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Ticagrelor is often administered to patients with acute coronary syndromes. However, when these patients require urgent or emergent cardiothoracic (CT) surgery the presence of ticagrelor significantly increases surgical bleeding. The goal of the current trial is to evaluate the effectiveness and safety of the DrugSorb-ATR hemoadsorption device for the intraoperative removal of ticagrelor to reduce postoperative bleeding in the above patient population. The Safe and Timely Antithrombotic Removal - Ticagrelor (STAR-T) Trial is a multi-center, double-blind, randomized, controlled trial enrolling patients who require cardiothoracic surgery on cardiopulmonary bypass (CPB) within 48 hours of last ticagrelor dose.Subjects will be randomized 1:1 to receive either the DrugSorb-ATR device or an identical sham device during CPB. The study will enroll up to 120 subjects at 20 U.S centers, and the primary outcome is the composite of fatal perioperative bleeding, moderate/severe/massive bleeding according to the Universal Definition of Perioperative Bleeding in Cardiac Surgery (UDPB), and 24 hours chest tube drainage. The components of the composite are hierarchically ranked according to clinical significance and the primary analysis will utilize the Win Ratio method. Percent change in ticagrelor levels before and after CPB (drug removal) will be the key secondary endpoint. An independent Clinical Events Committee will adjudicate all clinical endpoints including safety endpoints relating to postoperative thrombotic events. Subjects will be followed through 30 days after the index operation.The results from STAR-T, if positive, will potentially support FDA market approval for DrugSorb-ATR, and provide a solution to an important unmet clinical need.

Background Most pivotal transcatheter aortic valve replacement (TAVR) trials have excluded patients with bicuspid aortic stenosis (AS). This study compared TAVR in low-risk patients with bicuspid AS to those with tricuspid AS, incorporating data from prospective trials. Methods We selected prospective US low-risk TAVR trials containing a bicuspid arm for this meta-analysis, examining outcomes at 30 days. Study results were pooled using a hierarchical Bayesian random-effects model. Results Included were 3 Food and Drug Administration (FDA)-approved investigational device exemption (IDE) trials that enrolled a total of 1810 low-risk patients with symptomatic severe AS for TAVR. We compared 380 bicuspid patients with 1430 tricuspid patients. Event rates at 30 days overall were low, with similar mortality (odds ratio [OR], 0.38; 95% credible interval [CrI]: 0.08, 1.78; I2, 0%), non-disabling stroke (OR, 0.45; 95% CrI: 0.15, 1.07; I2 , 9%), and permanent pacemaker implantation (OR, 0.86; 95% CrI: 0.41, 1.47; I 2, 59%). There were statistically significant differences in disabling stroke (OR, 0.16; 95% CrI: 0.01, 0.90; I2 , NA) and coronary obstruction (OR, 0.21; 95% CrI: 0.05, 0.91) that disappeared after sensitivity analysis by adding a single event to the tricuspid arm. Hemodynamics were similar at 30 days. Conclusions Preliminary data from the FDA-approved IDE trials of low-risk patients with bicuspid AS undergoing TAVR demonstrated 30-day outcomes comparable to low-risk tricuspid patients, except for a trend toward higher stroke in bicuspid patients. Randomized trials are warranted to reassure the safety and long-term outcome of TAVR in patients with severe bicuspid AS.

The unprecedented public health burdens of coronavirus disease 2019 (COVID-19) have intensified the urgency to identify effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (Awake Prone Positioning for Early Hypoxemia in COVID-19 [APPEX-19]). Key innovations of this trial include: 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment; 2) a Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs; 3) remote electronic collection of patient-reported outcomes and electronic medical record data; and 4) pragmatic prospective utilization of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).

Background The day of the week (DOW) for performing procedures and operations has been shown to affect clinical and resource utilization outcomes. Limited published data are available on vascular surgery operations. Our primary objective was to assess outcomes by DOW for infrainguinal lower extremity bypass (LEB) performed for claudication or rest pain. The secondary objective was to assess outcomes by DOW for LEBs performed for tissue loss. Methods The Vascular Quality Initiative was queried from 2003 to 2018 for all elective index infrainguinal LEBs performed for claudication or rest pain. Cases performed for acute limb ischemia as well as concomitant peripheral vascular intervention, nonelective LEBs, sequential grafts, and weekend cases were excluded. LEBs were grouped by DOW: Monday–Tuesday (early weekdays) versus Wednesday–Friday (later weekdays). Baseline data, operative details, and outcomes were collected. Univariate and multivariable analyses were performed. LEBs performed for claudication/rest pain were analyzed together while tissue loss was assessed separately. Results There were 12,084 LEBs identified—44.5% performed on Monday–Tuesday and 55.5% on Wednesday–Friday. Overall, the mean age was 65.6 years, 68.6% were male, and 82.8% were Caucasian. LEBs were performed for claudication in 57.4% of cases. An autogenous great saphenous vein was used in 58.8% of cases, whereas a prosthetic graft was used in 35.1% of cases. The most common bypass origin was the femoral artery (94.1%), and target was the popliteal artery (70.1%). Significant differences between Monday–Tuesday versus Wednesday–Friday, respectively, were mean body mass index (27.8 kg/m2 vs. 28 kg/m2), preoperative aspirin use (74.2% vs. 72.5%), continuous vein harvest technique (41.9% vs. 44%), and mean operative time (mins) (216.2 vs. 222.6) (all P 0.05). However, LEBs performed for tissue loss on Wednesday–Friday versus Monday–Tuesday had similar cardiac complications (P > 0.05). Conclusions Elective LEBs performed on later weekdays for claudication/rest pain were associated with cardiac complications and prolonged LOS, whereas tissue loss confirmed association with prolonged LOS. Further investigations are needed to identify whether increased resources or allocation of resources should be focused on later weekdays to optimize patient outcomes.

Aims: Despite the prevalence of hypogonadism (testosterone deficiency [TD]) and widespread use of testosterone therapy (TTh), the effectiveness and safety of long-term testosterone use rem...

There are limited data on access type when treating ruptured abdominal aortic aneurysms (AAAs) with endovascular aneurysm repair (EVAR). Our study's objective was to evaluate if the type of access in ruptured AAAs affected outcomes.The Vascular Quality Initiative was queried from 2009 to 2018 for all ruptured AAAs treated with an index EVAR. Procedures were grouped by access type: percutaneous, open, and failed percutaneous that converted to open access. Patients with iliac access, both percutaneous and open access, and concurrent bypass were excluded. Baseline characteristics, procedure details, and outcomes were collected. Univariable and multivariable analyses were performed.There were 1,206 ruptured AAAs identified-739 (61.3%) was performed by percutaneous access, 416 (34.5%) by open access, and 51 (4.2%) by failed percutaneous that converted to open access. Percutaneous access, compared with open access and failed percutaneous access, respectively, had the shortest operative time (min, median) (111 vs. 138 vs. 180, P 0.001) and was most often performed under local anesthesia (16.7% vs. 5% vs. 9.8%, P 0.001). The amount of contrast used was similar between the approaches. Univariable analysis comparing percutaneous access, open access, and failed percutaneous access showed differences in 30-day mortality (19.9% vs. 24.8% vs. 39.2%, P = 0.002), postoperative complications (33.7% vs. 40.2% vs. 54%, P = 0.003), and cardiac complications (18.2% vs. 19.8% vs. 34.7%, P = 0.018). However, multivariable analysis did not show access type to have a significant effect on cardiac complications, pulmonary complications, any complications, return to the operating room, or perioperative mortality. Open access was independently associated with a prolonged length of stay (means ratio 1.17, 95% confidence interval (CI) 1.04-1.33, P = 0.012). Factors independently associated with failed percutaneous were prior bypass (odds ratio (OR) 9.77, 95% CI 2.44-39.16, P = 0.001) and altered mental status (OR 2.45, 95% CI 1.17-5.15, P = 0.018).Access type for ruptured AAAs was not independently associated with major morbidity or mortality but did have a differential effect on length of stay. Access during these emergent procedures should be based on surgeon preference and experience.

Objectives The aim of this study was to compare late-term clinical outcomes among patients treated with ultrathin-strut (60-μm) bioresorbable-polymer sirolimus-eluting stents (BP SES) and ...

Background Previous studies examining the use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) have largely focused on patients newly initiating therapy. Little is known about the prevalence/patterns of switching to DOACs among AF patients initially treated with warfarin. Hypothesis To examine patterns of anticoagulation among patients chronically managed with warfarin upon the availability of DOACs and identify patient/practice‐level factors associated with switching from chronic warfarin therapy to a DOAC. Methods Prospective cohort study of AF patients in the NCDR PINNACLE registry prescribed warfarin between May 1, 2008 and May 1, 2015. Patients were followed at least 1 year (median length of follow‐up 375 days, IQR 154‐375) through May 1, 2016 and stratified as follows: continued warfarin, switched to DOAC, or discontinued anticoagulation. To identify significant predictors of switching, a three‐level multivariable hierarchical regression was developed. Results Among 383 008 AF patients initially prescribed warfarin, 16.3% (n = 62 620) switched to DOACs, 68.8% (n = 263 609) continued warfarin, and 14.8% (n = 56 779) discontinued anticoagulation. Among those switched, 37.6% received dabigatran, 37.0% rivaroxaban, 24.4% apixaban, and 1.0% edoxaban. Switched patients were more likely to be younger, women, white, and have private insurance (all P

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. Methods: The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm 2 with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. Results: Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite end point than those in the conservative arm (hazard ratio, 0.46 [95% CI, 0.23–0.90]; P =0.02). There was no statistical difference in secondary end points, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome. Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02436655.

Background Coronary stenting without angioplasty pretreatment (direct stenting) may simplify procedures in appropriate lesions. Direct stenting is facilitated by smaller profile coronary stent platforms. The present study was designed for regulatory approval of a novel drug-eluting coronary stent and incorporates both randomized comparison for non-inferiority to an approved predicate device as well as a nested evaluation of subjects eligible for direct stenting. Study Design and Objectives. Prospective, single-blind, randomized, active-control, multi-center study designed to assess the safety and efficacy of the novel Svelte sirolimus-eluting stent (SES) systems. A total of 1630 subjects with up to 3 target lesions will be randomized 1:1 to the Svelte SES versus either the Xience or Promus everolimus-eluting stents (control). Randomization will be stratified by whether or not a direct stenting strategy is planned by the investigator. The primary endpoint is target lesion failure (TLF) at 12 months post index procedure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization, and the primary analysis is a non-inferiority test with a non-inferiority margin of 3.58%. Secondary clinical endpoints include individual components of TLF, stent thrombosis and measures of procedural resource utilization including contrast administration, fluoroscopy exposure and procedural resource utilization as well as costs. Conclusion The OPTMIZE Trial will evaluate the safety, efficacy and clinical value of the novel Svelte SES in subjects with up to 3 lesions, and will provide a comparison of direct stenting between randomized devices.

The choice for surgical revascularisation for aortoiliac occlusive disease is often tempered by patient comorbidities. This study compares peri-operative outcomes and the association between choice of operation and one year major adverse limb event (MALE) free survival and five year mortality.The Vascular Study Group of New England (VSGNE) dataset for supra-inguinal bypass operations from 2009 to 2015 was queried. This study excluded cases with bypass other than aortofemoral (AFB), axillofemoral (AXB), and femorofemoral (FFB), and those with endovascular interventions or femoral endarterectomy. Cases combined with other procedures, indications other than occlusive disease, and missing pathology were also excluded. Patients were divided into three groups: AFB, AXB, and FFB. Thirty day post-operative death (POD) and adverse events were compared using univariable and multivariable analyses. One year MALE free survival was compared between groups with log rank test and Kaplan-Meier plot. Proportional hazard Cox regression was used for adjusted comparison of MALE free and five year survival.In total, 1,602 cases were included: 207 (12.9%) AXB; 872 (54.4%) AFB; 523 (32.6%) FFB. AXB patients were older with more comorbidities. Post-operative complications and POD rates were significantly higher for AXB (p .05). On adjusted analyses, AXB increased the hazard of one year MALE (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.12-2.78; p = .014) and five year mortality (HR 1.54; 95% CI 1.11-2.41; p = .009). Both FFB and AFB had similar one year MALE free survival but significantly better one year MALE free survival than AXB.After adjusting for confounding variables, and while acknowledging limitations related to the VSGNE data set, FFB led to significantly lower rates of post-operative complications than AXB. FFB may serve as the extra-anatomical operation of choice in high risk patients with extensive disease, who cannot undergo AFB, provided that anatomy permits. AFB should be performed preferentially in low risk patients with appropriate anatomy. Owing to its higher complications rates, the study suggests that AXB should be limited to patients with no other option for revascularisation.

Severity of cardiac involvement remains the leading determinant of survival in light chain (AL) amyloidosis. Until recently, cardiac response after treatment relied on reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP). In this study, 94 patients with AL amyloidosis (baseline BNP ≥150 pg/ml) had BNP measured at 6 months following treatment. Median overall survival was not reached for cardiac response (≥50 pg/ml and ≥ 30% decrease in BNP), 9·2 years for cardiac stability (

Light chain (AL) amyloidosis is a protein folding disorder that can affect many different organ systems, in addition to the coagulation pathway. D-dimer, a measurement of fibrin degradation, is commonly elevated in hematologic malignancies, but the prevalence and significance of D-dimer elevation in AL amyloidosis is unknown. We conducted an analysis of 921 patients with AL amyloidosis that presented to the Boston University Amyloidosis Center. Baseline characteristics and laboratory data of the 897 patients included in the final cohort were analyzed. Four hundred twenty three patients (47%) had an elevated D-dimer (0.5 μg/mL). Multivariate analysis demonstrated that a normal D-dimer level of ≤0.5 μg/mL, and a level of0.5 μg/mL but1 μg/mL, conferred a lower risk of mortality (HR 0.49 and 0.59, respectively) when compared to a D-dimer level ≥ 1 μg/mL. The increased risk of mortality in patients with a D-dimer level ≥ 1 μg/mL was present in all cardiac stages. The median overall survival based on D-dimer range of ≤0.5,0.5 but1, and ≥ 1 μg/mL was 5.86, 4.04, and 2.08 years, respectively (P .001). This retrospective analysis demonstrates the high prevalence of D-dimer elevation in AL amyloidosis and confirms that this laboratory finding is independently associated with decreased survival.

Cardiac involvement in systemic amyloidosis (AL) occurs in ~50% of all AL patients. However once symptomatic heart failure develops, therapeutic options are limited thereby conferring a poor overall prognosis. The median survival is treatment-naïve, AL cardiac amyloidosis with heart failure. Patients with biopsy-proven AL cardiac amyloid, who presented with heart failure and did not received prior AL treatment, were enrolled between 2004–2014, at the initial visit to the Amyloidosis Center at Boston University Medical Center. Routine laboratory tests, physical examination and echocardiography data were collected. There were 165 predominantly white (76.4%), and male (61%) patients, with a mean age of 61.6 ± 9.5 years. Median survival was 10.9 months (95% CI 6.2–14.7). By multivariate analysis increased relative wall thickness (RWT) [HR 6.70; 95% CI 2.45–18.30), older age (HR 1.04; 95% CI 1.01–1.06), higher New York Heart Association (NYHA) functional class (HR 1.50; 95% CI 1.02–2.2), log brain natriuretic peptide (BNP) levels (HR 1.45; 95% CI 1.15–1.81) and C-reactive protein (CRP) levels (HR 1.02; 95% CI 1.00–1.04) were significant predictors for increased mortality. In conclusion, in treatment-naïve, AL cardiac amyloidosis patients with heart failure symptoms who lack these high-risk features may have a better outcome. These findings might allow for better risk stratification although outcomes are still poor.

Background: Five years of prospective clinical trials confirm that the paclitaxel drug-coated balloon (DCB) (IN.PACT Admiral, Medtronic, Dublin, Ireland) is safe and effective to treat femo...

Goal We performed a systematic review and meta-analysis aiming to clarify the relationship between acid-suppressive medication (ASM) and the risk of pneumonia in acute stroke. Methods The included studies examined patients with an acute ischemic and/or hemorrhagic stroke, assessed the relationship of one or both groups of ASM, histamine-2 receptor antagonist (H2RA) and proton-pump inhibitor (PPI), as a variable of interest, and used the occurrence of hospital-acquired pneumonia (HAP) as an outcome measure. The search was conducted in MEDLINE, Cochrane, Embase, and Google Scholar. Random-effects meta-analyses were used to obtain pooled estimates of the effect. Results 5 retrospective cohort-studies fulfilled study criteria. The results revealed a higher risk of pneumonia for both, patients receiving PPI (adjusted relative risk [RR] 2.37, 95% confidence interval [CI] 1.36–4.17, I2 0%) and H2RAs (adjusted RR 1.73, 95% CI 0.74–4.25, I2 68.3%), although the latter did not reach statistical significance. A comparison of the overall acid versus non-acid groups using unadjusted values yielded likewise an increased risk for pneumonia for patients receiving ASM (unadjusted RR 4.65, 95% CI 1.64–13.16, I2 93.3%). Conclusion Results of this meta-analysis show an increased risk for HAP in acute stroke patients who receive ASM, particularly those exposed to PPIs. Larger, well-controlled studies in acute stroke populations are needed to establish a clearer association between ASM and HAP. These results, however, urge caution when prescribing ASM – especially to stroke patients considered to be at high risk for pneumonia.

