Severe COVID-19: understanding the role of immunity, endothelium, and coagulation in clinical practice.

SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis.

Good Things in Small Packages: an Innovative Delivery Approach for Inhaled Insulin.

PURPOSE: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 µm particle size distribution. METHODS: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea. Human factors use testing was designed to determine the ability to perform inspiratory manuevers with LED guidance within target flow limits. In vivo testing with healthy normal subjects of radiolabeled aerosol compared 2 breathing patterns for lung deposition efficiency, distribution, and subject preference. RESULTS: CFD demonstrated that flows ≤5 L/min and ≥15 L/min reduced the delivery efficiencg. Prototypes tested with inspiratory flow of 10 L/min provided up to 70% of dose delivered distal to the model throat with aerosols of 3 to 6 µm. Users guided by LED were able to inhale for 8-24 s with 5 s breath hold. Lung dose >70% with peripheral to central ratios >2.0 were achieved, with subject preference for the longer inspiratory time with breath hold. CONCLUSION: The device design phase integration led to a novel design and inspiratory pattern with greater levels of peripheral deposition than previously reported with commercial inhalers. The rationale and process of the application of these methods are described with implications for use in future device development.

Impact of pelvic magnetic resonance imaging findings in the indication of uterine artery embolization in the treatment of myoma.

OBJECTIVES: To assess the impact of pelvic magnetic resonance imaging (MRI) findings in the indication for uterine-artery embolization in women with fibroids, as well as the correlation between MRI and ultrasound (US) examinations for diagnosing adenomyosis. MATERIAL AND METHODS: A retrospective observational study was performed through the analysis of the medical records of 263 women referred for uterine-artery embolization as treatment for fibroids after undergoing US and MRI examinations. To compare uterine volume and fibroid measurement in US and MRI, the Wilcoxon test was used; for the number of fibroids, the McNemar test was used. The kappa coefficient was used to evaluate the correlation between US and MRI findings for diagnosing adenomyosis. RESULTS: The mean age of patients was 37.9 ± 6.8 years and 191 (72.6%) were nulliparous. Forty-three patients with adenomyosis associated with fibroid were diagnosed by MRI; US indicated the presence of adenomyosis in 12 (4.56%) women. There was agreement between MRI and US in the diagnosis of adenomyosis in 218/263 (82.9%) patients (p < 0.05). In the US examination, the mean uterine volume was lower (389 ± 340.8 cm³) than that observed in MRI (472.2 ± 415.9 cm³; p < 0.001). Regarding the number of fibroids, MRI showed a greater number of patients with multiple fibroids (68.8% vs. 57.4%, MRI and US, respectively; p < 0.001). CONCLUSIONS: In women with fibroids referred for uterine-artery embolization, MRI findings led to the revision of the initial diagnosis in 17.1% cases. US showed a lower sensitivity for diagnosing adenomyosis than MRI.

Increased Hepatic Arterial Blood Flow Measured by Hepatic Perfusion Index in Hepatosplenic Schistosomiasis: New Concepts for an Old Disease.

BACKGROUND: Portal vein obstructive lesions associated with hypertrophy of the hepatic artery territory are observed in Schistosoma mansoni schistosomiasis. Liver perfusion scintigraphy is a method used for evaluation of hepatic perfusion changes in liver diseases. It has been suggested that, like in cirrhosis, where compensatory increase in perfusion through the hepatic artery is documented, perfusion changes occur in hepatosplenic schistosomiasis (HSS). AIMS: This study aims to determine changes in liver hemodynamics using hepatic perfusion scintigraphy and correlate them with clinical and laboratory variables and ultrasound findings in HSS. METHODS: Nineteen patients with schistosomiasis underwent ultrasound evaluation of degree of liver fibrosis, splenic length, and splenic and portal vein diameter, digestive endoscopy, and quantification of platelets. Subsequently, perfusion scintigraphy with measurement of hepatic perfusion index (HPI) was performed. RESULTS: It was observed that patients with hepatosplenic schistosomiasis had significantly higher HPI compared with normal individuals (p = 0.0029) and that this increase correlated with splenic length (p = 0.038) and diameter of esophageal varices (p = 0.0060). Angioscintigraphy showed high accuracy for predicting presence of large esophageal varices. CONCLUSIONS: Angioscintigraphy could show that patients with HSS had increased HPI, featuring greater liver "arterialization," as previously described for cirrhotic patients. Correlations were also observed between HPI and longitudinal splenic length, caliber of esophageal varices, caliber of portal vein, and blood platelet count. Angioscintigraphy is a promising technique for evaluation of hepatosplenic schistosomiasis.

Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity. / Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade.

The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Phenotypic and Positron Emission Tomography with [18F]fluordeoxyglucose (FDG PET) differences in corticobasal syndrome: comparison of two cases.

Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with cortical signs (apraxia, alien hand or cortical sensory deficit), usually asymmetric. We aimed to report and compare the clinical and neuroimaging presentation of two patients diagnosed with CBS. While case 1 had severe non-fluent aphasia associated with mild apraxia and limb rigidity, case 2 had a more posterior cognitive impairment, with a different language pattern associated with marked visuospatial errors and hemineglect. FDG PET played a significant role in diagnosis, suggesting, in the first case, corticobasal degeneration and, in the second, Alzheimer's disease pattern. CBS has been widely studied with the advent of new in vivo methods such as brain FDG PET. Studies that deepen the phenotypic and biomarker heterogeneity of CBS will be of great importance for better classification, prognosis, and treatment of the condition.

A síndrome corticobasal (SCB) é uma causa rara de demência e compreende combinações variadas de sinais subcorticais (parkinsonismo acinético-rígido, distonia ou mioclonias) com sinais corticais (apraxia, mão alienígena ou déficit sensorial cortical), geralmente assimétricos. Nosso objetivo foi relatar e comparar as apresentações clínica e de neuroimagem de dois pacientes com diagnóstico de SCB. Enquanto o caso 1 apresentava afasia grave não fluente associada a apraxia leve e rigidez de membros, o caso 2 exibia comprometimento cognitivo mais posterior, com padrão de linguagem distinto, erros visuoespaciais e heminegligência. O FDG PET teve papel significativo no diagnóstico, sugerindo, no primeiro caso, degeneração corticobasal e, no segundo, padrão Alzheimer. A SCB tem sido amplamente estudada com o advento de novos métodos in vivo, como o FDG PET cerebral. Estudos que aprofundem a heterogeneidade fenotípica e de biomarcadores da SCB serão de grande importância para melhor classificação, prognóstico e tratamento da doença.

Endothelial function, arterial stiffness and heart rate variability of patients with cardiovascular diseases hospitalized due to COVID-19.

BACKGROUND: The novel coronavirus disease (COVID-19) may cause vascular (e.g., endothelial dysfunction, and arterial stiffness), cardiac, autonomic (e.g., heart rate variability [HRV]), and systemic inflammatory response via direct viral attack, hypoxia-induced injury, or immunological dysregulation, especially in those patients with pre-existing cardiovascular diseases (CVD). However, to date, no study has shown prevalence of endothelial dysfunction, arterial stiffness and heart rate variability assessed by bedside peripheral arterial tonometry in patients with previous CVD hospitalized in the acute phase of COVID-19. OBJECTIVE: This study aimed to assess the prevalence of endothelial dysfunction, arterial stiffness, and altered HRV in patients with CVD hospitalized due to COVID-19. METHODS: This cross-sectional study was conducted from July 2020 to February 2021. Included male and female adult patients aged 40 to 60 years with previous CVD and diagnosed with COVID-19. Anthropometric data, comorbidities, and blood tests were analyzed. Endothelial function, arterial stiffness, and HRV were assessed using peripheral arterial tonometry (PAT), and the statistical significance was set at 5%. RESULTS: Fourteen (51.8%) patients presented endothelial dysfunction (reactive hyperemia index = 1.2 ± 0.3) and enhancement in the high-frequency component of HRV (p < 0.05). There was a high prevalence of endothelial dysfunction, especially in patients with chronic heart failure (10 (71.4%)). Patients with preserved endothelial function showed a high augmentation index normalized to a heart rate of 75 bpm (p < 0.01), suggesting arterial stiffness. CONCLUSION: Patients with CVD hospitalized due to COVID-19 presented endothelial dysfunction assessed using PAT, which could be used as a biomarker for arterial stiffness and altered HRV. The possibility of detecting vascular and autonomic changes during phase II of COVID-19 may help to prevent possible long-term complications.

Value of stimulated pre-ablation thyroglobulin as a prognostic marker in patients with differentiated thyroid carcinoma treated with radioiodine.

OBJECTIVE: To determine which Thyroglobulin (Tg) level after levothyroxine (LT4) withdrawal (stimulated thyroglobulin - sTg) measured before radioiodine therapy (RAIT) is able to predict incomplete response to treatment of differentiated thyroid carcinoma (DTC) with greater sensitivity and specificity one year after initial treatment with I131. METHODS: A chart review was performed in which 375 patients with DTC treated with RAIT were included. The sTg was measured in all patients prior to treatment with I131. Follow up were then performed one year later. Initial sTg levels were associated to DTC outcomes. A receiver operating characteristic (ROC) curve was performed to achieve a sTg level able to predict which patients would have a greater chance of having an incomplete response to RAIT. RESULTS: Incomplete response to treatment was found in 122 patients (32.5%), this group had a mean sTg of 23.2 ng/mL. ROC curve showed that the optimal cut-off sTg level was 4.4 ng/mL. (sensitivity: 72.1%; specificity: 72.3%; accuracy: 72.2%; positive predictive value of 55.7%; and negative predictive value: 84.3%). CONCLUSION: sTg pre-ablation is a valuable predictor of DTC incomplete response to treatment one year after RAIT. Levels of 4.4 ng/ml or more showed higher accuracy to predict this outcome.

Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study.

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.

Ultrasound findings in severe COVID-19: a deeper look through the carotid arteries.

Objective: To investigate vascular and perivascular abnormalities in the carotid arteries using ultrasound, as well as to evaluate their association with mortality and clinical variables in hospitalized patients with coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study in which 53 hospitalized patients with severe COVID-19 were evaluated and underwent carotid ultrasound. We documented the carotid ultrasound findings in these patients. Clinical, demographic, laboratory, and imaging features were analyzed and compared by statistical analysis to detect correlations between them. Results: Carotid ultrasound demonstrated luminal surface irregularity in 29 patients (55%), carotid plaques in 30 (57%), perivascular infiltration in four (8%), and increased intima-media thickness (IMT) in 31 (58%). Of the 31 patients with increased IMT, 19 (61%) died, and the association between increased IMT and COVID-19-related mortality was significant (p = 0.03). Logistic regression showed that the risk of death was 85% in patients who had increased IMT in combination with acute kidney injury at admission or a history of chronic kidney disease (p < 0.05). Conclusion: In hospitalized patients with severe COVID-19, carotid ultrasound can show increased IMT, luminal surface irregularity, carotid plaques, and perivascular infiltrates. The combination of increased IMT and kidney damage appears to increase the risk of death in such patients.

Objetivo: Investigar anormalidades vasculares e perivasculares nas artérias carótidas por meio de ultrassonografia e avaliar sua associação com mortalidade e variáveis clínicas em pacientes hospitalizados com COVID-19. Materiais e Métodos: Neste estudo prospectivo, 53 pacientes hospitalizados com COVID-19 grave foram avaliados e submetidos a ultrassonografia de carótida. Descrevemos os achados ultrassonográficos de carótida nesses pacientes. As correlações de características clínicas, demográficas, laboratoriais e de imagem foram analisadas e comparadas por meio de análise estatística. Resultados: A ultrassonografia carotídea demonstrou irregularidade da superfície luminal em 29 pacientes (55%), placas carotídeas em 30 pacientes (57%), infiltração perivascular em quatro pacientes (7,5%) e aumento da espessura médio-intimal (EMI) em 31 pacientes (58%). Dos pacientes com EMI aumentada, 19 (61%) morreram, com associação observada entre EMI aumentada e mortalidade por COVID-19 (p = 0,03). Um modelo de regressão logística mostrou que a probabilidade de óbito foi de 85% em pacientes com EMI aumentada e história de nefropatia crônica ou lesão renal aguda na internação (p < 0,05). Conclusão: Aumento da EMI, irregularidade da superfície luminal, placas carotídeas e infiltrados perivasculares foram encontrados na ultrassonografia carotídea em pacientes hospitalizados com COVID-19 grave. O aumento da EMI associado a danos nos rins pode aumentar o risco de morte.

Exploratory analysis of radiomic as prognostic biomarkers in 18F-FDG PET/CT scan in uterine cervical cancer.

Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) radiomic features to predict overall survival (OS) in patients with locally advanced uterine cervical carcinoma. Methods: Longitudinal and retrospective study that evaluated 50 patients with cervical epidermoid carcinoma (clinical stage IB2 to IVA according to FIGO). Segmentation of the 18F-FDG PET/CT tumors was performed using the LIFEx software, generating the radiomic features. We used the Mann-Whitney test to select radiomic features associated with the clinical outcome (death), excluding the features highly correlated with each other with Spearman correlation. Subsequently, ROC curves and a Kaplan-Meier analysis were performed. A p-value < 0.05 were considered significant. Results: The median follow-up was 23.5 months and longer than 24 months in all surviving patients. Independent predictors for OS were found-SUVpeak with an AUC of 0.74, sensitivity of 77.8%, and specificity of 72.7% (p = 0.006); and the textural feature gray-level run-length matrix GLRLM_LRLGE, with AUC of 0.74, sensitivity of 72.2%, and specificity of 81.8% (p = 0.005). When we used the derived cut-off points from these ROC curves (12.76 for SUVpeak and 0.001 for GLRLM_LRLGE) in a Kaplan-Meier analysis, we can see two different groups (one with an overall survival probability of approximately 90% and the other with 30%). These biomarkers are independent of FIGO staging. Conclusion: By radiomic 18F-FDG PET/CT data analysis, SUVpeak and GLRLM_LRLGE textural feature presented the best performance to predict OS in patients with cervical cancer undergoing chemo-radiotherapy and brachytherapy.

COVID-19 and obesity: the meeting of two pandemics.

COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.

Mapping COVID-19 functional sequelae: the perspective of nuclear medicine.

Severe acute respiratory syndrome coronavirus 2 infection is capable of affecting several organs. Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage. The impairment of four organs stands out among severe patients: lung, heart, kidney, and endothelium. The nuclear medicine field holds accurate and safe exam techniques, such as positron emission tomography-computed tomography and scintigraphy, that allow the anatomophysiological study of the majority of human organ systems. By choosing the most appropriate method and radiopharmaceutical, analyzing the presence of inflammation, fibrosis, changes in perfusion, and function of desired organs is possible. Therefore, its use in the monitoring of patients with coronavirus disease 2019 becomes relevant, especially for monitoring sequelae. In this review, we discuss the use of Nuclear Medicine in the detection, monitoring, and therapeutic evaluation of pulmonary and extrapulmonary sequelae by coronavirus disease 2019.

Effectiveness of inspiratory muscle training associated with a cardiac rehabilitation program on sympathetic activity and functional capacity in patients with heart failure: a study protocol for a randomized controlled trial.

BACKGROUND: Individuals affected by heart failure (HF) may present fatigue, dyspnea, respiratory muscle weakness, and sympathetic activity hyperstimulation of the myocardium, among other symptoms. Conducting cardiac rehabilitation (CR) programs can be associated with inspiratory muscle training. The aim of this study was to evaluate the efficacy of inspiratory muscular training (IMT) associated with a CR program on modulating myocardial sympathetic activity and maximal functional capacity, submaximal functional capacity, thickness, and mobility of the diaphragm muscle in patients with HF. METHODS: We will conduct a clinical, controlled, randomized, double-blind trial that will include sedentary men and women who are 21-60 years old and who have diagnosed systolic HF and a left ventricular ejection fraction of less than 45%. Participants will be randomly assigned to one of two groups: experimental and control. The control group will follow the conventional CR protocol, and the experimental group will follow the conventional CR protocol associated with IMT 7 days a week. The two proposed exercise protocols will have a frequency of three times a week for a period of 12 weeks. The sympathetic innervation of the cardiac muscle, the maximum and submaximal functional capacity, diaphragm mobility and thickness, and the quality of life of the participants will be evaluated before and after the intervention protocol. DISCUSSION: This clinical trial will be the first study to investigate the additional effects of IMT on CR in sympathetic hyperstimulation in the myocardium. The results of this study will contribute to developing therapeutic strategies collaborating to elucidate whether the association of IMT with CR can induce clinical benefits for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02600000. Registered November 9, 2015. Retrospectively registered.

A mesh nebulizer is more effective than jet nebulizer to nebulize bronchodilators during non-invasive ventilation of subjects with COPD: A randomized controlled trial with radiolabeled aerosols.

