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The importance of registries is vital for almost every human disease but crucial for rare disorders, where the centralized collection, organization, and quality check of data create a platform from where multiple analyses and scientific advances are possible. In this article, the authors review the creation of the United States Immunodeficiency Network registry, its role, and the numerous scientific achievements generated from the collective effort of many.

We performed a retrospective study of coronavirus disease 2019 (COVID-19) in people with human immunodeficiency virus (PWH). PWH with COVID-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin 6, interleukin 8, and tumor necrosis factor α were commonly elevated. In all, 19 of 72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of COVID-19 despite antiretroviral therapy and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.

BACKGROUND: B-cell affinity maturation in germinal center relies on regulated actin dynamics for cell migration and cell-to-cell communication. Activating mutations in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) cause X-linked neutropenia (XLN) with reduced serum level of IgA. OBJECTIVE: We investigated the role of B cells in XLN pathogenesis. METHODS: We examined B cells from 6 XLN patients, 2 of whom had novel R268W and S271F mutations in WASp. By using immunized XLN mouse models that carry the corresponding patient mutations, WASp L272P or WASp I296T, we examined the B-cell response. RESULTS: XLN patients had normal naive B cells and plasmablasts, but reduced IgA+ B cells and memory B cells, and poor B-cell proliferation. On immunization, XLN mice had a 2-fold reduction in germinal center B cells in spleen, but with increased generation of plasmablasts and plasma cells. In vitro, XLN B cells showed reduced immunoglobulin class switching and aberrant cell division as well as increased production of immunoglobulin-switched plasma cells. CONCLUSIONS: Overactive WASp predisposes B cells for premature differentiation into plasma cells at the expense of cell proliferation and immunoglobulin class switching. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:3 pages:1069-1084 ispartof: location:United States status: published

Monoclonal antibodies block specific inflammatory pathways involved in the pathogenesis of asthma. These pathways are important in host defense against pathogens, and in particular, against parasites. Despite theoretical concerns about infection risk, biologics seem to have a favorable safety profile. Data from large clinical trials and postmarketing surveillance for these drugs have not shown increases in severe infections, including those from parasitic organisms. This may be due to redundancy of effector cells within the immune system. Certain drugs have special considerations and precautions, and therefore, the prescribing physician should be familiar with product recommendations and warnings.

Interstitial lung disease (ILD) is a common complication in patients with common variable immunodeficiency (CVID) and often associated with other features, such as bronchiectasis and autoimmunity. As the ILD term encompasses different acute and chronic pulmonary conditions, the diagnosis is commonly made based on imaging features; histopathology is less frequently available. From a cohort of 637 patients with CVID followed at our center over 4 decades, we reviewed the data for 46 subjects (30 females, 16 males) who had lung biopsies with proven ILD. They had a median age at CVID diagnosis of 26 years old, with a median IgG level at diagnosis of 285.0 mg/dL with average isotype switched memory B cells of 0.5%. Lung biopsy pathology revealed granulomas in 25 patients (54.4%), lymphoid interstitial pneumonia in 13 patients (28.3%), lymphoid hyperplasia not otherwise specified in 7 patients (15.2%), cryptogenic organizing pneumonia in 7 patients (15.2%), follicular bronchitis in 4 patients (8.7%), and predominance of pulmonary fibrosis in 4 patients (8.7%). Autoimmune manifestations were common and were present in 28 (60.9%) patients. Nine patients (19.6%) died, with a median age at death of 49-years-old. Lung transplant was done in 3 of these patients (6.5%) who are no longer alive. These analyses reveal the high burden of this complication, with almost one-fifth of the group deceased in this period. Further understanding of the causes of the development and progression of ILD in CVID patients is required to define the best management for this patient population.

Food allergy affects up to 10% of the population. The identification of modifiable risk factors including skin barrier dysfunction, vitamin D deficiency, microbiome, and route and timing of allergen exposure is leading to effective prevention strategies, and some of which are now included in public health guidelines. An increasing understanding of the pathophysiology has improved diagnostic options and revealed novel manifestations such as delayed anaphylaxis to mammalian meat related to sensitization to a sugar moiety triggered by tick bites. Current diagnosis has improved with the commercialization of allergen component testing, and the diagnostics pipeline shows imminent advances for predicting reactivity, threshold and severity. The first FDA-approved food allergy therapy has come to fruition with superb additional approaches under investigation.

Monoclonal antibodies block specific inflammatory pathways involved in the pathogenesis of asthma. These pathways are important in host defense against pathogens, and in particular, against parasites. Despite theoretical concerns about infection risk, biologics seem to have a favorable safety profile. Data from large clinical trials and postmarketing surveillance for these drugs have not shown increases in severe infections, including those from parasitic organisms. This may be due to redundancy of effector cells within the immune system. Certain drugs have special considerations and precautions, and therefore, the prescribing physician should be familiar with product recommendations and warnings.

Some centers, mostly in Europe, have demonstrated the feasibility of a minimally invasive strategy (MIS; i.e., local anesthesia and conscious sedation, performed in the cath laboratory without transesophageal echocardiography guidance). Nonetheless, the experience of MIS for TAVI using both commercially available valves is lacking in the United States. We, therefore, retrospectively studied all transfemoral TAVI cases performed at our institution between March 2011 and November 2014 to assess the safety and efficacy of MIS. Patients were dichotomized according to the strategy (MIS vs conventional strategy [CS]) used for the procedure. One hundred sixteen patients were included in the MIS group and 91 patients were included in the CS group. Baseline characteristics were similar, and procedural success was comparable (99.1% in MIS and 98.9% in CS, p = 1). One intraprocedural death occurred in each group, whereas conversion rates to general anesthesia were low (3.4%). Comparable device success was obtained. Rates of complications and >mild paravalvular leak before discharge were low and comparable. Length of hospital stay was significantly reduced in the MIS (median, 3.0 [2.0 to 5.0] days) compared with than that in CS group (median 6.0 days [3.5, 8.0]). At a median follow-up of 230 days, no significant difference in survival rate was detected (89% vs 88%, p = 0.9). On average, MIS was associated with remarkable cost saving compared with CS ($16,000/case). In conclusion, TAVI through MIS was associated with a shorter postprocedural hospital stay, lower costs, and similar safety profile while keeping procedural efficacy compared with CS.

Introduction: There are several risk scores for stratification of patients with ST-segment elevation myocardial infarction (STEMI), the most widely used of which are the TIMI and GRACE scores. However, these are complex and require several variables. The aim of this study was to obtain a reduced model with fewer variables and similar predictive and discriminative ability. Methods: We studied 607 patients (age 62 years, SD=13; 76% male) who were admitted with STEMI and underwent successful primary angioplasty. Our endpoints were all-cause in-hospital and 30-day mortality. Considering all variables from the TIMI and GRACE risk scores, multivariate logistic regression models were fitted to the data to identify the variables that best predicted death. Results: Compared to the TIMI score, the GRACE score had better predictive and discriminative performance for in-hospital mortality, with similar results for 30-day mortality. After data modeling, the variables with highest predictive ability were age, serum creatinine, heart failure and the occurrence of cardiac arrest. The new predictive model was compared with the GRACE risk score, after internal validation using 10-fold cross validation. A similar discriminative performance was obtained and some improvement was achieved in estimates of probabilities of death (increased for patients who died and decreased for those who did not). Conclusion: It is possible to simplify risk stratification scores for STEMI and primary angioplasty using only four variables (age, serum creatinine, heart failure and cardiac arrest). This simplified model maintained a good predictive and discriminative performance for short-term mortality. Resumo: Introdução: Existem vários scores para estratificação de risco em doentes com enfarte agudo miocárdico com elevação segmento ST (EAMCEST), sendo os mais utilizados o TIMI e o GRACE. Contudo, são complexos e necessitam de várias variáveis para o seu cálculo. Este estudo teve como objetivo encontrar um modelo de predição de risco, com menos variáveis e idêntica capacidade preditiva/discriminativa. Métodos: Estudaram-se 607 doentes (62 anos, SD=13; 76% sexo masculino), admitidos por EAMCEST e submetidos a angioplastia primária com sucesso. Consideraram-se como outcomes, a mortalidade intra-hospitalar e aos 30 dias de seguimento. Para identificar quais das variáveis dos referidos scores se revelaram mais influentes na previsão da mortalidade, foram efetuadas análises de regressão logística. Resultados: Dos dois scores clássicos, o GRACE foi o que apresentou melhor capacidade preditiva/discriminativa para a mortalidade intra-hospitalar, com resultados semelhantes para a mortalidade aos 30 dias. Na construção do modelo reduzido, as variáveis selecionadas foram a idade, a creatinina, a insuficiência cardíaca e a paragem cardíaca. As estimativas das probabilidades de morte intra-hospitalar, obtidas através de validação cruzada, foram comparadas com as do modelo original do score GRACE. As capacidades discriminativas foram idênticas tendo ainda sido obtida alguma melhoria nas estimativas das probabilidades de morte (aumento/diminuição para os doentes que morreram/não morreram). Conclusões: É possível uma simplificação dos scores de estratificação de risco para EAMCEST e angioplastia primária com apenas as variáveis idade, creatinina, insuficiência cardíaca e paragem cardíaca. O modelo simplificado manteve um bom desempenho preditivo/discriminativo para a mortalidade a curto-prazo. Keywords: Risk scores, Acute coronary syndromes, Prognosis, Palavras-chave: Scores de risco, Síndromas coronárias agudas, Prognóstico

