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1.
J Magn Reson Imaging ; 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38006298

RESUMO

BACKGROUND: Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four-dimensional (4D) flow MRI-derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable. PURPOSE: To assess the reproducibility of 4D flow MRI-derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth. STUDY TYPE: Prospective single-arm study. POPULATION: A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm. FIELD STRENGTH/SEQUENCE: A 3.0 T/Free-breathing 4D flow MRI phase-contrast acquisition with retrospective ECG-gating. ASSESSMENT: Patients underwent two consecutive 4D flow MRI scans 1-week apart. Aortic volumes were segmented from time-averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate. STATISTICAL TESTS: For reproducibility assessment, Bland-Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant. RESULTS: Test-retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity (R = 0.75) and inversely correlated with mean lumen diameter (R = -0.73). No significant associations were found between 4D flow MRI-derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22). DATA CONCLUSION: A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

2.
Eur Heart J ; 41(43): 4181-4187, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-32548624

RESUMO

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (ß-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and ß-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and ß-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and ß-blocker treatment in patients with MFS.


Assuntos
Dissecção Aórtica , Losartan , Síndrome de Marfan , Adulto , Dissecção Aórtica/cirurgia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Seguimentos , Humanos , Losartan/uso terapêutico , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Resultado do Tratamento
3.
Eur J Vasc Endovasc Surg ; 60(1): 49-55, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32331994

RESUMO

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.


Assuntos
Aneurisma Ilíaco/cirurgia , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/mortalidade , Procedimentos Endovasculares/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Aneurisma Ilíaco/epidemiologia , Aneurisma Ilíaco/mortalidade , Aneurisma Ilíaco/patologia , Artéria Ilíaca/patologia , Artéria Ilíaca/cirurgia , Masculino , Países Baixos/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
4.
J Vasc Interv Radiol ; 30(7): 987-994.e4, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109852

RESUMO

PURPOSE: To evaluate whether the biomechanical marker known as rupture risk equivalent diameter (RRED) was superior to the actual abdominal aortic aneurysm (AAA) diameter in estimating future rupture risk in patients who had undergone pre-rupture computed tomography (CT) angiography. MATERIALS AND METHODS: A retrospective study was conducted in 13 patients with ruptured AAAs who had undergone CT angiography before and after rupture between 2001 and 2015. The median time between the 2 scans was 731 days. Biomechanical and geometrical markers such as maximal AAA diameter, peak wall stress (PWS), and RRED were calculated with AAA-dedicated software. The main analyses determined whether RRED was higher than the actual diameter and the threshold diameter for elective surgery (55 mm for men, 50 mm for women) in AAAs before and after rupture. Differences between diameter and biomechanical markers before and after rupture were tested with appropriate statistical tests. RESULTS: RRED before and after rupture was smaller than the actual diameter in 7 of 13 cases. Post-rupture RRED was estimated to be smaller than the threshold diameter for elective repair in 4 cases, again suggesting a low rupture risk. The median PWS before and after rupture was 181.7 kPa (interquartile range [IQR], 152.1-244.2 kPa) and 274.1 kPa (IQR, 172.2-377.2 kPa), respectively. CONCLUSIONS: RRED was smaller than the actual diameter in more than half of pre-rupture AAAs, suggesting a lower rupture risk than estimated with the actual diameter. The results suggest that the currently available biomechanical imaging markers might not be ready for use in clinical practice.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/etiologia , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Tomografia Computadorizada Multidetectores , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/fisiopatologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/fisiopatologia , Fenômenos Biomecânicos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Países Baixos , Modelagem Computacional Específica para o Paciente , Valor Preditivo dos Testes , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estresse Mecânico
5.
Eur J Vasc Endovasc Surg ; 58(6): 813-820, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706741

