Endovascular Revascularization of Below-the-Knee Arteries: Prospective Short-Term Angiographic and Clinical Follow-up

PURPOSE: To evaluate arterial lesion characteristics and their impact on angiographic and clinical outcomes after endovascular below-the-knee (BTK) revascularization. MATERIALS AND METHODS: Between April 2008 and June 2009, 33 patients (mean age 74.9 years) with 34 limbs and 50 arterial segments (mean lesion length 59.3 mm) undergoing endovascular BTK revascularization agreed to undergo prospective clinical and intraarterial angiographic 6-month follow-up evaluation. Clinical indication for BTK revascularization was critical limb ischemia (CLI) in 18 patients and delayed wound healing without hemodynamic evidence of CLI and intermittent claudication (IC) in 15 patients. RESULTS: Binary restenosis was observed in 40% of treated segments at 6 months. Primary sustained clinical improvement was 82.4% and 55.9% at 3 months and 6 months. Lesion length was independently associated with binary restenosis (hazard ratio [HR] 1.013, 95% confidence interval [CI] 1.000-1.016, P = .05) and lower rates of primary sustained clinical improvement (HR 1.024, 95% CI 1.006-1.042, P = .008). CONCLUSIONS: Endovascular BTK revascularization yields clinical and angiographic benefits both for patients with IC and for patients with CLI. Although arterial lesion length adversely affects angiographic and clinical outcomes after endovascular revascularization, limb salvage rates were substantially higher compared with the comparatively low patency rates after BTK angioplasty.

Assessment of coronary artery disease by post-mortem cardiac MR

Minimally invasive or virtual autopsies are being advocated as alternative to traditional autopsy, but have limited abilities to detect coronary artery disease. It was the objective of this study to assess if the occurrence of chemical shift artifacts (CSA) along the coronary arteries on non-contrast, post-mortem cardiac MR may be used to investigate coronary artery disease.

Gender differences of atrial and ventricular remodeling and autonomic tone in nonelite athletes

Veteran endurance athletes have an increased risk of developing atrial fibrillation (AF), with a striking male predominance. We hypothesized that male athletes were more prone to atrial and ventricular remodeling and investigated the signal-averaged P wave and factors that promote the occurrence of AF. Nonelite athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Of the 873 marathon and nonmarathon runners who were willing to participate, 68 female and 70 male athletes were randomly selected. The runners with cardiovascular disease or elevated blood pressure (>140/90 mm Hg) were excluded. Thus, 121 athletes were entered into the final analysis. Their mean age was 42 ± 7 years. No gender differences were found for age, lifetime training hours, or race time. The male athletes had a significantly longer signal-averaged P-wave duration (136 ± 12 vs 122 ± 10 ms; p <0.001). The left atrial volume was larger in the male athletes (56 ± 13 vs 49 ± 10 ml; p = 0.001), while left atrial volume index showed no differences (29 ± 7 vs 30 ± 6 ml/m²; p = 0.332). In male athletes, the left ventricular mass index (107 ± 17 vs 86 ± 16 g/m²; p <0.001) and relative wall thickness (0.44 ± 0.06 vs 0.41 ± 0.07; p = 0.004) were greater. No differences were found in the left ventricular ejection fraction (63 ± 4% vs 66 ± 6%; p = 0.112) and mitral annular tissue Doppler e' velocity (10.9 ± 1.5 vs 10.6 ± 1.5 cm/s; p = 0.187). However, the tissue Doppler a' velocity was higher (8.7 ± 1.2 vs 7.6 ± 1.3 cm/s; p < 0.001) in the male athletes. Male athletes had a higher systolic blood pressure at rest (123 ± 9 vs 110 ± 11 mm Hg; p < 0.001) and at peak exercise (180 ± 15 vs 169 ± 19 mm Hg; p = 0.001). In the frequency domain analysis of heart rate variability, the sympatho-vagal balance, represented by the low/high-frequency power ratio, was significantly greater in male athletes (5.8 ± 2.8 vs 3.9 ± 1.9; p < 0.001). Four athletes (3.3%) had at least one documented episode of paroxysmal AF, all were men (p = 0.042). In conclusion, for a comparable amount of training and performance, male athletes showed a more pronounced atrial remodeling, a concentric type of ventricular remodeling, and an altered diastolic function. A higher blood pressure at rest and during exercise and a higher sympathetic tone might be causal. The altered left atrial substrate might facilitate the occurrence of AF.

Comparing pneumococcal conjugate vaccine schedules based on 3 and 2 primary doses: systematic review and meta-analysis

Background Pneumococcal conjugate vaccines (PCV) were first licensed for use with 3 primary doses in infancy and a booster dose. The evidence for the effects of different schedules was examined in this systematic review and meta-analysis. Methods We searched 12 databases and trial registers up to March 2010. We selected randomised controlled trials (RCTs), cohort and case–control studies making direct comparisons between PCV schedules with (2p) or (3p) primary doses, with (+1) or without (+0) a booster dose. We extracted data on clinical, nasopharyngeal carriage and immunological outcomes and used meta-analysis to combine results where appropriate. Results Seropositivity levels (antibody concentration ≥0.35 μg/ml) following 3p and 2p PCV schedules were high for most serotypes (5 RCTs). Differences between schedules were generally small and tended to favour 3p schedules, particularly for serotypes 6B and 23F; between-study heterogeneity was high. Seropositivity levels following 3p+1 and 2p+1 schedules were similar but small differences favouring 3p+1 schedules were seen for serotypes 6B and 23F. We did not identify any RCTs reporting clinical outcomes for these comparisons. In 2 RCTs there was weak evidence of a reduction in carriage of S. pneumoniae serotypes included in the vaccine when 3p+0 schedules were compared to 2p+0 at 6 months of age. Conclusions Most data about the relative effects of different PCV schedules relate to immunological outcomes. Both 3p and 2p schedules result in high levels of seropositivity. The clinical relevance of differences in immunological outcomes between schedules is not known. There is an absence of clinical outcome data from RCTs with direct comparisons of any 2p with any 3p PCV schedule.

Resting-state EEG in schizophrenia: auditory verbal hallucinations are related to shortening of specific microstates

Abnormal perceptions and cognitions in schizophrenia might be related to abnormal resting states of the brain. Previous research found that a specific class (class D) of sub-second electroencephalography (EEG) microstates was shortened in schizophrenia. This shortening correlated with positive symptoms. We questioned if this reflected positive psychotic traits or present psychopathology.

Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients

Several members of the human kallikrein-related peptidase family, including KLK6, are up-regulated in ovarian cancer. High KLK6 mRNA or protein expression, measured by quantitative polymerase chain reaction and enzyme-linked immunoassay, respectively, was previously found to be associated with a shortened overall and progression-free survival (OS and PFS, respectively). In the present study, we aimed at analyzing KLK6 protein expression in ovarian cancer tissue by immunohistochemistry. Using a newly developed monospecific polyclonal antibody, KLK6 immunoexpression was initially evaluated in normal tissues. We observed strong staining in the brain and moderate staining in the kidney, liver, and ovary, whereas the pancreas and the skeletal muscle were unreactive, which is in line with previously published results. Next, both tumor cell- and stromal cell-associated KLK6 immunoexpression were analyzed in tumor tissue specimens of 118 ovarian cancer patients. In multivariate Cox regression analysis, only stromal cell-associated expression, besides the established clinical parameters FIGO stage and residual tumor mass, was found to be statistically significant for OS and PFS [high vs. low KLK6 expression; hazard ratio (HR), 1.92; p=0.017; HR, 1.80; p=0.042, respectively]. These results indicate that KLK6 expressed by stromal cells may considerably contribute to the aggressiveness of ovarian cancer.

Evaluation of radial distribution of cartilage degeneration and necessity of pre-contrast measurements using radial dGEMRIC in adults with acetabular dysplasia

Background The purpose of the present study was to investigate the radial distribution patterns of cartilage degeneration in dysplastic hips at different stages of secondary osteoarthritis (OA) by using radial delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and to assess whether pre-contrast measurements are necessary. Methods Thirty-five hips in 21 subjects (mean age ± SD, 27.6 ± 10.8 years) with acetabular dysplasia (lateral CE angle < 25°) were studied. Severity of OA was assessed on radiographs using Tönnis grading. Pre- (T1pre) and post-contrast T1 (T1Gd) values were measured at 7 sub-regions on radial reformatted slices acquired from a 3-dimensional (3D) T1 mapping sequence using a 1.5 T MR scanner. Values of radial T1pre, T1Gd and ΔR1 (1/T1Gd - 1/T1pre) of subgroups with different severity of OA were compared to those of the subgroup without OA using nonparametric tests, and bivariate linear Pearson correlations between radial T1Gd and ΔR1 were analyzed for each subgroup. Results Compared to the subgroup without OA, the subgroup with mild OA was observed with a significant decrease in T1Gd in the anterosuperior to superior sub-regions (mean, 476 ~ 507 ms, p = 0.026 ~ 0.042) and a significant increase in ΔR1 in the anterosuperior to superoposterior and posterior sub-regions (mean, 0.93 ~ 1.37 s-1, p = 0.012 ~ 0.042). The subgroup with moderate to severe OA was observed with a significant overall decrease in T1Gd (mean, 404 ~ 452 ms, p = 0.001 ~ 0.020) and an increase in ΔR1 (mean, 1.17 ~1.69 s-1, p = 0.001 ~ 0.020). High correlations were observed between radial T1Gd and ΔR1 for all subgroups (r = −0.869 ~ −0.944, p < 0.001). Conclusions Radial dGEMRIC without pre-contrast measurements is useful for evaluating different patterns of cartilage degeneration in the entire hip joint of patients with hip dysplasia, particularly for those in early stages of secondary OA.

