Early utilization of hypertonic peritoneal dialysate and subsequent risks of non-traumatic amputation among peritoneal dialysis patients: a nationwide retrospective longitudinal study

BACKGROUND: The hemodialysis (HD) population has a particularly high incidence of amputation, which is likely associated with decreased tissue oxygenation during HD. However, information about the risk factors leading to amputation in peritoneal dialysis (PD) patients is limited. Here, we have investigated the association between the use of hypertonic peritoneal dialysate (HPD) and subsequent amputation in PD patients. METHODS: Based on the data from the Taiwan National Health Insurance research database, this observational cohort study enrolled 203 PD patients who had received HPD early during treatment and had not undergone amputation and 296 PD controls who had not undergone amputation. Subjects were followed through until the end of 2009 and the event rates of new non-traumatic amputation were compared between groups. RESULTS: The incidence of amputation was 3 times higher for the HPD cohort than for the comparison cohort (23.68 vs. 8.01 per 1000 person-years). The hazard ratio (HR) for this group, estimated using a multivariable Cox model, was 2.48 (95% confidence interval [CI] = 1.06–5.79). The HR for patients with both diabetes and early adoption of HPD increased to 44.34 (95% CI = 5.51-357.03), compared to non-HPD non-diabetic PD controls. CONCLUSION: Early utilization of HPD in PD patients is associated with increasing risk of amputation; this risk considerably increases for those with concomitant diabetes

Assessment of Sarcopenia and Obesity in Patients with Myasthenia Gravis Using Dual-Energy X-ray Absorptiometry: A Cross-Sectional Study

Sarcopenia and obesity can negatively impact quality of life and cause chronic fragility, and are associated with neuromuscular diseases, including myasthenia gravis (MG). The long-term consequences of body composition changes in chronic MG remain unknown; we therefore evaluated changes in body composition, including sarcopenia, obesity, lean body mass, and the prevalence of sarcopenic obesity in patients. In this cross-sectional study, 35 patients with MG (mean age: 56.1 years) and 175 matched controls were enrolled. Body fat mass and skeletal muscle mass were measured using whole body dual-energy X-ray absorptiometry. Patients with MG exhibited a higher prevalence of obesity and higher android adiposity and total body fat percentage than those of controls. Although the prevalence of sarcopenia and sarcopenic obesity did not increase with age, there was a decrease in arm and android muscle mass in patients with MG compared with controls. Lower muscle mass percentages were correlated with increased age and MG severity, but not with corticosteroid use. Thus, MG is associated with increased risk for obesity and decreased muscle mass with aging, regardless of corticosteroid use. Therefore, accurate diagnosis of body composition changes in MG could facilitate the application of appropriate therapies to promote health, improve quality of life, and prevent fragility

Changes in Physical Fitness and Body Composition Associated with Physical Exercise in Patients with Myasthenia Gravis: A Longitudinal Prospective Study

There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity remains unknown. In this prospective study, we enrolled 34 patients with MG with stable condition and evaluated the disease severity, physical fitness parameters, and body composition (measured using whole-body dual-energy X-ray absorptiometry (DXA)), before and after conducting a 24-week physical exercise regimen of aerobic and resistance strength training. The outcomes were measured by DXA, quantitative MG (QMG) score, quality of life score, handgrip strength and walking speed. During the training regimen, participants were free to decide how many exercise sessions per week and regularly reported their weekly exercise time. The physical exercise program was well tolerated by the participants, the parameters of the QMG score and handgrip strength improved, and participants’ body composition did not change significantly. The high exercise group experienced greater deterioration in muscle mass in the arms, but exhibited a greater improvement in forced vital capacity, walking speed, and symptom severity. The group with low QMG scores improved more in terms of physical fitness, including walking speed. These findings indicate that physical exercise is well tolerated by patients with MG, and is accompanied by improved muscular and physical functions. We propose that physical exercise is safe, effective, and appropriate for patients with well-regulated MG

Utilization of Decision Tree Algorithms for Supporting the Prediction of Intensive Care Unit Admission of Myasthenia Gravis: A Machine Learning-Based Approach

Myasthenia gravis (MG), an acquired autoimmune-related neuromuscular disorder that causes muscle weakness, presents with varying severity, including myasthenic crisis (MC). Although MC can cause significant morbidity and mortality, specialized neuro-intensive care can produce a good long-term prognosis. Considering the outcomes of MG during hospitalization, it is critical to conduct risk assessments to predict the need for intensive care. Evidence and valid tools for the screening of critical patients with MG are lacking. We used three machine learning-based decision tree algorithms, including a classification and regression tree, C4.5, and C5.0, for predicting intensive care unit (ICU) admission of patients with MG. We included 228 MG patients admitted between 2015 and 2018. Among them, 88.2% were anti-acetylcholine receptors antibody positive and 4.7% were anti-muscle-specific kinase antibody positive. Twenty clinical variables were used as predictive variables. The C5.0 decision tree outperformed the other two decision tree and logistic regression models. The decision rules constructed by the best C5.0 model showed that the Myasthenia Gravis Foundation of America clinical classification at admission, thymoma history, azathioprine treatment history, disease duration, sex, and onset age were significant risk factors for the development of decision rules for ICU admission prediction. The developed machine learning-based decision tree can be a supportive tool for alerting clinicians regarding patients with MG who require intensive care, thereby improving the quality of care

MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D3 in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells

Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH)2D3 analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH)2D3 in inhibiting cell growth in a dose- and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G0/G1 phase as compared to 1α,25(OH)2D3, possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH)2D3 in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted

Determination of Epicenters before Earthquakes Utilizing Far Seismic and GNSS Data: Insights from Ground Vibrations

Broadband seismometers, ground-based Global Navigation Satellite Systems (GNSS), and magnetometers that were located within an epicentral distance of approximately 150 km consistently observed the novel anomalous behaviors of the common-mode ground vibrations approximately 5–10 days before the M6.6 Meinong earthquake in Taiwan. The common-mode ground vibrations with amplitudes near 0.1 m at frequencies ranging from 8 × 10−5 to 2 × 10−4 Hz were generated near the region close to the epicenter of the impending earthquake. The common-mode vibrations were consistently observed in seismic and GNSS data associated with five other earthquakes in four distinct areas. The results reveal that the common-mode vibrations could be a typical behavior before earthquakes. The causal mechanism of common-mode vibrations can be attributed to crustal resonance excitations before fault dislocations occur. Potential relationships with other pre-earthquake anomalies suggest that the common-mode vibrations could be ground motion before earthquakes, which was investigated for a significant length of time

Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer

Advanced prostate cancer is a very heterogeneous disease reflecting in diverse regulations of oncogenic signaling pathways. Aberrant spatial dynamics of epidermal growth factor receptor (EGFR) promote their dimerization and clustering, leading to constitutive activation in oncogenesis. The EphB2 and Src signaling pathways are associated with the reorganization of the cytoskeleton leading to malignancy, but their roles in regulating EGFR dynamics and activation are scarcely reported. Using single-particle tracking techniques, we found that highly phosphorylated EGFR in the advanced prostate cancer cell line, PC3, was associated with higher EGFR diffusivity, as compared with LNCaP and less aggressive DU145. The increased EGFR activation and biophysical dynamics were consistent with high proliferation, migration, and invasion. After performing single-cell RNA-seq on prostate cancer cell lines and circulating tumor cells from patients, we identified that upregulated gene expression in the EphB2 and Src pathways are associated with advanced malignancy. After dasatinib treatment or siRNA knockdowns of EphB2 or Src, the PC3 cells exhibited significantly lower EGFR dynamics, cell motility, and invasion. Partial inhibitory effects were also found in DU145 cells. The upregulation of parts of the EphB2 and Src pathways also predicts poor prognosis in the prostate cancer patient cohort of The Cancer Genome Atlas. Our results provide evidence that overexpression of the EphB2 and Src signaling pathways regulate EGFR dynamics and cellular aggressiveness in some advanced prostate cancer cells