Epicardial ultrasonic ablation of atrial fibrillation during concomitant cardiac surgery is a valid option in patients with ischemic heart disease.

BACKGROUND: Surgical therapy of atrial fibrillation concomitant to coronary bypass grafting using epicardial Ultrasound technology was assessed after a minimum 6-month follow-up. METHODS AND RESULTS: A cohort of 98 consecutive patients with a mean age of 72+/-7.58 years and a primary diagnosis of ischemic heart disease had surgery for structural disease. Coronary artery bypass grafting was isolated (n=51) or associated (n=47) with various combinations of aortic, mitral, tricuspid, and left ventricular restoration surgery. Atrial fibrillation duration ranged from 6 to 360 months (mean 71 months) and was permanent in 47 patients, paroxysmal in 34, and persistent in 17. Left atrial mean diameter was 48+/-6.71 mm. A circumferential ablation was performed off-pump, before the concomitant procedure, and was always associated with an epicardial mitral line lesion using the same technology. At 3-, 6-, and 12-month visits, patients were routinely evaluated by physical examination, ECG, chest X-ray, and 24-hour Holter. There were 1 early death (1%) and 4 extracardiac late deaths. A pacemaker was implanted in 4 patients. Mean follow-up time was 325 days, 2 patients being lost to follow-up. Freedom from atrial fibrillation and flutter at the 6-month visit was 84% for the entire population, 76% in patients with permanent, and 91% in patients with paroxysmal atrial fibrillation. At the 1-year visit, 85% were free from atrial fibrillation or flutter. CONCLUSIONS: Epicardial beating heart ablation using therapeutic ultrasound is safe, reliable, and can easily treat atrial fibrillation in a difficult surgical population of patients with primary ischemic heart disease.

Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients.

BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) has been linked to local immunosuppression independent of major ICI targets (e.g., PD-1). Clinical experience with response prediction based on PD-L1 expression suggests that other factors influence sensitivity to ICIs in non-small cell lung cancer (NSCLC) patients. METHODS: Tumor specimens from 120 NSCLC patients from 10 institutions were evaluated for PD-L1 expression by immunohistochemistry, and global proliferative profile by targeted RNA-seq. RESULTS: Cell proliferation, derived from the mean expression of 10 proliferation-associated genes (namely BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, and TOP2A), was identified as a marker of response to ICIs in NSCLC. Poorly, moderately, and highly proliferative tumors were somewhat equally represented in NSCLC, with tumors with the highest PD-L1 expression being more frequently moderately proliferative as compared to lesser levels of PD-L1 expression. Proliferation status had an impact on survival in patients with both PD-L1 positive and negative tumors. There was a significant survival advantage for moderately proliferative tumors compared to their combined highly/poorly counterparts (p = 0.021). Moderately proliferative PD-L1 positive tumors had a median survival of 14.6 months that was almost twice that of PD-L1 negative highly/poorly proliferative at 7.6 months (p = 0.028). Median survival in moderately proliferative PD-L1 negative tumors at 12.6 months was comparable to that of highly/poorly proliferative PD-L1 positive tumors at 11.5 months, but in both instances less than that of moderately proliferative PD-L1 positive tumors. Similar to survival, proliferation status has impact on disease control (DC) in patients with both PD-L1 positive and negative tumors. Patients with moderately versus those with poorly or highly proliferative tumors have a superior DC rate when combined with any classification schema used to score PD-L1 as a positive result (i.e., TPS ≥ 50% or ≥ 1%), and best displayed by a DC rate for moderately proliferative tumors of no less than 40% for any classification of PD-L1 as a negative result. While there is an over representation of moderately proliferative tumors as PD-L1 expression increases this does not account for the improved survival or higher disease control rates seen in PD-L1 negative tumors. CONCLUSIONS: Cell proliferation is potentially a new biomarker of response to ICIs in NSCLC and is applicable to PD-L1 negative tumors.

Is Surgical Intervention the Optimal Therapy for the Treatment of Aortic Valve Stenosis for Patients With Intermediate Society of Thoracic Surgeons Risk Score?

BACKGROUND: Patients at intermediate risk (IR) according to The Society of Thoracic Surgeons risk score are today frequently oriented toward the transfemoral aortic valve replacement (TAVR) option. Our goal was to evaluate the best treatment strategies for IR patients with severe aortic stenosis. METHODS: Of a consecutive series of 1,144 surgical aortic valve replacements (AVRs) performed in our institution between 2008 and 2014, we reviewed the early and late outcomes of two different groups: a low-risk (LR) group of 470 patients, and an IR group of 620. We eliminated from the analysis 54 high-risk patients who were currently candidates for TAVR. All patients underwent surgical AVR with or without concomitant coronary artery bypass grafting. Social Security database interrogation provided long-term information. RESULTS: The early mortality rate (30 days) between LR and IR patients was similar (1.70% vs 2.74%, p = 0.25) and both lower than predicted mortality rates. However, cumulative 5-year survival was significantly higher in LR patients (86.3%) than in IR patients (75.4%; p = 0.0007 by log-rank test), although excellent in IR group. Comparing IR survivors and nonsurvivors, ages at operation were 69.5 ± 12.7 years for survivors vs 75.4 ± 9.6 years for those experiencing late deaths (p = 0.002). Risk factors for late deaths after multivariate analysis were age, hemodialysis, and chronic lung disease. CONCLUSIONS: Most IR patients today should undergo surgical AVR, but because of survival rates combined with still unavailable late structural deterioration rates in TAVR valves, patients in the IR group with high Society of Thoracic Surgeons scores and known risk factors may be better served with TAVR as data regarding late percutaneous valve function accrue.

