Focus on Internal Urethrotomy as Primary Treatment for Untreated Bulbar Urethral Strictures: Results from a Multivariable Analysis

Background: The use of internal urethrotomy for treatment of urethral stricture remains a controversial topic in urology.Objective: To investigate outcomes and predictors of failure for internal urethrotomy as primary treatment for untreated bulbar urethral strictures.Design, setting, and participants: We performed a retrospective analysis of patients who underwent internal urethrotomy. Patients with bulbar urethral stricture who did not receive any previous treatment were included. Patients with traumatic, penile or posterior urethral strictures, lichen sclerosus, failed hypospadias repair, or stricture length >4 cm were excluded.Outcome measurements and statistical analysis: The primary outcome was treatment failure. Kaplan-Meyer plots were used to depict treatment failure-free survival. Univariate and multivariable Cox regression analyses were used to test the association between predictors (age, body mass index, diabetes, history of smoking, etiology, stenosis type and length, preoperative maximum flow [pQ(max)]) and treatment failure.Results and limitations: Overall, 136 patients were included. The median stricture length was 2 cm. Median follow-up was 55 mo. At 5-yr follow-up the failure-free survival rate was 57%. On univariate analysis, diabetes, nonidiopathic etiology, stricture length of 3-4 cm, and pQ(max) were significantly associated with treatment failure. These predictors were included in a multivariable analysis, in which pQ(max) was the only significant predictor of treatment failure.Conclusions: Failure of internal urethrotomy for untreated bulbar urethral strictures greatly depends on pQ(max) flow at uroflowmetry. Patients with pQ(max >) 8 ml/s have a high probability of success, while patients with pQ(max) <5 ml/s have a low probability of success.Patient summary: The use of internal urethrotomy in patients with an untreated bulbar urethral stricture should only be considered in selected cases. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved

Role of Mastoid Pneumatization in Temporal Bone Fractures

ABSTRACT BACKGROUND AND PURPOSE: The mastoid portion of the temporal bone has multiple functional roles in the organism, including regulation of pressure in the middle ear and protection of the inner ear. We investigated whether mastoid pneumatization plays a role in the protection of vital structures in the temporal bone during direct lateral trauma

StopCOVID cohort : An observational study of 3,480 patients admitted to the Sechenov University hospital network in Moscow city for suspected COVID-19 infection

© 2020 Oxford University Press. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record is available online at: https://doi.org/10.1093/cid/ciaa1535.BACKGROUND: The epidemiology, clinical course, and outcomes of COVID-19 patients in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically-diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow, between April 8 and May 28, 2020. RESULTS: Of the 4261 patients hospitalised for suspected COVID-19, outcomes were available for 3480 patients (median age 56 years (interquartile range 45-66). The commonest comorbidities were hypertension, obesity, chronic cardiac disease and diabetes. Half of the patients (n=1728) had a positive RT-PCR while 1748 were negative on RT-PCR but had clinical symptoms and characteristic CT signs suggestive of COVID-19 infection.No significant differences in frequency of symptoms, laboratory test results and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive SARS-CoV-2 RT-PCR.In a multivariable logistic regression model the following were associated with in-hospital mortality; older age (per 1 year increase) odds ratio [OR] 1.05 (95% confidence interval (CI) 1.03 - 1.06); male sex (OR 1.71, 1.24 - 2.37); chronic kidney disease (OR 2.99, 1.89 - 4.64); diabetes (OR 2.1, 1.46 - 2.99); chronic cardiac disease (OR 1.78, 1.24 - 2.57) and dementia (OR 2.73, 1.34 - 5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features were sufficient to diagnoseCOVID-19 infection indicating that laboratory testing is not critical in real-life clinical practice.Peer reviewe

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Cotton in the new millennium: advances, economics, perceptions and problems

Cotton is the most significant natural fibre and has been a preferred choice of the textile industry and consumers since the industrial revolution began. The share of man-made fibres, both regenerated and synthetic fibres, has grown considerably in recent times but cotton production has also been on the rise and accounts for about half of the fibres used for apparel and textile goods. To cotton’s advantage, the premium attached to the presence of cotton fibre and the general positive consumer perception is well established, however, compared to commodity man-made fibres and high performance fibres, cotton has limitations in terms of its mechanical properties but can help to overcome moisture management issues that arise with performance apparel during active wear. This issue of Textile Progress aims to: i. Report on advances in cotton cultivation and processing as well as improvements to conventional cotton cultivation and ginning. The processing of cotton in the textile industry from fibre to finished fabric, cotton and its blends, and their applications in technical textiles are also covered. ii. Explore the economic impact of cotton in different parts of the world including an overview of global cotton trade. iii. Examine the environmental perception of cotton fibre and efforts in organic and genetically-modified (GM) cotton production. The topic of naturally-coloured cotton, post-consumer waste is covered and the environmental impacts of cotton cultivation and processing are discussed. Hazardous effects of cultivation, such as the extensive use of pesticides, insecticides and irrigation with fresh water, and consequences of the use of GM cotton and cotton fibres in general on the climate are summarised and the effects of cotton processing on workers are addressed. The potential hazards during cotton cultivation, processing and use are also included. iv. Examine how the properties of cotton textiles can be enhanced, for example, by improving wrinkle recovery and reducing the flammability of cotton fibre

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

EDEM3 Domains Cooperate to Perform Its Overall Cell Functioning

EDEM3 recognizes and directs misfolded proteins to the ER-associated protein degradation (ERAD) process. EDEM3 was predicted to act as lectin or as a mannosidase because of its homology with the GH47 catalytic domain of the Man1B1, but the contribution of the other regions remained unresolved. Here, we dissect the molecular determinants governing EDEM3 function and its cellular interactions. LC/MS analysis indicates very few stable ER interactors, suggesting EDEM3 availability for transient substrate interactions. Sequence analysis reveals that EDEM3 consists of four consecutive modules defined as GH47, intermediate (IMD), protease-associated (PA), and intrinsically disordered (IDD) domain. Using an EDEM3 knock-out cell line, we expressed EDEM3 and domain deletion mutants to address EDEM3 function. We find that the mannosidase domain provides substrate binding even in the absence of mannose trimming and requires the IMD domain for folding. The PA and IDD domains deletions do not impair the trimming, but specifically modulate the turnover of two misfolded proteins, NHK and the soluble tyrosinase mutant. Hence, we demonstrate that EDEM3 provides a unique ERAD timing to misfolded glycoproteins, not only by its mannose trimming activity, but also by the positive and negative feedback modulated by the protease-associated and intrinsically disordered domain, respectively