Constitutional SMARCB1 mutations at 22q11.23 have been found in ~50% of familial and <10% of sporadic schwannomatosis cases1. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ~80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1.
Introduction Hip arthroplasty (HA) is commonly performed to treat various hip pathologies. Its volume is expected to rise further due to the increasing age of the population. Complication rates are low; however, periprosthetic femoral fractures (PFF) are a rare, albeit serious, complication with substantial economic impact. While current guidelines propose revision with long-stemmed prostheses for all Vancouver B2 and B3 PFF, some recent research papers suggest that open reduction with internal fixation (ORIF) could lead to an equivalent outcome. Our aim was to summarize the evidence, elucidating under which circumstances ORIF leads to a favorable outcome after B2 and B3 PFF compared with revision surgery. Materials and methods A systematic literature search was performed to identify studies on patients treated with ORIF and with stem revision after B2 and/or B3 fractures. Extracted information included initial pathology, stem fixation mechanism, bone quality and stem stability at the time of PFF, clinical outcomes, and mortality. Results of individual studies were summarized in a table in lieu of a quantitative data synthesis due to a lack of standardized information. Results We identified 14 original research articles including both patients treated with ORIF and with stem revision after B2 and/or B3 PFF. Five studies included statistical comparisons, all were in favor of ORIF or indeterminate. The common lack of rigorous statistical analyses and significant methodological weaknesses made identification of outcome predictors impossible. Conclusion The choice of treatment modality for PFF depends on fracture, implant, and bone characteristics. Recent data show that successful outcome can be achieved without revising loose stems. ORIF may be a viable option if bone stock is adequate around uncemented or tapered polished stems with an intact cement mantle and the fracture geometry allows stable anatomic reconstruction. Conceptional considerations support this idea, but more data are needed to identify outcome predictors.
ObjectiveTo gain information about the advantages/disadvantages of an implementation of patient-reported outcome measures (PROM) into the clinical routine of trauma/orthopaedic surgeons, and to identify the technical constraints confronting a successful implementation of PROMs.DesignOnline survey.ParticipantsSurgeons who are members of the AO Foundation.MeasuresParticipants answered questions regarding demographics, their familiarity with specific and generic PROMs and the use of PROMs in clinical routine. Furthermore, reasons for/against using PROMs, why not used more often, prerequisites to implement PROMs into clinical routine and whether PROMs would be implemented if adequate tools/technologies were available, were solicited. Χ2 tests and multivariable logistic regressions were conducted to evaluate the effect of the AO Region, surgeon specialisation, current position, clinical experience, and workplace on the familiarity with disease-specific PROMs, the familiarity with generic PROMs and the current use of PROMs. Exploratory factor analysis was used to identify issues underlying the extent of PROM usage.Results1212 surgeons completed the survey (response rate: 6.8%; margin of error: ±2.72%): 54.2% were trauma/orthopaedic surgeons, 16.6% were spine surgeons, 27.9% were craniomaxillofacial surgeons and 16 had no defined specialty. Working in a certain AO Region, surgical specialisation and current workplace were associated with a higher familiarity of disease-specific PROMs and the use of PROMs in daily clinical routine (p≤0.05). Exploratory factor analysis identified four categories important for the use of PROMs and two categories preventing the use of PROMs. In case of the availability of an adequate tool, 66.2% of surgeons would implement PROMs in clinical routine.ConclusionsOur survey results provide an understanding of the use of PROMs in clinical routine. There is consensus on the usefulness of PROMs. User-friendly and efficient tools/technologies would be a prerequisite for the daily use of PROMs. Additionally, educational efforts and/or policies might help.
Background and purposeTo achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF.Patients and methodsWe included children and adolescents (0–17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs.ResultsOf 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures.Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents.InterpretationThe pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome.
Purpose: Congenital disorders of glycosylation (CDG) result from mutations in N-glycan biosynthesis. Mutations in phosphomannomutase (PMM2) cause CDG-Ia. Here, we report four clinically mild patients and their mutations in PMM2. Methods: Analysis of the PMM2 cDNA and gene revealed the mutations affecting the glycosylation efficiency. Results: The patients have 30% to 50% normal PMM activity in fibroblasts due to different mutations in PMM2, and we studied the effect of each mutation on the PMM activity in a Saccharomyces cerevisiae expression system. Conclusions: Each patient carried a severe mutation that decreased the PMM activity to less than 10% as well as a relatively mild mutation. A new mutation, deletion of base 24, changed the reading frame. The C9Y, C241S, and L32R mutations showed 27% to 45% activity when expressed in the eukaryotic expression system, and the more severe D148N was shown to be thermolabile. Genet Med 2001:3(6):393-398.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.