Sex-, Age-, and Race-Related Normal Values of Right Ventricular Diastolic Function Parameters: Data from the World Alliance Societies of Echocardiography Study.

BACKGROUND: Although the assessment of right ventricular (RV) diastolic function is feasible, it has garnered far less momentum for use compared with its left ventricular counterpart. The scarcity of data defining normative RV diastolic function and the fact that implications of RV diastolic dysfunction in different disease states on outcomes are less well known both hinder integration into routine clinical assessment. The aim of this study was to establish normal values of RV diastolic parameters stratified by sex, age, and race using data from the World Alliance Societies of Echocardiography study. METHODS: A subset of 888 normal subjects from the World Alliance Societies of Echocardiography database were analyzed, including measurements of tricuspid valve (TV) inflow E- and A-wave velocities, E-wave deceleration time, and TV annular tissue Doppler e' and a' velocities. Additionally, right atrial (RA) maximal volume and RA peak reservoir strain were measured. Patients were grouped by age (<40, 41-65, and >65 years) and stratified by sex and race. Differences were analyzed using unpaired t tests. RESULTS: Compared with men, women had significantly higher TV e' and E-wave and A-wave velocities, though differences were modest. Increasing age was associated with stepwise lower TV E wave, e' velocity, and TV E/A ratio and higher a' velocity and E/e' ratio. RA peak reservoir strain was also lower, and RA end-systolic volume trended toward being smaller for older age groups. Asian subjects demonstrated significantly higher a' velocities, lower E wave, the smallest RA end-systolic volumes, and the lowest RA peak strain values compared with white subjects of both sexes. CONCLUSIONS: This study provides normal values for parameters used in the assessment of RV diastolic function stratified by race, sex, and age. The results demonstrate significant differences in RV diastolic parameters between age groups, which manifest in both individual parameters and composite ratios of TV inflow and annular velocities. Although limited sex- and race-related differences were also noted, age appears to have the most significant impact on RV diastolic parameters. These findings may aid in refining current normative values.

Racial Differences in Ischaemia/Bleeding Risk Trade-Off during Anti-Platelet Therapy: Individual Patient Level Landmark Meta-Analysis from Seven RCTs

BACKGROUND: Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischemia/bleeding risk trade-off. METHODS: We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335). RESULTS: Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001). CONCLUSION: We suggest that the ischemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischemic risk, while significantly increases the bleeding risk. (AU)

Changes in the tumor necrosis factor-α level after an ultrasound-guided femoral nerve block in elderly patients with a hip fracture / Alterações no nível de TNF-α após bloqueio do nervo femoral guiado por ultrassom em idosos com fratura de quadril

Abstract Background and objectives: An ultrasound guided femoral nerve block is an established analgesic method in patients with a hip fracture. Elevated cytokine levels correlate with poor patient outcomes after surgery. Hence, the aim of the study was to describe the levels of tumor necrosis factor-α after an ultrasound-guided femoral nerve block in elderly patients having a femoral neck fracture. Methods: A total of 32 patients were allocated into two treatment groups: 16 patients (femoral nerve block group; ultrasound-guided femoral nerve block with up to 20 mL of 0.3 mL.kg−1 of 0.5% bupivacaine and intravenous tramadol) and 16 patients (standard management group; up to 3 mL of 0.9% saline in the femoral sheath and intravenous tramadol). Tumor necrosis factor-α and visual analogue scale scores were evaluated immediately before the femoral nerve block and again at 4, 24, and 48 h after the femoral nerve block. All surgery was performed electively after 48 h of femoral nerve block. Results: The femoral nerve block group had a significantly lower mean tumor necrosis factor-α level at 24 (4.60 vs. 8.14, p < 0.001) and 48 h (5.05 vs. 8.56, p < 0.001) after the femoral nerve block, compared to the standard management group. The femoral nerve block group showed a significantly lower mean visual analogue scale score at 4 (3.63 vs. 7.06, p < 0.001) and 24 h (4.50 vs. 5.75, p < 0.001) after the femoral nerve block, compared to the standard management group. Conclusions: Ultrasound-guided femoral nerve block using 0.3 mL.kg−1 of 0.5% bupivacaine up to a maximum of 20 mL resulted in a significant lower tumor necrosis factor-α level.

