RESUMO
The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.
Assuntos
Infecções por HIV , HIV-1 , Humanos , Feminino , HIV-1/genética , HIV-1/efeitos dos fármacos , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Adulto , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Motivos de Aminoácidos , Carga Viral , Proteína gp120 do Envelope de HIV/genética , Estudos de Coortes , Brasil , Terapia Antirretroviral de Alta Atividade , Progressão da Doença , MutaçãoRESUMO
Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.
Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Masculino , Humanos , Feminino , Infecções por HIV/complicações , Estudos Prospectivos , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD8-Positivos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Fármacos Anti-HIV/uso terapêutico , Carga ViralRESUMO
OBJECTIVE: COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). METHOD: This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. RESULTS: Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. CONCLUSION: Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.
Assuntos
COVID-19 , Tromboinflamação , Tromboembolia Venosa , Humanos , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , América Latina/epidemiologia , Hospitais Públicos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Incidência , Fatores de Risco , Anticoagulantes/administração & dosagem , Masculino , Feminino , Tempo de InternaçãoRESUMO
Interferon-gamma (IFN-γ) plays a crucial role in viral infections by preventing viral replication and in the promotion of innate and adaptive immune responses. However, IFN-gamma can exert distinct effects in different persistent viral infections. The long-term overproduction of IFN-γ in retroviral infections, such as the human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), and human endogenous retroviruses (HERVs), resulting in inflammation, may cause neuronal damage. This review is provocative about the role of IFN-γ during persistent retroviral infections and its relationship with the causation of some neurological disorders that are important for public health.
Assuntos
Infecções por HIV , Vírus Linfotrópico T Tipo 1 Humano , Citocinas , Humanos , Inflamação , Interferon gamaRESUMO
Antiretroviral treatment has significantly increased the survival of patients infected with HIV-1. However, with increased survival, cognitive changes associated with HIV are frequently observed in this population. The clinical manifestations of HIV changes can vary as a result of several aspects, including the virus transmission route. Several studies have pointed out premature neurological changes in vertically infected patients, while the manifestation of cognitive damage in adults may take a longer time. Objective: The aim of this study was to verify the prevalence of cognitive changes in patients with HIV via vertical transmission after the highly active antiretroviral therapy and the cognitive performance of these patients compared to a group of sexually infected patients. Methods: A total of 48 patients were evaluated, 25 with vertical transmission and 23 with sexual transmission, between May 2013 and February 2015 at the Institute of infectology Emilio Ribas. Neuropsychological tests were applied to assess cognitive performance, scales to assess symptoms of anxiety and depression, and sociodemographic questionnaire. Results: The results demonstrate that the frequency of cognitive impairment in vertically transmitted patients was higher than in sexually transmitted patients. Conclusions: These findings suggest that the deleterious effects of the HIV virus on the development of the central nervous system reverberate more strongly than in patients who acquire it after adulthood.
O tratamento antirretroviral tem aumentado significativamente a sobrevida de pacientes contaminados pelo HIV-1. Entretanto, com o aumento da sobrevida, observam-se frequentemente alterações cognitivas associadas ao HIV nessa população. As manifestações clínicas das alterações do HIV podem variar em decorrência de diversos aspectos, entre eles a via de transmissão do vírus. Diversos estudos têm apontado alterações neurológicas prematuras em pacientes contaminados por via vertical, enquanto a manifestação de danos cognitivos em adultos pode levar um tempo maior. Objetivo: O objetivo deste estudo foi verificar a prevalência das alterações cognitivas em pacientes com HIV via transmissão vertical após a era da terapia antirretroviral altamente ativa e o desempenho cognitivo desses pacientes comparado ao de um grupo de pacientes contaminados por via sexual. Métodos: Foram avaliados 48 pacientes, sendo 25 com transmissão vertical e 23 com transmissão sexual no período entre maio de 2013 e fevereiro de 2015, no Instituto de Infectologia Emílio Ribas. Foram aplicados testes neuropsicológicos para avaliar o desempenho cognitivo, escalas para avaliar sintomas de ansiedade e depressão e questionário sociodemográfico. Resultados: Os resultados demonstraram que a frequência de comprometimento cognitivo em pacientes contaminados via transmissão vertical foi maior do que naqueles contaminados via transmissão sexual. Conclusões: Essas descobertas sugerem que os efeitos deletérios do vírus HIV na formação do sistema nervoso central repercutem de forma mais acentuada do que em pacientes que o adquiriram após a vida adulta.
RESUMO
Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.
Assuntos
Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/etiologia , Deficiências do Desenvolvimento/diagnóstico , Suscetibilidade a Doenças , Febre , Síndromes de Imunodeficiência/diagnóstico , Fenótipo , Alelos , Biópsia , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , MutaçãoRESUMO
The demand for high value health care uncovered a steady trend in laboratory tests ordering and inappropriate testing practices. Residents' training in laboratory ordering practice provides an opportunity for quality improvement. We collected information on demographics, the main reason for the appointment, preexisting medical conditions and presence of co-morbidities from first-visit patients to the internal medicine outpatient service of our university general hospital. We also collected information on all laboratory tests ordered by the attending medical residents. At a follow-up visit, we recorded residents' subjective perception on the usefulness of each ordered laboratory test for the purposes of diagnosis, prognosis, treatment or screening. We observed that 17.3% of all ordered tests had no perceived utility by the attending resident. Tests were usually ordered to exclude differential diagnoses (26.7%) and to help prognosis estimation (19.1%). Age and co-morbidity influenced the chosen category to legitimate usefulness of tests ordering. This study suggests that clinical objectives (diagnosis, prognosis, treatment or prevention) as well as personalization to age and previous health conditions should be considered before test ordering to allow a more appropriate laboratory tests ordering, but further studies are necessary to examine this framework beyond this medical training scenario.
Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Atitude do Pessoal de Saúde , Técnicas de Laboratório Clínico , Medicina Interna/educação , Internato e Residência/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.
Assuntos
Biomarcadores , COVID-19 , Biomarcadores/análise , Proteína C-Reativa , COVID-19/diagnóstico , COVID-19/terapia , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Estudos Prospectivos , Receptores Imunológicos/análise , SARS-CoV-2RESUMO
OBJECTIVE To estimate the magnitude and identify patterns of change in prostate cancer mortality in the state of São Paulo and in the 17 regional health care networks, according to age groups from 50 years onwards, in the period between 2000 to 2015. METHODS Age-adjusted mortality rates (per 100,000 men) were calculated by the direct method using the Segi world population as standard. Joinpoint regression was used to calculate the average annual percent change (AAPC), with a confidence interval of 95% (95%CI), by regional network and age group (50-59, 60-69, 70-79 and 80 years or more). RESULTS For the state of São Paulo, age-adjusted mortality rates were 15.2, 13.3 and 11.9 per 100,000 men, respectively, in the periods between 2000 to 2005, 2006 to 2010 and 2011 to 2015, with a significant decrease trend (AAPC = -2.10%; 95%CI -2.42 - -1.79) each year. Among the 17 networks, 11 presented significant mean annual reductions, ranging from -1.72% to -3.05%. From the age of 50 onwards, there was a sharper reduction in the groups from 50 to 59 (AAPC = -2.33%; 95%CI -3.04 - -1.62) and 60 to 69 years (AAPC = -2.84%; 95%CI - 3.25 - -2.43). CONCLUSION Although reductions in mortality are still slight, they indicate progress in prostate cancer control actions. Screening actions and changes in therapeutic behaviors in recent decades may be modifying incidence and survival, resulting in changes in the mortality profile. More detailed studies will be useful in understanding the factors that lead to the interregional variations found.
Assuntos
Neoplasias da Próstata/mortalidade , Idoso , Brasil/epidemiologia , Meio Ambiente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Neoplasias da Próstata/patologiaRESUMO
Coronavirus disease 19 (COVID-19) is caused by SARS-Cov-2 and the manifestations of this infection range from an absence of symptoms all the way up to severe disease leading to death. To estimate the prevalence of past infection in a population, the most readily available method is the detection of antibodies against the virus. This study has investigated the prevalence of anti-SARS-CoV-2 antibodies in outpatients of the Hospital das Clinicas, in Sao Paulo city (Brazil), which is a large university hospital belonging to the public health system that cares for patients with complex diseases who need tertiary or quaternary medical care. Our serological inquiry was carried out for 6 weeks, with once-a-week blood sampling and included 439 patients from several outpatient services. Overall, 61 patients tested positive for anti-SARS-CoV-2 IgG (13.9%); 56.1 % of the patients live in Sao Paulo city, with the remaining living in other towns of the metropolitan area; 32.8% of the patients testing positive for IgG antibodies to SARS-CoV-2 were asymptomatic, 55.7% developed mild or moderate disease and 11.5% had to be hospitalized. The prevalence of SARS-CoV-2 positive serology was lower among patients who had received the seasonal influenza vaccine compared to the ones who did not. These findings may indicate that those individuals care more about health issues, and/or that they have a better access to health care and/or a better quality of health care service. The large proportion of patients who were unaware of having had contact with SARS-CoV-2 deserves attention, reflecting the scarcity of tests performed in the population.
Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Pacientes Ambulatoriais , Pneumonia Viral/diagnóstico , Betacoronavirus , Brasil/epidemiologia , COVID-19 , Humanos , Pandemias , Prevalência , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
ABSTRACT The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.
RESUMO
ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.
RESUMO
OBJECTIVE: We evaluated the association between cognitive deficits and leukocyte telomere length (LTL) in HIV-1-infected individuals. DESIGN: 73 HIV-1-infected patients undergoing neuropsychological evaluation and 91 healthy controls were included in this study. Fifteen HIV-1 positive patients did not have cognitive disorders whereas 26 had asymptomatic neurocognitive disorder (ANI), 13 presented mild to moderate neurocognitive disorder (MND), and 10 had HIV-associated dementia (HAD). METHODS: DNA from the peripheral blood of HIV-1-infected patients was used for measurement of telomere length by real-time PCR. HIV-1 viral load was determined in blood. RESULTS: LTL decreased with age in healthy controls (p=0.0001). Regardless of the HIV status, age-matched LTL from HIV patients, including those with ANI and MND, were shortened in comparison to the healthy control group (p=0.0073); however, no association was found among the HIV-1-infected individuals with cognitive deficits (p=0.01). In addition, no gender-related association with LTL was observed (p=0.80), smoking, physical exercise, and plasma viral load were not correlated to telomere length (p=0.66). CONCLUSIONS: We concluded that leukocyte telomere length may not be a marker of cellular senescence in individuals with HIV infection and neurocognitive disorders.
Assuntos
Infecções por HIV/genética , Infecções por HIV/psicologia , HIV-1 , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/virologia , Homeostase do Telômero/genética , Telômero/genética , Fatores Etários , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos/virologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Estatísticas não Paramétricas , Inquéritos e Questionários , Carga ViralRESUMO
Abstract Objective COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). Method This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. Results Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. Conclusion Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.
RESUMO
INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a complex disease, triggered by a hypersensitivity reaction to the allergens of Aspergillus fumigatus, a fungus that opportunistically colonizes the lungs of patients with asthma. The diagnosis of ABPA is difficult. A major problem is the lack of standardized allergens used in the determination of specific IgE, but the use of recombinant allergens has been proposed to overcome this. The aim of the present study is to evaluate whether serological tests for IgE specific to recombinant allergens of A. fumigatus (rAsp) can aid in the detection of sensitization to this fungus and in the diagnosis of ABPA. METHODS: This was an observational, cross-sectional study. The diagnosis of ABPA, using classical criteria, was searched in 65 asthmatics patients with immediate cutaneous reactivity to A. fumigatus. After that, serum titers of IgE against rAsp f 1, rAsp f 2, rAsp f 3, rAsp f 4 and rAsp f 6 were determined. In order to compare the differences between patients with confirmed and excluded diagnosis of ABPA, the two-tailed Fisher's exact test was used. RESULTS: Although 19 of 65 patients had IgE against at least one recombinant, the disease was diagnosed in only six patients by classical criteria. One of them had IgE against all recombinant allergens tested and another one had antibody against Asp f 3. DISCUSSION: The determination of serum IgE against recombinant A. fumigatus allergens in this group was not helpful to make the diagnosis of ABPA, neither to detect sensitization to fungus.
Assuntos
Alérgenos/imunologia , Aspergilose Broncopulmonar Alérgica/diagnóstico , Proteínas Fúngicas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/isolamento & purificação , Antígenos de Plantas , Aspergilose Broncopulmonar Alérgica/sangue , Aspergilose Broncopulmonar Alérgica/imunologia , Aspergillus fumigatus , Criança , Estudos Transversais , Diagnóstico Diferencial , Feminino , Proteínas Fúngicas/isolamento & purificação , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Testes Intradérmicos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/isolamento & purificação , Índice de Gravidade de Doença , Superóxido DismutaseRESUMO
ABSTRACT Interferon-gamma (IFN-γ) plays a crucial role in viral infections by preventing viral replication and in the promotion of innate and adaptive immune responses. However, IFN-gamma can exert distinct effects in different persistent viral infections. The long-term overproduction of IFN-γ in retroviral infections, such as the human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), and human endogenous retroviruses (HERVs), resulting in inflammation, may cause neuronal damage. This review is provocative about the role of IFN-γ during persistent retroviral infections and its relationship with the causation of some neurological disorders that are important for public health.
RESUMO
As síndromes autoinflamatórias são doenças raras, genéticas de envolvimento prioritário da imunidade inata. Avanços nas técnicas de sequenciamento genético permitiram dissecar os genes envolvidos nestas doenças, continuamente organizando o quebra-cabeça genético e fisiopatológico de tais desordens. Este artigo revisa os últimos achados genéticos com seus respectivos fenótipos, código OMIM e ORPHA. Além disso, sugere cautela na triagem clínica e na indicação de métodos restritivos de sequenciamentos genéticos.
Autoinflammatory diseases comprise a group of rare, genetic disorders with priority involvement of innate immunity. Advances in genetic sequencing techniques allowed genetic dissection of genes involved in these diseases, with continuous organization of the genetic and pathophysiologic puzzle of these disorders. This article reviews the most recent genetic findings linked to respective phenotypes and OMIM and ORPHA codes. Moreover, it suggests caution in clinical screening and genetic sequencing indication with restrictive genetic panels.
Assuntos
Humanos , Doenças Hereditárias Autoinflamatórias , Doenças Genéticas Inatas , Imunidade Inata , Programas de Rastreamento , Triagem , Bases de Dados Genéticas , Doenças RarasRESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.
Assuntos
Humanos , Biomarcadores/análise , COVID-19/diagnóstico , COVID-19/terapia , Proteína C-Reativa , Produtos de Degradação da Fibrina e do Fibrinogênio , Receptores Imunológicos/análise , Estudos Prospectivos , SARS-CoV-2RESUMO
ABSTRACT OBJECTIVE To estimate the magnitude and identify patterns of change in prostate cancer mortality in the state of São Paulo and in the 17 regional health care networks, according to age groups from 50 years onwards, in the period between 2000 to 2015. METHODS Age-adjusted mortality rates (per 100,000 men) were calculated by the direct method using the Segi world population as standard. Joinpoint regression was used to calculate the average annual percent change (AAPC), with a confidence interval of 95% (95%CI), by regional network and age group (50-59, 60-69, 70-79 and 80 years or more). RESULTS For the state of São Paulo, age-adjusted mortality rates were 15.2, 13.3 and 11.9 per 100,000 men, respectively, in the periods between 2000 to 2005, 2006 to 2010 and 2011 to 2015, with a significant decrease trend (AAPC = -2.10%; 95%CI -2.42 - -1.79) each year. Among the 17 networks, 11 presented significant mean annual reductions, ranging from -1.72% to -3.05%. From the age of 50 onwards, there was a sharper reduction in the groups from 50 to 59 (AAPC = -2.33%; 95%CI -3.04 - -1.62) and 60 to 69 years (AAPC = -2.84%; 95%CI - 3.25 - -2.43). CONCLUSION Although reductions in mortality are still slight, they indicate progress in prostate cancer control actions. Screening actions and changes in therapeutic behaviors in recent decades may be modifying incidence and survival, resulting in changes in the mortality profile. More detailed studies will be useful in understanding the factors that lead to the interregional variations found.
RESUMO OBJETIVO Estimar a magnitude e identificar padrões de mudança na mortalidade por câncer de próstata no estado de São Paulo e nas 17 redes regionais de atenção à saúde, segundo grupos etários a partir dos 50 anos, no período de 2000 a 2015. MÉTODOS As taxas de mortalidade ajustadas por idade (por 100 mil homens) foram calculadas pelo método direto usando a população mundial de Segi como padrão. A análise de regressão Joinpoint foi utilizada para calcular as variações percentuais anuais médias (AAPC), com intervalo de confiança de 95% (IC95%), por rede regional e grupo etário (50-59, 60-69, 70-79 e 80 anos ou mais). RESULTADOS Para o estado de São Paulo, as taxas ajustadas de mortalidade foram de 15,2, 13,3 e 11,9/100 mil homens, respectivamente, nos períodos de 2000 a 2005, 2006 a 2010 e 2011 a 2015, com tendência de decréscimo significativo (AAPC = -2,10%; IC95% -2,42 - -1,79) a cada ano. Das 17 redes, 11 apresentaram reduções médias anuais significativas, que variaram entre -1,72% e -3,05%. A partir dos 50 anos, verificou-se redução mais acentuada nos grupos de 50 a 59 (AAPC = -2,33%; IC95% -3,04 - -1,62) e 60 a 69 anos (AAPC = -2,84%; IC95% -3,25 - -2,43). CONCLUSÕES Embora as reduções na mortalidade ainda sejam discretas, indicam progresso nas ações de controle do câncer de próstata. Ações de rastreamento e mudanças nas condutas terapêuticas nas últimas décadas podem estar modificando a incidência e a sobrevida, resultando em mudanças no perfil de mortalidade. Estudos mais detalhados serão úteis na compreensão dos fatores que levam às variações inter-regionais encontradas.