Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

Background  

Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain.     

GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles—continuous outcomes

Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of the outcome measure are not easily interpretable, choosing a threshold to create a binary outcome and presenting relative and absolute effects become a more attractive alternative.When studies use different measures of the same construct, calculating summary measures requires converting to the same units of measurement for each study. The longest standing and most widely used approach is to divide the difference in means in each study by its standard deviation and present pooled results in standard deviation units (standardized mean difference). Disadvantages of this approach include vulnerability to varying degrees of heterogeneity in the underlying populations and difficulties in interpretation. Alternatives include presenting results in the units of the most popular or interpretable measure, converting to dichotomous measures and presenting relative and absolute effects, presenting the ratio of the means of intervention and control groups, and presenting the results in minimally important difference units. We outline the merits and limitations of each alternative and provide guidance for meta-analysts and guideline developers.     

Prognostic factors associated with survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation: an Australian multicenter cohort study

Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom...     

COVID-19 therapeutics: Challenges and directions for the future

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the next pandemic challenge and to allow rapid and cost-effective development of new therapeutics with equitable delivery.     

Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study

PurposeTo define the risk of hypogonadism following microdissection testicular sperm extraction in cases of non-obstructive azoospermia. While sperm retrieval by open testicular sperm extraction can be associated with an increased risk of hypogonadism, there is limited data addressing which procedures and which patients harbor the greatest risk.MethodsWe report on a community-acquired, nested, case-cohort of non-obstructive azoospermic patients referred to one clinic after failed bilateral microdissection testicular sperm extraction. Patients were health-matched (1:2) to surgically naïve controls and divided into 2 cohorts based on risk factors for hypogonadism. Among microdissection patients, we compared total testosterone and gonadotropin levels before and > 6 months after surgery. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Hormone levels were compared to risk-matched controls. Comparative statistics were used to assess hormone levels within and between cohorts.ResultsThere were no significant differences in baseline testosterone levels between microdissection patients (n = 26) and risk-matched controls (n = 52). At a mean of 26 months (range 6.2–112.8) post-procedure, mean testosterone levels decreased significantly (73 ng/dL or 16%; CI − 27, − 166; p < 0.01, paired t-test). Among microdissection patients with baseline testosterone > 300 ng/dL, 8/22 (36%) experienced hypogonadism post-procedure. There was a corresponding increase in follicle stimulating hormone (p = 0.05) and a trending increase in luteinizing hormones (p = 0.10).ConclusionA durable decrease in testosterone levels occurs after failed microdissection testicular sperm extraction regardless of baseline risk of hypogonadism. In addition, a significant proportion of eugonadal patients will become hypogonadal after failed testicular microdissection procedures.     

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Background To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.Methods Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.Results Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.Conclusions These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.Subject terms: Prognostic markers, Colorectal cancer