Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Levantamento etnobotânico de plantas medicinais na cidade de Ipameri - GO Ethnobotanical survey of medicinal plants in Ipameri City - Goiás State

Os objetivos deste trabalho foram: identificar as espécies vegetais utilizadas com fins medicinais pela comunidade de Ipameri (Estado de Goiás); investigar as preferências com relação à produção e comercialização dessas plantas; e diagnosticar o perfil de gênero e as faixas etárias e salariais de seus usuários. Para isso, foram realizadas entrevistas estruturadas com 200 famílias da cidade e coletadas as plantas visando-se a sua correta identificação. O material foi herborizado, identificado e depositado no Herbário da Universidade Estadual de Goiás (HUEG). Das 200 famílias entrevistadas, 75 disseram não fazer uso de plantas com fins medicinais (37,5%), enquanto 125 afirmaram fazê-lo (62,5%). O grupo que utiliza relacionou 35 espécies mais empregadas: hortelã-rasteira (Mentha x villosa L.), boldo-sete-dores (Plectranthus barbatus Andrews.), capim-cidreira (Cymbopogon citratus (DC.) Stapf.), quebra-pedra (Phyllanthus niruri L.), camomila (Chamomilla recutita (L.) Rauschert.), poejo (Mentha pulegium L.), guaco (Mikania glomerata Spreng.), mentrasto (Ageratum conyzoides L.), alfavacão (Ocimum gratissimum L.), losna (Artemisia canphorata Vill.), bálsamo (Eysenhardtia platycarpa Mich.), carqueja (Baccharis trimera (Less.) DC.), funcho (Foeniculum vulgare Mill.), babosa (Aloe vera L.) e malva (Althaea officinalis L.). Todas as famílias consumidoras (100%) afirmaram preferir as plantas cultivadas de forma orgânica, selecionando-as através da boa aparência (68% das famílias) e consumindo-as in natura (sem beneficiamento, 100%). A utilização de plantas medicinais em Ipameri é independente do sexo (54%, mulheres e 46%, homens) e se estende às várias faixas etárias e também sócio-econômicas, configurando-se assim, um bom mercado consumidor.The aims of this study were: to identify the plant species used for medicinal purposes by the community at Ipameri (Goiás State); to investigate the preferences with respect to the production and marketing of these plants; and to diagnose the gender profile and the age and wage ranges of users. Thus, structured interviews were conducted with 200 families in the city and plants were collected for their correct identification. The material was herborized, identified and deposited in the Herbarium of "Universidade Estadual de Goiás" (HUEG). Of the 200 families interviewed, 75 said they did not make use of plants for medicinal purposes (37.5%), while 125 said they do use them (62.5%). The latter group reported the 35 most used species: "hortelã-rasteira" (Mentha x villosa L.), "boldo-sete-dores" (Plectranthus barbatus Andrews.), lemon grass (Cymbopogon citratus (DC.) Stapf.), "quebra-pedra" (Phyllanthus niruri L.), chamomile (Chamomilla recutita (L.) Rauschert.), pennyroyal (Mentha pulegium L.), guaco (Mikania glomerata Spreng.), mentrasto (Ageratum conyzoides L.), clove basil (Ocimum gratissimum L.), wormwood (Artemisia canphorata Vill.), balm (Eysenhardtia platycarpa Mich.), broom (Baccharis trimera (Less.) DC.), fennel (Foeniculum vulgare Mill.), aloe (Aloe vera L.) and mallow (Althaea officinalis L.). All consumer families (100%) stated to prefer plants grown organically, to select the plants based on their good appearance (68% families) and to eat them in natura (unprocessed, 100%). The use of medicinal plants in Ipameri is independent of gender (54% womem and 46% men) and extends to several age and socioeconomic ranges, configuring thus a good consumer market

Different patterns of presentation and evolution of Non-Determined Leucoencephalopathy (NDLE) in HIV positive subjects.

Background: The introduction of highly active antiretroviral therapy (HAART) has significantly modified the pattern of HIV-related neurological diseases and the occurrence of opportunistic infections of the central nervous system (CNS). Among leucoencephalopathies, more and more cases have been reported where no viral agent was involved, being classified as NDLE. Methods: In our prospective study were enrolled HIV positive patients of the HIV Clinic in Pavia from May 2003 to June 2005, either asymptomatic but on HAART for at least 7 years or with neurological symptoms, possibly related to the presence of NDLE, regardless the duration of the infection. A neurological examination and a brain MRI were performed in eligible subjects. Patients presenting white matter lesions at the MRI underwent spinal puncture at baseline ad every six months. CSF was tested for JCV, CMV, HSV-1, HSV-2, EBV, VZV using PCR. NDLE was diagnosed in presence of lesions of white matter without the detection of any infectious cause. Results: 105 subjects were enrolled in the study, 26 of these being symptomatic. Fifteen patients had a positive MRI (2 neurotoxoplasmosis, 1 cryptococcal meningitis, 1lymphoma, Eleven cases of NDLE were identified, M/F ratio 5/6, median age: 41.3 years old, the median CD4 cells count at diagnosis was 324 cells/microl. Nine patients were classified as C3 according to CDC classification, one was B2 and one was A1. Plasma HIV RNA was undetectable in 9 patients, one patient was na\uefve and one was in stop therapy. The MRI lesions were hyperintense in T2 and isointense in T1, there was no perilesional oedema and gadolinium enhancement. The lesions had a heterogeneous distribution, the majority of them were multiple and involved more then one site. During the follow up (median: 20 months) 2 patients had a CNF positive for JCV virus and diagnosed with progressive multifocal leucoencephalopathy (PML). Only one of the nine subjects currently on follow up had a clinical progression of the neurological disease, the others are stable. Conclusions: In our study, 11/26 HIV positive patients with neurological symptoms presented white matter lesions, 9 of them being currently followed for NDLE. At the moment we can\u2019t exclude the possibility of further detection of other PML cases in our NDLE group of patient