BOH) received statutory authority in 2006 to conduct Health Impact Reviews (HIRs). HIRs analyze the potential impacts of proposed legislation and budget decisions on health and health disparities. Public health professionals who are aware of HIRs are interested in adopting a similar process in their states; however, there is limited information about HIRs, how they are perceived, and how they could advance HiAP. Methods This research involved a descriptive analysis of a sample of HIRs and semi-structured interviews with a purposive sample of 17 key informants. For the descriptive analysis, all HIRs requested or completed between January 1, 2007 and April 1, 2016 that had a request form submitted by a legislator or the governor that was available in the BOH’s online database were reviewed. Information was collected on several variables including the bill number and title, sponsor and political affiliation, and the sector to which the bill or budgetary proposal pertained. A purposeful sample of legislators, staff, advocates, and lobbyists who were involved with HIRs during the study period were invited to participate in semi-structured interviews. Topic coding was used to identify key themes from the qualitative data. Results During the study period, 20 legislators requested 36 HIRs; 32 HIRs were completed. HIRs were requested for several bill topics, including education (11/36) and labor and employment (9/36). Legislators who requested HIRs felt they provided valuable data on health and health disparities for proposed bills. Individuals who were less supportive of HIRs perceived them as an advocacy or political tool. The main barrier to widespread use of HIRs in Washington was a lack of awareness among legislators. Conclusions HIRs are one strategy to advance HiAP for state policy decisions. HIRs are a potentially effective tool for highlighting how legislative proposals and budgets positively and negatively impact health and health disparities. Future efforts should promote awareness and highlight shared benefits of HIRs among legislators and their staff, as well as their scientific integrity, methodological rigor, and objectivity.

Purpose: Soft tissue sarcomas (STS) represent a heterogeneous group of diseases, and selection of individualized treatments remains a challenge. The goal of this study was to determine whether radiomic features extracted from magnetic resonance (MR) images are independently associated with overall survival (OS) in STS. Methods and Materials: This study analyzed 2 independent cohorts of adult patients with stage II-III STS treated at center 1 (N = 165) and center 2 (N = 61). Thirty radiomic features were extracted from pretreatment T1-weighted contrast-enhanced MR images. Prognostic models for OS were derived on the center 1 cohort and validated on the center 2 cohort. Clinical-only (C), radiomics-only (R), and clinical and radiomics (C+R) penalized Cox models were constructed. Model performance was assessed using Harrell's concordance index. Results: In the R model, tumor volume (hazard ratio [HR], 1.5) and 4 texture features (HR, 1.1-1.5) were selected. In the C+R model, both age (HR, 1.4) and grade (HR, 1.7) were selected along with 5 radiomic features. The adjusted c-indices of the 3 models ranged from 0.68 (C) to 0.74 (C+R) in the derivation cohort and 0.68 (R) to 0.78 (C+R) in the validation cohort. The radiomic features were independently associated with OS in the validation cohort after accounting for age and grade (HR, 2.4; P = .009). Conclusions: This study found that radiomic features extracted from MR images are independently associated with OS when accounting for age and tumor grade. The overall predictive performance of 3-year OS using a model based on clinical and radiomic features was replicated in an independent cohort. Optimal models using clinical and radiomic features could improve personalized selection of therapy in patients with STS.

Abstract Background Active play and physical activity are important for preventing childhood obesity, building healthy bones and muscles, reducing anxiety and stress, and increasing self-esteem. Unfortunately, safe and accessible play places are often lacking in under-resourced communities. Play Streets (temporary closure of streets) are an understudied intervention that provide safe places for children, adolescents, and their families to actively play. This systematic review examines how Play Streets impact opportunities for children and adolescents to engage in safe active play and physical activity, and for communities and neighborhoods. Methods for evaluating Play Streets were also examined. Methods A systematic literature review was conducted in Academic Search Complete, CINHAL, PsycINFO, PubMED, Web of Science, and Google Scholar. Peer-reviewed intervention studies published worldwide were included if they were published in English, through December 2017 and documented free-to-access Play Streets or other temporary spaces that incorporated a designated area for children and/or adolescents to engage in active play. Systematic data extraction documented sample, implementation, and measurement characteristics and outcomes. Results Of 180 reviewed abstracts, 6 studies met inclusion criteria. Studies were conducted in five different countries (n = 2 in U.S.), using mostly cross-sectional study designs (n = 4). Physical activity outcomes were measured in half of the studies; one used observational and self-report measures, and two used device-based and self-report measures. In general, Play Streets provided safe places for child play, increased sense of community, and when measured, data suggest increased physical activity overall and during Play Streets. Conclusions Play Streets can create safe places for children to actively play, with promise of increasing physical activity and strengthening community. Given the popularity of Play Streets and the potential impact for active play, physical activity, and community level benefits, more rigorous evaluations and systematic reporting of Play Streets’ evaluations are needed.

Background: The 2019 United Nations General Assembly High-Level Meeting on Universal Health Coverage and the 2018 Declaration of Astana reaffirm the highest level of political commitment by United Nations Member States to achieve access to health services and primary healthcare for all. Both documents emphasize the importance of person-centered care in both healthcare services and systems design. However, there is limited consensus on how to build a strong primary healthcare system to achieve these goals. Methods: We convened a diverse group of global stakeholders for a high-level dialogue on how to create a person-centered primary healthcare system, using the country examples of the Republic of Kenya and the Socialist Republic of Vietnam. We focused our discussion on four themes to enable the creation of person-centered primary healthcare systems in Kenya and Vietnam: (1) strengthened community, person and patient engagement in subnational and national decision making; (2) improved service delivery; (3) impactful use of innovation and technology; and (4) meaningful and timely use of measurement and data. Findings: Here, we present a summary of our convening’s proceedings, with specific insights on how to enable a person-centered primary healthcare system within each of these four domains. Conclusions: Following the 2019 United Nations General Assembly High-Level Meeting on Universal Health Coverage and the 2018 Declaration of Astana, there is high-level commitment and global consensus that a person-centered approach is necessary to achieve high-quality primary healthcare and universal health coverage. We offer our recommendations to the global community to catalyze further discourse and inform policy-making and program development on the path to Universal Health Coverage by 2030.

Background Adoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a ‘cold’ tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-γ), which could improve the efficacy of ACT for SS.Case presentation We launched a phase I trial incorporating four weekly doses of IFN-γ in an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns.Conclusion We describe a new and serious toxicity of immunotherapy from IFN-γ combined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γ should not be used concurrently with HD Cy or with low dose IL-2, IFN-γ may still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γ during the immediate period before/after cell infusion.Trial registration numbers NCT04177021, NCT01957709, and NCT03063632.

Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam’s National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country’s HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam’s experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building.

Gastrointestinal stromal tumor (GIST) is a devastating disease, especially in the setting of metastasis. The natural progression of GIST has been significantly altered by the development of small molecule tyrosine kinase inhibitors (TKIs), including imatinib, sunitinib, and regorafenib, all of which are FDA approved. However, TKIs are not always well-tolerated, and the refractory disease continues to be a problem. For these reasons, alternative treatments are needed. In this report, we discuss a patient with metastatic wild-type (WT) GIST refractory to multiple TKIs, but with a durable clinical response to the anti-programmed cell death protein 1 (PD-1) antibody, nivolumab. This report suggests that continued research evaluating checkpoint inhibitors in GIST is warranted.