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A review of the literature has shown that there are many similarities in the presentation of neuroleptic malignant syndrome (NMS) and catatonia. Attempts to reconcile the differences have been made by suggesting that NMS and catatonia may represent different presentations of the same illness or that they lie within the same spectrum of a poorly understood clinical syndrome. The described case is of a patient who presented with NMS and catatonia which was difficult to diagnose, but which responded to treatment with intravenous diazepam.

Background: The aim of this study is to evaluate the source of infectious complications following contemporary left ventricular assist device (LVAD) implantation and to determine the impact of infections on patient outcomes. Methods: All patients who underwent centrifugal LVAD implantation between 2014 and 2020 at a single center were retrospectively reviewed. Postimplant infections were categorized as VAD‐specific, VAD‐related, or non‐VAD according to previously published definitions. Postoperative survival and freedom from readmission were assessed using Kaplan–Meier analysis. Univariable and multivariable analyses were performed to determine the risk factors for postoperative infectious complications. Results: A total of 212 patients underwent centrifugal LVAD implantation (70 HeartMate 3, 142 HeartWare HVAD) during the study period. One hundred and two patients (48.1%) developed an infection, including 34 VAD‐specific, 11 VAD‐related, and 57 non‐VAD. Staphylococcus species were the most common source of postoperative infection (n = 57, 33.7%). In multivariable analysis, diabetes significantly impacted overall postoperative infection rate. At 12 and 24 months, respectively, Kaplan–Meier survival was 81.1% and 61.6% in the infection group and 83.4% and 78.1% in the noninfection group (p = 0.006). Within the total cohort, 12‐ and 24‐month freedom from infection were 46.2% and 31.9%, respectively. Patients with infectious complication had significantly lower rate of transplantation (16.4% vs. 43.6%; p < 0.001), increased overall mortality (46.3% vs. 17.3%, p < 0.001), and increased rates of noncardiac readmission (58.2% vs. 37.3%, p = 0.007). Conclusions: Infections are common following contemporary LVAD implantation and are most commonly non‐VAD related. Patients with postoperative infectious complications have significantly reduced rates of transplantation, survival, and freedom from noncardiac readmission. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the impact of early massive transfusion and blood component ratios on outcomes following left ventricular assist device (LVAD) implantation. Methods: Adults undergoing LVAD implantation between 2009 and 2018 at a single institution were included. Transfusions were analyzed during the intraoperative and the initial 24‐h postoperative period. Patients were stratified into massive and nonmassive transfusion groups. The primary outcome was survival, and secondary outcomes included postoperative complications. Sub‐analyses were performed to evaluate the impact of balanced transfusion. Results: A total of 278 patients were included. A total of 45.3% (n = 126) required massive transfusions. The massive transfusion group experienced significantly higher rates of postimplant adverse events, including reoperation, renal failure, and hepatic dysfunction (all, p ≤.05). Furthermore, the massive transfusion group had significantly lower 30‐day, 90‐day, 1‐year, 2‐year, and overall survival rates following LVAD implantation (all, p <.05). In multivariable analysis, massive transfusion significantly impacted overall risk‐adjusted mortality rate (hazard ratio: 2.402, 95% confidence Interval: 1.677–3.442, p <.001). In the sub‐analyses evaluating the impact of balanced massive transfusion, balanced fresh frozen plasma to packed red blood cell (pRBC) transfusion did not provide any survival benefit (all, p >.05). However, balanced platelet to pRBC massive transfusion did improve 2‐year and overall mortality rates in the massive transfusion cohort (both, p ≤.05). Conclusions: This study demonstrates a significant association between early massive transfusion and adverse outcomes following LVAD implantation. Balancing platelet to pRBC transfusion in the early postoperative period may help mitigate some of these detrimental effects of massive transfusion on subsequent survival. [ABSTRACT FROM AUTHOR]

Background: This single-center, retrospective study evaluates the impact of hepatic steatosis on outcomes after continuous-flow left ventricular assist device (LVAD) implantation.Methods: Adults undergoing LVAD implantation between 2004 and 2018 with a preoperative noncontrast-enhanced chest and abdominal computed tomography scan were included in the study. Patients were stratified as with and without radiographic signs of hepatic steatosis. The primary outcome was survival, and secondary outcomes included rates of postimplant adverse events.Results: A total of 203 patients were included in the study. 27.6% (n = 56) had radiographic signs of hepatic steatosis. Hepatic steatosis group had a higher body mass index (30.1 vs. 27.0, p < .01), model for end-stage liver disease excluding international normalized ratio score (16.8 vs. 15.1, p = .05), and incidence of diabetes (53.6% vs. 35.4%, p = .02). The rates of postimplant adverse events, including bleeding, infection, reoperation, renal failure, hepatic dysfunction, stroke, and right ventricular failure, were similar between the groups (all, p > .05). Unadjusted survival was comparable between the groups at 30-days, 90-days, 1-year, and 2-year following LVAD implantation (all, p > .05). In addition, hepatic steatosis did not impact risk-adjusted overall mortality when modeled as a categorical variable (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.46-1.13; p = .15).Conclusions: This study demonstrates that the presence of preoperative hepatic steatosis on imaging is not predictive of increased morbidity or mortality following LVAD implantation. Despite the association with obesity, metabolic diseases, and heart failure, hepatic steatosis on imaging appears to have a limited role in patient selection or prognostication in LVAD patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the predictive utility of preoperative right ventricular (RV) global longitudinal strain (GLS) and free wall strain (FWS) on outcomes following left ventricular assist devices (LVADs) implantation.Methods: Preoperative transthoracic echocardiograms were retrospectively reviewed in adults undergoing continuous-flow LVAD implantation between 2004 and 2018 at a single center. Patients undergoing pump exchange were excluded. RV GLS and FWS were calculated using commercially available software with the apical four-chamber view. The primary outcome was RV failure as defined by the Interagency Registry for Mechanically Assisted Circulatory Support within 1-year post-LVAD insertion.Results: A total of 333 patients underwent continuous-flow LVAD implantation during the study period and 137 had adequate preoperative studies for RV strain evaluation. RV FWS was found to be a significant predictor of postoperative RV failure in univariate analysis (odds ratio [OR] = 1.12, p = .03), and this finding persisted after risk adjustment in multivariable analysis (OR = 1.14, p = .04). Using the optimal cutoff value of -5.64%, the c-index of FWS in predicting RV failure was 0.65. RV GLS was not associated with post-LVAD RV failure (OR = 1.07, p = .29). PCWP was the only additional significant predictor of RV failure using multivariable analysis (OR = 0.90, p = .02).Conclusion: Pre-implant RV FWS is predictive of RV failure in the first postoperative year after LVAD implantation. [ABSTRACT FROM AUTHOR]

Background: With septuagenarians undergoing orthotopic heart transplantation (OHT) more frequently, we aimed to develop a risk score for 1‐year mortality in this population. Methods: Septuagenarian OHT recipients were identified from the UNOS registry between 1987 and 2018. The primary outcome was 1‐year post‐OHT mortality. Patients were randomly divided into derivation and validation cohorts. Associated covariates were entered into a multivariable logistic regression model. A risk score was created using the magnitudes of the odds ratios from the derivation cohort, and its 1‐year post‐OHT mortality prediction capacity was tested in the validation cohort. Results: A total of 1156 septuagenarians were included, and they were randomly divided into derivation (66.7%, n = 771) and validation (33.3%, n = 385) cohorts. An 11‐point risk score incorporating 4 variables was created, which included mechanical ventilation, serum bilirubin, serum creatinine, and donor age. The predicted 1‐year mortality ranged from 4.2% (0 points) to 48.1% (11‐points) (p <.001). After cross‐validation, the c‐index was 0.67 with a Brier score of 0.10. Risk scores above 3 points portended a survival disadvantage at 1‐year follow‐up (p <.001). Conclusions: This 11‐point risk score for septuagenarians is predictive of mortality within 1‐year of OHT and has potential utilization in improving recipient evaluation and selection of elderly patients. [ABSTRACT FROM AUTHOR]

