Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Effectiveness of dual external direct current cardioversion for initial cardioversion in atrial fibrillation.

INTRODUCTION: Dual external direct current cardioversion (dual-DCCV) is a rhythm control strategy for persistent atrial fibrillation (AF), involving simultaneous delivery of two shocks from two defibrillators. The long-term effectiveness of this approach has not been studied in the biphasic cardioversion era. METHODS: Seventy-seven consecutive patients at a single center were identified to receive dual-DCCV at the time of their initial cardioversion for AF, when maximum output standard external direct current cardioversion failed in two vectors. Logistic regression was used to analyze risk factors for dual-DCCV in a historical control group of 77 patients undergoing standard cardioversion and Cox proportional hazard models were used to compare time to AF recurrence. RESULTS: The dual-DCCV group had a significantly larger body mass index (BMI), but similar AF duration and left atrial size as controls. Multivariable logistic regression revealed that BMI and absence of prior paroxysmal AF were risk factors for dual-DCCV (P < 0.05). There was no difference observed between dual-DCCV and control groups (adjusted hazard ratio = 0.57; P = .12) after adjusting for number of shocks and age. Transient hypoxia was the only acute complication in either group (P > .999). CONCLUSION: Dual-DCCV appears to be a safe and effective cardioversion strategy for patients with AF. The need for dual-DCCV in the treatment of AF appears to be influenced more by body habitus than atrial substrate.

Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma.

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semiquantitative characterization of metabolic activity (glycolytic phenotype) by calculation of glucose uptake. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) have the potential to improve the value of this approach and enhance the prognostic value of disease burden measures. This study aims to determine whether TLG and MTV are associated with progression-free survival (PFS) and overall survival (OS), and whether they improve risk assessments such as International Staging System (ISS) stage and GEP70 risk.Experimental Design: 192 patients underwent whole body PET/CT in the Total Therapy 3A (TT3A) trial and were evaluated using three-dimensional region-of-interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal.Results: In multivariate analysis, baseline TLG > 620 g and MTV > 210 cm3 remained a significant factor of poor PFS and OS after adjusting for baseline myeloma variables. Combined with the GEP70 risk score, TLG > 205 g identifies a high-risk-behaving subgroup with poor expected survival. In addition, TLG > 205 g accurately divides ISS stage II patients into two subgroups with similar outcomes to ISS stage I and ISS stage III, respectively.Conclusions: TLG and MTV have significant survival implications at baseline and offer a more precise quantitation of the glycolytic phenotype of active disease. These measures can be assessed more readily than before using FDA-approved software and should be standardized and incorporated into clinical trials moving forward. Clin Cancer Res; 23(8); 1981-7. ©2016 AACR.

Effect of garlic-derived organosulfur compounds on mitochondrial function and integrity in isolated mouse liver mitochondria.

The objectives of this work were to evaluate the direct effects of diallysulfide (DAS) and diallyldisulfide (DADS), two major organosulfur compounds of garlic oil, on mitochondrial function and integrity, by using isolated mouse liver mitochondria in a cell-free system. DADS produced concentration-dependent mitochondrial swelling over the range 125-1000µM, while DAS was ineffective. Swelling experiments performed with de-energized or energized mitochondria showed similar maximal swelling amplitudes. Cyclosporin A (1µM), or ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 1mM) were ineffective in inhibiting DADS-induced mitochondrial swelling. DADS produced a minor (12%) decrease in mitochondrial membrane protein thiols, but did not induce clustering of mitochondrial membrane proteins. Incubation of mitochondria with DADS (but not DAS) produced an increase in the oxidation rate of 2',7' dichlorofluorescein diacetate (DCFH-DA), together with depletion of reduced glutathione (GSH) and increased lipid peroxidation. DADS (but not DAS) produced a concentration-dependent dissipation of the mitochondrial membrane potential, but did not induce cytochrome c release. DADS-dependent effects, including mitochondrial swelling, DCFH-DA oxidation, lipid peroxidation and loss of mitochondrial membrane potential, were inhibited by antioxidants and iron chelators. These results suggest that DADS causes direct impairment of mitochondrial function as the result of oxidation of the membrane lipid phase initiated by the GSH- and iron-dependent generation of oxidants.

Laparoscopic cryoablation of renal masses: single-center long-term experience.

