Non-invasive sound wave brain stimulation with Transcranial Pulse Stimulation (TPS) improves neuropsychiatric symptoms in Alzheimer's disease.

BACKGROUND: This study explores Transcranial Pulse Stimulation (TPS) as a potential non-invasive treatment for Alzheimer's disease (AD), focusing on its impact on cognitive functions and behavioral symptoms. METHODS: In a prospective, one-arm open-label trial, ten patients with mild to moderate dementia due to AD were assessed using the Alzheimer's Disease Assessment Scale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Pfeffer Functional Activities Questionnaire, and Zarit Caregiver Burden Interview. Assessments occurred at 30- and 90-days post-treatment. The TPS protocol consisted of 10 sessions over five weeks, using the Neurolith® device to deliver 6000 focused shockwave pulses at 0.25 mJ/mm2 and a frequency of 4 Hz. RESULTS: TPS significantly reduced neuropsychiatric symptoms, with NPI scores decreasing by 23.9 points (95% CI: -39.19 to -8.61, p = 0.0042) after 30 days, and by 18.9 points (95% CI: -33.49 to -2.91, p = 0.022) after 90 days. These changes had large effect sizes (Cohen's dz = 1.43 and dz = 0.94, respectively). A decreasing trend was observed in the ADAS-Cog score (-3.6, 95% CI: -7.18 to 0.00, p = 0.05) after 90 days, indicating a potential reduction in cognitive impairment, though not statistically significant. CONCLUSION: The preliminary results indicate that TPS treatment leads to significant improvement in neuropsychiatric symptoms in AD patients, showing promise as a therapeutic approach for AD. Further research is needed to fully establish its effectiveness, especially concerning cognitive functions.

Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. (AU)

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation.

BACKGROUND: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors. PATIENTS AND METHODS: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. RESULTS: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. CONCLUSIONS: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.

The Institute of Physical Medicine and Rehabilitation, Hospital das Clínicas University of São Paulo School of Medicine comprehensive rehabilitation program for elderly people with knee osteoarthritis.

Background: Knee osteoarthritis (OA) is a leading cause of disability in the elderly population. Chronic disabling pain is associated with maladaptive neuroplastic changes in brain networks, commonly associated with central sensitization. The main clinical features of nociplastic pain conditions include combined peripheral and central sensitization, and it is crucial to recognize this type of pain, as it responds to different therapies than nociceptive and neuropathic pain. Objective: To report the effect of the Institute of Physical Medicine and Rehabilitation (IMREA) comprehensive rehabilitation program to reduce pain and to improve functioning in elderly people with knee OA, under the DEFINE cohort. Methods: This is a retrospective observational cohort of 96 patients with knee OA, recruited from October 2018 to December 2019. All patients were evaluated by a trained multidisciplinary team using the Kellgren Lawrence classification, bilateral knee ultrasonography, the visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, rigidity and difficulty scores, the Timed Up and Go Test (TUG), 10-m and 6-min walking test (10 and 6 MWT), Berg Balance Scale, isokinetic dynamometry for knee extension and flexion strength, and pain pressure thresholds. The rehabilitation program included paraspinous lidocaine blocks, focal extracorporeal shockwaves combined with radial pressure waves and functional electrical stimulation according to individual needs. The baseline was compred with the treatment results with a paired t-test. Results: The study sample is composed of 96 participants, mostly females (n = 81, 84.38%), with bilateral osteoarthritis (n = 91, 94.79%), and a mean age of 68.89 (SD 9.73) years. Functional improvement was observed in TUG (p = 0.019), 6-mwt (p = 0.033), right knee flexion strength (p < 0.0001), WOMAC rigidity and difficulty domains (p < 0.0001). Pain was reduced from baseline as measured by WOMAC pain domain (p < 0.0001), VAS for both knees (p < 0.0001), and SF-36 pain domain (p < 0.0001). Pressure pain threshold was modified above the patella (p = 0.005 and p = 0.002 for right and left knees, respectively), at the patellar tendons (p = 0.015 and p = 0.010 for right and left patellar tendons, respectively), left S2 dermatome (p = 0.017), and L1-L2 (p = 0.008). Conclusions: The IMREA comprehensive rehabilitation program improved functioning and reduced disabling pain in elderly people with knee OA. We highlight the relevance and discuss the implementation of our intervention protocol. Although this is an open cohort study, it is important to note the significant improvement with this clinical protocol.

