An updated meta-analysis on the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor treatment of anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses. METHODS: A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias. RESULTS: Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety. CONCLUSIONS: HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial.

BACKGROUND: A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA. METHODS: Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan-Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF. RESULTS: A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8-62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7-60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ±â€Š15.9 mL/h vs. 169.0 ±â€Š15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study. CONCLUSIONS: When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice. REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR-IPR-17012629).

Clinical Characteristics and Short-Term Outcomes of Severe Patients With COVID-19 in Wuhan, China.

Background: A novel pneumonia (COVID-19) spread rapidly throughout worldwide, in December, 2019. Most of the deaths have occurred in severe and critical cases, but information on prognostic risk factors for severely ill patients is incomplete. Further research is urgently needed to guide clinicians, and we therefore prospectively evaluate the clinical outcomes of 114 severely ill patients with COVID-19 for short-term at the Union Hospital in Wuhan, China. Methods: In this single-centered, prospective, and observational study, we enrolled 114 severely ill patients with confirmed COVID-19 from Jan 23, 2020, to February 22, 2020. Epidemiological, demographic, laboratory, treatment, and outcome data were recorded, and the risk factors for poor outcome were analyzed. Results: Among the 114 enrolled patients with a mean age of 63.96 ± 13.41 years, 94 (82.5%) patients were classified as a good outcome group. Common clinical manifestations included fever, cough, and fatigue. Compared with the good outcome group, 20 (17.5%) patients in the poor outcome group more frequently exhibited lymphopenia, and lower levels of albumin, partial arterial oxygen pressure, higher levels of lactate dehydrogenase, creatine kinase, hypersensitive troponin I, C-reactive protein, ferritin, blood urea nitrogen, and D-dimer, as well as markedly higher levels of IL-6 and IL-10. Absolute numbers of T lymphocytes, CD8 + T cells, decreased in almost all the patients and were markedly lower in the poor outcome group than the good outcome group. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from a severe to mild condition. In addition, univariate and multivariate Cox analyses of potential factors for poor outcome patients indicated that cytokine storms and uncontrolled inflammation responses as well as liver, kidney, and cardiac dysfunction are related to the development of a poor outcome. Conclusion: In summary, we reported this single-centered, prospective, and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storms and uncontrolled inflammation responses as well as liver, kidney, and cardiac dysfunction may play important roles in the final outcome of severely ill patients with COVID-19. Our study will allow clinicians to benefit and rapidly estimate the likelihood of a short-term poor outcome for severely ill patients.

Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components.

The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 µg/L (83.17-107.41) vs. 92.66 µg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 µg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 µg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 µg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 µg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 µg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.

Procyanidins Extracted from Lotus Seedpod Ameliorate Amyloid-ß-Induced Toxicity in Rat Pheochromocytoma Cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is characterized by extracellular senile plaque deposits, intracellular neurofibrillary tangles, and neuronal apoptosis. Amyloid-ß (Aß) plays a critical role in AD that may cause oxidative stress and downregulation of CREB/BDNF signaling. Anti-Aß effect has been discussed as a potential therapeutic strategy for AD. This study aimed to identify the amelioration of procyanidins extracted from lotus seedpod (LSPC) on Aß-induced damage with associated pathways for AD treatment. Rat pheochromocytoma (PC12) cells incubated with Aß 25-35 serve as an Aß damage model to evaluate the effect of LSPC in vitro. Our findings illustrated that LSPC maintained the cellular morphology from deformation and reduced apoptosis rates of cells induced by Aß 25-35. The mechanisms of LSPC to protect cells from Aß-induced damage were based on its regulation of oxidation index and activation of CREB/BDNF signaling, including brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP-responsive element-binding (CREB), protein kinase B (also known as AKT), and the extracellular signal-regulated kinase (ERK). Of note, by high-performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS), several metabolites were detected to accumulate in vivo, part of which could take primary responsibility for the amelioration of Aß-induced damage on PC12 cells. Taken together, our research elucidated the effect of LSPC on neuroprotection through anti-Aß, indicating it as a potential pretreatment for Alzheimer's disease.