OBJECTIVE: To evaluate perioperative and long-term functional and oncological outcomes of laparoscopic cryoablation (LCA) performed at Washington University. METHODS: A retrospective chart review was performed evaluating 62 consecutive patients who underwent LCA at our institution between 2000 and 2005. RESULTS: Mean age-adjusted Charlson Comorbidity Index (CCI) was 6.1 (SD, 2.1; 95% confidence interval [CI], 5.6-6.6). Mean tumor size was 2.52 cm (SD, 0.99; CI, 2.3-2.8). Mean operative time was 162.0 minutes (SD, 66.6; CI, 142.0-182.1). Mean estimated blood loss was 84.9 mL (SD, 102; CI, 58.6-111.2). Mean hospital stay was 2.6 days (SD, 1.90; CI, 2.1-3.1). The perioperative complication rate was 9.7% (Clavien 1-2). Among patients with biopsy proven, localized renal cell carcinoma, the 6-year Kaplan-Meier estimated disease-free survival (DFS) was 80%; cancer-specific survival (CSS) was 100%; and overall survival (OS) was 76.2%. Mean follow-up in this subset was 76.0 months (SD, 39.3; CI, 62.7-89.4; n = 35), whereas mean time to cancer recurrence was 27.6 months (SD, 11.2; CI, 15.9-39.3; n = 6). Tumor size ≥2.6 cm was the only predictor of cancer recurrence in a multivariate Cox proportional hazards model (hazard ratio [HR] = 28.9; P = .046; n = 35). Mean preoperative estimated glomerular filtration rate (eGFR) was 68.3 (SD, 22.3; CI, 62.1-74.5), compared to 64.5 mL/min/1.73 m(2) (SD, 28.9; CI, 56.5-72.6) at last follow-up (P = .12; n = 52). Excluding patients requiring secondary ablative or extirpative treatments for recurrent renal cell carcinoma, preoperative eGFR <60 mL/min/1.73 m(2) (odds ratio [OR] = 88.3; P = .036) and age-adjusted CCI ≥6 (OR = 32.4; P = .046) were the only factors predicting renal disease progression on multiple logistic regression (n = 47). CONCLUSION: We report what is by far the longest follow-up to date of postlaparoscopic cryoablation changes in eGFR and note excellent long-term renal functional outcomes. For those willing to accept the potential need for retreatment for recurrent disease, LCA offers excellent long-term CSS.

Laparoscopic retroperitoneal lymph node dissection for low-stage cancer: a Washington University update.

BACKGROUND AND PURPOSE: At present, open retroperitoneal lymph node dissection (RPLND) remains the preferred approach at many high-volume centers for the surgical treatment of patients with low-stage testis cancer. Despite the potential advantages of a minimally invasive approach, including improved cosmesis and shorter recovery times, there remain concerns over the quality of dissection and oncologic control offered through a minimally invasive approach. Our objective was to critically evaluate the safety and intermediate-term oncologic efficacy of laparoscopic RPLND (L-RPLND). PATIENTS AND METHODS: A retrospective chart review was performed, evaluating all patients who underwent L-RPLND between 2003 and 2009. Patient records were updated by telephone interview. RESULTS: A total of 59 patients underwent L-RPLND during the study period, of which 13 had previously undergone chemotherapy. Mean age at treatment was 32 years. Mean operative time and estimated blood loss were 291 minutes (176-620 min) and 184 mL (range 0-1800 mL), respectively. Mean lymph node count was 21.6 (range 5-48). Mean hospital stay was 2 days (range 1-4 d). There were three open conversions because of intraoperative complications. One patient needed a transfusion. Five patients had six (8.5%) postoperative complications: three lymphoceles, two chylous ascites, and one deep venous thrombosis/pulmonary embolus. Of 18 patients with node-positive pathology, 13 received adjuvant chemotherapy and 5 underwent surveillance. Retroperitoneal recurrence did not develop in any patient undergoing surveillance during a mean follow-up of 21.3 months. One postchemotherapy RPLND (1.7%) patient experienced a retroperitoneal recurrence. CONCLUSIONS: L-RPLND is a diagnostic and therapeutic treatment option for patients with low-stage testis cancer, offering excellent oncologic control and acceptable perioperative morbidity. Intermediate-term results suggest that L-RPLND is a viable alternative to the open surgical procedure. Carefully selected patients may be candidates for L-RPLND in the postchemotherapy setting.