Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.

Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

Recurrent acquired ocular toxoplasmosis associated with Kyrieleis plaques and documented allergy to sulfonamide-A treatment proposal for two rare conditions.

The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide.

Are we ready to stratify BI-RADS 4 lesions observed on magnetic resonance imaging? A real-world noninferiority/equivalence analysis / Estamos prontos para estratificar lesões BI-RADS 4 na ressonância magnética? Uma análise de não inferioridade/equivalência do mundo real

Abstract Objective: To demonstrate that positive predictive values (PPVs) for suspicious (category 4) magnetic resonance imaging (MRI) findings that have been stratified are equivalent to those stipulated in the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) for mammography and ultrasound. Materials and Methods: This retrospective analysis of electronic medical records generated between January 4, 2016 and December 29, 2021 provided 365 patients in which 419 suspicious (BI-RADS category 4) findings were subcategorized as BI-RADS 4A, 4B or 4C. Malignant and nonmalignant outcomes were determined by pathologic analyses, follow-up, or both. For each subcategory, the level 2 PPV (PPV2) was calculated and tested for equivalence/noninferiority against the established benchmarks. Results: Of the 419 findings evaluated, 168 (40.1%) were categorized as malignant and 251 (59.9%) were categorized as nonmalignant. The PPV2 for subcategory 4A was 14.2% (95% CI: 9.3-20.4%), whereas it was 41.2% (95% CI: 32.8-49.9%) for subcategory 4B and 77.2% (95% CI: 68.4-84.5%) for subcategory 4C. Multivariate analysis showed a significantly different cancer yield for each subcategory (p < 0.001). Conclusion: We found that stratification of suspicious findings by MRI criteria is feasible, and malignancy probabilities for sub-categories 4B and 4C are equivalent to the values established for the other imaging methods in the BI-RADS. Nevertheless, low suspicion (4A) findings might show slightly higher malignancy rates.

Resumo Objetivo: Demonstrar que os valores preditivos positivos (VPPs) para lesões suspeitas (categoria 4) identificadas por ressonância magnética (RM) são equivalentes aos estipulados no ACR BI-RADS para mamografia e ultrassonografia. Materiais e Métodos: Análise retrospectiva de dados em prontuário eletrônico, entre 4 de janeiro de 2016 e 29 de dezembro de 2021, resultou em 365 pacientes elegíveis, com 419 lesões classificadas como BI-RADS 4A, 4B ou 4C. Desfechos malignos e não malignos foram determinados por estudo patológico e/ou acompanhamento. Realizamos o cálculo do VPP nível 2 (VPP2) para cada subcategoria e testamos para não inferioridade/equivalência em relação aos valores de referência. Resultados: Dos 419 achados, 168 (40,1%) foram malignos e 251 (59,9%), não malignos. O VPP2 para subcategoria 4A foi 14,2% (IC 95%: 9,3-20,4%), para 4B foi 41,2% (IC 95%:, 32,8-49,9%) e para 4C foi 77,2% (IC 95%: 68,4-84,5%). Análise multivariada demonstrou diferenças estatisticamente significantes entre as subcategorias (p < 0,001). Conclusão: A estratificação de achados suspeitos por RM é factível, sendo que a probabilidade de malignidade das subcategorias 4B e 4C é equivalente à estabelecida para outros métodos de imagem pelo BI-RADS. Contudo, lesões de baixa suspeição (4A) podem apresentar taxas mais altas de malignidade.

Vitreoretinal Surgery in Uveitis: From Old to New Concepts - A Review.

PURPOSE: The aim of this article is to do a comprehensive literature review about the current role of pars plana vitrectomy in uveitis and in its different structural complications such as cystoid macular edema, epiretinal membrane, macular hole, and retinal detachment. METHODS: This comprehensive literature review was performed based on a search on PubMed, BioMed Central, Science Open, and CORE databases, of relevant articles abording pars plana vitrectomy in uveitis. DISCUSSION: Uveitis is a complex disease with multiple etiologies and pathogenic mechanisms. Therapeutic pars plana vitrectomy (PPV) may aid in uveitic structural complications such as cystoid macular edema, epiretinal membranes, macular hole, and retinal detachments even though some cases may present unpredictable visual outcomes. Diagnostic PPV with appropriate ancillary testing is also a valuable tool for the assessment and diagnosis of uveitis in a large proportion of patients. CONCLUSION: Over the years, pars plana vitrectomy has undergone significant transformations since its invention nearly 5 decades ago, however, the quality of evidence in the literature regarding its use for uveitis has not improved in the same way. Even though some structural uveitis complications (as previously mentioned) may respond well to surgery, there is still a certain unpredictability regarding its visual outcomes. On the other hand, diagnostic vitrectomy with appropriate ancillary testing is also a valuable tool for the assessment and diagnosis of uveitis in a large proportion of patients.

Endophytic species of Induratia from coffee and carqueja plants from Brazil and its potential for the biological control of toxicogenic fungi on coffee beans by means of antimicrobial volatiles.

Several endophytic fungi have been reported to have produced bioactive metabolites. Some of them, including the Induratia species, have the capacity to emit volatile compounds with antimicrobial properties with broad spectrum against human and plant pathogens. The present study aimed to prospect the Induratia species producing volatile organic compounds (VOCs), in carqueja plants used in alternative medicine and coffee plants in Brazil. A total of 11 fungal isolates producing volatile metabolites were obtained by a parallel growth technique, using I. alba 620 as a reference strain. Phylogenetic relationships revealed the presence of at least three distinct species, I. coffeana, I. yucatanensis, and Induratia sp. SPME/GC/MS analyses of the VOCs in the headspace above the mycelium from Induratia species cultured for 10 days on PDA revealed the volatile profile emitted by I. coffeana CCF 572, I. coffeana COAD 2055, I. yucatanensis COAD 2062, and Induratia sp. COAD 2059. Volatile organic compounds produced by I. coffeana isolates presented antimicrobial activity against Aspergillus ochraceus, A. sclerotiorum, A. elegans, A. foetidus, A. flavus, A. tamari, A. tubingensis, A. sydowii, A. niger, A. caespitosus, A. versicolor, and A. expansum, sometimes by decreasing the growth rate or, mainly, by fully inhibiting colony growth. Fifty-eight percent of the target species died after 6 days of exposure to VOCs emitted by I. coffeana CCF 572. In addition, VOCs emitted by the same fungus inhibited the growth in A. ochraceus inoculated into coffee beans, which indicates that plants which have I. coffeana as an endophyte may be protected from attacks by this plant pathogen.

Are we ready to stratify BI-RADS 4 lesions observed on magnetic resonance imaging? A real-world noninferiority/equivalence analysis.

Objective: To demonstrate that positive predictive values (PPVs) for suspicious (category 4) magnetic resonance imaging (MRI) findings that have been stratified are equivalent to those stipulated in the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) for mammography and ultrasound. Materials and Methods: This retrospective analysis of electronic medical records generated between January 4, 2016 and December 29, 2021 provided 365 patients in which 419 suspicious (BI-RADS category 4) findings were subcategorized as BI-RADS 4A, 4B or 4C. Malignant and nonmalignant outcomes were determined by pathologic analyses, follow-up, or both. For each subcategory, the level 2 PPV (PPV2) was calculated and tested for equivalence/noninferiority against the established benchmarks. Results: Of the 419 findings evaluated, 168 (40.1%) were categorized as malignant and 251 (59.9%) were categorized as nonmalignant. The PPV2 for subcategory 4A was 14.2% (95% CI: 9.3-20.4%), whereas it was 41.2% (95% CI: 32.8-49.9%) for subcategory 4B and 77.2% (95% CI: 68.4-84.5%) for subcategory 4C. Multivariate analysis showed a significantly different cancer yield for each subcategory (p < 0.001). Conclusion: We found that stratification of suspicious findings by MRI criteria is feasible, and malignancy probabilities for sub-categories 4B and 4C are equivalent to the values established for the other imaging methods in the BI-RADS. Nevertheless, low suspicion (4A) findings might show slightly higher malignancy rates.

