Angelica sinensis extract induces telomere dysfunction, cell cycle arrest, and mitochondria-mediated apoptosis in human glioblastoma cells.

Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12-15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.

Sunitinib-related high-grade proteinuria and allograft dysfunction in a kidney recipient: a rare case report.

BACKGROUND: Sunitinib-induced high-grade proteinuria and irreversible renal allograft dysfunction are rare conditions. Here, we present a patient who had received renal allograft and later developed metastatic clear cell renal cell carcinoma(cc-mRCC), for which he was prescribed sunitinib. High-grade proteinuria, hypoalbuminemia, peripheral edema and renal allograft dysfunction (manifesting as an increase in the serum creatinine concentration) occurred 5 months after sunitinib prescription. CASE PRESENTATION: The patient was a 58-year-old male who had end-stage renal disease with regular hemodialysis through arteriovenous fistula for 17 years since 1998 and received a renal allograft from a deceased kidney donor in 2015. Unfortunately, in 2019, the patient developed cc-mRCC originating from the left native kidney. We suggested a needle biopsy on left native kidney or radical left nephrectomy, but the patient refused. Sunitinib was prescribed. Follow-up urine analysis showed proteinuria (500 mg/dL) 2 weeks after sunitinib prescription. He was hospitalized 5 months later because of body weight gain, decreased urine output, pitting edema of both lower extremities, and shortness of breath. The image studies showed progression in his cc-mRCC. His serum creatinine level and spot urine protein at admission increased to 4.26 mg/dL and 300 mg/dL, respectively. He agreed on a biopsy for the renal allograft and the pathology studies showed focal segmental glomerulosclerosis, acute interstitial nephritis, and acute tubular injury. Based on the time sequence of clinical presentations with the laboratory and pathological findings, sunitinib-induced renal allograft dysfunction secondary to high-grade proteinuria was most likely. Despite of discontinuation of sunitinib and increased dose of everolimus, renal impairment progressed. Thus, he had to receive hemodialysis starting 2 week after hospitalization. Unfortunately, the patient died of advanced metastasis despite of aggressive medical treatments 3 weeks after admission. CONCLUSION: This case report is a reminder that renal allograft dysfunction can happen secondary to proteinuria after taking sunitinib. Hence, clinicians must regularly check renal function and urine protein for renal allograft recipients. Monitoring and modifying drug prescription, especially sunitinib, is necessary if persistent proteinuria accompanied by deteriorating serum creatinine level occurs. Renal biopsy may be considered if more evidence is required to make a differential diagnosis.

Parathyroidectomy Improves the Consumption of Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease (ESRD) patients, and it can suppress erythropoiesis. We aimed to investigate the relationship between the consumption of erythropoiesis-stimulating agents (ESAs) and parathyroidectomy (PTX) in ESRD patients with SHPT and to determine the predictors for anemia improvement. The current standard of chronic kidney disease anemia therapy relies on the prescription of iron supplementation, and ESA. We retrospectively analyzed 81 ESRD patients with PTX at Ditmanson Medical Foundation Chiayi Christian Hospital from July 2004 to Dec 2018. The requirement of ESA therapy markedly declined from a dose of 41.6 (interquartile range [IQR], 0−91.2) to 10.3 (IQR, 0−59.5, p = 0.001) unit/kg/week. In addition, 63.7% of patients required iron replacement therapy preoperatively and the proportion reduced to 52.5% after PTX (p < 0.001). The hemoglobin (Hb) level showed an insignificant change from a median value of 10.7 g/dL (9.5−11.6 g/dL) before PTX to 10.5 g/dL (9.6−11.2 g/dL) at 6 months after PTX. A preoperative Hb level ≤ 10 mg/dL (odds ratio [OR], 20.1; 95% confidence interval [CI], 4.71−125, p < 0.001) and transferrin saturation (TSAT) < 25% (OR, 12.8; 95% CI, 2.51−129, p < 0.001) were predictors for anemia improvement. Our study demonstrated that PTX markedly decreased the requirement of ESA. Patients with a low preoperative Hb level or low TSAT showed an increase in the Hb level after PTX. PTX may be considered not only for SHPT with refractory anemia but also for high ESA-dependent patients.

Risk of acute coronary syndrome after parathyroidectomy in patients with end-stage renal disease: A population-based cohort study in Taiwan.

AIM: Patients with end-stage renal disease (ESRD) who received parathyroidectomy (PTX) had persistently reduced levels of parathyroid hormone. This study investigated the risk of acute coronary syndrome (ACS) in patients with ESRD who underwent PTX using a nationwide health insurance claims database. METHODS: Of all ESRD patients, we selected 1047 individuals who had undergone PTX between 2000 and 2008 as the PTX group and 4188 patients who did not undergo PTX (non-PTX group) matched by propensity score. Multivariable Cox proportional hazards regression analysis was conducted for assessing the excess ACS risk for the PTX group compared to the non-PTX group. RESULTS: The mean follow-up periods were 4.63 and 4.04 years for the PTX and non-PTX groups, respectively. A significant reduction in the risk of ACS (adjusted hazard ratio = 0.74, 95% confidence interval = 0.57-0.96) was observed for the ESRD patients after PTX. CONCLUSIONS: Parathyroidectomy is associated with reduced risk of ACS in patients with ESRD.

