Hao Wang

Background: Urinary tract infections (UTIs) are one of the most common infections worldwide, but little is known about their global scale and long-term trends. We aimed to estimate the spatiotemporal patterns of UTIs' burden along with its attributable risk factors at a global level, as well as the variations of the burdens according to socio-demographic status, regions, nations, sexes, and ages, which may be helpful in guiding targeted prevention and treatment programs. Methods: Data from the Global Burden of Disease Study 2019 were analyzed to depict the incidence, mortality, and disability-adjusted life years (DALYs) of UTIs in 204 countries and territories from 1990 to 2019 by socio-demographic status, nations, region, sex, and age. Results: Globally, 404.61 million cases, 236,790 deaths, and 520,200 DALYs were estimated in 2019. In particular, 2.4 times growth in deaths from 1990 to 2019 was observed, along with an increasing age-standardized mortality rate (ASMR) from 2.77/100,000 to 3.13/100,000. Age-standardized incidence rate (ASIR) was consistently pronounced in regions with higher socio-demographic index (SDI), which presented remarkable upward trends in ASMR and age-standardized DALY rate (ASDR). In contrast, countries with a low SDI or high baseline burden achieved a notable decline in burden rates over the past three decades. Although the ASIR was 3.6-fold higher in females than males, there was no sex-based difference in ASMR and ASDR. The burden rate typically increased with age, and the annual increasing trend was more obvious for people over 60 years, especially in higher SDI regions. Conclusions: The burden of UTIs showed variations according to socio-demographic status, nation, region, sex, and age in the last three decades. The overall increasing burden intimates that proper prevention and treatment efforts should be strengthened, especially in high-income regions and aging societies.

Importance: Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. Objective: To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. Design, Setting, and Participants: A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. Interventions: Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. Main Outcomes and Measures: The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. Results: The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%). Conclusions and Relevance: Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT1896232.

Electrospun hybrid nanofibers prepared using combinations of natural and synthetic polymers have been widely investigated in cardiovascular tissue engineering. In this study, electrospun gelatin/polycaprolactone (PCL) and collagen/poly(l-lactic acid-co-ε-caprolactone) (PLCL) scaffolds were successfully produced. Scanning electron micrographs showed that fibers of both membranes were smooth and homogeneous. Water contact angle measurements further demonstrated that both scaffolds were hydrophilic. To determine cell attachment and migration on the scaffolds, both hybrid scaffolds were seeded with human umbilical arterial smooth muscle cells. Scanning electron micrographs and MTT assays showed that the cells grew and proliferated well on both hybrid scaffolds. Gross observation of the transplanted scaffolds revealed that the engineered collagen/PLCL scaffolds were smoother and brighter than the gelatin/PCL scaffolds. Hematoxylin and eosin staining showed that the engineered blood vessels constructed by collagen/PLCL electrospun membranes formed relatively homogenous vessel-like tissues. Interestingly, Young's modulus for the engineered collagen/PLCL scaffolds was greater than for the gelatin/PCL scaffolds. Together, these results indicate that nanofibrous collagen/PLCL membranes with favorable mechanical and biological properties may be a desirable scaffold for vascular tissue engineering.

BACKGROUND:: The prognostic significance of serum albumin levels in patients with sepsis has previously been reported; however, these studies have not excluded the potential confounding effect of exogenous albumin administration. In this study, we investigate the predictive value of serum albumin for the prognosis of severe sepsis without the interference of exogenous albumin administration. METHODS:: A prospective cohort study was conducted from April to November 2014 in the internal and surgical intensive care units of a tertiary care hospital. During the study period, due to a supply shortage, patients were not treated with human albumin. Serum albumin levels were measured, and laboratory and clinical data were collected at the onset of severe sepsis. Prognostic factors were analyzed using receiver operating characteristic curve and multivariate Cox proportional hazard regression analysis. Survival was assessed by Kaplan-Meier method. RESULTS:: One hundred sixteen patients were included in the study. The overall 28-day mortality was 26.7%. The most common infection sources were lower respiratory tract, abdomen/pelvis, and bloodstream. Compared to patients who survived, those who died had lower serum albumin levels and higher Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Receiver operating characteristic curves demonstrate that albumin level is a strong predictor of 28-day mortality, and the optimal cutoff value maximizing sensitivity and specificity is 29.2 g/L. Through multivariate Cox regression analysis, low serum albumin levels (<29.2 g/L) and APACHE II scores are identified as independent risk factors for mortality. Patients with lower serum albumin levels more often had abdominal/pelvic sources of infection, acute kidney or liver injury, septic shock, and higher APACHE II and SOFA scores. The 28-day survival rate was lower for patients with serum albumin below 29.2 g/L than for patients with serum albumin at or above this level. CONCLUSION:: Having excluded potential confounding effect of exogenous albumin administration, low serum albumin levels are associated with an increased risk of death in patients with severe sepsis.