Effects of moderate-to-high intensity resistance training in patients with chronic heart failure.

AIM: To systematically review the methodological quality of and summarize the effects of moderate-to-high intensity resistance training (alone or in combination with endurance training) in patients with clinically stable chronic heart failure (CHF). METHODS AND RESULTS: Four non-randomized controlled trials and 6 randomized controlled trials have been identified, reviewed for relevant results, and assessed for safety monitoring and methodological quality. None of the 10 trials scored positive for all methodological criteria on the Delphi list. Failure to conceal treatment allocation, failure to blind the outcome assessor(s), failure to blind care provider and failure to use an intention-to-treat analysis strategy were the most prevalent methodological shortcomings. The effects of resistance training (alone or in combination with endurance training) are inconclusive for outcomes like exercise capacity and disease-specific quality of life. CONCLUSIONS: The current peer-reviewed literature does not provide appealing evidence that moderate-to-high intensity resistance training has statistically significant and clinically relevant positive effects on important outcome measures, such as peak aerobic capacity and disease-specific quality of life. In fact, a majority of the trials had severe methodological limitations. Even though moderate-to-high intensity resistance training does not seem be harmful for patients with CHF, the current peer-reviewed evidence seems inadequate to generally recommend incorporation of resistance training into exercise-based rehabilitation programs for patients with CHF

Effects of neuromuscular electrical stimulation of muscles of ambulation in patients with chronic heart failure or COPD: a systematic review of the English-language literature.

Despite optimal drug treatment, many patients with CHF or COPD still suffer from disabling dyspnea, fatigue and exercise intolerance. They also exhibit significant changes in body composition. Attempts to rehabilitate these patients are often futile because conventional exercise training modalities are limited by the severity of exertional dyspnea. Therefore, there is substantial interest in new training modalities that do not evoke dyspnea, such as transcutaneous neuromuscular electrical stimulation (NMES). Herein, we systematically review the literature that addresses the effects of NMES applied to the muscles of ambulation. We focused on the effects of NMES on strength, exercise capacity, and disease-specific health status in patients with CHF or COPD. We also address the methodological quality of the reported studies as well as the safety of NMES. Manuscripts published prior to December 2007 were identified by searching the Medline /PubMed, Embase, Cochrane Controlled Trials Register, CINAHL and The Physical Therapy Evidence Database (PEDro) databases. Fourteen trials were identified: nine trials that examined NMES in CHF and five in COPD. PEDro scores for methodological quality of the trials were generally moderate tot good. Many of the studies reported significant improvements in muscle strength, exercise capacity and/or health status. Nonetheless the limited number of studies, the disparity in patient populations and variability in NMES methodology prohibit the use of meta-analysis. Yet, from the viewpoint of a systematic review NMES looks promising as a means of rehabilitating patients with COPD and CHF. At least, there is sufficient evidence to warrant more large prospective RCTs

PD-L1 checkpoint blockade promotes regulatory T cell activity that underlies therapy resistance.

Despite the clinical success of immune checkpoint blockade (ICB), in certain cancer types, most patients with cancer do not respond well. Furthermore, in patients for whom ICB is initially successful, this is often short-lived because of the development of resistance to ICB. The mechanisms underlying primary or secondary ICB resistance are incompletely understood. Here, we identified preferential activation and enhanced suppressive capacity of regulatory T cells (T(reg) cells) in αPD-L1 therapy-resistant solid tumor-bearing mice. T(reg) cell depletion reversed resistance to αPD-L1 with concomitant expansion of effector T cells. Moreover, we found that tumor-infiltrating T(reg) cells in human patients with skin cancer, and in patients with non-small cell lung cancer, up-regulated a suppressive transcriptional gene program after ICB treatment, which correlated with lack of treatment response. αPD-1/PD-L1-induced PD-1(+) T(reg) cell activation was also seen in peripheral blood of patients with lung cancer and mesothelioma, especially in nonresponders. Together, these data reveal that treatment with αPD-1 and αPD-L1 unleashes the immunosuppressive role of T(reg) cells, resulting in therapy resistance, suggesting that T(reg) cell targeting is an important adjunct strategy to enhance therapeutic efficacy