OBJECTIVE Type 2 diabetes (T2D) is a public health threat. Prediabetes represents a window of opportunity for intervention to prevent T2D. Men with T2D and prediabetes often have low testosterone. Since testosterone improves glycemic control in T2D, we investigated whether testosterone therapy (TTh) in men with hypogonadism and prediabetes prevents progression to T2D. RESEARCH DESIGN AND METHODS Three hundred and sixteen men with prediabetes (defined as HbA1c 5.7–6.4%) and total testosterone levels ≤12.1 nmol/L combined with symptoms of hypogonadism were analyzed. Two hundred and twenty-nine men received parenteral testosterone undecanoate (T-group), and 87 men with hypogonadism served as untreated control subjects. Metabolic and anthropometric parameters were measured twice yearly for 8 years. RESULTS HbA1c decreased by 0.39 ± 0.03% (P < 0.0001) in the T-group and increased by 0.63 ± 0.1% (P < 0.0001) in the untreated group. In the T-group, 90% achieved normal glucose regulation (HbA1c 6.5%). TTh was also associated with significant improvements in fasting glucose, triglyceride:HDL ratio, triglyceride-glucose index, lipid accumulation product, total cholesterol, LDL, HDL, non-HDL, triglycerides, and Aging Males’ Symptoms (AMS) scale. Significant deterioration in all these parameters was seen in the untreated group. Mortality was 7.4% in the T-group and 16.1% in the untreated group (P < 0.05). The incidence of nonfatal myocardial infarction was 0.4% in the T-group and 5.7% in the untreated group (P < 0.005). CONCLUSIONS Long-term TTh completely prevents prediabetes progression to T2D in men with hypogonadism and improves glycemia, lipids, and AMS score. TTh holds tremendous potential for the large and growing population of men with prediabetes and hypogonadism.

The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the Boston University Amyloidosis Center. Outcomes were analyzed according to date of diagnosis: 1980-1989 (era 1), 1990-1999 (era 2), 2000-2009 (era 3), and 2010-2019 (era 4). Overall survival increased steadily with median values of 1.4, 2.6, 3.3, and 4.6 years for eras 1–4, respectively (P 10 years after diagnosis). Under changing standards of care, survival improved and early mortality declined over the last 40 years. These findings support a more optimistic outlook for patients with AL amyloidosis.

Aims The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. Methods and results LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93–9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06–6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P Conclusion Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (

AimsDiabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. The multicentre, prospective Lipid-Rich Plaque trial (LRP) examined non-culprit (NC) non-obstructive coronary segments with a combined near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) catheter. This study assessed the differences in NC plaque characteristics and their influence on major adverse cardiac events (MACE) in diabetic and non-diabetic patients.Methods and resultsPatients with known DM status were divided into no diabetes, diabetes not treated with insulin (non-ITDM), and insulin-treated diabetes (ITDM). The association between presence and type of DM and NC-MACE was assessed at both the patient and coronary segment levels by Cox proportional regression modelling. Out of 1552 patients enrolled, 1266 who had their diabetes status recorded were followed through 24 months. Female sex, hypertension, chronic kidney disease, peripheral vascular disease, and high body mass index were significantly more frequent in diabetic patients. The ITDM group had more diseased vessels, at least one NC segment with a maxLCBI4 mm ≥400 in 46.2% of patients, and maxLCBI4 mm ≥400 in nearly one out of six Ware segments (15.2%, 125/824 segments). The average maxLCBI4 mm significantly increased from non-diabetic patients (NoDM) to non-insulin-treated diabetic patients (non-ITDM) to insulin-treated diabetic patients (ITDM; 137.7 ± 161.9, 154.8 ± 173.6, 182.9 ± 193.2, P 400 further increased the NC-MACE rate to 21.6% (Kaplan–Meier estimate).ConclusionCholesterol-rich NC plaques detected by NIRS-IVUS were significantly more frequent in diabetic patients, especially those who were insulin-treated, and were associated with an increased NC-MACE during follow-up.

Background Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known. Methods This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was defined as an increase in serum creatinine to ≥1.5 times the baseline occurring within the first 30 days of HDM/SCT. Results The median age was 58 years (range: 30–77). Kidney and cardiac involvement were present in 86.1% and 56.8%, respectively. The median estimated glomerular filtration rate (eGFR) was 83.5 mL/min/1.73 m2 (range: 9–213) and proteinuria was 2899 mg/day (range: 0–19 966). AKI occurred in 29.1% of patients. Dialysis was initiated in 15 patients (6.7%) and of these 12 (80%) were able to discontinue dialysis. Most of the episodes of AKI occurred within the first 2 weeks; with a median follow-up of 4.5 years (range: 0.1–16.5), AKI was associated with increased overall mortality [hazard rato (HR) = 4.53, 95% confidence interval (CI) 2–10.23]. The 10-year overall survival was 87.1% without AKI, versus 56.9% with AKI. AKI was also associated with an increased risk for end-stage kidney disease (ESKD) (HR = 4.6, 95% CI 1.44–14.38). The risk of developing ESKD at 10 years was 18.9% with AKI, versus 8.1% without AKI. Several risk factors were found and using multivariate logistic regression, a prediction model was developed that included three readily available variables: eGFR 12 mm and albumin Conclusions AKI is common in the post-HDM/SCT period and it leads to increased risk for ESKD and death. Our prediction model is an easily deployable tool in clinical settings as part of the discussion with patients who are being prepared for HDM/SCT.

This study sought to evaluate inappropriate prescribing practices in an atrial fibrillation (AF) population, as outlined by the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults with Atrial Fibrillation or Atrial Flutter document. The 2016 AF quality measures document specified medications to avoid in certain AF populations, including aspirin and anticoagulant combination therapy in patients without cardiovascular disease, and non-dihydropyridine calcium channel blockers in patients with reduced ejection fraction. Using data from the NCDR PINNACLE registry, a national outpatient cardiology practice registry, we assessed rates of inappropriate prescription of two types of medications among AF outpatients from 5/1/2008-5/1/2016. Overall rates of inappropriate prescription and variation by practice were calculated. Patient and practice factors associated with inappropriate prescription were assessed in adjusted analyses. A total of 107,759 of 658,250 (16.4%) patients without cardiovascular disease were inappropriately prescribed an antiplatelet and anticoagulant together, and 5,731 of 150,079 (3.8%) patients with reduced ejection fraction were inappropriately prescribed a non-dihydropyridine calcium channel blocker. Overall, 14.8% of AF patients were prescribed medications that were not recommended. Both patient and practice factors were associated with inappropriate prescribing, and the adjusted practice-level median odds ratio for inappropriate prescription was 1.70 (95% CI: 1.61-1.82), indicating a 70% likelihood that 2 random practices would treat identical AF patients differently. In a large registry of AF patients treated in cardiology practices, overall rates of inappropriate prescription practices, as defined by the 2016 AF quality measures, were relatively low, but significant practice variation was present.

