Human risk assessment of benzene after a gasoline station fuel leak

OBJETIVO: Avaliar os riscos à saúde da exposição ao benzeno de comunidade afetada por acidente de vazamento de combustível. MÉTODOS: Dados de acidente de vazamento de combustível ocorrido em Brasília, DF, em 2002, foram obtidos dos relatórios produzidos pelo distribuidor de combustível e submetidos a autoridade ambiental. Informação sobre a população afetada foi obtida em grupos focais com oito participantes. Foram estimados o tempo de exposição e concentração de benzeno na água usando modelo de fluxo subterrâneo acoplado a outro de transporte. A avaliação de risco foi conduzida de acordo com a metodologia da Agência de Registro de Substâncias Tóxicas e Doenças ( Agency for Toxic Substances and Disease Registry ). RESULTADOS: Alta percepção de risco à saúde relacionada ao acidente foi observada na população afetada (22 indivíduos), provavelmente devido à falta de assistência e à comunicação de risco deficiente do governo e agente poluidor. A comunidade esteve exposta a níveis inseguros de benzeno na água (>; 5 µg/L) a partir de dezembro de 2001, cinco meses antes de ser reportado o vazamento. A concentração média de benzeno na água consumida (72,2 µg/L) foi maior que aquela estimada pelo distribuidor usando a metodologia Ação Corretiva Baseada em Risco ( Risk Based Corrective Action ) (17,2 µg/L). A ingestão estimada de benzeno pelo consumo de água e frutas alcançou 0,0091 µg/kg pc/dia (risco de 5 x 10-7 câncer per 106 indivíduos). O nível de benzeno no vapor d´água durante o banho atingiu 7,5 µg/m3 para crianças (risco de câncer de até 1 per 104). O risco carcinogênico total foi de 110 a 200 per 106 indivíduos. CONCLUSÕES: A população afetada pelo vazamento de combustível esteve exposta a concentração de benzeno que pode ter representado risco à saúde. Autoridades governamentais necessitam desenvolver estratégias mais efetivas para rapidamente responder a esses acidentes e proteger a saúde da população afetada e do meio ambiente.OBJETIVO: Evaluar los riesgos para la salud de la exposición al benceno en comunidad afectada por accidente de derrame de combustible. MÉTODOS: Datos del accidente ocurrido en el Distrito Federal (Brasil), fueron obtenidos de los informes realizados por el distribuidor de combustible y sometidos a la autoridad ambienta. Información sobre la población afectada fue obtenida en grupos focales con 8 participantes. Se hicieron estimaciones del tiempo de exposición y concentración de benceno en el agua usando modelo de flujo subterráneo acoplado a otro de transporte. La evaluación de riesgo fue conducida de acuerdo con la metodología de la "Agency for Toxic Substances and Disease Registry". RESULTADOS: Alta percepción de riesgo para la salud relacionada con el accidente fue observada en la población afectada (22 individuos), probablemente debido a la falta de asistencia y a la comunicación de riesgo deficiente del gobierno y agente contaminante. La comunidad estuvo expuesta a niveles inseguros de benceno en el agua (>;5 µg/L) a partir de diciembre de 2001, cinco meses antes de ser reportado el derrame. La concentración promedio de benceno en el agua consumida (72,2 µg/L) fue mayor que la estimada por el distribuidor usando la metodología "Risk Based Corrective Action" (17,2 µg/L). La ingestión estimada de benceno por el consumo de agua y frutas alcanzó 0,0091 µg/kg pc/día (riesgo de 5 x 10-7 de cáncer per 106 individuos). El nivel de benceno en el vapor de agua durante el baño alcanzó 7,5 µg/m3 en niños (riesgo de cáncer de hasta 1 per 104). El Riesgo carcinogénico total fue de 110 a 200 per 106 individuos. CONCLUSIONES: La población afectada por el derrame de combustible estuvo expuesta a concentración de benceno que puede haber representado riesgo para la salud. Autoridades gubernamentales necesitan desarrollar estrategias más efectivas para rápidamente responder a estos accidentes y proteger la salud de la población afectada por el medio ambiente.OBJECTIVE: To assess the health risk of exposure to benzene for a community affected by a fuel leak. METHODS: Data regarding the fuel leak accident with, which occurred in the Brasilia, Federal District, were obtained from the Fuel Distributor reports provided to the environmental authority. Information about the affected population (22 individuals) was obtained from focal groups of eight individuals. Length of exposure and water benzene concentration were estimated through a groundwater flow model associated with a benzene propagation model. The risk assessment was conducted according to the Agency for Toxic Substances and Disease Registry methodology. RESULTS: A high risk perception related to the health consequences of the accident was evident in the affected community (22 individuals), probably due to the lack of assistance and a poor risk communication from government authorities and the polluting agent. The community had been exposed to unsafe levels of benzene (>; 5 µg/L) since December 2001, five months before they reported the leak. The mean benzene level in drinking water (72.2 µg/L) was higher than that obtained by the Fuel Distributer using the Risk Based Corrective Action methodology (17.2 µg/L).The estimated benzene intake from the consumption of water and food reached a maximum of 0.0091 µg/kg bw/day (5 x 10-7 cancer risk per 106 individuals). The level of benzene in water vapor while showering reached 7.5 µg/m3 for children (1 per 104 cancer risk). Total cancer risk ranged from 110 to 200 per 106 individuals. CONCLUSIONS: The population affected by the fuel leak was exposed to benzene levels that might have represented a health risk. Local government authorities need to develop better strategies to respond rapidly to these types of accidents to protect the health of the affected population and the environment

