Spectro-ViT: A vision transformer model for GABA-edited MEGA-PRESS reconstruction using spectrograms.

This study investigated the use of a Vision Transformer (ViT) for reconstructing GABA-edited Magnetic Resonance Spectroscopy (MRS) data from a reduced number of transients. Transients refer to the samples collected during an MRS acquisition by repeating the experiment to generate a signal of sufficient quality. Specifically, 80 transients were used instead of the typical 320 transients, aiming to reduce scan time. The 80 transients were pre-processed and converted into a spectrogram image representation using the Short-Time Fourier Transform (STFT). A pre-trained ViT, named Spectro-ViT, was fine-tuned and then tested using in-vivo GABA-edited MEGA-PRESS data. Its performance was compared against other pipelines in the literature using quantitative quality metrics and estimated metabolite concentration values, with the typical 320-transient scans serving as the reference for comparison. The Spectro-ViT model exhibited the best overall quality metrics among all other pipelines against which it was compared. The metabolite concentrations from Spectro-ViT's reconstructions for GABA+ achieved the best average R2 value of 0.67 and the best average Mean Absolute Percentage Error (MAPE) value of 9.68%, with no significant statistical differences found compared to the 320-transient reference. The code to reproduce this research is available at https://github.com/MICLab-Unicamp/Spectro-ViT.

Angiopoietin2 is associated with coagulation activation and tissue factor expression in extracellular vesicles in COVID-19.

Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF+ EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity.

Results of the 2023 ISBI challenge to reduce GABA-edited MRS acquisition time.

PURPOSE: Use a conference challenge format to compare machine learning-based gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) reconstruction models using one-quarter of the transients typically acquired during a complete scan. METHODS: There were three tracks: Track 1: simulated data, Track 2: identical acquisition parameters with in vivo data, and Track 3: different acquisition parameters with in vivo data. The mean squared error, signal-to-noise ratio, linewidth, and a proposed shape score metric were used to quantify model performance. Challenge organizers provided open access to a baseline model, simulated noise-free data, guides for adding synthetic noise, and in vivo data. RESULTS: Three submissions were compared. A covariance matrix convolutional neural network model was most successful for Track 1. A vision transformer model operating on a spectrogram data representation was most successful for Tracks 2 and 3. Deep learning (DL) reconstructions with 80 transients achieved equivalent or better SNR, linewidth and fit error compared to conventional 320 transient reconstructions. However, some DL models optimized linewidth and SNR without actually improving overall spectral quality, indicating a need for more robust metrics. CONCLUSION: DL-based reconstruction pipelines have the promise to reduce the number of transients required for GABA-edited MRS.

Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome.

BACKGROUND: Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. RESULTS: Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4-20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures. CONCLUSIONS: Brain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.

Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Quantitative ultrasonography reveals skeletal muscle abnormalities in carriers of DMD pathogenic variants.

INTRODUCTION/AIMS: Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. METHODS: Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. RESULTS: None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. DISCUSSION: cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.

Improving deep neural network generalization and robustness to background bias via layer-wise relevance propagation optimization.

Features in images' backgrounds can spuriously correlate with the images' classes, representing background bias. They can influence the classifier's decisions, causing shortcut learning (Clever Hans effect). The phenomenon generates deep neural networks (DNNs) that perform well on standard evaluation datasets but generalize poorly to real-world data. Layer-wise Relevance Propagation (LRP) explains DNNs' decisions. Here, we show that the optimization of LRP heatmaps can minimize the background bias influence on deep classifiers, hindering shortcut learning. By not increasing run-time computational cost, the approach is light and fast. Furthermore, it applies to virtually any classification architecture. After injecting synthetic bias in images' backgrounds, we compared our approach (dubbed ISNet) to eight state-of-the-art DNNs, quantitatively demonstrating its superior robustness to background bias. Mixed datasets are common for COVID-19 and tuberculosis classification with chest X-rays, fostering background bias. By focusing on the lungs, the ISNet reduced shortcut learning. Thus, its generalization performance on external (out-of-distribution) test databases significantly surpassed all implemented benchmark models.

Perioperative analysis of patients undergoing liver transplantation at the Hospital de Clínicas da Unicamp in the context of the SARS-CoV-2 pandemic / Análise perioperatória dos pacientes submetidos a transplante hepático no Hospital de Clínicas da Unicamp no contexto da pandemia de SARS-CoV-2

Introduction: SARS-CoV-2 began in 2020 and caused important changes in the number of transplants performed in hospitals and in the protocols for admitting candidates to perform the procedure. The Brazilian Association of Organ Transplantation (ABTO) recommends not performing transplants from donors with active COVID-19 infection, positive test results or with Severe Acute Respiratory Syndrome. The hepatic repercussions related to COVID-19 are presented in some reports in the medical literature. Liver changes resulting from other corona viruses such as SARS-CoV and MERS-CoV are well documented. The Hospital de Clínicas of the State University of Campinas is a tertiary center that performs solid organ transplants. Objectives: To carry out a perioperative, retrospective, descriptive analysis of liver transplants in the context of the SARS-CoV-2 pandemic carried out at the Hospital das Clínicas of the State University of Campinas from March 2020 to July 2021. Materials and Methods: Retrospective, descriptive, longitudinal cohort study based on the review of medical records of patients undergoing liver transplantation in the context of the SARS-CoV-2 pandemic from March 2020 to July 2021 at the clinical hospital of the State University of Campinas. Results: Retrospective analysis was performed on 57 patients in the period. Only 1 patient needed to be excluded because he was under 18 years old. Of the 56 patients, 52 underwent RT-PCR laboratory testing and chest tomography (CT). Of these 52 patients, only 2 tested positive, one pre-transplant (TX) and one post-operatively (post-op). Regarding chest CT scans, none of them showed typical changes for COVID pre-TX, in the post-op 4 patients presented typical chest CT scans. The average age was 55.86 years. The mortality rate was 38% and no deaths were attributed to COVID 19. The average MELD-Na scale was 20.94. Conclusion: The present study carried out at the Hospital de Clínicas da Unicamp analyzed the clinical, laboratory and radiological association to better elucidate the variables determined by COVID-19 in its diagnosis and in-hospital management. It is concluded that the SARS-CoV-2 pandemic had an impact on the routine of liver transplantation worldwide and on the service in which the study was carried out.

Introdução: A pandemia causada pelo SARS-CoV-2 teve início no ano de 2020 e ocasionou mudanças importantes no número de transplantes realizados nos hospitais e nos protocolos de admissão de candidatos para realização do procedimento. A Associação Brasileira de Transplante de Orgãos (ABTO) recomendava não realizar transplante de doadores com infecção COVID-19 ativa, teste positivo ou com Síndrome Respiratória Aguda Grave. As repercussões hepáticas relacionadas a COVID-19 são apresentadas em alguns relatos presentes na literatura médica. Estão bem documentadas as alterações hepáticas decorrentes de outros coronavírus tais como SARS-CoV e MERS-CoV. O Hospital de Clínicas da Universidade Estadual de Campinas é um centro terciário que realiza transplantes de órgãos sólidos. Objetivos: Realizar a análise retrospectiva descritiva perioperatória dos transplantes hepáticos no contexto da pandemia por SARS-CoV-2 realizados no hospital das clínicas da Universidade Estadual de Campinas no período de Março de 2020 a Julho de 2021. Materiais e Métodos: Estudo retrospectivo, descritivo de coorte longitudinal baseado na revisão dos prontuários dos pacientes submetidos ao transplante hepático no contexto da pandemia por SARS-CoV-2 no período de Março de 2020 a Julho de 2021 no hospital de clínicas da Universidade Estadual de Campinas. Resultados: A análise retrospectiva foi realizada em 57 pacientes no período. Apenas 1 paciente precisou ser excluído por ter menos de 18 anos. Dos 56 pacientes, 52 realizaram coleta do exame laboratorial RT-PCR e tomografia (TC) de tórax. Desses 52 pacientes apenas 2 positivaram o exame, um pré transplante (TX) e um no pós-operatório (pós-op). Em relação às TC de tórax nenhuma apresentava alterações típicas para COVID pré TX, no pós-op 4 pacientes apresentaram TC típicas. A média de idade foi de 55,86 anos. A taxa de mortalidade foi de 38% e nenhum óbito foi atribuído ao COVID 19. A escala de MELDNa média foi de 20,94. Conclusão: O presente estudo realizado no Hospital de Clínicas da Unicamp analisou a associação clínica, laboratorial e radiológica para melhor elucidar as variáveis determinadas pela COVID-19 no seu diagnóstico e manejo intra-hospitalar. Conclui-se que a pandemia por SARS-CoV-2 teve impacto na rotina de realização do transplante hepático mundialmente e no serviço no qual o estudo foi realizado.

EPIDEMIOLOGY OF POST-TRAUMATIC SPINAL CORD INJURY IN A TERTIARY HOSPITAL.

Objective: to outline the profile of risk groups for spinal cord injury (SCI) at the Hospital de Clinicas de Campinas by an epidemiological survey of 41 patients with SCI. Methods: Data from patients with SCI were collected and analyzed: demographic data, level of neurological injury, visual analogue scale (VAS), and the current American Spinal Injury Association (ASIA) impairment scale (AIS), using questionnaires, medical records, and imaging tests. Fisher's exact test was used to assess the relationship between categorical variables, Spearman's correlation coefficient was used for numerical variables, and the Mann-Whitney and Kruskal-Wallis tests were used to analyze the relationship between categorical and numerical variables, with significance level of 5%. Results: There was a prevalence of 82.9% of men, a mean age of 26.5 years, and traffic accidents as the cause of SCI in 56.1% of cases. Conclusion: Results suggest the importance of SCI prevention campaigns directed at this population. Level of Evidence II, Retrospective Study.

Objetivo: Traçar o perfil dos grupos de risco para trauma raquimedular (TRM) do Hospital das Clínicas de Campinas através de levantamento epidemiológico de 41 pacientes vítimas de TRM. Métodos: Foram coletados e analisados dados demográficos, nível da lesão neurológica, escala visual analógica (EVA) e American Spinal Injury Association impairment scale (AIS) atuais, através da aplicação de questionários, análise de prontuários e de exames de imagem. Para avaliar a relação entre as variáveis categóricas foi utilizado o teste exato de Fisher; para as variáveis numéricas foi utilizado o coeficiente de correlação de Spearman; e para a análise da relação entre variáveis categóricas e numéricas foram utilizados os testes de Mann-Whitney e Kruskal-Wallis, adotando nível de significância de 5%. Resultados: Houve prevalência de 82,9% do sexo masculino, média de idade de 26,5 anos e de 56,1% casos de TRM causados por acidente automobilístico. Conclusão: Os resultados sugerem a importância da realização de campanhas de prevenção ao TRM voltadas para essa população. Nível de Evidência II, Estudo Retrospectivo.

Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19.

Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 ± 0.880 vs 3.254 ± 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings.

Head-to-head comparison of ventilation/perfusion single photon emission computed tomography/computed tomography and multidetector computed tomography angiography for the detection of acute pulmonary embolism in clinical practice.

INTRODUCTION: Computed tomography angiography (CTA) and ventilation/perfusion (V/Q) single photon emission computed tomography/CT (SPECT/CT) images have been widely used to detect PE, but few studies have performed a direct comparison between them. We aimed to evaluate the performance of these tests in the same group of patients, selected from the routine practice of a general hospital. METHODS: Patients with suspected acute PE were prospectively submitted to CTA and V/Q SPECT/CT. General radiologists and nuclear physicians, respectively, interpreted the images. Data regarding age, sex, time between examinations, symptoms, and Wells score were also recorded. The final diagnosis was decided through a consensus among the clinicians, taking into account clinical, laboratory, follow-up, and all imaging procedures data. RESULTS: Twenty-eight patients (15 male, 13 female, and median age of 51.5 years) were studied. Median duration of the onset of symptoms was 4 (1-14) days, and the median Wells score was 3.5 (1.5-6). Sensitivity, specificity, positive and negative predictive values, and accuracy were 84.6%, 80.0%, 78.6%, 85.7%, and 82.1% for V/Q SPECT/CT, and 46.1%, 100%, 100%, 68.2%, and 75.0% for CTA. The overall agreement between the methods was 57.1%. Of the 22 patients with negative CTA, 10 (45.4%) had positives V/Q SPECT/CT and seven of them classified as true positives. CONCLUSIONS: Our results suggest that V/Q SPECT/CT is more sensitive and accurate than CTA when interpreted by general radiologists and nuclear medicine physicians.

Construction of a nomogram for predicting COVID-19 in-hospital mortality: A machine learning analysis.

Background and objectives: We aim to verify the use of ML algorithms to predict patient outcome using a relatively small dataset and to create a nomogram to assess in-hospital mortality of patients with COVID-19. Methods: A database of 200 COVID-19 patients admitted to the Clinical Hospital of State University of Campinas (UNICAMP) was used in this analysis. Patient features were divided into three categories: clinical, chest abnormalities, and body composition characteristics acquired by computerized tomography. These features were evaluated independently and combined to predict patient outcomes. To minimize performance fluctuations due to low sample number, reduce possible bias related to outliers, and evaluate the uncertainties generated by the small dataset, we developed a shuffling technique, a modified version of the Monte Carlo Cross Validation, creating several subgroups for training the algorithm and complementary testing subgroups. The following ML algorithms were tested: random forest, boosted decision trees, logistic regression, support vector machines, and neural networks. Performance was evaluated by analyzing Receiver operating characteristic (ROC) curves. The importance of each feature in the determination of the outcome predictability was also studied and a nomogram was created based on the most important features selected by the exclusion test. Results: Among the different sets of features, clinical variables age, lymphocyte number and weight were the most valuable features for prognosis prediction. However, we observed that skeletal muscle radiodensity and presence of pleural effusion were also important for outcome determination. Integrating these independent predictors was successfully developed to accurately predict mortality in COVID-19 in hospital patients. A nomogram based on these five features was created to predict COVID-19 mortality in hospitalized patients. The area under the ROC curve was 0.86 ± 0.04. Conclusion: ML algorithms can be reliable for the prediction of COVID-19-related in-hospital mortality, even when using a relatively small dataset. The success of ML techniques in smaller datasets broadens the applicability of these methods in several problems in the medical area. In addition, feature importance analysis allowed us to determine the most important variables for the prediction tasks resulting in a nomogram with good accuracy and clinical utility in predicting COVID-19 in-hospital mortality.

Epidemiology of post-traumatic spinal cord injury in a tertiary hospital / Epidemiologia do lesado medular pós-traumático em um hospital terciário

ABSTRACT Objective: to outline the profile of risk groups for spinal cord injury (SCI) at the Hospital de Clinicas de Campinas by an epidemiological survey of 41 patients with SCI. Methods: Data from patients with SCI were collected and analyzed: demographic data, level of neurological injury, visual analogue scale (VAS), and the current American Spinal Injury Association (ASIA) impairment scale (AIS), using questionnaires, medical records, and imaging tests. Fisher's exact test was used to assess the relationship between categorical variables, Spearman's correlation coefficient was used for numerical variables, and the Mann-Whitney and Kruskal-Wallis tests were used to analyze the relationship between categorical and numerical variables, with significance level of 5%. Results: There was a prevalence of 82.9% of men, a mean age of 26.5 years, and traffic accidents as the cause of SCI in 56.1% of cases. Conclusion: Results suggest the importance of SCI prevention campaigns directed at this population. Level of Evidence II, Retrospective Study.

RESUMO Objetivo: Traçar o perfil dos grupos de risco para trauma raquimedular (TRM) do Hospital das Clínicas de Campinas através de levantamento epidemiológico de 41 pacientes vítimas de TRM. Métodos: Foram coletados e analisados dados demográficos, nível da lesão neurológica, escala visual analógica (EVA) e American Spinal Injury Association impairment scale (AIS) atuais, através da aplicação de questionários, análise de prontuários e de exames de imagem. Para avaliar a relação entre as variáveis categóricas foi utilizado o teste exato de Fisher; para as variáveis numéricas foi utilizado o coeficiente de correlação de Spearman; e para a análise da relação entre variáveis categóricas e numéricas foram utilizados os testes de Mann-Whitney e Kruskal-Wallis, adotando nível de significância de 5%. Resultados: Houve prevalência de 82,9% do sexo masculino, média de idade de 26,5 anos e de 56,1% casos de TRM causados por acidente automobilístico. Conclusão: Os resultados sugerem a importância da realização de campanhas de prevenção ao TRM voltadas para essa população. Nível de Evidência II, Estudo Retrospectivo.

A Systematic Review of Automated Segmentation Methods and Public Datasets for the Lung and its Lobes and Findings on Computed Tomography Images.

OBJECTIVES: Automated computational segmentation of the lung and its lobes and findings in X-Ray based computed tomography (CT) images is a challenging problem with important applications, including medical research, surgical planning, and diagnostic decision support. With the increase in large imaging cohorts and the need for fast and robust evaluation of normal and abnormal lungs and their lobes, several authors have proposed automated methods for lung assessment on CT images. In this paper we intend to provide a comprehensive summarization of these methods. METHODS: We used a systematic approach to perform an extensive review of automated lung segmentation methods. We chose Scopus, PubMed, and Scopus to conduct our review and included methods that perform segmentation of the lung parenchyma, lobes or internal disease related findings. The review was not limited by date, but rather by only including methods providing quantitative evaluation. RESULTS: We organized and classified all 234 included articles into various categories according to methodological similarities among them. We provide summarizations of quantitative evaluations, public datasets, evaluation metrics, and overall statistics indicating recent research directions of the field. CONCLUSIONS: We noted the rise of data-driven models in the last decade, especially due to the deep learning trend, increasing the demand for high-quality data annotation. This has instigated an increase of semi-supervised and uncertainty guided works that try to be less dependent on human annotation. In addition, the question of how to evaluate the robustness of data-driven methods remains open, given that evaluations derived from specific datasets are not general.

Plasma Angiotensin II Is Increased in Critical Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1-7), and angiotensin (1-9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1-7), and angiotensin (1-9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy.

Background: Chronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR). Methods: We performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death. Results: A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death. Conclusion: In patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.

Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19.

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.