Trends in the incidence of AIDS-defining and non-AIDS-defining cancers in people living with AIDS: a population-based study from Sao Paulo, Brazil

People living with AIDS are at increased risk of developing certain cancers. Since the introduction of the highly active antiretroviral therapy (HAART), the incidence of AIDS-defining cancers (ADCs) has decreased in high-income countries. The objective of this study was to analyse trends in ADCs and non-AIDS-defining cancers (NADCs) in HIV-positive people with a diagnosis of AIDS, in comparison to the general population, in Sao Paulo, Brazil. A probabilistic record linkage between the 'Population-based Cancer Registry of Sao Paulo' and the AIDS notification database (SINAN) was conducted. Cancer trends were assessed by annual per cent change (APC). In people with AIDS, 2074 cancers were diagnosed. Among men with AIDS, the most frequent cancer was Kaposi's sarcoma (469;31.1%), followed by non-Hodgkin lymphoma (NHL;304;20.1%). A decline was seen for ADCs (APC = -14.1%). All NADCs have increased (APC = -7.4%/year) significantly since the mid-2000s driven by the significant upward trends of anal (APC = -24.6%/year) and lung cancers (APC = -15.9%/year). In contrast, in men from the general population, decreasing trends were observed for these cancers. For women with AIDS, the most frequent cancer was cervical (114;20.2%), followed by NHL (96;17.0%). Significant declining trends were seen for both ADCs (APC = -15.6%/ year) and all NADCs (APC = -15.8%/ year), a comparable pattern to that found for the general female population. Trends in cancers among people with AIDS in Sao Paulo showed similar patterns to those found in developed countries. Although ADCs have significantly decreased, probably due to the introduction of HAART, NADCs in men have shown an opposite upward trend

The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer

Lung cancer is the leading cause of cancer deaths in the United States. Current therapies are inadequate. Histone deacetylase inhibitors (HDACi) are a recently developed class of anticancer agents that cause increased acetylation of core histones and nonhistone proteins leading to modulation of gene expression and protein activityin - volved in cancer cell growth and survival pathways. We examined the efficacyof the HDACi panobinostat (LBH589) in a wide range of lung cancers and mesotheliomas. Panobinostat was cytotoxic in almost all 37 cancer cell lines tested. IC50 and LD50 values were in the low nmol/L range (4–470 nmol/L; median, 20 nmol/L). Small cell lung cancer (SCLC) cell lines were among the most sensitive lines, with LD50 values consistently <25 nmol/L. In lung cancer and mesothelioma animal models, panobinostat significantlyde creased tumor growth byan average of 62% when compared with vehicle control. Panobinostat was equallye ffective in immunocompetent and severe combined immunodeficiencymic e, indicating that the inhibition of tumor growth by panobinostat was not due to direct immunologic effects.Panobinostat was, however, particularlyeffective in SCLC xenografts, and the addition of the chemotherapyag ent etoposide augmented antitumor effects. Protein analysis of treated tumor biopsies revealed elevated amounts of cell cycle regulators such as p21 and proapoptosis factors, such as caspase 3 and 7 and cleaved poly[ADP-ribose] polymerase, coupled with decreased levels of antiapoptotic factors such as Bcl-2 and Bcl-XL. These studies together suggest that panobinostat maybe a useful adjunct in the treatment of thoracic malignancies, especiallySCLC

Adolescence, sexual life and reproductive planning of adolescents of Serra Pelada, Pará