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.

Rapid and Sensitive Qualitative Duoplex Real-Time PCR Method for Discriminatory and Confirmatory Diagnosis of HTLV-1 and HTLV-2 Infections: Brazilian Multicentric Study.

Human T cell lymphotropic virus (HTLV) is the caustive agent of two main conditions i. e., the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the adult T-cell leukemia/lymphoma (ATLL). HTLV diagnosis is based on serological and molecular approaches; however, an accurate and validated method is still needed. The objective of this study was to establish a rapid and sensitive molecular test to confirm and discriminate HTLV 1/2 types. The test validation was performed as a multicentric study involving HTLV confirmation centers throughout Brazil. Proviral DNA was extracted from whole blood and the amplification was performed using in-house designed primer and probe sets targeting the pol genomic region. An internal control to validate the extraction and amplification was also included. The limit of detection (LoD) of the assay was four copies/reaction for HTLV-1 and 10.9 copies/reaction for HTLV-2. The diagnostic sensitivity of the platform was 94.6% for HTLV-1, 78.6% for HTLV-2, and the specificity was 100% for both viruses. Cross-reactions of the test with human viruses including HAV, HBV, HCV, HIV-1/2, and parvovirus B19 were not observed. During the multicentric validation, the test was used to screen a total of 692 blood samples obtained from previously confirmed HTLV-positive individuals. From these, 91.1% tested positive being concordant with the previously obtained results. In conclusion, our duoplex-RT-PCR-HTLV1 /2 presented adequate efficiency for HTLV-1/2 differentiation showing high sensitivity and specificity. Therefore, it can be a suitable tool for confirmation of suspected and inconclusive HTLV cases, prenatal and pre-transplant diagnosis, in Brazil and in other countries HTLV-endemic countries.

Strengths, Weaknesses, Opportunities and Threats (SWOT) Analysis of the Implementation of Public Health Policies on HTLV-1 in Brazil.

Human T lymphotropic virus 1 (HTLV-1) is a public health issue for most countries and imposes important consequences on patients' health and socioeconomic status. Brazil is one of the global leaders of the public health response to these viruses. The country has challenges to overcome to implement meaningful policies aiming to eliminate HTLV-1/2. An analysis of strengths, weaknesses, opportunities, and threats (SWOT) for the implementation of public health policies on HTLV-1/2 was performed. The strengths identified were the Brazilian Unified Health System (SUS); Brazilian expertise in public health programs successfully implemented; currently available policies targeting HTLV; and strong collaboration with researchers and patient's representative. Lack of awareness about HTLV, insufficient epidemiological data, lack of reference centers for patient care, insufficient availability of confirmatory tests, lack of universal antenatal screening, and absence of cost-effectiveness studies were identified as weaknesses. Some interesting opportunities included the increased interest from international organizations on HTLV, possibility of integrating HTLV into other programs, external funding for research, available online platforms, opportunity to acquire data from HTLV-1/2 surveillance to gather epidemiological information, and HTLV policies that were implemented independently by states and municipalities. In addition to the COVID-19 pandemic, existing demands from different diseases, the country's demography and its marked sociocultural diversity and the volatility of the technical team working with HTLV-1/2 at the Brazilian Ministry of Health are threats to the implementation of public policies on HTLV-1/2. This SWOT analysis will facilitate strategic planning to allow continuous progress of the Brazilian response to HTLV-1/2 infection.

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.

