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Background Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. Methods Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. Results Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. Conclusion Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

Delays in obtaining care may lead to perforated appendicitis, increasing risk of morbidity and mortality. We previously explored the role of social determinants in patients undergoing cholecystectomy, finding that emergent presentation is associated with neighborhood Social Vulnerability Index (SVI). We hypothesize that social vulnerability is associated with increased incidence of perforated appendicitis.We retrospectively identified patients presenting to our urban, academic hospital with acute appendicitis during a 9-month timeframe (11/2019 - 7/2020). Patients were classified as perforated or non-perforated. Patient SVI was determined using geocoding at the census tract level. Because rates of perforation were higher in older patients, we performed a subset analysis of patients ≥ 40 years.190 patients were included. Patients with perforated appendicitis (n = 48, 25%) were older and were more likely to present to a clinic versus the emergency department (P = 0.009). Perforated patients had longer delay before seeking care (56% versus 6% with72 hours of symptoms, P0.001). However, there were no differences between groups in terms of sex, race/ethnicity, insurance type, language barrier, having a primary care physician, or any of the SVI subscales. Of patients ≥ 40 years, a higher proportion were perforated (28/80, 35%) despite similar rates of delayed care. In this cohort, higher overall SVI as well as the socioeconomic status and household composition/disability subscales were associated with perforation.Contrary to our hypothesis, while perforation was associated with delayed care in this population, we did not find overall that social vulnerability or individual social determinants accounted for this delay.

Background Adults with atherosclerotic cardiovascular disease (ASCVD) at very high-risk for recurrent events who have low-density lipoprotein cholesterol ≥ 70 mg/dL despite maximally-tolerated statin therapy are recommended to initiate ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Objective Compare the initiation of ezetimibe and a PCSK9 inhibitor after a myocardial infarction (MI) among very high-risk ASCVD patients by race/ethnicity and sex. Methods We analyzed data from 374,786 adults ≥ 66 years of age with Medicare fee-for-service coverage who had an MI between July 1, 2015 and December 31, 2018, were not taking ezetimibe or a PCSK9 inhibitor, and had very high-risk ASCVD defined by the 2018 American Heart Association/American College of Cardiology multi-society cholesterol guideline. Pharmacy claims through December 31, 2018 were used to determine ezetimibe and PCSK9 inhibitor initiation. Results Overall, 6980 (1.9%) beneficiaries initiated ezetimibe, and 1433 (0.4%) initiated a PCSK9 inhibitor. Adjusted hazard ratios (aHR) for ezetimibe initiation among non-Hispanic Black, Hispanic, and Asian versus non-Hispanic White beneficiaries were 0.77 (95% confidence interval [95%CI]: 0.70–0.86), 0.92 (95%CI: 0.76–1.11) and 0.73 (95%CI: 0.59–0.89), respectively. Compared to non-Hispanic White beneficiaries, the aHRs for PCSK9 inhibitor initiation were 0.63 (95%CI: 0.48–0.81) among non-Hispanic Black, 0.70 (95%CI: 0.43–1.13) among Hispanic, and 0.93 (95%CI: 0.62–1.39) among Asian beneficiaries. The aHRs for ezetimibe and PCSK9 inhibitor initiation comparing women to men were 1.11 (95%CI: 1.06–1.17) and 1.13 (95%CI: 1.01–1.25), respectively. Conclusion There are race/ethnic and sex disparities in the initiation of ezetimibe and a PCSK9 inhibitor following MI among very high-risk ASCVD patients.

Objective: EMS use of lights and sirens has long been employed in EMS systems, despite an increased risk of motor vehicle collisions associated with their use. The specific aims of this study were ...

Hospital readmission is an important quality-of-care indicator. We sought to examine the rates and predictors of unplanned readmission for the high-risk non-trauma emergency laparotomy patient.This is a post hoc analysis of a multicenter prospective observational study. Between April 2018 and June 2019, a total of 19 centers enrolled all adult patients undergoing emergency laparotomies and systematically collected preoperative, operative, and 30-day postoperative variables. For the purpose of this study, we defined unplanned readmission as a readmission occurring within 30 days from discharge and one that was immediately preceded by an emergency department visit. Patients were excluded if they died during the index admission, were discharged to hospice, or were transferred to other hospitals. Predictors of unplanned readmission were evaluated using a multivariable logistic regression model, adjusting for patient demographics, comorbidities, laboratory variables, and preoperative acuity of disease variables.A total of 1,347 patients were included, of which 234 (17.4%) had an unplanned readmission. The median patient age was 60 y, 49.4% were male, and 71.4% were white. The most common diagnoses were hollow viscus perforation (28.1%) and small bowel obstruction (24.5%). Predictors of unplanned readmission included patient factors (eg, disseminated cancer [odds ratio: 2.22, confidence interval: 1.35-3.64, P = .002], weight loss10% in the past 6 months [odds ratio: 1.65, confidence interval: 1.07-2.54, P = .023], dyspnea at baseline [odds ratio: 1.62, confidence interval: 1.06-2.48, P = .026], wound complications [odds ratio: 2.23, confidence interval: 1.55-3.19, P.001], and discharge to nursing homes [odds ratio: 1.68, confidence interval: 1.02-2.80, P = .044]).Unplanned readmission after emergency laparotomies are common, especially for patients with wound complications or requiring nursing homes. These system factors are potential quality improvement targets to reduce readmissions.

Emerging adults are at high risk for opioid-use disorders (OUDs); however, their service use and co-occurring needs are infrequently described. This study analyzed county-level Medicaid claims acro...