BACKGROUND: Beneficial effects from non-invasive ventilation (NIV) in acute COPD are well-established, but the impact of nebulization during NIV has not been well described. AIM: To compare pulmonary deposition and distribution across regions of interest with administration of radiolabeled aerosols generated by vibrating mesh nebulizers (VMN) and jet nebulizer (JN) during NIV. METHODS: A crossover single dose study involving 9 stable subjects with moderate to severe COPD randomly allocated to receive aerosol administration by the VMN Aerogen and the MistyNeb jet nebulizer operating with oxygen at 8 lpm during NIV. Radiolabeled bronchodilators (fill volume of 3 mL: 0.5 mL salbutamol 2.5 mg + 0.125 mL ipratropium 0.25 mg and physiologic saline up to 3 mL) were delivered until sputtering during NIV (pressures of 12 cmH2O and 5 cmH2O - inspiratory and expiratory, respectively) using an oro-nasal facemask. Radioactivity counts were performed using a gamma camera and regions of interest (ROIs) were delimited. Aerosol mass balance based on counts from the lungs, upper airways, stomach, nebulizer, circuit, inspiratory and expiratory filters, and mask were determined and expressed as a percentage of the total. RESULTS: Both inhaled and lung doses were greater with VMN (22.78 ±â€¯3.38% and 12.05 ±â€¯2.96%, respectively) than JN (12.51 ±â€¯6.31% and 3.14 ±â€¯1.71%; p = 0.008). Residual drug volume was lower in VMN than in JN (3.08 ±â€¯1.3% versus 46.44 ±â€¯5.83%, p = 0.001). Peripheral deposition of radioaerosol was significantly lower with JN than VMN. CONCLUSIONS: VMN deposited > 3 fold more radioaerosol into the lungs of moderate to severe COPD patients than JN during NIV.

Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade / Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity

Resumo O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Abstract The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

Global Longitudinal Strain Predicts Poor Functional Capacity in Patients with Systolic Heart Failure.

BACKGROUND: Left ventricular global longitudinal strain value (GLS) can predict functional capacity in patients with preserved left ventricular ejection fraction (LVEF) heart failure (HF) and to assess prognosis in reduced LVEF HF. OBJETIVE: Correlate GLS with parameters of Cardiopulmonary Exercise Test (CPET) and to assess if they could predict systolic HF patients that are more appropriated to be referred to heart transplantation according to CPET criteria. METHODS: Systolic HF patients with LVEF < 45%, NYHA functional class II and III, underwent prospectively CPET and echocardiography with strain analysis. LVEF and GLS were correlated with the following CPET variables: maxVO2, VE/VCO2 slope, heart rate reduction during the first minute of recovery (HRR) and time needed to reduce maxVO2 in 50% after physical exercise (T1/2VO2). ROC curve analysis of GLS to predict VO2 < 14 mL/kg/min and VE/VCO2 slope > 35 (heart transplantation's criteria) was performed. RESULTS: Twenty six patients were selected (age, 47 ± 12 years, 58% men, mean LVEF = 28 ± 8%). LVEF correlated only with maxVO2 and T1/2VO2. GLS correlated to all CPET variables (maxVO2: r = 0.671, p = 0.001; VE/VCO2 slope: r = -0.513, p = 0.007; HRR: r = 0.466, p = 0.016, and T1/2VO2: r = -0.696, p = 0.001). GLS area under the ROC curve to predict heart transplantation's criteria was 0.88 (sensitivity 75%, specificity 83%) for a cut-off value of -5.7%, p = 0.03. CONCLUSION: GLS was significantly associated with all functional CPET parameters. It could classify HF patients according to the functional capacity and may stratify which patients have a poor prognosis and therefore to deserve more differentiated treatment, such as heart transplantation.

Benefits granted due to cardiovascular disease in Recife, Pernambuco, Brazil, 2011-2015.

BACKGROUND: Social security benefits reflect the socioeconomic impact of work incapacity by disease. Cardiovascular diseases (CVD) are the main cause of mortality and mortality worldwide. OBJECTIVE: To evaluate benefits granted due to CVD in Recife, Pernambuco, Brazil, from 2011 to 2015, from the clinical and economic perspective. METHODS: Cross-sectional and descriptive study which collected and analyzed data on benefits granted for disability caused by CVD by the executive management of the National Social Security Institute in Recife, via the Unified System of Information on Benefits. RESULTS: 186,058 benefits were granted from 2011 to 2015, 8,968 (4.8%) corresponded to CVD, of which 6,049 (67.5%) were selected for analysis because they corresponded to the most frequent diseases. About 78% of the beneficiaries were male and 63.8% were within age range 45 to 59 years old. Stroke and heart failure (HF) accounted for the longest sick leaves (133 to 138 days) and highest benefit amounts (about BRL 3,900.00 per month). CONCLUSION: While hypertension does not result in as long leaves and costs, it should be prevented for being a significant cause of stroke and HF, both of which account for longer sick leaves and higher social security costs. Improving the quality of life of the population seeks to reduce their impacts on the social security system, the world of work and society at large.