Cardiovascular disease is among the main causes of mortality and morbidity worldwide. Despite significant advances in medical and interventional therapy, the prognosis of conditions such as ischemic heart disease is still dismal. There is thus a need to investigate new therapeutic tools, one of which is stem cell therapy. Hematopoietic stem cells are the most studied type, and the fact that their biology is relatively well understood has led to their being used in preclinical research and clinical trials. However, the results of some of these studies have been controversial, which has opened the way for studies on other cell types, such as mesenchymal stem cells. These cells have immunomodulatory properties which suggest that they have therapeutic potential in cardiology. In the present article, the authors review the state of the art regarding mesenchymal stem cells, from basic and translational research to their use in clinical trials on ischemic heart disease, heart failure and arrhythmias, and discuss possible future uses. Resumo: A doença cardiovascular é uma das principais causas de mortalidade e morbilidade em todo o mundo e, apesar de os avanços na terapêutica médica e intervenção percutânea, o prognóstico de doenças como a cardiopatia isquémica e o pós-enfarte do miocárdio continuam a ser consideravelmente inferiores ao desejado. Essa situação justifica a aposta na investigação de novas ferramentas terapêuticas, como é o caso da terapia com células estaminais. O conhecimento mais vasto das células de linhagem hematopoiética levou à sua utilização numa primeira fase, tanto em investigação pré-clínica como clínica. A existência de alguns resultados controversos e de uma melhoria correspondente às expectativas iniciais abriu a caminho a outros tipos celulares com potencial terapêutico, como é o caso das células precursoras do mesênquima. Estas células têm características imunomoduladoras que lhes conferem um racional de utilidade terapêutica em várias áreas da Cardiologia. Neste artigo, os autores efetuam a revisão do estado da arte relativo à utilização de células precursoras do mesênquima, desde a sua investigação pré-clínica até à sua utilização em ensaios clínicos em doentes com cardiopatia isquémica, insuficiência cardíaca de várias etiologias ou disritmias. É ainda perspetivado o futuro da utilização destas células. Keywords: Mesenchymal stem cells, Cardiovascular system, Myocardial ischemia, Heart failure, Arrhythmias, Translational research, Palavras-chave: Células precursoras do mesênquima, Sistema cardiovascular, Cardiopatia isquémica, Insuficiência cardíaca, Disritmias, Investigação translacional

Introduction The use of fractional flow reserve (FFR) as the gold standard for functional assessment of intermediate coronary stenosis has been well documented. Intracoronary imaging techniques such as intravascular ultrasound (IVUS) have been used for additional coronary lesion resolution and some of its anatomic parameters have been studied as having possible correlation with FFR, particularly IVUS minimal lumen area (MLA). We performed a comprehensive review of the available literature in the area. Evidence acquisition A Pubmed search was performed for all the literature involving comparison of diagnostic accuracy of IVUS-MLA with FFR. Evidence synthesis An extensive description of all the available data regarding IVUS-MLA diagnostic value regarding the FFR of stenotic lesions, for both non-left main (non-LM) and left main (LM) lesions. Conclusions For non-LM lesions IVUS-MLA cutoff values to identify specific FFR thresholds have marked heterogeneity and perform particularly poorly in terms of specificity and positive predictive value. For LM lesions IVUS-MLA performs better and shows a better correlation with FFR, though more data is needed to confirmed that trend.

