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Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.
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Proteínas de Membrana , Neoplasias , Biotecnologia , Biologia Computacional , Bases de Dados Factuais , ÁguaRESUMO
BACKGROUND: To investigate the potential of intravenously administered porcine recombinant interferon-ß1a (IFN-ß1a) for myocardial protection during acute ischemia-reperfusion (IR) injury in an experimental animal model. METHODS: Twenty-two piglets (mean ± standard deviation, 26.7 ± 1.65 kg) were assigned to either the IFN group (n = 12) or the control group (n = 10). IR injury was induced by occluding the distal left descending coronary artery for 30 minutes, with a reperfusion period of 6 h. In the IFN group, the animals received 12.5 µg IFN-ß1a intravenously repeatedly; the control group received saline solution. The levels of interleukin-6 (IL-6) and cardiac troponin I (TnI) were measured, and the amount of myocardial damage was quantified by analyzing myocardial apoptosis and the mean fluorescence intensity (MFI) of methylene blue-stained cardiac tissue. RESULTS: In the IFN group, significantly more premature deaths occurred compared with the control group (25% versus 17%, P = .013). Between the groups, the mean heart rate was higher in the IFN group (102 ± 22 versus 80 ± 20 beats per minute, P = .02). IL-6 and TnI levels were comparable between the groups, with no significant difference, and there was no difference between the study groups in myocardial apoptosis in the infarcted myocardium. The percentage of MFI differed significantly between the IFN and control groups (90.75% ± 4.90% versus 96.02% ± 2.73%, P = .01). CONCLUSION: In this acute IR injury animal model, IFN-ß1a did not protect the myocardium from IR injury, but rather increased some of the unfavorable outcomes studied.
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Interferon beta-1a/administração & dosagem , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/patologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Apoptose , Modelos Animais de Doenças , Injeções Intravenosas , Infarto do Miocárdio/diagnóstico , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/etiologia , SuínosRESUMO
Objectives. To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design. A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality. Results. There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups. Conclusions. In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.
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Sistema ABO de Grupos Sanguíneos , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Procedimentos Cirúrgicos Vasculares , Doença Aguda , Idoso , Dissecção Aórtica/sangue , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/sangue , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Cognitivas Pós-Operatórias/mortalidade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Países Escandinavos e Nórdicos/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
OBJECTIVE: The prevalence of intracranial aneurysms (IAs) is higher in patients with aortic aneurysms. However, there are lack of studies investigating prevalence of thoracic aortic aneurysms (TAAs) in patients with IAs. The objective of this study was to evaluate the prevalence and risk factors for thoracic aortic dilatations (TADs) and TAAs in patients with IAs. METHODS: We retrospectively reviewed data from 1777 patients with diagnosed IAs at our institution between 2006 and 2016. We included 411 patients with saccular IAs and available imaging studies (computed tomography or magnetic resonance imaging) of all thoracic aortic segments. TAD was defined according to age- and sex-matched normograms, and TAA as a diameter of greater than 4.0 cm. RESULTS: A total of 83 patients (20%) had TAD or TAA. The prevalence of TADs and TAAs were 18% (n = 74) and 8% (n = 31) without significant difference between unruptured and ruptured IAs (P = .7). Of the 74 patients with TAD, 22 (30%) had multiple TADs and 66% of the TADs located in the aortic arch. Older age (odds ratio [OR], 1.04; P = .006), rheumatic disease (OR, 4.73; P = .009) and alcohol abuse (OR, 4.77; P = .01) were significant risk factors for TAD/TAA. CONCLUSIONS: The prevalence of TADs and TAAs is considerably greater in patients with IAs compared with reports from the general population, suggesting that IAs might be associated with aortopathy and might share a similar pathogenetic background with TADs/TAAs. Especially patients with IAs and a history of rheumatic disease and/or alcohol abuse are at high risk for TADs/TAAs.
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Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/epidemiologia , Doenças da Aorta/epidemiologia , Aneurisma Intracraniano/complicações , Idoso , Doenças da Aorta/patologia , Dilatação Patológica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Average CT has been shown to be more accurate than conventional helical CT in quantitation of the PET data. The risk of CT irradiation of a cardiac implantable electronic device (CIED) causing an adverse event is low and is generally outweighed by the clinical benefit of a medically indicated examination. However, irradiation of CIED over one breath cycle in cine CT scan for average CT could impose risks on a patient who is pacing dependent. The purpose of this study was to demonstrate that low-dose average CT can be safe for CIED. METHODS: A Medtronic CIED of model Protecta VR was submerged in a saline bath for a series of 4-s cine CT scans on a GE CT scanner programmed to deliver a 2-cm-wide radiation at a dose rate of 0.9 to 41.2 mGy/s to the CIED. The number of over-sensings was recorded as the interference of radiation to the CIED. RESULTS: Dose rates ≥ 1.9 mGy/s caused over-sensing. The higher the dose rate, the more over-sensings there were. The lowest dose rate of 0.9 mGy/s did not cause any over-sensing. CONCLUSIONS: Low-dose average CT at 0.9 mGy/s can be safe for a CIED patient who is pacing dependent.
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Desfibriladores Implantáveis/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Tomografia Computadorizada por Raios X/efeitos adversos , Idoso de 80 Anos ou mais , Simulação por Computador , Desenho de Equipamento , Tomografia Computadorizada Quadridimensional , Humanos , Masculino , Segurança do Paciente , Reprodutibilidade dos Testes , Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagemRESUMO
The aims of the study are to describe the long-term survival of patients undergoing primary open ascending aortic surgery and to portray the evolution of aortic surgery during six decades in a single centre. Included were all 614 patients who underwent primary ascending aortic surgery in 1968-2014 at one Nordic university hospital. Patients were identified and data were collected from patient records and surgical logs. Mortality data were acquired from the national registry. Median follow-up was 11.2 years using reverse Kaplan-Meier method. Overall 30-day survival was 91.2% and for 30-day survivor rates were 86.9, 77.6, 52.1, 38.3 and 26.7% at 5, 10, 20, 30 and 40 years. There was no significant difference in long-term survival for 30-day survivors (p = 0.105) between patients treated emergently for dissection/rupture and electively (mainly ascending aortic aneurysms). On Cox regression era of surgery (p = 0.006), increasing age (p < 0.001) and indication (p < 0.001) were predictors of 30-day mortality. Arch involvement indicated twofold risk (HR 2.09, p = 0.05) compared to non-arch involved. Only increasing age (p < 0.001) predicted long-term mortality. There was a sixfold risk of 30-day mortality in the earliest era compared to the latest (p = 0.03). After the early postoperative phase following ascending aortic surgery, the surgical indication and urgency of the index operation have no significant impact on long-term survival. The very long term survival after ascending aortic surgery is excellent for 30-day survivors and improved through the era. Surgical treatment has improved and perioperative mortality has decreased significantly in 47 years.
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Aorta/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Previsões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Feminino , Finlândia/epidemiologia , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90-54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.
