Charcot foot reconstruction outcomes: A systematic review

BackgroundCharcot neuroarthropathy is a complex condition characterised by progressive deformity, limited treatment options and a high amputation rate. Surgical reconstruction of Charcot foot has been proposed as a method to preserve the foot. However, limited information exists on the different methods of reconstruction available, their outcomes and complications.MethodsWe systematically analysed published data from Jan 1993 to Dec 2018 to assess methods of fixation and associated outcomes for the surgical reconstruction in Charcot neuroarthropathy. Statistical analyses were undertaken to determine the amputation rates, return to ambulation and complications associated with these techniques.ResultsA total of 1116 feet (1089 patients) were reported to have undergone reconstruction with significant heterogeneity in patient selection. Of these, 726 (65%) were reported to undergo internal fixation, 346 feet (31%) external fixation and 44 (4%) undergoing simultaneous internal and external fixation. No single technique demonstrated a significant benefit over the other. Overall, the bone fusion rate was 86.1%. Complications directly attributable to the technique employed were noted in 36% of individuals. The reported post-reconstruction amputation rate was only 5.5% with 91% apparently returning to ambulation.ConclusionsAlthough no preferential method of fixation was identified, we find that the current options for surgical reconstruction could offer limb salvage with a low amputation risk in a highly selected population. However, the lack of controlled studies, inconsistent reporting of outcomes and heterogeneity of patient selection mean that the quality of evidence is low.     

Gd-EOB-DTPA增强MRI评估功能性肝体积与肝功能Child-Pugh分级的相关性

目的：对比解剖性肝脏体积（ALV）和功能性肝脏体积（FLV）与肝功能Child-Pugh分级的相关性。方法：选择温州医科大学附属第二医院育英儿童医院2014年1月至2019年4月同时行增强CT和Gd-EOB-DTPA增强MRI扫描的肝硬化患者25例。对所有患者进行肝功能Child-Pugh评分，检测所有入组患者每个肝段的Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号对比增强率（CER），以CT扫描的数据为基础利用MI-3DVS计算每个肝段的ALV和全肝的FLV。分析ALV和FLV与肝功能Child-Pugh分级的相关性。结果：肝功能Child-Pugh分级与ALV呈负相关（r=-0.792，P＜0.001），曲线拟合的决定系数（R2）=0.63；肝功能Child-Pugh分级与FLV亦呈负相关（r=-0.911，P＜0.001），曲线拟合的R2=0.80。FLV与肝功能Child-Pugh分级有更显著的负相关性。结论：结合Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号CER和ALV计算所得的FLV较ALV能更好地反映肝脏的功能状态。     

Decellularized porcine conjunctiva as an alternative substrate for tissue-engineered epithelialized conjunctiva

PurposeThe long-term success of visual rehabilitation in patients with severe conjunctival scarring is reliant on the reconstruction of the conjunctiva with a suitable substitute. The purpose of this study is the development and investigation of a re-epithelialized conjunctival substitute based on porcine decellularized conjunctiva (PDC).MethodsPDC was re-epithelialized either with pre-expanded human conjunctival epithelial cells (PDC + HCEC) or with a human conjunctival explant placed directly on PDC (PDC + HCEx). Histology and immunohistochemistry were performed to evaluate epithelial thickness, proliferation (Ki67), apoptosis (Caspase 3), goblet cells (MUC5AC), and progenitor cells (CK15, ΔNp63, ABCG2). The superior construct (PDC + HCEx) was transplanted into a conjunctival defect of a rabbit (n = 6). Lissamine green staining verified the epithelialization in vivo. Orbital tissue was exenterated on day 10 and processed for histological and immunohistochemical analysis to examine the engrafted PDC + HCEx. A human-specific antibody was used to detect the transplanted cells.ResultsFrom day-14 in vitro onward, a significantly thicker epithelium and greater number of cells expressing Ki67, CK15, ΔNp63, and ABCG2 were noted for PDC + HCEx versus PDC + HCEC. MUC5AC-positive cells were found only in PDC + HCEx. The PDC + HCEx-grafted rabbit conjunctivas were lissamine-negative during the evaluation period, indicating epithelial integrity. Engrafted PDC + HCEx showed preserved progenitor cell properties and an increased number of goblet cells comparable to those of native conjunctiva.ConclusionPlacing and culturing a human conjunctival explant directly on PDC (PDC + HCEx) enables the generation of a stable, stratified, goblet cell-rich construct that could provide a promising alternative conjunctival substitute for patients with extensive conjunctival stem and goblet cell loss.     

A Snapshot of the Guidelines on Vesicoureteral Reflux in Children

The main goal in the management of patients with vesicoureteral reflux (VUR) is the preservation of kidney function by minimizing the risk of pyelonephritis. By defining and analyzing the risk factors for each patient depending on age, sex, grade of reflux, lower urinary tract dysfunction, anatomic abnormalities, and kidney status, it is possible to identify those patients with a potential risk of upper urinary tract infection and resulting renal scarring. This paper gives a brief overview of the European Association of Urology guidelines for the management and treatment of VUR in children. These guidelines are based on the best currently available knowledge and evidence.     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.