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Outcomes in patients with smaller body size after HeartMate 3 left ventricular assist device (HM3) implantation are not well characterized. We sought to evaluate outcomes in smaller vs larger body surface area (BSA) patients in the MOMENTUM 3 pivotal trial and its Continued Access Protocol cohort. The analysis cohort included 1015 HM3 patients divided into 2 groups: BSA ≤1.70 m2 (small patients, n = 82) and BSA >1.70 m2 (large patients, n = 933). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or to remove a malfunctioning device. Adverse events were compared between groups. Smaller patients were more frequently women (56.1% vs 17.7%; P <.001) and had lower prevalence of diabetes (28.1% vs 43.9%; P =.005) and hypertension (51.2% vs 71.9%; P <.001), larger median indexed LVEDD (normalized by BSA, 40 vs 33 mm/m2; P <.001), and lower median serum creatinine concentration (1.1 vs 1.3 mg/dL; P <.001). The proportion of patients achieving the composite end point at 2 years was 77% in both groups (adjusted hazard ratio, 1.14; 95% CI, 0.68-1.91; P =.62). Two-year adverse event rates were also similar between groups except for sepsis (6.1% vs 14.9%; P =.029) and cardiac arrhythmias (24.4% vs 35.3%; P =.005), which were higher in the larger patients. Outcomes after HM3 implantation were comparable between small and large patients. Smaller body size should not be used to deny HM3 implantation in patients who are otherwise suitable candidates for durable mechanical circulatory support. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac injury has been reported in up to 20%-to-30% of patients with COVID-19, and severe disease can lead to cardiopulmonary failure. The role of mechanical circulatory support in these patients remains undetermined. The authors here aimed to determine the characteristics and outcomes of patients with COVID-19 requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) or veno-arterial-venous (VAV) ECMO support. A multicenter, retrospective case series. The cohort consisted of adult patients (18 years of age and older) with confirmed COVID-19 requiring VA ECMO or VAV ECMO support in the period from March 1, 2020, to April 30, 2021. Outcomes were recorded until July 31, 2021. To show factors related to death during hospitalization, patients were grouped as survivors and nonsurvivors. Kaplan-Meier analysis was used to estimate 90-day in-hospital mortality. Overall, 37 patients from 12 centers comprised the study cohort. The median patient age was 44 years old (interquartile range [IQR], 35-52), and 12 (32%) were female patients. The duration of ECMO support ranged from 2-to-132 days. At the end of the follow-up period, 13 patients (35%) were discharged or transferred alive, and 24 patients (65%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 64% (95% confidence interval: 47-81). During the time from intubation to VA ECMO or VAV ECMO initiation (1 day [IQR 0-7.5] v 6 days [IQR 2.5-14], p = 0.0383), body mass index (32 [IQR 26-36] v 37 [IQR 33-40], p = 0.009), and baseline C-reactive protein (7.15 v 38.9 mg/dL, p = 0.009) were higher in those who expired. Only one-third of the patients with COVID-19 requiring VA ECMO or VAV ECMO survived to discharge. Close monitoring of at-risk patients with early initiation of ECMO with circulatory support may further improve outcomes. [ABSTRACT FROM AUTHOR]

Background: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field.Methods: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers.Results: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied.Conclusions: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support. [ABSTRACT FROM AUTHOR]

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices. [Display omitted] [ABSTRACT FROM AUTHOR]

The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. Patients (≥19 years of age) enrolled into STS Intermacs between August 2017 and June 2019 were stratified by device type (continuous flow, centrifugal left ventricular assist device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by 3 statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). Of 4448 patients, 2012 (45.2%) received the CF-HL and 2436 (54.8%) received the CF-FML. One-year survival for the CF-FML was 88% vs 79% for the CF-HL (overall P <.001), with a hazard ratio for mortality of 3.18 for the CF-HL (P <.0001) after risk adjustment. With propensity score matching (n = 1400 each cohort), 1-year survival was 87% for the CF-FML vs 80% for the CF-HL, with a hazard ratio of 3.20 for mortality with the CF-HL (P <.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving the CF-HL was associated with a hazard ratio of 3.11 (P <.0001). Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of the CF-FML vs CF-HL. [ABSTRACT FROM AUTHOR]

The twelfth annual report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 26 688 continuous-flow left ventricular assist device (LVAD) patients over the past decade (2011-2020). In 2020, we observed the largest drop in yearly LVAD implant volumes since the registry's inception, which reflects the effects of the COVID-19 pandemic on cardiac surgical volumes in the United States. The 2018 heart transplant allocation policy change in the United States continues to affect LVAD implantation volumes and device strategy, with 78.1% of patients now receiving LVAD implants as destination therapy. Despite an older and sicker patient cohort, survival in the recent era (2016-2020) at 1 and 2 years continues to improve at 82.8% and 74.1%. Patient adverse event profile has also improved in the recent era, with significant reductions in stroke, gastrointestinal bleeding, infection, and device malfunction/pump thrombosis. Finally, we review the burden of readmissions after LVAD implant and highlight an opportunity to improve patient outcomes by reducing this frequent and vexing problem. [Display omitted] [ABSTRACT FROM AUTHOR]

Diffuse intimal hyperplasia and graft irregularity adversely affect the long-term patency of saphenous vein grafts (SVGs) and clinical outcomes of patients undergoing coronary artery bypass grafting (CABG). The VEST trial evaluated the efficacy of external graft support in limiting the development of intimal hyperplasia (IH) at 1 year postsurgery. In the present secondary analysis, we explored the associations between graft disease and IH and clinical events. We also examined risk factors for early graft occlusion. VEST is a within-patient randomized, multicenter trial that enrolled 224 patients with multivessel coronary disease undergoing CABG surgery, of whom 203 were evaluated by 1 year postsurgery. Intimal hyperplasia, lumen uniformity, graft stenosis, and graft perfusion were measured by intravascular ultrasound and angiography. Major cardiac and cerebrovascular events (MACCE; including death, myocardial infarction, stroke, and revascularization) were recorded over a median follow-up of 3 years. Worse lumen uniformity, greater stenosis, and worse graft perfusion were associated with higher IH values and an increased incidence of clinical events. Consistent with previous findings, we identified endoscopic vein harvesting, female sex, and transit time flow measurement of pulsatility index and flow as risk factors for SVG occlusion during the first year postsurgery. In this secondary analysis of the VEST trial, we observed an association between intimal hyperplasia area and clinical measures of SVG disease at 1 year postsurgery. More severe SVG disease and larger areas of IH were associated with a higher incidence of 3-year MACCE. Ongoing follow-up to 5 years will further elucidate the impact of SVG disease on long-term clinical outcomes of CABG. [Display omitted] [ABSTRACT FROM AUTHOR]

The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

The impact of different types of regional wall motion abnormalities (RWMAs), including the Takotsubo syndrome–like (TTS-like) phenotype, on posttransplant outcomes when using donor hearts with transient left ventricular systolic dysfunction (LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis and posttransplant outcomes when using donor hearts with transient LVSD. From all adult (≥18 years) heart transplants in United Network of Organ Sharing between January 2007 and September 2015, we identified 472 donor hearts with improving or transient LVSD, defined as left ventricular ejection fraction ≤ 40% on initial transthoracic echocardiogram (TTE) that improved to ≥50% on follow-up TTE during donor evaluation. These improved LVSD donors were then subdivided into 3 groups based on RWMAs on the initial TTE, TTS-like (49, 10.38%), non-TTS RWMAs (74, 15.68%), and diffuse global hypokinesis (349, 73.94%), and compared for baseline characteristics and posttransplant outcomes with follow up until June 2018. Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year posttransplant mortality. Posttransplant functional status scores of recipients (at 1 year) and donor left ventricular ejection fraction (at median follow-up of 3.6 years) improved in all 3 subgroups. Rates of stroke or pacemaker predischarge were also similar. In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE, but this was not associated with adverse posttransplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs. [ABSTRACT FROM AUTHOR]

Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation. Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001). Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke. [ABSTRACT FROM AUTHOR]

We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients. [ABSTRACT FROM AUTHOR]

Background Limited data exist on factors predicting prolonged survival in left ventricular assist device (LVAD) recipients. We sought to identify patient characteristics and complications associated with prolonged survival. Methods We conducted retrospective review of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database, including primary continuous-flow LVAD recipients, between May 2012 and March 2013. Patients were identified as having survived with a device in place after 3 years or not, conditional on having initially survived 6 months. Patients who received a transplant, underwent explant due to recovery, or were lost to follow-up before 3 years were excluded. Multivariate logistic regression evaluated perioperative factors and adverse events within 6 months associated with long survival. Results Of 1,116 patients who survived past the initial 6 months, 725 (65%) survived beyond 3 years. On univariate analysis, long-term survivors were significantly younger, were less likely to be white, supported for destination therapy, have diabetes, solid-organ cancer, or take amiodarone. On multivariate analysis, factors associated with increased odds of death at 3 years included diabetes, amiodarone use, and developing stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis within 6 months of implantation. Conclusions Preoperative diabetes and amiodarone use were associated with poor long-term survival in LVAD recipients. Development of early complications of stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis was also associated with poor long-term survival. Early diagnosis and treatment of these complications may improve survival in LVAD recipients. [ABSTRACT FROM AUTHOR]

Objectives: A recent theoretical economic model suggested that oversized vials of cancer drugs lead to $1.8 billion of drug wastage annually in the United States. It is currently unknown how precisely this theoretical model is consistent with the real world. We performed a real-world analysis to assess the economic impact of drug wastage.Methods: We performed a systematic examination of the usage and wastage of all intravenous cancer drugs in the cancer center of a large tertiary care hospital in Israel. During a period of 1 month, we collected usage and wastage data from the hospital's pharmacy dispensing computerized logs. We calculated the local financial impact using Israeli drug prices list (June 2016) from the ministry of health. We performed an additional analysis using discounted U.S. prices, using the October 2016 Average Sales Prices from the Centers of Medicare and Medicaid Services.Results: Seventy-four injectable anticancer drugs were used during March 2016, and 68 Israeli drug prices were available. The total amount spent on wasted drugs in 1 month was then extrapolated to calculate the annual spending, which was $141,196 per month (5.11% of the total cost) or $1,694,352 per year. Using U.S. prices, the total wastage would be $2,208,876 annually. The 5 drugs that led to the highest expenditure on wastage were bortezomib, trastuzumab, azacytidine, pemetrexed and carfilzomib. There was no wastage of 24 of the 74 drugs.Conclusion: This real-world study demonstrates the economic impact of wastage of anticancer drugs on health systems. To decrease wastage, particular attention should be paid to drugs with high usage rates, high cost, and oversized vials. [ABSTRACT FROM AUTHOR]

Background Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes. Methods A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression. Results Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (β = –6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC ( p = 0.01). Conclusions Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal. [ABSTRACT FROM AUTHOR]

Background Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Methods Cox proportional hazard models were used to analyze patients enrolled in the “as-treated cohort” ( n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Results Baseline characteristics were well balanced among HM3 ( n = 151) and HMII ( n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. Conclusions This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned. [ABSTRACT FROM AUTHOR]

Background: Patients with restrictive (RCM) and hypertrophic (HCM) cardiomyopathies are felt to be a difficult population to treat with left ventricular assist device (LVAD) therapy. Scarce data exist on outcomes of continuous-flow (CF) LVAD support in these challenging patient cohorts.Methods: The Interagency Registry for Mechanically Assisted Circulatory Support Registry was queried for all patients with RCM (n = 94) and HCM (n = 104) who underwent CF LVAD implantation between March 2008 and March 2014. Survival, adverse event rates, baseline demographics, echocardiography parameters, and competing outcomes were compared with patients with dilated cardiomyopathy (DCM) (n = 8749).Results: Left ventricular size was smaller and baseline EF was higher in RCM and HCM compared with DCM patients. Nonetheless, these parameters were not completely normal in the RCM and HCM groups, suggesting that most of these patients exhibited features of a DCM and represented a mixed phenotype. In these specific patient populations, survival up to 4 years was not different among the 3 groups (log rank 0.25) and competing outcomes at 1 year were similar. In the subgroup of patients with very small ventricles (ie, < 5.0 cm), survival was far inferior. Finally, overall rates of right ventricular assist device requirement, hemolysis, pump dysfunction, and cardiac arrhythmias were similar among the 3 groups.Conclusion: Relatively few patients with HCM and RCM undergo CF LVAD implantation, and most that do display some features of a DCM. Overall survival and adverse event profiles of these patients were similar to traditional DCM patients; however, in those with very small ventricles, survival was inferior. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been reported to cause euglycemic diabetic ketoacidosis (eDKA), a diagnosis that may be challenging to establish in the emergency department (ED).Case Report: This is a case report of missed eDKA in a 47-year-old male taking empagliflozin (a SGLT2 inhibitor) that presented to the ED with generalized weakness. His past medical history included multiple sclerosis (MS) diagnosed 4 years ago and type 2 diabetes mellitus. The patient attributed his weakness to MS. His neurologist was consulted and agreed with the plan to discharge the patient with diagnoses of asthenia and dehydration and a prescription of prednisone. The patient returned to the ED the next day with similar symptoms and was admitted to the hospital for treatment of eDKA. He was eventually treated per the hospital diabetic ketoacidosis (DKA) protocol and discharged home with instructions to discontinue empagliflozin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The increasing utilization of SGLT2 inhibitor in patients with type 2 diabetes mellitus will inevitably lead to more cases of eDKA seen in the ED. Emergency physicians need to consider this diagnosis in patients taking these medications that present with symptoms including weakness, nausea, vomiting, abdominal pain, and dehydration. Patients taking these medications should be warned about these symptoms, especially because they may be falsely reassured by relatively low plasma glucose levels on home glucometer readings. [ABSTRACT FROM AUTHOR]

Background: Although animal studies have shown that exposure to glyphosate (a commonly used herbicide) does not result in glyphosate bioaccumulation in tissues, to our knowledge there are no published data on whether it is detectable in human milk and therefore consumed by breastfed infants. Objective: We sought to determine whether glyphosate and its metabolite aminomethylphosphonic acid (AMPA) could be detected in milk and urine produced by lactating women and, if so, to quantify typical consumption by breastfed infants. Design: We collected milk (n = 41) and urine (n = 40) samples from healthy lactating women living in and around Moscow, Idaho and Pullman, Washington. Milk and urine samples were analyzed for glyphosate and AMPA with the use of highly sensitive liquid chromatography– tandem mass spectrometry methods validated for and optimized to each sample matrix. Results: Our milk assay, which was sensitive down to 1 µg/L for both analytes, detected neither glyphosate nor AMPA in any milk sample. Mean ± SD glyphosate and AMPA concentrations in urine were 0.28 ± 0.38 and 0.30 ± 0.33 µg/L, respectively. Because of the complex nature of milk matrixes, these samples required more dilution before analysis than did urine, thus decreasing the sensitivity of the assay in milk compared with urine. No difference was found in urine glyphosate and AMPA concentrations between subjects consuming organic compared with conventionally grown foods or between women living on or near a farm/ranch and those living in an urban or suburban nonfarming area. Conclusions: Our data provide evidence that glyphosate and AMPA are not detectable in milk produced by women living in this region of the US Pacific Northwest. By extension, our results therefore suggest that dietary glyphosate exposure is not a health concern for breastfed infants. This study was registered at clinicaltrials.gov as NCT02670278. [ABSTRACT FROM AUTHOR]

Exposure and response prevention (ERP) is well-established as an effective treatment for obsessive-compulsive disorder (OCD), yet its availability is often limited by a shortage of trained mental health providers. ERP is most frequently provided on a weekly or twice weekly basis; however, research has demonstrated that intensive ERP for OCD is equally efficacious compared to longer-term weekly treatments (e.g., Oldfield, Salkovskis, & Taylor, 2011). Although intensive ERP can provide patients without access to weekly treatment an opportunity to receive treatment in an alternative format, its availability is also limited as most outpatient psychiatry clinics are not structured or experienced with offering this type of service. The goal of the current paper is to provide mental health providers with information and guidance on implementing—through the illustration of a case study—a short-term intensive individualized ERP program for OCD within an outpatient psychiatry clinic that does not routinely offer these services. Special considerations and potential challenges that should be considered when offering this type of intensive treatment are discussed. The overarching goal of the paper is to improve access to ERP for OCD by increasing the availability of intensive programs. [ABSTRACT FROM AUTHOR]

In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true "net health benefit" from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. [ABSTRACT FROM AUTHOR]

To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support. A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality. Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46). In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19. A multicenter, retrospective cohort study of 292 patients with COVID-19 given extracorporeal membrane oxygenation (ECMO) in 17 centers across the United States from March 1, 2020 to September 30, 2020. Clinical characteristics and outcomes were entered into a Research Electronic Data Capture (REDCap) database. The primary outcome of cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). [Display omitted] [ABSTRACT FROM AUTHOR]

Background: With health care reform firmly on the horizon, it is critical to understand the costs associated with new technologies such as continuous-flow left ventricular assist device (CF-LVAD) compared with well established treatments such as heart transplantation (HT). Scarce data exist describing the costs of these 2 therapies after 1 year of support. Methods and Results: The study population consisted of 20 consecutive subjects who underwent implantation of a CF-LVAD and 20 consecutive subjects who underwent HT and survived ≥ 1 year. Comprehensive cost calculation included all direct and indirect costs from day of operation through 365 days and were inflation adjusted to 2010 US dollars. Hospital charges were converted to costs with the use of hospital-specific cost-to-charge ratios and were analyzed by time segment as well as cost center. The total 1-year cost was higher in the CF-LVAD group, although this difference did not reach statistical significance ($369,519 [interquartile range [IQR] $321,020-$520,395] vs $329,648 [IQR $278,924-$395,456]; P = .242). In both groups, the index admission constituted >50% of the total 1-year cost and the major drivers of expense by cost center were organ/device acquisition, room and board, and professional fees. Conclusions: Patients surviving to 1 year on CF-LVAD support accrued costs similar to those of HT recipients; however, the total cost, at more than one-third of a million dollars, remains high. Reduction in the postoperative length of stay offers an avenue for significant cost savings. [ABSTRACT FROM AUTHOR]

Background Criteria for the identification of patients who may progress to advanced heart failure (HF) have been previously suggested. However, identification of appropriate non-inotrope-dependent (NID) patients for destination therapy (DT) remains a challenge, and referral rates are low. We surveyed expert provider opinion about patient selection for early DT. Methods An internet-based survey was sent to international HF providers to investigate opinions about clinical indicators for referral of NID patients for DT. Subjects were identified from membership lists of HF professional organizations. Respondents provided their level of agreement with the use of a 5-point Likert Scale (1 = strongly disagree to 5 = strongly agree) to 10 clinical criteria describing at-risk NID patients. Results A total of 231 respondents who had been in a position to recommend left ventricular assist device (LVAD) therapy for 7.6 ± 5.8 years identified themselves as HF providers: 41% HF cardiologists, 27% HF nurse practitioners, 21% cardiothoracic surgeons, 9% LVAD coordinators, and 2% general cardiologists. More than two-thirds of the respondents agreed or strongly agreed with 7 of the 10 items. Similar consensus was not seen for 6-minute walk (6MW) or B-type natriuretic peptide (BNP). When asked which criteria would have to be present for LVAD referral, only hemodynamic deterioration reached ≥50% affirmation among respondents. No criteria reached >50% response as being sufficient alone for DT. Conclusion We describe referral thresholds for early LVAD therapy among international HF providers. With the exception of BNP and 6MW, we found overall agreement on the proposed clinical parameters. Despite apparent consensus, in practice implantation rates for LVAD in NID patients remain low. The results of ongoing clinical trials in this population may lower thresholds for early referral for DT. [ABSTRACT FROM AUTHOR]

Summary: Increasing evidence points to an important role for the ribosome in the regulation of biological processes and as a target for deregulation in disease. Here, we describe a SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry approach to probing mammalian riboproteomes. Using a panel of cell lines, as well as genetic and pharmacological perturbations, we obtained a comparative characterization of the cellular riboproteome. This analysis identified a set of riboproteome components, consisting of a diverse array of proteins with a strong enrichment for RNA-binding proteins. Importantly, this global analysis uncovers a high incidence of genetic alterations to riboproteome components in cancer, with a distinct bias toward genetic amplification. We further validated association with polyribosomes for several riboproteome components and demonstrate that enrichment at the riboproteome can depend on cell type, genetics, or cellular stimulus. Our results have important implications for the understanding of how ribosomes function and provide a platform for uncovering regulators of translation. [Copyright &y& Elsevier]

Highlights: [•] How aging impacts the immune priming capabilities of dendritic cells is complex. [•] Some studies show reduced function, while others show preserved DC priming function with aging. [•] Lack of consensus may reflect subtle differences in the health status of mice and methods employed. [ABSTRACT FROM AUTHOR]