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Summary Despite the decades-old knowledge that diabetes mellitus is a major risk factor for cardiovascular disease, the reasons for this association are only partially understood. While this association is true for both type 1 and type 2 diabetes, different pathophysiological processes may be responsible. Lipids and other risk factors are indeed important, whereas the role of glucose is less clear. This lack of clarity stems from clinical trials that do not unambiguously show that intensive glycemic control reduces cardiovascular events. Animal models have provided mechanisms that link diabetes to increased atherosclerosis, and evidence consistent with the importance of factors beyond hyperglycemia has emerged. We review clinical, pathological, and animal studies exploring the pathogenesis of atherosclerosis in humans living with diabetes and in mouse models of diabetes. An increased effort to identify risk factors beyond glucose is now needed to prevent the increased cardiovascular disease risk associated with diabetes.

Objectives This study aimed to determine SARS-CoV-2 seroprevalence among pregnant women in the Scottish population during the second wave of the COVID-19 pandemic. Study design Prospective national serosurvey. Methods We tested 13,428 residual samples retrieved from pregnant women participating in the first trimester combined ultrasound and biochemical screening for fetal trisomy across Scotland for SARS-CoV-2 antibodies over a 6-month period from November 2020 to April 2021. Seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Results Seroprevalence rates in the antenatal samples significantly increased from 5.5% (95% confidence interval [CI] 4.7%–6.5%) in the 5-week period up to and including International Organization for Standardization (ISO) Week 51 (w/b Monday 14 December 2020) to 11.3% (95% CI 10.1%–12.6%) in the 5-week period up to and including ISO Week 14 (w/b Monday 5 April 2021). Increasing seroprevalence trends across the second wave were observed among all age groups. Conclusions By the end of the second wave of the COVID-19 pandemic, approximately one in 10 women tested around the end of the first trimester of pregnancy had antibodies to SARS-CoV-2, suggesting that the vast majority were still susceptible to COVID-19 as they progressed to the later stages of pregnancy, when risks from infection are elevated for both mother and baby.

Women with advanced lung disease, particularly Black and Hispanic women, are more likely than other patients to have anti-human leukocyte (HLA) antibodies against potential donors. Sensitized patients, especially those who are highly sensitized, are less likely to be listed for lung transplant or to be considered candidates for mechanical circulatory support. They are also at higher risk for waitlist death. Institutional variability in approach to HLA antibody screening and pre-transplant management creates barriers to transplant that disproportionately impact Black and Hispanic women. At the same time, our understanding of the clinical significance of pre-transplant antibodies lags behind the sophistication of our screening assays. The lack of national data on pre- and post-transplant HLA antibody characteristics hinders research into strategies to mitigate concerns about these antibodies and to improve access to lung transplant among sensitized patients. Ongoing work should be done to identify clinically higher risk antibodies, to develop better strategies for safely crossing antibodies at the time of transplant, and to model changes in lung allocation to give priority to sensitized patients for a HLA antibody-antigen compatible donors. These priorities mandate a commitment to collaborative, multicenter research and to real time translation of results to clinical practice and allocation policy.

Patients with dextro-transposition of the great arteries (d-TGA) require surgical repair as neonates. These patients are at risk for post-operative chylothorax. We sought to describe the presentation, imaging, and outcomes after intervention for patients with d-TGA with post-operative chylothorax. A retrospective chart review was performed in patients with repaired d-TGA who were referred from 1/1/2013 to 4/1/2020 for evaluation of chylothorax. Patient history, lymphatic imaging, and interventional data were collected. Impact of intervention on lymphatic drainage was evaluated with a student's t-test. Eight patients met inclusion criteria for this study. Five patients had a history of central venous thrombus leading to thoracic duct outlet occlusion. Five patients underwent intervention, two were managed conservatively, and one was not a candidate for intervention. Chylothorax resolved in six patients. There was a significant difference in output from 7 days prior to first intervention (114 mL/kg/day) compared to 28 days following final intervention (27 mL/kg/day, p = 0.034). There were no procedural complications. Chylothorax in patients with repaired transposition of the great arteries is often amenable to intervention. Early surveillance and management of central venous thrombosis may reduce the burden of lymphatic disease in these patients.

Although tissue uptake of fatty acids from chylomicrons is primarily via lipoprotein lipase (LpL) hydrolysis of triglycerides (TGs), studies of patients with genetic LpL deficiency suggest additional pathways deliver dietary lipids to tissues. Despite an intact endothelial cell (EC) barrier, hyperchylomicronemic patients accumulate chylomicron-derived lipids within skin macrophages, leading to the clinical finding eruptive xanthomas. We explored whether an LpL-independent pathway exists for transfer of circulating lipids across the EC barrier. We found that LpL-deficient mice had a marked increase in aortic EC lipid droplets before and after a fat gavage. Cultured ECs internalized chylomicrons, which were hydrolyzed within lysosomes. The products of this hydrolysis fueled lipid droplet biogenesis in ECs and triggered lipid accumulation in cocultured macrophages. EC chylomicron uptake was inhibited by competition with HDL and knockdown of the scavenger receptor-BI (SR-BI). In vivo, SR-BI knockdown reduced TG accumulation in aortic ECs and skin macrophages of LpL-deficient mice. Thus, ECs internalize chylomicrons, metabolize them in lysosomes, and either store or release their lipids. This latter process may allow accumulation of TGs within skin macrophages and illustrates a pathway that might be responsible for creation of eruptive xanthomas.

Police transport (PT) of penetrating trauma patients decreases the time between injury and trauma center arrival. Our study objective was to characterize trends in the rate of PT and its impact on mortality. We hypothesized that PT is increasing and that these patients are more injured.We conducted a single-center, retrospective cohort study of adult (≥18 years) patients presenting with gunshot wounds (GSWs) to a level 1 center from 2012 to 2018. Patients transported by police or ambulance (emergency medical service [EMS]) were included. The association between mode of transport (PT vs. EMS) and mortality was evaluated using χ2, t tests, Mann-Whitney U tests, and logistic regression.Of 2,007 patients, there were 1,357 PT patients and 650 EMS patients. Overall in-hospital mortality was 23.7%. The rate of GSW patients arriving by PT increased from 48.9% to 78.5% over the study period (p0.001). Compared with EMS patients, PT patients were sicker on presentation with lower initial systolic blood pressure (98 vs. 110, p0.001), higher Injury Severity Score (median [interquartile range], 10 [2-75] vs. 9 [1-17]; p0.001) and more bullet wounds (3.5 vs. 2.9, p0.001). Police-transported patients more frequently underwent resuscitative thoracotomy (19.2% vs. 10.0%, p0.001) and immediate surgical exploration (31.3% vs. 22.6%, p0.001). There was no difference in adjusted in-hospital mortality between transport groups. Of patients surviving to discharge, PT patients had higher Injury Severity Score (9.6 vs. 8.3, p = 0.004) and lower systolic blood pressure on arrival (126 vs. 130, p = 0.013) than EMS patients.Police transport of GSW patients is increasing at our urban level 1 center. Compared with EMS patients, PT patients are more severely injured but have similar in-hospital mortality. Further study is necessary to understand the impact of PT on outcomes in specific subsets in penetrating trauma patients.Epidemiological, level III.

OBJECTIVE Residents often are involved in discussions with families regarding brain death/death by neurologic criteria (BD/DNC); however, they receive no standardized training on this topic. We hypothesized that residents are uncomfortable with explaining BD/DNC and that formal didactic and simulated training will improve residents’ comfort and skill in discussions surrounding BD/DNC. DESIGN We partnered with our organ procurement organization (OPO) to create an educational program regarding BD/DNC consisting of a didactic component, and role-play scenarios with immediate individualized feedback. Residents completed pre- and post-training surveys. SETTING This study included participants from 16 academic and community institutions across New Jersey, Pennsylvania, and Delaware that are within our OPO's region. PARTICIPANTS Subjects were recruited using convenience sampling based on the institution and training programs’ willingness to participate. A total of 1422 residents at participated in the training from 2009 to 2020. 1389 (97.7%) participants competed the pre-intervention survey, while 1361 (95.7%) completed the post-intervention survey. RESULTS Prior to the training, only 56% of residents correctly identified BD/DNC as synonymous with death. Additionally, 40% of residents had explained BD/DNC to families at least once, but 41% of residents reported never having been taught how to do so. The biggest fear reported in discussing BD/DNC with families was being uncomfortable in explaining BD/DNC (48%). After participating in the training, 99% of residents understood the definition of BD/DNC and 92% of residents felt comfortable discussing BD/DNC with families. CONCLUSIONS Participation in a standardized curriculum improves residents’ understanding of BD/DNC and their comfort in discussing BD/DNC with families.

The transmembrane protein, cluster of differentiation 36 (CD36), facilitates tissue fatty acid uptake and is highly expressed in a variety of different cell types, including endothelial cells (ECs). Loss of EC Cd36 reduces parenchymal long-chain fatty acid uptake and improves whole-body glucose tolerance and insulin sensitivity; however, the mechanisms by which this occurs remain unclear. Here, we report that EC-specific deletion of Cd36 in chow-fed male mice (EC-Cd36-/-) leads to significant reductions in whole-body fat utilization during fasting, subsequently increasing plasma non-esterified fatty acid levels by 30% (P Conclusion: Taken together, these results demonstrate a key role for EC Cd36 in regulating parenchymal fuel selection and hepatic glucose production and provide insight into the mechanisms by which EC Cd36 controls systemic glucose and lipid metabolism. Disclosure L. Goedeke: None. N. Son: None. T. E. Lamoia: None. A. Nasiri: Employee; Spouse/Partner; Medtronic. M. Kahn: None. X. Zhang: None. G. Cline: None. I. J. Goldberg: Advisory Panel; Self; Akcea Therapeutics, Arrowhead Pharmaceuticals, Inc., Consultant; Self; Esperion. G. I. Shulman: Consultant; Self; 89bio, Inc., BridgeBio, Ionis Pharmaceuticals, Maze Therapeutics, Novo Nordisk, Other Relationship; Self; AstraZeneca, Esperion Therapeutics, Inc, Generian Pharmaceuticals, Inc., Gilead Sciences, Inc., iMetabolic Biopharma Corporation, Janssen Research & Development, LLC, Merck & Co., Inc., The Liver Company. Funding National Institutes of Health (HL150234, R01DK113984, R01DK045735)

BACKGROUND: Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.OBJECTIVE: In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).METHODS: Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.RESULTS: HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.CONCLUSION: HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

Objective: Fatty acid uptake and oxidation characterize the metabolism of alternatively activated macrophage polarization in vitro, but the in vivo biology is less clear. We assessed the roles of LpL (lipoprotein lipase)-mediated lipid uptake in macrophage polarization in vitro and in several important tissues in vivo. Approach and Results: We created mice with both global and myeloid-cell specific LpL deficiency. LpL deficiency in the presence of VLDL (very low-density lipoproteins) altered gene expression of bone marrow–derived macrophages and led to reduced lipid uptake but an increase in some anti- and some proinflammatory markers. However, LpL deficiency did not alter lipid accumulation or gene expression in circulating monocytes nor did it change the ratio of Ly6C high /Ly6C low . In adipose tissue, less macrophage lipid accumulation was found with global but not myeloid-specific LpL deficiency. Neither deletion affected the expression of inflammatory genes. Global LpL deficiency also reduced the numbers of elicited peritoneal macrophages. Finally, we assessed gene expression in macrophages from atherosclerotic lesions during regression; LpL deficiency did not affect the polarity of plaque macrophages. Conclusions: The phenotypic changes observed in macrophages upon deletion of Lpl in vitro is not mimicked in tissue macrophages.

Rheumatoid arthritis (RA) is the most common of the connective tissue diseases (CTD), affecting up to 0.75% of the United States (U.S.) population with an increasing prevalence. Interstitial lung disease is prevalent and morbid condition in RA (RA-ILD), affecting up to 60% of patients with RA, leading to premature death in 10% and accruing an average of US$170,000 in healthcare costs per patient over a 5-year period. Although there have been significant advances in the management of this joint disease, there are no ongoing randomized clinical trials looking at pharmacologic treatments for RA-ILD, and there currently are no U.S. Food and Drug Administration-approved drugs for RA-ILD. We describe the Treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) trial, a multicenter randomized, double-blind, placebo-controlled, phase 2 study of the safety, tolerability and efficacy of pirfenidone in patients with RA-ILD. The study will enroll approximately 270 subjects across a network of sites who have RA and ILD as defined by a fibrotic abnormality involving greater than 10% of the lung parenchyma. The primary endpoint of the study is the incidence of the composite endpoint of decline in percent predicted forced vital capacity of 10 or greater or death during the 52-week study period. A number of secondary and exploratory endpoints have been chosen to evaluate the safety and efficacy in different domains. The TRAIL1 trial is designed to evaluate the safety and efficacy of pirfenidone in RA-ILD, a disease with significant impact on patients’ quality of life and outcome. In addition to investigating the safety and efficacy of pirfenidone, this trial looks at a number of exploratory endpoints in an effort to better understand the impact of therapy on areas such as changes in quantitative high-resolution computed tomography scores and a patient’s quality of life. Biospecimens will be collected in order to investigate biomarkers that could potentially predict the subtype of disease, its behavior over time, and its response to therapy. Finally, by creating a network of institutions and clinician investigators with an interest in RA-ILD, this trial will pave the way for future studies of investigational agents in an effort to reduce or eliminate the burden of disease for those suffering from RA-ILD. Genentech, a member of the Roche Group. Clinicaltrials.gov, identifier NCT02808871.

Rationale: There is significant variation in approach to pre-lung transplant donor-specific antibodies (DSA), with some centers declining to cross any DSA. We implemented a protocol for transplantation for candidates with pretransplant DSA so long as a prospective complement-dependent cytotoxicity crossmatch was negative, regardless of number, specificity, class, or mean fluorescence intensity.Objectives: To compare post-transplant outcomes including overall survival, chronic lung allograft dysfunction-free survival, antibody-mediated rejection, and acute cellular rejection in lung transplant recipients where pretransplant DSA was and was not present.Methods: This was a single-center retrospective cohort study. For recipients with pretransplant DSA, if the prospective complement-dependent cytotoxicity crossmatch was negative, the donor offer was accepted and plasmapheresis was performed within 24 hours of transplantation and continued until retrospective crossmatch results returned. Immunosuppression and post-transplant management were not otherwise modified.Results: Of the 203 included recipients, 18 (8.9%) had pretransplant DSA. The median DSA mean fluorescence intensity was 4,000 (interquartile range, 2,975-5,625; total range, 2,100-17,000). The median number of DSA present per patient was one (interquartile range, 1-2). The presence of pretransplant DSA was not associated with increased mortality (hazard ratio, 1.2; 95% confidence interval [CI], 0.4-3.4) or decreased chronic lung allograft dysfunction-free survival (hazard ratio, 1.1; 95% CI, 0.6-2.1). Recipients with pretransplant DSA were more likely to require prolonged mechanical ventilation (adjusted odds ratio, 7.0; 95% CI, 2.3-21.6) and to have antibody-mediated rejection requiring treatment (adjusted odds ratio, 7.5; 95% CI, 1.0-55.8).Conclusions: A protocol of accepting donor offers for lung transplant candidates with preformed, complement-dependent cytotoxicity crossmatch-negative DSA is associated with increased need for prolonged mechanical ventilation and antibody-mediated rejection without affecting short-term overall or chronic lung allograft dysfunction-free survival.

BACKGROUND There are no published data characterizing burnout rates for pediatric orthopaedic surgeons. The primary purpose of this study was to identify the rates of self-reported personal and team burnout among members of the Pediatric Orthopaedic Society of North America (POSNA). A secondary aim was to determine whether specific demographic variables were more likely to be associated with self-reported burnout. METHODS During its 2018 annual meeting, the POSNA Wellness Taskforce launched a web-based survey in which members were asked to respond to 2 previously validated questions related to personal and team burnout. The survey was distributed by a closed POSNA membership e-mail list and responses were analyzed anonymously. Descriptive statistics were calculated. Pearson χ testing was used to analyze differences in burnout rates as a function of age and sex. RESULTS A total of 615 POSNA members completed the survey, a 47% response rate. Overall, 38% reported personal burnout and 46% reported team burnout. Women were more likely to report both personal (P

Background & Aims In 2016, the World Health Assembly passed a resolution to eliminate viral hepatitis as a public health threat by 2030. We aimed to examine the status of the global viral hepatitis response. Methods In 2017, the World Health Organization (WHO) asked the Ministries of Health in all 194 Member States to complete a Country Profile on Viral Hepatitis policy uptake indicators, covering national plans/funding, engagement of civil society, testing guidance, access to treatment, and strategic information. Results Of 194 Member States, 135 (70%) responded, accounting for 87% of the global population infected with hepatitis B virus (HBV) and/or C virus (HCV). Of those responding, 84 (62%) had developed a national plan, of which, 49 (58%) had dedicated funding, and 62 (46%) had engaged with civil society; those engaged with civil society were more likely to have a funded plan than others (52% vs. 23%, p = 0.001). Guidance on testing pregnant women (for HBV) and people who inject drugs (for HCV) was available in 70% and 46% of Member States, respectively; 59% and 38% of Member States reported universal access to optimal therapies for HBV and HCV, respectively. Conclusions Most people living with hepatitis B and C reside in a country with a national hepatitis strategy. Governments who engaged with civil society were more advanced in their response. Member States need to finance these national strategies and ensure that those affected have access to hepatitis services as part of efforts to achieve universal health coverage. Lay summary The World Health Organization’s goal to eliminate viral hepatitis as a public health threat by 2030 requires global action. Our results indicate that progress is being made by countries to scale-up national planning efforts; however, our results also highlight important gaps in current policies., Graphical abstract Unlabelled Image, Highlights • Countries are making progress across all WHO regions in responding to viral hepatitis • Governments engaged with Civil Society are more advanced in their national planning efforts • Financing remains an issue with a minority of countries with a national plan having some dedicated funding • Stronger surveillance and monitoring systems are needed to direct hepatitis elimination plans

Introduction Erectile dysfunction is defined as the inability to achieve and maintain an erection to satisfactorily complete intercourse. Treatment depends on the cause and includes phosphodiesterase 5 inhibitor medications, penile pumps, implants, and surgery. Low-intensity shockwave therapy has been shown to be effective and safe for the treatment of erectile dysfunction. Objective We explored the role of low-intensity radial shockwave therapy for erectile dysfunction treatment in a dermatology and/or medical aesthetic practice setting. Materials and methods A literature review was conducted on radial low-intensity shockwave technology in use for erectile rejuvenation to explore its positioning, safety, efficacy, tolerability, subject satisfaction, and usability in a dermatology and/or medical aesthetic setting. Results Low-intensity shockwave therapy was shown to be effective in subjects with organic erectile dysfunction, and the treatment effect was maintained for up to 2 years post-treatment. The treatment is reported to be safe and well-tolerated and have little downtime. Many dermatologists use low-intensity shockwave therapy for the treatment of cellulite and other conditions. This type of treatment is now available for erectile dysfunction and seems an attractive and safe option for subjects with organic vascular erectile dysfunction. Conclusions Studies and clinical experience suggest that male erectile rejuvenation using low-intensity radial shockwave therapy seems an attractive option. The treatment can be safely, and effectively, delivered by trained staff as part of the total package that is available to men in a dermatology and/or medical aesthetic practice.

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients. This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). Chronic lung allograft dysfunction (CLAD)-free survival was also evaluated based on HA and LYVE-1 levels. 78 recipients were enrolled with a total of 115 diagnostic biopsies and 1.5 years of median follow-up. Serum HA was correlated with BAL HA (r = 0.25, p = 0.01) and with serum LYVE-1 (r = 0.32, p = 0.002). There was significant variation in HA and LYVE-1 over time, regardless of ACR status. Levels of serum HA (median 74.7 vs 82.7, p = 0.69), BAL HA (median 149.4 vs 134.5, p = 0.39), and LYVE-1 (mean 190.2 vs 183.8, p = 0.72) were not associated with ACR. CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3–7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2–3.6, p = 0.93). These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients.

Let $$\left\{ A_t\right\} _{t\ge 0}$$ be a symmetric diffusion semigroup on $$L_p(X)$$ , for X a complete positive $$\sigma $$ -finite measure space. We establish an equivalence between the $$L_p$$ rate of approximation of $$A_t\phi $$ to $$\phi $$ (as $$t\rightarrow 0^+$$ ) and a measure of the smoothness of $$\phi $$ relative to the diffusion. The following is our main result: For $$10$$ independent of the semigroup so that for $$\phi \in L_p(X)$$ and $$0

In complete atrioventricular canal defect (CAVC), there are limited data on preoperative clinical and echocardiographic predictors of operative timing and postoperative outcomes. A retrospective, single-center analysis of all patients who underwent primary biventricular repair of CAVC between 2006 and 2015 was performed. Associated cardiac anomalies (tetralogy of Fallot, double outlet right ventricle) and arch operation were excluded. Echocardiographic findings on first postnatal echocardiogram were correlated with surgical timing and postoperative outcomes using bivariate descriptive statistics and multivariable logistic regression. 153 subjects (40% male, 84% Down syndrome) underwent primary CAVC repair at a median age of 3.3 (IQR 2.5–4.2) months. Median postoperative length of stay (LOS) was 7 (IQR 5–15) days. Eight patients (5%) died postoperatively and 24 (16%) required reoperation within 1 year. On multivariable analysis, small aortic isthmus (z score

Although interest in hospice and palliative care for companion animals is on the rise, formal training in these areas is limited. Veterinary teaching institutions, professional organizations, and accrediting bodies have much to gain from the human palliative medicine field. Core competencies, curricular milestones, and scope of practice for palliative medicine are identified. A formal palliative care intervention has been implemented in a US veterinary teaching institution, and preliminary evaluation data reflect significant potential for integration of palliative care training into veterinary teaching. Positive outcomes for veterinarian well-being and ability to cope with emotional demands are suggested.

Goals of care (GOC) conversations and resulting goal-concordant treatment are the heart of palliative medicine. Despite repeated evidence that GOC conversations offer significant benefit and minimal harm, barriers to widespread and high-quality implementation persist in human medicine. One strategy to overcoming these barriers has been utilization of a structured checklist format for serious illness conversations. The Serious Illness Conversation Guide was developed for human patients and has been modified for use in the veterinary profession. The guide promotes individualized, goal-concordant care planning even when conflict and emotional demands are high.

Background Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. Methods We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. Results A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. Conclusions In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

The purpose of this study was to develop a hepatitis C virus (HCV) and HIV screening program for patients evaluated by the trauma service and link to care. Patients were offered screening for HCV antibody and HIV. Demographics were collected on gender, race, age, and history of intravenous drug use. A navigator connected patients to treatment. In total, 1160 trauma patients were screened for HCV and/or HIV. There were 162 (14%) patients with HCV antibodies. Patients who inject drugs comprised 39.5% (64) of the HCV antibody positive group. Forty-six (68.7%) patients received linkage to care services and 55 (34%) patients were actively engaged in treatment. There were 155 (10.5%) of all eligible patients screened for HIV. Twenty-one (13.5%) patients were living with HIV (PLWH) and there were two (1.3%) new HIV infections. All new PLWH were linked to care and a total of 14 (73.7%) PLWH were on antiretroviral therapy. This is the first HCV and HIV screening and linkage to care program of trauma surgery patients. In this interim program evaluation, we found high prevalence of HCV antibody and HIV prevalence and high linkage to care rates. Trauma service HCV and HIV screening is an opportunity to diagnose, link, and re-engage a vulnerable population.

Background Novel Psychoactive Substance (NPS) use has increased in recent years and generated significant concern within public health. People who inject drugs (PWID) are at increased risk of blood borne viruses, in particular Hepatitis C virus (HCV). However, little is known about the extent of NPS injecting at a national level and its association with HCV. This study provides one of the first epidemiological analyses of the association between NPS injecting and HCV among a population level sample of PWID. Methods Five cross sectional surveys of almost 13,000 PWID attending services providing injecting equipment across Scotland between 2008 and 2016 were analysed. Logistic regression was used to determine associations between NPS injecting and HCV. Results The proportion of PWID reporting that they had injected NPS in the previous six months increased from 0.2% in 2008–09 to 11.0% in 2015–16. Those who reported injecting NPS were considerably more likely to be resident in the Lothian NHS Board area at the time of the study (AOR 5.6 (95% CI 4.1–7.5)) and to have had recent experience of homelessness (AOR 1.4 (95% CI 1.0–1.9)). People who injected NPS were also significantly more likely to be HCV positive (AOR 1.7 (95% CI 1.2–2.4)). In Lothian, HCV prevalence rose from around 30% between 2008 and 2012 to 41% and then 48% in 2013–14 and 2015–16 respectively. Increases in prevalent HCV infection in Lothian may be partly attributed to increases in NPS injecting. Conclusion In Scotland, people who had injected Novel Psychoactive Substances were at increased risk of hepatitis C virus. Novel Psychoactive Substance injecting poses a threat to HCV elimination strategies.

OBJECTIVE To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies. DESIGN Retrospective cohort study. SETTING Seven US healthcare delivery systems. PARTICIPANTS Adults with left ventricular systolic dysfunction receiving an implantable cardioverter-defibrillator (ICD) for primary prevention. MEASUREMENTS Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0-3, 4-5, 6-7 and 8-16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy. RESULTS Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4-8), with 98% having at least two comorbidities. During a mean 2.2 years of follow-up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14-3.31] for 4-5 comorbidities; HR = 2.25 [95% CI = 1.25-4.05] for 6-7 comorbidities; and HR = 2.91 [95% CI = 1.54-5.50] for 8-16 comorbidities). Participants with 8-16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43-3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67-6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07-2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies. CONCLUSIONS In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation.

The care of lung transplant recipients with prolonged index hospitalizations can be ethically complex, with conflicts arising over whether the expected outcomes justify ongoing intensive interventions. There are limited data to guide these conversations. The objective of this study was to evaluate survival to discharge for lung transplant recipients based on length of stay (LOS). This was a retrospective cohort study of adult lung transplant recipients in the Scientific Registry of Transplant Recipients. For each day of the index hospitalization the mortality rate among patients who survived to that length of stay or longer was calculated. Post-discharge survival was compared in those with and without a prolonged hospitalization (defined as the 97th percentile [>90 days]). Among the 19 250 included recipients, the index hospitalization mortality was 5.4%. Posttransplant stroke and need for dialysis were the strongest predictors of index hospitalization mortality. No individual or combination of available risk factors, however, was associated with inpatient mortality consistently above 50%. Recipients with >90 day index hospitalization had a 28.8% subsequent inpatient mortality. Their 1, 3 and 5 year survival following discharge was 53%, 26%, and 16%. These data provide additional context to goals of care conversations for transplant recipients with prolonged index hospitalizations.

BACKGROUND: Long-term trends in the incidence rates (IRs) and hospital case-fatality rates (CFRs) of ventricular tachycardia (VT) and ventricular fibrillation (VF) among patients hospitalized with acute myocardial infarction (AMI) have not been recently examined. METHODS AND RESULTS: We used data from 11,825 patients hospitalized with AMI at all 11 medical centers in central Massachusetts on a biennial basis between 1986 and 2011. Multivariable adjusted logistic regression modeling was used to examine trends in hospital IRs and CFRs of VT and VF complicating AMI. The median age of the study population was 71 years, 57.9% were men, and 94.7% were white. The hospital IRs declined from 14.3% in 1986/1988 to 10.5% in 2009/2011 for VT and from 8.2% to 1.7% for VF. The in-hospital CFRs declined from 27.7% to 6.9% for VT and from 49.6% to 36.0% for VF between 1986/1988 and 2009/2011, respectively. The IRs of both early (

Despite the magnitude and impact of acute coronary disease, there are limited population-based data in the United States describing relatively recent trends in the incidence rates of acute myocardial infarction (AMI). The objectives of this study were to describe decade long (2001-2011) trends in the incidence rates of initial hospitalized episodes of AMI, with further stratification of these rates by age, sex, and type of AMI, in residents of central Massachusetts hospitalized at 11 area medical centers. The study population consisted of 3,737 adults hospitalized with a first AMI at 11 medical centers in central Massachusetts on a biennial basis between 2001 and 2011. The median age of this study population was 70 years, 57% were men, and 90% were white. Patients hospitalized during the most recent study years (2009/11) were younger, more likely to be men, have more co-morbidities, and less in-hospital complications as compared with those in the earliest study years (2001/03). The overall age-adjusted hospital incidence rates (per 100,000 persons) of initial AMI declined (from 319 to 163), for men (from 422 to 219), women (from 232 to 120), for patients with a ST segment elevation (129 to 56), and for those with an non-ST segment elevation (190 to 107) between 2001 and 2011, respectively. In conclusion, the incidence rates of initial AMI declined appreciably in residents of central Massachusetts who were hospitalized with AMI during the years under study.

Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe. Although guidelines advocate aggressive management of lipid parameters in diabetes, most guidelines do not address treatment of dyslipidemia in prediabetes despite the increased atherosclerotic cardiovascular disease (ASCVD) risk. Several criteria are used to diagnose prediabetes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and HbA1c of 5.7-6.4%. Individuals with prediabetes have a greater risk of diabetes, a higher prevalence of dyslipidemia with a more atherogenic lipid profile and an increased risk of ASCVD. In addition to calculating ASCVD risk using traditional methods, an OGTT may further stratify risk. Those with 1-hour plasma glucose ≥8.6 mmol/L (155 mg/dL) and/or 2-hour ≥7.8 mmol/L (140 mg/dL) (IGT) have a greater risk of ASCVD. Diet and lifestyle modification are fundamental in prediabetes. Statins, ezetimibe and PCSK9 inhibitors are recommended in people requiring pharmacotherapy. Although high-intensity statins may increase risk of diabetes, this is acceptable because of the greater reduction of ASCVD. The LDL-C goal in prediabetes should be individualized. In those with IGT and/or elevated 1-hour plasma glucose, the same intensive approach to dyslipidemia as recommended for diabetes should be considered, particularly if other ASCVD risk factors are present.