RESUMO

OBJECTIVE: The aim was to compare peri-operative (30 day and/or in hospital) mortality between women and men in the Netherlands after elective repair of an asymptomatic abdominal aortic aneurysm (AAA). METHODS: This was a retrospective study using data from the Dutch Surgical Aneurysm Audit (DSAA), a mandatory nationwide registry of patients undergoing AAA repair in the Netherlands. Patients who underwent elective open surgical (OSR) or endovascular aneurysm repair (EVAR) of an asymptomatic abdominal aortic aneurysm (AAA) between 2013 and 2018 were included. Absolute risk differences (ARDs) with 95% confidence intervals (CIs) in peri-operative mortality between women and men were estimated. Logistic regression analyses were performed to estimate adjusted odds ratios (ORs) for mortality. Confounders included pre-operative cardiac and pulmonary comorbidity, serum haemoglobin, serum creatinine, type of AAA repair, and AAA diameter. RESULTS: Some 1662 women and 9637 men were included, of whom 507 (30.5%) women and 2056 (21.3%) men underwent OSR (p < .001). Crude peri-operative mortality was 3.01% in women and 1.60% in men (ARD = 1.41%, 95% CI 0.64-2.37). This significant difference was also observed for OSR (ARD = 2.63%, 95% CI 0.43-5.36), but not for EVAR (ARD = 0.36%, 95% CI -0.16 to 1.17). Female sex remained associated with peri-operative mortality after adjusting for confounders (OR = 1.79, 95% CI 1.20-2.65, p = .004), which was similarly observed for OSR (OR = 1.85, 95% CI 1.16-2.94, p = .01), but not for EVAR (OR = 1.46, 95% CI 0.72-2.95, p = .29). CONCLUSIONS: Peri-operative mortality after elective repair of an asymptomatic AAA in the Netherlands is higher in women than in men. This disparity might be explained by the higher peri-operative mortality in women undergoing OSR, because no such difference was found in patients undergoing EVAR. Yet, it is likely that there are unaccounted factors at play since female sex remained significantly associated with mortality after adjusting for type of repair.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Período Perioperatório/estatística & dados numéricos , Enxerto Vascular/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/transplante , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica , Doenças Assintomáticas/mortalidade , Doenças Assintomáticas/terapia , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Endovasculares/métodos , Feminino , Disparidades nos Níveis de Saúde , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Seleção de Pacientes , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Enxerto Vascular/métodos
6.
Eur J Vasc Endovasc Surg ; 57(2): 229-237, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30318394

RESUMO

OBJECTIVES: Diagnosing colonic ischaemia (CI) after ruptured abdominal aortic aneurysm (RAAA) repair is challenging. This study determined the diagnostic value of sigmoidoscopy in patients suspected of CI after RAAA repair. METHODS: This was a retrospective multicentre cohort study. Patients who underwent RAAA repair in three hospitals in Amsterdam, the Netherlands, between 2004 and 2011 (AJAX cohort) were included. Sigmoidoscopies were carried out based on clinical judgment. Endoscopy results were classified as "no ischaemia," "mild CI," or "moderate to severe CI." The surgical diagnosis was classified as "transmural" or "no transmural" CI. The value of sigmoidoscopy was assessed with calculation of positive and negative predictive values (PPV, NPV) with 95% CI for transmural CI. Logistic regression analysis was used to express the association of risk factors with CI as adjusted OR. RESULTS: Transmural CI was diagnosed in 23 of 351 patients (6.6%). Thirteen of sixteen patients (81%) who underwent direct laparotomy for high suspicion of CI indeed had transmural CI. Forty-six patients (13%) underwent sigmoidoscopy. The prevalence of transmural CI was 22% (10/46; 95% CI 12-36%) in these patients. The PPV for transmural CI of "moderate to severe CI" on sigmoidoscopy was 73% (8/11; 95% CI 43-90%). The PPV of "mild CI" on sigmoidoscopy was 11% (2/19; 95% CI 2.9-31%). The NPV of "no ischaemia" on sigmoidoscopy was 100% (95% CI 78-100%). Cardiac comorbidity (OR 3.1, 95% CI 1.19-7.97), low first haemoglobin (OR 0.6, 95% CI 0.47-0.87), and high vasopressor administration (OR 9.4, 95% CI 1.99-44.46) were independently associated with CI. CONCLUSIONS: Sigmoidoscopy increases the likelihood of correctly identifying the presence or absence of transmural CI, especially in patients with a moderate clinical suspicion for CI after RAAA repair.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Colite Isquêmica/diagnóstico , Sigmoidoscopia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colite Isquêmica/etiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Fatores de Risco
7.
J Vasc Surg ; 68(3): 900-915, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30146037

RESUMO

OBJECTIVE: Outcomes after repair of ruptured abdominal aortic aneurysm (RAAA) have improved in the last decade. It is unknown whether this has resulted in a reduction of postoperative bowel ischemia (BI). The primary objective was to determine BI prevalence after RAAA repair. Secondary objectives were to determine its major sequelae and differences between open repair (OR) and endovascular aneurysm repair (EVAR). METHODS: This systematic review (PROSPERO CRD42017055920) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. MEDLINE and Embase were searched for studies published from 2005 until 2018. The methodologic quality of observational studies was assessed with the Methodological Index for Non-Randomized Studies (MINORS) tool. The quality of the randomized controlled trials (RCTs) was assessed with the Cochrane Collaboration's tool for assessing risk of bias. BI prevalence and rates of BI as cause of death, reoperation, and bowel resection were estimated with meta-analyses with a random-effects model. Differences between OR and EVAR were estimated with pooled risk ratios with 95% confidence intervals (CIs). Changes over time were assessed with Spearman rank test (ρ). Publication bias was assessed with a funnel plot analysis. RESULTS: A total of 101 studies with 52,670 patients were included; 72 studies were retrospective cohort studies, 14 studies were prospective cohort studies, 12 studies were retrospective administrative database studies, and 3 studies were RCTs. The overall methodologic quality of the RCTs was high, but that of observational studies was low. The pooled prevalence of BI ranged from of 0.08 (95% CI, 0.07-0.09) in database studies to 0.10 (95% CI, 0.08-0.12) in cohort studies. The risk of BI was higher after OR than after EVAR (risk ratio, 1.79; 95% CI, 1.25-2.57). The pooled rate of BI as cause of death was 0.04 (95% CI, 0.03-0.05), and that of BI as cause of reoperation and bowel resection ranged between 0.05 and 0.07. BI prevalence did not change over time (ρ, -0.01; P = .93). The funnel plot analysis was highly suggestive of publication bias. CONCLUSIONS: The prevalence of clinically relevant BI after RAAA repair is approximately 10%. Approximately 5% of patients undergoing RAAA repair suffer from severe consequences of BI. BI is less prevalent after EVAR than after OR.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Intestinos/irrigação sanguínea , Isquemia/etiologia , Complicações Pós-Operatórias/etiologia , Humanos , Fatores de Risco
8.
Eur J Vasc Endovasc Surg ; 56(1): 120-128, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29685678

RESUMO

OBJECTIVE/BACKGROUND: Incisional hernia is a frequent late complication after open abdominal aortic aneurysm (AAA) repair. We aimed to determine whether prophylactic mesh reinforcement of the abdominal wall at open AAA repair via midline laparotomy reduces the rate of incisional hernia compared to standard sutured closure. METHODS: A systematic review and meta-analysis was carried out in accordance with the PRISMA statement (PROSPERO registration CRD42017072508). Randomised controlled trials (RCTs) comparing prophylactic mesh reinforcement with standard sutured closure were eligible for inclusion. MEDLINE, Embase, and the Cochrane Library were searched. A meta-analysis with a random effects model was carried out to estimate pooled risk ratios (RR) with 95% confidence intervals (CIs) for the incidence of, and re-operation rate for, incisional hernias. Assessments of methodological quality, quality of evidence, and strength of recommendations were done with the Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach. RESULTS: Four RCTs with a total of 388 patients were included in the meta-analysis. Pooled analysis showed that mesh reinforcement significantly reduced the risk of incisional hernia after AAA repair compared with standard sutured closure (RR 0.27, 95% CI 0.11-0.66). The pooled rate of re-operations was not different between groups (RR 0.23, 95% CI 0.11-1.05). Mesh reinforcement did not cause more intra-operative or post-operative complications than sutured closure. The risk of bias in studies was low and the quality of evidence was rated as moderate. CONCLUSION: Prophylactic mesh reinforcement of the abdominal wall after open AAA repair via midline laparotomy significantly reduces the risk of incisional hernia. However, no significant difference in re-operation for incisional hernia was found.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/instrumentação , Aneurisma da Aorta Abdominal/cirurgia , Hérnia Abdominal/prevenção & controle , Hérnia Incisional/prevenção & controle , Telas Cirúrgicas , Técnicas de Sutura , Procedimentos Cirúrgicos Vasculares , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Distribuição de Qui-Quadrado , Hérnia Abdominal/diagnóstico , Hérnia Abdominal/etiologia , Humanos , Hérnia Incisional/diagnóstico , Hérnia Incisional/etiologia , Razão de Chances , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Técnicas de Sutura/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
9.
Eur J Vasc Endovasc Surg ; 55(1): 83-91, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29158067

RESUMO

OBJECTIVES: Loss of muscle mass has been associated with poor survival in several surgical patient populations, including those with an abdominal aortic aneurysm (AAA). We wanted to replicate these findings and assess the association between psoas muscle area (PMA) and survival in patients with an asymptomatic AAA. METHODS: Patients with an asymptomatic infrarenal AAA who underwent computed tomography (CT) scanning between January 1, 2007, and December 31, 2013, were included in this single-centre retrospective cohort study. PMA was measured with thresholding on an axial image at the centre level of the third lumbar vertebra. The lowest tertile of PMA in all patients was used as a cutoff value for a low PMA. Then, in separate analyses for conservatively and surgically managed patients, survival was estimated with the Kaplan-Meier method. Differences in survival between patients with and without a low PMA were tested with the log-rank test. RESULTS: Of 228 patients, 104 were managed conservatively and 124 underwent AAA repair. Seventy-seven patients (62%) had an endovascular repair. In these 228 patients, the median PMA was 16.83 cm2, while the cutoff value for low PMA was 14.56 cm2. Patients who were managed conservatively were more often classified as having low PMA (45/104, 43%, vs. 31/124, 25%; p = .004) and were significantly older (mean 73.44 ± 9.05 years vs. 69.03 ± 7.46 years; p < .001). Low PMA was not associated with survival, either in patients managed conservatively, or in those who underwent AAA repair (p = .512 and p = .311, respectively). CONCLUSIONS: The association between low PMA and poor survival could not be replicated; in this study, low PMA was not associated with survival in patients with an asymptomatic AAA. Further research is recommended before PMA can be used for pre-operative risk stratification.


Assuntos
Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/mortalidade , Doenças Assintomáticas/mortalidade , Músculos Psoas/diagnóstico por imagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/terapia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Músculos Psoas/anatomia & histologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X , Procedimentos Cirúrgicos Vasculares/métodos
10.
Hum Mol Genet ; 24(4): 987-93, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25296916

RESUMO

Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the ion pore. The functional consequences of the identified mutation were studied using whole-cell and single-channel patch recordings. High-resolution analyses at the single-channel level showed that, when open, R1389H CaV2.2 channels carried less current compared with WT channels. Other biophysical channel properties were unaltered in R1389H channels including ion selectivity, voltage-dependent activation or voltage-dependent inactivation. CaV2.2 channels regulate transmitter release at inhibitory and excitatory synapses. Functional changes could be consistent with a gain-of-function causing the observed hyperexcitability characteristic of this unique myoclonus-dystonia-like syndrome associated with cardiac arrhythmias.


Assuntos
Canais de Cálcio Tipo N/genética , Distúrbios Distônicos/genética , Estudos de Associação Genética , Mutação , Potenciais de Ação , Canais de Cálcio Tipo N/metabolismo , Sinalização do Cálcio , Distúrbios Distônicos/diagnóstico , Exoma , Feminino , Ligação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Técnicas de Patch-Clamp , Linhagem , Fenótipo
11.
J Vasc Surg ; 66(6): 1712-1718.e2, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28899568

RESUMO

OBJECTIVE: Acute kidney injury (AKI) is a major complication of ruptured abdominal aortic aneurysm (RAAA). Severe AKI is associated with high morbidity and mortality in the short term. The objective of this study was to determine the association between AKI after RAAA repair and long-term survival. METHODS: We conducted a retrospective cohort study of all patients undergoing RAAA repair in three hospitals between 2004 and 2011. Outcomes were long-term survival after RAAA repair, incidence of postoperative AKI, and chronic dialysis rates. Survival rates were compared between different AKI groups (no AKI, Risk, Injury, Failure) with Kaplan-Meier survival analyses and log-rank tests. Univariable and multivariable Cox regression analyses were carried out to assess the association of survival with AKI, preoperative shock, postoperative shock, and sex. The main analysis focused on the group of patients surviving initial hospital stay. RESULTS: Our study encompassed 362 patients with RAAA. AKI occurred in 267 of 362 patients (74%). At discharge, 267 patients were alive (74%). Median survival in this group was 7.2 years. Survival was not significantly different between the four AKI groups (P = .07). However, the univariable Cox regression analysis demonstrated a significant association between Failure and reduced long-term survival compared with having no AKI (hazard ratio, 1.85; 95% confidence interval, 1.15-2.97). This association did not remain significant after multivariable adjustment. Four patients were discharged with chronic dialysis, and four other patients needed chronic dialysis later after discharge. CONCLUSIONS: This study demonstrates no significant independent association between AKI after RAAA repair and long-term survival. Only a small proportion of patients developed end-stage renal disease at a later stage in life.


Assuntos
Injúria Renal Aguda/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Masculino , Análise Multivariada , Países Baixos/epidemiologia , Alta do Paciente , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Mov Disord ; 30(3): 415-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25648840

RESUMO

BACKGROUND: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been established, indicating genetic heterogeneity. METHODS: Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M-D syndrome, we performed homozygosity mapping combined with exome sequencing in a three-generation M-D family and genetically screened 24 additional patients with M-D. RESULTS: We found co-segregation of the rare missense variant Thr1904Met in the RELN gene. By additional screening of an M-D cohort, we identified co-segregation of RELN variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic RELN mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 SGCE-negative M-D patients carried RELN rare missense variants. CONCLUSION: We propose that RELN mutations contribute to the genetic heterogeneity of M-D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Distúrbios Distônicos/genética , Proteínas da Matriz Extracelular/genética , Saúde da Família , Mutação/genética , Proteínas do Tecido Nervoso/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteína Reelina , Adulto Jovem
14.
BMJ Open ; 9(8): e028858, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375618

RESUMO

INTRODUCTION: The pathophysiology and natural course of abdominal aortic aneurysms (AAAs) are insufficiently understood. In order to improve our understanding, it is imperative to carry out longitudinal research that combines biomarkers with clinical and imaging data measured over multiple time points. Therefore, a multicentre biobank, databank and imagebank has been established in the Netherlands: the 'Pearl Abdominal Aortic Aneurysm' (AAA bank). METHODS AND ANALYSIS: The AAA bank is a prospective multicentre observational biobank, databank and imagebank of patients with an AAA. It is embedded within the framework of the Parelsnoer Institute, which facilitates uniform biobanking in all university medical centres (UMCs) in the Netherlands. The AAA bank has been initiated by the two UMCs of Amsterdam UMC and by Leiden University Medical Center. Participants will be followed during AAA follow-up. Clinical data are collected every patient contact. Three types of biomaterials are collected at baseline and during follow-up: blood (including DNA and RNA), urine and AAA tissue if open surgical repair is performed. Imaging data that are obtained as part of clinical care are stored in the imagebank. All data and biomaterials are processed and stored in a standardised manner. AAA growth will be based on multiple measurements and will be analysed with a repeated measures analysis. Potential associations between AAA growth and risk factors that are also measured on multiple time points can be assessed with multivariable mixed-effects models, while potential associations between AAA rupture and risk factors can be tested with a conditional dynamic prediction model with landmarking or with joint models in which linear mixed-effects models are combined with Cox regression. ETHICS AND DISSEMINATION: The AAA bank is approved by the Medical Ethics Board of the Amsterdam UMC (University of Amsterdam). TRIAL REGISTRATION NUMBER: NCT03320408.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/urina , Bancos de Sangue , Bancos de Tecidos , Adulto , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/patologia , Biomarcadores/sangue , Biomarcadores/urina , Humanos , Imageamento por Ressonância Magnética , Estudos Multicêntricos como Assunto , Países Baixos , Estudos Observacionais como Assunto , Projetos de Pesquisa , Tomografia por Raios X , Urina
15.
Eur J Emerg Med ; 24(1): 49-54, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26225615

RESUMO

BACKGROUND: Earlier studies assessing mortality in polytrauma patients have focused on improving trauma care and reducing complications during hospital stay. The same studies have shown that the complication rate in these patients is high, often resulting in death. The aim of this study was to assess the incidence and causes of mortality in polytrauma patients in our institute. Secondarily, we assessed the donation and autopsy rates and outcome in these patients. PATIENTS AND METHODS: All polytrauma patients (injury severity score≥16) transported to and treated in our institute during a period of 6 years were retrospectively analyzed. We included all patients who died during hospital stay. Prehospital and in-hospital data were collected on patients' condition, diagnostics, and treatment. The chance of survival was calculated according to the TRISS methodology. Patients were categorized according to the complications during treatment and causes of death. Logistic regression analysis was used to design a prediction model for mortality in major trauma. A statistical analysis was carried out. RESULTS: Of the 1073 polytrauma patients who were treated in our institute during the study period, 205 (19.1%) died during hospital stay. The median age of the deceased patients was 58.8 years and 125 patients were men. Their mean injury severity score was 30.4. The most common mechanism of injury involved fall from height, followed by bicycle accidents. Almost 50% of the patients underwent an emergency intervention. Almost 92% of the total population died because of the effects of the accident (primary trauma). Of these, 24% died during primary assessment in the emergency department. Most patients died because of the effects of severe head injury (63.4%), followed by exsanguination (17.6%). The most common type of complications causing death during treatment was respiratory failure (6.3%), followed by multiple organ failure (1.5%). Autopsy was performed in 10.4%. Organ donation procedure was performed in 14.5%. Permission for donation was not provided in almost 20% of the population. CONCLUSION: The mortality rate in polytrauma patients in our institute is considerable and comparable with the international literature. Most patients die because of the effects of the accident (primary trauma). Autopsy and organ donation rates are low in our institution and leave room for substantial improvements in the future.


Assuntos
Traumatismo Múltiplo/mortalidade , Centros de Traumatologia/estatística & dados numéricos , Acidentes por Quedas/mortalidade , Adulto , Autopsia/estatística & dados numéricos , Ciclismo/lesões , Causas de Morte , Traumatismos Craniocerebrais/mortalidade , Exsanguinação/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/etiologia , Países Baixos/epidemiologia , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos
16.
Int J Surg ; 43: 119-125, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28578083

RESUMO

BACKGROUND: A lasagna plot is a graphical tool that can display multiple longitudinal outcomes. To our knowledge, lasagna plots have not been used in publications of surgical studies before. The objective of this study was to demonstrate the results of surgical randomized controlled trials (RCTs) with lasagna plots in order to assess whether this can lead to new observations of the data presented in the original studies. MATERIAL AND METHODS: Lasagna plots were created with R for an RCT comparing endovascular and open repair for patients with a ruptured abdominal aortic aneurysm (AJAX trial), an RCT comparing laparoscopy or open surgery combined with either fast track or standard care for patients with colon cancer (LAFA trial) and an RCT comparing preoperative biliary drainage and early surgery for patients with pancreatic cancer (DROP trial). RESULTS: Regarding the AJAX trial, the original article had reported the rate of outcomes at 30 days after repair in two tables. The plots additionally demonstrated the moments of occurrence, increase and decrease of multiple outcomes such as renal replacement therapy and occurrence of death within one plot. These observations were not presented in the original article. The lasagna plots of the LAFA and DROP trial revealed similar new observations on multiple longitudinal outcomes. CONCLUSION: By revealing new observations of the previously published data, lasagna plots generate new hypotheses and theories regarding the outcomes. As such, lasagna plots may be a useful addition to traditional tables and figures and could improve the interpretation of results.


Assuntos
Procedimentos Cirúrgicos Operatórios , Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Neoplasias do Colo/cirurgia , Procedimentos Endovasculares , Humanos , Laparoscopia , Neoplasias Pancreáticas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Forensic Sci Int ; 257: 29-48, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26284976

RESUMO

BACKGROUND: Post-mortem imaging or virtual autopsy is a rapidly advancing field of post-mortem investigations of trauma victims. In this review we evaluate the feasibility of complementation or replacement of conventional autopsy by post-mortem imaging in trauma victims. MATERIALS AND METHODS: A systematic review was performed in compliance with the PRISMA guidelines. MEDLINE, Embase and Cochrane databases were systematically searched for studies published between January 2008 and January 2014, in which post-mortem imaging was compared to conventional autopsy in trauma victims. Studies were included when two or more trauma victims were investigated. RESULTS: Twenty-six studies were included, with a total number of 563 trauma victims. Post-mortem computer tomography (PMCT) was performed in 22 studies, post-mortem magnetic resonance imaging (PMMRI) in five studies and conventional radiography in two studies. PMCT and PMMRI both demonstrate moderate to high-grade injuries and cause of death accurately. PMCT is more sensitive than conventional autopsy or PMMRI in detecting skeletal injuries. For detecting minor organ and soft tissue injuries, autopsy remains superior to imaging. Aortic injuries are missed frequently by PMCT and PMMRI and form their main limitation. CONCLUSION: PMCT should be considered as an essential supplement to conventional autopsy in trauma victims since it detects many additional injuries. Despite some major limitations, PMCT could be used as an alternative for conventional autopsy in situations where conventional autopsy is rejected or unavailable.


Assuntos
Autopsia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Ferimentos e Lesões/diagnóstico por imagem , Ferimentos e Lesões/patologia , Causas de Morte , Medicina Legal/métodos , Humanos
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