Objectives: This study sought to use a new catheter technique to split the anterior mitral valve leaflet (AML) and prevent iatrogenic left ventricular outflow tract (LVOT) obstruction immediately before transcatheter mitral valve replacement (TMVR).
Background: LVOT obstruction is a life-threatening complication of TMVR, caused by septal displacement of the AML.
Methods: The procedure was used in patients with severe mitral valve disease and prohibitive surgical risk. Patients either had prior surgical mitral valve ring (n = 3) or band annuloplasty (n = 1) or mitral annular calcification with stenosis (n = 1). Iatrogenic LVOT obstruction or transcatheter heart valve dysfunction was predicted in all based on echocardiography and computed tomography. Transfemoral coronary guiding catheters directed an electrified guidewire across the center and base of the AML toward a snare in the left atrium. The externalized guidewire loop was then electrified to lacerate the AML along the centerline from base to tip, sparing chordae, immediately before transseptal TMVR.
Results: Five patients with prohibitive risk of LVOT obstruction or transcatheter heart valve dysfunction from TMVR successfully underwent LAMPOON, with longitudinal splitting of the A2 scallop of the AML, before valve implantation. Multiplane computed tomography modeling predicted hemodynamic collapse from TMVR assuming an intact AML. However, critical LVOT gradients were not seen following LAMPOON and TMVR. Doppler blood flow was seen across transcatheter heart valve struts that encroached the LVOT, because the AML was split. Transcatheter heart valve function was unimpeded.
Conclusions: This novel catheter technique, which resembles surgical chord-sparing AML resection, may enable TMVR in patients with prohibitive risk of LVOT obstruction or transcatheter heart valve dysfunction.
SETTING:
Multidrug-resistant tuberculosis (MDR-TB) treatment facility, Orel Oblast, Russian Federation. OBJECTIVES: To determine factors associated with poor outcome and to document status of patients after recording of TB outcomes.
DESIGN:
Retrospective review of prospective single cohort.
RESULTS:
Among 192 patients, factors significantly associated with poor outcome in multivariate analysis include three or more treatment interruptions during the intensive phase of therapy and alcohol or drug addiction (adjusted OR [aOR] 2.1, 95%CI 1.0-4.3 and aOR 1.9, 95%CI 1.0-3.7). Previous treatment was associated with poor outcome, but only among smear-positive patients (aOR 3.1, 95%CI 1.3-7.3). Ten patients (5%) developed extensively drug-resistant TB (XDR-TB) during treatment; of 115 patients with at least 6 months of follow-up data after outcomes were recorded, 13 (11%) developed XDR-TB.
CONCLUSION:
Interventions focused on supporting patient adherence during the intensive phase of treatment; the management of drug and alcohol addiction should be developed and studied. A substantial proportion of patients developed XDR-TB during and after treatment. Longer term follow-up data of patients treated for MDR-TB are needed to better inform programmatic policy.
Background:
Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly.
Methods:
Using 1997–2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls.
Results:
Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1,4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]).
Conclusions:
Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.
Objective: To investigate associations of a oxidative balance score (OBS) with blood levels of total cholesterol, low-density lipoprotein-(LDL)-cholesterol, high-density lipoprotein-(HDL) cholesterol and triglycerides, and biomarkers of inflammation (serum C-reactive protein [CRP], albumin and venous total white blood cell [WBC] counts) among 19,825 participants in a nationwide study.
Methods: Using cross-sectional data 14 dietary and lifestyle components were incorporated into the OBS and the resulting score (range 3–26) was then divided into five equal intervals. Multivariable-adjusted odds ratios (ORs) for abnormal biomarker levels and 95% confidence intervals (CIs) were calculated using logistic regression models.
Results: The ORs (95% CIs) comparing those in the highest relative to those in the lowest OBS equal interval categories were 0.50 (0.38–0.66) for CRP, 0.50 (0.36–0.71) for the total WBC count, and 0.75 (0.58–0.98) for LDL-cholesterol; all three p-values for trend were <0.001. The OBS-HDL-cholesterol association was statistically significantly inverse among females, but not among males. The OBS was not associated with serum albumin or triglycerides.