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium

BACKGROUND: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. METHODS: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). FINDINGS: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). INTERPRETATION: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. FUNDING: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH)

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study

Background: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. Methods: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. Results: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age \u3e50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. Conclusions: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes

COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Análise genética e funcional da resposta imune na toxoplasmose ocular humana

Exportado OPUSMade available in DSpace on 2019-08-10T07:45:53Z (GMT). No. of bitstreams: 1 tese_final_v7.2.pdf: 19652373 bytes, checksum: 08ae1c19e3ea8ad998d9fcf326fca157 (MD5) Previous issue date: 4A toxoplasmose  é  uma  infecção  parasitária  que  tem  como  o  agente  etiológico  o  protozoário  Toxoplasma  gondii. A  retinocoroidite (RC) é a manifestação mais comum da toxoplasmose em  pacientes imunocompetentes infectados por esse parasito. Nesse  estudo  foi  analisada a soroprevalência  da  toxoplasmose  em moradores  do Vale  do Jequitinhonha. Nessa região a soroprevalência é de 43,0%. Os moradores também foram submetidos à exame oftalmológico para identificação de RC causada por T. gondi. Foram identificados  68  casos  de  toxoplasmose  ocular  (TO)  crônica  (COT)  o  que  indica manifestação  de TO em 14,4% dos casos de toxoplasmose. Baseando-se no pedigree construído nas três vilas, os casos de TO foram separados em trios para a análise de associação alélica baseada em família (FBAT), que avaliou a possível associação de 43 polimorfimos distribuídos em 14 genes candidatos. Entre esses genes, estão IL-10, IFN-, TLR2, 4, 5 e 9,  TIRAP, MyD88, IRAK4, UNC93B1, NOD2, P2XR7, COL2A1 e ABCA4. Foraencontradas evidências de associação genética dos genes COL2A1, ABCA4, P2XR7, TLR9 e NOD2 com o desenvolvimento de TO. Analisou-se então, se os polimorfismos rs187084 e rs3135499, presentes nos genes de TLR9 e NOD2 e associados ao desenvolvimento de TO (p=0,042  e p=0,039,  respectivamente) interfeririam na  resposta  imune  frente  ao parasito. Para tanto, foi avaliada a produção de citocinas e a imunidade de células T de pacientes  com  COT  ou  com  TO  ativa  (AOT)  e  controles. Não  foram  encontradas diferenças  na  produção  de  citocinas Th1,  Th2  ou  Th17  em pacientes  carregando  os diferentes  genótipos do polimorfismo em TLR9. Também não foram encontradas diferenças nos níveis de citocinas produzidas por células Th1  (IFN-  e  IL-2) quando  comparados  pacientes  com COT ou com  TO ativa (AOT)  com indivíduos assintomáticos. No entanto, foi encontrada produção aumentada de IL-17 por PBMCs de pacientes com COT ou AOT. A produção  aumentada  também  foi associada  ao genótipo  heterozigoto para  o polimorfismo  de NOD2 (rs3135499).  A  IL-17 nesses indivíduos  é  produzida principalmente por células T CD4+/T-bet-/IFN--,  linfócitos  Th17, que estão presentes em  maior  frequência  em  indivíduos com  COT  ou  AOT. Em  conjunto,  esses  resultados sugerem que NOD2  influencia a produção de IL-17 por linfócitos T CD4+, que, por sua vez, medeiam processos inflamatórios que podem contribuir para o desenvolvimento de lesões oculares em pacientes infectados por T. gondii.Toxoplasmosis is a parasitic infection that has the protozoan Toxoplasma gondii as its aetiological  agent.  Retinochoroiditis (RC)  is  the  most  common  manifestation  of toxoplasmosis in immunocompetent patients  infected with the parasite. In this study, we  analize the  seroprevalence  of  toxoplasmosis in  the  inhabitants  of  Vale  do Jequitinhonha.  In  the  area,  the  seroprevalence  of  toxoplasmosis  was  of  43,0%.  The villagers were also submitted to ophthalmological examination for the identification of toxoplasmic RC.  A  total  of 68  cases  of chronic  ocular  toxoplasmosis  (COT)  which indicates  14,4%  of manifestation of ocular  toxoplasmosis (TO).  Based  on  the construction of  pedigrees for  the  three villages, the TO multicases families were splited into trios that  were analysed using  a  family  based  allelic  association  test  (FBAT) to evaluate  potential  associations ith 43 polymorphisms distributed in 14  candidate genes.  Among  these  genes,  are: IL-10, IFN-  and  IL-12,  TLR2,  4,  5  and  9,  MyD88, UNC93B1, TIRAP, NOD2, P2XR7, COL2A1  and  ABCA4.  We  found  evidence  of  genetic association of  the genes COL2A1, ABCA4, P2XR7, TLR9 and NOD2 with the development of TO. We then studied if the polymorphisms rs187084 and rs3135499, in the TLR9 and NOD2 genes  and  which  were  associated  with  the development  of TO  (p=0,042  e p=0,039,  respectively)  would  play  a  role  in  the  immune  response  to  the  parasite. Therefore, we characterized  the  production of citokynes and the T cell response in cases of COT and four cases of active TO (AOT) and controls. We found no differences in the production  of  Th1,  Th2  or  Th17 cytokines in  patients  bearing  any  of  the  possible genotypes for the rs178084 polymorphism in  TLR9 gene.  We also found no difference in cytokines (IFN- and IL-2) when comparing patients with AOT or COT to asymptomatic individuals.  However,  we  found  an  increased  production  of  IL-17  by PBMCs  from patients  with either stage of TO. The increased production of IL-17 was also associated with the heterozygous genotype on NOD2 polymorphism (rs3135499). The main source of IL-17 was shown to be CD4+/T-bet-/IFN--, Th17 lymphocytes, which were present in higher  frequency  in  patients  with  scarred  or  active  lesions  of  ocular  toxoplasmosis. Altogether,  our  results suggest that NOD2 influences the production of IL17 by CD4+T helper  lymphocytes,  which  in  turn  mediates  the  inflammatory  process  and  might contribute to the development of ocular lesions in  patients infected with T. gondii.

Human risk assessment of benzene after a gasoline station fuel leak

OBJECTIVE: To assess the health risk of exposure to benzene for a community affected by a fuel leak. METHODS: Data regarding the fuel leak accident with, which occurred in the Brasilia, Federal District, were obtained from the Fuel Distributor reports provided to the environmental authority. Information about the affected population (22 individuals) was obtained from focal groups of eight individuals. Length of exposure and water benzene concentration were estimated through a groundwater flow model associated with a benzene propagation model. The risk assessment was conducted according to the Agency for Toxic Substances and Disease Registry methodology. RESULTS: A high risk perception related to the health consequences of the accident was evident in the affected community (22 individuals), probably due to the lack of assistance and a poor risk communication from government authorities and the polluting agent. The community had been exposed to unsafe levels of benzene (> 5 µg/L) since December 2001, five months before they reported the leak. The mean benzene level in drinking water (72.2 µg/L) was higher than that obtained by the Fuel Distributer using the Risk Based Corrective Action methodology (17.2 µg/L).The estimated benzene intake from the consumption of water and food reached a maximum of 0.0091 µg/kg bw/day (5 x 10-7 cancer risk per 106 individuals). The level of benzene in water vapor while showering reached 7.5 µg/m3 for children (1 per 104 cancer risk). Total cancer risk ranged from 110 to 200 per 106 individuals. CONCLUSIONS: The population affected by the fuel leak was exposed to benzene levels that might have represented a health risk. Local government authorities need to develop better strategies to respond rapidly to these types of accidents to protect the health of the affected population and the environment