Totally endoscopic, robotic-assisted tricuspid valve repair and biatrial CryoMAZE.

We describe in detail our technique for totally endoscopic, robotic-assisted tricuspid valve repair for iatrogenic tricuspid regurgitation and biatrial cryoMAZE.

Outcomes of patients with advanced liver disease undergoing cardiac surgery.

Objective: Liver disease (LD) is considered a risk factor for inferior outcomes in general and cardiac surgery, yet current cardiac surgery risk estimators exclude LD, and literature on the topic remains scant. We sought to evaluate whether the presence of advanced LD is associated with inferior outcomes following cardiac surgery. Methods: This single-center, retrospective, observational study included 285 patients diagnosed with LD who underwent cardiac surgery in 2010 to 2020. The cohort contained 3 groups, Child-Turcotte-Pugh (CTP) class A (n = 219), CTP early-class B (n = 34), and CTP advanced-class B (n = 32). A model for end-stage liver disease score of 12.7 points (determined using a receiver-operating characteristic curve analysis on 30-day mortality) dichotomized class B into early- and advanced-groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of 30-day mortality. Results: Patients in CTP advanced-class B had the longest length of stay (14 days), highest incidence of prolonged ventilation (46.9%), renal failure (21.9%), 30-day mortality (18.8%), and in-hospital mortality (18.8%). Incidence of ≥1 postoperative complication was higher in CTP advanced-class B (59.4%), compared with CTP class A (37.9%) and CTP early-class B (38.2%). Multivariate logistic regression analysis demonstrated that female sex (odds ratio, 3.01; 95% CI, 1.07-8.77; P = .037) and peripheral vascular disease (odds ratio, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors of 30-day mortality in patients with advanced LD. Conclusions: Severity of LD influences perioperative outcomes following cardiac surgery. Our data suggest that patients in CTP class A and selected patients in CTP class B (model for end-stage liver disease score <12.7) can undergo surgery with acceptable risk.

Two hundred robotic mitral valve repair procedures for degenerative mitral regurgitation: the Yale experience.

Background: Robotic surgery has gained popularity over the past two decades due to the benefits related to smaller surgical incisions, enhanced technical dexterity and better intraoperative visualization. We present the Yale experience of the first two hundred totally endoscopic, robotic-assisted mitral valve repair procedures for the treatment of degenerative mitral regurgitation. Methods: We performed a retrospective cohort study of patients undergoing totally endoscopic, robotic-assisted isolated or concomitant mitral valve repair for degenerative mitral regurgitation at Yale-New Haven Hospital from October 2018 to April 2022. Mitral valve repair procedures for rheumatic or secondary functional mitral regurgitation and planned robotic-assisted mitral valve replacement cases were excluded. Results: Two hundred consecutive procedures were performed. The median age was 65 years (interquartile range, 58-73 years). Six patients (3.0%) had a history of mediastinal radiation, four patients (2.0%) had previous cardiac surgery, and one patient (0.5%) had cardiac dextroversion. Median cardiopulmonary bypass and aortic cross-clamp times were 122 and 79 minutes, respectively. Femoral vessel cannulation was performed percutaneously in 57 (28.5%) patients with no major access-site related complication. Aortic cross-clamping was performed with the endoaortic balloon occlusion device in 151 (75.5%) patients. No conversions to sternotomy occurred. Satisfactory repair was achieved in 100% of cases, with 184 (92.0%) and 16 (8.0%) of patients having trace/none or mild residual mitral regurgitation, respectively. Forty-two patients (21.0%) underwent concomitant Cox-maze procedure and 25 patients (12.5%) underwent concomitant tricuspid valve repair. Thirty-day mortality rate was 0.5%, with an observed-to-expected ratio of 0.53. Two patients (1.0%) underwent re-exploration for bleeding, one had early postoperative stroke (0.5%), five developed pneumothorax (2.5%) and two required dialysis for acute renal failure (1.0%). The median length of hospital stay was four days. Conclusions: Excellent short-term outcomes can be achieved in experienced centers for the treatment of degenerative mitral regurgitation with a totally endoscopic, robotic-assisted approach.

Redo mitral valve surgery: A totally endoscopic, robotic-assisted approach for adhesiolysis and complex repair.

We describe our technique for totally endoscopic, robotic-assisted thoracic and pericardial adhesiolysis and redo complex mitral valve repair.

Robotic, totally endoscopic excision of mitral valve papillary fibroelastoma.

Papillary fibroelastoma is a rare, benign tumor that affects males more frequently  than females and that tends to be diagnosed during the fifth or sixth decade of life. It tends to arise on cardiac valves, with the aortic valve being the most frequent location followed by the mitral valve, the tricuspid valve, and the pulmonary valve. We present the case of a robotic-assisted, totally endoscopic excision of a mitral valve papillary fibroelastoma.

Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19.

BACKGROUND: Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease. RESEARCH QUESTION: What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection? STUDY DESIGN AND METHODS: We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching. RESULTS: Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28-0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients. INTERPRETATION: Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.

Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion.

The induction of exhaustion on effector immune cells is an important limiting factor for cancer immunotherapy efficacy as these cells undergo a hierarchical loss of proliferation and cytolytic activity due to chronic stimulation. Targeting PD-1 has shown unprecedented clinical benefits for many cancers, which have been attributed to the prevention of immune suppression and exhaustion with enhanced anti-tumor responses. In this study, we sought to evaluate the role of the PD-1/PD-L1 pathway in murine natural killer (NK) cell activation, function, and exhaustion. In an in vivo IL-2-dependent exhaustion mouse model, neutralization of the PD-1/PD-L1 pathway improved NK cell activation after chronic stimulation when compared to control-treated mice. These cells displayed higher proliferative capabilities and enhanced granzyme B production. However, the blockade of these molecules during long-term in vitro IL-2 stimulation did not alter the progression of NK cell exhaustion (NCE), suggesting an indirect involvement of PD-1/PD-L1 on NCE. Given the expansion of CD8 T cells and regulatory T cells (Tregs) observed upon acute and chronic stimulation with IL-2, either of these two populations could influence NK cell homeostasis after PD-L1/PD-1 therapy. Importantly, CD8 T cell activation and functional phenotype were indeed enhanced by PD-1/PD-L1 therapy, particularly with anti-PD-1 treatment that resulted in the highest upregulation of CD25 during chronic stimulation and granted an advantage for IL-2 over NK cells. These results indicate a competition for resources between NK and CD8 T cells that arguably delays the onset of NCE rather than improving its activation during chronic stimulation. Supporting this notion, the depletion of CD8 T cells reversed the benefits of PD-1 therapy on chronically stimulated NK cells. These data suggest a bystander effect of anti-PD1 on NK cells, resulting from the global competition that exists between NK and CD8 T cells for IL-2 as a key regulator of these cells' activation. Thus, achieving an equilibrium between these immune cells might be important to accomplish long-term efficacy during anti-PD-1/IL-2 therapy.

Regulation of murine NK cell exhaustion through the activation of the DNA damage repair pathway.

NK cell exhaustion (NCE) due to sustained proliferation results in impaired NK cell function with loss of cytokine production and lytic activity. Using murine models of chronic NK cell stimulation, we have identified a phenotypic signature of NCE characterized by up-regulation of the terminal differentiation marker KLRG1 and by down-regulation of eomesodermin and the activating receptor NKG2D. Chronic stimulation of mice lacking NKG2D resulted in minimized NCE compared to control mice, thus identifying NKG2D as a crucial mediator of NCE. NKG2D internalization and downregulations on NK cells has been previously observed in the presence of tumor cells with high expression of NKG2D ligands (NKG2DL) due to the activation of the DNA damage repair pathways. Interestingly, our study revealed that during NK cell activation there is an increase of MULT1, and NKG2DL, that correlates with an induction of DNA damage. Treatment with the ATM DNA damage repair pathway inhibitor KU55933 (KU) during activation reduced NCE by improving expression of activation markers and genes involved in cell survival, by sustaining NKG2D expression and by preserving cell functionality. Importantly, NK cells expanded ex vivo in the presence of KU displayed increased anti-tumor efficacy in both NKG2D-dependent and -independent mouse models. Collectively, these data demonstrate that NCE is caused by DNA damage and regulated, at least in part, by NKG2D. Further, the prevention of NCE is a promising strategy to improve NK cell-based immunotherapy.