The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain

Clinical Benefit in Patients with Advanced Solid Tumors Treated with Modified Citrus Pectin: A Prospective Pilot Study

Purpose We conducted a pilot trial to assess the tolerability, clinical benefit and antitumoral efficacy of modified (hydrolysed) citrus pectin (MCP) in 49 patients with various solid tumors in an advanced state of progression. MCP are hydrolysed from polysaccharide pectin fibers, derived from citrus fruits and acting as a ligand for Galectin-3. Preclinical investigations revealed an efficient inhibition of tumor development and metastasis in various tumor models. Patients and Methods The treatment consisted of the oral intake of 5 g MCP three times a day. One cycle of therapy was defined as 4 weeks of treatment. Objectives were clinical benefit (pain, functional performance, weight change), safety, tumor response (RESIST criteria) and quality of life (EORTC QLQ30). Results 49 patients were enrolled, 29 patients were able to be evaluated for clinical benefit after 2 cycles of treatment. All patients tolerated the therapy well without any severe therapy-related adverse events. After 2 cycles of oral intake of MCP, 6/29 patients (20.7%) had an overall clinical benefit response associated with a stabilization or improvement of life quality. On an intent to treat basis 11/49 patients (22,5%) showed a stable disease (SD) after 2 cycles and 6/49 patients (12,3%) had a SD for a period longer than 24 weeks. One patient suffering from metastasized prostate carcinoma showed a 50% decrease in serum PSA level after 16 weeks of treatment associated with a significant increase of clinical benefit, quality of life and decrease in pain. Conclusion MCP seems to have positive impacts especially regarding clinical benefit and life quality for patients with far advanced solid tumors. The presented preliminary data encourage us to further investigate the role of MCP in cancer prevention and treatment

Randomized controlled trial of a structured training program in breast cancer patients with tumor-related chronic Fatigue

Background: Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated. Patients and Methods: 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2. Results: There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group. Conclusions: Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients