Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

International audienceObjectives The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population.Methods A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients.Results We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53– 62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36–47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and " recently diagnosed ageing " groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). " Experienced ageing " patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the " experienced ageing " patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001.Conclusions In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent

黃牛與荷蘭乳牛換毛期的研究

　　生物受到外在環境極大的影響，特別是身體表面，直接左右於外在環境的部分很多，與生理變化相同、形態上的變化也很顯著。覆蓋的毛髮掌管體溫調節與保護身體的功能，各種動物會依照品種，或者是個體，各自呈現著最適合各自生存環境的狀態。因此，熱帶地區的家畜與溫帶地區的家畜有所不同是極為理所當然的自然現象。與冷熱調節關係密切、依據季節轉變的覆蓋皮毛的換毛狀態亦是如此，不難想見溫帶地區的家畜、與熱帶地區的家畜身上顯現的差異性。本論文即為溫帶產乳牛Holstein與熱帶產牛的黃牛的換毛狀態比較調查。 　　研究內容如下所述。(1)換毛通常進行於春秋二季。不過，會因為品種的不同而有時期上的差異。Holstein在春天的5月開始換毛，秋天的話在10月以後才會開始。換毛最為明顯的時期是6月。黃牛的狀況是在春天的4月，秋天的9月開始換毛。4月中旬過後、以及9月底至10月初是換毛最為明顯的時期。這個換毛狀態也會因為不同個體而有些許的差異性。(2)除了春秋二季的定期換毛以外，每個月多少都會有一些換毛。將新生毛的比例加以平均的話，則可知Holstein在6月有34％，7月有12％，8月有31％的程度。黃牛則是在6月有12％，7月有16％，8月有26％這樣的程度。(3)只要換成夏毛的話，則其中不會混有冬毛。(4)覆蓋毛髮因應氣溫變化而有長度與粗細的不同，冬天細長，夏天粗短。(5) Holstein與黃牛互相比較，則換毛的顯著時期較遲。這是因為在因應氣候的方面，Holstein的反應程度比黃牛來得低。(6)一般而言，夏毛的生存期比冬毛短，夏毛在經過約略5個月之後轉為冬毛，而冬毛則是經過約略7個月後轉為夏毛。(7)髓質在夏天的時候不太發達。封面、書名頁、印記、目次頁 I　緒言 II　研究材料並ニ研究方法 　A）供試動物 　B）供試動物ノ飼養管理 　　i）黄牛ノ状態 　　ii）ホルスタインノ状態 　C）試驗期間及ビ採毛期日 　D）採毛方法 　E）調査方法 III　實驗結果 IV　實驗結果ノ觀察 　A）ホルスタイン 　B）黄牛 　C）ホルスタイント黄牛ノ比較 V　結論 VI　摘要 参【參】考文献 圖表 　（一） 　（二） 圖版、印記、封

Missed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT’AIDS cohort

Abstract Background HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat’AIDS cohort in 2016. Methods Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area. Results Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%). Conclusion With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access

Nevirapine Use Is Associated with Higher Bone Mineral Density in HIV-1 Positive Subjects on Long-Term Antiretroviral Therapy

International audienceWe assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA <50 c/mL in 89%, median CD4 of 619/mm3. Prevalence of low BMD was 18% in males and 6% in females. The factors associated with a Z-score < -2 in males were uric acid renal loss [adjusted odds ratio (aOR): 6.1; 95% confidence interval (CI): 1.2-31.5; p = .03], HCV coinfection (aOR: 4.0; 95% CI: 1.3-12.2; p = .02), and less frequent window of exposure to nevirapine (NVP) (aOR: 0.1; 95% CI: 0.02-0.6; p = .01). For the full study sample, there was a strong positive association between duration of exposure to NVP and lumbar spine Z-score (p = .004). HIV-positive patients exposed to long-term cART have a high incidence of low BMD. Tenofovir disoproxil fumarate and ritonavir-boosted protease inhibitors did not seem to be associated with increased risk of low BMD, whereas NVP exposure appeared to have an independent positive association