Aptidão funcional e qualidade de vida de idosos praticantes de Lian Gong, Tai Chi e Qigong / Aptitud funcional y calidad de vida de adultos mayores que practican Lian Gong, Tai Chi y Qigong / Functional fitness and quality of life of elderly Lian Gong, Tai Chi and Qigong practitioners

Resumo Objetivo Comparar a aptidão funcional e as dimensões da qualidade de vida de idosos participantes e não participantes das práticas orientadas Lian Gong, Tai Chi e Qigong. Métodos Estudo caso-controle, desenvolvido no município de São Paulo - SP, Brasil, com 118 idosos, pareados por sexo e idade: 59 no grupo caso, participantes das práticas corporais, divididos em subgrupos por tempo de adesão:< 24 meses e ≥ 24 meses; e 59 no grupo controle, não participantes das práticas. Para a coleta de dados, aplicaram-se: questionário com variáveis sociodemográficas e de saúde, testes funcionais e o instrumento Medical Outcomes Study 36- Item Short-Form Health Survey (SF36). As análises estatísticas foram realizadas com o programa R versão 3.3.2. Os dados foram inicialmente analisados de forma descritiva e, em seguida, efetuou-se regressão logística univariada e o teste Kruskal Wallis. Os aspectos éticos da pesquisa com seres humanos foram obedecidos. Resultados Verificou-se que, no grupo caso, idosos com tempo de adesão às práticas ≥ 24 meses apresentaram resultado superior no teste funcional de levantar e sentar da cadeira (p=0,006), bem como melhor desempenho nos seguintes domínios da qualidade de vida: dor (p= 0,003), vitalidade (p=0,021), aspectos emocionais (p=0,034) e saúde mental (p=0,020). Conclusão A participação nas práticas corporais, orientadas, Lian Gong, Tai Chi e Qigong pode contribuir para a qualidade de vida e a aptidão funcional de idosos.

Resumen Objetivo Comparar la aptitud funcional y las dimensiones de la calidad de vida de adultos mayores que participan y que no participan en prácticas orientadas Lian Gong, Tai Chi y Qigong. Métodos Estudio caso-control, realizado en el municipio de São Paulo - estado de São Paulo, Brasil, con 118 adultos mayores, pareados por sexo y edad: 59 en el grupo caso, participantes de las prácticas corporales, divididos en subgrupos por tiempo de participación: < 24 meses y ≥ 24 meses; y 59 en el grupo control, no participantes de las prácticas. Para la recopilación de datos, se aplicó un cuestionario con variables sociodemográficas y de salud, pruebas funcionales y el instrumento Medical Outcomes Study 36- Item Short-Form Health Survey (SF36). Los análisis estadísticos se realizaron con el programa R versión 3.3.2. Los datos se analizaron inicialmente de forma descriptiva y, a continuación, se realizó regresión logística univariada y la prueba de Kruskal Wallis. Los aspectos éticos de la investigación con seres humanos fueron cumplidos. Resultados Se verificó que, en el grupo caso, los adultos mayores con tiempo de participación en las prácticas ≥ 24 meses presentaron un resultado superior a la prueba funcional de levantarse y sentarse en la silla (p=0,006), como también un mejor desempeño en los siguientes dominios de calidad de vida: dolor (p= 0,003), vitalidad (p=0,021), aspectos emocionales (p=0,034) y salud mental (p=0,020). Conclusión La participación en las prácticas corporales orientadas Lian Gong, Tai Chi y Qigong puede contribuir para la calidad de vida y para la aptitud funcional de adultos mayores.

Abstract Objective To compare functional fitness and quality of life dimensions of elderly participants and non-participants of Lian Gong, Tai Chi and Qigong guided practices. Methods This is a case-control study, carried out in the city of São Paulo, SP, Brazil, with 118 elderly people, matched by sex and age: 59 in the case group, participants in body practices, divided into subgroups by time of compliance: < 24 months and ≥ 24 months; and 59 in the control group, non-participants in body practices. For data collection, the following were applied: a questionnaire with sociodemographic and health variables, functional tests and the Medical Outcomes Study 36- Item Short-Form Health Survey (SF-36). Statistical analyzes were performed using R version 3.3.2. The data were initially analyzed in a descriptive way and, then, a univariate logistic regression and the Kruskal Wallis test were performed. The ethical aspects of research with human beings were obeyed. Results It was found that, in the case group, elderly people with a time of compliance with practices ≥ 24 months showed a superior result in the functional 30-second chair stand test (p=0.006), as well as better performance in the following quality of life domains: bodily pain (p=0.003); vitality (p=0.021); role emotional (p=0.034); and mental health (p=0.020). Conclusion Participation in guided body practices, Lian Gong, Tai Chi and Qigong, can contribute to elderly people's quality of life and functional fitness.