BACKGROUND: Although mortality due to COVID-19 has been reportedly low among children with cancer, changes in health-care services due to the pandemic have affected cancer care delivery. This study aimed to assess the effect of the COVID-19 pandemic on childhood cancer care worldwide. METHODS: A cross-sectional survey was distributed to paediatric oncology providers worldwide from June 22 to Aug 21, 2020, through the St Jude Global Alliance and International Society for Paediatric Oncology listservs and regional networks. The survey included 60 questions to assess institution characteristics, the number of patients diagnosed with COVID-19, disruptions to cancer care (eg, service closures and treatment abandonment), adaptations to care, and resources (including availability of clinical staff and personal protective equipment). Surveys were included for analysis if respondents answered at least two thirds of the items, and the responses were analysed at the institutional level. FINDINGS: Responses from 311 health-care professionals at 213 institutions in 79 countries from all WHO regions were included in the analysis. 187 (88%) of 213 centres had the capacity to test for SARS-CoV-2 and a median of two (range 0-350) infections per institutution were reported in children with cancer. 15 (7%) centres reported complete closure of paediatric haematology-oncology services (median 10 days, range 1-75 days). Overall, 2% (5 of 213) of centres were no longer evaluating new cases of suspected cancer, while 43% (90 of 208) of the remaining centers described a decrease in newly diagnosed paediatric cancer cases. 73 (34%) centres reported increased treatment abandonment (ie, failure to initiate cancer therapy or a delay in care of 4 weeks or longer). Changes to cancer care delivery included: reduced surgical care (153 [72%]), blood product shortages (127 [60%]), chemotherapy modifications (121 [57%]), and interruptions to radiotherapy (43 [28%] of 155 institutions that provided radiotherapy before the pandemic). The decreased number of new cancer diagnoses did not vary based on country income status (p=0·14). However, unavailability of chemotherapy agents (p=0·022), treatment abandonment (p

Background Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. Objectives The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. Methods This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. Results Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = −0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. Conclusions SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062 )

Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.

Background Acute Heart Failure (AHF) is a common condition that often presents with acute respiratory distress and requires urgent medical evaluation and treatment. Arterial hypercapnia is common in AHF and has been associated with a higher rate of intubation and non-invasive ventilation in the Emergency Room (ER), but its prognostic value has never been studied in the prehospital setting. Methods A retrospective study was performed on the charts of all patients taken care of by a physician-staffed prehospital mobile unit between June 2016 and September 2019 in Geneva. After approval by the ethics committee, charts were screened to identify all adult patients with a diagnosis of AHF in whom a prehospital arterial blood gas (ABG) sample was drawn. The main predictor was prehospital hypercapnia. The primary outcome was the admission rate in an acute care unit (ACU, composite of intensive care and high-dependency units). Secondary outcomes were ER length of stay (LOS), orientation from ER (intensive care unit, high-dependency unit, general ward, discharge home), intubation rate at 24 h, hospital LOS and hospital mortality. Results A total of 106 patients with a diagnosis of AHF were analysed. Hypercapnia was found in 61 (58%) patients and vital signs were more severely altered in this group. The overall ACU admission rate was 48%, with a statistically significant difference between hypercapnic and non-hypercapnic patients (59% vs 33%, p = 0.009). ER LOS was shorter in hypercapnic patients (5.4 h vs 8.9 h, p = 0.016). Conclusions There is a significant association between prehospital arterial hypercapnia, acute care unit admission, and ER LOS in AHF patients.

Aim Pennsylvania (PA) first-episode psychosis (FEP) program evaluation is a statewide initiative, supported by the PA Office of Mental Health and Substance Abuse Services (PA-OMHSAS) and administered by PA Early Intervention Center/Heads Up, which evaluates fidelity and outcomes of PA Coordinated Specialty Care (CSC) programs. Programs participate in standard computerized measures of CSC outcomes using centralized informatics. The aims of the current report are to describe implementation of this core battery for program evaluation in PA and to present 6- and 12-month outcomes. Methods Participants (n = 697) from nine PA CSC programs completed the core battery at admission. The battery was re-administered at 6- and 12-month follow-up, and data were analysed for individuals (n = 230) who had completed 12-months of treatment. Domains assessed via clinician report and/or self-report included symptoms, role and social functioning, self-perceived recovery and service utilization. Results PA FEP CSC participants showed improvement over time in several domains, including decreased symptoms, higher role and social functioning, decreased hospitalizations, and improved self-perception of recovery, quality of life, and services satisfaction. Trends towards improvements were observed for participant happiness, hopelessness, and school-enrolment. Nearly all improvements were observed at 6-month follow-up, with earlier gains maintained at 12-months. Conclusions PA FEP CSC programs demonstrate the ability to assess and improve critical outcomes of coordinated specialty care in PA. Improved outcomes by 12 months in treatment provides evidence of an effective treatment model and supports the continuation of these programs in pursuit of our goal of reducing schizophrenia disease burden on individuals and society.

