Improving cancer-specific outcomes in solid organ transplant recipients: Where to begin?

In an article published in this issue of Cancer, D’Arcy et al link the incidence of cancer among recipients of solid organ transplantation (SOT) in the Scientific Registry of Transplant Recipients with data from regional and statewide cancer registries to examine cancer-specific mortality for common malignancies in SOT recipients. This analysis helps to illuminate the role of immune surveillance across a broad range of malignancies and compares the incidence of cancers due to virally mediated oncogenesis (lymphoma, squamous cell carcinoma of the aerodigestive epithelium, and hepatitis-induced liver cancer) with the incidence of other malignancies. The authors’ central finding is that cancer-specific mortality is significantly increased in SOT recipients in comparison with nontransplant recipients for multiple cancers, and the increased cancer incidence is not limited to the effects of viral oncogenesis. The authors document a significant increase in common epithelial malignancies that are currently treated with immune checkpoint antibodies, including melanoma, bladder cancer, colorectal cancer, cancers of the oral cavity/pharynx, kidney cancer, and lung cancer, and this supports the hypothesis that post-SOT immunosuppression affects immune surveillance in these cancers. Provocatively, the authors also document increases in the incidence and mortality of cancers not typically responsive to immune checkpoint therapies, including breast cancer and pancreatic cancer. The findings of D’Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration–approved antibodies to CTLA4 and PD-1/PD-L1.     

2018 ATC/TTS器官移植前沿热点回顾及进展概述

重点概述2018年美国移植大会及第27届国际移植大会有关器官移植基础、临床及转化医学研究的前沿热点及最新进展，包括供者特异性抗体、抗体介导排斥反应、临床免疫耐受、供器官合理利用、供肝保存新技术应用及移植相关病毒感染等概要内容。     

Ehlers-Danlos Syndrome: It’s Not Your Normal Hoofbeats

The purpose of this article is to acquaint the reader with the presentation, diagnosis, and management of Ehlers-Danlos syndrome (EDS), a group of genetic connective tissue disorders. Progressive weakness of connective tissue is the underlying cause of all types of EDS. The symptoms of EDS are numerous, with variability in presentation. However, decreased quality of life caused by chronic pain and fatigue is a commonality of all types of EDS. This article will assist the nurse practitioner in recognizing EDS and offer guidance for treatment.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

30-day adverse events,length of stay and re-admissions following surgical management of pelvic/acetabular fractures

IntroductionPelvic/acetabular fractures are associated with significant morbidity, mortality and cost to the society. We sought to utilize a national surgical database to assess the incidence and factors associated with prolonged length of stay (LOS), non-home discharge destination, 30-day adverse events and readmissions following surgical fixation of pelvic/acetabular fractures.Materials & methodsThe 2011–2016 ACS-NSQIP database files were queried using CPT codes (27215, 27217, 27218, 27226, 27227, 27228) for patients undergoing open reduction/internal fixation (ORIF) for pelvic/acetabular fractures. Patients undergoing additional procedures for associated fractures (vertebral fractures, distal radius/ulna fractures or femoral neck/hip fractures) were excluded from the analysis to ensure that a relevant population of patients with isolated pelvic/acetabular injuries were included in the analysis. A total of 572 patients were included in the final cohort. Severe adverse events (SAE) were defined as: death, ventilator use >48 h, unplanned intubation, stroke, deep venous thrombosis, pulmonary embolism, cardiac arrest, myocardial infarction, acute renal failure, sepsis, septic shock, re-operation, deep SSI and organ/space SSI. Minor adverse events (MAE) included – wound dehiscence, superficial SSI, urinary tract infection (UTI) and progressive renal insufficiency. An extended LOS was defined as >75th centile (>9days).ResultsFactors associated with AAE were partially dependent functional health status pre-operatively (p = 0.020), transfusion ≥1 unit of packed RBCs (p = 0.001), and ASA > II (p < 0.001). Experiencing a SAE was associated with congestive heart failure (CHF) pre-operatively [p = 0.005), total operative time >140 min (p = 0.034) and Hct <36 pre-operatively (p = 0.003). MAE was associated with transfusion≥1 unit of packed RBCs (p = 0.022) and ASA > II (p = 0.007). Patients with an ASA > II (p = 0.001), total operative time>140 min (p < 0.001) and Hct <36 (p = 0.006) were more likely to have a LOS >9 days. Male gender (p = 0.026), prior history of CHF (p = 0.024), LOS >9 days (p = 0.030) and >10% bodyweight loss in last 6 months before the procedure (p = 0.002) were predictors of 30-day mortality.ConclusionPatients with ASA grade > II, greater co-morbidity burden and prolonged operative times were likely to experience adverse events and have a longer length of stay. Surgeons can utilize this data to risk stratify patients so that appropriate pre-operative and post-operative medical optimization can take place.     

Pelvic obliquity as a compensatory mechanism leading to lower energy recovery: Characterization among the types of prostheses in subjects with transfemoral amputation

BackgroundSubjects with transfemoral amputation (TFA) show an asymmetric gait pattern associated with a decreased ability to recover mechanical energy and an increased metabolic cost of walking.Research questionThis study aimed to identify the spatio-temporal and kinematic gait variables correlated with mechanical energy values in subjects with TFA and to observe the ability of the identified parameters to discriminate between TFA and controls according to the type of prosthesis.MethodsThe gait of 40 subjects with TFA was evaluated with a motion 3-D optoelectronic system. Nine subjects wore a mechanical prosthesis (TFAm), seventeen a C-Leg prosthesis (TFAc), and fourteen a Genium prosthesis (TFAg). Spatio-temporal and pelvic kinematic parameters were measured. Energy recovery was measured relative to the whole-body center of mass (CoM) kinematics as the fraction of mechanical energy recovered during each walking step (R-step). Correlation tests and multiple linear regression analyses were used to evaluate the correlation and association between kinematic and energy variables, respectively. Receiver operating characteristics curves were plotted to assess the ability of the correlated parameter to distinguish subjects with TFA from controls, and optimal cutoff point values were calculated according to the type of prosthesis.ResultsAmong the spatio-temporal and kinematic parameters correlated to R-step, only pelvic obliquity of the prosthetic side was significantly associated with R-step. It showed an excellent ability to discriminate between TFA and controls. Furthermore, pelvic obliquity showed an excellent discriminative ability in identifying TFAm and TFAc and a good discriminative ability in identifying TFAg from controls.SignificancePelvic obliquity plays an important role in energy recovery during gait for subjects using prosthetics. This information might be exploited to monitor the adaptation of subjects with TFA to prosthetic devices, to lower the energetic cost of walking potentially, and to reduce the long-term risks of secondary physical complications in prosthetic users.     

基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用

目的分析基质金属蛋白酶(MMPs)在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用。方法选取2017年1月-2018年12月在温州市人民医院进行腹腔镜手术的60例子宫内膜异位症患者为观察组,选取同期进行腹腔镜手术的30例非子宫内膜异位症患者为对照组。观察组根据术中盆腔粘连程度分为1组(无或仅有轻度盆腔粘连,子宫内膜异位症Ⅰ~Ⅱ期,24例)和2组(中重度盆腔粘连,子宫内膜异位症Ⅲ~Ⅳ期,36例)。采集3组腹腔液和血清,采用ELISA法检测腹腔液及血清基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-3 (MMP-3)、基质金属蛋白酶-7 (MMP-7),血清雌二醇(E2)、黄体生成素(LH)、孕酮(P)、卵泡刺激素(FSH),白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平。结果 1组腹腔液MMP-2、MMP-3、MMP-7水平显著高于对照组,差异有统计学意义(均P<0. 05),2组腹腔液MMP-2、MMP-3、MMP-7水平显著高于1组(均P<0. 05)。1组血清FSH、LH水平显著高于对照组(均P<0. 05),2组血清FSH、LH水平显著高于1组(均P <0. 05)。1组血清E2、P水平显著低于对照组(均P<0. 05),2组血清E2、P水平显著低于1组(均P<0. 05)。1组血清IL-6、IL-8、TNF-α水平显著高于对照组(均P<0. 05),2组血清IL-6、IL-8、TNF-α水平显著高于1组(均P<0. 05)。结论子宫内膜异位症患者腹腔液中MMPs水平升高,可能与盆腔粘连的发生及严重程度相关。