Population doublings and percentage of S100-positive cells as predictors of in vitro chondrogenicity of expanded human articular chondrocytes

The aim of this study was to investigate the interconnection between the processes of proliferation, dedifferentiation, and intrinsic redifferentiation (chondrogenic) capacities of human articular chondrocyte (HAC), and to identify markers linking HAC dedifferentiation status with their chondrogenic potential. Cumulative population doublings (PD) of HAC expanded in monolayer culture were determined, and a threshold range of 3.57-4.19 PD was identified as indicative of HAC loss of intrinsic chondrogenic capacity in pellets incubated without added chondrogenic factors. While several specific gene and surface markers defined early HAC dedifferentiation process, no clear correlation with the loss of intrinsic chondrogenic potential could be established. CD90 expression during HAC monolayer culture revealed two subpopulations, with sorted CD90-negative cells showing lower proliferative capacity and higher chondrogenic potential compared to CD90-positive cells. Although these data further validated PD as critical for in vitro chondrogenesis, due to the early shift in expression, CD90 could not be considered for predicting chondrogenic potential of HAC expanded for several weeks. In contrast, an excellent mathematically modeled correlation was established between PD and the decline of HAC expressing the intracellular marker S100, providing a direct link between the number of cell divisions and dedifferentiation/loss of intrinsic chondrogenic capacity. Based on the dynamics of S100-positive HAC during expansion, we propose asymmetric cell division as a potential mechanism of HAC dedifferentiation, and S100 as a marker to assess chondrogenicity of HAC during expansion, of potential value for cell-based cartilage repair treatments.

Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation

Atrioventricular (AV) conduction impairment is well described after surgical aortic valve replacement, but little is known in patients undergoing transcatheter aortic valve implantation (TAVI). We assessed AV conduction and need for a permanent pacemaker in patients undergoing TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards Sapien Valve (ESV). Sixty-seven patients without pre-existing permanent pacemaker were included in the study. Forty-one patients (61%) and 26 patients (39%) underwent successful TAVI with the MCRS and ESV, respectively. Complete AV block occurred in 15 patients (22%), second-degree AV block in 4 (6%), and new left bundle branch block in 15 (22%), respectively. A permanent pacemaker was implanted in 23 patients (34%). Overall PR interval and QRS width increased significantly after the procedure (p <0.001 for the 2 comparisons). Implantation of the MCRS compared to the ESV resulted in a trend toward a higher rate of new left bundle branch block and complete AV block (29% vs 12%, p = 0.09 for the 2 comparisons). During follow-up, complete AV block resolved in 64% of patients. In multivariable regression analysis pre-existing right bundle branch block was the only independent predictor of complete AV block after TAVI (relative risk 7.3, 95% confidence interval 2.4 to 22.2). In conclusion, TAVI is associated with impairment of AV conduction in a considerable portion of patients, patients with pre-existing right bundle branch block are at increased risk of complete AV block, and complete AV block resolves over time in most patients.

Matrix metalloproteinases and angiogenic factors: predictors of survival after radical prostatectomy for clinically organ-confined prostate cancer?

The aim of the present study was to investigate whether biomarkers improve the prediction of recurrence-free, disease-specific, and overall survival in patients with clinically localized prostate cancer. A tissue microarray was constructed from prostate specimens of 278 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer. For immunohistochemical studies, antibodies were used against matrix metalloproteinase (MMP)-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19, as well as against vascular endothelial growth factor, hypoxia-induced factor 1 , basic fibroblast growth factor, and cluster of differentiation 31. Univariate and multivariable analyses were performed to evaluate the potential predictors of overall, disease-specific, and recurrence-free survival. In univariate analysis of patients with clinically organ-confined prostate cancer, only higher expression levels of MMP-9 (hazard ratio [0.6], 95% CI 0.45-0.8) had a protective effect in terms of overall survival. This positive effect of high MMP-9 expression was also observed for recurrence-free (HR 0.88, 95% CI 0.78-0.99) and disease-specific survival (HR 0.5, 95% CI 0.36-0.73). In multivariable analysis, none of these potential markers was found to be an independent prognostic factor of survival. Of all MMPs and angiogenic factors tested, MMP-9 expression has the potential as a prognostic marker in patients undergoing radical prostatectomy for clinically organ-confined cases of prostate cancer.

Predictors of readmission and health related quality of life in patients with chronic heart failure: a comparison of different psychosocial aspects

Psychological distress is common in patients with chronic heart failure. The impact of different psychological variables on prognosis has been shown but the comparative effects of these variables remain unclear. This study examines the impact of depression, anxiety, vital exhaustion, Type D personality, and social support on prognosis in chronic heart failure patients. One hundred eleven patients (mean age 57 ± 14 years) having participated in an exercise based ambulatory cardiac rehabilitation program were enrolled in a prospective cohort study. Psychological baseline data were assessed at program entry. Mortality, readmission, and health-related quality of life were assessed at follow up (mean 2.8 ± 1.1 years). After controlling for disease severity none of the psychological variables were associated with mortality, though severe anxiety predicted readmission [HR = 3.21 (95% CI, 1.04-9.93; P = .042)]. Health-related quality of life was independently explained by vital exhaustion, anxiety and either body mass index (physical dimension) or sex (emotional dimension). As psychological variables have a strong impact on health-related quality of life they should be routinely assessed in chronic heart failure patients` treatment.

Chronic posttraumatic stress and its predictors in patients living with an implantable cardioverter defibrillator

Patients with an implantable cardioverter defibrillator (ICD) show clinically relevant depression and anxiety, but little is known about their levels of posttraumatic stress. We assessed chronic posttraumatic stress attributable to a traumatic cardiac event and its predictors in patients at two time points after ICD placement.

Remission in schizophrenia: validity, frequency, predictors, and patients' perspective 5 years later

In March 2005, the Remission in Schizophrenia Working Group (RSWG) proposed a consensus definition of symptomatic remission in schizophrenia and developed specific operational criteria for its assessment. They pointed out, however, that the validity and the relationship to other outcome dimensions required further examination. This article reviews studies on the validity, frequency, and predictors of symptomatic remission in schizophrenia and studies on patients' perspectives. These studies have demonstrated that the RSWG remission criteria appear achievable and sustainable for a significant proportion of patients, and are related to a better overall symptomatic status and functional outcome and, to a less clear extent, to a better quality of life and cognitive performance. However, achieving symptomatic remission is not automatically concurrent with an adequate status in other outcome dimensions. The results of the present review suggest that the RSWG remission criteria are valid and useful. As such, they should be consistently applied in clinical trials. However the lack of consensus definitions of functional remission and adequate quality of life hampers research on their predictive validity on these outcome dimensions. Future research should therefore search for criteria of these dimensions and test whether the RSWG remission criteria consistently predict a "good" outcome with respect to functioning and quality of life.

Prevalence, predictors, and consequences of long-term refusal of antipsychotic treatment in first-episode psychosis

Studies investigating medication adherence in psychosis are limited by the need of a certain degree of medication adherence and the inclusion of mostly multiple-episode patients. By contrast, noninformed consent, epidemiological studies in first-episode psychosis (FEP) allow the assessment of an important subgroup of patients who persistently refuse antipsychotic medication and thereby never receive an adequate antipsychotic trial. The present study aims to assess the prevalence and predictors of such a "medication refusal" subgroup and its association with illness outcome.

Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis

Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest.