诱导分化治疗中端粒酶活性的改变及其意义

目的研究诱导分化治疗中端粒酶活性的变化规律。方法对白血病细胞株、正常骨髓和急性白血病的骨髓单个核细胞的端粒酶活性进行了检测,观察了全反式维甲酸(ATRA)在体外和体内分化诱导过程中端粒酶活性的改变。结果发现端粒酶表达下调是诱导分化的早期效应之一。诱导分化治疗可使急性白血病M3早幼粒细胞端粒酶活性水平降至正常。结论在体内和体外实验中,ATRA诱导分化过程中伴随着端粒酶活性下调。     

创伤后肺内炎性细胞凋亡与继发性坏死的观察及意义

目的 探讨严重创伤后肺内炎性细胞凋亡与继发性坏死在急性肺损伤发病机制中的地位和作用。方法 复制大鼠多发骨折合并休克模型,采用Annexin-V和PI双标法经流式细胞仪检测创伤后肺泡灌洗液中凋亡与坏死炎性细胞的数量变化,测定细胞分类计数及肺通透指数并作比较。结果伤后动物肺泡灌洗液中巨噬细胞数量减少,而白细胞数量增加。伤后凋亡炎性细胞数量增加,于伤后3h达到高峰。部分凋亡炎性细胞发生继发性坏死,其数量进行性升高并与肺通透指数变化显著相关（r=0.90,P<0.01）。结论 严重创伤后肺泡内炎性细胞发生凋亡,可能因为继发性坏死致炎性内容物外泄而引发急性肺损伤。     

Necrotizing pancreatitis

Acute pancreatitis is primarily caused by gallstone disease and excessive alcohol use. The clinical course is varied and those with severe disease may develop pancreatic necrosis and localized collections. Up to 30% of patients with pancreatic necrosis develop infection. This is difficult to diagnose but requires prompt treatment with antibiotics and often percutaneous, endoscopic or surgical intervention. The imprudent use of antibiotics risks the overgrowth of antibiotic-resistant organisms and makes the treatment of subsequent infections more challenging. Advances in biomarkers and imaging may improve the detection of infection, but the optimal timing of antibacterial and antifungal initiation and duration remain unresolved. Clinical trials are required to address these questions.     

A novel approach to delivery of extracorporeal support using a modified continuous flow ventricular assist device in a mid‐volume congenital heart program

Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device—based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty‐seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device‐based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Biomechanical evaluation of total ankle arthroplasty. Part II: Influence of loading and fixation design on tibial bone–implant interaction

Finite element (FE) models to evaluate the burden placed on the interaction between total ankle arthroplasty (TAA) implants and the bone often rely on peak axial forces. However, the loading environment of the ankle is complex, and it is unclear whether peak axial forces represent a challenging scenario for the interaction between the implant and the bone. Our goal was to determine how the loads and the design of the fixation of the tibial component of TAA impact the interaction between the implant and the bone. To this end, we developed a framework that integrated robotic cadaveric simulations to determine the ankle kinematics, musculoskeletal models to determine the ankle joint loads, and FE models to evaluate the interaction between TAA and the bone. We compared the bone–implant micromotion and the risk of bone failure of three common fixation designs for the tibial component of TAA: spikes, a stem, and a keel. We found that the most critical conditions for the interaction between the implant and the bone were dependent on the specimen and the fixation design, but always involved submaximal forces and large moments. We also found that while the fixation design influenced the distribution and the peak value of bone–implant micromotion, the amount of bone at risk of failure was specimen dependent. To account for the most critical conditions for the interaction between the implant and the bone, our results support simulating multiple specimens under complex loading profiles that include multiaxial moments and span entire activity cycles.     

Early and Direct Rehab Transfer Leads to Significant Cost Savings and Decreased Hospital Length of Stay for Total Joint Arthroplasty in a Veteran Population

BackgroundTotal joint arthroplasty is the most common elective orthopedic procedure in the Veterans Affairs hospital system. In 2019, physical medicine and rehabilitation began screening patients before surgery to select candidates for direct transfer to acute rehab after surgery. The primary outcome of this study was to demonstrate that the accelerated program was successful in decreasing inpatient costs and length of stay (LOS). The secondary outcome was to show that there was no increase in complication, reoperation, and readmission rates.MethodsA retrospective review of total joint arthroplasty patients was conducted with three cohorts: 1) control (n = 193), 2) transfer to rehab orders on postop day #1 (n = 178), and 3) direct transfers to rehab (n = 173). To assess for demographic disparities between cohorts, multiple analysis of variance tests followed by a Bonferroni P-value correction were used. Differences between test groups regarding primary outcomes were assessed with analysis of variance tests followed by pairwise t-tests with Bonferroni P-value corrections.ResultsThere were no significant differences between the cohort demographics or comorbidities. The mean total LOS decreased from 7.0 days in the first cohort, to 6.9 in the second, and 6.0 in the third (P = .00034). The mean decrease in cost per patient was $14,006 between cohorts 1 and 3, equating to over $5.6 million in savings annually. There was no significant change in preintervention and postintervention short-term complications (P = .295).ConclusionsSignificant cost savings and decrease in total LOS was observed. In the current health care climate focused on value-based care, a similar intervention could be applied nationwide to improve Veterans Affair services.