Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.

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 A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) 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 ß-integrin 1 (ITGß1). 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.

Phenotypic severity scoring system and categorisation for prune belly syndrome: application to a pilot cohort of 50 living patients.

OBJECTIVE: To design a novel system of scoring prune belly syndrome (PBS) phenotypic severity at any presenting age and apply it to a large pilot cohort. PATIENTS AND METHODS: From 2000 to 2017, patients with PBS were recruited to our prospective PBS study and medical records were cross-sectionally analysed, generating individualised RUBACE scores. We designed the pragmatic RUBACE-scoring system based on six sub-scores (R: renal, U: ureter, B: bladder/outlet, A: abdominal wall, C: cryptorchidism, E: extra-genitourinary, generating the acronym RUBACE), yielding a potential summed score of 0-31. The 'E' score was used to segregate syndromic PBS and PBS-plus variants. The cohort was scored per classic Woodard criteria and RUBACE scores compared to Woodard category. RESULTS: In all, 48 males and two females had a mean (range) RUBACE score of 13.8 (8-25) at a mean age of 7.3 years. Segregated by phenotypic categories, there were 39 isolated PBS (76%), six syndromic PBS (12%) and five PBS-plus (10%) cases. The mean RUBACE scores for Woodard categories 1, 2, and 3 were 20.5 (eight patients), 13.8 (25), and 10.6 (17), respectively (P < 0.001). CONCLUSIONS: 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.

Straight to the Operating Room: An Emergent Surgery Track for Acute Testicular Torsion Transfers.

OBJECTIVE: To assess the effect of implementing an emergency surgery track for testicular torsion transfers. We hypothesized that transferring children from other facilities diagnosed with torsion straight to the operating room (STOR) would decrease ischemia time, lower costs, and reduce testicular loss. STUDY DESIGN: Demographics, arrival to incision time, hospital cost in dollars, and testicular outcome (determined by testicular ultrasound) at follow-up were retrospectively compared in all patients transferred to our tertiary care children's hospital with a diagnosis of testicular torsion from 2012 to 2016. Clinical data for STOR and non-STOR patients were compared by Wilcoxon rank-sum, 2-tailed t test, or Fisher exact test as appropriate. RESULTS: Sixty-eight patients met inclusion criteria: 35 STOR and 33 non-STOR. Children taken STOR had a shorter median arrival to incision time (STOR: 54 minutes vs non-STOR: 94 minutes, P < .0001) and lower median total hospital costs (STOR: $3882 vs non-STOR: $4419, P < .0001). However, only 46.8% of STOR patients and 48.4% of non-STOR patients achieved surgery within 6 hours of symptom onset. Testicular salvage rates in STOR and non-STOR patients were not significantly different (STOR: 68.4% vs non-STOR: 36.8%, P = .1), but follow-up was poor. CONCLUSIONS: 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.

Copy number variations in a population with prune belly syndrome.

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 six patients; parental samples were unavailable in two 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.

Laparoscopic Appendectomy: A Report on 1164 Operations at a Single-Institution, Safety-Net Hospital.

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.

Violencia en áreas de emergencia del Hospital Dr. Domingo Luciani / Violence in emergency areas of the Hospital Dr. Domingo Luciani

Conocer la frecuencia, características y clasificación etaria de las agresiones hacia el personal del área de emergencia y la frecuencia y causas de su subregistro durante el año 2015 en el Hospital Dr. Domingo Luciani (tipo IV) en Caracas, Venezuela. Métodos: Estudio observacional, descriptivo, aplicando una encuesta previamente pilotada y validada por un grupo de expertos al personal tanto profesional como obrero del área de emergencia. Resultados: Del total de encuestas obtenidas (150) se encontraron 115 (73%) trabajadores agredidos, todos por agresión verbal y 18 (12%) acompañados de agresión física. De estos casos 85 (56%) no habrían sido reportados, los principales motivos fueron: creer que el registro es inútil (23%) y considerar normal este tipo de hechos (20%.) El perfil del profesional agredido: femenino, enfermera, 19-30 años, enfermera con turnos nocturnos. Perfil del agresor: familiar de paciente, masculino, entre 21-29 años. Conclusión: La violencia hacia el personal de emergencias se encontró presente en un alto porcentaje, pero a su vez la mayoría de estas agresiones no se registraron por lo que no es posible llevar a cabo las medidas preventivas. Por ello vemos necesario realizar campañas de información en cuanto a registro detallado de los hechos para establecer protocolos de acción en las situaciones con mayor frecuencia de agresión, como lo es la comunicación a familiares sobre difuntos, para de esta manera lograr prevenir futuros actos de violencia(AU)

To know the frequency, characteristics and classification group in aggression towards the staff of the emergency area and the frequency and causes of their under-reporting for the year 2015 at the Hospital Dr. Domingo Luciani (type IV) in Caracas, Venezuela. Methods: An observational study, descriptive, applying a survey previously piloted and validated by a group of experts to both professional and working-class area of emergency personnel. Results: Of the total number of surveys obtained (150), were found 115 (73%) workers assaulted, all verbal assault and 18 (12%) accompanied by physical assault. Of these 85 cases (56%) would have been unreported, the main reasons were: believe that registration is useless (23%) and be considered normal for this type of events (20%). Assaulted professional profile: female, nurse, 19-30 years, nurse with night shifts. Profile of the aggressor: patient family, male, aged 21-29. Conclusion: Violence against emergency personnel found in a high percentage, but at the same time most of these attacks were not recorded so it is not possible to carry out preventive measures. That is why we see necessary campaigns of information as detailed record of the facts to establish protocols for action in situations with higher frequency of aggression, such as communication to family members of deceased, thus preventing future acts of violence(AU)