Inferior Vena Cava Diameter Measurement Provides Distinct and Complementary Information to Right Atrial Pressure in Acute Decompensated Heart Failure.

BACKGROUND: Inferior vena cava (IVC) measurements correlate only modestly with right atrial pressure (RAP). Part of this inaccuracy is due to the high compliance of the venous system, where a large change in blood volume may result in only a small change in pressure. As such, the information provided by the IVC may be different rather than redundant. METHODS AND RESULTS: We analyzed patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial who had both pulmonary artery catheter and IVC measurements at baseline (n = 108). There was only a modest correlation between baseline RAP and IVC diameter (r = 0.41; P < 0.001). Hemoconcentration, defined as an increase in hemoglobin levels between admission and discharge, was correlated with decrease in IVC diameter (r = 0.35; P = 0.02) but not with a decrease in RAP (r = 0.01; P = 0.95). When patients had both IVC and RAP measurements that were below the median, survival rates were superior to the rates of those who had only 1 measurement below the median, and when both rates were above the median, patients fared the worst (P = 0.002). CONCLUSION: IVC and RAP have limited correlation with each another, and changes in intravascular volume appear to correlate better with IVC diameter rather than with RAP. Furthermore, complementary information is provided by pressure and volume assessments in acute decompensated heart failure.

An assessment of transesophageal echocardiography studies rated as rarely appropriate tests for infective endocarditis at an academic medical center.

PURPOSE: Endocardial involvement documented by echocardiography is a major criterion of the modified Duke criteria (MDC) for infective endocarditis (IE). Though transesophageal echocardiography (TEE) is sensitive in the diagnosis of IE, it can be inappropriately used. METHODS: This retrospective study included all patients who underwent TEE due to bacteremia, fever, and/or endocarditis in a single, tertiary academic medical center in 2013. Data collected from electronic medical charts were as follows: demographics, history, physical examination, blood cultures, and transthoracic (TTE) and TEE findings. Cases were categorized based on appropriate use criteria (AUC) and MDC. An infectious disease (ID) specialist reviewed cases with rarely appropriate TEE use. RESULTS: In the 194 patients included, 147 (75.8%) were rated as appropriate, 36 (18.6%) rarely appropriate, and 11 (5.6%) uncertain. Of the 36 with rarely appropriate TEEs, using MDC 31 (86%) were rejected and 5 (14%) were possible for IE. Retrospective chart review by an ID specialist determined that 10 of these patients warranted TEE due to compelling issues, including immunosuppression or complicated infection. CONCLUSIONS: In this retrospective cohort, almost one fifth of cases were rated as rarely appropriate. However, a review of these cases showed that TEE was often pursued when the clinical situation involved immunosuppression or complex infectious process. There remains room for improvement to our screening process for TEE and a need to implement a nuanced educational plan to better precisely identify appropriate cases for TEE usage.

Interplay between Target Sequences and Repair Pathways Determines Distinct Outcomes of AID-Initiated Lesions.

Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G mismatches, a rate-limiting step of Ab gene diversification. However, precise mechanisms regulating AID deamination frequency remain incompletely understood. Moreover, it is not known whether different sequence contexts influence the preferential access of mismatch repair or uracil glycosylase (UNG) to AID-initiated U:G mismatches. In this study, we employed two knock-in models to directly compare the mutability of core Sµ and VDJ exon sequences and their ability to regulate AID deamination and subsequent repair process. We find that the switch (S) region is a much more efficient AID deamination target than the V region. Igh locus AID-initiated lesions are processed by error-free and error-prone repair. S region U:G mismatches are preferentially accessed by UNG, leading to more UNG-dependent deletions, enhanced by mismatch repair deficiency. V region mutation hotspots are largely determined by AID deamination. Recurrent and conserved S region motifs potentially function as spacers between AID deamination hotspots. We conclude that the pattern of mutation hotspots and DNA break generation is influenced by sequence-intrinsic properties, which regulate AID deamination and affect the preferential access of downstream repair. Our studies reveal an evolutionarily conserved role for substrate sequences in regulating Ab gene diversity and AID targeting specificity.

AID-initiated DNA lesions are differentially processed in distinct B cell populations.

Activation-induced deaminase (AID) initiates U:G mismatches, causing point mutations or DNA double-stranded breaks at Ig loci. How AID-initiated lesions are prevented from inducing genome-wide damage remains elusive. A differential DNA repair mechanism might protect certain non-Ig loci such as c-myc from AID attack. However, determinants regulating such protective mechanisms are largely unknown. To test whether target DNA sequences modulate protective mechanisms via altering the processing manner of AID-initiated lesions, we established a knock-in model by inserting an Sγ2b region, a bona fide AID target, into the first intron of c-myc. Unexpectedly, we found that the inserted S region did not mutate or enhance c-myc genomic instability, due to error-free repair of AID-initiated lesions, in Ag-stimulated germinal center B cells. In contrast, in vitro cytokine-activated B cells display a much higher level of c-myc genomic instability in an AID- and S region-dependent manner. Furthermore, we observe a comparable frequency of AID deamination events between the c-myc intronic sequence and inserted S region in different B cell populations, demonstrating a similar frequency of AID targeting. Thus, our study reveals a clear difference between germinal center and cytokine-activated B cells in their ability to develop genomic instability, attributable to a differential processing of AID-initiated lesions in distinct B cell populations. We propose that locus-specific regulatory mechanisms (e.g., transcription) appear to not only override the effects of S region sequence on AID targeting frequency but also influence the repair manner of AID-initiated lesions.

Can the learning of laparoscopic skills be quantified by the measurements of skill parameters performed in a virtual reality simulator?

PURPOSE: To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). MATERIALS AND METHODS: Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. RESULTS: The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. CONCLUSION: The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills.

Continuous non-invasive hemodynamic monitoring in early onset severe preeclampsia.

OBJECTIVES: Continuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and total peripheral resistance (TPR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE). STUDY DESIGN: This prospective observational study included 12 pregnant patients with early PEC. CO and TPR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed. RESULTS: Compared to 3DE-CO, CS-CO was highly correlated (R2 = 0.70, p = <0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-TPR had strong correlation (R2 = 0.81, p = <0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias + 2.05 ±1.18 L/min, limit of agreement (LOA) -0.20 to 4.31) and underestimate TPR (bias -279 ±156 dyes/sec/cm5; LOA -580 to 18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and TPR. NICOM-CO had only moderate correlation with 3DE-CO (R2 = 0.29, p = 0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (-1.2 ±1.68 L/min) but wide 95% LOA (-4.41 to 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-TPR had poor correlation with 3DE-TPR (R2 = 0.32, p = 0.001) with high PE (67%), relatively low mean bias (238 ±256), and wide 95% LOA (-655 to 1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and TPR. CONCLUSIONS: Clearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and TPR monitoring in severe preeclampsia.

The importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial.

AIMS: Previous studies have suggested venous congestion as a stronger mediator of negative cardio-renal interactions than low cardiac output, with neither factor having a dominant role. While the influence of these parameters on glomerular filtration have been described, the impact on diuretic responsiveness is unclear. The goal of this analysis was to understand the hemodynamic correlates of diuretic response in hospitalized patients with heart failure. METHODS AND RESULTS: We analyzed patients from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) dataset. Diuretic efficiency (DE) was defined as the average daily net fluid output per doubling of the peak loop diuretic dose. We evaluated a pulmonary artery catheter hemodynamic-guided cohort (n = 190) and a transthoracic echocardiogram (TTE) cohort (n = 324) where DE was evaluated with hemodynamic and TTE parameters. Metrics of "forward flow" such as cardiac index, mean arterial pressure and left ventricular ejection fraction were not associated with DE (p > 0.2 for all). Worse baseline venous congestion was paradoxically associated with better DE as assessed by right atrial pressure (RAP), right atrial area (RAA), and right ventricular systolic and diastolic area (p < 0.05 for all). Renal perfusion pressure (capturing both congestion and forward flow) was not associated with diuretic response (p = 0.84). CONCLUSIONS: Worse venous congestion was weakly associated with better loop diuretic response. Metrics of "forward flow" did not demonstrate any correlation with diuretic response. These observations raise questions about the concept of central hemodynamic perturbations as the primary drivers of diuretic resistance on a population level in HF.

