Impacts of heat and wildfire on preterm birth.

BACKGROUND: Climate change continues to increase the frequency, intensity, and duration of heat events and wildfires, both of which are associated with adverse pregnancy outcomes. Few studies simultaneously evaluated exposures to these increasingly common exposures. OBJECTIVES: We investigated the relationship between exposure to heat and wildfire smoke and preterm birth (PTB). METHODS: In this time-stratified case-crossover study, participants consisted of 85,806 California singleton PTBs (20-36 gestational weeks) from May through October of 2015-2019. Birthing parent ZIP codes were linked to high-resolution daily weather, PM2.5 from wildfire smoke, and ambient air pollution data. Heat day was defined as a day with apparent temperature >98th percentile within each ZIP code and heat wave was defined as ≥2 consecutive heat days. Wildfire-smoke day was defined as a day with any exposure to wildfire-smoke PM2.5. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) comparing exposures during a hazard period (lags 0-6) compared to control periods. Analyses were adjusted for relative humidity, fine particles, and ozone. RESULTS: Wildfire-smoke days were associated with 3.0% increased odds of PTB (ORlag0: 1.03, CI: 1.00-1.05). Compared with white participants, associations appeared stronger among Black, Hispanic, Asian, and American Indians/Alaskan Native participants. Heatwave days (ORlag2: 1.07, CI: 1.02-1.13) were positively associated with PTB, with stronger associations among those simultaneously exposed to wildfire smoke days (ORlag2: 1.19, CI: 1.11-1.27). Similar findings were observed for heat days and when other temperature metrics (e.g., maximum, minimum) were used. DISCUSSION: Heat and wildfire increased PTB risk with evidence of synergism. As the occurrence and co-occurrence of these events increase, exposure reduction among pregnant people is critical, especially among racial/ethnic minorities.

Titania Mixed with Silica: A Low Thermal-Noise Coating Material for Gravitational-Wave Detectors.

Coating thermal noise is one of the dominant noise sources in current gravitational wave detectors and ultimately limits their ability to observe weaker or more distant astronomical sources. This Letter presents investigations of TiO_{2} mixed with SiO_{2} (TiO_{2}:SiO_{2}) as a coating material. We find that, after heat treatment for 100 h at 850 °C, thermal noise of a highly reflective coating comprising of TiO_{2}:SiO_{2} and SiO_{2} reduces to 76% of the current levels in the Advanced LIGO and Advanced Virgo detectors-with potential for reaching 45%, if we assume the mechanical loss of state-of-the-art SiO_{2} layers. Furthermore, those coatings show low optical absorption of <1 ppm and optical scattering of ≲5 ppm. Notably, we still observe excellent optical and thermal noise performance following crystallization in the coatings. These results show the potential to meet the parameters required for the next upgrades of the Advanced LIGO and Advanced Virgo detectors.

Comparing Virtual and In-Person Implementation of a School-Based Sexual Health Promotion Program in High Schools with Large Latino Populations.

Many sexual health programs transitioned to virtual implementation during the COVID-19 pandemic. Despite its devastation, the pandemic provided an opportunity to learn about virtual compared to in-person implementation of a sexual health promotion program-El Camino. This study assessed differences in program attendance, engagement, quality, and student ratings for virtual versus in-person implementation of El Camino as part of a rigorous evaluation in high schools with high Latino populations in Maryland. Drawing on positive youth development practices, El Camino helps participants identify personal goals and learn about sexual reproductive health and healthy relationships. This mixed-methods study incorporates data from performance measures, baseline and post-intervention participant surveys, observations, monthly implementation reports, and debriefs with facilitators to describe and compare virtual and in-person program implementation. At baseline, participants were an average of 16.2 years old; between 8 and 12th grade; 61% female; 79% Hispanic, Latino, or of Spanish origin; and 54% spoke mostly Spanish at home. Recruitment and retention of students outside of school classes were challenging for both forms of implementation. However, attendance was higher during in-person implementation and in schools where the organization implementing El Camino had a strong presence before the pandemic. Findings indicate high fidelity, excellent quality ratings, and positive student perceptions of the program and facilitators in both the virtual and in-person cohorts, which suggest that both forms of implementation were comparable and furthermore highlight the strength of the virtual adaptation of the El Camino program.

Primary care nurse practitioner practices to lower type 2 diabetes risks in women with a history of gestational diabetes mellitus.

BACKGROUND: Women with a gestational diabetes mellitus (GDM) history have increased lifetime type 2 diabetes (T2D) risk, with 16 times greater risk 3 to 6 years after the pregnancy, compared with women without GDM. Offspring from diabetes-complicated pregnancies also face increased health risks. PURPOSE: The study purpose was to describe the primary care practices of nurse practitioners (NPs) aimed at reducing T2D-related health risks in women with a history of GDM. METHODOLOGY: Florida-licensed primary care NPs (n = 47) completed a 57-item online survey that included an 8-item scale about recommended practices to reduce T2D risks for women with GDM history. Descriptive statistics, Chi Square test, and Fisher exact test were conducted. RESULTS: Most (67%) participants "often/always" screened for T2D every 1-3 years per guidelines, but only 31.8% "often/always" advised about pregnancy planning/preconception T2D assessment. Compared with "none" or ≤2 hours of GDM care education, participants with >2 hours were more likely (p < .05) to "often/always" perform five recommended practices: 1) counsel about increased T2D risks; 2) educate about self-advocacy for T2D screening; 3) T2D screening every 1-3 years; 4) counsel about breastfeeding to reduce T2D risk; and 5) discuss postpartum weight loss and increased physical activity to lower T2D risk. CONCLUSION: Findings indicate inconsistent care practices and suggest that >2 hours of education about care of women with GDM history may increase primary care NPs performing recommended practices to reduce T2D risks and prevent health problems for women and future offspring. IMPLICATIONS: Nurse practitioner education is needed involving care of women with GDM history to mitigate risks for T2D.

Social Support and Parenting Stress in Hispanic Parents of Children with Autism Spectrum Disorder.

The purpose of this integrative review is to synthesize the literature examining the relationship between parenting stress and social support in Hispanic parents of children with autism spectrum disorder (ASD). A database search of studies that evaluated parenting stress and social support in this population was conducted. Fourteen studies met inclusion criteria. Despite high stress levels, both informal and formal social supports improved parenting stress among Hispanic families. Few studies evaluated culturally sensitive social support interventions. With the increasing prevalence of ASD, the development of culturally sensitive social support interventions is necessary to promote the well-being of Hispanic families.

Young men of color lower on adult attachment anxiety have higher carotid-intima media thickness compared to white young men: The exploration of an unexpected finding.

Cardiovascular disease (CVD) remains the number one cause of death among men in the United States. Emerging research demonstrates that socioemotional mechanisms such as adult attachment, or the ways in which individuals are able to form and maintain socioemotional bonds, may impact physical health via alterations in physiological stress functioning. However, there may be key differences in the relation between attachment and physical health by race and sexual orientation. Thus, this study sought to examine the potential moderating effect of race and sexual orientation on the association between adult attachment and carotid-intima media thickness (cIMT), a measure of subclinical cardiovascular disease, among young men. The sample consisted of 72 young men (mean [SD] age = 22.92 [3.23]: 30.6 % identified as White, 30.6 % as Black, and 38.8 % as Other), each of which were surveyed and underwent an ultrasound to measure cIMT. Ordinary Least Squares (OLS) regression was used in order to examine our study hypotheses. We first ran a main effects model to examine adult attachment's (i.e., anxiety and avoidance) association with mean cIMT. We then ran two interaction models with an interaction between race/ethnicity and adult-related attachment and sexual orientation and adult attachment. We found that race significantly moderated the association between attachment-related anxiety and mean cIMT in our study sample. However, we did not find evidence to suggest that race moderated the association between attachment-related avoidance and mean cIMT in our study sample. In comparison to White individuals, Black individuals and those who identified as "Other" race with lower scores on attachment-related anxiety had higher mean cIMT. Additionally, higher scores on attachment-related anxiety were associated with lower mean cIMT among Black and "Other" respondents, but not among White respondents. We did not find evidence to suggest that sexual orientation moderated the association between adult attachment and mean cIMT in our study sample. Our findings suggest that adult attachment anxiety may be protective for young men of color but not for White young men. Future research should utilize longitudinal study designs in order to better understand how adult attachment influences CVD risk among racially/ethnically diverse young men.

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group.

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

Physical activity changes among non-Hispanic Black pregnant women.

