Genetic correlates in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with Hyper-CVAD/Hyper-CMAD plus dasatinib or Hyper-CVAD plus ponatinib

Department of Leukemia Research Department of Leukemia Department of Genomic Medicinehttps://openworks.mdanderson.org/edwk21/1004/thumbnail.jp

Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes

View full abstracthttps://openworks.mdanderson.org/leading-edge/1002/thumbnail.jp

Anatomical Research of the Three-dimensional Route of the Thoracodorsal Nerve, Artery, and Veins in Latissimus Dorsi Muscle

Background: The latissimus dorsi (LD) muscle flap has been widely used in facial reanimation surgery. However, there are no standards to what degree the muscle flap may be safely thinned because the three-dimensional positional relationship of thoracodorsal artery, vein, and nerve inside the LD muscle is poorly understood. Methods: From 18 formalin-fixed cadavers, we made 36 transparent specimens of LD muscles using a newly developed decoloration technique. In 26 specimens, nerve staining (Sihler’s staining method) and silicone rubber (Microfil) injection to the thoracodorsal artery were performed, and the relationship of the artery and the vein was examined in 10 specimens. Results: The thoracodorsal artery and vein always ran parallel in a deeper layer compared to the nerve. The thoracodorsal nerve constantly existed in a deeper layer than half (50%) of the muscle in the range of use of the muscle flap in facial reanimation surgery. Conclusions: The thoracodorsal nerves ran in a shallower layer, and the depth to the nerve in the muscle flap in actual facial reanimation surgery is safe enough to avoid damage to the nerves. The LD muscle may be thinned to half its original thickness safely

Clinical implications of serum adiponectin on progression of atrial fibrillation

Background: The association between circulating adiponectin levels and atrial fibrillation (AF) is uncertain. We, therefore, investigated whether an increased serum adiponectin level is implicated in the long-term recurrence of AF after ablation therapy. Methods: Our study included 100 consecutive patients (88 men; median age, 57.9±10.9 years) who underwent catheter ablation for AF at our hospital between 2011 and 2013. The adiponectin and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured before ablation and compared between those in whom AF recurred and those in whom AF did not recur. Results: Elevation in adiponectin levels was significantly associated with female sex, non-paroxysmal AF, heart failure, higher NT-proBNP and matrix metallo-proteinase-2 levels, and lower body mass index. After a stepwise adjustment for any potential confounding variables, the adiponectin levels remained significantly associated with female sex (beta=0.2601, P=0.0041), non-paroxysmal AF (beta=0.2708, P=0.0080), and higher NT-proBNP levels (beta=0.2536, P= 0.0138). During the median follow-up period of 26.2 months, AF recurred in 48 of the 100 patients. Stepwise multivariate adjustment showed that an increased log-transformed NT-proBNP (Hazard ratio [HR], 2.18; 95% confidence interval [CI] 1.25â4.00; P=0.0055), longer duration of AF (HR, 1.87; 95%CI 1.01â3.76; P=0.0465), and decreased left ventricular ejection fraction (HR, 0.96; 95%CI 0.93â0.99; P=0.0391) were independent predictors of recurrent AF after catheter ablation, but adiponectin was not. Conclusions: Our data indicated that adiponectin was partially responsible for progression of AF, but the correlation between adiponectin levels and AF recurrence was not significant. Keywords: Atrial fibrillation, Adiponectin, NT-proBNP, Ablatio

Impact of complete revascularization in coronary artery bypass grafting for ischemic cardiomyopathyCentral MessagePerspective

Objective: In patients with ischemic cardiomyopathy, coronary artery bypass grafting ensures better survival than medical therapy. However, the long-term clinical impact of complete revascularization remains unclear. This observational study aimed to evaluate the effects of complete revascularization on long-term survival and left ventricular functional recovery in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting. Methods: We retrospectively reviewed outcomes of 498 patients with ischemic cardiomyopathy who underwent complete (n = 386) or incomplete (n = 112) myocardial revascularization between 1993 and 2015. The baseline characteristics were adjusted using inverse probability of treatment weighting to reduce the impact of treatment bias and potential confounding. The mean follow-up duration was 77.2 ± 42.8 months in survivors. Results: The overall 5-year survival rate (complete revascularization, 72.5% vs incomplete revascularization, 57.9%, P = .03) and freedom from all-cause death and/or readmission due to heart failure (54.5% vs 40.1%, P = .007) were significantly greater in patients with complete revascularization than those with incomplete revascularization. After adjustments using inverse probability of treatment weighting, the complete revascularization group demonstrated a lower risk of all-cause death (hazard ratio, 0.61; 95% confidence interval, 0.43-0.86; P = .005) and composite adverse events (hazard ratio, 0.59; 95% confidence interval, 0.44-0.79; P < .001) and a greater improvement in the left ventricular ejection fraction 1-year postoperatively (absolute change: 11.0 ± 11.9% vs 8.3 ± 11.4%, interaction effect P = .05) than the incomplete revascularization group. Conclusions: In patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, complete revascularization was associated with better long-term outcomes and greater left ventricular functional recovery and should be encouraged whenever possible

Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated NSCLC: RELAY Japanese Subset

Introduction: The phase 3 RELAY global study (NCT02411448) revealed significant improvement in progression-free survival (PFS) with ramucirumab plus erlotinib (RAM + ERL) compared with placebo plus ERL (PL + ERL) in untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59 [95% confidence interval (CI): 0.46–0.76, p < 0.0001]). This prespecified analysis evaluates efficacy, safety, and postprogression EGFR T790M rates of RELAY patients enrolled in Japan. Methods: Patients were randomized (1:1) to oral ERL (150 mg/d) plus intravenous RAM (10 mg/kg) or PL every 2 weeks. End points included PFS (primary), safety (secondary), and biomarker analyses (exploratory). Plasma samples collected at baseline and poststudy treatment discontinuation were evaluated for EGFR T790M mutations by next-generation sequencing. Results: The Japanese subset included 211 of 449 (47.0%) RELAY patients (RAM + ERL, n = 106; PL + ERL, n = 105). Median PFS was 19.4 versus 11.2 months for RAM + ERL versus PL + ERL treatment (HR = 0.610 [0.431–0.864]) in the Japanese intent-to-treat population, 16.6 versus 12.5 months (HR = 0.701 [0.424–1.159]) in the EGFR exon 19 deletion subgroup, and 19.4 versus 10.9 months (HR = 0.514 [0.317–0.835]) in the EGFR exon 21 L858R subgroup, respectively. Adverse events of grade 3 or above with RAM + ERL included hypertension (24.8%, all grade 3) and dermatitis acneiform (23.8%). Postprogression treatment-emergent T790M rates were similar between arms (RAM + ERL: 47%, 9 of 19 patients; PL + ERL: 50%, 20 of 40 patients). Conclusions: Clinically meaningful efficacy was observed with RAM + ERL versus PL + ERL in the RELAY Japanese subset, with no new safety concerns. Postprogression T790M rates were similar across treatment arms, indicating the addition of RAM did not affect the ERL-associated EGFR T790M rates at disease progression