Unhealthy alcohol use, HIV infection and risk of liver fibrosis in drug users with hepatitis C

Aim To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values. Conclusions Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations.

Determinants of timely management of acute bacterial meningitis in the ED

PURPOSE: The purpose was to study the emergency management of patients with suspected meningitis to identify potential areas for improvement. METHODS: All patients who underwent cerebrospinal fluid puncture at the emergency department of the University Hospital of Bern from January 31, 2004, to October 30, 2008, were included. A total of 396 patients were included in the study. For each patient, we analyzed the sequence and timing for the following management steps: first contact with medical staff, administration of the first antibiotic dose, lumbar puncture (LP), head imaging, and blood cultures. The results were analyzed in relation to clinical characteristics and the referral diagnosis on admission. RESULTS: Of the 396 patient analyzed, 15 (3.7%) had a discharge diagnosis of bacterial meningitis, 119 (30%) had nonbacterial meningitis, and 262 (66.3%) had no evidence of meningitis. Suspicion of meningitis led to earlier antibiotic therapy than suspicion of an acute cerebral event or nonacute cerebral event (P < .0001). In patients with bacterial meningitis, the average time to antibiotics was 136 minutes, with a range of 0 to 340 minutes. Most patients (60.1%) had brain imaging studies performed before LP. On the other hand, half of the patients with a referral diagnosis of meningitis (50%) received antibiotics before performance of an LP. CONCLUSIONS: Few patients with suspected meningitis received antimicrobial therapy within the first 30 minutes after arrival, but most patients with pneumococcal meningitis and typical symptoms were treated early; patients with bacterial meningitis who received treatment late had complex medical histories or atypical presentations.

Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report

Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations. Although corticosteroids are the first-line therapy for many of these disorders, approaches to the treatment of patients who do not tolerate or are unresponsive to corticosteroids are poorly standardized. A multidisciplinary group of 37 clinicians and scientists participated in a workshop held in May 2005 in Bern, Switzerland to discuss current and future approaches to therapy for 3 eosinophil-mediated disorders: hypereosinophilic syndrome, Churg-Strauss syndrome, and eosinophil-associated gastrointestinal disease. The goal of the workshop was to summarize available data regarding treatment of these disorders to identify the most promising therapies and approaches for further study. There was consensus among all of the participants that the identification of markers of disease progression to assess treatment responses is a research priority for all 3 disorders. Furthermore, the need for newer therapeutic strategies and novel drugs, as well as multicenter trials to assess all treatment modalities, was emphasized.

Treating intermittent claudication with Tibetan medicine Padma 28: does it work?

Herbal drugs are being increasingly used in medical practice, often without appropriate scrutiny of their safety and efficacy. The medicinal product Padma 28 is a fixed combination with Tibetan origin, used in Europe since the 1960s for the symptomatic treatment of circulatory disorders, including those of peripheral arterial occlusive disease (PAOD). We have conducted an analysis of all available data on this herbal drug from published literature as well as from original data we obtained from contacting the authors of published papers, reports and the manufacturer. A total of 19 trials have reported on 2084 patients to date, 444 of whom were in six controlled clinical studies on PAOD. A meta-analysis of five trials showed Padma 28 to increase walking distance by >100m in 18.2% of the patients with verum, versus 2.1% with placebo (P<0.001; odds ratio: 10 [95% CI 3.03, 33.33]; RR: 0.12; number needed to treat=6.2). The safety profile appears to be favourable. Available evidence shows that Padma 28 provides significant relief from PAOD-related symptoms (i.e. walking distance), probably of the same order of magnitude as other employed medications. However, larger confirmatory RCTs are desirable.

Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome

PURPOSE: This study evaluated the long-term effect of pars plana vitrectomy (PPV) in children and adolescents with chronic uveitis on visual function, anatomical outcome, and the requirement of systemic treatment. Further, predictive preoperative factors associated with a beneficial visual outcome were assessed. METHODS: Retrospective review of 29 eyes of 23 consecutive paediatric and juvenile patients below 20 years of age with chronic uveitis who underwent a PPV for visually significant opacities in 25 eyes, vitreous haemorrhage in three eyes, and retinal detachment in one eye. The clinical diagnosis was chronic intermediate uveitis in 22 eyes and retinal vasculitis of different origin in seven eyes. RESULTS: LogMAR visual acuity improved from an average of 0.91 to 0.33 (P<0.001). Cystoid macular oedema (CME) was significantly reduced in eight of 10 eyes postoperatively (P=0.021). In the multiple regression analysis, a low preoperative logMAR visual acuity and the presence of a CME had a negative influence on the final logMAR visual acuity. Furthermore, the appearance of chronic uveitis relapses was significantly reduced from 15 eyes before to seven eyes after surgery (P=0.042). CONCLUSIONS: PPV has a beneficial effect on the course and the complications of chronic uveitis in paediatric and juvenile patients with respect to the anatomical and visual outcome. Preoperative logMAR visual acuity and clinically significant CME were the most accurate predictors for the functional outcome.