Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2 , including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.

A 72-year-old man presented with urinary retention, weight loss, haematuria and severe acute kidney injury. He had never before been admitted to hospital and his past medical history included only an inguinal hernia. On examination, he appeared uraemic and had a right-sided painful hernia. A three-way catheter was inserted, bladder washouts performed and irrigation started. An ultrasound showed severe bilateral hydronephrosis and a ‘thickened bladder’ and this was thought to be obstructive uropathy secondary to bladder cancer. Twenty-four hours later his hernia doubled in diameter, became incarcerated and a CT of the abdomen and pelvis showed an inguinal hernia of both bladder and bowel, with the catheter tip inside the bladder hernia. He was taken to theatres and an open mesh repair was performed with a rigid cystoscopy to assist in locating and reducing the bladder. He required intensive care and dialysis postoperatively and remains on regular dialysis following discharge.

Background. Point-of-care (POC) lung ultrasound (LUS) is widely used in the emergency setting and there is an established evidence base across a range of respiratory diseases, including previous viral epidemics. The necessity for rapid testing combined with the limitations of other diagnostic tests has led to the proposal of various potential roles for LUS during the COVID-19 pandemic. This systematic review and meta-analysis focused specifically on the diagnostic accuracy of LUS in adult patients presenting with suspected COVID-19. Methods. Traditional and grey-literature searches were performed on June 1st 2021. Two authors independently carried out the searches, selected studies and completed the Quality Assessment Tool for Diagnostic Test Accuracy Studies (QUADAS-2). Meta-analysis was carried out using established open-source packages in R. We report overall sensitivity, specificity, positive and negative predictive values and the hierarchical summary receiver operating characteristic curve for LUS. Heterogeneity was determined using the I2 statistic. Results. Twenty studies were included, providing data from a total of 4,314 patients. The prevalence and admission rates were generally high across all studies. Overall LUS was found to be 87.2% sensitive (95% CI 83.6-90.2) and 69.5% specific (95% CI 62.2-72.5) and demonstrated overall positive and negative predictive values of 3.0 (95% 2.3-4.1) and 0.16 (95% 0.12-0.22) respectively. Separate analyses for each reference standard revealed similar sensitivities and specificities for LUS. Heterogeneity between studies was found to be high, and QUADAS-2 assessment identified risks of bias in many studies. Conclusion. During a period of high prevalence, LUS is a highly sensitive diagnostic test for COVID-19. However, more research is required to confirm these results in more generalisable populations, including those less likely to be admitted to hospital.