Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

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.

Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop

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.

Immunothrombosis and COVID-19 ‒ a nested post-hoc analysis from a 3186 patient cohort in a Latin American public reference hospital

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.

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis.

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.

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis

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.

Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome.

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.

Atualizando e expandindo o universo de: "Uma nova classe de doenças ­ doenças autoinflamatórias" / Updating and expanding the universe of: "A new class of diseases ­ autoinflammatory disorders"

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.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study

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.

Trends in prostate cancer mortality in the state of São Paulo, 2000 to 2015.

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.

Trends in prostate cancer mortality in the state of São Paulo, 2000 to 2015 / Tendências na mortalidade por câncer de próstata no estado de São Paulo, 2000 a 2015

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.

Is the telomere length associated with neurocognitive disabilities in HIV-1-infected subjects?

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.

Fatores psicossociais e sociodemográficos associados à depressão pós-parto: um estudo em hospitais público e privado da cidade de São Paulo, Brasil / Psychosocial and sociodemographic factors associated with postpartum depression: a study in private and public hospitals in São Paulo, Brazil / Factores psicosociales y sociodemográficos asociados con la depresión posparto: un estudio realizado en hospital público y privado en la ciudad de São Paulo, Brasil

O estudo avaliou a prevalência de depressão pós-parto (DPP) e fatores associados em mulheres que deram à luz em dois hospitais da cidade de São Paulo: um público e outro privado. Foram aplicados questionários padronizados, a Escala de Depressão Pós-parto de Edimburgo (EDPE) e a Escala de Apoio Social de MOS (EAS) a 462 mulheres: 205, no hospital público e 257, no privado. Foram obtidos dados sociodemográficos, psicossociais, obstétricos e do recém-nascido (RN). Consideraram-se deprimidas mulheres com 12 ou mais pontos na EDPE, aplicada no 3º ou 4º mês após o parto. No hospital público, a prevalência de DPP foi de 26% e, no privado, de 9%. Características dos RN foram semelhantes nas duas amostras; idade, escolaridade, número de visitas de pré-natal e de cesarianas das mães foram maiores no hospital privado. Análise de regressão envolvendo características psicossociais das participantes revelou associação positiva de DPP com depressão anterior e com frequência de conflitos com o parceiro e relação negativa com anos de escolaridade e escore de apoio social.

This study evaluated the prevalence of postpartum depression (PPD) and associated factors in women who gave birth at two hospitals in São Paulo City: one public and other private. It was applied standardized questionnaires, the Edinburgh Postnatal Depression Scale (EPDS), and the MOS Social Support Scale to 462 women: 205 in the public hospitals and 257, in the private one. Data collected included sociodemographic, psychosocial, obstetric and newborn (NB) characteristics. It was considered depressed those women with 12 or more points in EPDS, applied in the 3rd. or 4th. month after delivery. In the public hospital, the prevalence of PPD was 26% and in the private, 9%. Characteristics of infants were similar in both samples, Mothers' age, education level, number of prenatal visits and cesarean were higher in the private hospital. Regression analysis involving psychosocial characteristics of women showed a positive association of PPD with previous occurrence of depression and frequency of conflicts with partner and negative relationship with years of schooling, and social support scores.

El estudio evaluó la prevalencia de la depresión posparto (DPP) y factores asociados en mujeres que dieron a luz en dos hospitales de la ciudad de São Paulo: un público y otro privado. Se aplicó dos instrumentos estandarizados, la escala de depresión posparto de Edimburgo (EDPE) y el Cuestionario MOS-SSS de Apoyo Social, a 462 mujeres: 205 en el hospital público y 257 en el hospital privado. Se obtuvieron datos sociodemográficos, psicosociales, obstétricos y del recién nacido (RN). Fueron consideradas deprimidas las mujeres con 12 o más puntos en la EDPE aplicada en el tercero o cuarto mes después del parto. En el hospital público, la prevalencia de DPP fue de 26% y en el privado, 9%. Características de los RN fueron similares en las dos muestras; la edad, la escolaridad, el número de consultas de prenatal y de cesáreas fueron mayores en el hospital privado. El análisis de regresión implicando características psicosociales de las participantes reveló una asociación positiva de la DPP con depresión previa y con frecuencia de conflictos con el compañero y una relación negativa con los años de escolaridad y con el escore de apoyo social.