The life conditions in which an adolescent develops determine his choices and influence his sexual life. The present study aimed to characterize the daily activities and sexual life of 108 adolescents aged between 11 and 15 years, living in Serra Pelada, a municipality of Curionópolis, state of Pará, through a quantitative and qualitative data analysis, distinguishing them according to gender. Results showed the strong presence of gender relations in some cases. Some relation was found between religion and sexual life only in the female sex: 58.5% of them followed some religion and 66.7% had not initiated sexual life at the age of 12 or below. When the adolescents were asked whether they had sexual intercourse with their boyfriends or girlfriends, 93.6% of the girls answered they did not, while 59.6% of the boys answered the same, showing that the girls avoid more the sexual intercourse. The great majority of the girls stated they used a contraceptive method in the first intercourse, while more than 50% of the boys said the opposite. This difference reveals that the responsibility for contraception is deemed as belonging to the female sex. Approximately 70% of the girls state they intend to marry the person with whom they are currently having sexual intercourse, while 60% of the boys say the opposite, which shows that the girls are more afraid to have children early, and more open to commitments.As condições de vida em que um adolescente se desenvolve determinam suas escolhas e influenciam sua vida sexual. O presente estudo visou caracterizar o cotidiano e vida sexual de 108 adolescentes entre 11 e 15 anos de idade, residentes em Serra Pelada, município de Curionópolis, PA, através de análise quantitativa e qualitativa de dados, diferenciando-os quanto ao gênero. Os resultados mostraram a forte presença das relações de gênero em alguns casos. Foi encontrada alguma relação entre religião e vida sexual somente no sexo feminino, em que se observa que 58,5% delas eram adeptas a alguma religião e 66,7 % não haviam iniciado a vida sexual aos 12 anos ou menos. Quando questionados se mantinham, ou não, relações sexuais enquanto namoravam, 93,6% das meninas afirmaram que não, enquanto 59,6% dos meninos disseram o mesmo, mostrando que as meninas evitam mais a relação sexual. A grande maioria das meninas afirmou ter feito uso de método para evitar filho na primeira relação, enquanto mais de 50% dos meninos afirmaram o contrário. Essa diferença reflete que a responsabilidade da contracepção é julgada como pertencente ao sexo feminino. Cerca de 70% das meninas afirmam ter a intenção de se casar com a pessoa com quem tem relação sexual atualmente, enquanto 60% dos meninos afirmam o contrário, o que mostra que as meninas se mostram mais receosas quanto a ter filho cedo, em relação aos garotos, e mostram-se mais abertas ao compromisso

Estimates of the global burden of cervical cancer associated with HIV.

BACKGROUND: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. METHODS: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. FINDINGS: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. INTERPRETATION: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. FUNDING: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief

Changes in the probability of hysterectomy in the city of Mainz and Mainz-Bingen region, Germany

Abstract Background To assess the hysterectomy probability by calendar period and age, the overall and the age-specific prevalence of hysterectomy in women aged 30–65 years. Methods Baseline data (2005–2007) from the population-based MARZY study conducted in Mainz and Mainz-Bingen, Germany, were analysed. 6429 women aged 30–65 years were asked whether they had undergone a hysterectomy and the date and indication of the procedure. We calculated the 5-year age-specific prevalence of hysterectomy and estimated the probability of undergoing a hysterectomy combining two approaches: 1) Kaplan–Meier and 2) Inverse probability weighting (IPW). We assessed potential changes over calendar periods by simulating survival curves, having hysterectomy as the event, employing a Cox proportional hazard model. Results Data on hysterectomy were available for 4719 women. Of these, 961 (20.4%) had undergone a hysterectomy between 1960 and 2006. The hysterectomy prevalence was highest among the 60–64 year-olds (40.7%). The IPW-corrected probability of having a hysterectomy up to the age of 65 years was 36.4%. The age-specific probability of hysterectomy increased from 0.1% (20–24 years), peaking at 45–49 years (7.8%) and declining thereafter to less than 5% among women aged 50 and older. Over time, women were hysterectomised at an increasingly older age. Most hysterectomies (86.7%) were done due to benign disease. Conclusions A shift to older age at hysterectomy with an advancing calendar period likely reflects changes in clinical practice in Germany. Trial registration Landesärztekammer Rheinland-Pfalz: 837.438.03 (4100)

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status