Prognosing the risk of COVID-19 death through a machine learning-based routine blood panel: A retrospective study in Brazil.

BACKGROUND: Despite an extensive network of primary care availability, Brazil has suffered profoundly during the COVID-19 pandemic, experiencing the greatest sanitary collapse in its history. Thus, it is important to understand phenotype risk factors for SARS-CoV-2 infection severity in the Brazilian population in order to provide novel insights into the pathogenesis of the disease. OBJECTIVE: This study proposes to predict the risk of COVID-19 death through machine learning, using blood biomarkers data from patients admitted to two large hospitals in Brazil. METHODS: We retrospectively collected blood biomarkers data in a 24-h time window from 6,979 patients with COVID-19 confirmed by positive RT-PCR admitted to two large hospitals in Brazil, of whom 291 (4.2%) died and 6,688 (95.8%) were discharged. We then developed a large-scale exploration of risk models to predict the probability of COVID-19 severity, finally choosing the best performing model regarding the average AUROC. To improve generalizability, for each model five different testing scenarios were conducted, including two external validations. RESULTS: We developed a machine learning-based panel composed of parameters extracted from the complete blood count (lymphocytes, MCV, platelets and RDW), in addition to C-Reactive Protein, which yielded an average AUROC of 0.91 ± 0.01 to predict death by COVID-19 confirmed by positive RT-PCR within a 24-h window. CONCLUSION: Our study suggests that routine laboratory variables could be useful to identify COVID-19 patients under higher risk of death using machine learning. Further studies are needed for validating the model in other populations and contexts, since the natural history of SARS-CoV-2 infection and its consequences on the hematopoietic system and other organs is still quite recent.

Alzheimer's disease: risk factors and potentially protective measures.

Alzheimer's disease (AD) is the most common type of dementia and typically manifests through a progressive loss of episodic memory and cognitive function, subsequently causing language and visuospatial skills deficiencies, which are often accompanied by behavioral disorders such as apathy, aggressiveness and depression. The presence of extracellular plaques of insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein (P-tau) in the neuronal cytoplasm is a remarkable pathophysiological cause in patients' brains. Approximately 70% of the risk of developing AD can be attributed to genetics. However, acquired factors such as cerebrovascular diseases, diabetes, hypertension, obesity and dyslipidemia increase the risk of AD development. The aim of the present minireview was to summarize the pathophysiological mechanism and the main risk factors for AD. As a complement, some protective factors associated with a lower risk of disease incidence, such as cognitive reserve, physical activity and diet will also be addressed.

Hemostatic Abnormalities in Dementia: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (PubMed), Scopus, Web of Science, ScienceDirect, Lilacs, Cinahl, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Among 5,278 studies identified, 32 were included in the final synthesis, and these included 485 patients with mild cognitive impairment, 568 with vascular dementia (VD), 1,781 with AD, and 2,855 participants without dementia. AD patients had increased plasma von Willebrand factor (VWF) (standardized mean difference [SMD]: 2.53; 95% confidence interval [CI]: 0.10-4.95), D-dimer (SMD: 0.50; 95% CI: 0.35-0.66), plasminogen activator inhibitor-1 (SMD: 3.34; 95% CI: 1.01-5.67), thrombomodulin (SMD: 1.08; 95% CI: 0.53-1.62), and homocysteine levels (SMD: 0.65; 95% CI: 0.15-1.15). In contrast, the VD group showed increased fibrinogen levels (SMD: 0.77; 95% CI: 0.13-1.41), activated factor VII (SMD: 0.36; 95% CI: 0.05-0.67), factor VIII (SMD: 0.57; 95% CI: 0.22-0.91), VWF (SMD: 2.34; 95% CI: 0.38-4.29), D-dimer (SMD: 1.14; 95% CI: 0.51-1.78), and homocysteine (SMD: 2.17; 95% CI: 1.67-2.68). AD showed an elevation in some markers of endothelial dysfunction, whereas VD presented mostly an involvement of coagulation cascade components.

Arterial Stiffness Use for Early Monitoring of Cardiovascular Adverse Events due to Anthracycline Chemotherapy in Breast Cancer Patients. A Pilot Study / Uso da Rigidez Arterial para Monitoramento Precoce de Eventos Adversos Cardiovasculares por Antracíclicos em Pacientes com Câncer de Mama. Um Estudo Piloto

Abstract Background: Chemotherapy with doxorubicin and cyclophosphamide, although efficient for treating breast cancer, is associated with cardiovascular complications. Recent studies seek to identify methods that can early detect cardiological and vascular changes as a strategy to decrease the incidence of cardiovascular comorbidities. Objective: To evaluate the role of arterial stiffness measurement in the monitoring of doxorubicin and cyclophosphamide-induced cardiotoxicity in breast cancer patients. Methods: Prospective longitudinal study in 24 breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity with the Mobil-O-Graph® 24H PWA device at three different times of the chemotherapy treatment (pre-chemotherapy, after the first and the fourth cycle). The left ventricular ejection fraction was also evaluated by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy cycle). Data were considered significant when p ≤ 0.05. Results: Patients had a mean age of 52.33 ± 8.85 years and body mass index of 31 ± 5.87 kg/m2. There was no significant difference between the hemodynamic parameters evaluated by the oscillometric method or in the left ventricular ejection fraction in the different evaluated periods. Conclusion: Evaluations of arterial stiffness by oscillometry and measurement of left ventricular ejection fraction by Doppler echocardiography showed equivalence in the values found, suggesting that the evaluation method of arterial stiffness studied could be used as a marker for cardiovascular adverse events associated with doxorrubicin-based chemotherapy drugs.

Resumo Fundamento: O tratamento quimioterápico com doxorrubicina e ciclofosfamida, apesar de eficiente no combate ao câncer de mama, está associado a complicações cardiovasculares. Trabalhos recentes identificam métodos que possam detectar alterações cardiológicas e vasculares precocemente, visando a uma estratégia para diminuição na incidência de comorbidades cardiovasculares. Objetivo: Avaliar o papel da medida da rigidez arterial no acompanhamento da ocorrência de eventos adversos cardiovasculares induzidos por doxorrubicina e ciclofosfamida em pacientes com câncer de mama. Métodos: Estudo longitudinal prospectivo realizado com 24 pacientes com câncer de mama em tratamento com doxorrubicina e ciclofosfamida. As pacientes foram submetidas à avaliação indireta da rigidez arterial, por mensuração não invasiva de parâmetros hemodinâmicos, como a velocidade de onda de pulso, pelo equipamento Mobil-O-Graph® 24H PWA em três diferentes momentos do tratamento quimioterápico (pré-quimioterapia, após o primeiro e após o quarto ciclos). Foi avaliada também a fração de ejeção do ventrículo esquerdo pelo ecoDopplercardiograma (pré-quimioterapia e após o quarto ciclo quimioterápico). Os valores de p ≤ 0,05 foram considerados significativos. Resultados: As pacientes apresentaram média de idade de 52,33 ± 8,85 anos e índice de massa corporal de 31 ± 5,87 kg/m2. Não houve diferença significativa entre os parâmetros hemodinâmicos avaliados pelo método oscilométrico ou na fração de ejeção do ventrículo esquerdo, nos diferentes períodos avaliados. Conclusão: As avaliações de rigidez arterial por oscilometria e medida da fração de ejeção do ventrículo esquerdo por ecoDopplercardiograma mostraram equivalência nos valores encontrados, sugerindo que o método de avaliação da rigidez arterial estudado possa ser utilizado como mais um marcador para eventos adversos cardiovasculares associados aos medicamentos quimioterápicos baseados em doxorrubicina.

Arterial Stiffness Use for Early Monitoring of Cardiovascular Adverse Events due to Anthracycline Chemotherapy in Breast Cancer Patients. A Pilot Study.

BACKGROUND: Chemotherapy with doxorubicin and cyclophosphamide, although efficient for treating breast cancer, is associated with cardiovascular complications. Recent studies seek to identify methods that can early detect cardiological and vascular changes as a strategy to decrease the incidence of cardiovascular comorbidities. OBJECTIVE: To evaluate the role of arterial stiffness measurement in the monitoring of doxorubicin and cyclophosphamide-induced cardiotoxicity in breast cancer patients. METHODS: Prospective longitudinal study in 24 breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity with the Mobil-O-Graph® 24H PWA device at three different times of the chemotherapy treatment (pre-chemotherapy, after the first and the fourth cycle). The left ventricular ejection fraction was also evaluated by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy cycle). Data were considered significant when p ≤ 0.05. RESULTS: Patients had a mean age of 52.33 ± 8.85 years and body mass index of 31 ± 5.87 kg/m2. There was no significant difference between the hemodynamic parameters evaluated by the oscillometric method or in the left ventricular ejection fraction in the different evaluated periods. CONCLUSION: Evaluations of arterial stiffness by oscillometry and measurement of left ventricular ejection fraction by Doppler echocardiography showed equivalence in the values found, suggesting that the evaluation method of arterial stiffness studied could be used as a marker for cardiovascular adverse events associated with doxorrubicin-based chemotherapy drugs.

Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach.

Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL-DOX (14.6 ±â€¯5.2%) compared to animals receiving free DOX (35.7 ±â€¯4.0%) or non-pH-sensitive liposomes (nSpHL-DOX) (47.0 ±â€¯9.8%). These results corroborate with SpHL-DOX biodistribution studies published by our group. In conclusion, the SpHL-DOX showed less toxic effects on mice compared to free DOX or nSpHL-DOX indicating that SpHL-DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX.

The polymorphism rs17782313 near MC4R gene is related with anthropometric changes in women submitted to bariatric surgery over 60 months.

OBJECTIVE: Evaluate whether the polymorphism rs17782313 near MC4R gene influences long-term outcomes after bariatric surgery. METHODS: The rs16782313 polymorphism was genotyped in 217 individuals undergoing bariatric surgery and analyzed in detail in 141 women. Data for comorbidities, BMI, excess weight loss (EWL), and body composition were obtained before and during 60 months after surgery. RESULTS: The risk allele was found in 65 (47%) of the 141 women. Pre-surgical body weight and BMI were higher in carriers of the rs17782313 polymorphism (CC + CT group) than in non-carriers (TT group) (p = 0.039 and 0.047, respectively). The number of women who acquired surgical success (EWL > 50%), was lower in CC + CT group compared to TT group (p = 0.015). The minimum BMI seen during the 60 months of follow-up was higher in CC + CT group compared to TT group (p = 0.028). The number of women who presented BMI < 30 kg/m2 (no longer classified as obesity) after 24 months of surgery was inferior in CC + CT group (6 out 35 patients - 17%) than in TT group (19 out 49 patients - 37%, p = 0.043). Moreover, the number of patients maintaining BMI > 35 kg/m2 were higher carriers (18 out 35 patients - 51%) compare to non-carriers (16 out 49 patients - 32%, p = 0.045). CONCLUSION: Women with extreme obesity carrying rs17782313 MC4R polymorphism present a higher pre-surgical BMI, are more unlikely to reach non-obesity BMI (<30 kg/m2) and tend to maintain a BMI > 35 kg/m2 that characterize treatment failure.

Alfa-Talassemias: aspectos moleculares e diagnóstico / Alpha-Thalassemias: molecular aspects and diagnosis

A α-talassemia é um dos distúrbios da síntese de hemoglobina mais comuns no mundo, sendo causada, principalmente,por mutações delecionais nos genes α-globínicos. De acordo com o número degenes mutados que varia de um a quatro, a α-talassemia pode ser divididaem quatro fenótipos: α-talassemia silenciosa, traço α-talassêmico, Doençade HbH e hidropsia fetal, espectivamente. Segundo a literatura, afrequência de α-talassemia no Brasil também é considerável, sendo de grande importância o diagnósticocorreto deste distúrbio, que pode ser realizado com auxílio de exames convencionais que apresentam vantagens e desvantagens. Contudo, em alguns casos, principalmente nas formas menores da α-talassemia, a confirmação diagnóstica só pode ser realizada através dos exames moleculares que, apesar de confirmatórios, não estão disponíveisem grande parte dos laboratórios de análises clínicas e, devido ao custo, não são acessíveis à população em geral..

Features associated with cognitive impairment and dementia in a community-based sample of illiterate elderly aged 75+ years: the Pietà study.

A higher level of educational attainment constitutes a protective factor against cognitive decline in the elderly. Nevertheless, the elements underpinning this association are yet not fully understood. OBJECTIVE: The primary aim of this study was to compare cognitively impaired illiterate elderly subjects with cognitively preserved counterparts, according to demographics, comorbidities, lifetime habits and APOE genotype. METHODS: This is a cross-sectional analysis of the illiterate subset of participants (n=174) from the Pietà study, a community-based survey of successful brain aging conducted in Caeté (MG), Brazil. Subjects were categorized into three diagnostic groups: cognitively normal (CN), cognitive impairment no-dementia (CIND) and dementia. The groups were then compared according to selected variables. RESULTS: Subjects with dementia were older and had an increased prevalence of reported stroke or transient ischemic attack. The three groups did not differ in relation to demographics, prevalence of comorbidities, socioeconomic level, previous occupation profile and APOE-ε4 allele frequency. Qualitatively evaluated lifetime habits, such as alcohol consumption, smoking and physical activity engagement were also similar across groups. CONCLUSION: No associations were found between cognitive impairment/dementia and the variables evaluated in this community-based sample of illiterate elderly.