Conclusion: Our findings suggest that an OBS may be associated with some, but not all, circulating lipids/lipoproteins and biomarkers of inflammation.
by
Weihong Tang;
Lu Yao;
Nicholas S. Roetker;
Alvaro Alonso;
Pamela L. Lutsey;
Carol C. Steenson;
Frank A. Lederle;
David W. Hunter;
Lindsay G.S. Bengtson;
Weihua Guan;
Emil Missov;
Aaron R. Folsom
Objective - Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. Approach and Results - In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. Conclusions - At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.
Among the many organ systems affected by harmful alcohol use, the lungs are particularly susceptible to infections and injury. The mechanisms responsible for rendering people with alcohol use disorder (AUD) vulnerable to lung damage include alterations in host defenses of the upper and lower airways, disruption of alveolar epithelial barrier integrity, and alveolar macrophage immune dysfunction. Collectively, these derangements encompass what has been termed the "alcoholic lung" phenotype. Alcohol-related reductions in antioxidant levels also may contribute to lung disease in people with underlying AUD. In addition, researchers have identified several regulatory molecules that may play crucial roles in the alcohol-induced disease processes. Although there currently are no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation.
Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness.We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/ Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore effective at improving both intestinal integrity and mortality following sepsis in mice with chronic alcohol ingestion. However, the efficacy of EGF in sepsis is blunted in the setting of chronic alcohol ingestion, as intestinal integrity and mortality in alcohol-fed mice given EGF improves animals to levels seen in water-fed mice given vehicle but does not approach levels seen in water-fed mice given EGF.
The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 26, 2010 in San Antonio, TX, as a satellite of the Research Society on Alcoholism meeting. The FASDSG membership includes clinical, basic, and social scientists who meet to discuss recent advances and issues in Fetal Alcohol Spectrum Disorder (FASD) research. The central theme of the meeting was " Glia and Neurons: Teamwork in Pathology and Therapy." Alcohol disruption of neuron development and alcohol-induced neurodegeneration is central to the pathology and clinical expression of FASD. The active role of glia as perpetrator, victim, or bystander in neurotoxicology and neurodegenerative processes has emerged at the forefront of adult central nervous system (CNS) disorders and therapy. Glia- and neuron-glial interactions hold the potential to elucidate causes and offer treatment of FASD as well. Growing evidence indicates that neurons and glia are direct targets of alcohol, but may also be vulnerable to molecules produced in peripheral systems as a result of alcohol exposure. Diagnostics and therapies can take advantage of these processes and biomarkers, and these may be applicable to CNS pathology in FASD. Two keynote speakers, Howard E. Gendelman, M.D., and Ernest M. Graham, M.D, addressed the role of glia and neuroinflammation in brain development and neurodegeneration. The invited speakers and FASDSG members discussed new paradigms in CNS development and discuss new strategies for understanding and treating neurodegenerative disease. Members of the FASDSG provided updates on new findings through presentation of breaking research in the FASt data sessions. Representatives of national agencies provided updates on programs, activities, and funding priorities. The Henry Rosett Award was presented to R. Louise Floyd, R.N., D.S.N., for her career contributions to the field of fetal alcohol research. The Student and Postdoctoral Fellow Research Merit Award was presented to Shonagh O'Leary-Moore, Ph.D., for her contributions to the field as a young investigator.
Patients with hypertrophic cardiomyopathy (HCM) may have delayed septal activation and left ventricular (LV) mechanical dyssynchrony, and may improve after alcohol septal ablation (ASA). This study used phase analysis of gated SPECT myocardial perfusion imaging (MPI) to evaluate septal activation and LV dyssynchrony in HCM patients pre- and post-ASA. Phase analysis was applied to 28 controls, and 32 HCM patients having rest MPI pre- and post-ASA to assess septal-lateral mechanical activation delay (SLD) and consequent LV dyssynchrony. In addition, phase analysis was applied to another group of 30 patients having serial MPI to measure variability of the LV dyssynchrony parameters on serial studies. ASA significantly reduced SLD and improved LV synchrony in the HCM patients with SLD<0° due to earlier activation of the lateral wall relative to the septum. Based on the measured variability, 12 HCM patients had significant (Z<-1.65, P<0.05) and 4 had moderate (Z<-1.00, P<0.15) improvement in LV synchrony post-ASA. SLD<0° predicted improvement in LV synchrony after ASA with a sensitivity of 81% and a specificity of 88%. SLD and LV dyssynchrony were frequent in HCM patients. HCM patients, whose septal activation became later than lateral activation, had significant reduction in septal activation delay and improvement in LV synchrony after ASA.