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OBJECTIVE: The optimal medical therapy after surgical aortic valve replacement (SAVR) for aortic stenosis remains unknown. Renin-angiotensin system (RAS) inhibitors could potentially improve cardiac remodelling and clinical outcomes after SAVR. METHODS: All patients undergoing SAVR due to aortic stenosis in Sweden 2006-2020 and surviving 6 months after surgery were included. The primary outcome was major adverse cardiovascular events (MACEs; all-cause mortality, stroke or myocardial infarction). Secondary endpoints included the individual components of MACE and cardiovascular mortality. Time-updated adjusted Cox regression models were used to compare patients with and without RAS inhibitors. Subgroup analyses were performed, as well as a comparison between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). RESULTS: A total of 11 894 patients (mean age, 69.5 years, 40.4% women) were included. Median follow-up time was 5.4 (2.7-8.5) years. At baseline, 53.6% of patients were dispensed RAS inhibitors, this proportion remained stable during follow-up. RAS inhibition was associated with a lower risk of MACE (adjusted hazard ratio (aHR) 0.87 (95% CI 0.81 to 0.93), p<0.001), mainly driven by a lower risk of all-cause death (aHR 0.79 (0.73 to 0.86), p<0.001). The lower MACE risk was consistent in all subgroups except for those with mechanical prostheses (aHR 1.07 (0.84 to 1.37), p for interaction=0.040). Both treatment with ACE inhibitors (aHR 0.89 (95% CI 0.82 to 0.97)) and ARBs (0.87 (0.81 to 0.93)) were associated with lower risk of MACE. CONCLUSION: The results of this study suggest that medical therapy with an RAS inhibitor after SAVR is associated with a 13% lower risk of MACE and a 21% lower risk of all-cause death.
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Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Feminino , Idoso , Masculino , Valva Aórtica/cirurgia , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Anti-Hipertensivos/uso terapêutico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/efeitos adversos , Fatores de RiscoRESUMO
AIMS: Early identification of patients with increased bleeding risk increases the possibility to individualize antithrombotic treatment. We validated the PRECISE-DAPT score, originally developed to estimate bleeding risk in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), in coronary artery bypass grafting (CABG) patients. METHODS AND RESULTS: All patients who underwent first time, isolated CABG in Sweden 2009-2020 and survived until discharge were included. The four-item PRECISE-DAPT score, based on age, estimated glomerular filtration rate, preoperative haemoglobin concentration, and previous spontaneous bleeding, was calculated in patients discharged on DAPT (n = 6 838), or antiplatelet monotherapy (n = 15 406). High bleeding risk was defined as a score ≥ 25 in accordance with previous studies and major bleeding as hospitalization due to bleeding. Associations were assessed by C-statistics and Cox regression models.Major bleeding occurred during the first postoperative year in 130 patients (1.9%) in the DAPT group, and in 197 patients (1.3%) in the monotherapy group. The score identified 32.9% of the patients in the DAPT group and 38.2% in monotherapy groups as having high bleeding risk. The area under the ROC-curve for the score was 0.67 (95%CI 0.62-0.72) for DAPT and 0.71 (0.67-0.74) for monotherapy. The hazard ratio for high bleeding risk vs. very low risk was 4.14 (2.07-8.26) for DAPT patients, and 4.95 (2.61-9.39) for monotherapy patients, both p < 0.001. CONCLUSIONS: The PRECISE-DAPT identifies patients with increased risk for major bleeding after discharge following CABG with moderate accuracy. The accuracy is comparable to what previously has been reported for patients after PCI.
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OBJECTIVE: To investigate the association between intracranial aneurysms (IAs) and thoracic aortic diameter. METHODS: This observational cohort study examined thoracic aortic diameters in patients with IA. Patients were categorized by IA size (<7 mm and ≥7 mm) and IA status (ruptured/unruptured) based on radiologic findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses. RESULTS: A total of 409 patients were included. Mean age was 60 (±11.7) years and 63% were women. Thoracic aortic diameters were greater among patients who had an IA ≥7 mm versus IA <7 mm (P < 0.05). In the univariate analysis, the diameter of the ascending aorta (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.129 per 1 mm; P = 0.002), aortic arch (OR, 1.10; 95% CI, 1.04-1.15 per 1 mm; P < 0.001), and descending aorta (OR, 1.10; 95% CI, 1.03-1.16 per 1 mm; P = 0.003) were associated with IAs ≥7 mm. In the multivariable regression model, larger ascending aorta (OR, 1.09; 95% CI, 1.01-1.17 per 1 mm; P = 0.018), aortic arch (OR, 1.12; 95% CI, 1.02-1.22 per 1 mm; P = 0.013), and descending aorta (OR, 1.20; 95% CI, 1.08-1.33 per 1 mm; P < 0.001) were associated with ruptured IA. CONCLUSIONS: Greater thoracic aortic diameters are associated with a higher risk of IA being larger than 7 mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides a basis for future considerations regarding screening and risk management.
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Aneurisma Intracraniano , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fatores de Risco , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/complicações , Estudos Retrospectivos , Estudos de Coortes , Aorta Torácica/diagnóstico por imagemRESUMO
OBJECTIVES: The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort. METHODS: All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006-2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities. RESULTS: A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71-0.83). P < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64-0.76)], P < 0.001. The results were consistent in all subgroups. CONCLUSIONS: The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Inibidores de Hidroximetilglutaril-CoA Redutases , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/cirurgia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Fatores de RiscoRESUMO
OBJECTIVE: The objective of this study was to evaluate the association of statin use after coronary artery bypass grafting (CABG) and long-term adverse events in a large population-based, nationwide cohort. METHODS: All 35,193 patients who underwent first-time isolated CABG in Sweden from 2006 to 2017 and survived at least 6 months after surgery were included. Individual patient data from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and 4 other nationwide registries were merged. Multivariable Cox regression models adjusted for age, sex, comorbidities, and time-updated treatment with other secondary preventive medications were used to evaluate the associations between statin treatment and outcomes. The primary end point was major adverse cardiovascular events (MACE). Median follow-up time to MACE was 5.3 (interquartile range, 2.5-8.2) years. RESULTS: Statins were dispensed to 95.7% of the patients six months after discharge and to 78.9% after 10 years. At baseline, 1.4% of patients were prescribed low-, 57.6% intermediate-, and 36.7% high-dose statins. Ongoing statin treatment was associated with markedly reduced risk of MACE (adjusted hazard ratio [aHR], 0.56 [95% CI, 0.53-0.59]), all-cause mortality (aHR, 0.53 [95% CI, 0.50-0.56]), cardiovascular death (aHR, 0.54 [95% CI, 0.50-0.59]), myocardial infarction (aHR, 0.61 [95% CI, 0.55-0.69]), stroke (aHR, 0.66 [95% CI, 0.59-0.73]), new revascularization (aHR, 0.79 [95% CI, 0.70-0.88]), new angiography (aHR, 0.81 [95% CI, 0.74-0.88]), and dementia (aHR, 0.74 [95% CI, 0.65-0.85]; all P < .01), irrespective of the statin dose. CONCLUSIONS: Ongoing statin use was associated with a markedly reduced incidence of adverse events and mortality after CABG. Initiating and maintaining statin medication is essential in CABG patients.
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Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Prevenção Secundária , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/etiologia , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Introduction: Sustained HIV viral suppression is the ultimate goal of HIV treatment. African American/Black and Latino persons with HIV (PWH) in the United States are less likely than their White peers to achieve and sustain viral suppression. To address these disparities, we developed a "low-touch" behavioral intervention drawing on motivational interviewing and behavioral economics. The intervention had three main components: (1) a motivational interviewing counseling session, (2) 16 weeks of automated text messages and quiz questions about HIV management, where participants earned points by answering quiz questions, and 3) a lottery prize, based on viral suppression status, number of points earned, and chance (max. $275). Materials and methods: The intervention was tested in a pre-test/post-test design. The present pilot study used mixed methods to explore the intervention's feasibility, acceptability, impact, and ways it could be improved. Participants engaged in a baseline assessment, qualitative interview, and two structured follow-up assessments over an 8-month period, and provided laboratory reports to document HIV viral load. We carried out descriptive quantitative analyses. Qualitative data were analyzed using a directed content analysis approach. Data integration was carried out using the joint display method. Findings: Participants (N = 40) were 50 years old, on average (SD = 11), and approximately half (58%) were male. Close to two-thirds (68%) were African American/Black and 32% were Latino. Participants were diagnosed with HIV 22 years ago on average (SD = 8). The intervention was feasible (e.g., mean number of quiz questions answered = 13/16) and highly acceptable. While not powered to assess efficacy, the proportion with suppressed HIV viral load increased from baseline to follow-up (46% participants at the first, 52% participants at the second follow-up evidenced HIV viral suppression). In qualitative analyses, perspectives included that overall, the intervention was acceptable and useful, it was distinct from other programs, lottery prizes were interesting and appreciated but not sufficient to motivate behavior change, and the structure of lottery prizes was not sufficiently clear. Regarding data integration, qualitative data shed light on and extended quantitative results, and added richness and context. Conclusion: This low-touch intervention approach is sufficiently promising to warrant refinement and study in future research.
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Infecções por HIV , Entrevista Motivacional , Economia Comportamental , Feminino , Infecções por HIV/terapia , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Projetos Piloto , Estados Unidos , Carga ViralRESUMO
OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated. CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
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Dissecção Aórtica , Lua , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , Estudos Cross-Over , Humanos , Incidência , Estudos Retrospectivos , RiscoRESUMO
Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54-0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68-0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.
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Dissecção Aórtica , Férias e Feriados , Humanos , Incidência , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , CidadesRESUMO
We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤-5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
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Aneurisma Aórtico , Dissecção Aórtica , Humanos , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/cirurgia , Incidência , Temperatura , Estudos Retrospectivos , Fatores de Risco , Doença Aguda , Resultado do Tratamento , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , Temperatura Alta , Temperatura BaixaRESUMO
OBJECTIVES: Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients. METHODS: The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014. RESULTS: Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P < 0.001), syncope (30.6% vs 17.6%, P < 0.001), cardiogenic shock (33.1% vs 20.7%, P < 0.001) and pericardial tamponade (25.9% vs 14.7%, P < 0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P = 0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P < 0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P < 0.001). CONCLUSIONS: Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
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Aneurisma Aórtico , Dissecção Aórtica , Acidente Vascular Cerebral , Doença Aguda , Dissecção Aórtica/complicações , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
OBJECTIVES: Our goal was to compare short- and midterm outcomes after coronary artery bypass grafting (CABG) using 2 different revascularization strategies. METHODS: A total of 6895 patients were included who had CABG in Sweden from 2009 to 2015 using the left internal mammary artery to the left anterior descending artery and either a single sequential saphenous vein graft connecting the left and right coronary territories to the aorta (snake graft, n = 2122) or separate vein grafts to both territories (n = 4773). Data were obtained from the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) and the Swedish Patient Registry. The groups were compared using adjusted logistic regression for short-term (30-day) and Cox regression and flexible parametric survival models for midterm outcomes. Primary outcome was a composite of all-cause mortality, myocardial infarction (MI), reangiography and new revascularization. The median follow-up time was 35 months. RESULTS: At 30 days, the incidences of the composite end point [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.03-1.68; P = 0.03] and reangiography (OR 1.51, 95% CI 1.07-2.14; P = 0.02) were higher in the snake group. There was also a trend towards higher mortality (OR 1.47, 95% CI 0.97-2.22; P = 0.07). The event rates during the complete follow-up period were 6.5 (5.9-7.2) and 5.7 (5.3-6.1) per 100 person-years for the snake group and the separate vein group, respectively. At the midterm follow-up, no significant difference between the groups could be shown for the composite end point [hazard ratio (HR) 1.08, 95% CI 0.95-1.22; P = 0.24], mortality (HR 0.95, 95% CI 0.79-1.14; P = 0.56), MI (HR 1.11, 95% CI 0.88-1.41; P = 0.39) or new revascularization (HR 1.19, 95% CI 0.94-1.50; P = 0.15), whereas reangiography remained more common in the snake group (HR 1.25, 95% CI 1.05-1.48; P = 0.01). CONCLUSIONS: Snake grafts were associated with a higher rate of early postoperative complications, possibly reflecting a more demanding surgical technique, whereas midterm outcomes were comparable. Based on these data, one strategy cannot be recommended over the other.
Assuntos
Ponte de Artéria Coronária/métodos , Veia Safena/transplante , Idoso , Estudos de Coortes , Ponte de Artéria Coronária/mortalidade , Doença das Coronárias/mortalidade , Doença das Coronárias/cirurgia , Feminino , Humanos , Masculino , Artéria Torácica Interna/transplante , Sistema de Registros , Análise de Sobrevida , Suécia , Resultado do TratamentoRESUMO
BACKGROUND: Aortic dissection type A requires immediate surgery. In general surgery populations, patients operated on during weekends have higher mortality rates compared with patients whose operations occur on weekdays. The weekend effect in aortic dissection type A has not been studied in detail. METHODS: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) registry includes data for 1,159 patients who underwent type A dissection surgery at 8 Nordic centers during 2005 to 2014. This study is based on data relating to surgery conducted during weekdays versus weekends and starting between 8:00 am and 8:00 pm ("daytime") versus from 8:00 pm to 8:00 am ("nighttime"), as well as time from symptoms, admittance, and diagnosis to surgery. The influence of timing of surgery on the 30-day mortality rate was assessed using logistic regression analysis. RESULTS: The 30-day mortality was 18% (204 of 1,159), with no difference in mortality between surgery performed on weekdays (17% [150 of 889]) and on weekends (20% [54 of 270], p = 0.45), or during nighttime (19% [87 of 467]) versus daytime (17% [117 of 680], p = 0.54). Time from symptoms to surgery (median 7.0 hours vs 6.5 hours, p = 0.31) did not differ between patients who survived and those who died at 30 days. Multivariable regression analysis of risk factors for 30-day mortality showed no weekend effect (odds ratio, 1.04; 95% confidence interval, 60.67 to 1.60; p = 0.875), but nighttime surgery was a risk factor (odds ratio, 2.43; 95% confidence interval, 1.29 to 4.56; p = 0.006). CONCLUSIONS: The 30-day mortality in surgical repair of aortic dissection type A was not significantly affected by timing of surgery during weekends versus weekdays. Nighttime surgery seems to predict increased 30-day mortality, after correction for other risk factors.
Assuntos
Plantão Médico , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Sistema de Registros , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Causas de Morte , Estudos de Coortes , Bases de Dados Factuais , Tratamento de Emergência/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Países Escandinavos e Nórdicos , Análise de Sobrevida , Fatores de TempoRESUMO
AIM OF THE STUDY: Patients presenting with acute type A aortic dissection (ATAAD) and cardiac arrest before surgery are considered to have very poor prognosis, but limited data is available. We used a large database to evaluate the outcome of ATAAD patients with a cardiac arrest before surgery. METHODS: We evaluated 1154 surgically treated ATAAD patients from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database between 2005 and 2014. Patients with (n = 44, 3.8%) and without preoperative cardiac arrest were compared and variables univariably associated with mortality in the cardiac arrest group were identified. Median follow-up time was 2.7 years (interquartile range 0.5-5.5). RESULTS: Thirty-day mortality in the arrest and non-arrest group was 43.2% and 16.6%, respectively (odds ratio [OR] 3.83, CI 2.06-7.09; P < 0.001). In the nine patients with ongoing cardiopulmonary resuscitation when cardiopulmonary bypass was initiated, five died intraoperatively and one died after 65 days. In patients surviving the operation, stroke was significantly more common in the arrest group (48.4% vs 18.2%; OR 4.21, CI 2.05-8.67; P < 0.001). In total, 50.0% (22/44) of the arrest patients survived to the end of follow-up. Non-survivors in the arrest group more often had DeBakey type I dissection, cardiac tamponade, cardiac malperfusion and higher preoperative serum lactate (all P < 0.05). CONCLUSIONS: Early mortality and complications after ATAAD surgery in patients with a preoperative cardiac arrest are high, but mid-term outcome after surviving the initial period is acceptable. Preoperative cardiac arrest should not be considered an absolute contraindication for a surgical ATAAD repair.