Presence of parasite DNA in clinically unaffected nasal mucosa during cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-12T18:17:17Z No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-02-12T18:30:42Z (GMT) No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5)Made available in DSpace on 2019-02-12T18:30:42Z (GMT). No. of bitstreams: 1 Canário, A. Presence of parasite DNA in clinically...2019.pdf: 248161 bytes, checksum: d71cb01c750c9ac331f7e6511eef667a (MD5) Previous issue date: 2019FAPESB e Brazil (SUS0024/ 2013). This study was financed in part by the Coordenaç~ao de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil / Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil / Hospital Santa Izabel. Santa Casa de Misericórdia da Bahia. Serviço de Otorrinolaringologia. Salvador, BA, Brazil.We aimed to detect Leishmania DNA carriage in nasal mucosa of individuals with cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. Methods: A cross-sectional study was performed in all individuals with CL without nasal lesions (n ¼ 153) attended within 2 years in an endemic area of L. (Viannia) braziliensis in Bahia (Brazil). An otorhinolaryngologist assessed the clinical status of the nasal mucosa by anterior rhinoscopy and endoscopic examinations. Swab samples were collected for parasite DNA detection by PCR from all individuals before standard treatment for leishmaniasis. A second evaluation 3 months after treatment was performed to assess clinical outcomes. Results: Parasite DNA was detected in 7.8% (12/153) of clinically healthy nasal mucosa of individuals with CL. Interestingly, DNA was more frequently identified in individuals with more skin lesions (median 1.5, interquartile range (IQR) 1e3.5 versus 1.0, IQR 1e1.5; p 0.044), or larger injuries (median 2.7, IQR 2e3.8 versus 1.6, IQR 1e2.5; p 0.013). Additionally, the disease of those individuals with positive PCR evolved more frequently to unusual forms of leishmaniasis (recidiva cutis and disseminated) (45.5% (5/11) versus 11.5% (14/122); p 0.009), and required more cycles of treatment to reach clinical cure (median 2, IQR 1e4 versus 1, IQR 1e2; p 0.05). Conclusion: These findings suggest an early parasite tropism to nasal mucosa in L. (Viannia) braziliensis infection and a clinical phenotype of CL cases associated with parasite DNA in nasal mucosa. Future studies should evaluate whether PCR of nasal swab samples could serve as a prognostic tool for individuals at risk of mucocutaneous leishmaniasis

Analyses of HTLV-1 sequences suggest interaction between ORF-I mutations and HAM/TSP outcome

The region known as pX in the 3' end of the human T-cell lymphotropic virus type 1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. HTLV-1 ORF-I produces the protein p12 and its cleavage product p8. The functions of these proteins have been linked to immune evasion and viral infectivity and persistence. It is known that the HTLV-1 infection does not necessarily imply the development of pathological processes and here we evaluated whether natural mutations in HTLV-1 ORF-I can influence the proviral load and clinical manifestation of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). For that, we performed molecular characterization, datamining and phylogenetic analysis with HTLV-1 ORF-I sequences from 156 patients with negative or positive diagnosis for HAM/TSP. Our analyses demonstrated that some mutations may be associated with the outcome of HAM/TSP (C39R, L40F, P45L, S69G and R88K) or with proviral load (P34L and F61L). We further examined the presence of mutations in motifs of HBZ and observed that P45L mutation is located within the HBZ nuclear localization signal and was found more frequently between patients with HAM/TSP and high proviral load. These results indicate that some natural mutations are located in functional domains of ORF-I and suggests a potential association between these mutations and the proviral loads and development of HAM/TSP. Therefore it is necessary to conduct functional studies aimed at evaluating the impact of these mutations on the virus persistence and immune evasion.status: publishe

Transient hearing loss in adults associated with Zika virus infection

In 2015, during the outbreak of Zika virus (ZIKV) in Brazil, we identified 3 cases of acute hearing loss after exanthematous illness. Serology yielded finding compatible with ZIKV as the cause of a confirmed (n = 1) and a probable (n = 2) flavivirus infection, indicating an association between ZIKV infection and transient hearing loss.status: publishe

Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-16T11:56:06Z No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-07-16T12:33:35Z (GMT) No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5)Made available in DSpace on 2019-07-16T12:33:35Z (GMT). No. of bitstreams: 1 Menezes, J.P. Proteomic Analysi...2019.pdf: 2216682 bytes, checksum: 42cced00b8b12eaae7f24baeecf4ae90 (MD5) Previous issue date: 2019Fundação de Amparo à Pesquisa do Estado da Bahia (PV http://www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical Disease (PV http://inct.cnpq.br/ web/inct-dt). VB, PV, and UL are senior investigators funded by CNPq.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Doenças Infecciosas de Vetores. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Medicine. Legal Medicine. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil / Federal University of Rio de Janeiro. Laboratory of Physiopathology. Department of Pathology. Macaé, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Inflamação e Biomarcadores. Salvador, BA, Brasil.Federal University of the Western of Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brazil.Fundação Oswaldo Cruz. Centro de Integração de Dados e Conhecimento para a Saúde. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Minas Gerais, BH, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Minas Gerais, BH, Brasil.Virginia Commonwealth University. Department of Microbiology and Immunology. Richmond, VA, United States.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Paraná, PR, Brasil.Federal University of Rio de Janeiro. Carlos Chagas Filho Biophysics Institute. Laboratory of Molecular Parasitology. Center of Health Science. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Carlos Chagas Filho Biophysics Institute. Laboratory of Molecular Parasitology. Center of Health Science. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Doenças Infecciosas de Vetores. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Hospedeiro-Parasita e Epidemiologia. Salvador, BA, Brasil / National Institute of Science and Technology of Tropical Disease. Patos, Brazil.CBA mice macrophages (MØ) control infection by Leishmania major and are susceptive to Leishmania amazonensis, suggesting that both parasite species induce distinct responses that play important roles in infection outcome. To evaluate the MØ responses to infection arising from these two Leishmania species, a proteomic study using a Multidimensional Protein Identification Technology (MudPIT) approach with liquid chromatography tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838 proteins detected in BMMØ, data mining approach found six proteins significantly associated with the tested conditions. To investigate their biological significance, enrichment analysis was performed using Ingenuity Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly associated with the infection process. NRF2 signatures were present in both CPs and UTFs pathways. Proteins involved in iron metabolism, such as heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62) were found in the NRF2 CPs and the NRF2 UTFs. Differences in the involvement of iron metabolism pathway in Leishmania infection was revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was strongly associated with L. amazonensis infection, while ferritin was regulated by both species. As expected, higher HO-1 and p62 expressions were validated in L. amazonensis-infected BMMØ, in addition to decreased expression of ferritin and nitric oxide production. Moreover, BMMØ incubated with L. amazonensis LPG also expressed higher levels of HO-1 in comparison to those stimulated with L. major LPG. In addition, L. amazonensis-induced uptake of holoTf was higher than that induced by L. major in BMMØ, and holoTf was also detected at higher levels in vacuoles induced by L. amazonensis. Taken together, these findings indicate that NRF2 pathway activation and increased HO-1 production, together with higher levels of holoTf uptake, may promote permissiveness to L. amazonensis infection. In this context, differences in protein signatures triggered in the host by L. amazonensis and L. major infection could drive the outcomes in distinct clinical forms of leishmaniasis

Risk of Zika microcephaly correlates with features of maternal antibodies

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-10T12:26:15Z No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-10T13:32:42Z (GMT) No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5)Made available in DSpace on 2019-10-10T13:32:42Z (GMT). No. of bitstreams: 1 Robbiani F D ...Risk.pdf: 2296966 bytes, checksum: 5e47aca9208f3f35c969fd82960279f4 (MD5) Previous issue date: 2019-01-07National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Fundação de Amparo `a Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O’Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded toWNPRC, at a facility constructed in part with support from Research Facilities Improvement Programgrants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Zika fast-track).The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA / Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven / Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Fudan University. School of Basic Medical Sciences. Shanghai Medical College. Key Laboratory of Medical Molecular Virology. Shanghai, China.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil / Universidade Federal de São Paulo. São Paulo, SP, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Secretaria de Saúde do Estado da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA.Universidade Federal de São Paulo. São Paulo, SP, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Santo Amaro. Salvador, BA, Brasil.Hospital Aliança. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven / Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.University of California. California National Primate Research Center. Davis, Davis, CA, USA.University of California. School of Veterinary Medicine. Department of Pathology, Microbiology, and Immunology. Davis, Davis, CA, USA.Washington National Primate Research Center. Seattle, WA, USA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Immunology. Seattle, WA, USA.Washington National Primate Research Center. Seattle, WA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Immunology. Seattle, WA, USA / University of Washington. Department of Global Health. Seattle, WA, USA.University of Washington. Department of Global Health. Seattle, WA, USA / University of Washington. Department of Pediatrics. Seattle, WA, USA / Seattle Children’s Research Institute. Center for Global Infectious Disease Research. Seattle, WA, USA.Washington National Primate Research Center. Seattle, WA, USA / University of Washington. Center for Innate Immunity and Immune Disease. Seattle, WA, USA / University of Washington. Department of Global Health. Seattle, WA, USA / University of Washington. Department of Obstetrics and Gynecology. Seattle, WA, USA.University of Wisconsin-Madison. Department of Pathology and Laboratory Medicine. Madison, WI, USA.University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA.University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA.University of Wisconsin-Madison. Department of Pathology and Laboratory Medicine. Madison, WI, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon National Primate Research Center. Pathology Services Unit, Division of Comparative Medicine. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA / Oregon Health and Science University. Department of Obstetrics and Gynecology. Portland, OR, USA.Oregon National Primate Research Center. Division of Reproductive and Developmental Sciences. Beaverton, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Oregon National Primate Research Center. Division of Pathobiology and Immunology. Beaverton, OR, USA / Oregon Health and Science University. Vaccine and Gene Therapy Institute. Portland, OR, USA.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Instituto da Saúde Coletiva. Salvador, BA, Brasil.University of California. California National Primate Research Center. Davis, Davis, CA, USA / University of California. School of Veterinary Medicine. Department of Pathology, Microbiology, and Immunology. Davis, Davis, CA, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, USA.The Rockefeller University. Laboratory of Molecular Immunology. New York, NY, USA / The Rockefeller University. Howard Hughes Medical Institute. New York, NY, USA.Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015-2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used