Sciatic Nerve Injury Secondary to a Gluteal Compartment Syndrome.

Gluteal compartment syndrome (GCS) is extremely rare, with a low index of suspicion among physicians, hence, it is highly overlooked. The underdiagnosis can lead to irreversible tissue ischemia and severe neurological deficits. GCS is a surgical emergency and requires immediate surgical intervention given its high morbidity and mortality. Based on the limited available literature, multiple etiologies have been postulated including traumatic and nontraumatic causes. This article presents a complex and unusual case of GCS after prolonged immobilization in an IV drug abuser who was subjected to initial missed diagnosis.

Effective Management of Femur Fracture Using Damage Control Orthopedics Following Fat Embolism Syndrome.

Fat embolism syndrome (FES) is a rare event following a traumatic injury, and its pathophysiologic mechanism continues to be elusive. Fat embolism syndrome generally occurs when a bone marrow fat enters the bloodstream resulting in a cascade of inflammatory response, hyper-coagulation, and an array of symptoms that generally begin within 24-48 hours. FES early symptoms include petechial rash, shortness of breath, altered mental status, seizures, fever, and may result in decreased urine output. The common etiologies of a fat embolism include long bone fractures, mainly femoral and pelvic fractures.  There are multiple management methods described in the literature to help prevent FES and other long bone fracture complications from occurring. Although not universally adopted, the damage control orthopedics (DCO) has been the major management option for patients with a long bone fracture. DCO is entertained by provisional immobilization of patients with long bone fractures and those who are considered severely traumatized patients (STP). Thus, immobilization can help minimize the traumatic effect and the subsequent second hit by performing non-life saving surgical procedures. In this case, a patient with a transverse femur fracture suffered disconcerting symptoms of fat embolism prior to definitive femur repair. Hence, damage control orthopedics was entertained with a postponement of his femur repair to facilitate stabilization. The use of damage control orthopedics was successful in this patient with no long term complications.

Revisiting disease genes based on whole-exome sequencing in consanguineous populations.

Assigning a causal role for genes in disease states is one of the most significant medical applications of human genetics research. The requirement for at least two different pathogenic alleles in the same gene in individuals with a similar phenotype to assign a causal link has not always been fully adhered to, and we now know that even two alleles may not necessarily constitute sufficient evidence. Autozygosity is a rich source of natural "knockout" events by virtue of rendering ancestral loss-of-function (LOF) variants homozygous. In this study, we exploit this phenomenon by examining 523 exomes enriched for autozygosity to call into question previously published disease links for several genes based on the identification of confirmed homozygous LOF variants in the absence of the purported diseases. This study highlights an additional advantage of consanguineous populations in the quest to improve the medical annotation of the human genome.

Molecular pathogenesis of congenital diaphragmatic hernia revealed by exome sequencing, developmental data, and bioinformatics.

Congenital diaphragmatic hernia (CDH) is a common and severe birth defect. Despite its clinical significance, the genetic and developmental pathways underlying this disorder are incompletely understood. In this study, we report a catalog of variants detected by a whole exome sequencing study on 275 individuals with CDH. Predicted pathogenic variants in genes previously identified in either humans or mice with diaphragm defects are enriched in our CDH cohort compared with 120 size-matched random gene sets. This enrichment was absent in control populations. Variants in these critical genes can be found in up to 30.9% of individuals with CDH. In addition, we filtered variants by using genes derived from regions of recurrent copy number variations in CDH, expression profiles of the developing diaphragm, protein interaction networks expanded from the known CDH-causing genes, and prioritized genes with ultrarare and highly disruptive variants, in 11.3% of CDH patients. These strategies have identified several high priority genes and developmental pathways that likely contribute to the CDH phenotype. These data are valuable for comparison of candidate genes generated from whole exome sequencing of other CDH cohorts or multiplex kindreds and provide ideal candidates for further functional studies. Furthermore, we propose that these genes and pathways will enhance our understanding of the heterogeneous molecular etiology of CDH.

Undergraduate research: an innovative student-centered committee from the Kingdom of Saudi Arabia.

INTRODUCTION: Concern has been expressed in recent times whether medical schools have adapted sufficiently to cater for the increasing demand of physician-scientists. Studies have shown that research involvement at the undergraduate level is vital to accommodate this growing need. Enhanced communication skills, improved problem-solving abilities and better future employment opportunities are among the other many benefits of undergraduate research (UR). Herein, we report projects run by a unique student driven undergraduate research committee (URC) at Alfaisal University, Riyadh, Saudi Arabia aimed at providing the future generation of physicians training opportunities for pursuing a research intensive career. METHODS: The article describes the unique structure of the URC and provides an in-depth description of the various programs and activities used in promoting students' research activities. We analyzed students' perception of URC activities via a questionnaire and analyzed research-output of the first graduating batches through their publication record. RESULTS: Overall, more than 60% of the graduating students were involved in the various research programs offered by the URC and around 50% published in peer-reviewed journals with an average impact factor of 2.4. CONCLUSIONS: Research involvement by medical students is an essential need of the twenty-first century and models like URC could provide crucial platform for research training to the new generation of physician-scientists.

Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes.

Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time.