Prevalence of infection by human T Cell lymphotropic viruses (HTLV-1/2) in adult population in Vitória-ES.

INTRODUCTION: Brazil has a high number of HTLV-1/2 infections which are unequally distributed in the country. Most prevalence studies have focused on specific populations, such as blood donors and pregnant women. Some areas, for example the state of Bahia, have robust information about HTLV-1/2 infection, however there is no information available about this infection in the general population of Vitória, Espírito Santo, Brazil. OBJECTIVE: To determine the prevalence of HTLV-1/2 infection in adults from the municipality of Vitoria, ES. METHODS: A cross sectional study was performed from September 2010 to December 2011, in individuals of both sexes, aged 18 or older living in Vitória-ES. Venous blood samples were collected and tested for anti-HTLV-1/2 antibodies by chemiluminescent immunoassay (CMIA). Individuals with CMIA reactive results were submitted to a new blood collection for retesting by CMIA, followed by PCR to confirm infection and discriminate the viral type. RESULTS: From 1502 tested samples, eight were reactive in CMIA and all were confirmed by PCR. Therefore, the prevalence of HTLV-1/2 was 0.53% (8/1502, 95% CI: 0.2-1.0%). The infection rate was 0.7% in men (5/711, 95% CI: 0.17-1.51%), and 0.38% in women (3/791, 95% CI: 0-0.81%). CONCLUSIONS: The prevalence of HTLV-1/2 infection was 0.53% (8/1502; 95% CI: 0.2-0.9%). Confirmatory test using real-time PCR (qPCR) identified seven individuals positive for HTLV-1 and one for HTLV-2. Considering the risk of infected individuals to develop high morbidity and mortality diseases, it would be important to implement public health policies aimed at stopping transmission of these viruses in this municipality.

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies.

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

Prognosis Markers for Monitoring HTLV-1 Neurologic Disease.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated not only with some severe manifestations, such as HTLV-1-associated myelopathy (HAM) and ATLL, but also with other, less severe conditions. Some studies have reported neurologic manifestations that did not meet all the criteria for the diagnosis of HAM in individuals infected with HTLV-1; these conditions may later progress to HAM or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. This study evaluated the prognostic value and looked for a possible association of those parameters with the intermediate syndrome (IS) status and HAM status. METHODS: Proviral load (PVL), spontaneous lymphoproliferation, interferon (IFN)-γ spontaneous production was quantified in samples of asymptomatic and HAM patients, as well as patients with IS. RESULTS: The critical age range was 50-60 years for IS outcome and more of 60 years for HAM outcome, with an increased risk of 2.5-fold for IS and 6.8-fold for HAM. IFN-γ was increased in patients with IS compared with asymptomatic carriers (ACs) (p = 0.007) and in patients with HAM compared with ACs (p = 0.03). Lymphoproliferation was increased in patients with HAM vs ACs (p = 0.0001) and patients with IS (p = 0.0001). PVL was similar between groups. CONCLUSION: IFN-γ has high specificity of prediction of subject remain asymptomatic compared with PVL and lymphoproliferation assay tests. IFN-γ has been shown to be a biomarker of progression to intermediate stage and to HAM. The association of other markers with manifestations associated with HTLV-1 infection that does not meet the HAM criteria should be verified.

Small cells lung epidermoid carcinoma in a HTLV1-infected patient: case report and literature review.

The human T cell lymphotropic virus type 1 (HTLV-1) is the first human retrovirus discovered. Since then, it has spread worldwide and is mainly associated with adult T cell leukemia/lymphoma (ATLL) and HTLV1-associated myelopathy (HAM). Its relationship, however, with other types of cancer is controversial. We describe the case of a patient presenting with small cells lung epidermoid carcinoma who had recently developed HAM, and a review of the literature related to these conditions. This is the first case of this type of lung cancer, the same of the first description in the literature, associated with HAM outside Japan.

AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from São Paulo, Brazil: The role of IFN-λ4 polymorphisms.

Few studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-λ4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-λ4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm3 or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-λ4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-λ4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-λ4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-λ4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.