Revision Total Shoulder Arthroplasty is Associated with Increased Thirty-Day Postoperative Complications and Wound Infections Relative to Primary Total Shoulder Arthroplasty

© 2017, Hospital for Special Surgery. Background: With an increasing volume of primary total shoulder arthroplasties (TSA), the number of revision TSA cases is expected to increase as well. However, the postoperative medical morbidity of revision TSA has not been clearly described. Questions/Purposes: The purpose of this study was to determine the rate of postoperative complications following revision TSA, relative to primary TSA. In addition, we sought to identify independent predictors of complications, as well as to compare operative time and postoperative length of stay between primary and revision TSA. Methods: Patients who underwent primary/revision TSA between 2005 and 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Differences in complications, readmission rates, operative time, length of stay, and predictors of complications were evaluated using bivariate and multivariate analyses. Results: A total of 10,371 primary TSA (95.4%) and 496 revision TSA cases (4.6%) were identified. The overall complication rate was 6.5% in primary and 10.7% in revision TSA patients (p \u3c 0.001). Multivariate analysis identified an increased risk of any complication (odds ratio 1.73, p \u3c 0.001), major complication (2.08, p = 0.001), and wound infection (3.45, p = 0.001) in revision TSA patients, relative to primary cases. Operative time was increased in revision cases (mean ± standard deviation, 125 ± 62.5), relative to primary (115 ± 47.7, p \u3c 0.001). Age \u3e 75, female sex, history of diabetes or chronic obstructive pulmonary disease, and American Society of Anesthesiologists classification ≥ 3 were associated with increased risk of any complication. Smoking history was the only significant predictor of wound infection. Conclusion: Revision TSA, in comparison to primary, poses an increased risk of postoperative complications, particularly wound infections. A history of smoking was an independent predictor of wound infections

A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25–65 when interviewed in 1990–92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93–1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02–1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86–1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09–1.64) compared with never users (SIR = 1.07, 95% CI 0.96–1.19). Breast cancer increased with increasing duration of use and for 48–120 months use the SIR was 1.92 (95% CI 1.32–2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use. © 2001 Cancer Research Campaign http://www.bjcancer.co

Post-Stall Aerodynamic Modeling and Gain-Scheduled Control Design

A multidisciplinary research e.ort that combines aerodynamic modeling and gain-scheduled control design for aircraft flight at post-stall conditions is described. The aerodynamic modeling uses a decambering approach for rapid prediction of post-stall aerodynamic characteristics of multiple-wing con.gurations using known section data. The approach is successful in bringing to light multiple solutions at post-stall angles of attack right during the iteration process. The predictions agree fairly well with experimental results from wind tunnel tests. The control research was focused on actuator saturation and .ight transition between low and high angles of attack regions for near- and post-stall aircraft using advanced LPV control techniques. The new control approaches maintain adequate control capability to handle high angle of attack aircraft control with stability and performance guarantee

PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity.

Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are crucial for efficient immune responses against malignancies and contribute to reduced relapse rates after transplantation. Chimeric antigen receptors (CAR) redirect effector cells to cell surface antigens and enhance killing of target cells. With this study, we aimed to combine enhanced cytotoxicity of CD19-CAR-iNKT cells against lymphoma cells with their tolerogenic properties. iNKT cells were isolated from peripheral blood mononuclear cells and transduced with an anti-CD19-CAR retrovirus. After in vitro expansion, the functionality of CD19-CAR-iNKT cells was assessed by flow cytometry, image stream analysis and multiplex analysis in single-stimulation or repeated-stimulation assays. Moreover, the immunoregulatory properties of CD19-CAR-iNKT cells were analyzed in apoptosis assays and in mixed lymphocyte reactions. The effect of checkpoint inhibition through nivolumab was analyzed in these settings. In this study, we could show that the cytotoxicity of CD19-CAR-iNKT cells was mediated either through engagement of their CAR or their invariant T-cell receptor, which may circumvent loss of response through antigen escape. However, encounter of CD19-CAR-iNKT cells with their target induced a phenotype of exhaustion. Consequently, checkpoint inhibition increased cytokine release, cytotoxicity and survival of CD19-CAR-iNKT cells. Additionally, they showed robust suppression of alloreactive immune responses. In this work, we demonstrate that CAR-iNKT cells are a powerful cytotherapeutic option to prevent or treat relapse while potentially reducing the risk of GVHD after allogeneic HCT

Statin use, hyperlipidaemia, and the risk of breast cancer

Hydroxymethyl glutaryl coenzyme A inhibitors (‘statins’) are carcinogenic in rodents and an increased incidence of breast cancer was reported among pravastatin users in one randomised trial. We conducted a case–control study in the General Practice Research Database to evaluate the risk of breast cancer among 50- to 79-year old women treated with statins for hyperlipidaemia. Case and control women were matched by age, general practice, duration of prescription history in the General Practice Research Database, and index date. Adjusting for history of benign breast disease, body mass index, and use of hormone replacement therapy, women currently treated with statins had an estimated relative risk for breast cancer of 1.0 (95% confidence interval 0.6–1.6) compared to women without hyperlipidaemia. Untreated hyperlipidaemia was associated with an increased risk of breast cancer (estimated relative risk 1.6; 95% confidence interval 1.1–2.5). The estimated relative risk among women currently receiving only non-statin lipid-lowering drugs was similar to that of women with untreated hyperlipidaemia (1.8; 95% confidence interval 0.9–3.4). We found no evidence for an increasing trend in breast cancer risk with increasing duration of statin use (median duration 1.8 years, maximum 8.6 years)

Ethnic differences in ovulatory function in nulliparous women

African-American women have a long-standing approximately 20% higher breast cancer incidence rate than USA White women under age 40 while rates among Latinas are lower than those of Whites. The reasons for this are not clear, however they may be due to ethnic differences in circulating oestradiol and progesterone levels. In a cross-sectional study, we investigated whether anovulation frequency and circulating serum oestradiol and/or progesterone levels vary among normally cycling nulliparous African-American (n=60), Latina (n=112) and non-Latina White (n=69) women. Blood and urine specimens were collected over two menstrual cycles among healthy 17- to 34-year-old women. Frequency of anovulation was greater among White women (nine out of 63, 14.3%) than African-American women (four out of 56, 7.1%) or Latina women (seven out of 102, 6.9%), although these differences were not statistically significant. African-American women had 9.9% (P=0.26) higher follicular phase oestradiol concentrations than Latina women and 17.4% (P=0.13) higher levels than White women. African-American women also had considerably higher levels of luteal phase oestradiol (vs Latinas, +9.4%, P=0.14; vs Whites, +25.3%, P=0.003) and progesterone (vs Latinas, +15.4%, P=0.07; vs Whites, +36.4%, P=0.002). Latina women were also observed to have higher follicular oestradiol, and luteal oestradiol and progesterone levels than White women (follicular oestradiol: +6.8%, P=0.48; luteal oestradiol: +14.6%, P=0.04; luteal progesterone: +18.2%, P=0.06). These results suggest that exposure to endogenous steroid hormones may be greater for young African-American and Latina women than for Whites

Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients

Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use. This represents a random sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 (excluding 1980 and 1981) with a 100% follow-up. Ever-use of hormone replacement therapy (HRT) prior to diagnosis was significantly associated with a longer overall survival in women with their breast cancer diagnosed at ages 45 and above, relative risk (RR) of dying 0.73 (95% confidence interval (CI) 0.62-0.87; P = 0.0005). Ever use of HRT prior to breast cancer diagnosis was significantly positively associated with overall longer survival after adjustment for T-stage, N-stage, M-stage, year of diagnosis and age at diagnosis, RR of dying 0.78 (95% CI 0.65-0.93; P = 0.006). Hormone replacement therapy use and oestrogen receptor positivity were independently significantly associated with overall longer survival, P = 0.005 and P < 0.0001, respectively, in one model. HRT use and progesterone receptor positivity were also independently significantly associated with longer overall survival, P = 0.003 and P = 0.0003, respectively, in another model. The mode of diagnosis was known in 705 women. Mammography screening was not more common among HRT users compared with never-users, where this information was available. Both mammography screening and HRT use were independently associated with longer survival, P = 0.002 and P = 0.038 respectively