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• The number of patients living with severe and advanced heart failure is growing and is expected to increase over time. • Patients who have progressed beyond stage C heart failure are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. • We provide an approach to the medical management of patients with severe and advanced heart failure based on limited current data and the clinical experiences of the authors who specialize in heart failure.' Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF. [Display omitted] [ABSTRACT FROM AUTHOR]

The HeartMate 3 Risk Score (HM3RS) is a tool derived and validated from the MOMENTUM 3 clinical trial population to predict mortality after left ventricular assist device (LVAD) implantation. However, the UNOS adult heart allocation policy was revised in October 2018, resulting in a drastic decrease in bridge-to-transplant LVAD use. In this study, we assessed the predictive accuracy of HM3RS at a single institution, both before and after the 2018 UNOS allocation policy change. We retrospectively analyzed all adult patients who received a HeartMate 3 (HM3) at Washington University School of Medicine in St. Louis between 2015 - 2021. We calculated the HM3RS for each patient, categorized as low (<1.58), medium (1.58-2.48), or high (>2.48). The primary outcome was mortality at 1 and 2 years, stratified before and after the date of the UNOS allocation policy change (10/1/2018). A total of 178 HM3 recipients were included, 61 of whom received a HM3 before 10/1/2018. Patient demographics were similar, although LVAD recipients were more likely to be INTERMACS 1 or 2 post-allocation system change compared to pre-allocation system change (78% vs. 47%). HM3RS accurately predicted 1- and 2-year mortality pre-10/2018 with AUC 0.76 and 0.71, respectively, comparable to the original study. However, post-allocation system change, HM3RS performed much worse, with AUC 0.56 at 1 year and 0.40 at 2 years, despite similar patient outcomes (Figure 1). HM3RS accurately predicted mortality in a real-world population before the 2018 UNOS allocation change although it had mediocre performance after. This score may need recalibration to better assess risk for current and future patients undergoing HM3 implantation. [ABSTRACT FROM AUTHOR]

Aims: To explore the association of changes in weight and fluid during treatment for acute heart failure (AHF) with clinical endpoints.Methods and Results: Weight and net fluid changes recorded at 72-96 hours in 708 AHF patients enrolled in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal Optimization Strategies Evaluation in Acute Heart Failure studies were compared with freedom from congestion at 72-96 hours and a composite endpoint of death, rehospitalization, and unplanned hospital visit at 60 days. Weight loss was concordant with net fluid loss in 55%, discordant and less than expected for fluid loss in 34%, and paradoxically discordant or more than expected for fluid loss in 11% of patients. Weight loss, but not fluid loss, was associated with freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03-1.19]) and a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss = 0.98 [0.95-1.00]). Outcomes were similar in patients with concordant and discordant weight-fluid loss.Conclusion: During treatment for AHF, early changes in weight may be more useful for identifying response to therapy and for predicting outcomes than net fluid output. Nearly one-half of patients receiving decongestive therapies demonstrate discordant changes in weight and fluid; however, discordance was not associated with outcomes. [ABSTRACT FROM AUTHOR]

Objective: The epidemiology of heart failure (HF) is changing. This study aimed to describe questions that arise during the routine care of HF patients that are unanswered by the current literature and describe how the type and focus of these questions has changed over time.Methods: Investigators from the National Heart, Lung, and Blood Institute-sponsored Heart Failure Apprentice Network collected and categorized questions from 5 academic hospitals over 12 months. A total of 174 unanswered questions were collected and analyzed.Results: Compared with 2004, there were more unanswered questions about "whether" to use therapies and fewer about "how" to use therapies. There were fewer questions about what therapeutic targets, therapy adjustment, and combination therapies. There were more questions about whether or how to stop therapies and how to add therapies back. Newly prominent topics, not observed in 2004, including novel therapeutics, refractory ventricular tachycardia, right heart failure, and nutrition/frailty, accounted for 24% of questions.Conclusions: Compared with 2004, there are fewer unanswered questions about how to use, adjust, and combine therapies. There were more unanswered questions about whether and how to stop therapies. Almost 25% of unanswered questions dealt with topics indicative of more advanced disease which were not observed in 2004. [ABSTRACT FROM AUTHOR]

De novo donor specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection (AMR) and worse prognosis in patients after orthotopic heart transplant (OHT). Viral infections have the potential to induce or reactivate the production of DSAs, yet the development of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has not been reported. In this observational study, we describe DSA titers after Coronavirus Disease 2019 (COVID-19) infection and relationship with AMR and graft dysfunction in a large OHT cohort at a tertiary academic medical center. : We predicted that COVID-19 infection would be associated with development of de novo DSAs or increase in pre-existing DSAs. We retrospectively analyzed all adult OHT patients followed at Washington University School of Medicine in St. Louis between 4/1/2020-12/31/2021. COVID-19 infection was defined by positive antigen or PCR test in setting of clinical exposure or symptoms. Patients were considered fully vaccinated 2 weeks after 2 doses of the BNT162b (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines or after a single dose of the AD26.COV2.S (Johnson & Johnson) vaccine. De novo DSAs were defined as newly detected MHC I or II antibody greater than 2000 mean fluorescence intensity (MFI) by single antigen beads or newly elevated antibody against angiotensin-II type 1 receptor (AT1R). In patients with pre-existing DSAs, a significant increase was defined by an MFI value that increased by 20% or more compared to their baseline value prior to SARS-CoV-2 infection. A total of 577 patients were followed during the study period and 117 cases of COVID-19 infection were identified. Baseline characteristics of COVID-19 positive patients are shown in Figure. Overall, 10% of patients infected with SARS-CoV-2 infection developed de novo DSAs or an increase in pre-existing DSAs, with unvaccinated patients having a higher incidence compared to vaccinated patients (15% vs. 2%, p=0.02). MHC class II-specific antibodies were the most common DSAs detected. There was a trend towards higher incidence of AMR in unvaccinated patients, although mortality and long-term graft dysfunction were similar. Unvaccinated patients had a higher incidence of developing de novo or an increase in pre-existing DSAs after SARS-CoV-2 infection. Future studies are necessary to investigate the long-term consequences of COVID-19 in the OHT population. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) reduce mortality and morbidity in patients with end-stage heart failure. Patients with LVADs require warfarin therapy, and bleeding occurs and complicates therapy in nearly half of these recipients. Predicting which patients will bleed after LVAD implant is challenging, and prediction rules for major bleeding have not been rigorously studied in this population. We aimed to validate previously described clinical prediction rules for bleeding in an LVAD cohort. This was a single-center, retrospective cohort study of patients who received an LVAD at Barnes-Jewish Hospital. Data used to tabulate risk scores and adjudicate outcomes were collected through chart review. The primary clinical endpoint was time to major gastrointestinal bleed or intracranial hemorrhage after implant. The secondary endpoint was time to any major bleed after hospital discharge. A total of 418 patients received an LVAD (135 HeartMate II, 125 HeartMate 3, 158 HVAD) between November 2009-January 2019. The primary endpoint occurred in 168 (40.1%) patients. C-statistics for the primary endpoint ranged 0.53-0.58 (P<0.05 for HAS-BLED, HEMORR 2 HAGES, ATRIA, Outpatient Bleeding Risk Index, and VTE-BLEED). The secondary endpoint occurred in 167 (40.0%) patients, and C-statistics ranged 0.52-0.58 (P<0.05 for HAS-BLED, Outpatient Bleeding Risk Index, and VTE-BLEED). After modifying the age threshold in each prediction rule to 59 years (the median age of the cohort), C-statistics ranged 0.55-0.61 for the primary and secondary endpoints. In a subgroup analysis of HeartMate 3 patients, prediction rules performed similarly. Existing clinical prediction rules for major bleeding, previously derived in other anticoagulated populations, had mediocre discrimination in an LVAD cohort. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are nano-sized, lipid bilayer-enclosed particles involved in intercellular communication. EVs are increasingly being considered as drug delivery vehicles or as cell-free approach to regenerative medicine. However, one of the major challenges for their clinical application is finding a scalable EV isolation method that yields functional EVs. Although the golden standard for EV isolation is ultracentrifugation (UC), a recent study suggested that isolation using size-exclusion chromatography (SEC) yielded EVs with more intact biophysical properties. Whether this also leads to differences in functionality remained to be investigated. Therefore, we investigated possible differences in functionality of cardiomyocyte progenitor cell-derived EVs isolated using UC and SEC. Western blot analysis showed higher pERK/ERK ratios in endothelial cells after stimulation with SEC-EVs compared to UC-EVs, indicating that SEC-EVs bear higher functionality. Therefore, we propose to use SEC-EVs for further investigation of EVs' therapeutic potential. Further optimization of isolation protocols may accelerate clinical adoption of therapeutic EVs. [ABSTRACT FROM AUTHOR]

Background: Hypoalbuminemia is common in patients with chronic heart failure and, as a marker of disease severity, is associated with an adverse prognosis. Whether hypoalbuminemia contributes to (or is associated with) worse outcomes in acute heart failure (AHF) is unclear. We sought to determine the implications of low serum albumin in patients receiving decongestive therapies for AHF.Methods and Results: Baseline serum albumin levels were measured in 456 AHF subjects randomized in the DOSE-AHF and ROSE-AHF trials. We assessed the relationship between admission albumin levels (both as a continuous variable and stratified by median albumin [≥3.5 g/dL]) and worsening renal function (WRF), worsening heart failure (WHF), and clinical decongestion by 72 hours; 7-day cardiorenal biomarkers; and post-discharge outcomes. The mean baseline albumin level was 3.5 ± 0.5 g/dL. Albumin was not associated with WRF, WHF, or clinical decongestion by 72 hours. Furthermore, there was no association between continuous albumin levels and symptom change according to visual analog scale or weight change by 72 hours. Albumin was not associated with 60-day mortality, rehospitalization, or unscheduled emergency room visits.Conclusions: Baseline serum albumin levels were not associated with short-term clinical outcomes for AHF patients undergoing decongestive therapies. These data suggest that serum albumin may not be a helpful tool to guide decongestion strategies. [ABSTRACT FROM AUTHOR]

Background: Readmission or death after heart failure (HF) hospitalization is a consequential and closely scrutinized outcome, but risk factors may vary by population. We characterized the risk factors for post-discharge readmission/death in subjects treated for acute heart failure (AHF).Methods and Results: A post hoc analysis was performed on data from 744 subjects enrolled in 3 AHF trials conducted within the Heart Failure Network (HFN): Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF), Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF). All-cause readmission/death occurred in 26% and 38% of subjects within 30 and 60 days of discharge, respectively. Non-HF cardiovascular causes of readmission were more common in the ≤30-day timeframe than in the 31-60-day timeframe (23% vs 10%, P = .016). In a Cox proportional hazards model adjusting a priori for left ventricular ejection fraction <50% and trial, the risk factors for all-cause readmission/death included: elevated baseline blood urea nitrogen, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) non-use, lower baseline sodium, non-white race, elevated baseline bicarbonate, lower systolic blood pressure at discharge or day 7, depression, increased length of stay, and male sex.Conclusions: In an AHF population with prominent congestion and prevalent renal dysfunction, early readmissions were more likely to be due to non-HF cardiovascular causes compared with later readmissions. The association between use of ACEI/ARB and lower all-cause readmission/death in Cox proportional hazards model suggests a role for these drugs to improve post-discharge outcomes in AHF. [ABSTRACT FROM AUTHOR]

Background: Though commonly noted in clinical practice, it is unknown if decongestion in acute heart failure (AHF) results in increased serum bicarbonate.Methods and Results: For 678 AHF patients in the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials, we assessed change in bicarbonate (baseline to 72-96 hours) according to decongestion strategy, and the relationship between bicarbonate change and protocol-defined decongestion. Median baseline bicarbonate was 28 mEq/L. Patients with baseline bicarbonate ≥28 mEq/L had lower ejection fraction, worse renal function and higher N-terminal pro-B-type natriuretic peptide than those with baseline bicarbonate <28 mEq/L. There were no differences in bicarbonate change between treatment groups in DOSE-AHF or ROSE-AHF (all P > .1). In CARRESS-HF, bicarbonate increased with pharmacologic care but decreased with ultrafiltration (median +3.3 vs -0.9 mEq/L, respectively; P < .001). Bicarbonate change was not associated with successful decongestion (P > .2 for all trials).Conclusions: In AHF, serum bicarbonate is most commonly elevated in patients with more severe heart failure. Despite being used in clinical practice as an indicator for decongestion, change in serum bicarbonate was not associated with significant decongestion. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins and are of great medical interest; serving as novel biomarkers and potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield and high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) and differential ultracentrifugation (UC). A significantly higher EV yield resulted from UF-LC as compared to UC, without affecting vesicle protein composition. Importantly, we provide novel evidence that, in contrast to UC-purified EVs, the biophysical properties of UF-LC-purified EVs are preserved, leading to a different in vivo biodistribution, with less accumulation in lungs. Finally, we show that UF-LC is scalable and adaptable for EV isolation from complex media types such as stem cell media, which is of huge significance for future clinical applications involving EVs. From the Clinical Editor Recent evidence suggests extracellular vesicles (EVs) as another route of cellular communication. These EVs may be utilized for future therapeutics. In this article, the authors compared ultrafiltration with size-exclusion liquid chromatography (UF-LC) and ultra-centrifugation (UC) for EV recovery. [ABSTRACT FROM AUTHOR]