Introduction: Stentless porcine xenografts are versatile bioprosthetic valves with the advantage of improved hemodynamics that mimic the function of the native aortic valve. However, these bioprostheses are challenging to implant in the subcoronary position.Methods: All consecutive patients who underwent a bioprosthetic aortic valve replacement (AVR) were included from our institutional database. Cox regression analysis was preformed to determine significant predictors for mid term mortality as well as all cause, cardiac, and heart failure readmission.Results: Patients in the subcoronary stentless group were older and more likely to be female and were likely to have a higher Society of Thoracic Surgery risk of mortality. Survival was superior in the stented AVR cohort at 30-days (96.4% vs 90.5%; P < .001), 1-year (90.5% vs 71.6%; P < .001), and 5-year (74.5% vs 56.9%; P < .001) follow up. Acute kidney injury (16.22% vs 5.22%; P < .001) and blood product transfusion (70.27% vs 44.0%; P < .001) were higher in the stentless group. Multivariable analysis revealed subcoronary stentless implantation as a significant independent risk factor for mortality (hazards ratio: 1.92 [1.35,2.72]; P < .001).Conclusion: Stentless porcine xenograft implantation with the Freestyle bioprosthetic in the subcoronary position can be successfully performed in select patients, but its use is associated with increased perioperative morbidity and mortality affecting midterm outcomes. Individual patient selection and surgeon experience are important to ensure favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate outcomes of left ventricular assist devices (LVADs) in patients who tested positive for hypercoagulable hematologic disorders.Methods: Adults undergoing continuous-flow LVAD implantation with preoperative hypercoagulability testing between 2004 and 2018 at a single center were reviewed. Hypercoagulability was defined as testing positive for antiphospholipid antibody, anticardiolipin antibody, lupus anticoagulant, protein C, protein S, factor V Leiden, and/or heparin-induced thrombocytopenia. The primary outcome was survival on the original LVAD. Secondary outcomes included rates of thromboembolic complications and readmission for intravenous heparin treatment.Results: A total of 270 LVAD patients with pre-implant hypercoagulability testing were included, and 157 (58%) tested positive for a hypercoagulable disorder. Of those testing positive, 10 (6.4%) had a clinical pre-LVAD history of thromboembolic events. Survival was comparable between hypercoagulable and non-hypercoagulable patients (1 year: 73.3% vs 78.9%, P = .2195, 2-year: 60.7% vs 62.8%, P = .3627). Rates of pump thrombosis (14.0% vs 13.3%, P = .8618), hemolysis (4.5% vs 3.5%, P = .3536), stroke (18.5% vs 14.2%, P = .3483) and readmission for IV heparin therapy (87.3% (n = 137) vs 77.9% (n = 88), P = .7560) were similar. Outcomes were comparable in patients with positive hypercoagulable tests when stratified by pre-implant clinical history of hypercoagulability as well as stratified by recent preoperative exposure to heparin or warfarin.Conclusions: In this series, positive laboratory tests for hypercoagulability were common amongst patients undergoing LVAD implantation although few had positive clinical histories. Survival and freedom from thromboembolic complications were comparable to non-hypercoagulable patients. Hypercoagulability alone should therefore not serve as a contraindication to LVAD implantation. [ABSTRACT FROM AUTHOR]

Background: This study evaluated outcomes of mitral valve surgery for severe ischemic mitral regurgitation (IMR).Methods: Patients undergoing coronary artery bypass grafting (CABG) with concomitant mitral valve repair (MVr) or replacement (MVR) for severe IMR at a single center between 2010 and 2017 were included. The primary outcome was 5-year survival. Secondary outcomes included operative mortality and morbidity, hospital readmission, recurrence of at least moderate mitral regurgitation (MR), and mitral valve reoperation.Results: A total of 358 patients underwent concomitant mitral valve surgery with CABG for severe IMR (275 MVr and 83 MVR). Unadjusted and risk-adjusted operative mortality was higher in MVR (16% vs 8%; P = .04). MVR patients had higher rates of postoperative renal failure, prolonged ventilation, and deep sternal wound infection. The unadjusted 5-year survival was similar (MVR 64% vs MVr 64%; P = .41), a finding that persisted after risk-adjustment. The 5-year freedom from mitral valve reoperation was 96% and 97% (P = .47). Freedom from at least moderate MR at 1-year and 3-years was 100% vs 86% (P = .09) and 100% vs 68% (P = .06) for MVR and MVr, respectively. However, only three MVr patients developed severe MR by 3 years. Cumulative hazards for all-cause readmission and heart failure-specific readmission were higher with MVR.Conclusions: Despite a trend towards higher risk of MR recurrence, patients undergoing MVr have similar rates of survival and mitral valve reoperation, with lower rates of readmission at 5-years. This, combined with lower operative mortality rates, makes MVr a reasonable choice particularly in sicker patients with higher operative risk and more limited life expectancy. [ABSTRACT FROM AUTHOR]

HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy. [ABSTRACT FROM AUTHOR]

The presence of 2 distinct populations of somatic or germline cells within a single individual harboring different genotypes is termed mosaicism. Recent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications. Although full TS1 is caused by a single missense mutation in the CACNA1C-encoded cardiac calcium channel, mosaic TS1 parents can display isolated syndactyly without additional phenotypic manifestations. A newborn boy presented with syndactyly at birth. The presence of syndactyly in his mother led to a diagnosis of benign familial syndactyly. However, at 9 months of age, during his first syndactyly-corrective surgery, intraoperative electrocardiograms revealed extreme QT prolongation and 2:1 atrioventricular block. A comprehensive cardiac evaluation was performed, and both mother and child were tested genetically, confirming a clinical suspicion of TS1. Only the patient tested positive for the TS1 mutation; however, more extensive molecular testing revealed a limited presence of the mutation in maternally-derived DNA. This case illustrates the potential of parental mosaicism to confound the diagnosis of potentially life-threatening genetic diseases, such as TS1. Here, a mother with a partial TS1 phenotype and genetically confirmed mosaicism transmitted the TS1-causative mutation to her son, resulting in fully expressive TS1. Thus, a shared partial phenotype should not be dismissed as a benign or insignificant finding, but should be evaluated further to rule out the possibility of parental mosaicism concealing a potentially fatal heritable disease.