Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

A Reproducible Technique for Arthroscopic Acromioclavicular Joint Excision

Arthroscopic acromioclavicular joint excision is a commonly performed but technically demanding procedure. Incomplete excision can leave residual symptoms. We present a simple, reproducible technique ensuring satisfactory excision of the joint.     

Symptoms During or Shortly After Isolated Carpal Tunnel Release and Problems Within 24?hours After Surgery

This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16 ± 8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.     

Polyethylene in knee arthroplasty: A review

Polyethylene (PE) has been used extensively in knee arthroplasty since the mid 20th century. Progress in material manufacturing and processing has led to newer polyethylenes over last few decades with different material properties. It has been established that PE wear in knee arthroplasty causes particle induced osteolysis which is the main reason for late failure and requires revision surgery. Although there are various causes of wear, the properties of PE have long been a matter of investigation as a contributory factor. The advent of newer highly cross linked PE has been shown to improve wear rates in hip arthroplasty but the benefits have not been shown to be of the same degree in knee arthroplasty. The laboratory and clinical studies so far are limited and slightly conflicting in their conclusions. The risks of using highly cross linked PE in knee arthroplasty include tibial post fracture, disruption of locking mechanism, liner fracture which can lead to increased wear and osteolysis. The current evidence suggests that highly cross linked polyethylenes should be used with caution and only considered in younger active patients. The results of a recently completed randomized trial to compare the conventional with high molecular weight PE in knee arthroplasty are awaited.     

Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.     

柯氏模型在重症医学科护理规培生身体约束培训中的应用

目的 探讨应用柯氏评估模型评价重症医学科护理规培生对身体约束培训的效果.方法 选取符合纳入和排除标准的57例重症医学科护理规培生,采用前后对照,2018年1月—6月的重症医学科护理规培生为对照组,28例;2018年7月—12月的重症医学科护理规培生为观察组,29例.对照组采用身体约束常规临床经验培训教育和管理,观察组采用规范化培训身体约束和管理.采用柯氏评估模型,对从反应层面、学习层面、行为层面3个方面进行效果评估,评估时间为干预前、干预第1个月、干预第2个月.结果 观察组对培训满意度、对身体约束知识掌握、对身体约束实施情况,与对照组比较,差异均具有统计学意义(P<0.05).结论 对重症医学科护理规培生采用规范化培训身体约束及管理,不仅能提高护理规培生对培训的满意度,还能随着时间的推移,加固对身体约束培训知识的掌握,改善对患者身体约束的情况.     

Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.