Objective To test the hypothesis that predisposition to childhood herpes simplex virus (HSV) type 1 encephalitis (HSE) may be determined in part by human genetic factors. Study design A genetic ...epidemiologic survey of childhood HSE (onset at age 3 months to 15 years) over a 20-year period (1985-2004) was conducted throughout France (comprising 29 university hospital neuropediatric centers). A total of 85 children fulfilled the diagnostic criteria for inclusion. Family and personal histories were obtained by face-to-face interview for 51 patients. Results No familial cases of HSE were identified in our survey; however, a high proportion (20%) of the children interviewed had a relevant family history: parental consanguinity (12% of patients), early-onset herpetic keratitis in a first-degree relative (6%), or both (2%). The narrow window of high susceptibility to HSE before age 3 years (62% of patients) further indicates that predisposition to HSE is tightly age-dependent. Conclusions This survey suggests that childhood HSE, although sporadic, may result from Mendelian predisposition (from autosomal recessive susceptibility in particular), at least in some children. There likely is incomplete penetrance, however, which may reflect, at least in part, the impact of age at the time of HSV-1 infection.
Objective To describe, from the point of view of anesthesia and intensive care specialists, the perioperative management of high-risk patients with aortic stenosis who underwent transcatheter ...(transfemoral and transapical) aortic valve implantation (TAVI). The authors specifically focused on immediate postoperative complications. Design Retrospective review of collected data. Setting Academic hospital. Participants Ninety consecutive patients with severe aortic stenosis who underwent TAVI. Interventions General anesthesia followed by postoperative care. Complications were defined by pre-established criteria. Measurements and Main Results Of 184 patients referred between October 2006 and February 2009, 90 were consecutively treated with TAVI because of a high surgical risk or contraindications to surgery. The transfemoral approach was used as the first option (n = 62), and the transapical approach when contraindications to the former were present (n = 28). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. Patients were 81 ± 8 years old, in New York Heart Association classes II (9%), III (54 %), or IV (37%); left ventricular ejection fraction was below 0.5 in 38% of patients. The predicted surgical mortality was 24% (16-32) and 15% (11-23) with the logistic EuroSCORE and STS-Predicted Risk of Mortality, respectively. The valve was implanted in 92% of the cases. The duration of anesthesia and (intra- and postoperative) mechanical ventilation was 190 (160-230) minutes and 245 (180-420) minutes, respectively. Hospital mortality was 11%. The most frequent cardiac complications were heart failure (20%) and atrioventricular block (16%), with 6% requiring a pacemaker. Vascular complications (major and minor) occurred in 29% of the patients. Conclusions Despite their severe comorbidities, the mortality of the patients in this cohort was below that predicted by cardiac surgery risk scores. Monitoring, hemodynamic instability, and the frequency of complications require management and follow-up of these patients in similar ways as for open cardiac surgery. The frequency of complications in this cohort was comparable to that published by other groups.
Background Patients with infantile nephropathic cystinosis have progressive accumulation of cystine in tissues leading to delayed extrarenal complications. No simple tool is available to evaluate the ...level of body cystine accumulation. Objective We sought to determine the value of in vivo reflectance confocal microscopy of the skin in patients with infantile nephrogenic cystinosis. Methods Nine patients and control subjects were recruited for this study. Images were acquired by means of a near-infrared reflectance confocal laser scanning microscope. Results Scattered bright particles within the papillary dermis were observed in all patients but not in control subjects. The density of particles ranged from numerous (+++) to very few (+/–) and their distribution was heterogeneous. Electron microscopy confirmed that these particles corresponded to cystine crystal deposits within dermal fibroblasts. The density of cystine crystals within the dermis was greater in older patients, in patients with a high leukocyte cystine concentration, and with delayed cysteamine therapy. There was no correlation between the density of cystine deposits and renal disease or hypopigmentation but high levels of deposition occurred in association with extrarenal manifestations. Limitations This is a preliminary study on a small sample of patients. Repeated examination and longer follow-up is necessary. Conclusion In vivo reflectance confocal microscopy of the skin appears to be a noninvasive means of assessing body cystine accumulation in infantile cystinosis and could be used as a complementary marker of treatment response in addition to leukocyte cystine measurement.
Abstract Background Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe ...complications have been assessed in relatively small populations and/or with limited follow-up. Objectives This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry. Methods The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used. Results A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p < 0.001), low body mass index, (p < 0.001), atrial fibrillation (p < 0.001), dialysis (p < 0.001), New York Heart Association functional class III or IV (p < 0.001), higher logistic EuroSCORE (p < 0.001), transapical or subclavian approach (p < 0.001 for both vs. transfemoral approach), need for permanent pacemaker implantation (p = 0.02), and post-implant periprosthetic aortic regurgitation grade ≥2 of 4 (p < 0.001). Severe events according to VARC criteria occurred mainly during the first month and subsequently in <2% of patients/year. Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up. Conclusions The FRANCE-2 registry represents the largest database available on late results of TAVR. Late mortality is largely related to noncardiac causes. Incidence rates of severe events are low after the first month. Valve performance remains stable over time.
Background A current debate concerning suspected superficial vein thrombosis (SVT) focuses on the need of performing a compression ultrasound (CUS) exploration for confirming the diagnosis of SVT. ...This study was conducted to determine the clinical relevance and optimal CUS exploration in patients with symptomatic SVT. Methods We analyzed the characteristics of SVT and concomitant deep vein thrombosis (DVT) in patients included in the Prospective Observational Superficial Thrombophlebitis (POST) multicenter, observational prospective study. All patients underwent complete bilateral lower limb CUS, exploring both the superficial and deep venous systems. Results A total of 844 patients with clinical symptoms of SVT were recruited, of which 99 isolated SVTs (21.4%) had saphenofemoral/popliteal junction involvement, and 198 (23.5%) had a concomitant DVT, with 41.8% of them proximal DVTs. In 83 patients (41.9%), DVT and SVT were not contiguous. Five of 639 patients (1%) had an isolated contralateral DVT (ie, not bilateral). Age ≥75 years (odds ratio OR, 2.3; 95% confidence interval CI, 1.6-3.4), inpatient status (OR, 5.4; 95% CI, 3.4-8.7), a personal history of DVT or pulmonary embolism (OR, 1.8; 95% CI, 1.2-2.8), and SVT on nonvaricose veins (OR, 3.3; 95% CI, 2.1-5.0) were significantly and independently associated with an increased risk of concomitant DVT. Half of the patients exhibited none of these risk factors, and the prevalence of concomitant DVT dropped to 11%. Conclusions In patients with symptomatic SVT, a CUS exploration screening the whole venous system of the affected limb is useful because it provides information that has important consequences for the management of these patients.
Abstract Background Recent studies have reported that obesity, metabolic syndrome, and diabetes are associated with left ventricular (LV) hypertrophy (LVH) and dysfunction in patients with aortic ...stenosis (AS). The purpose of this study was to examine the association between amount and distribution of body fat and LVH and systolic dysfunction in AS patients. Methods One hundred twenty-four patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study and underwent Doppler echocardiography and computed tomography scan. Presence and severity of LVH was assessed according to LV mass indexed for height2.7 and LV dysfunction according to global longitudinal strain (GLS). Computed tomography was used to quantify abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, and total adipose tissue (TAT). Results Body mass index (BMI) correlated strongly with TAT ( r = 0.85), moderately with VAT ( r = 0.70), and SAT ( r = 0.69), and weakly with the proportion of VAT (VAT/TAT ratio: r = 0.19). In univariate analysis, greater BMI, TAT, VAT, SAT, and VAT/TAT were associated with increased LV mass index and greater VAT and VAT/TAT ratio were associated with reduced GLS. Multivariate analysis revealed that larger BMI ( P < 0.0001) and greater VAT/TAT ratio ( P = 0.01) were independently associated with higher prevalence of LVH, and only the VAT/TAT ratio ( P = 0.03) was independently associated with reduced GLS. Conclusions The results of this study suggest that total and visceral adiposity are independently associated with LVH in patients with AS. Furthermore, impairment of LV systolic function does not appear to be influenced by total obesity but is rather related to excess visceral adiposity. These findings provide impetus for elaboration of interventional studies aiming at visceral adiposity in the AS population.
Abstract Background Waist circumference (WC) and body mass index (BMI) are clinically used to assess adiposity. The aim of the present study was to evaluate the association of WC with postoperative ...morbidity and mortality in patients who underwent isolated coronary artery bypass grafting (CABG) in relation to patients' BMI category. Methods We analyzed the associations of WC and BMI with short-term postoperative outcomes in a cohort of 7446 patients who underwent isolated CABG. We performed univariate and adjusted analyses on main postoperative outcomes after CABG for WC and BMI. Results Adverse events researched included postoperative mortality, intensive care unit and hospital length of stay, cardiovascular and cerebrovascular events, respiratory complications, infectious, hemostasis complications, and renal complications. WC was independently associated with all postoperative outcomes except prolonged intubation and mortality. Overall, patients in the upper WC quartile in each BMI category were at increased risk of adverse events compared with patients in the lower 3 WC quartiles, with a maximal incremental risk of 1.91 (95% confidence interval, 1.23-2.95) among patients with a BMI ≥ 35. This association was observed for men and women, across all overweight and obesity categories. Neither WC nor BMI was associated with short-term postoperative mortality. Conclusions In our large cohort of patients who underwent isolated CABG, WC was significantly associated with clinical adverse events, independently of BMI. These findings provide further evidence on the added value of measuring WC as a simple and easy to measure anthropometric marker to refine risk assessment beyond BMI among patients who undergo CABG.
Objective To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). Study design P1065 was a ...phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥15. Results Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. Conclusion In youth infected with HIV with a CD4% ≥15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.
Objective We investigated whether metabolic syndrome, defined in 3 different ways (2 commonly used and 1 novel) is associated with arterial alterations in obese children. Study design The study group ...comprised 384 obese children age 2.5 to 18 years. Blood pressure, fasting blood glucose, blood insulin, plasma lipids, and body composition were measured. Noninvasive ultrasound measurements were obtained in 161 patients to investigate arterial mechanical properties and endothelial function. Results The prevalence of metabolic syndrome was 10.4%. Intima-media thickness correlated positively with low-density lipoprotein cholesterol ( r = .21; P < .01) and negatively with high-density lipoprotein cholesterol ( r = −.17; P < .05). In adolescents (11 to 18 years), cross-sectional vascular compliance correlated negatively with abdominal fat ( r = −.22; P = .02). The only synergistic effects among individual metabolic syndrome components was an effect of insulinemia and systolic blood pressure on cross-sectional compliance (4.05; P < .05). No significant difference in vascular variables was found between the patients with and without metabolic syndrome using any of the 3 definitions. Conclusion Metabolic syndrome in obese children is not related to arterial variables, whereas several of its individual components are associated with vascular alterations. These data suggest that the value of the metabolic syndrome as a predictor of future cardiovascular events in children remains to be prospectively evaluated. In the meantime, individual cardiovascular risk factors should be evaluated and controlled.
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