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。     

Robotic-assisted pancreaticoduodenectomy with vascular resection. Description of the surgical technique and analysis of early outcomes

BackgroundDespite the potential benefits, the adoption of the minimally invasive surgery for the treatment of borderline resectable pancreatic cancer is still in the initial phase. We investigated the safety and feasibility of the robotic pancreaticoduodenectomy with venous resection/reconstruction (RPD SMV/PV).MethodsSince March 2013 to October 2019, a total of 73 RPD and 10 RPD SMV/PV were performed. The two groups were case-matched according to the preoperative characteristics.ResultsMean operative times and estimated blood loss were less in the RPD group in comparison to that in the RPD with SMV-PV group (525 vs 642 min, p = 0.003 and 290 vs 620 ml, p = 0.002, respectively). The mean length of hospital stay was similar in the RPD group in comparison to that in the RPD with SMV-PV group (10 days vs 13 days, p = 0.313). The two groups had similar overall postoperative morbidity rate (57.5% vs 60%, p = 0.686), although the severe complication rate was lower in the RPD group (11% vs 40%, p = 0.004).ConclusionsRPD with SMV-PV is associated with increased operative time, estimated blood loss, higher major complication rate compared with RPD.     

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.     

Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.