Biological Activity of 6,7-Dehydroxyroyleanone and Derivatives Obtained from Plectranthus aliciae (Codd) A.J.Paton.

The Plectranthus genus (Lamiaceae) is known to be rich in abietane diterpenes. The bioactive 6,7-dehydroxyroyleanone (DHR, 1) was previously isolated from Plectranthus madagascariensis var. madagascariensis and var. aliciae. This study aimed to explore the occurrence of DHR, 1, in P. aliciae and the potential bioactivities of new semisynthetic derivatives from DHR, 1. Several extraction methods were evaluated, and the hydrodistillation, using a Clevenger apparatus, afforded the highest yield (77.8 mg/g of 1 in the essential oil). Three new acyl derivatives (2-4) were successfully prepared from 1 (yields of 86-95%). Compounds 1-4 showed antioxidant activity, antibacterial effects, potent cytotoxic activity against several cell lines, and enhanced anti-inflammatory activity that surpassed dexamethasone (positive control). These findings encourage further exploration of derivatives 2-4 for potential mechanisms of antitumoral, antioxidant, and anti-inflammatory capabilities, studying both safety and efficacy.

Case report: Introduction of an Ahmed valve implant tube into the ciliary sulcus using a guide-wire.

BACKGROUND: Glaucoma is a progressive optic neuropathy and it is the main cause of irreversible blindness worldwide. Intraocular pressure (IOP) is the only modifiable one and trabeculectomy is commonly considered the surgical "gold standard" to decrease IOP. In particular cases, other kind of surgeries, as the Ahmed Glaucoma Valve (AGV) implant, are a reliable alternative. Usually, the silicone tube of AGV surgery is inserted into the anterior chamber. Sometimes it is necessary to place the AGV silicone tube in the ciliary sulcus, especially in cases of endothelial decompensation. This surgical procedure is not always easy to perform. CASE PRESENTATION: This article describes and presents a technique for inserting the AGV tube into the posterior chamber using a guide-wire, in a total of 12 cases are reported. This procedure has been mostly applied in a group of pseudophakic patients who need AGV placement to control elevated IOP. In exceptional situations, this procedure was applied in pseudophakic patients previously with AGV tube implanted in the anterior chamber and with loss of endothelial cells or in phakic patients with previously implanted AGV anterior chamber tube, simultaneously to cataract surgery. CONCLUSION: The purpose of these cases presentations attended at our service is to demonstrate the passage of the AGV silicone tube was performed with the aid of a guide wire.

Effectiveness and safety of lenvatinib in a series of advanced well-differentiated thyroid carcinomas from a single tertiary cancer center and literature review.

BACKGROUND: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC. METHODS: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed. RESULTS: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported. CONCLUSIONS: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient´s performance status and comorbidities.

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Pigment deposits in the retrolental space of Berger: a rare feature of pigment dispersion syndrome? / Depósitos de pigmento no espaço de Berger: uma característica rara de síndrome de dispersão pigmentar?

ABSTRACT Pigment dispersion syndrome is associated with clinical features such as Krukenberg's spindles, trabecular pigmentation, Scheie's stripe and Zentmayer's ring. Another less common feature of this syndrome is retrolental pigment deposits due to anterior hyaloid detachment or a defect in the Wieger's ligament. We present two cases of pigment deposits on the posterior lens capsule. In both cases, there is bilateral dispersion of pigment throughout the anterior segment. The retrolental deposits are unilateral in the first case and bilateral in the second. Both patients report a history of ocular trauma. This is a possible important clinical sign of pigment dispersion syndrome, rarely described.

RESUMO A síndrome de dispersão pigmentar associa-se a sinais clínicos característicos como fuso de Krukenberg, hiperpigmentação da malha trabecular, linha de Scheie e anel de Zentmeyer. Um sinal menos comum dessa síndrome é o depósito de pigmento posterior ao cristalino, que ocorre por um descolamento da hialoide anterior ou um defeito no ligamento de Wieger. Apresentamos dois casos de depósitos de pigmento posterior à cápsula posterior do cristalino. Em ambos os casos, existia dispersão bilateral de pigmento por todo o segmento anterior. No primeiro caso, os depósitos eram unilaterais e, no segundo, estavam presentes em ambos os olhos. Este pode corresponder a um sinal potencialmente importante da síndrome de dispersão pigmentar, raramente descrito.

Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis.

Paracoccidioides spp. is the etiologic agent of Paracoccidioidomycosis (PCM), a systemic disease with wide distribution in Latin America. Macrophages are very important cells during the response to infection by P. brasiliensis. In this study, we performed a proteomic analysis to evaluate the consequences of P. brasiliensis yeast cells on the human THP-1 macrophage proteome. We have identified 443 and 2247 upregulated or downregulated proteins, respectively, in macrophages co-cultured with yeast cells of P. brasiliensis in comparison to control macrophages unexposed to the fungus. Proteomic analysis revealed that interaction with P. brasiliensis caused metabolic changes in macrophages that drastically affected energy production pathways. In addition, these macrophages presented regulated many factors related to epigenetic modifications and gene transcription as well as a decrease of many proteins associated to the immune system activity. This is the first human macrophage proteome derived from interactions with P. brasiliensis, which contributes to elucidating the changes that occur during the host response to this fungus. Furthermore, it highlights proteins that may be targets for the development of new therapeutic approaches to PCM.

Diagnosis and Treatment of Advanced ALK Rearrangement-Positive Non-Small-Cell Lung Cancer in Portugal: Results of a National Questionnaire.

BACKGROUND: Rearrangements in the anaplastic lymphoma kinase (ALK) gene define a molecular subgroup of non-small-cell lung carcinoma (NSCLC) that should be treated with ALK-targeting tyrosine kinase inhibitors (TKIs). OBJECTIVE: This study aimed to portray the Portuguese reality about the diagnosis and treatment of stage IV ALK-positive NSCLC. METHODS: Institutions that treat lung cancer in Portugal were invited to participate in an anonymous electronic questionnaire. A total of 22/35 geographically dispersed institutions responded. A descriptive statistical analysis of the results was performed. RESULTS: Reflex molecular testing was done in 54.6% of the institutions. Next-generation sequencing (NGS) was the preferred diagnostic method (90.9%). Typically, physicians obtained molecular study results within 14-21 days. Alectinib was the most commonly used first-line treatment. For patients with brain metastases, 86.4% of the physicians preferred alectinib and 13.6% preferred first-line brigatinib. In the case of asymptomatic oligoprogression in the central nervous system, 85.7% of physicians performed local treatment and kept the patient on a TKI; if symptomatic, 66.7% gave local treatment and stayed with the TKI, while 28.6% gave local treatment and altered the TKI. For patients with symptomatic systemic progression, 47.6% and 38.1% of physicians prescribed lorlatinib after initial treatment with alectinib or brigatinib, respectively. After progression on lorlatinib, 42.9% of respondents chose chemotherapy and 57.1% requested detection of resistance mutations. CONCLUSIONS: NGS is widely used for the molecular characterization of ALK-positive NSCLC in Portugal. The country has access to up-to-date therapy. Overall, national clinical practice follows international recommendations for the diagnosis and treatment of ALK-positive NSCLC.

Depression and associated factors among Brazilian adults: the 2019 national healthcare population-based study.

BACKGROUND: Mental disorders represent a major public health challenge worldwide, affecting 80% of people living in low- and middle-income countries. Depression, a mental disorder, is a chronic disease of long duration that causes changes in the brain, resulting from a combination of genetic, physiologic, environmental, and behavioral factors. The aim of this study was to investigate possible factors associated with depression in Brazilian adults. METHODS: A population-based, cross-sectional study was carried out using the public domain database of the 2019 National Health Survey, conducted in Brazil. Depression was considered the dependent variable, and through hierarchical analysis, predictor variables were investigated such as, at the distal level-socioeconomic variables, at the intermediate level-variables related to lifestyle behavior, health condition, and history, and at the proximal level-demographic variables. Logistic regression analysis was used to obtain the adjusted Odds Ratio and the respective 95% confidence interval to identify possible factors associated with depression. RESULTS: The study included 88,531 participant records with 10.27% diagnosed with depression. The adjusted association measurements, after selecting the independent variables in the hierarchical analysis, showed the following factors associated with depression with differing magnitudes: age, brown and white race/skin color, female sex, poor, very poor, or regular self-reported health condition, diagnosis of cardiovascular disease, work-related musculoskeletal disorder, history of smoking habit, and macroeconomic region. CONCLUSIONS: An effective strategy for preventing and managing depression in Brazilian adults must include the control of health status and lifestyle behavior factors, with actions and programs to reduce people's exposure to these factors, understanding that socioeconomic-demographic differences of each population can potentially reduce the disease burden.

Acesso e utilização dos serviços de saúde e raça/cor/etnia entre mulheres: uma metanálise / Access to and utilization of health services and race/color/ethnicity among women: a meta-analysis / Acceso y utilización de los servicios de salud y raza/color/etnia entre las mujeres: un metaanálisis

Diversas barreiras podem comprometer o acesso aos serviços de saúde no Brasil, especialmente entre as mulheres negras, evidenciando a urgência em discutir esse tema à luz das iniquidades raciais e de gênero. O objetivo deste estudo foi realizar uma revisão sistemática com metanálise para avaliar as evidências científicas da associação entre raça/cor de pele/etnia e acesso e utilização dos serviços de saúde entre mulheres. A busca dos estudos foi realizada em cinco bases eletrônicas, incluindo literatura cinzenta, até março de 2022 e, após a extração de dados, foi realizada a avaliação da qualidade dos artigos. A metanálise estimou a medida de associação global (odds ratio) e seu intervalo de confiança de 95%. Também foi avaliado o indicador de Higgins e Thompson (I2) para classificação da heterogeneidade estatística dos dados. Foram identificados 428 registros, mas apenas três estudos atenderam aos critérios de elegibilidade. A raça/cor de pele/etnia negra esteve associada a desfechos negativos relacionados ao acesso/utilização dos serviços de saúde no Brasil (OR = 1,49; IC95%: 1,26-1,76; I2 = 24,01%). Neste estudo, verificou-se que existem iniquidades raciais no acesso/utilização dos serviços de saúde entre mulheres. No entanto, destaca-se a necessidade de mais estudos rigorosos para elucidar a influência da raça/cor/etnia e de elaboração de políticas públicas.

Several barriers can compromise access to health services in Brazil, especially among black women, highlighting the urgency of discussing this topic in the light of racial and gender inequalities. This study aimed to carry out a systematic review with meta-analysis to assess the scientific evidence on the association between race/skin color/ethnicity and access and use of health services among women. The search for studies was carried out in five electronic databases, including the gray literature, until March 2022, and, after data extraction, the quality of the articles was evaluated. The meta-analysis estimated the global association measure (odds ratio) and its 95% confidence interval. The Higgins and Thompson indicator (I2) was also evaluated to classify the statistical heterogeneity of the data. A total of 428 records were identified, but only three studies met the eligibility criteria. Black race/skin color/ethnicity was associated with negative outcomes related to access/use of health services in Brazil (OR = 1.49; 95%CI: 1.26-1.76; I2 = 24.01%). This study showed the presence of racial inequalities in the access/use of health services among women. However, it highlights the need for more rigorous studies to elucidate the influence of race/color/ethnicity and the elaboration of public policies.

Diversos obstáculos pueden dificultar el acceso a los servicios de salud en Brasil, principalmente para las mujeres negras, lo que muestra la necesidad de discutir el tema de las inequidades racial y de género. Este estudio tiene por objetivo realizar una revisión sistemática con metaanálisis para evaluar la evidencia científica de la asociación entre raza/color/etnia y el acceso y uso de los servicios de salud por las mujeres. Se realizó una búsqueda en cinco bases de datos electrónicas, incluida la literatura gris, en el periodo hasta marzo de 2022; y tras evaluados los datos, se llevó a cabo una evaluación de la calidad de los artículos. El metaanálisis estimó la asociación global (Odds Ratio) y su intervalo de confianza del 95%. También se evaluó el indicador de Higgins y Thompson (I²) para clasificar la heterogeneidad estadística de los datos. Se identificaron 428 registros, de los cuales solo tres estudios cumplieron los criterios de elegibilidad. La raza/color de piel/etnia negra se asoció con desenlaces negativos relacionados al acceso/uso de los servicios de salud en Brasil (OR = 1,49; IC 95%: 1,26-1,76; I² = 24,01%). Estos hallazgos destacan las inequidades raciales en el acceso/uso de los servicios de salud entre mujeres brasileñas. Sin embargo, se necesitan investigaciones más rigurosas sobre la influencia de la raza/color/etnia y la implementación de políticas públicas efectivas.

New Reports on the Portuguese Endemic Species, Santolina impressa: Secretory Structures, Essential Oil Composition and Antiviral Activity.

Santolina impressa is an aromatic Asteraceae species endemic to Portugal, traditionally used for its anti-inflammatory properties. The aim of this study was to characterize S. impressa secretory structures, analyze the essential oil (EO) from the aerial organs, and evaluate its antiviral activity against herpes simplex viruses HSV-1 and HSV-2. Secretory structures were investigated by light and scanning microscopy, and the secretion was histochemically characterized. The EO from the aerial organs in full blooming was analyzed by gas chromatography with flame ionization detection and gas chromatography-mass spectrometry. Antiviral assays were performed by direct contact with viral suspensions (virucidal effect), and in infected Vero E6 cells, at different time periods during the viral replication cycle. Two types of secretory structures were described, biseriate glandular trichomes and secretory ducts, producing an oleoresin and a resin rich in flavonoids, respectively. Fifty compounds were identified in S. impressa EO, accounting for 87% of the total constituents. Monoterpenes constituted the main EO fraction (82%), with ß-pinene (13%) and ß-phellandrene (10%) being their major components. The EO interacted with HSV-1 and HSV-2 in a dose-dependent manner, thereby inactivating both viral infections. The EO did not evidence a virucidal effect but inhibited the HSV-1 and HSV-2 infection in Vero cells in a dose-dependent manner. However, further studies are needed to investigate the mode of action in the replication cycle.

Prevalência de anemia em gestantes das Américas: uma revisão rápida com metanálise / Prevalence of anemia in pregnant women in the Americas: a rapid review with meta-analysis

A anemia em gestantes é um relevante problema de ampla expansão geográfica, típica de grandes centros urbanos que atinge diversos países, como os da América. Estimar a prevalência nas Américas de anemia materna e anemia ferropriva em gestantes.Revisão rápida com busca no Medline, via PubMed, Scopus, Web of Science, SciELO, Lilacs e Open Grey. Incluíram-se estudos do tipo transversal, que estimassem a prevalência de anemia materna e anemia ferropriva. Foram realizadas metanálises com efeito randômico. 5.148 artigos foram encontrados, apenas 39 atenderam aos critérios de elegibilidade. As metanálises apresentaram prevalência de 30% (IC95%: 28%; 32%. I2: 99,4%) para anemia materna e frequência de 32% (IC95%: 25%; 40%. I2: 96,6%) para anemia ferropriva.Anemia materna é um evento frequente na população das Américas, com 30% para anemia materna e 32% para anemia ferropriva, destacando a necessidade de medidas de prevenção e promoção à saúde mais eficazes.

Anemia in pregnant women is a relevant problem of wide geographical expansion, typical of large urban centers and that affects several countries, such as America. To estimate the prevalence of maternal anemia and iron deficiency anemia in pregnant women in the Americas.Rapid review with search in Medline, Pubmed, Scopus, Web of Science, SciELO, Lilacs and Open Grey databases. Cross-sectional studies that estimated the prevalence of maternal anemia and iron deficiency anemia were included. Random-effects meta-analyses were conducted. 5148 articles were found, only 30 met the eligibility criteria. Meta-analyses showed a prevalence of 30% (95%CI: 28%; 32%. I2: 99.4%) for maternal anemia and a frequency of 32% (95%CI: 25%; 40%. I2: 96.6%) for iron deficiency anemia. Maternal anemia is a frequent event in the population of the Americas, with prevalence of 30% for maternal anemia and 32% for iron deficiency anemia, highlighting the need for more effective prevention and health promotion measures.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.

BACKGROUND AIMS: The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed. RESULTS: In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively. CONCLUSIONS: This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.

Evaluation of Life Quality of Patients Submitted to Cataract Surgery with Implantation of Trifocal Intraocular Lenses.

This study aimed to evaluate the quality of life and the satisfaction level of Brazilian and Chinese patients who underwent cataract surgery for Acysof IQ PanOptix Model TFNT00 (Alcon Laboratories, Fort Worth, TX, USA) implantation. This retrospective study enrolled 51 patients from China and 51 patients from Brazil. At the 3-month follow-up, uncorrected distance visual acuity (UDVA) at 5 m, uncorrected intermediate visual acuity (UIVA) at 60 cm, and uncorrected near visual acuity (UNVA) at 40 cm were evaluated; Catquest 9SF and the Near Activity Visual Questionnaire (NAVQ) were administered to the patients. The results revealed that the Brazilian patients gained better UDVA and UNVA (p < 0.001), while the Chinese patients gained better UIVA (p = 0.001). With regards to the patients' overall satisfaction with their current vision, the Brazilian patients scored higher (p = 0.002). In situations related to distant and near vision, the Brazilian patients scored higher, while in situations related to intermediate vision, the Chinese patients scored higher. No differences were found between the gender or age subgroups, but the normal axial length (AL) subgroup showed the highest level of satisfaction (p = 0.002). The patients implanted with TFNT00 IOL obtained excellent objective and subjective outcomes in both cultures. The Brazilian patients showed higher satisfaction with their distant and near vision, while the Chinese patients were more satisfied with their intermediate vision.

Accuracy of mortality indicators due sepsis-associated deaths in the Federal District / Acurácia dos indicadores de mortalidade devido a sepse dos óbitos ocorridos no Distrito Federal / Precisión de los indicadores de mortalidad por sepsis de las defunciones ocurridas en el Distrito Federal

Background: Sepsis currently represents a challenge for health systems, this fact may be related to the spread of bacterial resistance, the increase in the population of elderly, immunosuppressed individuals, and the improvement of emergency care, favoring the survival of critically ill patients. This article aimed to evaluate the accuracy of mortality indicators due to sepsis in 2018. Method: Validation study of death certificates that occurred in the Federal District in 2018. Declarations whose basic causes of death identified were classified as garbage codes were identified, which were investigated by a multidisciplinary team, capable of reclassifying them with codes that allow for the improvement of health data. In order to assess accuracy, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of death certificates from sepsis were calculated, with 95% confidence intervals. Results: A total of 6.244 statements were evaluated, of which 233 (3.74%) presented sepsis as the underlying cause before being investigated and only 35 (0.56%) maintained it after the investigation. The filling of statements with sepsis as the underlying cause by physicians showed a sensitivity of 0.9% (95%CI: 0.6 to 1.3) and a specificity of 92.0% (95%CI: 90.9 to 93.1). Conclusion: The low accuracy of the declarations demonstrates the non-reliability of the underlying cause of death from sepsis, especially the completion of death certificates that occurred in the Federal District in 2018.(AU)

Justificativa: A sepse, atualmente, representa um desafio para os sistemas de saúde, tal fato pode estar relacionado com a disseminação da resistência bacteriana, o aumento da população de idosos, os indivíduos imunossuprimidos, e a melhoria do atendimento de emergência, favorecendo a sobrevivência de pacientes críticos. Este artigo teve por objetivo avaliar a acurácia dos indicadores de mortalidade devido à sepse em 2018. Método: Estudo de validação da causa básica dos óbitos ocorridos no Distrito Federal em 2018. Foram identificadas as declarações de óbito cujas causas básicas de morte apontadas foram classificadas como garbage code sepse, as quais foram investigadas por uma equipe multidisciplinar, capacitada para reclassificá-las com códigos que permitem o aprimoramento dos dados em saúde. A fim de avaliar a acurácia, foram calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo, razões de verossimilhança positiva e negativa das declarações dos óbitos por sepse, com intervalos de confiança de 95%. Resultados: Um total de 6.244 declarações foram avaliadas, das quais 233 (3,74%) apresentavam a sepse como causa básica antes de serem investigadas e apenas 35 (0,56%) mantiveram-na após a investigação. O preenchimento das declarações com a sepse enquanto causa básica pelos médicos apresentou sensibilidade de 0,9% (IC95%: 0,6 a 1,3) e especificidade de 92,0% (IC95%: 90,9 a 93,1). Conclusão: A baixa acurácia das declarações demonstra a não fidedignidade da causa básica de óbito por sepse, sobretudo, do preenchimento das declarações dos óbitos ocorridos no Distrito Federal em 2018.(AU)

Justificación: Sepsis representa en la actualidad un desafío para los sistemas de salud, este hecho puede estar relacionado con propagación de resistencias bacterianas, aumento de la población de ancianos, inmunodeprimidos, y mejora de la atención de urgencias, favoreciendo la supervivencia de los pacientes críticos. Este artículo tuvo como objetivo evaluar la precisión de los indicadores de mortalidad por sepsis en 2018. Método: Estudio de validación de causa básica de muertes ocurridas en Distrito Federal en 2018. Se identificaron actas de defunción cuyas causas básicas de muerte fueron clasificadas como sepsis código basura y fueron investigadas por un equipo multidisciplinario capacitado para reclasificarlas con códigos que permitan la mejora de datos de salud. Para evaluar la precisión, se calcularon sensibilidad, especificidad, valores predictivos positivo y negativo y razones de verosimilitud positiva y negativa de certificados de defunción por sepsis, con intervalos de confianza del 95%. Resultados: se evaluaron 6.244 declaraciones, de las cuales 233 (3,74%) tenían como causa básica la sepsis antes de ser investigadas y solo 35 (0,56%) mantuvieron después de investigación. Realización de declaraciones con sepsis como causa subyacente por parte de los médicos mostró sensibilidad del 0,9% (95%IC: 0,6 a 1,3) y especificidad del 92,0% (95%IC: 90,9 a 93,1). Conclusión: Baja precisión de las declaraciones demuestra la poca confiabilidad de la causa subyacente de muerte por sepsis, especialmente la finalización de los certificados de defunción ocurridos en Distrito Federal en 2018.(AU)

Preoperative serum inflammation-based scores in medullary thyroid cancer.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are prognostic factors in several tumours, though little is known in medullary thyroid cancer (MTC). OBJECTIVE: To evaluate the association between preoperative NLR, PLR and SII with MTC clinicopathological and molecular features, and their predictive value for lymph node and distant metastasis. METHODS: We retrospectively analysed 75 patients with MTC who underwent surgery at our institution. The familial form of MTC was found in 12% of patients. RESULTS: In our cohort, 56% were females, the median age at diagnosis was 57 years (44-69), the median tumour diameter was 25mm (15-50); 21.3% were multifocal and 34.7% had extrathyroidal extension. Lymph node and distant metastasis were observed in 36 (48.0%) and 8 (10.7%) patients, respectively. Higher NLR was associated with preoperative calcitonin, angioinvasion, extrathyroidal extension, moderate/severe fibrosis; higher PLR was associated with extrathyroidal extension and advanced T stages; lower SII and NLR were associated with biochemical cure after surgery. Increased PLR, NLR and SII were associated with advanced MTC stages. In the univariate analysis, only NLR was associated with lymph node metastasis (odds ratio (OR)=2.69, 95% confidence interval (CI): 1.50-5.84; p=0.004); however, in the multivariate model, NLR was no longer a predictive factor for lymph node metastasis. None of these serum inflammatory markers predicted the occurrence of distant metastasis. CONCLUSION: In conclusion, NLR, PLR and SII are associated with aggressive MTC, but do not predict lymph node or distant metastasis.

Malignant Hypercalcemia Due to the Ectopic Production of Calcitriol by an Abdominal Liposarcoma.

Hypercalcemia of malignancy (HM) is a common form of paraneoplastic syndrome associated with a poor prognosis of the disease. In solid tumors, HM occurs mainly due to the production of parathyroid hormone-related peptide (PTHrP). We present a case of a 60-year-old male with a 25 cm retroperitoneal liposarcoma diagnosed with severe hypercalcemia (16.8 mg/dL) by a preoperative blood sampling. Hypercalcemia workup showed suppressed parathyroid hormone (PTH), normal PTHrP, and high 1,25-dihydroxyvitamin D (1,25(OH)2D) serum levels. After surgery, hypercalcemia and calcitriol levels normalized. Immunohistochemical analysis of the tumor showed 1α-hydroxylase expression by tumor cells. To our knowledge, this is the first case of liposarcoma-associated hypercalcemia caused exclusively by the ectopic production of calcitriol. Despite being a rare cause of hypercalcemia, measuring 1,25(OH)2D should be considered in the workup of a patient with high serum calcium levels, suppressed PTH, and normal PTHrP.

Modified Technique of Ex-PRESS® Filtration Device Combined with a Scleral Pocket for Hereditary Transthyretin Amyloidosis (hATTR) Secondary Open-Angle Glaucoma.

Purpose: To evaluate the effectiveness and safety of a modified approach using the Ex-PRESS® implant combined with a scleral pocket in the management of secondary open-angle glaucoma in hereditary transthyretin amyloidosis (hATTR) at our department. Methods: This was a retrospective analysis. The primary endpoints included Intraocular pressure (IOP) evaluation (baseline, 1st day, 1st week, 1, 3, 6, 12 months and at last follow-up) and number of hypotensive drugs (baseline, 6th, 12th months and at last follow-up). As secondary endpoints surgical complications, the need for additional glaucoma surgery and LogMAR BCVA were evaluated. Qualified and complete success were defined as ≥ 30% IOP decrease from baseline, with or without additional medications, respectively. The minimum follow-up was 12 months. Results: A total of 32 eyes were included with a mean follow-up of 2.4±2.9 years. IOP decreased significantly from baseline (27.4±4.4 mmHg) to 1st day (5.00±2.9 mmHg), 1st week (6.9±4.1 mmHg), 1st month (11.7±7.8 mmHg), 3rd month (11.6±6.1 mmHg), 6th month (13.1±6.8 mmHg), 12th month (12.0±3.5 mmHg) and last visit (11.8±2.4 mmHg), p<0.001. There was also a significant reduction in the number of antiglaucoma medications from baseline (3.8±0.6) and last follow-up (0.4±0.8), p<0.001. LogMAR BCVA remained stable (0.25±0.26 at baseline and 0.25±0.24 at last follow-up), p=0.767. Transient hypotony occurred in 17 eyes (53.1%), but only 11 (34.4%) exhibited anterior chamber shallowing and needed additional care, namely cycloplegic drops and viscoelastic injection. Complete surgical success was achieved in 22 eyes (68.8%) and qualified success in 6 eyes (18.8%). Four eyes (12.5%) needed additional glaucoma surgery. Conclusion: The modified ExPRESS® technique appears to be effective, especially when low levels of IOP are required. Additionally, fewer anti-glaucoma drugs were necessary. In the other hand, hypotony was a common side effect with this procedure, although all patients were properly handled, preserving the surgical outcomes.

Precocious and accelerated puberty in children with neurofibromatosis type 1: results from a close follow-up of a cohort of 45 patients.

PURPOSE: Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. METHODS: A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. RESULTS: The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. CONCLUSION: Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.

The effect of probiotics on postsurgical complications in patients with colorectal cancer: a systematic review and meta-analysis.

CONTEXT: Clinical trials have investigated the effect of probiotics on postsurgical complications in colorectal cancer (CRC). However, so far, there are no systematic reviews evaluating the effect of probiotics and synbiotics on the clinical or infectious postsurgical complications of colorectal cancer. OBJECTIVE: The objective of this review was to synthesize the best available evidence on the effects of the use of probiotics or synbiotics on pre-, peri-, and post-operative complications of CRC surgical resection. DATA SOURCES: A search of the PubMed, Embase, LILACS, Scopus, Cochrane, Web of Science, ProQuest, and Google Scholar databases was conducted for clinical trials published up until January 2022. DATA EXTRACTION: The population characteristics, period and protocol of supplementation, and postoperative complications were extracted and reported. A random-effects model was used to estimate the effect of probiotic and synbiotic treatment on these variables. DATA SYNTHESIS: In total, 2518 studies were identified, of which 16 were included in the qualitative synthesis and 13 in the meta-analysis. Overall, probiotic supplementation reduced the incidence of ileus (odds ratio [OR] = .13, 95% confidence interval [CI]: .02, .78), diarrhea (OR = .32, 95% CI: .15, .69), abdominal collection (OR: .35, 95% CI: .13, .92), sepsis (OR = .41, 95% CI: .22, .80), pneumonia (OR = .39, 95% CI: .19, .83), and surgical site infection (OR = .53, 95% CI: .36, .78). The results of the subgroup analysis indicated that lower dose (<109 colony-forming units), higher duration of supplementation (>14 days), and being administrated ≤5 days before and >10 days after surgery was more effective at reducing the incidence of surgical site infection. CONCLUSION: Probiotics and synbiotics seem to be a promising strategy for the prevention of postoperative complications after CRC surgery. Larger, high-quality randomized controlled trials are needed to establish the optimal treatment protocol for the use of probiotics and synbiotics in preventing postoperative complications for CRC surgery.