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

BACKGROUND: The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. METHODS: The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. RESULTS: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%  = 1.82-31.72). CONCLUSION: Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.

Rational use of blood calcium determinations / Uso racional da dosagem de cálcio no sangue

CONTEXT AND OBJECTIVE: This study was motivated by the recent excessive increase in requests for blood calcium determinations and laboratory tests in general, in the Hospital das Clínicas complex of Faculdade de Medicina, Universidade de São Paulo (HCFMUSP). Its aim was to suggest rules for the determination of total and ionized calcium in our intensive care units, emergency department, wards and outpatient services, thus contributing towards improving the quality of medical care and achieving more appropriate use of human and financial resources. DESIGN AND SETTING: Critical analysis on clinical and laboratory data and the pertinent scientific literature, conducted by the study group for rational clinical laboratory use, which is part of the Central Laboratory Division, HCFMUSP. METHODS: The study group reviewed scientific publications, statistics and clinical and laboratory data concerning requests for total and ionized calcium determinations in the settings of intensive care units, emergency department, wards and outpatient services. RESULTS: From this critical analysis, clinical decision flow diagrams aimed at providing guidance for ordering these tests were constructed. CONCLUSIONS: Use of the proposed flow diagrams may help to limit the numbers of inappropriate requests for ionized and total calcium determinations, with consequent reductions in the number of tests, risks to patients and unnecessary costs. .

CONTEXTO E OBJETIVO: Este trabalho foi motivado pelo recente aumento excessivo de solicitações de dosagem de cálcio no sangue, assim como de exames laboratoriais em geral, no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Seu objetivo foi sugerir regras para a determinação de cálcio total e iônico nas nossas unidades de terapia intensiva, pronto-socorro, enfermarias e ambulatórios e contribuir para a melhoria da qualidade da assistência médica, com utilização mais adequada dos recursos humanos e financeiros. TIPO DO ESTUDO E LOCAL: Análise crítica de dados clínicos, laboratoriais e da literatura médica pertinente, realizada pelo grupo de estudos para o uso racional do laboratório clínico, vinculado à Divisão de Laboratório Central do HCFMUSP. MÉTODOS: O grupo de estudos reviu publicações científicas, estatísticas e dados clínico-laboratoriais relativos às solicitações de cálcio total e iônico nos ambientes das unidades de terapia intensiva, prontos-socorros, enfermarias e ambulatórios. RESULTADOS: A partir dessa análise crítica, foram construídos fluxogramas de decisão clínica que visam orientar a requisição desses testes. CONCLUSÕES: A utilização dos fluxogramas propostos pode ajudar a limitar a solicitação inadequada das dosagens de cálcio total e iônico, com consequente redução do número de exames, de riscos para os pacientes e de custos desnecessários. .

[Cancer mortality trends in Brazilian state capitals, 1980-2004].

OBJECTIVE: Cancer mortality rates began to decline in developed countries in the 1990s, but their behavior in developing countries is less well-known. An earlier study on cancer mortality in Brazil showed a declining mortality trend for cancer as a whole. however the quality of data results raised some criticism t. The population of state capitals comprises about a quarter of the total Brazilian population and for these cities mortality data available have a better quality than for the entire country, enabling analyses of trends in cancer rates based on more accurate data. METHODS: Mortality and population data were collected from government databases (SIM/DATASUS and IBGE, respectively). Age-adjusted (world standard) and age-specific mortality rates were calculated for both genders . Linear regression was used to investigate changes in trends. RESULTS: For all cancers as a whole mortality rates declined throughout the study period for both men and women (-4.6% and -10.5%, respectively). For both genders , the cancer that decreased most was stomach cancer. Among men, lung cancer death rates presented a slight reduction, while prostate cancer rates increased. Among women, "uterus, site unspecified' presented a downward trend, while lung cancer rates increased. The trend for breast cancer remained stable, and cervix uterus rates showed a slight increase at the end of the period. CONCLUSION: As already seen in developed countries, all cancer mortality rates tended to decline in Brazilian state capitals over the period 1980-2004, a tendency largely due to a decline in stomach cancer death rates for both genders.

Specific immunotherapy using Hymenoptera venom: systematic review / Imunoterapia específica com venenos de Hymenoptera: revisão sistemática

CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95 percent confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.

CONTEXTO E OBJETIVO: O único tratamento eficaz para pacientes que têm reações graves após ferroada de Hymenoptera é a imunoterapia com veneno. O objetivo deste estudo foi rever a literatura para avaliar os efeitos da imunoterapia com veneno em pacientes com reações graves após ferroada de Hymenoptera. TIPO DE ESTUDO E LOCAL: Foram revisados na literatura mundial ensaios clínicos controlados e aleatórios. O manuscrito foi realizado na Disciplina de Alergia e Imunologia Clínica, Universidade de São Paulo (USP). MÉTODOS: Ensaios clínicos controlados e aleatórios envolvendo imunoterapia com veneno de Hymenoptera versus placebo ou apenas acompanhamento dos pacientes foram avaliados. Realizada imunoterapia específica, o risco de reações sistêmicas foi avaliado através de cálculo do "odds ratio" e intervalo de confiança de 95 por cento. RESULTADOS: 2.273 resumos foram identificados na busca pelas palavras chave. Apenas quatro estudos foram incluídos nesta revisão. O teste qui-quadrado de heterogeneidade mostrou que dois estudos foram homogêneos e puderam ser incluídos na metanálise. Ao combinar os dois estudos, o "odds ratio" passou a ser significativo: 0.29 (0.10-0.87). Entretanto, ao analisar a gravidade das reações ocorridas após a imunoterapia, observou-se que os benefícios podem não ser tão relevantes, pois as reações foram, na grande maioria, ou mais leves ou semelhantes à reação original. CONCLUSÕES: A imunoterapia específica deve ser recomendada para adultos e crianças com reações moderadas a graves, porém não há necessidade de prescrevê-la para as crianças apenas com reações cutâneas, especialmente se a exposição é muito esporádica. No outro lado, a relação risco-benefício deve ser sempre avaliada em cada caso.

Tendências da mortalidade por câncer nas capitais dos estados do Brasil, 1980-2004 / Trends of cancer mortality in Brazilian state capitals, 1980-2004

OBJETIVO: A mortalidade por câncer iniciou declínio nos países desenvolvidos nos anos 90, mas seu comportamento nos países em desenvolvimento é menos conhecido. Estudo anterior abordando a mortalidade por câncer no Brasil mostrou queda na mortalidade pelo conjunto dos cânceres, mas a qualidade dos dados suscitou críticas quanto à validade dos resultados. As informações de mortalidade das capitais dos estados do Brasil são de melhor qualidade que aquelas para o país como um todo, possibilitando análise mais acurada das tendências. MÉTODOS: Os dados de mortalidade e população foram obtidos das bases de dados do Ministério da Saúde e do IBGE. Calcularam-se taxas ajustadas por idade e taxas específicas por idade, para ambos os sexos. Empregou-se regressão linear para avaliar a significância das mudanças de tendência. RESULTADOS: As taxas de mortalidade pelo conjunto dos cânceres declinaram, (-4,6 por cento para os homens e -10,5 por cento para as mulheres). O câncer de estômago mostrou queda de taxas nos dois sexos, assim como o câncer de pulmão entre os homens, enquanto as taxas do câncer de próstata aumentaram. No sexo feminino, “câncer do útero não especificado" apresentou redução e o câncer de pulmão, aumento de taxas. O câncer de mama mostrou-se estável, e o câncer do colo do útero aumentou suas taxas ao final do período. CONCLUSÃO: Conforme já registrado em países desenvolvidos, a mortalidade pelo conjunto dos cânceres nas capitais de estados brasileiros mostrou tendência de queda entre 1980 e 2004, o que se deveu fundamentalmente ao declínio da mortalidade por câncer de estômago.

OBJECTIVE: Cancer mortality rates began to decline in developed countries in the 1990s, but their behavior in developing countries is less well-known. An earlier study on cancer mortality in Brazil showed a declining mortality trend for cancer as a whole. however the quality of data results raised some criticism t. The population of state capitals comprises about a quarter of the total Brazilian population and for these cities mortality data available have a better quality than for the entire country, enabling analyses of trends in cancer rates based on more accurate data. METHODS: Mortality and population data were collected from government databases (SIM/DATASUS and IBGE, respectively). Age-adjusted (world standard) and age-specific mortality rates were calculated for both genders . Linear regression was used to investigate changes in trends. RESULTS: For all cancers as a whole mortality rates declined throughout the study period for both men and women (-4.6 percent and -10.5 percent, respectively). For both genders , the cancer that decreased most was stomach cancer. Among men, lung cancer death rates presented a slight reduction, while prostate cancer rates increased. Among women, "uterus, site unspecified' presented a downward trend, while lung cancer rates increased. The trend for breast cancer remained stable, and cervix uterus rates showed a slight increase at the end of the period. CONCLUSION: As already seen in developed countries, all cancer mortality rates tended to decline in Brazilian state capitals over the period 1980-2004, a tendency largely due to a decline in stomach cancer death rates for both genders.

[Mortality trends from uterine cervical cancer in the city of São Paulo from 1980 to 1999]. / Tendência da mortalidade por câncer do útero no Município de São Paulo entre 1980 e 1999.

Uterine cervical cancer shows a higher incidence in some Brazilian cities. It is a common cause of death in women from developing countries, despite the longstanding availability of an effective screening test, the Pap smear. This study aimed to evaluate the temporal trends of crude, age-adjusted, and age-specific mortality rates from cervical cancer, endometrial cancer, and cancer of the uterus not otherwise specified (NOS) in the city of São Paulo from 1980 to 1999. Results showed a slight reduction in cervical cancer rates, a decrease in NOS uterine cancer rates, and an increase in endometrial cancer mortality rates. The fall in mortality from NOS uterine cancer indicates an improvement in diagnostic accuracy and quality of information on death certificates and may point to an increase in coverage of cervical cancer screening using the Pap smear.

Tendência da mortalidade por câncer do útero no Município de São Paulo entre 1980 e 1999 / Mortality trends from uterine cervical cancer in the city of São Paulo from 1980 to 1999

O câncer do colo do útero apresenta grande incidência em algumas cidades brasileiras e considerável mortalidade em países em desenvolvimento, não obstante a disponibilidade já antiga de teste de rastreamento. O presente estudo visou avaliar a tendência da mortalidade por câncer de colo do útero, de corpo do útero e por câncer do útero não especificado, no Município de São Paulo, entre 1980 e 1999, por meio do exame das taxas brutas, idade-específica e ajustadas por idade. Os resultados mostraram discreta redução da mortalidade por câncer do colo do útero, queda da mortalidade por câncer de útero não especificado e aumento da mortalidade por câncer do corpo do útero. Conclui-se que a queda da mortalidade por câncer do útero não especificado sinaliza uma melhora na precisão do diagnóstico clínico e na qualidade do preenchimento do atestado de óbito, e indica aumento de cobertura do teste de Papanicolaou.