Does ablation of atrial fibrillation at the time of septal myectomy improve survival of patients with obstructive hypertrophic cardiomyopathy?

ObjectiveTo evaluate the outcomes after septal myectomy in patients with obstructive hypertrophic cardiomyopathy according to atrial fibrillation and surgical ablation of atrial fibrillation.MethodsWe reviewed patients with obstructive hypertrophic cardiomyopathy who underwent septal myectomy at the Mayo Clinic from 2001 to 2016. History of atrial fibrillation was obtained from patient histories and electrocardiograms. All-cause mortality was the primary end point.ResultsA total of 2023 patients underwent septal myectomy, of whom 394 (19.5%) had at least 1 episode of atrial fibrillation preoperatively. Among patients with atrial fibrillation, 76 (19.3%) had only 1 known episode, 278 (70.6%) had recurrent paroxysmal atrial fibrillation, and 40 (10.2%) had persistent atrial fibrillation. Surgical ablation was performed in 190 patients at the time of septal myectomy, including 148 with pulmonary vein isolation and 42 with the classic maze procedure. Among all patients, operative mortality was 0.4%, and there were no early deaths in patients undergoing surgical ablation. Over a median follow-up of 5.6 years, patients with preoperative atrial fibrillation had increased mortality (hazard ratio, 1.36; 95% confidence interval, 0.97-1.91; P = .070) after multivariable adjustment for comorbidities. When considering the impact of atrial fibrillation with or without surgical treatment, the adjusted hazard ratio for mortality in patients undergoing ablation compared with no ablation was 0.93 (95% confidence interval, 0.52-1.69; P = .824).ConclusionsAtrial fibrillation is present preoperatively in one-fifth of patients with obstructive hypertrophic cardiomyopathy undergoing myectomy and showed a trend toward higher all-cause mortality. Survival of patients undergoing septal myectomy with preoperative atrial fibrillation was similar between those who did and did not receive concomitant surgical ablation.     

Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy: A propensity score–matched cohort

Objectives

In patients with hypertrophic cardiomyopathy, obstruction of the left ventricular outflow tract can be relieved by surgical septal myectomy or alcohol septal ablation, but uncertainty remains regarding long-term results and comparative effectiveness of alcohol septal ablation. This study aims to compare short- and long-term outcomes of the 2 procedures.

Screw oversizing for anterior cruciate ligament graft fixation in primary and enlarged tibial tunnels: A biomechanical study in a porcine model

Background

Ideal diameter for tibial interference screw fixation of the anterior cruciate ligament (ACL) graft remains controversial. Tibial graft fixation with screws matching the tunnel diameter vs. one-millimetre oversized screws were compared.

Changes in brain functional connectivity patterns are driven by an individual lesion in MS: a resting-state fMRI study

Diffuse inflammation in multiple sclerosis (MS) extends beyond focal lesion sites, affecting interconnected regions; however, little is known about the impact of an individual lesion affecting major white matter (WM) pathways on brain functional connectivity (FC). Here, we longitudinally assessed the effects of acute and chronic lesions on FC in relapsing-remitting MS (RRMS) patients using resting-state fMRI. 45 MRI data sets from 9 RRMS patients were recorded using 3T MR scanner over 5 time points at 8 week intervals. Patients were divided into two groups based on the presence (n?=?5; MS+) and absence (n?=?4; MS-) of a lesion at a predilection site for MS. While FC levels were found not to fluctuate significantly in the overall patient group, the MS+ patient group showed increased FC in the contralateral cuneus and precuneus and in the ipsilateral precuneus (p?<?0.01, corrected). This can be interpreted as the recruitment of intact cortical regions to compensate for tissue damage. During the study, one patient developed an acute WM lesion in the left posterior periventricular space. A marked increase in FC in the right pre-, post-central gyrus, right superior frontal gyrus, the left cuneus, the vermis and the posterior and anterior lobes of the cerebellum was noted following the clinical relapse, which gradually decreased in subsequent follow-ups, suggesting short-term functional reorganization during the acute phase. This strongly suggests that the lesion-related network changes observed in patients with chronic lesions occur as a result of reorganization processes following the initial appearance of an acute lesion.     

Nonsyndromic types of ichthyoses – an update

Ichthyoses are genetically determined Mendelian disorders of cornification (MEDOC) that are characterized by universal scaling. Today we distinguish between non‐syndromic and syndromic forms. Ichthyosis vulgaris is the most frequent type (prevalence 1:100) and is caused by autosomal semi‐dominant filaggrin mutations. It is associated with a higher risk for the development of atopic diseases, such as atopic eczema and allergic rhinitis. Recessive X‐linked ichthyosis (RXLI) occurs almost exclusively in boys; in Germany it has a prevalence of around 1:4,000. It is caused by steroid sulfatase deficiency and is often associated with further clinical problems, such as cryptorchidism (～20%) or social communication deficits, such as attention deficit hyperactivity syndrome (40%) or autism (25%). Autosomal recessive congenital ichthyosis (ARCI) is genetically very heterogeneous and 8 different genes have been identified so far. The most frequent cause of ARCI is a transglutaminase 1 deficiency (prevalence 1:200, 000). Mutations in keratin genes are the cause of the keratinopathic ichthyoses, such as epidermolytic ichthyosis. They manifest at birth and often feature episodes of blistering. Most of these types are inherited as autosomal dominant traits, but autosomal recessive forms have also been described on occasion.     

Collateralization of an occluded left internal mammary artery coronary bypass graft

The left internal mammary artery (LIMA) is frequently utilized in coronary artery bypass grafting (CABG); adequate visualization of the LIMA bypass graft during diagnostic angiography is critical for determination of myocardial blood supply. We present a novel case of angiography via a left transradial approach demonstrating an occluded LIMA coronary bypass graft with antegrade flow maintained via a collateral branch from the ipsilateral thyrocervical trunk. Given the prevalence of LIMA use in CABG, it is critical to be aware of unusual configurations, including collateralization of a proximally occluded LIMA graft as described in this report.     

The membrane protein FeoB contains an intramolecular G protein essential for Fe(II) uptake in bacteria

G proteins are critical for the regulation of membrane protein function and signal transduction. Nevertheless, coupling between G proteins and membrane proteins with multiple membrane-spanning domains has so far been observed only in higher organisms. Here we show that the polytopic membrane protein FeoB, which is essential for Fe(II) uptake in bacteria, contains a guanine-nucleotide-specific nucleotide binding site. We identify the G4-motif, NXXD, responsible for guanine nucleotide specificity, and show that GTP hydrolysis occurs very slowly. In contrast to typical G proteins, the association and dissociation of GDP were found to be faster than for GTP, suggesting that in the absence of additional factors, FeoB's G protein domain may exist mostly in the GTP-bound form. Furthermore, the binding of GTP is required for efficient Fe(II) uptake through the FeoB-dependent system. Notably, even in bacteria, this covalent linkage between a G protein and a polytopic membrane protein appears, to our knowledge, to be unique. These findings raise the intriguing question whether FeoB represents a primordial archetype of G protein-regulated membrane proteins.     

C-Peptide induces vascular smooth muscle cell proliferation: involvement of SRC-kinase, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase 1/2

Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examined the effect of C-peptide on vascular smooth muscle cells (VSMCs) proliferation and evaluated intracellular signaling pathways involved. In early arteriosclerotic lesions of diabetic subjects, C-peptide colocalized with VSMCs in the media. In vitro, stimulation of human or rat VSMCs with C-peptide induced cell proliferation in a concentration-dependent manner with a maximal 2.6+/-0.8-fold induction at 10 nmol/L human C-peptide (P<0.05 compared with unstimulated cells; n=9) and a 1.8+/-0.2-fold induction at 0.5 nmol/L rat C-peptide (P<0.05 compared with unstimulated cells; n=7), respectively, as shown by [H3]-thymidin incorporation. The proliferative effect of C-peptide on VSMCs was inhibited by Src short interference RNA transfection, PP2, an inhibitor of Src-kinase, LY294002, an inhibitor of PI-3 kinase, and the ERK1/2 inhibitor PD98059. Moreover, C-peptide induced phosphorylation of Src, as well as activation of PI-3 kinase and ERK1/2, suggesting that these signaling molecules are involved in C-peptide-induced VSMC proliferation. Finally, C-peptide induced cyclin D1 expression as well as phosphorylation of Rb in VSMCs. Our results demonstrate that C-peptide induces VSMC proliferation through activation of Src- and PI-3 kinase as well as ERK1/2. These data suggest a novel mechanism how C-peptide may contribute to plaque development and restenosis formation in patients with insulin resistance and early type 2 diabetes mellitus.