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Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.
No full textMale hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH
Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation.
No full text[Figure: see text]
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.
No full textBACKGROUND & AIMS
Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease.
METHODS
We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals).
RESULTS
Single-marker association analyses found approximately 100 loci displaying P < 5 × 10, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively).
CONCLUSIONS
This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus
Treatment and outcome in children with tuberculous meningitis - a multi-centre Paediatric Tuberculosis Network European Trials Group study.
No full textINTRODUCTION
Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings.
METHODS
Multicentre, retrospective study involving 27 paediatric healthcare institutions in nine European countries via an established paediatric TB research network, before and after the 2014 revision of WHO dosing recommendations.
RESULTS
Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard four-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (IQR 4.5-21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of one or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention and mechanical ventilation as risk factors for unfavourable outcome.
DISCUSSION
There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future
Dermatological surgery: an update on suture materials and techniques. Part 2.
No full textThis is the second part of a two-part series summarizing the latest evidence related to suture materials and wound closure techniques in dermatological surgery. We critically appraised evidence focusing on the following consequences of suture choice: scar/cosmesis, pain, patient satisfaction, cost, infection and wound complications. We searched the databases MEDLINE, PubMed and Embase using the keywords 'skin surgery', 'dermatological surgery', 'sutures', 'braided sutures', 'monofilament sutures' and 'antibacterial sutures' to identify relevant English-language articles. This part of the review assesses the evidence for different types of buried sutures, including braided vs. monofilament sutures, longer-absorbing sutures and antibacterial sutures. The majority of trials were noted to be of poor quality, single-centre (thus lacking external validity) and underpowered, which presents challenges in comparing suture techniques in skin surgery. Future large-scale, multicentre, randomized trials are needed, with both surgeon and patient-assessed validated outcomes
Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis.
No full textBACKGROUND AND AIMS
Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).
METHODS
PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.
RESULTS
We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.
CONCLUSIONS
When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.
LAY SUMMARY
Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring
SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.
No full textB cell depleting agents are amongst the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B cell depleting agents: a cohort of patients treated for haematological B cell malignancy and another treated for rheumatological disease. B cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B cell reconstitution, however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses, however shorter intervals between vaccine doses (36m previously) vaccine non-responsiveness was independent of peripheral B cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2
Multi-omics-based identification of atopic dermatitis target genes and their potential associations with metabolites and miRNAs.
No full textAtopic dermatitis (AD), or atopic eczema, is one of the most common inflammatory skin diseases with up to 10% prevalence in adults, and approximately 15-20% in children in industrialized countries. As a result, there is an unmet need for faster, safer, and effective treatments for AD. AD pathogenesis represents a complex interplay between multiple factors, such as environmental factors or stimuli, genetic factors, immune dysfunctions. However, although multi-omics label studies have been very useful in understanding the pathophysiological mechanisms of AD and its clinical manifestations, there have been very few studies that integrate different labels of omics data. Here, we attempted to integrate gene expression and metabolomics datasets from multiple different publicly available AD cohort datasets and conduct an integrated systems-level AD analysis. We used four different GEO transcriptome data sets and, by applying an elastic net machine learning algorithm, identified robust hub genes that can be used as signatures, for example, H2AFX, MCM7, ESR1 and SF3A2. Moreover, we investigated potential associations of those genes by applying a pathway-based approach over metabolomics and miRNA datasets. Our results revealed potential novel associations between fatty acids and peroxisomal lipid metabolism pathways, as well as with several microRNAs
Ward-Based Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure Unrelated to Chronic Obstructive Pulmonary Disease.
No full textBackground
The use of ward-based noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) unrelated to chronic obstructive pulmonary disease (COPD) remains controversial. This study evaluated the outcomes and failure rates associated with NIV application in the ward-based setting for patients with AHRF unrelated to COPD.
Methods
A multicentre, retrospective cohort study of patients with AHRF unrelated to COPD was conducted. COPD was not the main reason for hospital admission, treated with ward-based NIV between February 2004 and December 2018. All AHRF patients were eligible; exclusion criteria comprised COPD patients, age < 18 years, pre-NIV pH < 7.35, or a lack of pre-NIV blood gas. In-hospital mortality was the primary outcome; univariable and multivariable models were constructed. The obesity-related AHRF group included patients with AHRF due to obesity hypoventilation syndrome (OHS), and the non-obesity-related AHRF group included patients with AHRF due to pneumonia, bronchiectasis, neuromuscular disease, or fluid overload.
Results
In total, 479 patients were included in the analysis; 80.2% of patients survived to hospital discharge. Obesity-related AHRF was the indication for NIV in 39.2% of all episodes and was the aetiology with the highest rate of survival to hospital discharge (93.1%). In the multivariable analysis, factors associated with a higher risk of in-hospital mortality were increased age (odds ratio, 95% CI: 1.034, 1.017-1.051, < 0.001) and pneumonia on admission (5.313, 2.326-12.131, < 0.001). In the obesity-related AHRF group, pre-NIV pH < 7.15 was associated with significantly increased in-hospital mortality (7.800, 1.843-33.013, =0.005); however, a pre-NIV pH 7.15-7.25 was not associated with increased in-hospital mortality (2.035, 0.523-7.915, =0.305).
Conclusion
Pre-NIV pH and age have been identified as important predictors of surviving ward-based NIV treatment. Moreover, these data support the use of NIV in ward-based settings for obesity-related AHRF patients with pre-NIV pH thresholds down to 7.15. However, future controlled trials are required to confirm the effectiveness of NIV use outside critical care settings for obesity-related AHRF
