Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients undergoing laparoscopic renal or prostatic surgery (BLISS trial): study protocol for a randomized controlled trial

Perioperative Medicine: Efficacy, Safety and Outcom

Transurethral and suprapubic mesh resection after Prolift® bladder perforation: a case report

Bladder perforation is a complication which can occur after a Prolift® procedure and may enhance vesicovaginal fistula formation. Different methods of management of bladder perforation caused by mesh procedures are described in the literature, and most authors advise complete excision of the mesh. In the case described in this article, we propose a combined transurethral and suprapubical approach as the optimal method for maximal tape removal, being both minimally invasive and less damaging to the vesical wall. A suprapubical catheter can be removed shortly after surgery to enable optimal tissue healing of the vesical mucosa

Guideline on urothelial carcinoma of the bladder

Urothelial carcinoma of the bladder is diagnosed predominantly in people over 60 years of age. The most common symptom is haematuria. Smoking is an important risk factor (relative risk 2.5 to 3). Cystoscopy is performed whenever bladder carcinoma is suspected. The recurrence rate of a non-muscle invasive urothelial carcinoma is high (31-78% within 5 years). A single intravesical instillation with a chemotherapeutic agent within 24 hours of transurethral resection (TUR) reduces the risk of recurrence. Carcinoma in situ (CIS) should be treated as high-grade urothelial carcinoma. Standard treatment for patients with non-metastasized muscle-invasive urothelial carcinoma is cystectomy in combination with extensive lymph node dissection. There are several possibilities for urinary diversion following cystectomy, none of which are any better than the others. Bladder-sparing brachytherapy may be used in patients with solitary T1 - T2 urothelial carcinoma &lt; 5 cm. Neoadjuvant cisplatin-containing chemotherapy prior to cystectomy in muscle-invasive carcinoma only slightly improves survival. Cisplatin-containing combination chemotherapy is the standard treatment for metastasized urothelial carcinoma.</p

Widespread genomic influences on phenotype in Dravet syndrome, a ‘monogenic’ condition

Dravet syndrome is an archetypal rare severe epilepsy, considered “monogenic”, typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. Polygenic risk scores for intelligence are lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study

Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Alzheimer's Society; FundRef: http://dx.doi.org/10.13039/501100000320Funder: Leverhulme Trust; FundRef: http://dx.doi.org/10.13039/501100000275Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Department of Health; FundRef: http://dx.doi.org/10.13039/501100000276Funder: Evelyn Trust; FundRef: http://dx.doi.org/10.13039/501100004282Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Abstract: Objective: To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design: Cohort study. Setting: National Health Service, England, including secondary and tertiary care. Participants: 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. Intervention: Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. Main outcome measure: Definite or probable genetic diagnosis. Results: A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. Conclusion: Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments