Citations

SummaryRheumatoid arthritis (RA) is associated with the presence of certain HLA class II genes. However, why some individuals carrying RA non‐associated alleles develop arthritis is still unexplained. The trans‐heterodimer between two RA non‐associated HLA genes can render susceptibility to develop arthritis in humanized mice, DQA1*0103/DQB1*0604, suggesting a role for DQ α chains in pathogenesis. In this study we determined the role of DQA1 in arthritis by using mice expressing DQA1*0103 and lacking endogenous class II molecules. Proximity ligation assay showed that DQA1*0103 is expressed on the cell surface as a dimer with CD74. Upon immunization with type II collagen, DQA1*0103 mice generated an antigen‐specific cellular and humoral response and developed severe arthritis. Structural modelling suggests that DQA1*0103/CD74 form a pocket with similarity to the antigen binding pocket. DQA1*0103 mice present type II collagen‐derived peptides that are not presented by an arthritis‐resistant DQA1*0103/DQB1*0601 allele, suggesting that the DQA1*0103/CD74 dimer may result in presentation of unique antigens and susceptibility to develop arthritis. The present data provide a possible explanation by which the DQA1 molecule contributes to susceptibility to develop arthritis.

Recently, several high impact randomised controlled trials have been published suggesting no greater benefit from orthopaedic surgery over conservative treatment, or limited surgical intervention. These studies can have profound effects on clinical practice, leading to the abandonment of previously widely-used operations. How do surgeons who believe these operations are beneficial over conservative treatment rationalise these findings, and justify their use with hospital administrators and health care funders who require evidence for the value and efficacy of surgical treatment? Cite this article: Bone Joint J 2015;97-B:1456–7.

Bariatric surgery has been advocated as a means of reducing body mass index (BMI) and the risks associated with total knee arthroplasty (TKA). However, this has not been proved clinically. In order to determine the impact of bariatric surgery on the outcome of TKA, we identified a cohort of 91 TKAs that were performed in patients who had undergone bariatric surgery (bariatric cohort). These were matched with two separate cohorts of patients who had not undergone bariatric surgery. One was matched 1:1 with those with a higher pre-bariatric BMI (high BMI group), and the other was matched 1:2 based on those with a lower pre-TKA BMI (low BMI group). In the bariatric group, the mean BMI before bariatric surgery was 51.1 kg/m2 (37 to 72), which improved to 37.3 kg/m2 (24 to 59) at the time of TKA. Patients in the bariatric group had a higher risk of, and worse survival free of, re-operation (hazard ratio (HR) 2.6; 95% confidence interval (CI) 1.2 to 6.2; p = 0.02) compared with the high BMI group. Furthermore, the bariatric group had a higher risk of, and worse survival free of re-operation (HR 2.4; 95% CI 1.2 to 3.3; p = 0.2) and revision (HR 2.2; 95% CI 1.1 to 6.5; p = 0.04) compared with the low BMI group. While bariatric surgery reduced the BMI in our patients, more analysis is needed before recommending bariatric surgery before TKA in obese patients. Cite this article: Bone Joint J 2015;97-B:1501–5.

Objectives/HypothesisExternal beam radiation to the neck is widely considered a contraindication for thyroplasty due to concern for infection and implant extrusion. We present a case series of our experience regarding thyroplasty performed in a previously radiated field.Study DesignRetrospective case study at a tertiary academic referral center.MethodsUsing the institution's clinical notes search tool, records from 1999 through 2014 documenting thyroplasty and radiation were identified and reviewed. Patients who received external beam radiation to the operative field prior to thyroplasty were included. Data including duration of radiation, timing and specifics of thyroplasty, postoperative complications, risk factors, clinical voice outcomes, and length of follow‐up were collected.ResultsFourteen patients met criteria for the study. Of all thyroplasty performed, 11 were Silastic implants, two were Gore‐Tex implants, six had concurrent arytenoid adduction, and one was a midline type II thyroplasty. In terms of risk factors for postoperative complications, two were diabetic, none were active smokers, and one had a splenectomy. All patients were given postoperative antibiotics. The median duration of follow‐up after surgery was 14.2 months. No patients were found to have postoperative complications. Pre‐ and postoperative voice data were assessed. Overall, there was improvement in voice outcomes.ConclusionsThyroplasty may be an option for patients who have previously undergone external beam radiation. Short‐term and intermediate outcomes in our patients showed no postoperative complications, and generally voice or dysphagia improved. Careful selection is still warranted when considering thyroplasty in a previously irradiated neck, and long‐term outcomes need further study.Level of Evidence4 Laryngoscope, 126:1849–1853, 2016

ObjectivesWe sought to develop a scoring system that predicts the risk of serious adverse events (SAE's) for individual pediatric patients undergoing cardiac catheterization procedures.BackgroundSystematic assessment of risk of SAE in pediatric catheterization can be challenging in view of a wide variation in procedure and patient complexity as well as rapidly evolving technology.MethodsA 10 component scoring system was originally developed based on expert consensus and review of the existing literature. Data from an international multi‐institutional catheterization registry (CCISC) between 2008 and 2013 were used to validate this scoring system. In addition we used multivariate methods to further refine the original risk score to improve its predictive power of SAE's. Results: Univariate analysis confirmed the strong correlation of each of the 10 components of the original risk score with SAE attributed to a pediatric cardiac catheterization (P < 0.001 for all variables). Multivariate analysis resulted in a modified risk score (CRISP) that corresponds to an increase in value of area under a receiver operating characteristic curve (AUC) from 0.715 to 0.741.ConclusionThe CRISP score predicts risk of occurrence of an SAE for individual patients undergoing pediatric cardiac catheterization procedures. © 2015 Wiley Periodicals, Inc.

Age is the major risk factor for developing Alzheimer’s disease (AD), and modifying age-related factors may help to delay the onset of the disease. The goal of this study was to investigate the relationship between age and the metabolic factors related to the risk of developing AD. The concentrations of insulin, amylin, and amyloid-β peptide (Aβ) in plasma were measured. We further measured the activity of serum Aβ degradation by using fluorescein- and biotin-labeled Aβ40. Apolipoprotein E4 allele (ApoE4) and cognitive impairment were characterized. Subjects were divided into three age groups: 60–70, 70–80, and ≥80 years old. We found that the older the subjects, the lower the concentration of insulin (p = 0.001) and the higher the concentration of Aβ1-40 (p = 0.004) in plasma. However, age was not associated with the concentration of another pancreatic peptide, amylin, and only marginally with Aβ1-42. These relationships remained in the absence of diabetes, cardiovascular disease, and stroke, and regardless of the presence of ApoE4 and cognitive impairment. Both age and ApoE4 were inversely associated with, while insulin was positively associated with, the activities of Aβ degradation in serum. Our study suggested that low concentration of insulin and high concentration of Aβ40 are aging factors related to the risk of AD.

AbstractBackgroundCachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied.MethodsTwenty‐eight male Wistar rats were divided into four groups: control (C), control supplemented with L‐glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L‐glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis.Key ResultsTumor‐bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake.Conclusions & InferencesThere are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L‐glutamine has differential and complex effects of ICC, it reduces tumor size and tumor‐associated cachexia, which supports its beneficial therapeutic role in cancer.

Purpose To assist in determining barriers to an oncology career incorporating cancer prevention, the American Society of Clinical Oncology (ASCO) Cancer Prevention Workforce Pipeline Work Group sponsored surveys of training program directors and oncology fellows. Methods Separate surveys with parallel questions were administered to training program directors at their fall 2013 retreat and to oncology fellows as part of their February 2014 in-training examination survey. Forty-seven (67%) of 70 training directors and 1,306 (80%) of 1,634 oncology fellows taking the in-training examination survey answered questions. Results Training directors estimated that ≤ 10% of fellows starting an academic career or entering private practice would have a career focus in cancer prevention. Only 15% of fellows indicated they would likely be interested in cancer prevention as a career focus, although only 12% thought prevention was unimportant relative to treatment. Top fellow-listed barriers to an academic career were difficulty in obtaining funding and lower compensation. Additional barriers to an academic career with a prevention focus included unclear career model, lack of clinical mentors, lack of clinical training opportunities, and concerns about reimbursement. Conclusion Reluctance to incorporate cancer prevention into an oncology career seems to stem from lack of mentors and exposure during training, unclear career path, and uncertainty regarding reimbursement. Suggested approaches to begin to remedy this problem include: 1) more ASCO-led and other prevention educational resources for fellows, training directors, and practicing oncologists; 2) an increase in funded training and clinical research opportunities, including reintroduction of the R25T award; 3) an increase in the prevention content of accrediting examinations for clinical oncologists; and 4) interaction with policymakers to broaden the scope and depth of reimbursement for prevention counseling and intervention services.