信号通路在肝细胞癌发展中的作用

目的 探讨EGFR信号通路、MAPK信号通路、IKB/NF-κB信号通路、PI3K/Akt信号通路、WNT/β-catenin信号通路和Hedgehog信号通路在肝细胞癌发展中的作用。方法 采用文献复习的方法,对信号通路在肝细胞癌发展中作用的相关文献进行综述。结果 在肝癌的发生发展过程中,EGFR、MAPK、IKB/NF-κB、PI3K/Akt、WNT/β-catenin、Hedgehog等信号通路之间复杂交织和相互作用,并且可能存在一些肿瘤标志物、抑癌基因、原癌基因和miRNA的协同作用。结论 分子信号通路的异常改变是肿瘤发生及发展的必要条件,并且信号通路在肝细胞癌发病中有着复杂的交叉和冗余。     

肾病综合征氧化低密度脂蛋白脂质肾损伤的实验研究

目的 通过观察氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）对系膜细胞（Mesangial Cells,MCs）分泌炎症介质功能的影响及MAPK信号通路和核因子-κB（nuclear factor kappa B,NF-κB）活性的改变,进一步阐明脂质在肾损伤中的作用机制.方法 利用ox-LDL诱导大鼠系膜细胞增殖,分别采用ELISA、real-time PCR、western blot技术检测MCs炎症介质、MAPK通路相关蛋白（p38、JNK、ERK）及NF-κB的表达水平.结果 利用ox-LDL诱导大鼠系膜细胞增殖并加入CXCR6受体后,其表面炎症因子[CXCL16、CD36、ADAM10、ADAM17、干扰素（IFN）、白细胞介素（IL6）、肿瘤坏死因子（TNF-α）]的表达水平以及MAPK信号通路（p38、JNK、ERK）、NF-κB的磷酸化水平显著升高（P〈0.01）.结论 ox-LDL可促使系膜细胞释放CXCL16、CD36、ADAM10、ADAM17、IFN、IL6、TNF-α等炎症介质,CXCR6可介导这一途径.ox-LDL激活MAPK信号转导通路,使p38、ERK1/2、SAPK/JNK的磷酸化水平升高,激活了NF-κB p65的活性,CXCR6-CXCL16介导MAPK信号途径.     

国外期刊摘译

联合应用周期素依赖性蛋白激酶与AKT抑制剂诱导转移性前列腺癌细胞凋亡;肿瘤蛋白D52的表达变化对前列腺癌细胞凋亡与迁移影响的研究;抑制NF-κB与激活AP-1可增强前列腺癌细胞的凋亡;厚朴酚通过抑制EGFR／PI3K／Akt信号通路诱导人前列腺癌细胞凋亡;转移性前列腺癌细胞中PI3K／Akt依赖的转录调控与NF-κB介导的BMP-2-Smad信号通路的激活……     

核转录因子κB抑制剂抑制表皮生长因子诱导胰腺癌细胞侵袭研究

表皮生长因子（epidermal growth factor，EGF）在胰腺癌组织中表达明显增高，核转录因子KB（nuclear factor kappaB，NF-κB）是参与调控肿瘤侵袭和转移的相关基因，二者均与肿瘤的侵袭和转移密切相关。本实验通过研究NF-κB抑制剂对EGF诱导胰腺癌细胞侵袭能力的影响，探讨抑制NF-κB信号转导通路在胰腺癌治疗中的作用。[第一段]     

靶向抑制PI3K对人体外周血破骨细胞分化p38/c-Fos 信号通路调控的研究

目的探讨靶向抑制磷脂酰肌醇3-激酶(PI3K)调控p38/c-Fos信号通路对破骨细胞分化的影响。方法采用人体外周血分离单个核细胞,并诱导形成破骨细胞,干预组应用靶向抑制PI3K的LY294002对细胞进行处理,通过细胞形态学观察并检测细胞活性,再分别采用RT-PCR和Western-Blot两种方法考察p38MAPK通路及下游转录因子c-fos基因和蛋白的表达水平。结果模型组与干预组细胞形态学观察均可见诱导培养的破骨细胞形态明显;与模型组比较,干预组破骨细胞样细胞的形成减少,活性减弱,具有统计学意义(P0.05);RT-PCR结果均显示,干预组p38MAPK通路下游转录因子c-fos表达水平较对照组下降,有显著性差异(P0.01);Western-Blot检测结果显示干预组c-fos蛋白表达水平较对照组降低,具有统计学意义(P0.05)。结论靶向抑制PI3K在体外细胞培养中可抑制破骨细胞形态,并可通过下调p38MAPK通路中c-fos基因和蛋白水平的表达,从而减弱破骨细胞吸收功能。     