Ultrasonic cardiac ablation for atrial fibrillation during concomitant cardiac surgery: long-term clinical outcomes.

BACKGROUND: Therapeutic ultrasound as an alternative to the maze procedure was evaluated in this large US experience. Safety and efficacy were assessed at 6-, 12-, and 18-month visits with systematic 24-hour Holter monitoring. METHODS: From February 2005 to February 2007, 220 patients were prospectively enrolled in a single center study, and among them 129 patients with concomitant cardiac surgery and at least 6-month follow-up were reviewed. Primary procedures were mitral surgery in 50% of the cases, coronary bypass in 32%, and aortic surgery in 16%. Atrial fibrillation was permanent in 66 (51.1%), paroxysmal in 43 (33.3%), and persistent in 20 (15.5%) patients. An epicardial and circumferential left atrial encircling line was created on the beating heart. Routinely a mitral isthmus line was also created from the left atrium epicardium using an ultrasonic handheld device. RESULTS: No morbidity or mortality was device-related. There were four (2.33%) early deaths and six late extra-cardiac deaths. Follow-up ranged from 6 to 670 days with a mean follow-up of 358.5 days, median 340 days with two patients lost to follow-up. Freedom from atrial fibrillation or left-sided flutter was 83.2%, 84.4%, and 86.2% at 6, 12, and 18 months, respectively. A pacemaker was implanted in seven patients (5.4%). Male gender and left atrial dimension were significant risk factors for failure. CONCLUSIONS: The study confirms the excellent safety record of the technology, and the efficacy at the level reported in a previous European multicenter study. Efficacy is also maintained at longer (12 and 18 months) follow-up.

Transplante lobar experimental em suinos: enxerto proporcional na disparidade entre receptor e doador / experimental lobar transplantation in swine: graft in the discrepancy between donor and recipient

OBJETIVO - Perante a crítica falta de orgäos disponíveis para transplante pulmonar pediátrico. Na grande disparidade de tamanho do doador adulto e a criança pequena receptora, o lobo médio ou segmento pulmonar representa um enxerto de restrito leito vascular. Este estudo experimental testa a hipótese de que esse tipo de enxerto pode desenvolver hipertensäo pulmonar no animal receptor, ao final do período de crescimento. MÉTODOS - Foi utilizado um modelode sobrevivência de transplante pulmonar à esquerda em leitöes. Constitutiram-se três grupos de comparaçäo: I (n = 4) - transplante de lobo superior de doador adulto, enxerto proporcional ao receptor, mas irrigado por apenas dois ramos anterior; II (n = 6) - transplante de pulmäo imaturo de leitäo doador proporcionado. Os animais transplantados tiveram a funçäo do enxerto pulmonar estudada ao final de 3 meses, quando completaram o período de crescimento. RESULTADOS - A pressäo da artéria pulmonar do enxerto do grupo I (51,8 ñ 2,1mmHg) foi mais elevada do que no grupo II (40,4 ñ 2,5mmHg) e do que no grupo III (34,8 ñ 1,5mmHg), atingindo significância estatística (p = 0,0003). CONCLUSÖES - O enxerto lobar proporcional ao receptor, mas de leito vascular restrito, teve desempenho hemodinâmico comprometido no animal em crescimento. Esses dados sugerem que a proporcionalidade do enxerto näo deve prioritária e, antes, ser secundária a um adequado leito vascular do enxerto

Pulmonary function after transplantation of grafts harvested from normothermic ischemia in a porcine survival model

We have previously shown the feasibility of lung procurement from nom-heart-beating donors in a porcine survival movel. Pulmonary function is now evaluated transplanted lungs subjected to 1 hour of normothermic ischemia in a similiar experimental model. Eight adult swine underwent left lung allotransplantation. Controls received lungs procured from heart-beating donors, and study group pigs received lungs harvest 1 hour after death from asphyxiation. Pulmonary function studies were undertaken 3 days after lung transplantation. Pulmonary vascular hemodynamics, pulmonary venous partial pressure of oxygen, dynamic airway compliance and resistence were equivalent in both grups. We conclude that transplanted lungs from non-heart-beating donors with 1 hour of warm ischemia are functionally viable