Association of obesity with venous thromboembolism and myocardial injury in COVID-19.

INTRODUCTION: Although both obesity and coronavirus disease 2019 (COVID-19) independently induce inflammation and thrombosis, the association between obesity class and risk of thrombosis in patients with COVID-19 remains unclear. METHODS: This retrospective cohort study included consecutive patients hospitalized with COVID-19 at a single institution. Patients were categorized based on obesity class. The main outcomes were venous thromboembolism (VTE) and myocardial injury, a marker of microvascular thrombosis in COVID-19. Adjustments were made for sociodemographic variables, cardiovascular disease risk factors and comorbidities. RESULTS: 609 patients with COVID-19 were included. 351 (58%) patients were without obesity, 110 (18%) were patients with class I obesity, 76 (12%) were patients with class II obesity, and 72 (12%) were patients with class III obesity. Patients with class I and III obesity had significantly higher risk-adjusted odds of VTE compared to patients without obesity (OR = 2.54, 95% CI: 1.05-6.14 for class I obesity; and OR = 3.95, 95% CI: 1.40-11.14 for class III obesity). Patients with class III obesity had significantly higher risk-adjusted odds of myocardial injury compared to patients without obesity (OR = 2.15, 95% CI: 1.12-4.12). Both VTE and myocardial injury were significantly associated with greater risk-adjusted odds of mortality. CONCLUSION: This study demonstrates that both macrovascular and microvascular thromboses may contribute to the elevated morbidity and mortality in patients with obesity and COVID-19.

Multimodality Imaging in the Diagnosis of Prosthetic Valve Endocarditis: A Brief Review.

Infective endocarditis is a common and treatable condition that carries a high mortality rate. Currently the workup of infective endocarditis relies on the integration of clinical, microbiological and echocardiographic data through the use of the modified Duke criteria (MDC). However, in cases of prosthetic valve endocarditis (PVE) echocardiography can be normal or non-diagnostic in a high proportion of cases leading to decreased sensitivity for the MDC. Evolving multimodality imaging techniques including leukocyte scintigraphy (white blood cell imaging), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), multidetector computed tomographic angiography (MDCTA), and cardiac magnetic resonance imaging (CMRI) may each augment the standard workup of PVE and increase diagnostic accuracy. While further studies are necessary to clarify the ideal role for each of these imaging techniques, nevertheless, these modalities hold promise in determining the diagnosis, prognosis, and care of PVE. We start by presenting a clinical vignette, then evidence supporting various modality strategies, balanced by limitations, and review of formal guidelines, when available. The article ends with the authors' summary of future directions and case conclusion.

Relation of Cardiovascular Risk Factors to Mortality and Cardiovascular Events in Hospitalized Patients With Coronavirus Disease 2019 (from the Yale COVID-19 Cardiovascular Registry).

