Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis

BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines

Cardiac Rehabilitation in German Speaking Countries of Europe—Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH—Part 2

Background: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients’ groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. Methods: Generation of evidence and search of literature have been described in part 1. Results: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for “distress management” and “lifestyle changes”. PE is able to increase patients’ knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients’ groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. Conclusions: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively

Evaluation of Aerobic Exercise Intensity in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus

(1) Background: Physical activity is recommended in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to reduce hyperglycemia and cardiovascular risk. Effective aerobic exercise intensity, however, is not well defined. (2) Methods: 60 consecutive patients performed cardiopulmonary exercise testing (CPX) of 30 min duration targeting a respiratory exchange ratio (RER) between 0.85 and 0.95, being strictly aerobic. Plasma glucose (PG) was measured before and after CPX as well as one and two h after exercise. Maximum exercise intensity was evaluated using a standard bicycle exercise test. (3) Results: 50 patients completed the protocol (62 ± 10 years, BMI (body mass index) 30.5 ± 4.9 kg/m2, HbA1c (glycated haemoglobin) 6.9 ± 0.8%, left ventricular ejection fraction 55 ± 8%). Aerobic exercise capacity averaged at 32 ± 21 Watt (range 4–76 Watt) representing 29.8% of the maximum exercise intensity reached. PG before and after CPX was 9.3 ± 2.2 and 7.6 ± 1.7 mmol/L, respectively (p < 0.0001). PG was further decreased significantly at one and two h after exercise to 7.5 ± 1.6 mmol/L and 6.0 ± 1.0 mmol/L, respectively (p < 0.0001 for both as compared to PG before CPX). (4) Conclusions: Aerobic exercise capacity is very low in patients with CAD and T2DM. Exercise at aerobic intensity allowed for significant reduction of plasma glucose. Individual and effective aerobic exercise prescription is possible by CPX

Additional effects of psychological interventions on subjective and objective outcomes compared with exercise-based cardiac rehabilitation alone in patients with cardiovascular disease: A systematic review and meta-analysis

Background Exercise-based cardiac rehabilitation (ebCR) often includes various psychological interventions for lifestyle change or distress management. However, the additional benefit of specific psychological interventions on depression, anxiety, quality of life, cardiac morbidity and cardiovascular or total mortality is not well investigated. Design Systematic review and meta-analysis. Methods Randomized controlled trials and controlled cohort trials published between January 1995 and October 2017 comparing ebCR with or without pre-specified psychosocial interventions were selected and evaluated on the basis of predefined inclusion and outcome criteria. Results Out of 15,373 records, 20 studies were identified, including 4450 patients with coronary artery disease (88.5%) or congestive heart failure (11.5%), respectively. Studies were of low to moderate quality and methodological heterogeneity was high. As compared with ebCR alone, additional psychological interventions for lifestyle change or distress management showed a trend to reduce depressive symptoms (standardized mean difference -0.13, 95% confidence interval (CI) -0.30; 0.05). Furthermore, during a follow-up of five years, distress management was associated with a trend to reduce cardiac morbidity (risk ratio 0.74, 95% CI 0.51; 1.07). There was no evidence for an additional impact of either psychological lifestyle change interventions or distress management on anxiety, quality of life, cardiovascular or total mortality. Conclusions Specific psychological interventions offered during ebCR may contribute to a reduction of depressive symptoms and cardiac morbidity, but there remains considerable uncertainty under which conditions these interventions exert their optimal effects. (CRD42015025920)

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing

AbstractOBJECTIVESThe study investigates the correlation between left ventricular function and QRS duration obtained by alternate right ventricular pacing sites.BACKGROUND1. Right ventricular apical pacing is associated with alterations of left ventricular contraction sequence. 2. A stimulation producing narrow QRS complexes is supposed to provide for better left ventricular contraction patterns.METHODSFourteen patients with third degree AV block received one ventricular pacing lead in apical position. The alternate lead was attached to that site on the septum that produced the smallest QRS complex as measured from the earliest to the last deflection in any of the orthogonal Frank leads (xyz). During atrial synchronous ventricular pacing, the AV delay was optimized individually and for each stimulation site using mitral valve doppler or impedance cardiography. By radionuclide ventriculography, the phase distribution histogram of left ventricular contraction was evaluated as area under the curve (AuC); systolic function was determined as ejection fraction (EF) and as absolute ejected counts (EC) in random order. The difference (Δ) in QRS duration between apical and septal stimulation (Δxyz) was correlated with the difference in phase distribution (ΔAuC) and ejection parameters (ΔEF, ΔEC).RESULTSQRS duration was shorter with septal than with apical pacing in 9 out of 14 patients (64%); it was longer in 4 (29%), and no difference was seen in 1 patient. There was a significant positive correlation between the change in QRS duration (Δxyz) and phase distribution (ΔAuC: r = 0.66393, p = 0.010) and a significant negative correlation to systolic function (ΔEF: r = 0.70931, p = 0.004; ΔEC: r = 0.74368, p = 0.002).CONCLUSIONSIn atrial synchronous right ventricular pacing, if the AV delay is adapted individually, decreased QRS duration obtained by alternate pacing sites is significantly correlated with homogenization of left ventricular contraction and with increased systolic function in acute tests