Exercise Training in Elderly People Undergoing Hemodialysis: A Systematic Review and Meta-analysis

Previous reviews have indicated the effectiveness of exercise in people undergoing hemodialysis. However, these analyses did not take into account whether the subjects were elderly. We performed a systematic review of the effects of exercise training in elderly people undergoing hemodialysis and updated the evidence of exercise for people undergoing hemodialysis by adding recent research data. Methods: We searched 8 electronic databases up to June 2016. Inclusion criteria were as follows: randomized controlled trial, English publication, subjects aged 18 and older undergoing hemodialysis, evaluation of physical function as an outcome of exercise intervention. We defined elderly as age 60 years and older. The main outcomes were exercise tolerance (peak/maximum oxygen consumption) and walking ability (6-minute walk distance). Secondary outcomes were lower extremity muscle strength and quality of life. Results: After screening of 10,923 references, 30 comparisons were entered into the analysis. However, because we found only 1 study in which elderly subjects were treated, we could not perform a meta-analysis for these people. For the general population undergoing hemodialysis, supervised exercise training was shown to significantly increase peak/maximum oxygen consumption (standard mean difference, 0.62; 95% confidence interval 0.38–0.87; P < 0.001), 6-minute walk distance (standard mean difference, 0.58; 95% confidence interval 0.24–0.93; P < 0.001), lower extremity muscle strength (standard mean difference, 0.94; 95% confidence interval 0.67–1.21; P < 0.001), and quality of life (standard mean difference, 0.53; 95% confidence interval 0.52–0.82; P < 0.001). Discussion: Our analysis on the effectiveness of exercise training in elderly people undergoing hemodialysis as compared with nonelderly people was somewhat inconclusive. Future studies should be carried out for elderly people to identify the most favorable exercise program for this population

The Distinct Roles of LKB1 and AMPK in p53-Dependent Apoptosis Induced by Cisplatin

Liver kinase B1 (LKB1) is a serine/threonine protein kinase that acts as a key tumor suppressor protein by activating its downstream kinases, such as AMP-activated protein kinase (AMPK). However, the regulatory actions of LKB1 and AMPK on DNA damage response (DDR) remain to be explored. In this study, we investigated the function of LKB1 in DDR induced by cisplatin, a representative DNA-damaging agent, and found that LKB1 stabilizes and activates p53 through the c-Jun N-terminal kinase (JNK) pathway, which promotes cisplatin-induced apoptosis in human fibrosarcoma cell line HT1080. On the other hand, we found that AMPK&alpha;1 and &alpha;2 double knockout (DKO) cells showed enhanced stabilization of p53 and increased susceptibility to apoptosis induced by cisplatin, suggesting that AMPK negatively regulates cisplatin-induced apoptosis. Moreover, the additional stabilization of p53 and subsequent apoptosis in AMPK DKO cells were clearly canceled by the treatment with the antioxidants, raising the possibility that AMPK suppresses the p53 activation mediated by oxidative stress. Thus, our findings unexpectedly demonstrate the reciprocal regulation of p53 by LKB1 and AMPK in DDR, which provides insights into the molecular mechanisms of DDR

Acute leukemias in pregnant women: Results of a retrospective study at a local tertiary‐care hospital in Japan

Abstract Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed cases of pregnancy‐associated leukemia consecutively diagnosed and treated at a local tertiary‐care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia [AML] and two acute lymphoblastic leukemia [ALL]). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy‐associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high‐risk features at the diagnosis (AML with an FLT3‐ITD mutation [n = 1] and relapsed ALL [n = 1]) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy‐associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care

Determinants of Slow Walking Speed in Ambulatory Patients Undergoing Maintenance Hemodialysis

<div><p>Walking ability is significantly lower in hemodialysis patients compared to healthy people. Decreased walking ability characterized by slow walking speed is associated with adverse clinical events, but determinants of decreased walking speed in hemodialysis patients are unknown. The purpose of this study was to identify factors associated with slow walking speed in ambulatory hemodialysis patients. Subjects were 122 outpatients (64 men, 58 women; mean age, 68 years) undergoing hemodialysis. Clinical characteristics including comorbidities, motor function (strength, flexibility, and balance), and maximum walking speed (MWS) were measured and compared across sex-specific tertiles of MWS. Univariate and multivariate logistic regression analyses were performed to examine whether clinical characteristics and motor function could discriminate between the lowest, middle, and highest tertiles of MWS. Significant and common factors that discriminated the lowest and highest tertiles of MWS from other categories were presence of cardiac disease (lowest: odds ratio [OR] = 3.33, 95% confidence interval [CI] = 1.26–8.83, P<0.05; highest: OR = 2.84, 95% CI = 1.18–6.84, P<0.05), leg strength (OR = 0.62, 95% CI = 0.40–0.95, P<0.05; OR = 0.57, 95% CI = 0.39–0.82, P<0.01), and standing balance (OR = 0.76, 95% CI = 0.63–0.92, P<0.01; OR = 0.81, 95% CI = 0.68–0.97, P<0.05). History of fracture (OR = 3.35, 95% CI = 1.08–10.38; P<0.05) was a significant factor only in the lowest tertile. Cardiac disease, history of fracture, decreased leg strength, and poor standing balance were independently associated with slow walking speed in ambulatory hemodialysis patients. These findings provide useful data for planning effective therapeutic regimens to prevent decreases in walking ability in ambulatory hemodialysis patients.</p></div

Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos

Abstract Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) triggers a noncanonical form of programmed cell death (PCD) called parthanatos, yet the mechanisms of its induction are not fully understood. We have recently demonstrated that the aggresome-like induced structures (ALIS) composed of the autophagy receptor SQSTM1/p62 and K48-linked polyubiquitinated proteins (p62-based ALIS) mediate parthanatos. In this study, we identified the D1 dopamine receptor agonist YM435 as a unique parthanatos inhibitor that acts as the disaggregating agent for the p62-based ALIS. We found that YM435 structurally reduces aggregability of the ALIS, and then increases its hydrophilicity and liquidity, which prevents parthanatos. Moreover, dopamine and L-DOPA, a dopamine precursor, also prevented parthanatos by reducing the aggregability of the ALIS. Together, these observations suggest that aggregability of the p62-based ALIS determines the sensitivity to parthanatos, and the pharmacological properties of YM435 that reduces the aggregability may be suitable for therapeutic drugs for parthanatos-related diseases such as neurodegenerative diseases

Differences in the clinical characteristics, maximum walking speed, and motor function across tertiles of maximum walking speed.

<p>Differences in the clinical characteristics, maximum walking speed, and motor function across tertiles of maximum walking speed.</p