In this individual patient data meta-analysis, age, site, injured nerve, and delay significantly influenced prognosis after microsurgical repair of median and ulnar nerve injuries.

No abstract

HOXD13, the most 5' gene of the HOXD cluster, encodes a homeodomain transcription factor with important functions in limb patterning and growth. Heterozygous mutations of human HOXD13, encoding polyalanine expansions or frameshifts, are believed to act by dominant negative or haploinsufficiency mechanisms and are predominantly associated with synpolydactyly phenotypes. Here, we describe two mutations of HOXD13 (923C-->G encoding Ser308Cys and 940A-->C encoding Ile314Leu) that cause missense substitutions within the homeodomain. Both are associated with distinctive limb phenotypes in which brachydactyly of specific metacarpals, metatarsals, and phalangeal bones is the most constant feature, exhibiting overlap with brachydactyly types D and E. We investigated the binding of synthetic mutant proteins to double-stranded DNA targets in vitro. No consistent differences were found for the Ser308Cys mutation compared with the wild type, but the Ile314Leu mutation (which resides at the 47th position of the homeodomain) exhibited increased affinity for a target containing the core recognition sequence 5'-TTAC-3' but decreased affinity for a 5'-TTAT-3' target. Molecular modeling of the Ile314Leu mutation indicates that this mixed gain and loss of affinity may be accounted for by the relative positions of methyl groups in the amino acid side chain and target base.

Data collection and analysis A minimum of two review authors independently reviewed search results to select studies for inclusion by using pre-specified criteria, assessed risk of bias of included studies and extracted data from included studies. We grouped outcomes into the following categories: (1) hand function, (2) other patient-reported outcomes (e.g. satisfaction, pain), (3) early objective outcomes (e.g. correction of angular deformity), (4) late objective outcomes (e.g. recurrence) and (5) adverse effects. Main results We included 14 articles describing 13 studies, comprising 11 single-centre studies and two multi-centre studies. These studies involved 944 hands of 940 participants; of these, 93 participants were reported twice in separate articles describing early and late outcomes of one trial. Three papers reported the outcomes of two trials comparing different procedures. One trial compared needle fasciotomy versus fasciectomy (125 hands, 121 participants), and the other compared interposition firebreak skin grafting versus z-plasty closure of fasciectomy (79 participants). The other 11 studies reported trials of technical refinements of procedures or rehabilitation adjuncts. Of these, three investigated effects of postoperative splinting on surgical outcomes. Ten studies (11 articles) were randomised controlled trials (RCTs) of varying methodological quality; one was a controlled clinical trial. Trial design was unclear in two studies awaiting classification. All trials had high or unclear risk of at least one type of bias. High risks of performance and detection bias were particularly common. We downgraded the quality of evidence (Grades of Recommendation, Assessment, Development and Evaluation-GRADE) of outcomes to low because of concerns about risk of bias and imprecision. Outcomes measured varied between studies. Five articles assessed recurrence; two defined this as reappearance of palpable disease and two as deterioration in angular deformity; one did not explicitly define recurrence. Hand function on the Disabilities of the Arm, Shoulder and Hand (DASH) Scale (scores between 0 and 100, with higher scores indicating greater impairment) was 5 points lower after needle fasciotomy than after fasciectomy at five weeks. Patient satisfaction was better after fasciotomy at six weeks, but the magnitude of effect was not specified. Fasciectomy improved contractures more effectively in severe disease: Mean percentage reduction in total passive extension deficit at six weeks for Tubiana grades I and II was 11% lower after needle fasciotomy than after fasciectomy, whereas for grades III and IV disease, it was 29% and 32% lower. Paraesthesia (defined as subjective tingling sensation without objective evidence of altered sensation) was more common than needle fasciotomy at one week after fasciectomy (228/1000 vs 67/1000), but reporting of complications was variable. By five years, satisfaction (on a scale from 0 to 10, with higher scores showing greater satisfaction) was 2.1/10 points higher in the fasciect...

A locus for triphalangeal thumb, variably associated with pre-axial polydactyly, was previously identified in the zone of polarizing activity regulatory sequence (ZRS), a long range limb-specific enhancer of the Sonic Hedgehog (SHH) gene at human chromosome 7q36.3. Here, we demonstrate that a 295T>C variant in the human ZRS, previously thought to represent a neutral polymorphism, acts as a dominant allele with reduced penetrance. We found this variant in three independently ascertained probands from southern England with triphalangeal thumb, demonstrated significant linkage of the phenotype to the variant (LOD = 4.1), and identified a shared microsatellite haplotype around the ZRS, suggesting that the probands share a common ancestor. An individual homozygous for the 295C allele presented with isolated bilateral triphalangeal thumb resembling the heterozygous phenotype, suggesting that the variant is largely dominant to the wild-type allele. As a functional test of the pathogenicity of the 295C allele, we utilized a mutated ZRS construct to demonstrate that it can drive ectopic anterior expression of a reporter gene in the developing mouse forelimb. We conclude that the 295T>C variant is in fact pathogenic and, in southern England, appears to be the most common cause of triphalangeal thumb. Depending on the dispersal of the founding mutation, it may play a wider role in the aetiology of this disorder.

Extravasation injuries are common emergencies in clinical practice. If they are not recognized and treated promptly, they can lead to deleterious functional and cosmetic outcomes. There is a vast range of agents involved in these injuries and marked paucity of evidence to support their specific management. Following an extensive literature review, we outline management principles for clinicians involved in the care of patients with extravasation injuries. Key parameters in deciding appropriate management plans include the volume/toxicity of the agent, the necrosis interval of the injury, patient-related factors, as well as the facilities and expertise available in the setting of individual cases of extravasation.

Several centres have already proved the technical and immunologic feasibility of partial or full-thickness abdominal wall transplantation. It is an effective option to achieve primary abdominal closure following intestinal transplantation and in its full-thickness form, it may be useful for monitoring rejection in visceral organs.

These authors contributed equally.Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 AE 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection.