Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD

Background: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). Methods: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. Results: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. Conclusions: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.     

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

IntroductionEarly diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe.MethodsWe analysed HIV test data from Zimbabwe''s nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV‐positive test after at least one HIV‐negative test in the programme. We used logistic regression to analyse test positivity over three time‐periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time‐periods.ResultsDuring the 10‐year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV‐negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2).ConclusionsTest positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.     

Current situation of donation after circulatory death in European countries

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000–2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000–2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short‐term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% (P = NS) and delayed graft function in 50.2% vs. 75.7% (P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% (P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short‐term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed.     

Noninflammatory pseudotumor simulating venous thrombosis after metal-on-metal hip resurfacing

Metal-on-metal hip resurfacing has become a widespread procedure, especially in young, physically active patients. Pseudotumor is a new complication that can occur after hip resurfacing and metal-on-metal total hip arthroplasty (THA). This article presents a case of a 37-year-old woman who underwent metal-on-metal resurfacing of the left hip for symptomatic osteoarthritis. Twelve months following implantation, the patient reported painless swelling of the left lower leg. There was no clinical evidence of a deep venous thrombosis. Ultrasound and computed tomography showed a solid cystic lesion in the iliopsoas muscle, which communicated with the hip joint and compressed the external iliac vein. As a consequence, the cystic lesion was resected marginally. A few months later, the patient reported some discomfort in the groin and symptoms of instability, metallic clicking, and a restricted range of motion. Clinical and radiological examination revealed normal findings. Determining the serum concentration of cobalt and chromium revealed high increased levels of these metal ions. Ten months following excision of the pseudotumor, the patient reported recurrent swelling of the left lower leg. Computed tomography of the affected area showed a lobulated cystic formation; therefore, a relapse was suspected. At the second revision, the mass was excised and the implant was revised to a conventional ceramic-on-ceramic THA. At 30-month follow-up, the patient was doing well and there were no signs of local recurrence. Additionally, the metal ion levels of cobalt and chromium in the blood had significantly decreased.     

A Process and Outcomes Evaluation of the International AIDS Conference: Who Attends? Who Benefits Most?

The objective of the study was to conduct a process and outcomes evaluation of the International AIDS Conference (IAC). Reaction evaluation data are presented from a delegate survey distributed at the 2004 IAC held in Thailand. Input and output data from the Thailand IAC are compared to data from previous IACs to ascertain attendance and reaction trends, which delegates benefit most, and host country effects. Outcomes effectiveness data were collected via a survey and intercept interviews. Data suggest that the host country may significantly affect the number and quality of basic science IAC presentations, who attends, and who benefits most. Intended and executed HIV work‐related behavior change was assessed under 9 classifications. Delegates who attended 1 previous IAC were more likely to report behavior changes than attendees who attended more than 1 previous IAC. The conference needs to be continually evaluated to elicit the required data to plan effective future IACs.     

Prophylactic Mastectomy in BRCA1/2 Mutation Carriers and Women at Risk of Hereditary Breast Cancer: Long-Term Experiences at the Rotterdam Family Cancer Clinic

Background BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce. Methods From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between 1994 and 2004, relevant data on the occurrence of BC in relation to PM, complications in relation to breast reconstruction (BR), mutation status, age at PM and preoperative imaging examination results were extracted from the medical records, and analyzed separately for women without (unaffected, n = 177) and with a BC history (affected, n = 181). Results No primary BCs occurred after PM (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC was detected almost 4 years after PM (primary BC not found). Median age at PM was younger in unaffected women (P < .001), affected women more frequently were 50% risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in 3% of the patients (in 5 affected, and 5 unaffected women, respectively). In 49.6% of the women opting for BR one or more complications were registered, totaling 215 complications, leading to 153 surgical interventions (71%). Complications were mainly related to cosmetic outcome (36%) and capsular formation (24%). Conclusions The risk of developing a primary BC after PM remains low after longer follow-up. Preoperative imaging and careful histological examination is warranted because of potential unexpected (pre)malignant findings. The high complication rate after breast reconstruction mainly concerns cosmetic issues.     

Australian emergency doctors' and nurses' acceptance and knowledge regarding brain death: a national survey

Healthcare staff's acceptance of brain death (BD) being a valid determination of death is essential for optimized organ and tissue donation (OTD) rates. Recently, resources to increase Australian OTD rates have been aimed at emergency departments (ED) as a significant missed donor potential was discovered. A cross-sectional survey was conducted to assess Australian ED clinicians' acceptance and knowledge regarding BD. Most (86%) of the 599 medical and 212 nursing staff accepted BD, but only 60% passed a 5-item-validated BD knowledge tool. BD knowledge was related to the acceptance of BD. Accepting BD influenced attitudes toward OTD, including willingness to donate. BD acceptance and knowledge were related to education/training regarding OTD, years of experience in EDs, experience with OTD-related tasks, and increased perceived competence and comfort with OTD-related tasks. Of concern, more than half of respondents who did not pass the BD test reported feeling competent and comfortable explaining BD to next of kin; of respondents who had recent experience with this, more than a third failed the BD test. Despite being generally positive toward OTD, Australian ED clinicians do not have a sound knowledge of BD. This may be hampering efforts to increase donation rates from the ED.     

The effects of preprimed oxygenators on gas transfer efficiency

Cancellation of on-pump coronary artery bypass grafting after the circuit is primed may result in the discarding of unused circuits. In some off-pump cases, a surgeon may request that the circuit be primed, but complete the surgical procedure without utilizing the circuit. The major concerns about the unused circuit are its sterility and the performance of the oxygenator after it has been primed for a long period of time. The goal of this study is to determine whether prepriming of the circuit with and without albumin has an effect on the gas transfer efficiency of oxygenators during simulated cardiopulmonary bypass. Monolyth integrated membrane lungs (Sorin Biomedical, Arvada, CO) were used to deoxygenate and oxygenate the bovine blood. Oxygenators were preprimed for 72 (N = 6) and 24 (N = 6) hours before testing. In control group (N = 6), oxygenators were tested immediately (0 h) after they were primed. Three different priming solutions were used: physiological saline solution (Group A); 1.25% of human albumin (Group B); and 5% human albumin (Group C). The blood was modified to the American Association of Medical Instrumentation Standards before testing. The blood flow through the oxygenators was set at 2 Lpm and 4 Lpm, with gas (FiO2 at 1.0) to blood flow ratio at 1:1. Cultures were also obtained from preprimed oxygenators to test circuit sterility. Oxygen transfer in oxygenators primed for 0 h at blood flow of 4 Lpm were 203 mL/min +/- 9.7 (Group A), 263.1 mL/min +/- 52.9 (Group B), and 270.5 mL/min +/- 13.1(Group C, p < .01 vs. Group A). In oxygenators preprimed for 72 h, the CO2 transfers were 135.0 mL/min +/- 21.8 (Group A), 104.9 mL/min +/- 2.4 (Group B), and 148.9 +/- 26.6 (Group C, p < .006 vs. Group B). In addition, the pressure drops were 56.5 mmHg +/- 5.5 (Group A), 82.6 mmHg +/- 13.4 (Group B), and 67.6 mmHg +/- 15.3 (Group C, p < .05 vs. Group B). In group A, O2 transfer were 203.5 mL/min +/- 9.7 (0 h), 272.4 mL/min +/- 66.6 (24 h), and 260.8 mL/min +/- 31.1 (72 h, p < .01 vs. 0 h). In group B, O2 transfer were 263.1 mL/min +/- 52.0 (0 h), 302.7 mL/min +/- 77.4 (24 h), and 235.2 mL/min +/- 16.5 (72 hr, p < .02 vs. 24 hr). Cultures obtained from 12 preprimed oxygenators presented no organism growth for up to 5 days. In conclusion, oxygen transfer increases in oxygenators preprimed with albumin immediately after they were primed. However, gas transfer decreased after they were primed with albumin for 72 h. Oxygenators preprimed for 24 h and 72 h with 0.9% saline had better O2 transfer than those primed for 0 h.