Resumo Justificativa e objetivos: O bloqueio do nervo femoral guiado por ultrassom é um método analgésico estabelecido em pacientes com fratura de quadril. Níveis elevados de citocinas estão correlacionados com resultados desfavoráveis para o paciente após a cirurgia. Portanto, o objetivo do estudo foi descrever os níveis do fator de necrose tumoral alfa após bloqueio do nervo femoral guiado por ultrassom em pacientes idosos com fratura do colo de fêmur. Métodos: No total, 32 pacientes foram alocados em dois grupos de tratamento: 16 pacientes (grupo bloqueio do nervo femoral; bloqueio do nervo femoral guiado por ultrassom com até 20 mL de bupivacaína a 0,5% (0,3 mL.kg−1) e tramadol intravenoso) e 16 pacientes (grupo tratamento padrão, até 3 mL de solução salina a 0,9% na bainha femoral e tramadol intravenoso). Os escores do fator de necrose tumoral alfa e da Escala Visual Analógica foram avaliados imediatamente antes do bloqueio do nervo femoral e novamente em 4, 24 e 48 horas pós-bloqueio do nervo femoral. Todas as cirurgias foram realizadas de forma eletiva após 48 horas de bloqueio do nervo femoral. Resultados: O grupo bloqueio do nervo femoral teve um nível médio de fator de necrose tumoral alfa significativamente menor em 24 (4,60 vs. 8,14, p < 0,001) e 48 horas (5,05 vs. 8,56, p < 0,001) pós-bloqueio do nervo femoral, comparado com o grupo tratamento padrão. O grupo bloqueio do nervo femoral apresentou uma média significativamente menor no escore da Escala Visual Analógica em 4 (3,63 vs. 7,06, p < 0,001) e 24 horas (4,50 vs. 5,75, p < 0,001) pós-bloqueio do nervo femoral, em comparação com o grupo tratamento padrão. Conclusões: O bloqueio do nervo femoral guiado por ultrassom utilizando 0,3 mL.kg−1 de bupivacaína a 0,5% até o máximo de 20 mL resultou em um nível significativamente menor de fator de necrose tumoral alfa.

[Changes in the tumor necrosis factor-α level after an ultrasound-guided femoral nerve block in elderly patients with a hip fracture]. / Alterações no nível de TNF­α após bloqueio do nervo femoral guiado por ultrassom em idosos com fratura de quadril.

BACKGROUND AND OBJECTIVES: An ultrasound guided femoral nerve block is an established analgesic method in patients with a hip fracture. Elevated cytokine levels correlate with poor patient outcomes after surgery. Hence, the aim of the study was to describe the levels of tumor necrosis factor-α after an ultrasound-guided femoral nerve block in elderly patients having a femoral neck fracture. METHODS: A total of 32 patients were allocated into two treatment groups: 16 patients (femoral nerve block group; ultrasound-guided femoral nerve block with up to 20mL of 0.3mL.kg-1 of 0.5% bupivacaine and intravenous tramadol) and 16 patients (standard management group; up to 3mL of 0.9% saline in the femoral sheath and intravenous tramadol). Tumor necrosis factor-α and visual analogue scale scores were evaluated immediately before the femoral nerve block and again at 4, 24, and 48h after the femoral nerve block. All surgery was performed electively after 48h of femoral nerve block. RESULTS: The femoral nerve block group had a significantly lower mean tumor necrosis factor-α level at 24 (4.60 vs. 8.14, p<0.001) and 48h (5.05 vs. 8.56, p<0.001) after the femoral nerve block, compared to the standard management group. The femoral nerve block group showed a significantly lower mean visual analogue scale score at 4 (3.63 vs. 7.06, p<0.001) and 24h (4.50 vs. 5.75, p<0.001) after the femoral nerve block, compared to the standard management group. CONCLUSIONS: Ultrasound-guided femoral nerve block using 0.3mL.kg-1 of 0.5% bupivacaine up to a maximum of 20mL resulted in a significant lower tumor necrosis factor-α level.

Geohealth: biology based mapping of vector borne disease in the Americas using NASA satellite data / Geosaúde: mapeamento da biologia das doenças vetoriais nas Américas utilizando dados de satélites da NASA

Implementation of a geospatial surveillance and response system data resource for vector borne disease in the Americas (GeoHealth) will be tested using NASA satellite data, geographic information systems and ecological niche modeling to characterize the environmental suitability and potential for spread of endemic and epizootic vector borne diseases. The initial focus is on developing prototype geospatial models for visceral leishmaniasis, an expanding endemic disease in Latin America, and geospatial models for dengue and other Aedes aegypti borne arboviruses (zika, chikungunya), emerging arboviruses with potential for epizootic spread from Latin America and the Caribbean and establishment in North America. Geospatial surveillance and response system open resource data bases and models will be made available, with training courses, to other investigators interested in mapping and modeling other vector borne diseases in the western hemisphere and contributing brokered data to an expanding GeoHealth data resource as part of the NASA AmeriGEOSS initiative.(AU)

A implementação de uma fonte de dados de vigilância e um sistema de resposta geoespacial para doenças transmitidas por vetores nas Américas (GeoHealth) será testada utilizando dados provenientes de satélites da NASA, sistemas de informações geográficas e modelagem do nicho ecológico, para caracterizar a suceptibilidade ambiental e o potencial de dispersão de doenças endêmicas e epizooticas transmitidas por vetores vetores. O foco inicial será o desenvolvimento de protótipos de modelos geoespaciais para a leishmaniose visceral, uma doença endêmica e em expansão na América Latina, e modelos geoespaciais para dengue e outros transmitidos pelo Aedes aegypti (zika, chikungunya), arbovírus emergentes com potencial para disseminação epizoótica pela América Latina e Caribe e estabelecimento na América do Norte. Sistemas de vigilância e resposta geoespacial e modelos de recursos em bases de dados abertas serão diponibilizados, com cursos de treinamento, para outros pesquisadores interessados em mapear e modelar outras doenças transmitidas por vetores no hemisfério ocidental e contribuir intermediando dados para uma fonte de dados GeoHealth em expansão, como parte da Iniciativa AmeriGEOSS, da NASA. (AU)

Geohealth: biology based mapping of vector borne disease in the Americas using NASA satellite data / Geosaúde: mapeamento da biologia das doenças vetoriais nas Américas utilizando dados de satélites da NASA

Implementation of a geospatial surveillance and response system data resource for vector borne disease in the Americas (GeoHealth) will be tested using NASA satellite data, geographic information systems and ecological niche modeling to characterize the environmental suitability and potential for spread of endemic and epizootic vector borne diseases. The initial focus is on developing prototype geospatial models for visceral leishmaniasis, an expanding endemic disease in Latin America, and geospatial models for dengue and other Aedes aegypti borne arboviruses (zika, chikungunya), emerging arboviruses with potential for epizootic spread from Latin America and the Caribbean and establishment in North America. Geospatial surveillance and response system open resource data bases and models will be made available, with training courses, to other investigators interested in mapping and modeling other vector borne diseases in the western hemisphere and contributing brokered data to an expanding GeoHealth data resource as part of the NASA AmeriGEOSS initiative.

A implementação de uma fonte de dados de vigilância e um sistema de resposta geoespacial para doenças transmitidas por vetores nas Américas (GeoHealth) será testada utilizando dados provenientes de satélites da NASA, sistemas de informações geográficas e modelagem do nicho ecológico, para caracterizar a suceptibilidade ambiental e o potencial de dispersão de doenças endêmicas e epizooticas transmitidas por vetores vetores. O foco inicial será o desenvolvimento de protótipos de modelos geoespaciais para a leishmaniose visceral, uma doença endêmica e em expansão na América Latina, e modelos geoespaciais para dengue e outros transmitidos pelo Aedes aegypti (zika, chikungunya), arbovírus emergentes com potencial para disseminação epizoótica pela América Latina e Caribe e estabelecimento na América do Norte. Sistemas de vigilância e resposta geoespacial e modelos de recursos em bases de dados abertas serão diponibilizados, com cursos de treinamento, para outros pesquisadores interessados em mapear e modelar outras doenças transmitidas por vetores no hemisfério ocidental e contribuir intermediando dados para uma fonte de dados GeoHealth em expansão, como parte da Iniciativa AmeriGEOSS, da NASA.

Geohealth: biology based mapping of vector borne disease in the Americas using NASA satellite data / Geosaúde: mapeamento da biologia das doenças vetoriais nas Américas utilizando dados de satélites da NASA

Implementation of a geospatial surveillance and response system data resource for vector borne disease in the Americas (GeoHealth) will be tested using NASA satellite data, geographic information systems and ecological niche modeling to characterize the environmental suitability and potential for spread of endemic and epizootic vector borne diseases. The initial focus is on developing prototype geospatial models for visceral leishmaniasis, an expanding endemic disease in Latin America, and geospatial models for dengue and other Aedes aegypti borne arboviruses (zika, chikungunya), emerging arboviruses with potential for epizootic spread from Latin America and the Caribbean and establishment in North America. Geospatial surveillance and response system open resource data bases and models will be made available, with training courses, to other investigators interested in mapping and modeling other vector borne diseases in the western hemisphere and contributing brokered data to an expanding GeoHealth data resource as part of the NASA AmeriGEOSS initiative.(AU)

A implementação de uma fonte de dados de vigilância e um sistema de resposta geoespacial para doenças transmitidas por vetores nas Américas (GeoHealth) será testada utilizando dados provenientes de satélites da NASA, sistemas de informações geográficas e modelagem do nicho ecológico, para caracterizar a suceptibilidade ambiental e o potencial de dispersão de doenças endêmicas e epizooticas transmitidas por vetores vetores. O foco inicial será o desenvolvimento de protótipos de modelos geoespaciais para a leishmaniose visceral, uma doença endêmica e em expansão na América Latina, e modelos geoespaciais para dengue e outros transmitidos pelo Aedes aegypti (zika, chikungunya), arbovírus emergentes com potencial para disseminação epizoótica pela América Latina e Caribe e estabelecimento na América do Norte. Sistemas de vigilância e resposta geoespacial e modelos de recursos em bases de dados abertas serão diponibilizados, com cursos de treinamento, para outros pesquisadores interessados em mapear e modelar outras doenças transmitidas por vetores no hemisfério ocidental e contribuir intermediando dados para uma fonte de dados GeoHealth em expansão, como parte da Iniciativa AmeriGEOSS, da NASA.(AU)

Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting

BACKGROUND:Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear.OBJECTIVES:The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs.METHODS:RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded.

Outcomes After Percutaneous Coronary Intervention or Bypass Surgery in Patients With Unprotected Left Main Disease.

BACKGROUND: Currently available randomized data on the comparison between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for the treatment of unprotected left main coronary disease (LMD) lacks statistical power due to low numbers of patients enrolled. OBJECTIVES: This study assessed long-term outcomes of PCI and CABG for the treatment of LMD in specific subgroups according to disease anatomic complexity. METHODS: We conducted a pooled analysis of individual patient-level data of the LMD patients included in the PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) and SYNTAX (Synergy Between PCI With TAXUS and Cardiac Surgery) trials. Incidences of major adverse cardiac events were assessed at 5 years follow-up. RESULTS: Study population comprised 1,305 patients. The incidence of major adverse cardiac and cerebrovascular events at 5 years was 28.3% in the PCI group and 23.0% in the CABG group (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.01 to 1.55; p = 0.045). This difference is mainly driven by a higher rate of repeat revascularization associated with PCI (HR: 1.85; 95% CI: 1.38 to 2.47; p < 0.001). The 2 strategies showed similar rates of the safety composite endpoint of death, myocardial infarction, or stroke (p = 0.45). In patients with isolated LM or LM + 1-vessel disease, PCI was associated with a 60% reduction in all-cause mortality (HR: 0.40; 95% CI: 0.20 to 0.83; p = 0.029) and 67% reduction in cardiac mortality (HR: 0.33; 95% CI: 0.12 to 0.88; p = 0.025) when compared with CABG. CONCLUSIONS: In patients with unprotected LMD, CABG, and PCI result in similar rates of the safety composite endpoint of death, myocardial infarction, or stroke. In patients with isolated LM or LM + 1-vessel disease, PCI is associated with lower all-cause and cardiac mortality when compared to CABG.

Use of a wiki as an interactive teaching tool in pathology residency education: Experience with a genomics, research, and informatics in pathology course.