Melioidotic necrotizing fasciitis presenting as a supraclavicular mass.

Melioidosis is an infection caused by Burkholderia pseudomallei that usually involves the respiratory tract. It may manifest as pneumonia, septicemia, or localized infection. We present here a case of melioidosis initially manifesting as a mass over the supraclavicular area and subsequently progressing to necrotizing fasciitis. With appropriate antimicrobial treatment and adequate surgical debridement, localized melioidosis can be treated successfully. Melioidosis should be considered in the differential diagnosis of neck masses, especially in patients who have traveled to or stayed in an endemic area.

Close correlation between the ankle-brachial index and symptoms of depression in hemodialysis patients.

BACKGROUND: As both of peripheral arterial disease (PAD) and depression carried a poor prognosis in patients on maintenance hemodialysis (MHD), we investigated the correlation between the ankle-brachial index (ABI), an indicator of subclinical PAD, and symptoms of depression in patients on MHD. METHODS: One hundred and twenty-nine patients on MHD (75 males and 54 females, mean age 64.8 ± 12 years) were enrolled in this cross-sectional study, which aimed at evaluating the relationship between symptoms of depression and ABI. Demographic as well as clinical and laboratory variables including status of diabetes, chronic hepatitis C infection, dialysis duration, Charlson comorbidity index (CCI), plasma levels of albumin, C-peptide, insulin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin, and lipid profile were obtained. The self-administered beck depression inventory (BDI) was used to determine the presence or absence of symptoms of depression, and depression was defined as a BDI score ≧14. Multivariable-adjusted linear regression models were constructed to confirm the independent association of biologic parameters of symptoms of depression. Significance was defined as P < 0.05. Statistical analyses were performed using SPSS/Windows software (SPSS Science, v. 15.0, Chicago, IL). RESULTS: The mode of multivariate analysis showed that diabetes (ß = 3.594; P = 0.040), hepatitis C infection (ß = 4.057; P = 0.008), levels of serum albumin (ß = -5.656; P = 0.024), C-peptide (ß = -0.292; P = 0.002), ABI (ß = -9.041; P = 0.031), and Ln-transformed hsCRP were significantly associated with BDI. CONCLUSIONS: Hepatitis C infection, serum levels of albumin, C-peptide, and ABI levels were found to be correlated with BDI (P < 0.05).

Factors Associated with the Choice of Peritoneal Dialysis in Patients with End-Stage Renal Disease.

BACKGROUND: The purpose of this study was to analyze the factors associated with receiving peritoneal dialysis (PD) in patients with incident end-stage renal disease (ESRD) in a hospital in Southern Taiwan. METHODS: The study included all consecutive patients with incident ESRD who participated in a multidisciplinary predialysis education (MPE) program and started their first dialysis therapy between January 1, 2008, and June 30, 2013, in the study hospital. We provided small group teaching sessions to advanced CKD patients and their family to enhance understanding of various dialysis modalities. Multivariate logistic regression models were used to analyze the association of patient characteristics with the chosen dialysis modality. RESULTS: Of the 656 patients, 524 (80%) chose hemodialysis and 132 chose PD. Our data showed that young age, high education level, and high scores of activities of daily living (ADLs) were positively associated with PD treatment. Patients who received small group teaching sessions had higher percentages of PD treatment (30.5% versus 19.5%; P = 0.108) and preparedness for dialysis (61.1% versus 46.6%; P = 0.090). CONCLUSION: Young age, high education level, and high ADL score were positively associated with choosing PD. Early creation of vascular access may be a barrier for PD.

Parathyroidectomy Is Associated with Reduced Mortality in Hemodialysis Patients with Secondary Hyperparathyroidism.

Secondary hyperparathyroidism increases morbidity and mortality in hemodialysis patients. The Kidney Disease Outcomes Quality Initiative Guidelines recommend parathyroidectomy for patients with chronic kidney disease and parathyroid hormone concentrations exceeding 800 pg/mL; however, this concentration represents an arbitrary cut-off value. The present study was conducted to identify factors influencing mortality in hemodialysis patients with parathyroid hormone concentrations exceeding 800 pg/mL and to evaluate the effects of parathyroidectomy on outcome for these patients. Two hundred twenty-one hemodialysis patients with parathyroid hormone concentrations > 800 pg/mL from July 2004 to June 2010 were identified. 21.1% of patients (n = 60) received parathyroidectomy and 14.9% of patients (n = 33) died during a mean follow-up of 36 months. Patients with parathyroidectomy were found to have lower all-cause mortality (adjusted hazard ratio [aHR]: 0.34). Other independent predictors included age ≥ 65 years (aHR: 2.11) and diabetes mellitus (aHR: 3.80). For cardiovascular mortality, parathyroidectomy was associated with lower mortality (HR = 0.31) but with a marginal statistical significance (p = 0.061). In multivariate analysis, diabetes was the only significant predictor (aHR: 3.14). It is concluded that, for hemodialysis patients with parathyroid hormone concentrations greater than 800 pg/mL, parathyroidectomy is associated with reduced all-cause mortality.