Background Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, older age, and impaired renal function. The influence of these factors on urinary methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown. Objective We investigated the impact of age, body mass index (BMI), and kidney function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected patients. Methods Retrospective data analysis of all adults in whom bone marrow investigations were performed because of high clinical suspicion and/or elevated tryptase, MH, or MIMA. Results 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did not influence MH or MIMA. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and 0.83). In subjects >50 years with a BMI >25 kg/m 2 , the diagnostic accuracy of MIMA was higher compared with that of tryptase (area under the curve 0.93 vs 0.74; P = .011). Conclusion In ISM-suspected patients >50 years with a BMI of >25 kg/m 2 , MIMA has a greater value compared with tryptase in estimating the need for bone marrow biopsy. [ABSTRACT FROM AUTHOR]

• A 2-factor structure TSK-11 was confirmed in a large mixed chronic pain population. • Two brief TSK versions (TSK-7 and TSK-5) had similar psychometrics compared with TSK-11. • Both TSK-7 and TSK-5 total scores and subscales had good convergent validity. To develop and validate a brief version of the Tampa Scale of Kinesiophobia (TSK) while preserving content validity in a mixed chronic pain population. Cross-sectional study. Tertiary care interdisciplinary chronic pain clinic. Adults with chronic pain (N=933; mean age, 53.5±15.7 years; 63% women). Not applicable. TSK-11 measured at intake. Self-reported data from a patient registry were extracted from November 2017 to October 2019. An exploratory factor analysis identified a 2-factor structure from the TSK-11 and item reduction resulted in a 7-item TSK (TSK-7) with 61.2% explained variance and Cronbach's alphas of 0.76 and 0.70 for each of the 2 factors. To maximally reduce the number of items without affecting internal consistency, a 5-item TSK (TSK-5) with 72% explained variance was also explored. Strong correlations were found between the newly developed brief TSK versions and TSK-11 (r >0.93), suggesting good concurrent validity. TSK-11, TSK-7, and TSK-5 had similar convergent validity with moderate correlations for pain catastrophizing (r =0.57, 0.58, 0.54), depression (r =0.45, 0.46, 0.42), pain interference (r =0.43, 0.44, 0.40), and pain acceptance (r =–0.57, –0.59, –0.55). These 2 brief versions of the TSK may help to simplify questionnaires across chronic pain centers where multiple outcome measures are used for a complete biopsychosocial assessment of patients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Antiepileptic drugs are a potentially effective treatment for epilepsy. Side-effects are, however, common and the negative consequences necessitate treatment ranging from minor interventions to very expensive hospitalization. This analysis has been conducted to provide insight into the costs of side-effects due to antiepileptic drugs in The Netherlands from a societal perspective. Method: Resources allocated to care (grouped according to health, patient and family and other) for five different categories of side-effect were measured using a questionnaire. Standard cost prices were derived from the Dutch costing manual. Chronic epilepsy patients were invited to complete the questionnaire if they had experienced side-effects during the previous 12 months. Results: Based on data from 203 patients, the total societal costs of common side-effects in 2012 are estimated to be €20,751 CI:15,049–27,196 (US$26,675 CI:19,345–34,960) per patient per year. These consist of: health care costs (mean €4458; US$5731), patient and family costs (i.e. informal care, mean €10,526; US$13,531) and other costs (i.e. productivity losses, mean €5761; US$7406). Examining the different categories of side-effects separately, ranging from the most to the least expensive category, the cost estimates per patient per year were as follows: other (mean €13,228; US$17,005), behavioral (mean €9689; US$12,455), general health (mean €7454; US$9582), cognitive (mean €7285; US$9365) and cosmetic side-effects (mean €2845; US$3657). Subgroup analyses showed significant differences in costs between patients using monotherapy and those using polytherapy when looking at cognitive and cosmetic side-effects. Conclusion: These estimates should be considered in the overall assessment of the economic impact of a pharmacotherapy. [Copyright &y& Elsevier]

Background: Increased basal serum tryptase (bsT) levels are a well-described risk factor for Hymenoptera venom–induced anaphylaxis (HVAn) in patients allergic to Hymenoptera venom. Increased bsT levels might also indicate the presence of mastocytosis. In this study we evaluated whether the risk of HVAn increases with increasing mast cell load in patients with mastocytosis. Methods: Consecutive patients with different subtypes of mastocytosis (n = 329) admitted to the University Medical Center Groningen were retrospectively assessed. As markers for mast cell load, levels of both bsT and the urinary histamine metabolites methylhistamine and methylimidazole acetic acid (MIMA) were used. Results: In the entire patient group, irrespective of disease subtype and Hymenoptera venom exposure, HVAn prevalence gradually increased with increasing marker levels to a maximum of 36% to 47% at a bsT level of 28.0 μg/L, a methylhistamine level of 231.0 μmol/mol creatinine, and a MIMA level of 2.7 mmol/mol creatinine but decreased thereafter with a further increase in these levels. In patients with indolent systemic mastocytosis with a history of Hymenoptera venom exposure after age 15 years or greater (n = 152), MIMA and age at the most recent Hymenoptera sting were independent predictors for HVAn (odds ratios of 0.723 [P = .001] and 1.062 [P < .001], respectively). Conclusions: In patients with mastocytosis, HVAn prevalence does not increase constantly with increasing levels of mast cell load parameters: after a gradual increase to a maximum of near 50%, it decreases with a further increase in these levels. In the indolent systemic mastocytosis population, all mast cell load markers were independent negative predictors of HVAn. These findings suggest a complex pathophysiologic association between mast cell load and HVAn risk in patients with mastocytosis. [Copyright &y& Elsevier]

Abstract: Background: Variations in colonoscopy practice exist, which may be related to healthcare quality. Aims: To determine factors associated with three performance indicators of colonoscopy: complete colonoscopy, adenomatous polyp diagnosis, and duration. Patients: Consecutive patients referred for colonoscopy from 21 centres in 11 countries. Methods: This prospective observational study used multiple variable regression analyses to identify determinants of the quality indicators. Results: Six thousand and four patients were included in the study. Patients from private, open-access centres (odds ratio: 3.17, 95% confidence interval: 1.87–5.38) were more likely to have a complete colonoscopy than patients from public, gatekeeper centres. Patients from centres where over 50% of the endoscopists were of senior rank were roughly twice as likely to have an adenoma diagnosed, and longer average withdrawal duration (odds ratio: 1.08, 95% confidence interval: 1.07–1.09) was associated with more frequent adenoma diagnoses. Patients who had difficulty during colonoscopy had longer durations to caecum (time ratio: 2.87, 95% confidence interval: 2.72–3.01) and withdrawal durations (time ratio: 1.26, 95% confidence interval: 1.18–1.33) than patients who had no difficulties. Conclusions: Multiple factors have been identified as being associated with key quality indicators. The non-modifiable factors permit the identification of patients who may be at greater risk of not having quality colonoscopy, while changes to the modifiable factors may help improve the quality of colonoscopy. [Copyright &y& Elsevier]

BACKGROUND: Screening for colorectal cancer (CRC) has been shown to decrease mortality. OBJECTIVE: To examine determinants associated with having (1) a screening colonoscopy, (2) an appropriate indication for screening, and (3) a significant diagnosis at screening. DESIGN: Prospective observational study. SETTING: Twenty-one endoscopy centers from 11 countries. PATIENTS: Asymptomatic patients who underwent a colonoscopy for the purpose of detecting CRC and who did not have a history of polyps or CRC, a lesion observed at a recent barium enema or sigmoidoscopy, or a recent positive fecal occult blood test. INTERVENTION: Screening colonoscopy. MAIN OUTCOME MEASUREMENTS: Appropriateness according to the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria and significant diagnoses (cancer, adenomatous polyps, new diagnoses of inflammatory bowel disease, angiodysplasia). RESULTS: Of 5069 colonoscopies, 561 (11%) were performed for screening purposes. Patients were more likely to have a screening colonoscopy if they were aged 45 to 54 years (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.60-3.99). Screening colonoscopies were appropriate, uncertain, and inappropriate in 26%, 60%, and 14% of cases, respectively. Eighty-one significant diagnoses were made, including 4 cancers. Significant diagnoses were more often made for uncertain/appropriate indications (OR 3.20, 95% CI 1.12-9.17) than for inappropriate indications. LIMITATIONS: Although data completeness was asked of all centers, it is possible that not all consecutive patients were included. Participating centers were a convenience sample and thus may not be representative. CONCLUSIONS: About 1 of 10 colonoscopies were performed for screening, preferentially in middle-aged individuals. A higher diagnostic yield in uncertain/appropriate indications suggests that the use of appropriateness criteria may enhance the efficient use of colonoscopy for screening. [ABSTRACT FROM AUTHOR]

Studies the use diagnostic radiology by chiropractors in Switzerland with the aim of determining their contribution to the annual radiation collective dose. Number of chiropractic radiographic examinations performed in Switzerland, mainly spinal and pelvic examinations; Associated annual collective dose; Chiropractic contribution to the total dose due to conventional radiography.

Exosomes are cell-derived extracellular vesicles of 30-150 nm in size and are involved in intercellular communication. Because of their bioactive cargo, consisting of proteins, RNA and lipids, and their natural ability to deliver these biomolecules to recipient cells, exosomes are increasingly being studied as novel drug delivery vehicles or as cell-free approaches to regenerative medicine. However, one of the major hurdles for clinical translation of therapeutic strategies based on exosomes is their low yield when produced under standard culture conditions. Exosomes are vesicles of endocytic origin and are released when multivesicular endosomes fuse with the plasma membrane. Here, we demonstrate that interfering with endolysosomal trafficking significantly increases exosome release. Furthermore, these exosomes retain their regenerative bioactivity as demonstrated by pro-survival and angiogenesis assays using both cardiomyocytes and endothelial cells. These results may be employed to increase exosome production for studying biological functions or to improve clinical translation of exosome-based therapeutics. Exosomes are cell-derived vesicles and are involved in intercellular communication. Exosomes have great potential as drug delivery systems or mediators of regenerative medicine; however, low exosome yield is a major challenge for development of exosome-based therapeutics. Here, we demonstrate that interfering with endolysosomal trafficking enhances release of exosomes with regenerative bioactivity. Unlabelled Image [ABSTRACT FROM AUTHOR]

Heart failure and obesity are two growing epidemics in the United States with significant overlap in patient populations. Morbid obesity is currently a relative contraindication to cardiac transplantation as previous data has shown decreased survival with extremes of body mass index (BMI). However, there is limited data that explores the relationship between BMI and adverse outcomes following left ventricular assist device (LVAD) implantation. This study aims to determine if there is an association between higher BMI and exchange-free survival at one year post LVAD implantation. This was a single-center, retrospective cohort study with patients who had undergone LVAD implantation at Barnes-Jewish Hospital between 2005 and 2018. Patients with age<18, BMI<18.5, or no available BMI information were excluded. Patients were divided into four groups: 18.5≤BMI<30 (BMI<30 group), 30≤BMI<35 (BMI 30-35 group), 35≤BMI<40 (BMI 35-40 group), and BMI≥ 40 group. Subjects were censored for heart transplant. The groups were compared for death or LVAD exchange using the log-rank test. We examined 734 patients who underwent LVAD implantation, including 574 HeartMate II devices (78%), 124 HeartWare HVAD devices (17%), and 36 HeartMate III devices (5%). Compared to BMI<30 group, higher BMI groups were more likely to be younger, female, black race, and have diabetes mellitus. Higher BMI groups also had more HVAD and HeartMate III models (57% and 33%, respectively, in BMI≥40 group). Cumulative exchange-free LVAD survival was worse for higher BMI categories (one year exchange free survival BMI <30 = 75%, BMI 30-35 = 69%, BMI 35-40 = 66%, BMI≥40 = 66%, p-value for trend 0.034) (Figure 1). In this cohort, higher BMI is associated with decreased exchange-free survival in LVAD patients. Further studies are needed to clarify impact of BMI on adverse clinical outcomes. [ABSTRACT FROM AUTHOR]