BACKGROUND: The need for informatics and genomics training in pathology is critical, yet limited resources for such training are available. In this study we sought to critically test the hypothesis that the incorporation of a wiki (a collaborative writing and publication tool with roots in "Web 2.0") in a combined informatics and genomics course could both (1) serve as an interactive, collaborative educational resource and reference and (2) actively engage trainees by requiring the creation and sharing of educational materials. MATERIALS AND METHODS: A 2-week full-time course at our institution covering genomics, research, and pathology informatics (GRIP) was taught by 36 faculty to 18 second- and third-year pathology residents. The course content included didactic lectures and hands-on demonstrations of technology (e.g., whole-slide scanning, telepathology, and statistics software). Attendees were given pre- and posttests. Residents were trained to use wiki technology (MediaWiki) and requested to construct a wiki about the GRIP course by writing comprehensive online review articles on assigned lectures. To gauge effectiveness, pretest and posttest scores for our course were compared with scores from the previous 7 years from the predecessor course (limited to informatics) given at our institution that did not utilize wikis. RESULTS: Residents constructed 59 peer-reviewed collaborative wiki articles. This group showed a 25% improvement (standard deviation 12%) in test scores, which was greater than the 16% delta recorded in the prior 7 years of our predecessor course (P = 0.006). CONCLUSIONS: Our use of wiki technology provided a wiki containing high-quality content that will form the basis of future pathology informatics and genomics courses and proved to be an effective teaching tool, as evidenced by the significant rise in our resident posttest scores. Data from this project provide support for the notion that active participation in content creation is an effective mechanism for mastery of content. Future residents taking this course will continue to build on this wiki, keeping content current, and thereby benefit from this collaborative teaching tool.

Crystallization and preliminary X-ray diffraction analysis of importin-alpha complexed with NLS peptidomimetics.

Importin-alpha is the nuclear import receptor that recognizes cargo proteins with nuclear localization sequences (NLSs). The study of NLS peptidomimetics can provide a better understanding of the requirements for the molecular recognition of cargo proteins by importin-alpha, and potentially engender a large number of applications in medicine. Importin-alpha was crystallized with a set of six NLS peptidomimetics, and X-ray diffraction data were collected in the range 2.1-2.5 A resolution. Preliminary electron density calculations show that the ligands are present in the crystals.

Pentoxifylline downregulares nitric oxide and tumor necrosis factor-a induced by mycobacterial lipoarabinomannan in a macrophage cell line

Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.

Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine macrophages: effects of interferon-B and taurine-chloramine

We examined the effects of interferon beta (IFN-beta) on the production of liporabinomannan (LAM)-induced nitric oxide (NO) in peritoneal macrophages from low-responder and high-responder (C3H/HeJ and C3H/OuJ) mice. NO was produced in a dose response when induced by lipo-polysaccharide (LPS) or LAM plus interferon gamma (IFN-gamma) or IFN-beta in both high- and low-responder mice. In contrast to IFN-gamma, both high- and low-responder mice failed to induce nitrite production when IFN-beta was added, except at a high concentration of IFN-beta. Tau-Cl (0.5 mM) inhibited NO production about 50% in the high-responder strain when cells were activated with LPS or LAM in combination with either IFN-beta or IFN-gamma, and almost abolished NO production at 1.0 mM. In the low-responder strain, Tau-Cl (0.5 mM) significantly inhibited NO production when cells were activated with IFN-gamma or IFN-beta in addition to LPS or LAM, but did not completely inhibit NO production at 1.0 mM. Tau-Cl appears to play a potent role in regulating inflammatory reaction-induced bacterial or mycobacterial organisms. These data indicate a pivotal role for IFN-gamma and IFN-beta for the production of LPS and LAM initiated NO in peritoneal macrophages from low-responder (C3H/HeJ) mice.

Routine radiographic screening of the chest in pregnant women: is it indicated?

Experience with routine antepartum chest radiographic screening from July 1, 1976, through June 30, 1977, in a city-county hospital which serves a predominantly black indigent population was reviewed. The 5422 routine screening chest radiographs produced an extremely low yield of pathology (11 cases), and only 3 of the 11 cases were not suspected from the history of physical examination. Only 2 cases of active pulmonary tuberculosis were discovered, and both patients were recent immigrants from countries with a much higher incidence of tuberculosis. This low case finding probably reflects the general decline in incidence of pulmonary tuberculosis in the United States and suggests that routine screening chest radiographs (done primarily to exclude tuberculosis) are not longer indicated in our pregnant population (AU)