Um alcance educacional mais elevado constitui um fator protetivo contra o declínio cognitivo em idosos. Todavia, os elementos subjacentes a esta associação ainda são pouco compreendidos. OBJETIVO: O principal objetivo deste estudo foi comparar indivíduos analfabetos com comprometimento cognitivo com analfabetos cognitivamente normais, de acordo com aspectos demográficos, morbidades, hábitos de vida e genótipo APOE. MÉTODOS: Este é um estudo transversal da amostra de participantes analfabetos (n=174) do Estudo Pietà, um levantamento de base comunitária sobre envelhecimento cerebral bem sucedido, conduzido em Caeté (MG), Brasil. Os sujeitos foram categorizados em três grupos diagnósticos: cognitivamente normais, comprometimento cognitivo não demência e demência. Os grupos foram então comparados conforme variáveis selecionadas. RESULTADOS: Indivíduos com demência eram mais idosos e apresentaram uma maior prevalência de relato de acidente vascular encefálico ou ataque isquêmico transitório. Os três grupos não se mostraram diferentes em relação à demografia, prevalência de comorbidades, nível socioeconômico, perfil ocupacional prévio e frequência do alelo APOE-ε4. A avaliação qualitativa de hábitos de vida, como o consumo de bebida alcoólica, fumo e engajamento em atividade física também foi semelhante entre os grupos. CONCLUSÃO: Não encontramos associações entre comprometimento cognitivo/demência e as variáveis investigadas nesta amostra comunitária de idosos analfabetos.

Comparison of discriminative indices for iron deficiency anemia and ß thalassemia trait in a Brazilian population.

To discriminate iron deficiency anemia (IDA) from ß thalassemia trait (ßTT), several indices obtained from modern blood count analyzers have been reported. Discrimination power of seven indices to differentiate between IDA and ßTT, such as Green and King Index (GKI), RDW Index (RDWI), Srivastava Index (SRI), Mentzer Index (MI), Shine and Lal Index (SLI), Ehsani Index (EI), and Sirdah Index (SI), were evaluated. These indices were applied on 47 patients with ßTT and on 289 patients with IDA, as confirmed by gold standard tests. Sensitivity, specificity, positive and negative predictive values, efficiency, area under receiver-operating characteristics curve (AUC), and Youden's Index (YI) were calculated. GKI and RDWI showed the highest reliability, as they had the largest AUCs (0.919, 0.912, respectively) and Youden's Index (70.4, 74.6, respectively). Conversely, SLI presented a less satisfactory performance (AUC = 0.786 and YI = 6.6). Data taken together suggest the superiority of GKI and RDWI to discriminate between IDA and ßTT.

Evaluation of the presence of hereditary and acquired thrombophilias in Brazilian children and adolescents with diagnoses of portal vein thrombosis.

OBJECTIVE: The aim of this study was to describe the prevalence of main hereditary thrombophilias, Janus kinase 2 (JAK2) V617F mutation, antiphospholipid antibody syndrome (APS), and hyperhomocysteinemia in Brazilian children and adolescents diagnosed with portal vein thrombosis (PVT) without associated hepatic disease. METHODS: A cross-sectional study was carried out with 32 children with PVT in accompaniment at Hospital das Clínicas of the Universidade Federal de Minas Gerais from January 1990 to July 2011. Laboratory evaluation of thrombophilias was performed from September 2010 to July 2011. RESULTS: Thirty-two patients were evaluated; 59% were boys. Median age at diagnosis was 2.4 years. Mean time of patients' accompaniment was between 4.7 and 5.2 years. The presence of hereditary and acquired thrombophilias occurred in 34.4% of patients, and 9 of them also showed other risk factors in the previous history evaluation. Risk factors were absent in the previous history of 18 patients (56.3%). Two patients showed persistent high titres of anticardiolipin antibodies. Hyperhomocysteinemia was not observed. One patient was heterozygous for factor V Leiden and prothrombin G20210A mutation (3.1%). Eleven patients (34.4%) showed heterozygous methylenetetrahydrofolate reductase (MTHFR) C677T, and no patient had the JAK2V617F mutation. CONCLUSIONS: Even after investigation of main hereditary and acquired thrombophilia, PVT remains without apparent cause in most patients. Nevertheless, association of local and systemic risk factors seems to be important also in the pediatric age group. Therefore, despite the low prevalence, a complete investigation, which includes both hereditary and acquired thrombophilias, may be necessary.

Hemostatic changes in patients with end stage renal disease undergoing hemodialysis.

Patients undergoing hemodialysis may show both thrombotic complications and bleeding abnormalities. Hemostatic changes in patients on hemodialysis may result from alterations in vessel wall integrity and platelet function, and reduced blood flow in the native arteriovenous fistula. Vascular complications represent 20-25% of all hospitalizations of patients on hemodialysis. Literature survey revealed that changes in the hemostatic system may play a major role in vascular complications observed in these patients. Thus, it is essential to investigate hemostatic alterations in patients on hemodialysis so that adequate regimes for anticoagulant therapy could be implemented. In this review we discuss hemostatic abnormalities in end stage renal disease patients undergoing hemodialysis.

Isolamento, diferenciação e aspectos bioquímicos de células-tronco de líquido amniótico / Isolation, differentiation and biochemical aspects of amniotic fluid stem cell

As células-tronco mesenquimais (MSCs) são células com grande potencial de diferenciação e estão sendo recentemente introduzidas na clínica para tratamento de várias doenças. Possuem várias vantagens incluindo sua estabilidade fenotípica in vitro. OBJETIVO: isolamento das MSCs de líquido amniótico, sua expansão e a demonstração da sua capacidade de se diferenciar em células miogênicas e adipogênicas, sem alterar a estabilidade cromossomal em meio de cultura. MÉTODOS: a fim de avaliar a mudança funcional destas células, foram avaliados parâmetros bioquímicos nas células adipogênicas já diferenciadas e antes da diferenciação através da dosagem de triglicérides. A diferenciação em células musculares foi avaliada comparando os níveis de creatinofosfoquinase - CK, desidrogenase lática - LDH e aldolase produzidas por estas células antes e após diferenciação. RESULTADOS: os níveis de triglicérides foram significativamente maiores nas células diferenciadas, mostrando ainda a formação de grânulos intracitoplasmáticos. Todos os outros valores obtidos foram significativamente maiores nas células miogênicas diferenciadas quando comparadas às não diferenciadas. CONCLUSÃO: os resultados sugerem que estes protocolos podem ser usados para avaliar diferenciação de células-tronco em células adipogênicas e miogênicas, e que o líquido amniótico pode ser uma fonte para obtenção destas células.

The mesenchymals stem cells (MSCs) are cells with the great potential of differentiation are being introduced in the clinic for treatment of several diseases. Mesenchymal stem cells have several advantages including the stability of their phenotype in vitro. BACKGROUND: isolation of MSCs in amniotic fluid, its expansion and the demonstration of the capacity of these cells to differentiate in adipogenic and miogenic cells, without to change the chromosomal stability of the MSCs in culture. METHODS: in order to evaluate the functional change of these cells, were gotten values of the differentiated adipogenic cells and not differentiated through the dosage of triglycerides. The miogenic nature of the differentiated cells was analyzed comparing the creatine kinase - CK, lactic dehydrogenase - LDH and aldolase produced by the cells. RESULTS: the values of triglycerides were significantly higher in differentiated cells, showing intracitoplasmatic granule form after differentiation. All the biochemical characters were significantly higher in differentiated miogenic cells. CONCLUSIONS: this study suggests that the standardized protocol of differentiation can be used in the attainment of cells with characteristics of adipogenic and muscular cells, from amniotic fluid.

[Isolation, differentiation and biochemical aspects of amniotic fluid stem cell]. / Isolamento, diferenciação e aspectos bioquímicos de células-tronco de líquido amniótico.

UNLABELLED: The mesenchymals stem cells (MSCs) are cells with the great potential of differentiation are being introduced in the clinic for treatment of several diseases. Mesenchymal stem cells have several advantages including the stability of their phenotype in vitro. BACKGROUND: isolation of MSCs in amniotic fluid, its expansion and the demonstration of the capacity of these cells to differentiate in adipogenic and myogenic cells, without to change the chromosomal stability of the MSCs in culture. METHODS: in order to evaluate the functional change of these cells, were gotten values of the differentiated adipogenic cells and not differentiated through the dosage of triglycerides. The myogenic nature of the differentiated cells was analyzed comparing the creatine kinase--CK, lactic dehydrogenase--LDH and aldolase produced by the cells. RESULTS: the values of triglycerides were significantly higher in differentiated cells, showing intracytoplasmatic granule form after differentiation. All the biochemical characters were significantly higher in differentiated myogenic cells. CONCLUSIONS: this study suggests that the standardized protocol of differentiation can be used in the attainment of cells with characteristics of adipogenic and muscular cells, from amniotic fluid.