Objetivo: Demonstrar que os valores preditivos positivos (VPPs) para lesões suspeitas (categoria 4) identificadas por ressonância magnética (RM) são equivalentes aos estipulados no ACR BI-RADS para mamografia e ultrassonografia. Materiais e Métodos: Análise retrospectiva de dados em prontuário eletrônico, entre 4 de janeiro de 2016 e 29 de dezembro de 2021, resultou em 365 pacientes elegíveis, com 419 lesões classificadas como BI-RADS 4A, 4B ou 4C. Desfechos malignos e não malignos foram determinados por estudo patológico e/ou acompanhamento. Realizamos o cálculo do VPP nível 2 (VPP2) para cada subcategoria e testamos para não inferioridade/equivalência em relação aos valores de referência. Resultados: Dos 419 achados, 168 (40,1%) foram malignos e 251 (59,9%), não malignos. O VPP2 para subcategoria 4A foi 14,2% (IC 95%: 9,3­20,4%), para 4B foi 41,2% (IC 95%:, 32,8­49,9%) e para 4C foi 77,2% (IC 95%: 68,4­84,5%). Análise multivariada demonstrou diferenças estatisticamente significantes entre as subcategorias (p < 0,001). Conclusão: A estratificação de achados suspeitos por RM é factível, sendo que a probabilidade de malignidade das subcategorias 4B e 4C é equivalente à estabelecida para outros métodos de imagem pelo BI-RADS. Contudo, lesões de baixa suspeição (4A) podem apresentar taxas mais altas de malignidade.

Large inferior retinectomies for proliferative vitreoretinopathy in silicone oil-filled eyes.

BACKGROUND: To describe the anatomical and functional outcomes and late complications in patients who developed inferior proliferative vitreoretinopathy (PVR) in silicone oil-filled eyes and who required reoperation with large inferior retinectomy. METHODS: This is a single-center, retrospective, interventional case series analysis. The study involved 18 individuals with tractional retinal re-detachment due to PVR development inferiorly in eyes who had undergone prior pars plana vitrectomy and silicone oil as a tamponade. All patients included in the study underwent secondary surgery with large inferior retinectomy (from 120° to 270°) and silicone oil filling. RESULTS: The mean follow-up period was 44.0 ± 31.5 (± SD) months (range: 4 to 96 months. The anatomical success, defined as the complete reattachment of the retina until the last follow-up, was observed in 88.9% of the cases. The postoperative visual acuity ranged from 20/100 to hand motion at 60 cm. Only two cases (11.1%) did not achieve anatomical success at the last follow-up due to recurrent PVR and retinal re-detachment (one including hypotony). All of the patients were pseudophakic. The PVR grade, as well as the presence of PVR prior to primary surgery, showed no statistical correlation with BCVA, the extent of retinectomies, and final macular status. There was a statistically significant correlation between "Final BCVA" and "Initial BCVA" (r = 0.654) and between "Final BCVA" and "Extent of Retinectomy" (r = 0.615). CONCLUSIONS: Reoperation in eyes filled with silicone oil may be required when PVR is developed. Secondary surgery in these cases with large inferior retinectomy and silicone oil implantation may reach good anatomical success with low rates of late complications, besides improving visual acuity. A better BCVA at the time of re-RD diagnosis and cases of retinectomies with greater extensions showed a positive correlation with better functional outcomes. Trial registration Research Ethics Committee of the Suel Abujamra Institute reviewed and approved this study protocol (approval number, 5.404.961).

Central retinal artery occlusion secondary to presumed traumatic carotid artery dissection in a healthy child.

PURPOSE: To describe a rare case of a 13 years-old healthy child that presented CRAO secondary to carotid artery dissection, which occurred after a neck rotation movement. METHODS: Case report with prospective literature review. PATIENTS: One patient described in the case report. RESULTS: Not applicable. DISCUSSION/CONCLUSION: Internal carotid artery dissection is a rare condition, specially in children, that can lead to serious cerebral-ocular ischemic events. It may occur due to direct vessel trauma or spontaneously. Prompt imaging screening is of paramount importance because early antithrombotic treatment or surgical intervention may significantly reduce the incidence of devastating ischemic events, such as stroke or central retinal artery occlusion.

Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice.

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum.

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.

Enlightening new underpinnings in hydration retinal folds.

PURPOSE: To describe and value a peculiar alteration typically found in rhegmatogenous retinal detachment raising news foundations of its role in the photoreceptors and visual prognosis. DESIGN: Case description and rationale formulation. SUBJECTS: An isolated case. INTERVENTION: We report a case of a 52-year-old male patient complaining of sudden visual acuity (VA) loss in the left eye. Fundoscopic findings revealed rhegmatogenous retinal detachment, macula off, and an isolated horseshoe tear in the infero-temporal periphery. Spectral-domain optical coherence tomography (SD-OCT) evinced prominent hydration retinal folds. MAIN OUTCOME MEASURES: Restructuring of the retinal layers, visual acuity and complaints. RESULTS: The patient underwent scleral buckling surgery with complete re-attachment of the retina and significant improvement of the hydration retinal folds. In addition, there was resolution of visual symptoms, with a final VA of 20/30. CONCLUSIONS: We speculate that the increase in arc length of the outer retina generates a centripetal force towards the fovea. Its association with the higher density of photoreceptors in this region, generates resistance in the water inflow, preventing swelling and cellular damage of the central photoreceptors.

Estágios da doença renal crônica e suas associações com o nível de atividade física, qualidade de vida e perfil nutricional / Stages of chronic kidney disease and their associations with the level of physical activity, quality of life and nutritional profile

Estudos apresentaram resultados benéficos da prática de exercício físico no tratamento adjuvante à doença renal crônica (DRC). O objetivo desse estudo foi comparar e associar os estágios da evolução da DRC dos pacientes em tratamento conservador com o nível de atividade física, qualidade de vida e o perfil nutricional. A amostra foi composta por pacientes de ambos os sexos, com idade superior aos 18 anos em tratamento conservador para DRC. Foram avaliados o perfil nutricional (índice de massa corporal, circunferência de cintura e percentual de gordura); nível de atividade física (IPAQ); nível de qualidade de vida (WHOQOL-Bref ). Participaram do estudo 52 pacientes com idade média de 60,30 ± 9,10 anos, 53,8% mulheres, 57,6% diabéticos e 76,9% hipertensos. Para o perfil nutricional e nível de atividade física, 38,4% eram pessoas com obesidade; 82,6% com valores elevados de circun-ferência da cintura (CC); e 67% apresentaram baixos níveis baixos de atividade física. Para o nível de qualidade de vida, menores escores em satisfação com saúde (2,98 ± 0,83) e meio ambiente (2,75 ± 0,38); melhores escores em domínio psicológico (3,80 ± 0,53) e relações sociais (3,58 ± 0,58). Não houve associação significativa entre as variáveis do estudo e a estratificação dos pacientes em níveis de filtração glomerular. A correlação foi positiva do estágio DRC somente com a dimensão de relações sociais (rho = 0,247, p = 0,07) do nível de qualidade de vida. Os sujeitos apresentaram baixos níveis de atividade física e elevado prevalência de excesso de peso/obesidade, mas estes níveis não se alteraram em associação com os estágios da DRC

Studies have shown beneficial results of the practice of physical exercise in the adjuvant treatment of chronic kidney disease (CKD). The aim of this study was to compare and associate the stages of evolution of CKD in patients undergoing conservative treatment with the level of physical activity, quality of life and nutri-tional profile. The sample consisted of patients of both genders, aged over 18 years, undergoing conservative treatment for CKD. The nutritional profile (body mass index, waist circumference and fat percentage) were evaluated; level of physical activity (IPAQ); level of quality of life ( WHOQOL-Bref ). The study included 52 patients with a mean age of 60.30 ± 9.10 years, 53.8% women, 57.6% diabetic and 76.9% hypertensive. For the nutritional profile and level of physical activity, 38.4% were obese people; 82.6% with higher waist circumference ( WC) values; and 67% had low levels of physical activity. For the level of quality of life, lower scores in satisfaction with health (2.98 ± 0.83) and environment (2.75 ± 0.38); better scores in the psychological domain (3.80 ± 0.53) and social relationships (3.58 ± 0.58). There was no significant associa-tion between study variables and patients' stratification in glomerular filtration levels. The correlation was positive for the DRC stage only with the dimension of social relationships (rho = 0.247, p = 0.07) of the level of quality of life. The subjects had low levels of physical activity and a high prevalence of overweight/obesity, but these levels did not change in association with the stages of CKD

A patient with X-linked retinoschisis and exudative retinal detachment associated with a pathogenic hemizygous variant c.304c>T in RS1.

BACKGROUND: X-linked retinoschisis (XLRS) is a rare retinal dystrophy due to pathogenic variants in the RS1 gene. The hallmark of the disease is a foveal spoke-wheel appearance. The purpose of this report is to expand the phenotypic spectrum of XLRS reporting a patient with atypical phenotype of XLRS associated with Coats-like phenotype. MATERIALS AND METHODS: This is a case report of a patient diagnosed with XLRS who underwent ophthalmologic multimodal imaging and next-generation sequencing panel. RESULTS: The proband is a 14-year-old male patient who presented at Instituto Suel Abujamra with a history of Coats Disease in the right eye treated with retinal laser in both eyes two years ago. His best-corrected visual acuity was count finger at 1 foot in the right eye and 20/40 in the left eye. Fundus exam showed an extensive area of exudation and retinal detachment in the right eye and cystic change at the fovea in a spoke-wheel pattern in the left eye. The next-generation sequencing panel targeting inherited retinal diseases with 236 genes found a pathogenic hemizygous variant c.304C>T (p.Arg102Trp) in RS1 that has already been reported. CONCLUSIONS: The association of peripheral vascular incompetence and XLRS has already been described. Retinal exudation in the setting of XLRS is probably the result of vascular disruption and compromise. The loss of retinoschisin function that leads to foveal retinoschisis may also lead to vascular anomalies.

Pachychoroid disease spectrum: review article.

PURPOSE: The aim of this article is to do a comprehensive literature review about the current understandings of the pachychoroid disease spectrum, describing its multimodal imaging analysis, pathophysiology, differential diagnosis, and current types of management. METHODS: This comprehensive literature review was performed based on a search on the PubMed database, of relevant pachychoroid published papers according to our current knowledge. DISCUSSION: The pachychoroid disease spectrum, according to some authors, includes the following: pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV)/aneurysmal type 1 neovascularization (AT1), and more recently focal choroidal excavation (FCE) and peripapillary pachychoroid syndrome (PPS). Each one of these entities will be described and discussed in this article. CONCLUSION: Significant advances in multimodal imaging have enabled a better understanding of the typical choroidal changes in pachychoroid disease spectrum. The clinical knowledge and managing options about this disease significantly increased in the last years. However, it is still unclear why some eyes with typical pachychoroid disease phenotype show no evidence of RPE damage and subretinal fluid (uncomplicated pachychoroid) while others present progressive tissue damage, neovascularization, and atrophy.

Gravidez na adolescência: perfil sociodemográfico de adolescentes grávidas no período de 2015 até 2019 / Embarazo en adolescentes: perfil sociodemográfico de las adolescentes embarazadas en el periodo de 2015 a 2019 / Adolescent pregnancy: sociodemographic profile of pregnant adolescents from 2015 to 2019

Objetivo: analisar o perfil sociodemográfico de adolescentes grávidas no Brasil entre os anos de 2015 até 2019. Método: estudo transversal descritivo, com abordagem quantitativa, proveniente do Departamento de Informática do Sistema Único de Saúde. A análise de dados utilizou frequências absolutas e relativas (%). Resultados: foram registradas 2.405.248 adolescentes grávidas. A maioria das gestações ocorreram em meninas de 15 a 19 anos (95,2%), de cor parda (65,4%), solteiras (64,9%), com 8 a 11 anos de instrução materna (66,9%). Quanto as características da gestação, 98,7% foram gravidez única, com duração de 37 a 41 semanas (81,7%) e tipo de parto vaginal (61,2%). A análise temporal apresentou queda de 2015 a 2019. Conclusão: a gravidez na adolescência constitui-se como um evento complexo em que a atenção deve abordar um contexto biopsicossocial. Assim, delinear o perfil sociodemográfico dessas adolescentes é necessário, pois possibilita conhecer a população em estudo e suas condições de vulnerabilidade.

