Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2‐macrophages and amyloid‐β protein adjacent to loose total joint implants

We sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast‐lineage or an adipocyte‐lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2‐macrophage phenotype was observed in parallel with pathologic accumulations of amyloid‐β, τ‐protien and 3‐nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2‐macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:615–624, 2014.     

Bone Tissue Properties Measurement by Reference Point Indentation in Glucocorticoid‐Induced Osteoporosis

Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment‐induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca+D) supplements or anti‐osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual‐energy X‐ray absorptiometry (DXA). Although Ca+D‐treated patients exhibited substantial and significant deterioration, risedronate‐treated patients exhibited no significant change, and both denosumab‐ and teriparatide‐treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids. © 2015 American Society for Bone and Mineral Research.     

The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: Salmon oil versus vegetable oils

The lower plasma lipid levels and lower incidence of atherosclerotic diseases in Greenland Eskimos suggested that the unusual fatty acids present in their diet of seal and fish may be anti-atherogenic. These fatty acids are eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids and are of the omega-3 fatty acid family. We have compared a salmon oil diet containing high levels of these unique fatty acids to a control diet high in saturated fat and to a vegetable oil diet high in linoleic acid (C18:2). All diets contained 40% of the total calories as fat and 500 mg of cholesterol; they differed only in fatty acid composition. In 4 wk the salmon oil diet reduced plasma cholesterol levels from 188 to 162 mg/dl (p < 0.001) and triglyceride levels from 77 to 48 mg/dl (p < 0.005). LDL and VLDL cholesterol levels changed from 128 to 108 and 13 to 8 mg/dl (p < 0.005), respectively. HDL cholesterol levels did not change. The vegetable oil diet caused similar decreases in cholesterol levels but did not lower triglyceride levels. The omega-3 fatty acids comprised up to 30% of the total fatty acids in each plasma lipid class after the salmon diet. Fish oils contain fatty acids which may be metabolically unique and potentially useful in the control of both hypercholesterolemia and hypertriglyceridemia.     

Pneumatic dilation for the treatment of achalasia in untreated patients and patients with failed Heller myotomy

BACKGROUND: Laparoscopic Heller myotomy (HM) has become an increasingly preferred modality to treat achalasia. However, the treatment course after a failed myotomy is controversial with fears that pneumatic dilation (PD) has high perforation risk. GOAL: To compare success and safety of graded PD with Rigiflex balloons in achalasia patients without a prior HM (untreated cases) and those with a failed HM. STUDY: A total of 108 patients were retrospectively evaluated: 96 untreated cases (53 male, 43 female, mean age 51 years) and 12 failed HM(7 male, 5 female, mean age 54 years). Symptoms (dysphagia and regurgitation) and physiologic studies, lower esophageal sphincter pressure (LESP) and timed barium swallow, assessed pre- and post-PD. Success was defined as: 1) symptom improvement to /=80% decrease in 5-minute barium column height from initial timed barium swallow. RESULTS: A total of 139 PDs performed (117 untreated cases, 22 failed HM): 2 perforations in untreated cases and none in failed HM group. Baseline demographics were similar, but failed HM patients had significantly lower LESP and timed barium swallow columns. Despite less LES resistance, failed HM group (symptom and physiologic success: 50% and 10%) did not do as well after PD as compared with untreated cases (symptom and physiologic success: 74% and 52%, respectively). Five failed HM patients had good symptom relief after PD compared with poor responders these patients were older (>50 years) and had LESP >17 mm Hg. CONCLUSIONS: PD perforation risk is not higher after HM. Despite lower LES pressure, patients undergoing PD after failed HM do not do as well as untreated cases. Factors predicting better outcome include older age and higher LES pressure.     

Successful Delivery of RRT in Ebola Virus Disease

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.     

Preventable Major Cardiovascular Events Associated With Uncontrolled Glucose,Blood Pressure,and Lipids and Active Smoking in Adults With Diabetes With and Without Cardiovascular Disease: A Contemporary Analysis

OBJECTIVEThe objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking.RESULTSMean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD.CONCLUSIONSAdditional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.     

Development of an international online learning platform for hepatopancreatobiliary surgical training: a needs assessment

BackgroundThe Americas Hepato-Pancreato-Biliary Association (AHPBA) and the Australian and New Zealand Hepatic, Pancreatic and Biliary Association (ANZHPBA) are developing an online distance learning curriculum to facilitate an interactive didactic experience for hepatopancreatobiliary (HPB) fellows in the operationalization of existing HPB fellow curricula. Two needs assessment surveys were carried out to identify the optimal structure and process for deployment in fellow education.MethodsA 22-question survey querying fellows'' learning styles and current and anticipated use of learning tools was disseminated electronically to 38 North American and Australasian HPB fellows. A follow-up 20-question survey was administered to assess fellows'' feelings regarding online content.ResultsResponse rates were 55% (n = 21) for the first survey and 42% for the second (n = 16). In the first survey, 67% of respondents claimed familiarity with the required HPB curriculum, and 43% indicated dissatisfaction with current personal study strategies. A total of 62% (n = 13) reported studying with focused clinical relevance versus using a prescribed curriculum (n = 1, 5%). Fellows anticipated participating using online tools once (n = 10, 48%) or two or three times (n = 5, 24%) per week. Most respondents (n = 18, 86%) would meaningfully follow one or two discussions per month. The second survey identified themes for improvement such as discussion topics of interest, avoidance of holiday timing and mandatory participation.ConclusionsAn international online distance learning format is an appealing mechanism for improved dissemination and operationalization of the established HPB fellow curricula. Fellows will engage in interactive discussions monthly. Controversial topics or those requiring complex decision making are best suited to this learning format.     

Systematic review of pathophysiological changes following hepatic resection

Objectives

Major hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.

Methods

The MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were ‘hepatectomy/’, ‘liver function/’, ‘liver failure/’ and ‘physiology/’.

Results

Predictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.

Conclusions

The pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.