INTRODUÇÃO: Os benefícios previdenciários refletem o impacto socioeconômico gerado pela incapacidade ao trabalho por motivo de doença. As doenças cardiovasculares (DCV) são as principais causas de mortalidade e morbidade no mundo. OBJETIVO: Avaliar, clínica e economicamente, os benefícios previdenciários concedidos por DCVs no Recife, Pernambuco, no quinquênio 2011-2015. MÉTODOS: Estudo descritivo, de corte transversal, com coleta de informações e análise dos benefícios por incapacidade pelas DCVs na gerência executiva do Instituto Nacional do Seguro Social no Recife, por intermédio do Sistema Único de Informações de Benefícios. RESULTADOS: No quinquênio 2011-2015 foram concedidos 186.058 benefícios. Destes, 8.968 (4,8%) foram por DCVs, entre os quais 6.049 (67,5%) foram selecionados por serem as doenças mais frequentes. Dos beneficiários, 78% são masculinos e 63,8% estavam na faixa etária entre 45 e 59 anos. O acidente vascular encefálico (AVE) e a insuficiência cardíaca (IC) foram responsáveis pela maior duração de afastamento ao trabalho (entre 135 e 138 dias) e pelo maior valor do benefício (próximo de R$ 3.900 mensais). CONCLUSÃO: Embora a hipertensão arterial sistêmica não acarrete um afastamento tão longo e não seja tão dispendiosa, ela deveria ser prevenida, por ser causa importante de AVE e IC, duas das principais DCVs responsáveis por maior custo e número de dias de absenteísmo. A melhoria da qualidade de vida da população visa à atenuação do impacto na Previdência Social, no mundo do trabalho e na sociedade como um todo.

Anatomically Based Analysis of Radioaerosol Distribution in Pulmonary Scintigraphy: A Feasibility Study in Asthmatics.

INTRODUCTION: Manual analysis of two-dimensional (2D) scintigraphy to evaluate aerosol deposition is usually subjective and has reduced sensitivity to quantify regional differences between central and distal airways. AIMS: (1) To present a method to analyze 2D scans based on three-dimensional (3D)-linked anatomically consistent regions of interest (ROIs); (2) to evaluate peripheral-to-central counts ratio (P/C2D) and penetration indices (PIs) for a set of 16 subjects with moderate-to-severe asthma; and (3) to compare the reproducibility of this method against one with manually traced ROIs. METHODS: Two-dimensional scans were analyzed using custom software that scaled onto 2D-projections' 3D anatomical features, obtained from population-averaged computed tomography (CT) chest scans. ROIs for a rectangular box (bROI) and an anatomically shaped ROI (aROI) were defined by computer and by manually tracing the standard rectangular box (manual ROI [mROI]). These ROIs were defined five nonconsecutive times for each scan and average value and variability of the P/C2D were estimated. Based on CT estimates of lung and airways, volumes lying under the bROI and aROI, a 2D penetration index (PI2D) and a 3D penetration index (PI3D), were defined as volume-normalized ratios of aerosol deposition in central and peripheral ROIs and in central and distal airways, respectively. RESULTS: P/C2D values and their variability, were influenced by the shape and method to define the ROIs: The P/C2D was systematically greater and more variable for mROI versus bROI (p < 0.005). The P/C2D for aROI was higher and its variability lower than those for the bROI (p < 0.001). The PI2D was in average the same for aROI and bROI, and is substantially (∼30 × ) greater than PI3D (p < 0.001). Both PI2D and PI3D, obtained with our analysis, compared well with literature values obtained with two scans (deposition and volume). CONCLUSION: Our results demonstrate that 2D scintigraphy can be analyzed using anatomically based ROIs from 3D CT data, allowing objective and enhanced reproducibility values describing the distribution pattern of radioaerosol deposition in the tracheobronchial tree.