The diagnosis of acute respiratory diseases in children can be challenging, and no single objective diagnostic test exists for common pediatric respiratory diseases. Previous research has demonstrated that ResAppDx, a cough sound and symptom-based analysis algorithm, can identify common respiratory diseases at the point of care. We present the study protocol for SMARTCOUGH-C 2, a prospective diagnostic accuracy trial of a cough and symptom-based algorithm in a cohort of children presenting with acute respiratory diseases. The objective of the study is to assess the performance characteristics of the ResAppDx algorithm in the diagnosis of common pediatric acute respiratory diseases.

Background and aims In this Lipid Rich Plaque (LRP) sub-study, 1551 patients undergoing coronary angiography for acute coronary syndromes or stable angina were examined with near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). We aimed to assess the correlation of patient age with the presence of high-risk plaques, defined as maximum 4-mm Lipid Core Burden Index (maxLCBI4mm) >400 and plaque burden >70%, and 2-year incidence of non-culprit major adverse cardiovascular events (NC-MACE). Methods The study population was divided into four groups according to age: Results Average maxLCBI4mm and percentage of patients with at least one segment with maxLCBI4mm > 400 were similar across the four age groups at both the patient and coronary segment levels. Having at least one segment with maxLCBI4mm > 400 was strongly associated with NC-MACE, and that association did not differ significantly across age subgroups. Although less common (prevalence of 0.8%–1.3%), a similar trend toward greater NC-MACE rates was seen in patients with plaque burden >70% at the maximum LCBI site across age subgroups. Conclusions Lipid-rich plaques were as frequent in older as in younger patients and predicted a higher incidence of NC-MACE over 2-year follow-up irrespective of age.

In marked contrast to multiple myeloma, racial/ethnic minorities are underrepresented in publications of systemic light-chain (AL) amyloidosis. The impact of race/ethnicity is therefore lacking in the narrative of this disease. To address this gap, we compared disease characteristics, treatments, and outcomes across racial/ethnic groups in a referred cohort of patients with AL amyloidosis from 1990 to 2020. Among 2416 patients, 14% were minorities. Non-Hispanic Blacks (NHBs) comprised 8% and had higher-risk sociodemographic factors. Hispanics comprised 4% and presented with disproportionately more BU stage IIIb cardiac involvement (27% vs. 4–17%). At onset, minority groups were younger in age by 4–6 years. There was indication of more aggressive disease phenotype among NHBs with higher prevalence of difference between involved and uninvolved free light chains >180 mg/L (39% vs. 22–33%, P = 0.044). Receipt of stem cell transplantation was 30% lower in Hispanics compared to non-Hispanic White (NHWs) on account of sociodemographic and physiologic factors. Although the age/sex-adjusted hazard for death among NHBs was 24% higher relative to NHWs (P = 0.020), race/ethnicity itself did not impact survival after controlling for disease severity and treatment variables. These findings highlight the complexities of racial/ethnic disparities in AL amyloidosis. Directed efforts by providers and advocacy groups are needed to expand access to testing and effective treatments within underprivileged communities.

Adaptive Disclosure (AD) is a new emotion-focused psychotherapy for combat-related PTSD. As a second step in the evaluation process, we conducted a non-inferiority (NI) trial of AD, relative to Cognitive Processing Therapy – Cognitive Therapy version (CPT-C), an established first-line psychotherapy. Participants were 122 U.S. Marines and Sailors. The primary endpoint was PTSD symptom severity change from pre- to posttreatment, using the Clinician Administered PTSD Scale for DSM-IV. Secondary endpoints were depression (Patient Health Questionnaire-9; PHQ-9) and functioning (Veterans Rand Health Survey-12; VR-12). For cases with complete data, the mean difference in CAPS-IV change scores was 0.33 and the confidence interval (CI) did not include the predefined NI margin (95% CI =-10.10, 9.44). The mean difference in PHQ-9 change scores was -1.01 and the CI did not include the predefined margin (95% CI = -3.31, 1.28), as was the case for the VR-12 Physical Component and VR-12 Mental Component subscale scores (0.27; 95% CI = -4.50, 3.95, and -2.10; 95% CI = -7.03, 2.83, respectively). A series of intent-to-treat sensitivity analyses confirmed these results. The differential effect size for CAPS-IV was d = 0.01 (nonsignificant). As predicted, Adaptive Disclosure was found to be no less effective than a first-line psychotherapy.

Therapies for AL amyloidosis have dramatically improved, leading to longer patient survival; however, more AL amyloidosis patients are reaching end-stage renal disease (ESRD). There are no clear guidelines regarding eligibility for kidney transplantation in patients with AL amyloidosis, and data on outcomes are limited. We evaluated the clinical and laboratory data of 49 patients who were followed in the Amyloidosis Center at Boston University and underwent kidney transplantation at a center in the United States between 1987-2017. During a median follow-up of 7.2 years (range 0-19), the median patient survival from diagnosis was 15.4 years, and from kidney transplantation was 10.5 years. One, three, and five-year graft survival were 94%, 89%, and 81%, respectively. Patients with hematologic complete response or very good partial response prior to kidney transplantation had significantly better patient survival than patients with partial response or no response, and the median time to graft loss was 10.4 years versus 5.5 years, respectively. This is the largest published series of kidney transplantation in patients with AL amyloidosis, suggesting that kidney transplantation can have a good outcome in carefully selected patients, particularly in those who have achieved a complete response or very good partial response at the time of kidney transplantation.

Introduction Many studies have reported that 5α-reductase inhibitors (finasteride and dutasteride) raise serum testosterone (T) levels, yet there is lack of consistency among studies on this point. Aim To review and meta-analyze available studies reporting changes in serum T concentrations in men treated with 5α-reductase inhibitors (5α-RIs). Methods A Medline search using PubMed and EMBASE was performed including the following key words: “finasteride,” “dutasteride,” “testosterone and 5α-reductases.” Main Outcome Measure Relevant studies were extracted, evaluated, and analyzed. Of these, 40 studies were analyzed qualitatively and 11 were included in the meta-analysis. A random effects model was used to conduct the meta-analysis. Results In 11 studies comprising 1,784 patients with age ranging between 18 and 83 years and average treatment follow-up of 17 months, meta-analytic estimate of the mean baseline change was 27 (95% confidence interval 1–54). The meta-analysis did not demonstrate unequivocal significant increase in serum T levels. The increase was not uniform among all studies reported. Sensitivity analysis showed that no single study contributed decisively to the outcome or could be attributed to drug action. The reported increases in T levels with finasteride or dutasteride in men with low baseline serum T may be attributed, in part, to increased trapping of T by unsaturated sex hormone binding globulin (SHBG) due to dissociation of 5α-dihydrotestosterone. In men with high baseline T levels, there appears to be no change in serum T levels. 10 studies reported luteinizing hormone, follicle-stimulating hormone, SHBG, and estradiol values and none reported significant changes in their levels, suggesting that observed changes in serum T levels are unlikely mediated by gonadotropins levels or peripheral conversion of T to estradiol. Conclusion 5α-RI therapy is not associated with consistent and significant increases in serum T levels. Traish AM, Krakowsky Y, Doros G, et al. Do 5α-reductase inhibitors raise circulating serum testosterone levels? A comprehensive review and meta-analysis to explaining paradoxical results. Sex Med Rev 2019;7:95–114.

Aims To investigate whether testosterone therapy (TTh) in men with hypogonadism and type 2 diabetes mellitus (T2DM) improves glycaemic control and insulin sensitivity, and results in remission of T2DM. Material and Methods A total of 356 men who had total testosterone levels ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism were included in the study and followed up for 11 years. All patients received standard diabetes treatment and 178 patients additionally received parenteral testosterone undecanoate 1000 mg every 12 weeks following an initial 6‐week interval. A control group comprised 178 hypogonadal patients who opted not to receive TTh. Results Patients with hypogonadism and T2DM treated with testosterone had significant progressive and sustained reductions in fasting glucose, glycated haemoglobin (HbA1c) and fasting insulin over the treatment period. In the control group, fasting glucose, HbA1c and fasting insulin increased. Among the patients treated with testosterone 34.3% achieved remission of their diabetes and 46.6% of patients achieved normal glucose regulation. Of the testosterone‐treated group, 83.1% reached the HbA1c target of 47.5 mmol/mol (6.5%) and 90% achieved the HbA1c target of 53.0 mmol/mol (7%). In contrast, no remission of diabetes or reductions in glucose or HbA1c levels were noted in the control group. There were fewer deaths, myocardial infarctions, strokes and diabetic complications in the testosterone‐treated group. Conclusions Long‐term TTh in men with T2DM and hypogonadism improves glycaemic control and insulin resistance. Remission of diabetes occurred in one‐third of the patients. TTh is potentially a novel additional therapy for men with T2DM and hypogonadism.

Purpose To analyze data from an observational, prospective, cumulative registry study in 805 hypogonadal men stratified by mild or moderate-to-severe lower urinary tract symptoms (LUTS) according to International Prostate Symptom Score. Materials and methods A total of 412 men underwent testosterone therapy (TTh) with injectable testosterone undecanoate, 393 men served as untreated controls. Measures of urinary function, anthropometric and metabolic parameters were performed at least twice per year. Results Data from 615 men with mild LUTS (253 treated, 362 untreated) and 190 with moderate-to-severe LUTS (159 treated, 31 untreated) were available. During a follow-up period of 8 years a significant improvement of LUTS was noted for all TTh-patients whereas the control-groups showed deterioration or fluctuation around initial values. Despite advancing age, TTh fully prevented worsening of symptoms. In parallel, a considerable improvement of anthropometric parameters, lipids and glycemic control, blood pressure, C-reactive protein, and quality of life was found. Moderate-to-severe LUTS was associated with worse cardiometabolic risk profile at baseline as well as worse cardiovascular outcomes during follow-up in comparison to mild LUTS. Effect size of TTh was more pronounced in men with moderate-to-severe than with mild LUTS. Conclusions Correcting hypogonadism by TTh is highly effective and safe for improving LUTS in hypogonadal men. TTh may also improve cardiometabolic risk and major adverse cardiovascular events.

Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype - a group of Black people with asthma who are at high risk of repeat exacerbation within one year - exists in asthma independent of clinical control.We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6-18 month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5).Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (p 0.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; p 0.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations.Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.

Introduction The HeartLight laser balloon ablation system was US Food and Drug Administration approved in 2016 for the treatment of paroxysmal atrial fibrillation (AF), but there have been numerous single-center and multicenter studies published reporting its outcomes, in addition to a few randomized trials. We aimed to systematically review and synthesize currently published outcome data on AF ablation using the laser balloon ablation system. Methods and results We performed a systematic review and meta-analysis of published studies of AF ablation performed using the laser balloon ablation system. Human studies reporting acute procedural results with a minimum of 6 months follow-up were included. Outcomes of interest included acute and 12-month procedural efficacy, safety, and procedure duration. Aggregated data were analyzed with random effects models, using a Bayesian hierarchical approach. We identified 17 published manuscripts comprising a sample of 1188 patients (mean age 61 years, 80% paroxysmal). At procedure end, 98.8% of targeted pulmonary veins were successfully isolated. The pooled estimate for 12-month freedom from atrial arrhythmia without use of antiarrhythmic drugs for patients with paroxysmal AF was 74.3% (95% confidence interval [CI], 59.9% to 86.4%), and for all AF types combined was 72.9% (65.3% to 79.9%). The most commonly reported procedural complication was phrenic nerve injury (pooled incidence 2.6%; 95% CI, 1.4% to 3.9%), which resolved during follow-up in most cases. Conclusion Laser balloon ablation is highly effective at achieving pulmonary vein isolation. Although comparisons are mainly indirect, safety and 12-month efficacy compare favorably with those observed using other currently used AF ablation technologies.

In clinical trials, placebo response can affect the inference about efficacy of the studied treatment. It is important to have a robust way to classify trial subjects with respect to their response to placebo. Simple, criterion-based classification may lead to classification error and bias the inference. The uncertainty about placebo response characteristic has to be factored into the treatment effect estimation. We propose a novel approach that views the placebo response as a latent characteristic and the study sample as an unlabeled mixture of “placebo responders” and “placebo nonresponders.” The likelihood-based methodology is used to estimate the treatment effect corrected for placebo response as defined within sequential parallel comparison design.

AIMS Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt. METHODS AND RESULTS Patients with biopsy-proven ATTRwt cardiac amyloidosis (n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected. Patients were classified as AF or non-AF and followed for survival for a median of 41.4 ± 27.1 months. Means testing, univariable, and multivariable regression models were employed. A systematic review was performed. AF was observed in 70% (n = 102). Mean age was similar (AF, 75 ± 6 vs. non-AF, 74 ± 5 years, P = 0.22). Anticoagulant treatment of patients with AF was as follows: 78% warfarin, 17% novel anticoagulant, and 6% no anticoagulation. Amiodarone was prescribed to 24%. There were no differences in left ventricular ejection fraction (P = 0.09) or left atrial volume (P = 0.87); however, mean diastolic dysfunction grade was higher in AF (mean 2.7 ± 0.5 vs. 2.4 ± 0.5, P = 0.01). While creatinine (P = 0.52) and B-type natriuretic peptide (P = 0.48) were similar, patients with AF had lower serum transthyretin concentrations (221 ± 51 vs. 250 ± 52 μg/mL, P

Reoperative carotid endarterectomy (CEA) can be technically challenging because of significant scarring as a consequence of the initial CEA procedure. There are limited data that describe outcomes after reoperative CEA, and as such, our goal was to determine the effect of reoperative CEA on perioperative outcomes.The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients undergoing index and reoperative CEA between 2005 and 2014. Multivariate analysis was performed to assess the effect of reoperative CEA on outcomes including stroke, major adverse cardiovascular event, and procedure time.There were 75,943 index and 140 reoperative CEAs identified. No differences were found in baseline demographics or comorbidities except that the reoperative group had a higher incidence of patients with end-stage renal disease (3.6% vs 1.1%; P = .004). Prior stroke with deficit (20.8% vs 15.4%; P = .137) and without deficit (11.5% vs 9.1%; P = .43) were similar between reoperative and index CEA groups. Both the reoperative and index initial CEA cohorts had comparable rates of surgical site infection (0.7% vs 0.3%; P = .462), return to the operating room (3.6% vs 4%; P = .816), readmission with 30 days (2.1% vs 6.9%; P = .810), myocardial infarction (2.1% vs 0.9%; P = .125), and perioperative death (0.7% vs 0.9%; P = .853). The reoperative cohort had a significantly higher rate of perioperative stroke (5.0% vs 1.6%; P = .002) and a longer operative duration (137 ± 54 vs 116 ± 49 minutes; P .001). Multivariate analysis revealed that reoperative CEA was an independent factor for postoperative stroke (odds ratio, 3.71; 95% confidence interval [CI], 1.61-8.57; P = .002), major adverse cardiovascular event (odds ratio, 2.76; 95% CI, 1.32-5.78; P = .007), and longer procedure time (means ratio, 1.21; 95% CI, 1.12-1.30; P .001).Reoperative carotid surgery is associated with a longer operative time and higher risk for perioperative stroke compared with index CEA. This information informs the risk-benefit analysis for reoperation.

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP

In this observational analysis from the Practice Innovation and Clinical Excellence Registry®, we examined changes in guideline‐directed medical therapies relative to changes in symptom severity in ambulatory patients with heart failure with reduced ejection fraction, finding change in medication more often occurring when patients were changing their New York Heart Association symptom severity, rather than during periods of stable symptoms. Additionally, despite being available for a year during the time of our analysis, the use of sacubitril/valsartan was extremely low, and most often added in the context of worsening symptoms, not how this drug was studied and not how the guidelines articulate its use.

Importance Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration ClinicalTrials.gov Identifier:NCT01928446

Objective The purpose of this study is to externally validate a recently reported Vascular Study Group of New England (VSGNE) risk predictive model of postoperative mortality after elective abdominal aortic aneurysm (AAA) repair and to compare its predictive ability across different patients' risk categories and against the established risk predictive models using the Vascular Quality Initiative (VQI) AAA sample. Methods The VQI AAA database (2010-2015) was queried for patients who underwent elective AAA repair. The VSGNE cases were excluded from the VQI sample. The external validation of a recently published VSGNE AAA risk predictive model, which includes only preoperative variables (age, gender, history of coronary artery disease, chronic obstructive pulmonary disease, cerebrovascular disease, creatinine levels, and aneurysm size) and planned type of repair, was performed using the VQI elective AAA repair sample. The predictive value of the model was assessed via the C -statistic. Hosmer-Lemeshow method was used to assess calibration and goodness of fit. This model was then compared with the Medicare, Vascular Governance Northwest model, and Glasgow Aneurysm Score for predicting mortality in VQI sample. The Vuong test was performed to compare the model fit between the models. Model discrimination was assessed in different risk group VQI quintiles. Results Data from 4431 cases from the VSGNE sample with the overall mortality rate of 1.4% was used to develop the model. The internally validated VSGNE model showed a very high discriminating ability in predicting mortality (C = 0.822) and good model fit (Hosmer-Lemeshow P = .309) among the VSGNE elective AAA repair sample. External validation on 16,989 VQI cases with an overall 0.9% mortality rate showed very robust predictive ability of mortality (C = 0.802). Vuong tests yielded a significant fit difference favoring the VSGNE over then Medicare model (C = 0.780), Vascular Governance Northwest (0.774), and Glasgow Aneurysm Score (0.639). Across the 5 risk quintiles, the VSGNE model predicted observed mortality significantly with great accuracy. Conclusions This simple VSGNE AAA risk predictive model showed very high discriminative ability in predicting mortality after elective AAA repair among a large external independent sample of AAA cases performed by a diverse array of physicians nationwide. The risk score based on this simple VSGNE model can reliably stratify patients according to their risk of mortality after elective AAA repair better than other established models.