The success and procedural complexities of percutaneous left atrial appendage (LAA) closure depends largely on the LAA anatomy, and on the anatomic relations between access to the left atrium via the fossa ovalis to the LAA. These anatomic features and three-dimensional cardiac structural relationships are distinctly depicted on cardiac computed tomography angiography (CCTA), especially since the LAA has minimal dynamic role during the cardiac cycle. The spatial resolution and three-dimensional structural depiction of CCTA offers unique imaging planes not appreciated with transesophageal echocardiography (TEE), which has been the conventional pre-imaging modality-of-choice for LAA closure. As with other structural cardiac interventions, the noninvasiveness, superiority in imaging resolution and relational portrayal have progressively established CCTA as instrumental preplanning imaging tool, and is anticipated to overtake TEE as the pre-imaging modality-of-choice for LAA closure. For preplanning imaging, CCTA allows not only anatomic LAA assessment, but also ruling out preexisting thrombus in the LAA that would exclude attempt at LAA closure. In addition, post-surveillance of LAA closure is necessary to rule out device-related thrombus and residual leak, and CCTA can contribute to this important role. This chapter will review the practical utility of CCTA in preplanning and guiding LAA closure, and post-procedural surveillance.

Objectives: to determine the predictors of neurocognitive performance (NP) of patients with Congenital Heart Disease (CHD), analysing its relation to parameters of fetal development, as head circumference (HC), weight (W) and length (L) at birth, neonatal parameters (APGAR 1, 5), quality of life (QOL), psychiatric morbidity (PM), psychosocial adjustment (PSA) and traits of personality (TP); to identify different phenotypes of NP in CHD patients. Methods: 337 CHD patients, 189 male, ages 12 to 30 years (mean= 16.34 ± 3.12), 117 cyanotic, and 119 healthy controls (56 males, mean=18.41±3.20) participated. Clinical data were collected. Neuropsychological assessment included Wechsler’s Digit Test (direct and reverse) and Symbol Search, Rey’s Complex Figure, BADS’s Key Searching Test, Color-Word Stroop Test, Trail Making Test (A, B) and Logical Memory Task. Participants were interviewed on social support, family educational style, self-image, physical limitations, completed a psychiatric interview (SADS-L) and self-report questionnaires on QOL (WHOQOL-BREF), PSA (YSR and ASR) and TP (NEOPI-R). HC, W and L and APGAR were collected. Results: CHD patients had a significantly worse NP than healthy controls in all tests, and the cyanotic worse than the acyanotic patients. Several correlations were apparent between fetal parameters (HC, W and L) and neuropsychological abilities in CHD. However, the HC was the main predictor of bad NP later on in CHD patients (R=0.435; R2=0.189; F=14.692; p=0.000; β=0.201; t=2.487; p=0.016). We identified 3 neurocognitive phenotypes in CHD patients, minimally, moderately and globally impaired. The last showed lower HC (p=0.003), W (p=0.022) and L, and a bigger number of retentions in school (p=0.017) than the first. The last reported more aggressive behaviors.than the other 2 (p=0.007; p=0.006) and their caregivers reported more social (p=0.025), thought (p=0.041) and attention problems (p=0.001) in their children than the parents of the other 2. Conclusion: CHD patients have worse NP than controls; small HC at birth was the main predictor of poor NP; We identified 3 patterns of neurocognitive disability among CHD patients: mild, moderate and severely impaired, all showing significant differences compared to controls.

Objective— Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS. Approach and Results— We used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8 + T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells. Conclusions— In this exploratory analysis, naïve CD8 + T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.

Background aims The therapeutic application of CD34+ circulating progenitor cells (which includes endothelial progenitor cells) has been hampered by the quantity and quality of isolated circulating CD34 + cells from the patient's peripheral blood. Our group had previously established a suspension culture system for human CD34 + cells, with increased quantity and quality (QQ) of the angiogenic cell product. We successfully scaled up the expansion process with the use of culture bags because there is the need to move toward a dynamic and fully controlled bioreactor system to meet Good Manufacturing Practice (GMP) standards and attain clinically meaningful cell doses in a time- and cost-effective way. Methods CD34 + cells isolated from mobilized peripheral blood of healthy donors were expanded ex vivo for 7 days in QQ medium (serum-free) in cell culture bags (30 mL) and pre- and post-expansion cells were characterized by means of flow cytometry and quantitative polymerase chain reaction; angiogenic potential was assessed by use of the in vitro tube formation assay. Results Our data show effective expansion of the cultured population (7-fold) while maintaining the stem/progenitor content and increasing the endothelial population. Moreover, post-expanded cells showed higher tube formation capacity compared with pre-expanded cells. In addition, an upregulation of the anti-inflammatory gene expression and a downregulation of pro-inflammatory genes were observed, which suggests that the increase in angiogenic potential is not paired with an increase in the inflammatory profile. Conclusions The QQ expansion method was successfully scaled up to cell culture bags and was able to meet GMP standards, with a higher in vitro angiogenic profile.