lncRNA HOXA11-AS抑制骨关节炎大鼠软骨细胞凋亡与基质降解的作用研究

目的研究长链非编码RNA(long-nocoding RNA,lncRNA)HOXA11-AS在骨关节炎(osteoarthritis,OA)的大鼠软骨细胞中的表达情况,及其对软骨细胞凋亡、基质降解以及核因子κB(nuclear factor kappa B,NF-κB)信号通路的影响。方法采用弗氏完全佐剂注射大鼠构建OA大鼠模型,造模后分离培养软骨细胞;小干扰RNA(small interfering RNA,siRNA)技术抑制软骨细胞中HOXA11-AS表达;细胞计数试剂盒(cell counting kit-8,CCK-8)检测转染siRNA不同时间后软骨细胞的活力;实时荧光定量聚合酶链式反应(quantitative real-time PCR,qRT-PCR)检测软骨细胞中HOXA11-AS及基质金属蛋白酶13(matrix metallo protein-13,MMP-13)、血小板结合蛋白基序的解聚蛋白样金属蛋白酶5(a disintesrin and metalloprotease with thrombospondin type 5 motifs,ADAMTS-5)、Ⅱ型胶原(CollagenⅡ)、聚集蛋白聚糖(aggrecan)mRNA的表达情况;流式细胞术检测软骨细胞的凋亡情况;酶联免疫吸附测定法(enzyme-linked immune sorbent assay,ELISA)检测软骨细胞上清液中Bcl-2相关X蛋白(Bcl 2-associated X protein,Bax)、B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、半胱氨酸蛋白酶3(caspase-3)的表达情况;蛋白质印迹法(western blot)检测MMP-13、ADAMTS-5、CollagenⅡ、aggrecan和抗核因子κB抑制蛋白(anti-nuclear factor kappa B inhibitory protein,IκBα)、抗磷酸化核因子κB抑制蛋白(anti-phosphorylated nuclear factor kappa B inhibitory protein,p-IκBα)、抗核因子κB 65(nuclear factor kappa B,NF-κB 65)的表达,免疫荧光染色检测NF-κB在软骨细胞细胞核中的表达情况。结果与正常组大鼠软骨细胞相比,HOXA11-AS在OA大鼠软骨细胞中高表达;与NC siRNA组比较,HOXA11-AS siRNA组细胞活力显著下降,细胞凋亡率及促凋亡因子Bax、Caspase-3的表达水平显著升高,而抑凋亡因子Bcl-2的表达水平显著下降;同时,与NC siRNA组比较,HOXA11-AS siRNA组细胞collagenⅡ和aggrecan的基因和蛋白表达水平明显降低,MMP-13和ADAMTS-5基因及蛋白表达水平明显升高,IκBα蛋白表达水平显著下降而p-IκBα和NF-κB p65的表达水平显著增高,此外,NF-κB在HOXA11-AS siRNA组细胞核中明显表达。结论 lncRNA HOXA11-AS可以抑制骨关节炎大鼠软骨细胞的凋亡以及基质降解,并阻止NF-κB信号通路的激活。     

Indian Hedgehog信号通路在软骨细胞成熟及转分化过程中的调控作用

目的 探究Indian Hedgehog（IHH）信号通路对软骨内成骨过程中软骨细胞成熟以及转分化的影响。方法 取10日龄野生型小鼠的胫骨组织,采用原位杂交和免疫组织化学染色检测生长板区域IHH信号通路相关分子Ihh、Ptch1和Gli1的表达水平。构建肥大软骨细胞特异性Ihh基因敲除小鼠（Col10a1^Cre/+; Ihh^null/C）,并采用影像学检查和阿利新蓝染色评估该小鼠的骨骼发育状况。构建肥大软骨细胞IHH信号通路持续激活小鼠（Col10a1^Cre/+; R26Smo^M2/M2和 Col10a1^Cre/+; Ptch1^LacZ/C）,采用HE染色、原位杂交和TUNEL染色分别对受精15.5天胎鼠胫骨组织形态结构、Ihh（肥大软骨细胞分子标志物）和Col1a1（成骨细胞分子标志物）以及肥大软骨细胞凋亡水平进行检测;另外应用HE染色对10日龄小鼠的胫骨组织进行组织学分析。结果 肥大软骨细胞合成分泌IHH,但不表达Ptch1和Gli1。抑制肥大软骨细胞合成IHH蛋白会导致出生后小鼠出现侏儒症;X线检查结果显示小鼠出现严重的骨骼发育不良,包括胸廓狭小、球形头骨以及椎骨发育异常等表现。持续启动IHH信号通路时,胚胎早期软骨细胞成熟分化过程虽未见异常,但是出生后小鼠的骨小梁、骨内膜以及皮质骨等结构均出现一定的异常表现。结论 IHH信号通路虽然不参与肥大软骨细胞的终末分化过程,但在软骨细胞转分化的过程中起到了重要的调控作用。     