Purpose: We investigated the effects of long-term testosterone therapy on urinary and sexual function, and quality of life in hypogonadal men.Materials and Methods: We performed an observational, prospective, cumulative registry study in 656 men with a mean ± SD age of 60.7 ± 7.2 years who had total testosterone 12.1 nmol/l or less and symptoms of hypogonadism. In the testosterone treated group 360 men received parenteral testosterone undecanoate 1,000 mg/12 weeks for up to 10 years. The 296 men who elected against testosterone therapy served as controls. From each group 82 patients were propensity matched by age, waist circumference and body mass index, resulting in 82 matched pairs of 164 men. Data were analyzed and estimated differences between the groups were adjusted for components of metabolic syndrome and quality of life.Results: We found significant decreases in I-PSS (International Prostate Symptom Score) and post-void bladder volume (each p

Background: Natural history studies, which describe changing disease outcomes under real-world clinical practice, can help support drug development for rare diseases by defining appropriate endpoints for clinical trials. The current study provides natural history information on survival and mortality in light chain (AL) amyloidosis, a rare disease that was historically considered inevitably fatal. With the recent expansion of effective therapeutics, patients with this disease are living longer, which in turn necessitates a better understanding of the factors leading to death in later disease course. Aims: To evaluate (1) trends in overall survival (OS) over time and (2) primary causes of death across the course of AL amyloidosis disease. Methods: We identified 2,337 patients diagnosed with systemic AL amyloidosis between 1980 and 2019 from the prospectively maintained database at the Boston University Amyloidosis Center (ClinicalTrials.gov Identifier: NCT00898235). Disease outcomes were analyzed according to date of tissue diagnosis: 1980-1989 (era 1, n = 185), 1990-1999 (era 2, n = 575), 2000-2009 (era 3, n = 865) and 2010-2019 (era 4, n =712). Survival information was verified through yearly clinical evaluations, contact by phone/letter for patients who did not return for follow-up, or the U.S. Social Security Death Index if contact was not established. We defined deaths as AL amyloidosis-related when clinical data indicated organ progression or complications from plasma cell-directed therapy. Deaths occurring while in remission, off treatment and without evidence of organ progression were considered disease-unrelated. Results: OS increased steadily across eras 1-4 with median values of 1.4, 2.6, 3.3 and 4.6 years, respectively (P < .001). Six-month mortality decreased over time from 23% to 13%. Notably, median age at diagnosis increased from 59 to 63 years (P < .001), and time interval to diagnosis from patient-reported symptom onset shortened from 10 months to 6 months (P = .065). At data cutoff (October 2020), 1,660 (71%) patients had died. Primary cause of death was ascertainable for 1,160 (70%) cases. Organ failure was most common, accounting for 564 (49%) deaths, amongst which cardiac failure predominated. Sudden unexpected death was the next most frequent cause, contributing to 266 (23%) deaths. Together, cardiac failure and sudden death decreased in proportion with longer survival from diagnosis, representing 67% (236/354) of deaths occurring within ≤6 months; 56% (322/575) within >6 months to ≤5 years; 36% (54/151) within >5 years to ≤10 years; and 36% (29/80) after >10 years (P < .001). Meanwhile, renal failure and infections emerged as important causes of later-occurring deaths. There was sufficient data on 1,243 (75%) deaths to assign relation to AL amyloidosis. The vast majority were disease-related. Yet, disease-unrelated deaths increased with longer survival from diagnosis, accounting for 2% (9/373) of deaths occurring within ≤6 months; 8% (48/616) within >6 months to ≤5 years; 16% (25/161) within >5 years to ≤10 years; and 29% (27/93) after >10 years (P < .001). Conclusions: Under changing standards of care, OS improved and early mortality declined over the last 40 years, supporting a much-improved outlook for current and future patients with AL amyloidosis. Cardiac failure and sudden deaths decreased across the course of disease. Even so, progression of amyloidosis remained a top cause of death even among long-term survivors. Figure 1 Figure 1. Disclosures Sanchorawala: Takeda: Research Funding; Celgene: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Karyopharm: Research Funding.

Background Timing of carotid endarterectomy (CEA) after onset of neurologic symptoms remains controversial. We assessed the association of CEA timing with postoperative outcomes. Methods The Vascular Study Group of New England (VSGNE) database (2003-2014) was queried to identify CEA performed for symptomatic carotid stenosis during the same hospitalization. Cases were divided into four groups based on the time from onset of neurologic symptoms to CEA: group I, χ 2 test and t -test were used to compare demographics, medical history, modified Rankin scores, and outcomes (30-day postoperative death, stroke, myocardial infarction, and aggregate events [stroke/myocardial infarction]). Multivariable logistic regression was used to compare the association of time to surgery with outcomes while adjusting for confounding variables. Kaplan-Meier and Cox proportional hazards regression analyses were performed at 1 year to evaluate survival and stroke rates between the groups. Results There were 989 of 14,864 VSGNE CEA cases that fit the inclusion criteria. The frequency of cases was highest in group II (36.6%), followed by groups I (31.9%), III (18.9%), and IV (12.4%). Age, gender, and comorbidity compositions were similar between groups, although group III had the highest rates of diabetes mellitus, coronary artery disease, coronary artery bypass graft procedures, congestive heart failure, and American Society of Anesthesiologists class 4 and the highest modified Rankin score ( P P = .016), whereas group III had the highest rate of discharges to nursing facilities (37.2%; P Conclusions Our results suggest that CEAs performed 2 to 5 days after a neurologic event have similar outcomes to CEAs performed ≥6 days later. Early CEA should be considered an area for quality improvement among these patients.

Introduction: Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Methods: Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). Results: There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P < .001), type IV thoracoabdominal extent (OR: 3.09, 95% CI: 1.01-9.46, P = .048), suprarenal extent (OR: 1.89, 95% CI: 1.07-3.34, P = .029) and juxtarenal (OR: 1.43, 95% CI: 1.01-2.02, P = .004), non-Caucasian race (OR: 2.80, 95% CI: 1.77-4.41, P < .001), chronic obstructive pulmonary disease (OR: 1.76, 95% CI: 1.20-2.59, P = .004), not-from-home admission (OR: 1.91, 95% CI: 1.13-3.24), and age greater than 70 (OR: 1.49, 95% CI: 1.08-2.05, P = .014). Conclusion: We identified patient and aneurysm characteristics independently associated with protracted LOS following open AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.