Objectives: to study neurocognitive performance (NP) of CHD patients and to determine whether is related to parameters of fetal development registered at birth, head circumference (HC), weight (W) and length (L) and neonatal parameters (APGAR 1, 5); to study their quality of life (QOL), psychiatric morbidity (PM), psychosocial adjustment (PSA) and traits of personality (TP). Methods: 266 CHD patients, 148 male, aged from 12 to 30 years (mean= 18.00 ± 3.22), 103 cyanotic, and 119 healthy controls (56 males, mean=18.41±3.20) participated. Clinical data were collected. Neuropsychological assessment included Wechsler’s Digit Test (direct and reverse) and Symbol Search, Rey’s Complex Figure, BADS’s Key Searching Test, Color-Word Stroop Test, Trail Making Test (A, B) and Logical Memory Task. Participants were interviewed on social support, family educational style, self-image, physical limitations, completed a psychiatric interview (SADS-L) and self-report questionnaires on QOL (WHOQOL-BREF), PSA (YSR and ASR) and TP (NEOPI-R). HC, W and L and APGAR were collected. Results: CHD patients had a significantly worse NP than healthy controls in all tests, and the cyanotic worse than the acyanotic patients (but not significantly). Several correlations were apparent between fetal parameters (HC, W and L) and neuropsychological abilities in CHD. However, low weight at birth, cyanosis and male gender are the main predictors of bad NP later on in CHD patients (R=0.414; R2=0.171; F=5.787; p=0.001; β=1.654; t=2.858; p=0.005; β=1.881; t=2.377; p=0.020; b=1.624; t=2.062; p=0.042). We found a 15.3% lifetime prevalence of psychopathology (18.5% in females). Comparing to normal population, our patients have better QOL in environmental (t=6.907; p=0.000), social relationships (t=5.102; p=0.000) and general dimensions (t=2.558; p=0.011). Complex CHD reported worse QOL in physical dimension (U=3576.500; p=0.001) than those with moderate/mild forms of disease; Female patients showed worse PSA, with more withdrawal, anxiety/depression and internalization. Conclusion: CHD patients have worse NP than controls; low weight at birth, male gender and the presence of cyanosis predict bad NP in CHD patients; patients seem to be more prone to PM, worse PSA and SP.

Introduction: The public health burden of atherosclerosis remains unacceptably high despite existing measures aimed at primary prevention. Although the detection of subclinical atherosclerotic disease as measured by quantification of coronary artery calcium score (CACS) by computed tomography (CT) refines risk estimation, this approach is costly and may not be feasible as a global strategy. We sought to analyze peripheral blood mononuclear cells (PB-MNC) using polychromatic flow cytometry in patients undergoing cardiac CT to determine cellular correlates of early atherosclerosis. Methods: We enrolled 286 patients with recent CT for CACS determination (125 CACS=0 / 161 CACS>0). PB-MNCs were isolated for flow cytometry determination using a panel of cell markers, to quantify CD34+CD45dim circulating progenitor cells (CPC). We performed multivariable logistic regression analysis to identify independent predictors of CACS=0. Integer chance weights were assigned to each independent risk variable as a point scoring system. Summed scores were used to define chance groups in quartiles. Predicted chances of CACS=0 were compared with the observed chances and a score calibration test (Hosmer-Lemeshow) was performed. Results: High levels of circulating CPC independently predicted the absence of subclinical atherosclerosis in addition to age, female gender, and nonsmoking status. A risk score calibration test demonstrated the predicted and observed chances of this outcome were similar by risk group (p > 0.05). The area under the ROC for the model indicates a 78% chance that the model assigned a lower probability to a patient with CACS=0 than to a patient with subclinical atherosclerosis. Conclusion: In our sample, the proportion of CPC was shown to be an independent predictor of absence of coronary disease and the generated score showed a robust correlation between predicted and observed values of CACS.

We present the evaluation of a haptic rendering algorithm based on the Voxmap-Pointshell algorithm which was integrated in the physics engine Bullet. Our algorithm uses voxelized distance fields and multi-resolution point-sampled representations and it is able to compute collision forces between arbitrary complex bodies at 1 kHz. Current experiments show that the integrated algorithm outperforms standard collision detection engines in Bullet in terms of speed if high resolutions and accuracies are required, enabling physically more realistic behaviors.

Resumo: A doença cardiovascular é uma das principais causas de mortalidade e morbilidade em todo o mundo e, apesar de os avanços na terapêutica médica e intervenção percutânea, o prognóstico de doenças como a cardiopatia isquémica e o pós-enfarte do miocárdio continuam a ser consideravelmente inferiores ao desejado. Essa situação justifica a aposta na investigação de novas ferramentas terapêuticas, como é o caso da terapia com células estaminais. O conhecimento mais vasto das células de linhagem hematopoiética levou à sua utilização numa primeira fase, tanto em investigação pré-clínica como clínica. A existência de alguns resultados controversos e de uma melhoria correspondente às expectativas iniciais abriu a caminho a outros tipos celulares com potencial terapêutico, como é o caso das células precursoras do mesênquima. Estas células têm características imunomoduladoras que lhes conferem um racional de utilidade terapêutica em várias áreas da Cardiologia. Neste artigo, os autores efetuam a revisão do estado da arte relativo à utilização de células precursoras do mesênquima, desde a sua investigação pré-clínica até à sua utilização em ensaios clínicos em doentes com cardiopatia isquémica, insuficiência cardíaca de várias etiologias ou disritmias. É ainda perspetivado o futuro da utilização destas células. Abstract: Cardiovascular disease is among the main causes of mortality and morbidity worldwide. Despite significant advances in medical and interventional therapy, the prognosis of conditions such as ischemic heart disease is still dismal. There is thus a need to investigate new therapeutic tools, one of which is stem cell therapy. Hematopoietic stem cells are the most studied type, and the fact that their biology is relatively well understood has led to their being used in preclinical research and clinical trials. However, the results of some of these studies have been controversial, which has opened the way for studies on other cell types, such as mesenchymal stem cells. These cells have immunomodulatory properties which suggest that they have therapeutic potential in cardiology. In the present article, the authors review the state of the art regarding mesenchymal stem cells, from basic and translational research to their use in clinical trials on ischemic heart disease, heart failure and arrhythmias, and discuss possible future uses. Palavras-chave: Células precursoras do mesênquima, Sistema cardiovascular, Cardiopatia isquémica, Insuficiência cardíaca, Disritmias, Investigação translacional, Keywords: Mesenchymal stem cells, Cardiovascular system, Myocardial ischemia, Heart failure, Arrhythmias, Translational research

Atrial fibrillation is prevalent and percutaneous left atrial appendage (LAA) closure is increasingly performed worldwide. This procedure is technically challenging and the success and procedural complexities depend on anatomy of the LAA and surrounding structures. These are readily depicted on cardiac computed tomography angiography (CCTA), which offers unique imaging planes. CCTA allows not only preplanning anatomic LAA assessment, but can also be used to evaluate for pre-existing LAA thrombus, and done postprocedure for surveillance for device-related thrombus, residual leak, and complications. In this article, we review the practical utility of CCTA for LAA closure.

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Reportamos o caso de um doente de 31 anos, sexo masculino, fumador, com internamento previo em Servico de Medicina por pancreatite necro-hemorragica alitiasica. Reinternado um mes apos alta por queixas de cansaco facil para pequenos esforcos, dispneia de esforco, ortopneia, astenia, suores nocturnos e emagrecimento (6 kg num mes 10 % do peso total). Foi transferido para o nosso servico com diagnostico de derrame pericardico com tamponamento cardiaco e pancreatite necro-hemorragica alitiasica. A chegada ao SU o doente apresentava-se taquipneico (FR-22cpm) com TA-96/60 mmHg, FC-120 bpm, ingurgitamento jugular total a 30o e hepatoesplenomegalia. AC-S1 e S2 com intensidade diminuida, AP-MV presente bilateralmente contudo diminuido na base direita, ECG em ritmo sinusal com frequencia de 125 bpm, ma progressao da onda R nas derivacoes precordiais. O ecocardiograma transtoracico realizado no hospital de origem revelou volumoso derrame pericardico, massa de 12x16 mm aderente ao tecto da auricula direita (AD) e colapso diastolico do ventriculo direito (VD) mantendo funcao biventricular preservada (fi g. 1). A TAC toraco-abdominal evidenciou area hipodensa com cerca de 3 cm de maior diâmetro sugestiva de pancreatite com componente necrotico envolvendo a cauda do pâncreas, IMAGENS EM CARDIOLOGIA