Individuals with established cardiovascular disease or a high burden of cardiovascular risk factors may be particularly vulnerable to develop complications from coronavirus disease 2019 (COVID-19). We conducted a prospective cohort study at a tertiary care center to identify risk factors for in-hospital mortality and major adverse cardiovascular events (MACE; a composite of myocardial infarction, stroke, new acute decompensated heart failure, venous thromboembolism, ventricular or atrial arrhythmia, pericardial effusion, or aborted cardiac arrest) among consecutively hospitalized adults with COVID-19, using multivariable binary logistic regression analysis. The study population comprised 586 COVID-19 positive patients. Median age was 67 (IQR: 55 to 80) years, 47.4% were female, and 36.7% had cardiovascular disease. Considering risk factors, 60.2% had hypertension, 39.8% diabetes, and 38.6% hyperlipidemia. Eighty-two individuals (14.0%) died in-hospital, and 135 (23.0%) experienced MACE. In a model adjusted for demographic characteristics, clinical presentation, and laboratory findings, age (odds ratio [OR], 1.28 per 5 years; 95% confidence interval [CI], 1.13 to 1.45), previous ventricular arrhythmia (OR, 18.97; 95% CI, 3.68 to 97.88), use of P2Y12-inhibitors (OR, 7.91; 95% CI, 1.64 to 38.17), higher C-reactive protein (OR, 1.81: 95% CI, 1.18 to 2.78), lower albumin (OR, 0.64: 95% CI, 0.47 to 0.86), and higher troponin T (OR, 1.84; 95% CI, 1.39 to 2.46) were associated with mortality (p <0.05). After adjustment for demographics, presentation, and laboratory findings, predictors of MACE were higher respiratory rates, altered mental status, and laboratory abnormalities, including higher troponin T (p <0.05). In conclusion, poor prognostic markers among hospitalized patients with COVID-19 included older age, pre-existing cardiovascular disease, respiratory failure, altered mental status, and higher troponin T concentrations.

Machine Learning Applications to Resting-State Functional MR Imaging Analysis.

Machine learning is one of the most exciting and rapidly expanding fields within computer science. Academic and commercial research entities are investing in machine learning methods, especially in personalized medicine via patient-level classification. There is great promise that machine learning methods combined with resting state functional MR imaging will aid in diagnosis of disease and guide potential treatment for conditions thought to be impossible to identify based on imaging alone, such as psychiatric disorders. We discuss machine learning methods and explore recent advances.

Combined deletion of Xrcc4 and Trp53 in mouse germinal center B cells leads to novel B cell lymphomas with clonal heterogeneity.

BACKGROUND: Activated B lymphocytes harbor programmed DNA double-strand breaks (DSBs) initiated by activation-induced deaminase (AID) and repaired by non-homologous end-joining (NHEJ). While it has been proposed that these DSBs during secondary antibody gene diversification are the primary source of chromosomal translocations in germinal center (GC)-derived B cell lymphomas, this point has not been directly addressed due to the lack of proper mouse models. METHODS: In the current study, we establish a unique mouse model by specifically deleting a NHEJ gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in GC B cells, which results in the spontaneous development of B cell lymphomas that possess features of GC B cells. RESULTS: We show that these NHEJ deficient lymphomas harbor translocations frequently targeting immunoglobulin (Ig) loci. Furthermore, we found that Ig translocations were associated with distinct mechanisms, probably caused by AID- or RAG-induced DSBs. Intriguingly, the AID-associated Ig loci translocations target either c-myc or Pvt-1 locus whereas the partners of RAG-associated Ig translocations scattered randomly in the genome. Lastly, these NHEJ deficient lymphomas harbor complicated genomes including segmental translocations and exhibit a high level of ongoing DNA damage and clonal heterogeneity. CONCLUSIONS: We propose that combined NHEJ and p53 defects may serve as an underlying mechanism for a high level of genomic complexity and clonal heterogeneity in cancers.

Surgical performance during laparoscopic radical nephrectomy is improved with training in a porcine model.

BACKGROUND AND PURPOSE: Becoming proficient in laparoscopic surgery is dependent on the acquisition of specialized skills that can only be obtained from specific training. This training could be achieved in various ways using inanimate models, animal models, or live patient surgery--each with its own pros and cons. Currently, there are substantial data that support the benefits of animal model training in the initial learning of laparoscopy. Nevertheless, whether these benefits extent themselves to moderately experienced surgeons is uncertain. The purpose of this study was to determine if training using a porcine model results in a quantifiable gain in laparoscopic skills for moderately experienced laparoscopic surgeons. MATERIALS AND METHODS: Six urologists with some laparoscopic experience were asked to perform a radical nephrectomy weekly for 10 weeks in a porcine model. The procedures were recorded, and surgical performance was assessed by two experienced laparoscopic surgeons using a previously published surgical performance assessment tool. The obtained data were then submitted to statistical analysis. RESULTS: With training, blood loss was reduced approximately 45% when comparing the averages of the first and last surgical procedures (P=0.006). Depth perception showed an improvement close to 35% (P=0.041), and dexterity showed an improvement close to 25% (P=0.011). Total operative time showed trends of improvement, although it was not significant (P=0.158). Autonomy, efficiency, and tissue handling were the only aspects that did not show any noteworthy change (P=0.202, P=0.677, and P=0.456, respectively). CONCLUSIONS: These findings suggest that there are quantifiable gains in laparoscopic skills obtained from training in an animal model. Our results suggest that these benefits also extend to more advanced stages of the learning curve, but it is unclear how far along the learning curve training with animal models provides a clear benefit for the performance of laparoscopic procedures. Future studies are necessary to confirm these findings and better understand the impact of this learning tool on surgical practice.

Can the learning of laparoscopic skills be quantified by the measurements of skill parameters performed in a virtual reality simulator?

Purpose To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). Materials and Methods Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. Results The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. Conclusion The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills. .

Fatores determinantes para a escolha da especialidade médica no Brasil / Defining factors for choosing medical specialty in Brazil

Fundamento. A escolha da especialidade médica é complexa e multifatorial. A importância dos diferentes fatores varia mundialmente e está associada a diferentes valores e sistemas de educação. O objetivo do estudo é identificar os fatores que determinam essa escolha no Brasil. Métodos. Um questionário foi enviado, via internet (eletronic mail), para graduandos dos seis anos do curso de medicina, solicitando informações demográficas e a avaliação de fatores que influenciam na escolha da especialidade médica. Resultados. A idade média foi de 22 anos. Quanto à influência de familiares, 42,5% dos alunos têm pelo menos um médico como parente próximo, sendo as especialidades mais comuns desse parente: Pediatria, Ginecologia e Obstetrícia e Oftalmologia. A quantidade de respondentes que declararam certeza da carreira a ser seguida ao entrar na faculdade foi 19%, enquanto essa certeza foi de 22,2% na ocasião da pesquisa. Afinidade pela especialidade e estilo de vida foram fatores avaliados como importantes ou muito importantes por mais de 95% dos respondentes. Urgência em ganhar dinheiro rápido, tempo curto de residência, alto rendimento inicial e influência familiar foram os fatores avaliados como menos importantes pelos respondentes na escolha de sua especialidade. Quase metade dos respondentes (49,7%) descartaram uma especialidade que cogitaram fortemente, as principais razões para isso foram ter descoberto não ter afinidade pela especialidade pela qualidade de vida. Conclusões. Afinidade e estilo de vida são os fatores determinantes da escolha e da rejeição de especialidade médica em nosso meio.

Background. Choosing medical specialty is complex and depends on multiple factors. The importance of the different factors varies across the world, according to different values and systems of education. The purpose of this study is to identify the determining factors involved in this choice among medical students in Brazil. Methods. A questionnaire was sent by email to medical students from first to sixth year of a selected institution, asking demographic information and the evaluation of factors that may influence the choice of the medical specialty. Results. The mean age was 22 years. Regarding the influence of relatives, 42.5% of the students has at least one physician as a close relative, the most common specialties of this relative were: Pediatrics, Gynecology and Obstetrics and Ophthalmology. 19% of the respondents declared being sure of the career when they entered University, while 22.2% of them were sure about the choice at the occasion of the study. Affinity for the specialty and lifestyle were evaluated as important or very important by more than 95% of respondents. Urge to earn money fast, short time of medical residency, high initial profit and family influence were the factors evaluated as less important by the respondents. Almost half of the respondents (49.7%) rejected a specialty they had strongly cogitated once. The main reasons for this were the lifestyle and the fact that they discovered not having affinity for the specialty. Conclusions. Affinity and medical lifestyle are the defining factors in choosing and rejecting a medical specialty in Brazil.