Commentary: The best is yet to come Dufendach, Keith A.; Chu, Danny
The Journal of thoracic and cardiovascular surgery,
January 2023, 2023-01-00, 20230101, Letnik:
165, Številka:
1
Journal Article
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.
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.
Trileaflet aortic valve neocuspidization (AVN) using autologous pericardium (Ozaki procedure) is an emerging surgical treatment option for aortic valve diseases. Although excellent results have been ...reported from Japan, data pertaining to its use in the United States are sparse.
All adult patients who underwent AVN (AVN group) or surgical aortic valve replacement (SAVR) with a bioprosthetic valve (SAVR group) between 2015 and 2022 were identified. Propensity score matching was used to adjust the baseline characteristics between the 2 groups.
A total of 101 patients underwent AVN, and 1816 patients underwent SAVR with a bioprosthetic valve. None in the AVN group required conversion to SAVR. Before matching, mean age in the AVN group was 68.5 ± 8.8 years, and 56 patients (55.4%) underwent concomitant procedures. Preoperatively, 3 (3%) had endocarditis. Bicuspid valve was observed in 38 (38.4%). None died at 30 days in the AVN group. The median follow-up duration was 3.2 years. After propensity score matching, the expected survival and freedom from at least moderate aortic regurgitation at 5 years was 91.7% ± 3.1% and 97.6% ± 1.7%, respectively. Propensity score matching yielded 77 patients in each group. The Kaplan-Meier curve demonstrated equivalent survival at 5 years between the 2 groups (P = .95). Additionally, freedom from at least moderate aortic regurgitation was comparable at 5 years (P = .23).
AVN can be safely performed for a variety of aortic valve diseases, with or without concomitant operations. AVN demonstrated similar midterm outcomes compared with SAVR with a bioprosthetic valve in the United States adult population.
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.
Acute type A aortic dissection (TAAD) is a complex disease associated with extremely high morbidity and mortality for which we advocate a coordinated, protocol-driven system of care delivery that ...begins at patient diagnosis and continues throughout and beyond aortic reconstruction. Essential components of TAAD repair include prompt restoration of true lumen blood flow with obliteration of the false lumen flow, resection of the primary tear sites, restoration of valvular competency, and elimination of any organ malperfusion. This article focuses specifically on extent of repair of the aortic arch and explains our protocols regarding cannulation location and technique, cerebral and distal organ protection strategy, management of the brachiocephalic vessels, and extent of distal aortic reconstruction. We describe an operative strategy for TAAD repair that includes (1) continuous neurocerebral monitoring in all cases, (2) uninterrupted antegrade and/or retrograde cerebral perfusion (depending upon extent of arch repair) during open arch reconstruction, (3) aortic arch replacement technique with or without brachiocephalic vessel replacement using a custom trifurcate graft, and (4) descending aortic stabilization with or without the use of an elephant or frozen elephant trunk (distal stent graft). Our protocol for extent of aortic arch and brachiocephalic reconstruction has been standardized and is predicated on distinct pathoanatomic findings and/or cerebral malperfusion that are outlined.
Neuroleptic Malignant Syndrome or Catatonia? A Case Report Rodriguez, Sebastian; Dufendach, Keith A.; Weinreib, Robert M.
Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures),
07/2020, Letnik:
6, Številka:
3
Journal Article
Recenzirano
Odprti dostop
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.
The case concerns a 22-year-old male admitted for pulmonary hypertension to an intensive care unit (ICU). Three days following admission, he developed a high fever that did not respond to antibiotics. The patient then developed rigidity, nocturnal agitation, decreased responsiveness, and somnolence. Without the use of bromocriptine (Novartis, Basel, Switzerland) or dantrolene (Par Pharmaceuticals, Chestnut Ridge, USA) discontinuation of neuroleptics combined with intravenous diazepam (Pfizer, NY, USA) led to a very rapid response and marked improvement in the case.
Early recognition and management of NMS and MC in a complex, gravely ill patient, may be accomplished in the ICU despite obfuscation of traditional signs and symptoms of the NMS and MC syndrome. Such interventions can have life-saving effects on patients in danger of fatal autonomic instability.
Background
Surgical implantation of a prosthetic aortic valve is typically done with multiple interrupted sutures. We adapted a running suture line technique for prostheses implantation to decrease ...the rate of complete heart block necessitating permanent pacemaker.
Methods
374 patients undergoing isolated aortic valve replacements were identified between 2015 and 2017. Patients with preoperative heart block, patients undergoing concomitant MAZE procedure and those undergoing multivalve procedures were excluded. Interrupted technique was performed with multiple non-pledgeted sutures. Running technique was performed with three 2–0 polypropylene sutures. Propensity-score matching (caliper distance = 0.10) was used to match based on patient age, gender, BMI, diabetes mellitus, renal failure, heart failure, arrythmias, use of anti-arrhythmics, and STS PROM.
Results
Propensity score matching yielded 103 pairs of running technique and interrupted technique patients for analysis. Within the propensity score-matched cohort, there were no differences in sustained complete heart block and need for pacemaker, 4 (3.8%) for running technique vs 3 (2.9%) for interrupted technique (
p
= 0.307). At 4 weeks, there was no difference in mean prosthetic aortic valve gradients calculated on transthoracic echocardiogram (6.39 ± 2.47 mmHg vs 6.46 ± 2.86,
p
= 0.850). There was no difference in paravalvular leak (0 (0%) vs 2 (1.9%),
p
= 0.070).
Conclusions
Surgical implantation of a prosthetic aortic valve may be performed with a running suture technique without any significant increase in risk of heart block, need for permanent pacemaker or paravalvular leak. Long-term data will be critical to evaluate any development of paravalvular leaks in the future.
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