RUBACE is a practical, organ/system level, phenotyping tool designed to grade PBS severity and categorise patients into isolated PBS, syndromic PBS, and PBS-plus groups. This standardised system will facilitate genotype-phenotype correlations and future prospective multicentre studies assessing medical and surgical treatment outcomes.

Background: Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases. Methods: We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations. Results: We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin ) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19-21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1). Conclusions: FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

Laparoscopic appendectomy (LA) is the standard of care for the treatment of acute appendicitis. There is an ongoing debate regarding the optimal management of appendicitis, which led us to study outcomes after an appendectomy at a large safety-net hospital. We hypothesize that despite a high-risk population, LA remains a safe and effective treatment for acute appendicitis. A retrospective review was performed of all patients who underwent an appendectomy from 2011 to 2013. The primary end point was significant morbidity defined as a score of three or greater on the Clavien-Dindo scale of surgical morbidity. Thousand hundred and sixty-four patients underwent an appendectomy. A total of 1102 (94.7%) patients underwent either an LA or laparoscopic converted to open appendectomy, and 62 (5.3%) patients underwent an open appendectomy (OA). Two hundred and forty six patients (21.1%) had complicated appendicitis. Laparoscopic converted to OA conversion rate was 4.4 per cent and differed between years (P < 0.001). LA had a significantly shorter length of stay, shorter length of postoperative antibiotics, and less postoperative morbidity. When limited to only patients with complicated appendicitis, major morbidity was still greater in the OA group (22.6 vs 52.0%, P = 0.001). Length of stay was significantly longer in the OA group [3.42 (2.01, 5.97) vs 7.04 (5.05, 10.13), P < 0.001]. Odds for complication were 2.6 times greater in the OA group compared with the LA group. In the absence of peritonitis and systemic illness necessitating urgent laparotomy, patients who are laparoscopic surgical candidates should be offered an LA. Our study demonstrates that these patients have better outcomes and shorter hospital stays.

STOR decreased arrival to incision time and hospital cost but did not affect testicular loss. The bulk of ischemia time in torsion transfers occurred before arrival at our tertiary care center. Further interventions addressing delays in diagnosis and transfer are needed to truly improve testicular salvage rates in these patients.

Prune Belly Syndrome (PBS) is a congenital multisystem myopathy with mild to lethal severity. While of uncertain etiology, 95% male predominance and familial occurrence suggest a genetic basis. As copy number variations (CNVs) can cause unexplained genetic disorders, we tested for novel CNVs in a large PBS population. We genotyped 21 unrelated PBS patients by high-resolution array comparative genomic hybridization (aCGH) and phenotyped using a novel PBS severity scoring system. Available parents were screened for detected CNV via quantitative PCR (qPCR). We additionally screened for recurrence of identified novel candidate CNVs on 106 PBS probands by qPCR. We identified 10 CNVs in 8 of 21 PBS patients tested (38%). Testing confirmed inheritance from an unaffected biological parent in 6 patients; parental samples were unavailable in 2 probands. One candidate CNV includes duplication of the X-chromosome AGTR2 gene, known to function in urinary tract development. Subsequent screening of the larger PBS cohort did not identify any recurrent CNVs. Presence of CNV did not correlate with PBS severity scoring. CNVs were uncommon in this large PBS population, but analysis of identified variants may inform disease pathogenesis and reveal targets for therapeutic intervention for this rare, severe disorder.

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