吡拉西坦通过MAPK通路治疗大鼠脊髓损伤的疗效观察与机制研究

目的: 探讨吡拉西坦通过丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)通路治疗脊髓损伤大鼠的作用机制。方法: 将54只体重为80~100 g的6周龄SD雌性健康大鼠采用随机数字表法分为假手术组、脊髓损伤组、吡拉西坦组,每组18只。脊髓损伤组、吡拉西坦组使用打击器建立脊髓损伤模型,假手术组不损伤脊髓。吡拉西坦组按照5 ml·kg-1标准予尾静脉注射吡拉西坦,连续干预3 d,每日1次;其他2组注射等剂量、等次数、等时长的生理盐水。分别于术后1、3、7 d处死大鼠并取材,观察并比较大鼠脊髓损伤行为学评分(Basso,Beattie and Bresnahan locomotor rating scale,BBB)的变化,使用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测脊髓炎症因子白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平变化,HE染色观察脊髓损伤大鼠的形态学变化,免疫组化观察水通道蛋白-4(aquaporin 4,AQP4)表达水平,蛋白质免疫印迹法(western blotting,WB)观察脊髓损伤后MAPK信号通路在大鼠脊髓中的激活状态。结果: 假手术组1、3、7 d的BBB评分均为21分;脊髓损伤组分别为(1±1)、(4±1)、(7±2)分;吡拉西坦组分别为(1±1)、(5±1)、(9±2)分;脊髓损伤组与假手术组比较,差异有统计学意义(P<0.05);吡拉西坦组与脊髓损伤比较,差异有统计学意义(P<0.05)。HE染色结果显示,假手术组形态未见异常。脊髓损伤组在术后1 d时,脊髓组织出现出血、变性;术后3 d,脊髓组织内出现片状坏死区;术后7 d,脊髓组织开始缓慢修复。吡拉西坦组术后1 d,脊髓损伤出血面积较脊髓损伤组减小;术后3 d,坏死区域较脊髓损伤组减少,细胞核消失范围较脊髓损伤组缩小;术后7 d,脊髓开始缓慢恢复。假手术组大鼠造模后1、3、7 d脊髓组织中AQP4染色较淡;脊髓损伤组AQP4染色加深,面积增大;吡拉西坦组AQP4染色较脊髓损伤组变淡,较假手术组阳性细胞略增多,染色微深。造模第1、3、7天,脊髓损伤组IL-6,IL-10,IL-1β和TNF-α水平高于手术组和吡拉西坦组(P<0.05)。与脊髓损伤组比,吡拉西坦组HE染色脊髓出血及坏死区域面积减小,免疫组化显示AQP4染色变淡。WB结果显示,造模第3天,脊髓损伤组p-ERK,p-JNK和p-p38水平高于假手术组和吡拉西坦组(P<0.05)。结论: 吡拉西坦不仅在促进脊髓损伤后的运动功能恢复方面表现出显著效果,而且在减少病变面积、调节AQP4表达以减轻水肿,以及通过调控MAPK信号通路降低炎症反应方面均显示出积极的治疗潜力。     

载骨形成蛋白2和肌肤生对兔胫骨慢性骨髓炎修复作用的实验研究

目的：探讨在骨髓炎兔的实验模型中,载骨形成蛋白2联合肌肤生一期治疗的效果评价。方法：选取3月龄雄性新西兰大白兔30只,体重（2.0±0.5）kg,制备兔胫骨慢性骨髓炎模型,并于术后4周进行模型验证。将30只兔慢性骨髓炎随机分为3组,每组10只。模型组于病灶清除后不做任何处理;治疗组A于病灶清除及骨缺损处植入肌肤生;治疗组B于病灶清除及骨缺损处植入载骨形成蛋白2-肌肤生。术后8周通过血液生化、微生物、影像学、病理学及免疫组化等检查进行治疗作用评价。结果：造模术后4周,30只骨髓炎兔模型验证成功,其中血清学检查结果显示,造模术后2周及4周模型组的超敏C反应蛋白显著高于空白组（P<0.01、P<0.05）,白细胞计数显著高于空白组（P<0.05、P<0.01）。治疗术后8周,血液指标检测,治疗A组与治疗B组的白细胞计数、超敏C反应蛋白显著低于模型组（P<0.05）,但治疗A与治疗B组差异无统计学意义。治疗术后8周,骨缺损面积测量,治疗A组与治疗B组的骨体积/总体积（BV/TV）及骨矿化密度大于模型组（P<0.05）,且治疗B组的骨体积/总体积（BV/TV）及骨矿化密度大于治疗A组（P<0.05）,骨缺损修复接近完全,骨体积与骨密度显著升高。治疗术后8周,骨组织病理学检测,治疗A组与治疗B组的HE染色指标成骨细胞数/骨组织面积（N.Ob/T.Ar）、成骨细胞数/骨组织周长（N.Ob/B.Pm）高于模型组（P<0.05）,且治疗B组的N.Ob/T.Ar和N.Ob/B.Pm大于治疗A组（P<0.05）;治疗A组与治疗B组的骨组织周围TNF-α和IL-6免疫组化阳性染色率少于模型组（P<0.05）,但治疗组B与治疗组A差异无统计学意义。结论：载骨形成蛋白2-肌肤生联合应用能共同促进骨修复,并减轻病灶部位炎症,可以一期治疗兔慢性骨髓炎,为骨髓炎临床治疗策略制订提供客观依据,进一步促进临床研究。     

The role of clinical care pathways: an experience with distal pancreatectomy

Background

Previous studies have indicated that clinical pathways may shorten hospital length of stay (HLOS) among patients undergoing distal pancreatectomy (DP). Here, we evaluate an institutional standardized care pathway (SCP) for patients undergoing DP.

Materials and methods

A retrospective review of patients undergoing DP from November 2006 to November 2012 was completed. Patients treated before and after implementation of the SCP were compared. Multivariable linear regression was then performed to identify independent predictors of HLOS.

Results

There were no differences in patient characteristics between SCP (n = 50) and pre-SCP patients (n = 100). Laparoscopic technique (62% versus 13%, P < 0.001), splenectomy (52% versus 38%, P = 0.117), and concomitant major organ resection (24% versus 13%, P = 0.106) were more common among SCP patients. Overall, important complication rates were similar (24% versus 26%, P = 0.842). SCP patients resumed a normal diet earlier (4 versus 5 d, P = 0.025) and had shorter HLOS (6 versus 7 d, P = 0.026). There was no increase in 30-d resurgery or readmission. In univariate comparison, SCP, cancer diagnoses, intraductal papillary mucinous neoplasm diagnoses, neoadjuvant therapy, operative technique, major organ resection, and feeding tube placement were associated with HLOS; however, after multivariable adjustment, only laparoscopic technique (−33%, P = 0.001), concomitant major organ resection (+38%, P < 0.001), and feeding tube placement (+68%, P < 0.001) were independent predictors of HLOS.

Conclusions

Implementation of a clinical pathway did not improve HLOS at our institution. The increasing use of laparoscopy likely accounts for shorter HLOS in the SCP cohort. In the future, it will be important to identify clinical scenarios most likely to benefit from implementation of a clinical pathway.     

经线粒体途径相关信号通路对成骨细胞的影响

骨质疏松是骨科的常见病症,是以骨微观结构改变、骨脆性增加、骨量减少为特征的全身代谢性骨质病变。成骨细胞与破骨细胞对骨组织形成、破坏作用的失衡是骨量丢失的主要成因。因此,抑制成骨细胞的凋亡是治疗骨质疏松的关键。现已知,成骨细胞的凋亡主要是由线粒体凋亡途径有关的多种信号通路和多种细胞因子作用导致。本文主要对线粒体凋亡途径及相关信号通路PI3K-Akt、MAPK、Wnt/β-catenin、NF-κB通路和其中的关键靶点作一综述,并阐述部分信号通路之间的作用及其对成骨细胞凋亡的影响,对深入研究骨质疏松的发病机制及研发有关治疗新药有重大意义。     

The molecular genetics of medulloblastoma: an assessment of new therapeutic targets

Medulloblastoma is the most common pediatric primary malignant intracranial neoplasm. The 5-year survival rates vary from 40% to 70% depending on clinical prognostic criteria, and many of the patients who survive exhibit long-term neurocognitive and/or neuroendocrine sequelae. Because of these results, research is required to increase our understanding of the basic biology of medulloblastoma, helping to refine patient stratification, decrease side effects of treatments, identify novel prognostic markers, and discover new less toxic therapies. The recognition that some medulloblastomas occur in familial cancer syndromes has led to some important discoveries in the molecular pathogenesis of medulloblastoma. These syndromes provide us with clues regarding alterations in key signaling or growth factor activation pathways that contribute to medulloblastoma formation. A better understanding of the molecular pathways involved in medulloblastoma formation may allow the discovery of new drugs that act on specific targets, yet many steps must still be taken before clinical use of new drugs. In addition, the identification of a novel signaling pathways in medulloblastoma is often accompanied by the quest for novel pharmacotherapeutics that have the potential to act favorably on this disease.     

线粒体途径相关信号通路对成骨细胞凋亡的作用

骨质疏松症是由于多种原因导致的骨质量和骨密度下降,骨微结构遭到破坏,造成骨脆性增加,从而容易发生骨折的一种全身性代谢性骨病变。其中,成骨细胞是促进骨形成的主要功能细胞,是骨质疏松发生的关键细胞,其功能退变和异常凋亡将会引起骨量丢失,诱导骨质疏松发生。因此,探究成骨细胞的凋亡机制对预防和治疗骨质疏松症具有重要意义。其中,线粒体途径是成骨细胞凋亡的主要途径,是由多基因参与、多通路相互作用而形成的复杂过程。因此,本文综述了线粒体途径的凋亡过程及其众多相关信号通路:PI3k/Akt信号通路、MAPK信号通路、Ca~(2+)/CaM信号通路以及其他信号通路和因子(Keap1/Nrf2信号通路、PHB、FoxO家族、cAMP/CREB),同时还归纳了这些信号通路在成骨细胞经线粒体途径凋亡的过程中发挥的促进或者抑制作用,以及他们在成骨细胞凋亡中的一些相互作用。这为进一步探究成骨细胞的凋亡机制和骨质疏松的发病机制提供了可靠依据,也为更深入研究安全、有效的抗骨质疏松药物提供了一些可能的作用靶点(如:Akt、ERK、JNK、p38、Ca~(2+)、PHB、FoxO3a、CREB、Keap1/Nrf2等)。     

乙酰胆碱、蛙皮素和P物质对人食管下括约肌张力调节的细胞内信号转导机制

目的 观察蛋白激酶C(PKC)和钙调蛋白信号转导通路在乙酰胆碱、蛙皮素和P物质对人食管下括约肌钩状纤维和套索纤维张力调节中的作用.方法 应用PKC信号通路特异性阻断剂H7和钙调蛋白信号通路特异性阻断剂CGS9343B,以食管和胃底环形肌作对照,测定抑制套索纤维和钩状纤维肌细胞收缩的情况.结果 乙酰胆碱与蛙皮素和P物质引起的收缩,应用H7(5±1)%、(5±2)%、(6±2)%和无钙培养(4±1)%、(6±1)%、(3±1)%的方法,可以有效阻断钩状纤维的收缩(22±1)%、(23±1)%、(24±1)%;以CGS9343B(3±1)%、(4±2)%、(6±1)%和4mmol/L锶离子处理(5±2)%、(3±1)%、(6±2)%可以有效阻断套索纤维(23±2)%、(24±2)%、(26±1)%的收缩.结论 人食管下括约肌的套索纤维细胞依赖钙调蛋白信号通路和内源性钙离子释放产生最大收缩效应.钩状纤维细胞依赖PKC信号通路和外源性钙离子流入产生最大收缩效应.     