Background The Emergency Surgery Score (ESS) was recently validated as an accurate mortality risk calculator for emergency general surgery. We sought to prospectively evaluate whether ESS can predict the need for respiratory and/or renal support (RRS) at discharge after emergent laparotomies (EL). Methods This is a post hoc analysis of a 19-center prospective observational study. Between April 2018 and June 2019, all adult patients undergoing EL were enrolled. Preoperative, intraoperative, and postoperative variables were systematically collected. In this analysis, patients were excluded if they died during the index hospitalization, were discharged to hospice, or transferred to other hospitals. A composite variable, the need for RRS, was defined as the need for one or more of the following at hospital discharge: tracheostomy, ventilator dependence, or dialysis. Emergency Surgery Score was calculated for all patients, and the correlation between ESS and RRS was examined using the c-statistics method. Results From a total of 1,649 patients, 1,347 were included. Median age was 60 years, 49.4% were men, and 70.9% were White. The most common diagnoses were hollow viscus organ perforation (28.1%) and small bowel obstruction (24.5%); 87 patients (6.5%) had a need for RRS (4.7% tracheostomy, 2.7% dialysis, and 1.3% ventilator dependence). Emergency Surgery Score predicted the need for RRS in a stepwise fashion; for example, 0.7%, 26.2%, and 85.7% of patients required RRS at an ESS of 2, 12, and 16, respectively. The c-statistics for the need for RRS, the need for tracheostomy, ventilator dependence, or dialysis at discharge were 0.84, 0.82, 0.79, and 0.88, respectively. Conclusion Emergency Surgery Score accurately predicts the need for RRS at discharge in EL patients and could be used for preoperative patient counseling and for quality of care benchmarking. Level of evidence Prognostic and epidemiological, level III.

Background Cervical cancer is a preventable cancer; therefore, countries should provide strategic, evidence-based health services to reduce its incidence and impact on their populations. Two packages of health services that group together all the services related to cervical cancer, the Essential Cancer Package (9 interventions) and the Primary Care Package (5 interventions), are defined in this article with the aim of assessing the global status of the availability of health services and their coverage in 194 countries worldwide. Methods The study was based on the 2017 World Health Organization (WHO) Noncommunicable Disease Country Capacity Survey. Although the survey covered multiple noncommunicable diseases, this report examined only those results pertaining to cervical cancer in the 194 WHO member states divided by WHO region and World Bank income. Results Only 21% of the countries reported providing all 9 interventions of the Essential Cancer Package, with the highest proportions being found in Europe (45.3%) and among high-income countries (HICs; 54.3%). As for the Primary Care Package, only 19.1% of countries provided all 5 interventions, with the highest proportions being found in Europe (39.6%) and among HICs (45.5%). Conclusions The complete development and appropriate coverage of each service listed in both the Essential Cancer Package and the Primary Care Package are essential to reduce the impact of cervical cancer worldwide, and they should be integrated into all cancer control planning efforts.

Psoriasis is an immune-mediated skin disease with various presentations. HIV infection affects the immune system and aggravates psoriasis lesions. Therefore, psoriasis management in HIV patients poses a great challenge for dermatologists. In this report, 2 HIV patients with erythrodermic psoriasis received anti-IL-17 and experienced significant clearance of lesions. No recurrence or opportunistic infection was noted. In conclusion, anti-IL-17 monoclonal antibodies are an effective and promising treatment option for HIV-infected patients with psoriasis.

Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p

Introduction Rural compared to urban populations in the US have increased colorectal cancer (CRC) incidence with known disparity in screening rates and mortality. We hypothesize that rural-urban disparities are different at a regional level. Methods We assessed screening rates according to the 2016 Behavioral Risk Factor Surveillance System guidelines using state and city-level data for county level estimates and correlating with county CRC mortality data from the National Cancer Institute. We used multivariable modeling to examine associations between rurality, screening rates, and mortality. Results Highest screening rate states had the smallest urban-rural disparities; lowest screening rate states had the largest disparities. Percent screened and urban-rural classification correlated significantly with mortality. Rural counties experienced ∼5 more deaths per 100,000 population even controlling for screening rates. Conclusions National urban-rural disparities in CRC screening mask greater state/regional disparities, not fully explaining the urban-rural mortality gap. Other factors (i.e. access to care, treatment differences) must be considered.

BACKGROUND: We investigated the prevalence and impact of heavy alcohol use on the hepatitis C virus (HCV) care continuum among HIV/HCV co-infected persons who use drugs. METHODS: In the CHAMPS study, 144 HIV/HCV co-infected persons were randomized to contingent cash incentives, peer-mentors, and usual care to evaluate the impact on HCV care. Alcohol use was ascertained using the 10-item AUDIT (hazardous: male ≥ 8, female ≥ 4) and phosphatidylethanol (PEth) (heavy: ≥ 50 ng/ml), an alcohol biomarker. Log binomial regression was used to evaluate the association between heavy alcohol use and failure to initiate treatment and to achieve sustained virologic response (SVR). RESULTS: Of the 135 participants with PEth data, median age was 55 years, 59% were male, 92% were Black, 91% reported a history of drug use, and 97% were on antiretroviral therapy. Hazardous drinking was reported on AUDIT by 28% of participants and 35% had heavy alcohol use by PEth. Of the 47 individuals with a PEth ≥ 50 ng/ml, 23 (49%) reported no or minimal alcohol use by AUDIT. HCV treatment was initiated in 103 of 135 participants and SVR was achieved in 92%. PEth ≥ 50 ng/ml (Relative Risk [RR] 0.72, 95% CI 0.35–1.48) was not significantly associated with failure to initiate HCV treatment or failure to achieve SVR (RR 0.85, 95% CI 0.46–1.57). CONCLUSIONS: Alcohol use was common and frequently not detected by self-report. However, heavy alcohol use, even when measured objectively, was not associated with failure to initiate HCV treatment or to achieve cure.

At Kingsman University (KU), fraternity and sorority life is as central to campus culture as its athletic teams. Included in that culture are alcohol abuse, mistrust of the institution, and failure to act when a situation turns dire. Furthermore, some people suspect that fraternities and sororities perpetuate racism. Following a near-fatal incident of a first-year student by fraternity hazing at a chapter that was already on alert, the KU President called leaders from around campus to spearhead an overdue culture change. Undergraduate students worked alongside upper-level administrators and campus departments to formulate recommendations to eliminate KU’s notorious hazing culture.

BACKGROUND AND OBJECTIVES: Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up. METHODS: Participants included children ( RESULTS: Both groups improved during active treatment in all subdomains of parent stress (β = −1.42, −1.25, −0.92; P < 0.001), depressive symptoms, and anxiety symptoms (β = −0.62 and −0.78, respectively; P < 0.05). Parents who received MBSR had greater improvements than those receiving P-ESDM only in parental distress and parent-child dysfunctional interactions (β = −1.91 and −1.38, respectively; P < 0.01). Groups differed in change in mindfulness during treatment (β = 3.15; P < .05), with P-ESDM plus MBSR increasing and P-ESDM declining. Treatment group did not significantly predict change in depressive symptoms, anxiety symptoms, or life satisfaction. Differences emerged on the basis of parent sex, child age, and child behavior problems. CONCLUSIONS: Results suggest that manualized, low-intensity stress-reduction strategies may have long-term impacts on parent stress. Limitations and future directions are described.

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by bone deformities and fractures caused by low bone mass and impaired bone quality. OI is a genetically heterogeneous disorder that most commonly arises from dominant mutations in genes encoding type I collagen (COL1A1 and COL1A2). In addition, OI is recessively inherited with the majority of cases resulting from mutations in prolyl-3-hydroxylation complex members, which includes cartilage-associated protein (CRTAP). OI patients are at an increased risk of fracture throughout their lifetimes. However, non-union or delayed healing has been reported in 24% of fractures and 52% of osteotomies. Additionally, refractures typically go unreported, making the frequency of refractures in OI patients unknown. Thus, there is an unmet need to better understand the mechanisms by which OI affects fracture healing. Using an open tibial fracture model, our study demonstrates delayed healing in both Col1a2 G610c/+ and Crtap -/- OI mouse models (dominant and recessive OI, respectively) that is associated with reduced callus size and predicted strength. Callus cartilage distribution and chondrocyte maturation were altered in OI, suggesting accelerated cartilage differentiation. Importantly, we determined that healed fractured tibia in female OI mice are biomechanically weaker when compared with the contralateral unfractured bone, suggesting that abnormal OI fracture healing OI may prime future refracture at the same location. We have previously shown upregulated TGF-β signaling in OI and we confirm this in the context of fracture healing. Interestingly, treatment of Crtap -/- mice with the anti-TGF-β antibody 1D11 resulted in further reduced callus size and predicted strength, highlighting the importance of investigating dose response in treatment strategies. These data provide valuable insight into the effect of the extracellular matrix (ECM) on fracture healing, a poorly understood mechanism, and support the need for prevention of primary fractures to decrease incidence of refracture and deformity in OI patients. © 2020 American Society for Bone and Mineral Research.

TP53 mutations drive colorectal cancer development, with missense mutations frequently leading to accumulation of abnormal TP53 protein. TP53 alterations have been associated with poor prognosis and chemotherapy resistance, but data remain controversial. Here, we examined the predictive utility of TP53 overexpression in the context of current adjuvant treatment practice for patients with stage III colorectal cancer. A prospective cohort of 264 stage III patients was tested for association of TP53 expression with 5-year disease-free survival, grouped by adjuvant treatment. Findings were validated in an independent retrospective cohort of 274 stage III patients. Overexpression of TP53 protein (TP53+) was found in 53% and 52% of cases from the prospective and retrospective cohorts, respectively. Among patients receiving adjuvant chemotherapy, TP53+ status was associated with shorter disease-free survival (p ≤ 0.026 for both cohorts), while no difference in outcomes between TP53+ and TP53- cases was observed for patients treated with surgery alone. Considering patients with TP53- tumors, those receiving adjuvant treatment had better outcomes compared with those treated with surgery alone (p ≤ 0.018 for both cohorts), while no treatment benefit was apparent for patients with TP53+ tumors. Combined cohort-stratified analysis adjusted for clinicopathological variables and DNA mismatch repair status confirmed a significant interaction between TP53 expression and adjuvant treatment for disease-free survival (pinteraction = 0.030). For the combined cohort, the multivariate hazard ratio for TP53 overexpression among patients receiving adjuvant chemotherapy was 2.03 (95% confidence interval 1.41-2.95, p

Background Mild-traumatic brain injury (mTBI) and concussions cause significant morbidity. To date, synthesis of specific health care disparities and gaps in care for rural mTBI/concussion patients remains needed. Methods A comprehensive literature search was performed using PubMed database for English articles with keywords “rural” and (“concussion” or “mild traumatic brain injury”) from 1991 to 2019. Eighteen articles focusing on rural epidemiology (n = 5), management/cost (n = 5), military (n = 2), and concussion prevention/return to play (n = 6) were included. Results mTBI/concussion incidence was higher in rural compared with urban areas. Compared with urban patients, rural patients were at increased risk for vehicular injuries, lifetime number of concussions, admissions for observation without neuroimaging, and injury-related costs. Rural patients were less likely to utilize ambulatory and mental health services following mTBI/concussion. Rural secondary schools had decreased access to certified personnel for concussion evaluation, and decreased use of standardized assessment instruments/neurocognitive testing. While school coaches were aware of return-to-play laws, mTBI/concussion education rates for athletes and parents were suboptimal in both settings. Rural veterans were at increased risk for postconcussive symptoms and posttraumatic stress. Telemedicine in rural/low-resource areas is an emerging tool for rapid evaluation, triage, and follow-up. Conclusions Rural patients are at unique risk for mTBI/concussions and health care costs. Barriers to care include lower socioeconomic status, longer distances to regional medical center, and decreased availability of neuroimaging and consultants. Due to socioeconomic and distance barriers, rural schools are less able to recruit personnel certified for concussion evaluation. Telemedicine is an emerging tool for remote triage and evaluation.

Intrauterine growth restriction (IUGR) is a result of limited substrate supply to the developing fetus in utero, and can be caused by either placental, genetic or environmental factors. Babies born IUGR can have poor long-term health outcomes, including being at higher risk of developing cardiovascular disease. Limited substrate supply in the IUGR fetus not only changes the structure of the heart but may also affect metabolism and function of the developing heart. We have utilised two imaging modalities, two-photon microscopy and phase-contrast MRI (PC-MRI), to assess alterations in cardiac metabolism and function using a sheep model of IUGR. Two-photon imaging revealed that the left ventricle of IUGR fetuses (at 140-141 d GA) had a reduced optical redox ratio, suggesting a reliance on glycolysis for ATP production. Concurrently, the use of PC-MRI to measure foetal left ventricular cardiac output (LVCO) revealed a positive correlation between LVCO and redox ratio in IUGR, but not control fetuses. These data suggest that altered heart metabolism in IUGR fetuses is indicative of reduced cardiac output, which may contribute to poor cardiac outcomes in adulthood. Refereed/Peer-reviewed

Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.

Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76–[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB); DOE: DE-AC02-05CH11231 (DM)., eLife digest Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord, often leading to permanent changes in strength, sensation and body functions, and in severe cases paralysis. Scientists around the world work hard to find ways to treat or even repair spinal cord injuries but few patients with complete immediate paralysis recover fully. Immediate paralysis is caused by direct damage to neurons and their extension in the spinal cord. Previous research has shown that blood pressure regulation may be key in saving these damaged neurons, as spinal cord injuries can break the communication between nerves that is involved in controlling blood pressure. This can lead to a vicious cycle of dysregulation of blood pressure and limit the supply of blood and oxygen to the damaged spinal cord tissue, exacerbating the death of spinal neurons. Management of blood pressure is therefore a key target for spinal cord injury care, but so far, the precise thresholds to enable neurons to recover are poorly understood. To find out more, Torres-Espin, Haefeli et al. used machine learning software to analyze previously recorded blood pressure and heart rate data obtained from 118 patients that underwent spinal cord surgery after acute spinal cord injury. The analyses revealed that patients who suffered from either low or high blood pressure during surgery had poorer prospects of recovery. Statistical models confirming these findings showed that the optimal blood pressure range to ensure recovery lies between 76 to 104-117 mmHg. Any deviation from this narrow window would dramatically worsen the ability to recover. These findings suggests that dysregulated blood pressure during surgery affects to odds of recovery in patients with a spinal cord injury. Torres-Espin, Haefeli et al. provide specific information that could improve current clinical practice in trauma centers. In the future, such machine learning tools and models could help develop real-time models that could predict the likelihood of a patient’s recovery following spinal cord injury and related neurological conditions.

BACKGROUND Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study examined the prevalence of and risk factors for primary hypothyroidism and its associations with physical, neurocognitive, and psychosocial outcomes. METHODS This was a retrospective study with a cross-sectional health outcome analysis of an established cohort comprising 2965 survivors of childhood cancer (52.8% male; median current age, 30.9 years, median time since cancer diagnosis, 22.3 years). Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between primary hypothyroidism and cancer-related risk factors, cardiovascular disease risk factors, frailty, neurocognitive and QOL outcomes, social attainment, and subsequent thyroid carcinoma. Associations between serum free thyroxine and thyrotropin levels at assessment and health outcomes were explored. RESULTS The prevalence of primary hypothyroidism was 14.7% (95% CI, 13.5%-16.0%). It was more likely in females (OR, 1.06; 95% CI, 1.03-1.08), was less likely in non-Whites (OR, 0.96; 95% CI, 0.93-0.99), was associated with thyroid radiotherapy (higher risk at higher doses), and was more common if cancer was diagnosed at an age ≥ 15.0 years versus an age

Background Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. Methods Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking Results Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50–5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. Conclusions Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

BACKGROUND: Management of duodenal neuroendocrine tumors (DNETs) is not standardized, with smaller lesions (

Background Acute Heart Failure (AHF) is a potentially lethal pathology and is often encountered in the prehospital setting. Although an association between prehospital arterial hypercapnia in AHF patients and admission in high-dependency and intensive care units has been previously described, there is little data to support an association between prehospital arterial hypercapnia and mortality in this population. Methods This was a retrospective study based on electronically recorded prehospital medical files. All adult patients with AHF were included. Records lacking arterial blood gas data were excluded. Other exclusion criteria included the presence of a potentially confounding diagnosis, prehospital cardiac arrest, and inter-hospital transfers. Hypercapnia was defined as a PaCO2 higher than 6.0 kPa. The primary outcome was in-hospital mortality, and secondary outcomes were 7-day mortality and emergency room length of stay (ER LOS). Univariable and multivariable logistic regression models were used. Results We included 225 patients in the analysis. Prehospital hypercapnia was found in 132 (58.7%) patients. In-hospital mortality was higher in patients with hypercapnia (17.4% [23/132] versus 6.5% [6/93], p = 0.016), with a crude odds-ratio of 3.06 (95%CI 1.19–7.85). After adjustment for pre-specified covariates, the adjusted OR was 3.18 (95%CI 1.22–8.26). The overall 7-day mortality was also higher in hypercapnic patients (13.6% versus 5.5%, p = 0.044), and ER LOS was shorter in this population (5.6 h versus 7.1 h, p = 0.018). Conclusion Prehospital hypercapnia is associated with an increase in in-hospital and 7-day mortality in patient with AHF.

Background Retained surgical foreign bodies (RFB) are associated with inferior clinical and financial outcomes. The present work examined a nationally representative sample of all major operations to identify factors associated with RFB. Study Design The 2005-2017 National Inpatient Sample was used to identify adults undergoing cardiac, neurosurgical, orthopedic, genitourinary, gastrointestinal, vascular, and thoracic operations. International Classifications of Diseases 9th-10th Revisions diagnosis codes were used to identify instances of RFB. Results Of an estimated 71,445,042 hospitalizations, .02% had a diagnosis of RFB, with decreasing incidence from .03 to .02% over the study period (NPtrend < .001). Relative to vascular operations, gastrointestinal (adjusted odds ratio [AOR] 2.12), thoracic (AOR 1.80), and multi-cavity (AOR 2.17) were associated with greater odds of RFB. Laparoscopic approach (AOR .33) and trauma-associated admission (AOR .52, all P < .001) were associated with reduced odds of RFB. Despite similar mortality, RFB was associated with increased odds of pulmonary infection (AOR 1.62), sepsis (AOR 1.26), and wound infection (AOR 5.15), as well as a 2.3-day increment in length of stay and $7700 in hospitalization costs (all P < .001). Conclusion The development of novel mitigation strategies may reduce the incidence of RFB in high-risk populations, such as those undergoing gastrointestinal, thoracic, and multi-cavity operations.

INTRODUCTION As the incidence of elderly spinal cord injury rises, improved understanding of risk profiles and outcomes is needed. This review summarizes clinical characteristics, management, and outcomes specific to the elderly (≥65-years) with acute traumatic central cord syndrome in the USA. EVIDENCE AQUISITION Literature review of the PubMed, Embase, and CINAHL databases (01/2007-03/2020) regarding elderly subjects with acute traumatic central cord syndrome. EVIDENCE SYNTHESIS Nine studies met inclusion criteria. Acute traumatic central cord syndrome was more common among married (50%), Caucasian (22-71%) males (63-86%) with an annual income

Each year ~429,000 children and adolescents aged 0 to 19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in high-income countries (HICs) but are less than 30% for the 384,000 children in lower-middle-income countries (LMICs). Improved survival rates in HICs have been achieved through multidisciplinary care and research, with treatment regimens using mostly generic medicines and optimized risk stratification. Children’s outcomes in LMICs can be improved through global collaborative partnerships that help local leaders adapt effective treatments to local resources and clinical needs, as well as address common problems such as delayed diagnosis and treatment abandonment. Together, these approaches may bring within reach the global survival target recently set by the World Health Organization: 60% survival for all children with cancer by 2030.

Objectives Patients with dementia are at high risk for hip fractures and often have poor outcomes when a fracture is sustained. Despite this poor prognosis, little data are available on what factors should be prioritized to guide surgical decision making in these cases. We aimed to understand the decision-making process for older dementia patients hospitalized after hip fractures. Design We performed a qualitative analysis of in-depth elite interviews conducted with a clinical care team involved in management of patients with dementia after hospitalization for hip fractures. Setting Interviews were conducted with an interprofessional team involved in the care of patients with dementia after being hospitalized for hip fractures. Participants Interviewees included nine orthopaedic surgeons, three hospitalists, three geriatricians, five nurses, three occupational therapists, three physical therapists, and two clinical ethicists. Measurements Verbatim transcripts of the interviews were analyzed and coded using QSR International's NVivo 10 qualitative database management software. Results The three main themes that most interviewees discussed were pain control, functional status, and medical comorbidities. Interviewees brought up many factors related to restoring functional status including baseline functional status, rehabilitation potential, social support, and the importance of mobility. Dementia and its impact on rehabilitation potential were mentioned by all geriatricians. Conclusion Although frailty, prognosis, and life expectancy were largely absent from the responses, the emphasis on dementia, advanced directives, and involving family or caregivers by the three geriatricians indicates the importance of including geriatricians in the decision-making team for these patients.

Background Early blood product resuscitation reduces trauma patient mortality from hemorrhage. This mortality benefit depends on a system that can rapidly identify actively bleeding patients, initiate massive transfusion protocol (MTP), and mobilize resources to the bedside. We hypothesized that process improvement efforts that identify patients early and mobilize appropriate blood products to the bedside for immediate use would improve mortality. Study Design Pre-implementation, MTP activation was at the discretion of the trauma surgeon, and only PRBCs were immediately available. In June 2016, the Assessment of Blood Consumption (ABC) score was incorporated in our pre-hospital triage process, and a process for thawed plasma to be available was developed. We performed a retrospective review of patients who were hypotensive on arrival or had MTP activated. We compared mortality and MTP component ratios 15 months pre- vs 15 months post-implementation. Results Activations of MTP increased 6-fold, while the specificity of the process remained the same. In patients receiving MTP, appropriate blood product transfusion ratios increased 44%. Overall and penetrating trauma mortality improved by 23% and 41%, respectively. When divided by the Injury Severity Score (ISS), penetrating trauma mortality decreased by 65% for the ISS subgroup 15 to 24 and by 38% for ISS subgroup ≥ 25. Length of stay, ICU length of stay, and readmission rates were not significantly different. Conclusions Delivery of balanced blood product resuscitation is essential to confer mortality benefits. Process improvement directed at early recognition of the hemorrhagic patient, immediate product availability, and product delivery to the bedside for transfusion allows for mortality reduction without increased resource use.

Introduction: Risk factors for young adults with mTBI are not well understood. Improved understanding of age and sex as risk factors for impaired six-month outcomes in young adults is needed.Methods: Young adult mTBI subjects aged 18-39 years (18-29y; 30-39y) with six-month outcomes were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Multivariable regressions were performed for outcomes with age, sex, and the interaction factor age-group*sex as variables of interest, controlling for demographic and injury variables. Mean-differences (B) and 95% CIs are reported.Results: One hundred mTBI subjects (18-29y, 70%; 30-39y, 30%; male, 71%; female, 29%) met inclusion criteria. On multivariable analysis, age-group*sex was associated with six-month post-traumatic stress disorder (PTSD; PTSD Checklist-Civilian version); compared with female 30-39y, female 18-29y (B= -19.55 [-26.54, -4.45]), male 18-29y (B= -19.70 [-30.07, -9.33]), and male 30-39y (B= -15.49 [-26.54, -4.45]) were associated with decreased PTSD symptomatology. Female sex was associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended (GOSE): B= -0.6 [1.0, -0.1]). Comparatively, 30-39y scored higher on six-month nonverbal processing speed (Wechsler Adult Intelligence Scale-Processing Speed Index (WAIS-PSI); B= 11.88, 95% CI [1.66, 22.09]).Conclusions: Following mTBI, young adults aged 18-29y and 30-39y may have different risks for impairment. Sex may interact with age for PTSD symptomatology, with females 30-39y at highest risk. These results may be attributable to cortical maturation, biological response, social modifiers, and/or differential self-report. Confirmation in larger samples is needed; however, prevention and rehabilitation/counseling strategies after mTBI should likely be tailored for age and sex.

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice – a phenotype that correlates with the tendon pathology.

Prcis Kaplan-Meier analysis was used to compare the rate of corneal grafting after glaucoma drainage device placement in pediatric and adult patients. Adults were at an increased risk of receiving a corneal graft after device placement. Purpose The goal of this study was to compare the rate of corneal graft implantation after glaucoma drainage device placement in pediatric and adult patients. Patients Patients receiving a glaucoma drainage device between January 1, 1985 and December 31, 2017 were selected from the medical records. Patients receiving their first device while Methods We compared the rate of receiving a corneal graft after glaucoma drainage device implantation using Kaplan-Meier analysis. Baseline patient characteristics and surgical characteristics were compared using a generalized estimating equation. Results Corneal grafting occurred in 8.6% of adults and 4.7% of children from the original cohort.The rate of receiving a corneal graft at 5, 10, and 15 years was 9.4%, 16.8%, 39.4% and 1.6%, 1.6%, 12.5% for adults and children respectively. However, certain characteristics were different between the two groups. Conclusion Adult patients were more likely to receive a corneal graft after glaucoma drainage device placement. However, pediatric and adult patients differed in the prevalence of preexisting corneal disease, glaucoma type, glaucoma drainage device type used, and types of previous surgeries. Elucidation of the impact of these factors on corneal graft rate requires a larger cohort size.

Optimal management of duodenal neuroendocrine tumors (DNETs) has not been well-defined, especially for DNETs 1-2 cm in size. Recent studies comparing endoscopic mucosal resection (EMR) and surgical resection demonstrate EMR is safe and effective for these intermediate-sized DNETs. Expert and consensus guidelines could consider updating recommendations to reflect the outcomes of EMR in DNETs and the importance of endoscopic surveillance in these patients to evaluate for local recurrence.

BACKGROUND –: Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes. METHODS –: We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period. RESULTS –: RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R(2)=0.76, P

INTRODUCTION Liver transplantation (LT) is a life-saving treatment for end-stage liver disease patients that requires significant resources. We used national data to evaluate LT outcomes and factors associated with hospital resource use. METHODS Using the National Inpatient Sample, we identified all patients undergoing LT from 2009 to 2017 and defined high-resource use (HRU) as having costs ≥ 90th percentile. Hierarchical regression models were used to assess factors associated with length of stay (LOS) and HRU. RESULTS Over the study period, approximately 53,000 patients underwent LT, increasing from 5,582 in 2009 to 7,095 in 2017 (nptrend

Research shows that higher dietary protein of up to 1.2 g/kgbodyweight/day may help prevent sarcopenia and maintain musculoskeletal health in older individuals. Achieving higher daily dietary protein levels is challenging, particularly for older adults with declining appetites and underlying health conditions. The negative impact of these limitations on aging muscle may be circumvented through the consumption of high-quality sources of protein and/or supplementation. Currently, there is a debate regarding whether source of protein differentially affects musculoskeletal health in older adults. Whey and soy protein have been used as the most common high-quality proteins in recent literature. However, there is growing consumer demand for additional plant-sourced dietary protein options. For example, pea protein is rapidly gaining popularity among consumers, despite little to no research regarding its long-term impact on muscle health. Therefore, the objectives of this review are to: (1) review current literature from the past decade evaluating whether specific source(s) of dietary protein provide maximum benefit to muscle health in older adults; and (2) highlight the need for future research specific to underrepresented plant protein sources, such as pea protein, to then provide clearer messaging surrounding plant-sourced versus animal-sourced protein and their effects on the aging musculoskeletal system.

Background Early infant diagnosis of HIV infection is challenging in sub-Saharan Africa, particularly in rural areas, leading to delays in diagnosis and treatment. Use of a point-of-care test would overcome many challenges. This study evaluated the validity of a novel point-of-care p24 antigen detection test (LYNX) in rural and urban settings in southern Zambia. Methods Two studies were conducted: a cross-sectional study from 2014 to 2015 at Macha Hospital (LYNX Hospital study) and a longitudinal study from 2016 to 2018 at 12 health facilities in Southern Province, Zambia (NSEBA study). In both studies, children attending the facilities for early infant diagnosis were enrolled and a blood sample was collected for routine testing at the central lab and immediate on-site testing with the LYNX test. The performance of the LYNX test was measured in comparison to nucleic acid-based testing at the central lab. Results In the LYNX Hospital study, 210 tests were performed at a median age of 23.5 weeks (IQR: 8.9, 29.0). The sensitivity and specificity of the test were 70.0 and 100.0%, respectively. In the NSEBA study, 2608 tests were performed, including 1305 at birth and 1222 on children ≥4 weeks of age. For samples tested at birth, sensitivity was 13.6% (95% CI: 2.9, 34.9) and specificity was 99.6% (95% CI: 99.1, 99.9). While specificity was high for all ages, sensitivity increased with age and was higher for participants tested at ≥4 weeks of age (80.6%; 95% CI: 67.4, 93.7). Children with positive nucleic acid tests were more likely to be negative by the LYNX test if their mother received antiretroviral therapy during pregnancy (60.7% vs. 24.2%; p = 004). Conclusions Considering the high specificity and moderate sensitivity that increased with age, the LYNX test could be of value for early infant diagnosis for infants ≥4 weeks of age, particularly in rural areas where centralized testing leads to long delays. Point-of-care tests with moderate sensitivity and high specificity that are affordable, easy-to-use, and easily implemented and maintained should be developed to expand access to testing and deliver same-day results to infants in areas where it is not feasible to implement nucleic acid-based point-of-care assays.

Despite minimum volume recommendations, the majority of esophagectomies are performed at centers with fewer than 20 annual cases. The present study examined the impact of institutional esophagectomy volume on in-hospital mortality, complications, and resource use after esophageal resection.The 2010-2018 Nationwide Readmissions Database was queried to identify all adult patients undergoing esophagectomy for malignancy. Hospitals were categorized as a high-volume hospital (HVH) if performing at least 20 esophagectomies annually and as a low-volume hospital (LVH) if performing fewer than 20 esophagectomies annually. Multivariable models were developed to study the impact of volume on outcomes of interest, which included in-hospital mortality, complications, duration of hospitalization, inflation adjusted costs, readmissions, and nonhome discharge.Of an estimated 23,176 hospitalizations, 45.6% occurred at HVHs. Incidence of esophagectomy increased significantly along with median institutional caseload over the study period, while the proportion on hospitals considered HVHs remained steady at approximately 7.4%. After adjusting for relevant patient and hospital characteristics, HVH status was associated with decreased mortality (AOR, 0.65), length of stay (β = -1.83), pneumonia (AOR, 0.69), prolonged ventilation (AOR, 0.50), sepsis (AOR, 0.80), and tracheostomy (AOR, 0.66) but increased odds of nonhome discharge (AOR, 1.56; all P.01), with LVH status as reference.Many clinical outcomes of esophagectomy are improved with no increment in costs when performed at centers with an annual caseload of at least 20, as recommended by patient advocacy organizations. These findings suggest that centralization of esophageal resections to high-volume centers may be congruent with value-based care models.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease affecting up to 6.5% of the general population. There is no simple definition of NASH, and the molecular mechanism underlying disease pathogenesis remains elusive. Studies applying single omics technologies have enabled a better understanding of the molecular profiles associated with steatosis and hepatic inflammation—the commonly accepted histologic features for diagnosing NASH, as well as the discovery of novel candidate biomarkers. Multi-omics analysis holds great potential to uncover new insights into disease mechanism through integrating multiple layers of molecular information. Despite the technical and computational challenges associated with such efforts, a few pioneering studies have successfully applied multi-omics technologies to investigate NASH. Here, we review the most recent technological developments in mass spectrometry (MS)-based proteomics, metabolomics, and lipidomics. We summarize multi-omics studies and emerging omics biomarkers in NASH and highlight the biological insights gained through these integrated analyses.

Background Surgical re-exploration following cardiac surgery has been associated with increased in-hospital complications and mortality in limited series. The present study examined trends in reoperation and its impact on clinical outcomes and resource use in a nationally-representative cohort. We sought to determine patient and hospital factors associated with re-exploration and reoperative mortality, defined as failure-to-rescue-surgical (FTR-S). Methods Adult hospitalizations entailing cardiac operations (coronary artery bypass and/or valve) were identified using the 2005-2018 National Inpatient Sample. Procedures were tabulated using International Classification of Diseases codes. Hospitals were ranked into tertiles according to risk-adjusted mortality, with the lowest stratified as high-performing. Multivariable regression models examined factors associated with re-exploration as well as clinical outcomes including FTR-S and resource utilization. Results Of an estimated 3,490,245 hospitalizations, 78,003 (2.23%) required re-exploration with decreasing incidence over time. Valvular procedures, preoperative intra-aortic balloon pump and liver disease were associated with greater likelihood of re-exploration. Reoperation was associated with increased odds of mortality (adjusted odds ratio (AOR): 3.86, 95%CI: 3.61-4.12), perioperative complications and resource utilization. Increasing time from index operation to re-exploration was associated with higher odds of mortality (AOR:1.10/day, 95%CI: 1.07-1.12). High-performing hospitals were associated with lower odds of re-exploration (AOR: 0.88, 95%CI: 0.82-0.95) and FTR-S (AOR: 0.29, 95%CI: 0.23-0.35). Conclusions Surgical re-exploration following cardiac surgery has declined over time. High performing hospitals demonstrated lower rates of re-exploration and subsequent failure-to-rescue. Although unable to identify specific practices, our study highlights the presence of significant variation in takeback rates and further study of underlying factors is warranted.