OBJECTIVE: To examine aerobic physical activity (PA) among non-Hispanic Black pregnant women. DESIGN: Longitudinal prospective cohort study. SAMPLE: A subset of 161 non-Hispanic Black pregnant women from the Midwestern US participating in a larger study completed questionnaires about aerobic physical activity (PA) before pregnancy (reported at 24.46±2.13 weeks gestation), mid-pregnancy (24.46±2.13 weeks gestation), and late pregnancy (31.78±1.95 weeks gestation). MEASUREMENTS: Aerobic PA was measured using the Rapid Assessment of Physical Activity (RAPA). RESULTS: Most participants reported being active prior to pregnancy (n = 101, 63%), with 60 (37%) underactive/sedentary. Aerobic RAPA scores were highest pre-pregnancy (3.29±1.11, median = 4, interquartile range [IQR] = 1) compared with mid-pregnancy (3.05±1.26, median = 4, IQR = 2) and late pregnancy (3.05±1.24, median = 4, IQR = 2). Pre-pregnancy scores were significantly higher than mid-pregnancy scores (Wilcoxon test = 1472, p = .008) and late pregnancy scores (Wilcoxon test = 1854, p = .01). CONCLUSION: Most Black pregnant participants reported high levels of aerobic PA both before pregnancy and during pregnancy. However, many were underactive or sedentary. Aerobic PA decreased during pregnancy compared with pre-pregnancy, without the drop in third trimester PA found in other populations. Providers should assess PA across pregnancy and promote adequate PA for maternal and infant health, particularly among Black women.

Air pollution and preterm birth: A time-stratified case-crossover study in the San Joaquin Valley of California.

BACKGROUND: Air pollution is linked to preterm birth (PTB), but existing studies are primarily focused on chronic exposures, conducted in areas with moderate pollution, and/or subject to confounding. OBJECTIVES: We investigated short-term associations between two pollutants [particulate matter <2.5 microns (PM2.5 ) and ozone] and PTB, and estimated excess PTB cases potentially attributed to these pollutants. METHODS: This time-stratified case-crossover study includes 196,970 singleton pregnancies affected by PTB and early term birth from the San Joaquin Valley (SJV), California, USA (2007-2015). Daily ozone and PM2.5 concentrations were estimated by the SJV Air Pollution Control District and geospatially linked to maternal zip code. We used conditional logistic regression models to estimate the odds ratio (OR) and 95% confidence intervals (CI) for the associations between an interquartile range (IQR) increase in pollutants and very preterm (VPTB, 20-34 weeks), moderate preterm (MPTB, 34-36 weeks) and early term births (ETB, 37-38 weeks). We adjusted all models for co-pollutants and meteorological factors. RESULTS: During warm seasons (May-October), an IQR increase in ozone was associated with 9-11% increased odds of VPTB from lag 0 (ORlag0 1.09, 95% CI 1.04,1.16) to lag 7 (ORlag7 1.11, 95% CI 1.04,1.16). Findings were consistent for MPTB and ETB. Ozone was potentially responsible for an excess of 3-6 VPTBs, 7-9 PTBs and 24-42 ETBs per 1,000 singleton deliveries. During cold seasons (November-April), increased PM2.5 exposure was associated with 5-6% increased odds of VPTB beginning at lag 3 (ORlag3 1.06, 95% CI 1.02,1.11). PM2.5 was associated with an excess of 1-3 VPTBs, 0-3 MPTBs and 6-18 ETBs per 1,000 singleton deliveries. CONCLUSIONS: PM2.5 and ozone are associated with increased risk of VPTB, MPTB and ETB within one week of exposure and are potential contributors to the increasing PTB trend. More research is needed to further understand the role of air pollution on PTB risk.

Associations between Disability and Infertility among U.S. Reproductive-Aged Women.

We aim to evaluate the association between self-reported disabilities and infertility and whether disabilities are associated with decreased likelihood of seeking infertility-related care. This US nationally representative cross-sectional analysis includes 3789 non-pregnant women aged 18-49 years without history of hysterectomy or oophorectomy (NHANES, 2013-2018). Disabilities and infertility were both self-reported in personal interviews with trained interviewers. Logistic regression models estimated the adjusted odds ratio (aOR) and 95% confidence intervals for the association between disabilities and infertility and related care seeking. Models adjusted for potential confounders and complex probability sampling. Compared to women without disabilities, women with disabilities (WWD) had higher odds of infertility (aOR: 1.78 (1.31-2.40)). Similar findings were observed for sensory (2.32 (1.52-3.52)) and cognitive disabilities (1.77 (1.28-2.44)). Among women with infertility, WWD were less likely to seek infertility-related care (0.68 (0.32-1.44)) but these estimates were not statistically significant. WWD have increased odds of reporting infertility, and if affected, are less likely to visit a health care provider for this condition. While more research is needed to understand reproductive health issues and needs among WWD, it is important to push for more equitable policies and practices to address the health needs of this underserved population.

Consequences of Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients.

Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patients, 76% were male with a mean age of 57.5 ± 10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End-Stage Liver Disease (MELD) score was 19 (12-28). Only 1 patient was positive for MRSA; 19% of patients (n = 47) had ESBLE fecal carriage at the time of wait-list placement and 15% (n = 37) had it after LT. Infection-free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC-free survival at 6 and 12 months was significantly lower in ESBLE fecal carriage (HR, 1.6; P = 0.04). MELD score >19 (HR, 3.0; P = 0.01) and occurrence of infection during the first 3 months on the wait list (HR, 4.13; P < 0.001) were independent risk factors for LRC occurrence in the multivariate analysis. Our study is the first showing that in a cohort of patients with cirrhosis waiting for LT LRC-free survival was lower in patients with ESBLE fecal carriage but that infection-free survival was not different between the 2 groups.

Evidence of polyamorphic transitions during densified SiO2 glass annealing.

In situ X-ray scattering monitoring is carried out during temperature annealing on different densified SiO2 glasses. Density fluctuations and intermediate range coherence from X-ray scattering (small-angle X-ray scattering) and diffraction (wide angle X-ray scattering) evidence a maximum in their evolution at the same relaxation time. These extrema confirm the existence of an intermediate transitory disordered state between the two more ordered high and low density amorphous states. We propose that the existence of this transitory state confirms the existence of two mega basins in the energy landscape and therefore an amorphous-amorphous transition. Including older Raman results, we show that this intermediate disorder state implies similar mechanisms at all length scales from a few angstroms to 5 nm.

An Examination of Factors Affecting Quality of Life for Children With Asthma and Their Caregivers in Southeastern Georgia.

INTRODUCTION: Despite effective treatments and interventions, asthma continues to affect children's health-related quality of life (QOL). This study explored factors affecting QOL of children with asthma and their caregivers. METHODS: A mixed-model design was used. Children (7-17 years) completed the Paediatric Asthma Quality of Life Questionnaire, and parents/caregivers completed the Paediatric Asthma Caregiver's Quality of Life Questionnaire. These surveys focused on activity limitations, emotional function, and child symptoms. RESULTS: The sample included 104 children and 104 caregivers. Analysis showed emergency department (ED) visits as a significant predictor of QOL for children in the domains of Physical Activity, Emotional, and Symptoms. Increased ED visits and reliever medication use predicted lower emotional QOL and physical QOL for parents, whereas increased use of controller medications predicated improved physical QOL. DISCUSSION: Factors contributing to QOL, along with characteristics of those with the lowest QOL indicators, have been determined. Identification of interventions to reduce ED visits warrants further investigation.

Relaxation study of pre-densified silica glasses under 2.5 MeV electron irradiation.

We examined the "relaxation properties" of pre-densified synthetic fused silica glass under 2.5 MeV electron irradiation. The densification of the glass was either obtained by hot compression (5 GPa-350 °C and 5 GPa-1000 °C) or via a thermal treatment increasing its fictive temperature (Tf = 1050, 1250 and 1400 °C). Under irradiation, the pre-densified silica glasses exhibit a relaxation of their macroscopic density with increasing integrated dose. Density was reduced for hot compressed silica and increased for Tf samples with different relaxation rates but it is remarkable that all sample densities follow a trend towards the same equilibrium value around 2.26 for a dose larger than 10 GGy despite a different final topology. After irradiation of hot compressed silica, the Raman spectra display a significant increment of 4 and almost 3-membered rings whereas they exhibit a glass density reduction; demonstrating that a D2 band increase cannot be considered as an absolute marker of the glass compaction. The correlation between density and D2 intensity remains valid until silica density remains lower than 2.26. In contrast, the FWHM of the main band peaking at 440 cm-1 appears to remain correlated to the silica glass density for all investigated samples.

Large-vessel vasculitis in human immunodeficiency virus-infected patients.

OBJECTIVE: The objective of this study was to describe large-vessel vasculitis (LVV) in patients with human immunodeficiency virus (HIV) infection. It is a retrospective single-center study conducted between 2000 and 2015 through a university hospital of 11 HIV-infected patients with LVV. METHODS: The characteristics and outcome of 11 HIV-infected patients with LVV (7 patients fulfilled international criteria for Takayasu arteritis, 5 patients had histologic findings of vasculitis, and 5 patients had imaging features of aortitis) were analyzed and compared with those of 82 patients with LVV but without HIV infection. RESULTS: Concerning the HIV-infected patients with LVV (n = 11), the mean age was 40 years (range, 36-56 years), and 55% of patients were female. At diagnosis of LLV, the mean initial CD4 cell count was 455 cells/mm3 (range, 166-837 cells/mm3), and the median HIV viral load was 9241 copies. Vascular lesions were located in the aorta (n = 7), in supra-aortic trunks (n = 7), and in digestive arteries (n = 3). Inflammatory aorta infiltrates showed a strong expression of interferon-γ and interleukin 6. In HIV-negative LVV patients (n = 82), the median age was 42 years, and 88% of the patients were women. Thirty patients had an inflammatory syndrome. Seventy patients had been treated with glucocorticosteroids and 57 with immunosuppressive treatments. Compared with their negative counterparts, HIV-positive patients with LVV were more frequently male (P = .014), had more vascular complications (ie, Ishikawa score; P = .017), and had more frequent revascularization (P = .047). After a mean follow-up of 96 months, four relapses of vasculitis were reported, and one patient died. Regardless of the HIV virologic response, antiretroviral therapy improved LVV in only one case. CONCLUSIONS: LVV in HIV-infected patients is a rare and severe entity.

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

Trends in survival after cancer diagnosis among HIV-infected individuals between 1992 and 2009. Results from the FHDH-ANRS CO4 cohort.

Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan-Meier survival rates were estimated for four periods: 1992-1996, 1997-2000, 2001-2004 and 2005-2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001-2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992-1996) and early-cART (1997-2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005-2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001-2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.

DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia.

Idiopathic CD4 lymphopenia (ICL) is a rare heterogeneous immunological syndrome of unclear etiology. ICL predisposes patients to severe opportunistic infections and frequently leads to poor vaccination effectiveness. Chronic immune activation, expansion of memory T cells, and impaired T-cell receptor (TCR) signaling have been reported in ICL, but the mechanistic and causative links remain unclear. We show that late-differentiated T cells in 20 patients with ICL displayed defective TCR responses and aging markers similar to those found in T cells from elderly subjects. Intrinsic T-cell defects were caused by increased expression of dual-specific phosphatase 4 (DUSP4). Normalization of DUSP4 expression using a specific siRNA improved CD4(+) T-cell activity in ICL, as this restored TCR-induced extracellular signal-regulated kinase activation and increased the expression of the costimulatory molecules CD27 and CD40L. Conversely, repeated TCR stimulation led to defective signaling and DUSP4 overexpression in control CD4(+) T cells. This was associated with gradual acquisition of a memory phenotype and was curtailed by DUSP4 silencing. These findings identify a premature T-cell senescence in ICL that might be caused by chronic T-cell activation and a consequential DUSP4-dependent dampening of TCR signaling.

Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort.

OBJECTIVES: Improved survival among HIV-infected individuals after the advent of combination antiretroviral therapy (cART) had drawn attention on non-AIDS-defining cancers. We evaluated the incidence and risk trends of lung cancer, Hodgkin's lymphoma, liver and anal cancers, focusing on patients with CD4 cell recovery and age at diagnosis, by comparison with the general population. DESIGN: Cohort study. METHODS: Standardized incidence rates were calculated in the HIV-infected individuals followed in the FHDH and the general population in France in 1997-2000, 2001-2004, and 2005-2009. We estimated standardized incidence ratios for each period and for patients with CD4 cell count at least 500 cells/µl for at least 2 years on cART. RESULTS: Among the 84,504 HIV-infected individuals, the risk of lung and anal cancers fell during the cART era, whereas that of Hodgkin's lymphoma and liver cancer remained stable. In 2005-2009, the standardized incidence ratios for lung cancer, Hodgkin's lymphoma, liver and anal cancers were, respectively, 2.8 [95% confidence interval (CI) 2.5-3.1], 26.5 (95% CI 23.2-30.1), 10.9 (95% CI 9.6-12.3) and 79.3 (95% CI 69.5-90.1). Among patients with CD4 cell recovery on cART, the risk was close to that of the general population for lung cancer, nine-fold higher for Hodgkin's lymphoma, and 2.4-fold higher for liver cancer. Age at diagnosis was significantly younger among HIV-infected individuals for lung cancer (-3.3 years), Hodgkin's lymphoma (-1 year) and liver cancer (-10.1 years). CONCLUSION: HIV-infected patients were at a higher risk for the four cancers over 1997-2009. CD4 cell recovery appears to control the excess risk of lung cancer. For liver cancer and Hodgkin's lymphoma, our results suggest that CD4 should never drop below 500/µl 500 cells/µl to avoid the excess risk.