补体在IgA肾病发生发展中的作用

IgA肾病的发生与自身免疫相关，其特征为肾小球系膜区IgA沉积。IgA肾病的发病机制尚不清楚，但现已证实补体异常活化在IgA肾病发生发展中起重要作用，参与IgA肾病发生发展过程的主要为补体替代途径和凝集素途径。本文就补体系统在IgA肾病发生发展中的作用进行了综述。     

Immunoglobulin M-enriched intravenous immunoglobulin inhibits classical pathway complement activation, but not bactericidal activity of human serum

Abstract:  Acute or even hyperacute humoral graft rejection, mediated by classical pathway complement activation, occurs in allo- and xenotransplantation due to preformed anti-graft antibodies. Intravenous immunoglobulin (IVIg) preparations can prevent complement-mediated tissue injury and delay hyperacute xenograft rejection. It is known that IgM-enriched IVIg (IVIgM) has a higher capacity to block complement than IVIgG. Different IVIgs were therefore tested for specificity of complement inhibition and effect on anti-bacterial activity of human serum. IVIgM-I (Pentaglobin^®, 12% IgM), IVIgM-II (IgM-fraction of IVIgM-I, 60% IgM), and three different IVIgG (all >95% IgG) were used. The known complement inhibitor dextran sulfate was used as control. Hemolytic assays were performed to analyze pathway-specificity of complement inhibition. Effects of IVIg on complement deposition on pig cells and Escherichia coli were assessed by flow cytometry and cytotoxicity as well as bactericidal assays. Complement inhibition by IVIgM was specific for the classical pathway, with IC50 values of 0.8 mg/ml for IVIgM-II and 1.7 mg/ml for IVIgM-I in the CH50 assay. Only minimal inhibition of the lectin pathway was seen with IVIgM-II (IC50 15.5 mg/ml); no alternative pathway inhibition was observed. IVIgG did not inhibit complement in any hemolytic assay. Classical pathway complement inhibition by IVIgM was confirmed in an in vitro xenotransplantation model with PK15 cells. In contrast, IVIgM did not inhibit (mainly alternative pathway mediated) killing of E. coli by human serum. In conclusion, IgM-enriched IVIg is a specific inhibitor of the classical complement pathway, leaving the alternative pathway intact, which is an important natural anti-bacterial defense, especially for immunosuppressed patients.     

Relationship between deep and superficial sensitivity assessments and gait analysis in diabetic foot patients

Peripheral neuropathy is a prevalent complication of diabetes that can lead to gait impairment and its adverse consequences. This study explored the potential utility of different parameters of gait analysis using a single sensor unit as a simple tool to detect peripheral neuropathy in 85 diabetic patients (DP) with diabetic foot in whom different somato-sensitivity tests in the feet were performed. Gait spatiotemporal parameters were examined by sensor inertial measurement placed in the lumbar area, while the superficial sensitivity pathway was assessed by nociception tests and deep sensitivity was examined by light touch-pressure and vibration sensitivity tests. Correlations between each sensory test and gait parameters were analysed in a logistic regression model in order to assess if gait parameters are associated with two different sensory pathways. Impaired deep sensory pathways were significantly (P < .05) correlated with lower gait speed, reduced cadence, smaller stride length, longer stance periods, and a higher risk of falling on the Tinetti Scale, while all gait parameters were significantly (P < .01) correlated with the superficial sensory pathway. Type 2 diabetics have significantly (P < .05) higher impairment in vibratory sensitivity than type 1 diabetics, and the years with diabetes mellitus (DM) diagnosis have a significant (P < .05) association with reduced vibration sensitivity. These findings indicate relationships between the deep sensory pathway and gait impairments in DP measured by inertial sensors, which could be a useful tool to diagnose gait alterations in DP and to evaluate the effect of treatments to improve gait and thus the risk of falls in diabetic patients.     

One and done? Outcomes from 3961 patients managed via a virtual fracture clinic pathway for paediatric fractures

PurposeThe aim of this paper is to describe our experience with a virtual fracture management pathway in the setting of a paediatric trauma service.MethodsAll patients referred to the virtual fracture clinic service from the Paediatric Emergency Department (PED) were prospectively collected. Outcome data of interest (patients discharged, referred for urgent operative treatment, referred back to emergency department for further evaluation, referred for face-to-face clinical assessment and all patients who re-presented on an unplanned basis for further management of the index injury) were compiled and collated. Cost analysis was performed using established costing for a virtual fracture clinic within the Irish Healthcare System.ResultsThere were a total of 3961 patients referred to the virtual fracture clinic from the PED. Of these, 70% (n = 2776) were discharged. In all, 26% (n = 1033) were referred to a face-to-face appointment. Of discharged patients, 7.5% (n = 207) required an unplanned face-to-face evaluation. A total of 0.1% (n = 3) subsequently required operative treatment relating to their index injury. Implementation of the virtual fracture clinic model generated calculated savings of €254 120.ConclusionThis prospective evaluation has demonstrated that a virtual fracture clinic pathway for minor paediatric trauma is safe, effective and brings significant cost savings.Level of EvidenceII