Impact of B-type natriuretic peptide on short-term clinical outcomes following transcatheter aortic valve implantation

Aims: We aimed to assess the impact of B-type natriuretic peptide (BNP) on short-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: Of 500 consecutive patients with severe aortic stenosis undergoing TAVI at our institution, we studied 340 patients who had a BNP assessment prior to TAVI. Patients were divided into tertiles - low: BNP ≤201 pg/mL (n=114), mid: BNP 202-595 pg/mL (n=113) and high: BNP ≥596 pg/mL (n=113). The primary endpoint was all-cause mortality, cardiac death and major adverse cardiac and cerebrovascular events (MACCE; death, major stroke and myocardial infarction) at 30 days. Compared with low tertile, high tertile patients were at higher baseline surgical risk (STS score 5.5±3.0 vs. 7.4±4.1, p=0.002). On echocardiography, high tertile patients had smaller valve areas (0.74±0.21 vs. 0.66±0.23 cm2, p=0.008), higher left ventricular (LV) mass indices (123.40±33.66 vs. 168.22±47.96 g/m2, p<0.001) and lower LV ejection fractions (61.59±7.18 vs. 42.65±15.41%, p<0.001) as compared with low tertile patients. At 30 days, a significantly higher incidence of death (hazard ratio [HR] 7.41, p=0.001) cardiac death (HR 5.82, p=0.006) and MACCE (HR 9.04, p<0.001) was observed among high as compared to low tertile patients. Conclusions: In TAVI patients, higher BNP values at baseline are associated with an increased risk for an adverse event periprocedurally and after 30 days, respectively.

Prevalence of cam and pincer-type deformities on hip MRI in an asymptomatic young Swiss female population: a cross-sectional study

OBJECTIVES Femoroacetabular impingement is proposed to cause early osteoarthritis (OA) in the non-dysplastic hip. We previously reported on the prevalence of femoral deformities in a young asymptomatic male population. The aim of this study was to determine the prevalence of both femoral and acetabular types of impingement in young females. METHODS We conducted a population-based cross-sectional study of asymptomatic young females. All participants completed a set of questionnaires and underwent clinical examination of the hip. A random sample was subsequently invited to obtain magnetic resonance images (MRI) of the hip. All MRIs were read for cam-type deformities, increased acetabular depths, labral lesions, and impingement pits. Prevalence estimates of cam-type deformities and increased acetabular depths were estimated, and relationships between deformities and signs of joint damage were examined using logistic regression models. RESULTS The study included 283 subjects, and 80 asymptomatic females with a mean age of 19.3 years attended MRI. Fifteen showed some evidence of cam-type deformities, but none were scored to be definite. The overall prevalence was therefore 0% [95% confidence interval (95% CI) 0-5%]. The prevalence of increased acetabular depth was 10% (95% CI 5-19). No association was found between increased acetabular depth and decreased internal rotation of the hip. Increased acetabular depth was not associated with signs of labral damage. CONCLUSIONS Definite cam-type deformities in women are rare compared to men, whereas the prevalence of increased acetabular depth is higher, suggesting that femoroacetabular impingement has different gender-related biomechanical mechanisms.

Safety climate and its association with office type and team involvement in primary care

OBJECTIVE To assess differences in safety climate perceptions between occupational groups and types of office organization in primary care. METHODS Primary care physicians and nurses working in outpatient offices were surveyed about safety climate. Explorative factor analysis was performed to determine the factorial structure. Differences in mean climate scores between staff groups and types of office were tested. Logistic regression analysis was conducted to determine predictors for a 'favorable' safety climate. RESULTS 630 individuals returned the survey (response rate, 50%). Differences between occupational groups were observed in the means of the 'team-based error prevention'-scale (physician 4.0 vs. nurse 3.8, P < 0.001). Medical centers scored higher compared with single-handed offices and joint practices on the 'team-based error prevention'-scale (4.3 vs. 3.8 vs. 3.9, P < 0.001) but less favorable on the 'rules and risks'-scale (3.5 vs. 3.9 vs. 3.7, P < 0.001). Characteristics on the individual and office level predicted favorable 'team-based error prevention'-scores. Physicians (OR = 0.4, P = 0.01) and less experienced staff (OR 0.52, P = 0.04) were less likely to provide favorable scores. Individuals working at medical centers were more likely to provide positive scores compared with single-handed offices (OR 3.33, P = 0.001). The largest positive effect was associated with at least monthly team meetings (OR 6.2, P < 0.001) and participation in quality circles (OR 4.49, P < 0.001). CONCLUSIONS Results indicate that frequent quality circle participation and team meetings involving all team members are effective ways to strengthen safety climate in terms of team-based strategies and activities in error prevention.

Type A aortic dissection after nonaortic cardiac surgery

BACKGROUND Cardiac surgery with cardiopulmonary bypass is associated with mechanical manipulation of the ascending aorta that occasionally leads to type A aortic dissection (AAD). METHODS AND RESULTS One hundred three patients with surgical repair for AAD following nonaortic cardiac surgery were identified. With the use of logistic regression modeling, coronary artery bypass surgery (CABG), either isolated or combined with another procedure in the initial operation, was associated with significantly higher operative mortality in comparison with patients with non-CABG procedures at the time of AAD repair both for all patients (odds ratio, 2.90; 95% confidence interval, 1.09-7.72; P=0.033) and for patients with acute and chronic AAD≥30 days after the initial operation (odds ratio, 3.62; 95% confidence interval, 1.13-11.54; P=0.03). In patients who developed AAD late after the initial operation, operative mortality was highest in patients without preoperative coronary angiography and appropriate management of their native coronary artery disease and graft disease (odds ratio, 5.36; 95% confidence interval, 1.68-17.0; P=0.002). Nearly all the intimal dissection tears were located at sites of previous surgical trauma. Most of the ascending aortas that had dissected initially had a diameter≥40 mm with histological evidence of medial degeneration in resected tissue samples. CONCLUSIONS In patients who have undergone previous cardiac surgery, preexisting aortic wall pathology contributes to AAD with typical intimal damage at sites of mechanical trauma. The operative mortality was the highest in patients with previous CABG in comparison with patients with non-CABG procedures. Preoperative coronary angiography and operative management of native coronary and graft disease were significantly associated with outcome in patients with previous CABG.

An analysis of variance type method to describe and compare steady states in clinical data

Identifying and comparing different steady states is an important task for clinical decision making. Data from unequal sources, comprising diverse patient status information, have to be interpreted. In order to compare results an expressive representation is the key. In this contribution we suggest a criterion to calculate a context-sensitive value based on variance analysis and discuss its advantages and limitations referring to a clinical data example obtained during anesthesia. Different drug plasma target levels of the anesthetic propofol were preset to reach and maintain clinically desirable steady state conditions with target controlled infusion (TCI). At the same time systolic blood pressure was monitored, depth of anesthesia was recorded using the bispectral index (BIS) and propofol plasma concentrations were determined in venous blood samples. The presented analysis of variance (ANOVA) is used to quantify how accurately steady states can be monitored and compared using the three methods of measurement.

Circadian blood pressure during the early course of type 1 diabetes. Analysis of 1,011 ambulatory blood pressure recordings in 354 adolescents and young adults

OBJECTIVE Little information is available on the early course of hypertension in type 1 diabetes. The aim of our study, therefore, was to document circadian blood pressure profiles in patients with a diabetes duration of up to 20 years and relate daytime and nighttime blood pressure to duration of diabetes, BMI, insulin therapy, and HbA1c. RESEARCH DESIGN AND METHODS Ambulatory profiles of 24-h blood pressure were recorded in 354 pediatric patients with type 1 diabetes (age 14.6 +/- 4.2 years, duration of diabetes 5.6 +/- 5.0 years, follow-up for up to 9 years). A total of 1,011 profiles were available for analysis from patients not receiving antihypertensive medication. RESULTS Although daytime mean systolic pressure was significantly elevated in diabetic subjects (+3.1 mmHg; P < 0.0001), daytime diastolic pressure was not different from from the height- and sex-adjusted normal range (+0.1 mmHg, NS). In contrast, both systolic and diastolic nighttime values were clearly elevated (+7.2 and +4.2 mmHg; P < 0.0001), and nocturnal dipping was reduced (P < 0.0001). Systolic blood pressure was related to overweight in all patients, while diastolic blood pressure was related to metabolic control in young adults. Blood pressure variability was significantly lower in girls compared with boys (P < 0.01). During follow-up, no increase of blood pressure was noted; however, diastolic nocturnal dipping decreased significantly (P < 0.03). Mean daytime blood pressure was significantly related to office blood pressure (r = +0.54 for systolic and r = +0.40 for diastolic pressure); however, hypertension was confirmed by ambulatory blood pressure measurement in only 32% of patients with elevated office blood pressure. CONCLUSIONS During the early course of type 1 diabetes, daytime blood pressure is higher compared with that of healthy control subjects. The elevation of nocturnal values is even more pronounced and nocturnal dipping is reduced. The frequency of white-coat hypertension is high among adolescents with diabetes, and ambulatory blood pressure monitoring avoids unnecessary antihypertensive treatment.

Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials

BACKGROUND The optimal schedule and the need for a booster dose are unclear for Haemophilus influenzae type b (Hib) conjugate vaccines. We systematically reviewed relative effects of Hib vaccine schedules. METHODS We searched 21 databases to May 2010 or June 2012 and selected randomized controlled trials or quasi-randomized controlled trials that compared different Hib schedules (3 primary doses with no booster dose [3p+0], 3p+1 and 2p+1) or different intervals in primary schedules and between primary and booster schedules. Outcomes were clinical efficacy, nasopharyngeal carriage and immunological response. Results were combined in random-effects meta-analysis. RESULTS Twenty trials from 15 countries were included; 16 used vaccines conjugated to tetanus toxoid (polyribosylribitol phosphate conjugated to tetanus toxoid). No trials assessed clinical or carriage outcomes. Twenty trials examined immunological outcomes and found few relevant differences. Comparing polyribosylribitol phosphate conjugated to tetanus toxoid 3p+0 with 2p+0, there was no difference in seropositivity at the 1.0 μg/mL threshold by 6 months after the last primary dose (combined risk difference -0.02; 95% confidence interval: -0.10, 0.06). Only small differences were seen between schedules starting at different ages, with different intervals between primary doses, or with different intervals between primary and booster doses. Individuals receiving a booster were more likely to be seropositive than those at the same age who did not. CONCLUSIONS There is no clear evidence from trials that any 2p+1, 3p+0 or 3p+1 schedule of Hib conjugate vaccine is likely to provide better protection against Hib disease than other schedules. Until more data become available, scheduling is likely to be determined by epidemiological and programmatic considerations in individual settings.

hp-dGFEM for Second-Order Elliptic Problems in Plyhedra II: Exponential Convergence

The goal of this paper is to establish exponential convergence of $hp$-version interior penalty (IP) discontinuous Galerkin (dG) finite element methods for the numerical approximation of linear second-order elliptic boundary-value problems with homogeneous Dirichlet boundary conditions and piecewise analytic data in three-dimensional polyhedral domains. More precisely, we shall analyze the convergence of the $hp$-IP dG methods considered in [D. Schötzau, C. Schwab, T. P. Wihler, SIAM J. Numer. Anal., 51 (2013), pp. 1610--1633] based on axiparallel $\sigma$-geometric anisotropic meshes and $\bm{s}$-linear anisotropic polynomial degree distributions.

Lions-type compactness and Rubik actions on the Heisenberg group

In this paper we prove a Lions-type compactness embedding result for symmetric unbounded domains of the Heisenberg group. The natural group action on the Heisenberg group TeX is provided by the unitary group U(n) × {1} and its appropriate subgroups, which will be used to construct subspaces with specific symmetry and compactness properties in the Folland-Stein’s horizontal Sobolev space TeX. As an application, we study the multiplicity of solutions for a singular subelliptic problem by exploiting a technique of solving the Rubik-cube applied to subgroups of U(n) × {1}. In our approach we employ concentration compactness, group-theoretical arguments, and variational methods.

B-type natriuretic peptide for diagnosis and treatment of congestive heart failure

BACKGROUND Prognostic classification of congestive heart failure (CHF) is difficult and only possible with the help of additional diagnostic tools. B-type natriuretic peptide (BNP) has been used as a diagnostic and prognostic marker for patients (pts) with CHF. In this study, the clinical value of BNP for stratification and treatment of pts with CHF was evaluated. PATIENTS AND METHODS 33 out-pts with CHF (age 57 +/- 12 years) were included. Left-ventricular (LV) ejection fraction (EF) was 27 +/- 8% (mean +/- SD) and NYHA-class 2.4 +/- 0.7. Following parameters were measured: BNP and sodium from blood samples, exercise performance from 6-minute walking test (6MWT, meters) (n = 18), LV end-diastolic diameter (LVEDD) and LV mass (LVM) from 2D-echocardiography (n = 33), as well as LV end-diastolic pressure (LVEDP, n = 23) and systemic vascular resistance (SVR, n = 20) from heart-catheterisation. Ten pts were hospitalised in the preceding 6 months because of worsening CHF or for optimisation of medical therapy. BNP was measured at the beginning and end of the hospital-stay. Follow-up was for 1 year. RESULTS Pts with a high NYHA-class had a higher BNP (pg/ml) than those with a low NYHA- class: NYHA I 51 +/- 20, II 281 +/- 223, III 562+/-346 and IV 1061 +/- 126 pg/ml (p = 0.002). BNP correlated with LVEDP (r = 0.50, p <0.02), SVR (r =0.49, p <0.03) and inversely with 6MWT (r =-0.60, p <0.009), LVEF (r = -0.49, p <0.004) and sodium (r = -0.36, p = 0.04). In the hospitalised pts, mean BNP (pg/ml) was 881 +/- 695 at admission,and 532 +/- 435 at discharge (n.s.). Decrease in BNPduring hospitalisation paralleled weight-loss and was significantly greater in patients with >1000 pg/ml BNP at admission (n = 5) as compared to the 5 patients with BNP <1000 (p <0.03). Patients with an adverse event during 1-year follow-up had significantly higher BNP both at steady-state (603 +/-359 pg/ml) and at time of decompensation than patients with a favourable outcome (227 +/- 218 pg/ml,p <0.001). CONCLUSIONS BNP correlates well with the clinical severity of CHF (NYHA-class) and is directly related to filling pressure (LVEDP), LV function(LVEF) and exercise performance (6 MWT). Furthermore, BNP has prognostic impact with regard to adverse clinical events.

The Effect of Open-Irrigated Radiofrequency Catheter Ablation of Atrial Fibrillation on Left Atrial Pressure and B-Type Natriuretic Peptide

Background Open-irrigated radiofrequency catheter ablation (oiRFA) of atrial fibrillation (AF) imposes a volume load and risk of pulmonary edema. We sought to assess the effect of volume administration during ablation on left atrial (LA) pressure and B-type natriuretic peptide (BNP). Methods LA pressure was measured via transseptal sheath at the beginning and end of 44 LA ablation procedures in 42 patients. BNP plasma levels were measured before and after 10 procedures. Results A median of 3,255 (interquartile range [IQR], 2,014)-mL saline was administered during the procedure. During LA ablation, the median fluid balance was +1,438 (IQR, 1,109) mL and LA pressure increased by median 3.7 (IQR, 5.9) mm Hg (P < 0.001). LA pressure did not change in the 19 procedures with furosemide administration (median ΔP = −0.3 [IQR, 7.1] mm Hg, P = 0.334). The correlation of LA pressure and fluid balance was weak (rs = 0.383, P = 0.021). BNP decreased in all four procedures starting in AF or atrial tachycardia and then converting to sinus rhythm (P = 0.068), and increased in all six procedures starting and finishing in sinus rhythm (P = 0.028). After ablation, symptomatic volume overload responding to diuresis occurred in three patients. Conclusions A substantial intravascular volume load during oiRFA can be absorbed with little change in LA pressure, such that LA pressure is not a reliable indicator of the fluid balance. Subsequent redistribution of the volume load imposes a risk after the procedure. Conversion to sinus rhythm may improve ability to acutely accommodate the volume load.

Growth plate alteration precedes cam-type deformity in elite basketball players

BACKGROUND Vigorous sporting activity during the growth years is associated with an increased risk of having a cam-type deformity develop. The underlying cause of this osseous deformity is unclear. One may speculate whether this is caused by reactive bone apposition in the region of the anterosuperior head-neck junction or whether sports activity alters the shape of and growth in the growth plate. If the latter is true, then one would expect athletes to show an abnormal shape of the capital growth plate (specifically, the epiphyseal extension) before and/or after physeal closure. QUESTIONS/PURPOSES We therefore raised three questions: (1) Do adolescent basketball players show abnormal epiphyseal extension? (2) Does the epiphyseal extension differ before and after physeal closure? (3) Is abnormal epiphyseal extension associated with high alpha angles? METHODS We performed a case-control comparative analysis of young (age range, 9-22 years) male elite basketball athletes with age-matched nonathletes, substratified by whether they had open or closed physes. We measured epiphyseal extension on radial-sequence MRI cuts throughout the cranial hemisphere from 9 o'clock (posterior) to 3 o'clock (anterior). Epiphyseal extension was correlated to alpha angle measurements at the same points. RESULTS Epiphyseal extension was increased in all positions in the athletes compared with the control group. On average, athletes showed epiphyseal extension of 0.67 to 0.83 versus 0.53 to 0.71 in control subjects. In the control group epiphyseal extension was increased at all measurement points in hips after physeal closure compared with before physeal closure. In contrast, the subgroup of athletes with a closed growth plate only had increased epiphyseal extension at the 3 o'clock position compared with the athletes with an open [corrected] growth plate (0.64-0.70). We observed a correlation between an alpha angle greater than 55° and greater epiphyseal extension in the anterosuperior femoral head quadrant: the corresponding Spearman r values were 0.387 (all hips) and 0.285 (alpha angle>55°) for the aggregate anterosuperior quadrant. CONCLUSIONS These findings suggest that a cam-type abnormality in athletes is a consequence of an alteration of the growth plate rather than reactive bone formation. High-level sports activity during growth may be a new and distinct risk factor for a cam-type deformity.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07

BACKGROUND We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2.

PURPOSE Women with epilepsy apparently have a higher incidence of polycystic ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying disease or the antiepileptic drug (AED) treatment is responsible for this increased risk is unknown, although clinical reports implicate valproic acid (VPA) as a potential cause. The steroidogenic enzymes 3beta HSDII (3beta-hydroxysteroid dehydrogenase) and P450c17 (17alpha-hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS. METHODS To determine whether the AEDs VPA, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human 3beta HSDII and P450c17, we added them to yeast expressing human P450c17 or 3beta HSDII and assayed enzymatic activities in the microsomal fraction. RESULTS Concentrations of VPA < or = 10 mM had no effect on activities of P450c17; however, VPA inhibited 3beta HSDII activity starting at 0.3 mM (reference serum unbound concentration, 0.035-0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG did not influence 3beta HSDII or P450c17 activities at typical reference serum unbound concentrations, but did inhibit 3beta HSDII and P450c17 at concentrations >10-fold higher. CONCLUSIONS None of the tested AEDs influenced 3beta HSDII or P450c17 activities at concentrations normally used in AED therapy. However, VPA started to inhibit 3beta HSDII activity at concentrations 3 times above the typical reference serum unbound concentration. Because inhibition of 3beta HSDII activity will shift steroidogenesis toward C19 steroid production when P450c17 activities are unchanged, very high doses of VPA may promote C19 steroid biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3beta HSDII and P450c17 only at toxic concentrations.

Metabolic control in children and adolescents with diabetes mellitus type I in Berne: a cross-sectional study.

AIMS/HYPOTHESIS In diabetes mellitus type I, good glycaemic control is crucial in preventing long-term diabetic complications. The aim of this study was to determine the current level of metabolic control in children and adolescents in our diabetes outpatient clinic at the University Children's Hospital, Berne. Furthermore, the impact of different factors such as age, pubertal stage, sex, duration of diabetes and insulin regimen on glycaemic control was studied. METHODS In a cross-sectional, prospective study 168 children and adolescents with type I diabetes mellitus (f:m = 87:81; prepubertal 48 [mean age 4.4 years, mean duration of diabetes 2.8 years]; pubertal 120 [mean age 9.4 years; mean duration of diabetes 5.2 years]) were studied for three months. Clinical data and HbA1c levels (latex immunoagglutination test) were recorded, statistically analysed and compared with the international literature. RESULTS In our type I diabetic children and adolescents the overall HbA1c was 8.07 +/- 1.15% (mean +/- SD; test-specific norm for healthy subjects: 4.1-6.1%). Glycaemic control was significantly worse in the pubertal group compared to the prepubertal (HbA1c 8.22 +/- 1.25% vs. 7.81 +/- 0.87%; p < 0.01). In addition, we found better metabolic control in patients with duration of diabetes below 2 years in children and adolescents (HbA1c prepubertal < 2 years: 7.45 +/- 0.67% vs. > 2 years: 8.05 +/- 0.93%, p < 0.05; pubertal < 2 years: 7.62 +/- 0.75% vs. > 2 years: 8.31 +/- 1.29%, p < 0.005). Importantly, sex and insulin regimen did not significantly influence glycaemic control. CONCLUSION/INTERPRETATION The current level of metabolic control in our children and adolescents with diabetes mellitus type I is comparable to the glycaemic control of the intensively treated adolescent group of the DCCT-study, in whom decreased risk of long-term diabetic complications was found. In contrast, our patients were intensively treated in terms of frequent contacts with the diabetes team, but were not necessarily on an intensified insulin regimen. The impact of biopsychosocial support from multidisciplinary diabetes team on good metabolic control in children and adolescents with type I diabetes mellitus and their families seems to be very important.