Objective: to analyze the sociodemographic profile of pregnant adolescents in Brazil between 2015 and 2019. Method: descriptive cross-sectional study, with a quantitative approach, coming from the Information Technology Department of the Unified Health System. Data analysis used absolute and relative frequencies (%). Results: 2,405,248 pregnant adolescents were registered. The majority of pregnancies occurred in girls aged 15 to 19 years (95.2%), of a brown color (65.4%), single (64.9%), with 8 to 11 years of maternal education (66.9%). As for the characteristics of pregnancy, 98.7% were single pregnancy, lasting 37 to 41 weeks (81.7%) and vaginal type of delivery (61.2%). The temporal analysis showed a drop from 2015 to 2019. Conclusion: teenage pregnancy is a complex event in which attention must address a biopsychosocial context. Thus, delineating the sociodemographic profile of these adolescents is necessary, as it makes it possible to get to know the population under study and its vulnerability conditions.

Objetivo: analizar el perfil sociodemográfico de las adolescentes embarazadas en Brasil entre los años 2015 y 2019. Método: estudio descriptivo transversal, con enfoque cuantitativo, del Departamento de Informática del Sistema Único de Salud. En el análisis de los datos se utilizaron frecuencias absolutas y relativas (%). Resultados: se registraron 2.405.248 adolescentes embarazadas. La mayoría de los embarazos se produjeron en chicas de entre 15 y 19 años (95,2%), morenas (65,4%), solteras (64,9%), con entre 8 y 11 años de educación materna (66,9%). En cuanto a las características del embarazo, el 98,7% fueron embarazos únicos, con una duración de 37 a 41 semanas (81,7%) y tipo de parto vaginal (61,2%). El análisis temporal mostró un descenso de 2015 a 2019. Conclusión: el embarazo en la adolescencia constituye un evento complejo en el que se debe prestar atención a un contexto biopsicosocial. Por lo tanto, es necesario delinear el perfil sociodemográfico de los adolescentes, ya que permite conocer a la población en estudio y sus condiciones de vulnerabilidad.

Medidas de segurança ocupacional no transoperatório de quimioterapia hipertérmica intraperitoneal: scoping review / Medidas de seguridad ocupacional en el transoperatorio de quimioterapia hipertérmica intraperitoneal: scoping review / Occupational safety measures in the intraoperative period of hyperthermic intraperitoneal chemotherapy: scoping review

Resumo Objetivo Mapear as medidas de segurança ocupacional recomendadas aos profissionais envolvidos no atendimento transoperatório de pacientes submetidos à Quimioterapia Intraperitoneal Hipertérmica. Métodos Estudo qualitativo com ênfase em scoping review, fundamentado no Instituto Joanna Briggs. Realizou-se buscas nas bases de dados Pubmed, BVS, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library e literatura cinzenta. Pergunta de pesquisa utilizou o acrônimo PCC: quais medidas de segurança ocupacional são necessárias no Centro Cirúrgico para profissionais que atuam, direta ou indiretamente, no transoperatório da HIPEC? A Busca de artigos ocorreu entre 2015 a 2019. Resultados Evidenciou-se escassa literatura sobre a temática. Selecionados dez artigos: uma revisão sistemática; dois casos-controle; dois estudos descritivos; quatro estudos de revisão bibliográfica; um relato de experiência. Análise dos artigos evidenciou as medidas de segurança recomendadas para profissionais que atuam direta ou indiretamente nesse procedimento cirúrgico, a saber: educação e capacitação da equipe envolvida; utilização de equipamentos de proteção individual e coletiva; oferecer infraestrutura e orientações gerais. Conclusão Medidas de segurança recomendadas para os profissionais envolvidos no atendimento transoperatório do paciente submetido à Quimioterapia Intraperitoneal Hipertérmica são: capacitação da equipe; utilização de equipamentos específicos de proteção individual e coletiva; infraestrutura necessária como ajuste do ar condicionado com pressão maior dentro da sala cirúrgica; e orientações gerais em relação à organização da sala cirúrgica, descarte dos resíduos, limpeza da sala/materiais utilizados e acompanhamento da saúde ocupacional da equipe envolvida em procedimento cirúrgico.

Resumen Objetivo Mapear las medidas de seguridad ocupacional recomendadas a los profesionales involucrados en la atención transoperatoria de pacientes sometidos a Quimioterapia Intraperitoneal Hipertérmica. Métodos Estudio cualitativo con énfasis en el scoping review, fundamentado en el Instituto Joanna Briggs. Se realizaron búsquedas en las bases de datos Pubmed, BVS, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library y literatura gris. Pregunta de encuesta utilizó el acrónimo PCC: ¿qué medidas de seguridad ocupacional se hacen necesarias en el Quirófano para profesionales que actúan, directa o indirectamente, en el transoperatorio de la HIPEC? La búsqueda de los artículos ocurrió entre el 2015 y el 2019. Resultados Se puso en evidencia una escasa literatura sobre la temática. Seleccionados diez artículos: una revisión sistemática; dos casos-control; dos estudios descriptivos; cuatro estudios de revisión bibliográfica; un relato de experiencia. Análisis de los artículos evidenció las medidas de seguridad recomendadas para profesionales que actúan directa o indirectamente en ese procedimiento quirúrgico, a saber: educación y capacitación del equipo involucrado; utilización de equipos de protección individual y colectiva; brindar infraestructura y orientaciones generales. Conclusión Representan medidas de seguridad recomendadas para los profesionales involucrados en la atención transoperatoria del paciente sometido a Quimioterapia Intraperitoneal Hipertérmica: capacitación del equipo; utilización de equipos específicos de protección individual y colectiva; infraestructura necesaria como ajuste del aire acondicionado con una presión más alta dentro del quirófano; y orientaciones generales con relación a la organización del quirófano, descarte de los deshechos, limpieza de la sala/materiales utilizados y acompañamiento de la salud ocupacional por el equipo involucrado en el procedimiento quirúrgico.

Abstract Objective To map the occupational safety measures recommended to professionals involved in the intraoperative care of patients undergoing Hyperthermic Intraperitoneal Chemotherapy. Methods Qualitative scoping review based on the Joanna Briggs Institute. Searches were performed in Pubmed, VHL, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library databases and gray literature. The PCC acronym was used in the research question: what occupational safety measures are necessary in the operating room for professionals working directly or indirectly in the intraoperative period of HIPEC? A search for articles published between 2015 and 2019 was performed. Results Literature on the subject was scarce. Ten articles were selected: a systematic review; two control cases; two descriptive studies; four literature review studies; an experience report. In the analysis of articles, the recommended safety measures for professionals who work directly or indirectly in this surgical procedure was evidenced, namely: education and training of the staff involved; use of individual and collective protective equipment; provision of infrastructure and general guidelines. Conclusion Recommended safety measures for professionals involved in the intraoperative care of patients undergoing Hyperthermic Intraperitoneal Chemotherapy are: team training; use of specific individual and collective protection equipment; necessary infrastructure, such as adjusting the air conditioning to higher pressure inside the operating room; and general guidelines regarding the organization of the operating room, waste disposal, cleaning of the room/materials used, and monitoring of the occupational health of the team involved in the surgical procedure.

Polyclonal F(ab')2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency.

We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:106, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT90). Plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab')2 preparation with PRNT90 titers 150-fold higher than the neutralizing titers in human convalescent plasma. Challenge studies were carried out in hamsters and showed the in vivo ability of equine F(ab')2 to reduce viral load in the pulmonary tissues and significant clinical improvement determined by weight gain. The neutralization curve by F(ab')2 was similar against the WT and P.2 variants, but displaced to higher concentrations by 0.39 log units against the P.1 (Gamma) variant. These results support the possibility of using equine F(ab')2 preparation for the clinical treatment of COVID patients.

Yellow fever vaccine protects mice against Zika virus infection.

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.

Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series.

Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances. Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT). Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15-33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25-10.75) and altered visuospatial construction with a median of four points (IQR 4-9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-Co Conclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.

Expanding the Phenotypic and Genotypic Spectrum of Bietti Crystalline Dystrophy.

The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802-8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder.