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1.
Eur J Intern Med ; 119: 99-108, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37689549

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in around 90% of the patients; also 2% of patients harbor pathogenic variants at SMAD4 and GDF2. Importantly, the genetic cause of 8% of patients with clinical HHT remains unknown. Here, we present new putative genetic drivers of HHT. METHODS: To identify new HHT genetic drivers, we performed exome sequencing of 19 HHT patients and relatives with unknown HHT genetic etiology. We applied a multistep filtration strategy to catalog deleterious variants and prioritize gene candidates based on their known relevance in endothelial cell biology. Additionally, we performed in vitro validation of one of the identified variants. RESULTS: We identified variants in the INHA, HIF1A, JAK2, DNM2, POSTN, ANGPTL4, FOXO1 and SMAD6 genes as putative drivers in HHT. We have identified the SMAD6 p.(Glu407Lys) variant in one of the families; this is a loss-of-function variant leading to the activation of the BMP/TGFß signaling in endothelial cells. CONCLUSIONS: Variants in these genes should be considered for genetic testing in patients with HHT phenotype and negative for ACVRL1/ENG mutations.


Assuntos
Células Endoteliais , Telangiectasia Hemorrágica Hereditária , Humanos , Células Endoteliais/patologia , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia , Mutação , Testes Genéticos , Endoglina/genética , Receptores de Activinas Tipo II/genética
2.
Circulation ; 149(12): 944-962, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38126211

RESUMO

BACKGROUND: Distinct endothelial cell cycle states (early G1 versus late G1) provide different "windows of opportunity" to enable the differential expression of genes that regulate venous versus arterial specification, respectively. Endothelial cell cycle control and arteriovenous identities are disrupted in vascular malformations including arteriovenous shunts, the hallmark of hereditary hemorrhagic telangiectasia (HHT). To date, the mechanistic link between endothelial cell cycle regulation and the development of arteriovenous malformations (AVMs) in HHT is not known. METHODS: We used BMP (bone morphogenetic protein) 9/10 blocking antibodies and endothelial-specific deletion of activin A receptor like type 1 (Alk1) to induce HHT in Fucci (fluorescent ubiquitination-based cell cycle indicator) 2 mice to assess endothelial cell cycle states in AVMs. We also assessed the therapeutic potential of inducing endothelial cell cycle G1 state in HHT to prevent AVMs by repurposing the Food and Drug Administration-approved CDK (cyclin-dependent kinase) 4/6 inhibitor (CDK4/6i) palbociclib. RESULTS: We found that endothelial cell cycle state and associated gene expressions are dysregulated during the pathogenesis of vascular malformations in HHT. We also showed that palbociclib treatment prevented AVM development induced by BMP9/10 inhibition and Alk1 genetic deletion. Mechanistically, endothelial cell late G1 state induced by palbociclib modulates the expression of genes regulating arteriovenous identity, endothelial cell migration, metabolism, and VEGF-A (vascular endothelial growth factor A) and BMP9 signaling that collectively contribute to the prevention of vascular malformations. CONCLUSIONS: This study provides new insights into molecular mechanisms leading to HHT by defining how endothelial cell cycle is dysregulated in AVMs because of BMP9/10 and Alk1 signaling deficiencies, and how restoration of endothelial cell cycle control may be used to treat AVMs in patients with HHT.


Assuntos
Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Humanos , Camundongos , Animais , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Malformações Arteriovenosas/metabolismo , Células Endoteliais/metabolismo , Fator 2 de Diferenciação de Crescimento/metabolismo , Pontos de Checagem do Ciclo Celular
3.
Medicina (Kaunas) ; 59(9)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37763652

RESUMO

Herein, we present the first described hereditary hemorrhagic telangiectasia (HHT) patient treated with aflibercept for severe GI involvement after tachyphylaxis to bevacizumab, with promising results. HHT is a rare genetic disease characterized by systemic vascular malformations. Gastrointestinal telangiectasia is one of the major involvements that can produce chronic severe iron-deficiency anemia. Nowadays, support treatment with iron replacement therapy, red blood cell transfusions, and antiangiogenic drugs-mainly bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)-are the main therapeutic options for this complication. The evidence of alternative drugs in patients with failure to this approach, such as tachyphylaxis to bevacizumab, is scarce. Aflibercept is a VEGF inhibitor with antiangiogenic properties approved for the treatment of different types of cancer and ocular neovascularization diseases.


Assuntos
Anemia Ferropriva , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Inibidores da Angiogênese/uso terapêutico
5.
Front Med (Lausanne) ; 10: 1146080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250655

RESUMO

Background: Chronic bleeding due to gastrointestinal (GI) involvement in patients with hemorrhagic hereditary telangiectasia (HHT) can provoke severe anemia with high red blood cells (RBC) transfusion requirements. However, the evidence about how to deal with these patients is scarce. We aimed to assess the long-term efficacy and safety of somatostatin analogs (SA) for anemia management in HHT patients with GI involvement. Methods: This is a prospective observational study including patients with HHT and GI involvement attended at a referral center. SA were considered for those patients with chronic anemia. Anemia-related variables were compared in patients receiving SA before and during treatment. Patients receiving SA were divided into responders (patients with minimal hemoglobin levels improvement >10 g/L and maintaining hemoglobin levels ≥80 g/L during treatment), and non-responders. Adverse effects during follow-up were collected. Results: Among 119 HHT patients with GI involvement, 67 (56.3%) received SA. These patients showed lower minimal hemoglobin levels (73 [60-87] vs. 99 [70.2-122.5], p < 0.001), and more RBC transfusion requirements (61.2% vs. 38.5%, p = 0.014) than patients without SA therapy. Median treatment period was 20.9 ± 15.2 months. During treatment, there was a statistically significant improvement in minimum hemoglobin levels (94.7 ± 29.8 g/L vs. 74.7 ± 19.7, p < 0.001) and a reduction of patients with minimal hemoglobin levels <80 g/L (39 vs. 61%, p = 0.007) and RBC transfusions requirement (33.9% vs. 59.3%, p < 0.001). Sixteen (23.9%) patients showed mild adverse effects, mostly diarrhea or abdominal pain, leading to treatment discontinuation in 12 (17.9%) patients. Fifty-nine patients were eligible for efficacy assessment and 32 (54.2%) of them were considered responders. Age was associated with non-responder patients, OR 95% CI; 1.070 (1.014-1.130), p = 0.015. Conclusion: SA can be considered a long-term effective and safe option for anemia management in HHT patients with GI bleeding. Older age is associated with poorer response.

6.
Genes (Basel) ; 14(3)2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36981042

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of the patients undergoing molecular testing. The identification of variants of unknown significance is often seen as a challenge in clinical practice that makes family screening and genetic counseling difficult. Here, we show that the implementation of cDNA analysis to assess the effect of splice site variants on mRNA splicing is a powerful tool. METHODS: Gene panel sequencing of genes associated with HHT and other arteriovenous malformation-related syndromes was performed. To evaluate the effect of the splice site variants, cDNA analysis of ENG and ACVRL1 genes was carried out. RESULTS: three novel splice site variants were identified in ENG (c.68-2A > T and c.1311+4_1311+8del) and ACVLR1 (c.526-6C > G) genes correspondingly in three individuals with HHT that met ≥ 3 Curaçao criteria. All three variants led to an aberrant splicing inducing exon skipping (ENG:c.68-2A > T and ACVRL1:c.526-6C > G) or intron retention (ENG:c.1311+4_1311+8del) allowing the confirmation of the predicted effect on splicing and the reclassification from unknown significance to pathogenic/likely pathogenic of two of them. CONCLUSIONS: RNA analysis should be performed to assess and/or confirm the impact of variants on splicing. The molecular diagnosis of HHT patients is crucial to allow family screening and accurate genetic counseling. A multidisciplinary approach including clinicians and geneticists is crucial when dealing with patients with rare diseases.


Assuntos
Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genética , DNA Complementar , Mutação , Endoglina/genética , Éxons/genética , Receptores de Activinas Tipo II/genética
7.
J Clin Med ; 11(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36233492

RESUMO

The aim was to describe three patients with hemorrhagic hereditary telangiectasia (HHT) requiring liver transplantation (LT) and to perform a systematic review focusing on surgical complications and long-term follow-up. Unrestricted searches of the Medline and Embase databases were performed through February 2022. Forty-five studies were selected including 80 patients plus the three new reported patients, 68 (81.9%) were female and mean age was 50 (27-72) years. Main indications for LT were high-output cardiac failure (n = 40; 48.2%), ischemic cholangitis (n = 19; 22.9%), and a combination of both conditions (n = 13;15.6%). Mean cold ischemic time and red blood cell units transfused during LT were 554 (300-941) minutes and 11.4 (0-88) units, respectively. Complications within 30 days were described in 28 (33.7%) patients, mainly bleeding complications in 13 patients, hepatic artery (HA) thrombosis in four and hepatic vein thrombosis in one. Mean follow-up was 76.4 (1-288) months, and during it, four new patients developed thrombotic complications in HA, HA aneurysm, celiac artery, and the portal-splenic-mesenteric vein. HHT relapse in the transplant allograft was detected in 13 (17.1%) patients after 1-19 years (including two fatal recurrences). Overall mortality was 12%. In conclusion, previous assessment of HA anatomy and hyperdynamic circulatory state could reduce LT complications. The risk of relapse in the hepatic graft supports a multidisciplinary follow-up for HHT patients with LT.

8.
J Clin Med ; 10(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34682839

RESUMO

(1) Background: Catheter-directed therapies (CDT) may be considered for selected patients with pulmonary embolism (PE); (2) Methods: Retrospective observational study including all consecutive patients with acute PE undergoing CDT (mechanical or pharmacomechanical) from January 2010 through December 2020. The aim was to evaluate in-hospital and long-term mortality and its predictive factors; (3) Results: We included 63 patients, 43 (68.3%) with high-risk PE. All patients underwent mechanical CDT and, additionally, 27 (43%) underwent catheter-directed thrombolysis. Twelve (19%) patients received failed systemic thrombolysis (ST) prior to CDT, and an inferior vena cava (IVC) filter was inserted in 28 (44.5%) patients. In-hospital PE-related and all-cause mortality rates were 31.7%; 95% CI 20.6-44.7% and 42.9%; 95% CI 30.5-56%, respectively. In multivariate analysis, age > 70 years and previous ST were strongly associated with PE-related and all-cause mortality, while IVC filter insertion during the CDT was associated with lower mortality rates. After a median follow-up of 40 (12-60) months, 11 more patients died (mortality rate of 60.3%; 95% CI 47.2-72.4%). Long-term survival was significantly higher in patients who received an IVC filter; (4) Conclusions: Age > 70 years and failure of previous ST were associated with mortality in acute PE patients treated with CDT. In-hospital and long-term mortality were lower in patients who received IVC filter insertion.

9.
PLoS One ; 15(12): e0243533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370304

RESUMO

BACKGROUND: A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. METHODS: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. RESULTS: Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. CONCLUSIONS: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/administração & dosagem , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Idoso , Angiografia por Tomografia Computadorizada , Feminino , Testes Hematológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
10.
Int J Infect Dis ; 101: 290-297, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33035673

RESUMO

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.


Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/virologia , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia
11.
Eur J Intern Med ; 79: 43-50, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32482595

RESUMO

BACKGROUND: Anticoagulant treatment is recommended in patients with thrombosis and antiphospholipid syndrome (APS). Conflicting results have been reported on the role of direct oral anticoagulants (DOACs) in these patients. We performed a meta-analysis of randomized controlled trials (RCTs) focused on this issue. METHODS: We searched MEDLINE and EMBASE for RCTs comparing DOACs and vitamin K antagonists (VKAs) for secondary thromboprophylaxis in patients with thrombotic APS. The primary objective was to assess the efficacy of DOACs compared to VKAs to prevent recurrence of thromboembolic events. Risk difference (RD) was reported as weighted RD according to Mantel-Haenszel random-effect method. RESULTS: Three RCTs (426 patients) were included, all comparing rivaroxaban with VKAs. The proportion of recurrences (either arterial or venous) was higher among rivaroxaban patients when compared with those receiving VKAs (9.5% vs 2.8%; RD 6%, 95% CI, -0.05 - 0.18, p=0.29), although non-statistically significant. In patients with an arterial index event, thromboembolic recurrences were more frequent in those treated with rivaroxaban compared to those treated with VKAs (25% vs 6.2%; RD 19%, 95% CI, 0.04 - 0.33; p =0.01; I2 49%). In triple aPL positive patients, rivaroxaban showed higher rates of thromboembolic recurrences compared with VKAs (12% vs 3%; RD 9%, 95% CI, 0.02 - 0.15; p= 0.01; I2 13%). Non-statistically significant differences were observed in major bleeding events or mortality. CONCLUSIONS: The use of rivaroxaban in APS patients is associated with an increased rate of thromboembolic recurrences compared to VKAs, at least in those with arterial index event or triple aPL positivity.


Assuntos
Síndrome Antifosfolipídica , Administração Oral , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Rivaroxabana/uso terapêutico , Vitamina K/uso terapêutico
12.
Orphanet J Rare Dis ; 14(1): 196, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399146

RESUMO

BACKGROUND: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). METHODS: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). RESULTS: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. CONCLUSIONS: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis.


Assuntos
Telangiectasia Hemorrágica Hereditária/patologia , Tromboembolia Venosa/patologia , Trombose Venosa/patologia , Adulto , Idoso , Hemorragia/patologia , Humanos , Pessoa de Meia-Idade , Sistema de Registros
13.
Cells ; 8(9)2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450639

RESUMO

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.


Assuntos
Células Endoteliais/citologia , Fosfatidilinositol 3-Quinase/metabolismo , Telangiectasia Hemorrágica Hereditária/patologia , Receptores de Activinas Tipo II/genética , Adulto , Idoso , Biópsia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Endoglina/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/metabolismo
14.
J Thromb Haemost ; 17(8): 1217-1228, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063646

RESUMO

Essentials Debated is the role of residual pulmonary obstruction (RPO) in predicting venous thromboembolism. Whether right ventricular dysfunction (RVD) predicts recurrent venous thromboembolism is unknown. 15 studies on RPO and 4 on RVD and venous thromboembolism were included in this meta-analysis. RPO is a predictor of recurrent venous thromboembolism when assessed by perfusion lung scan. RVD after acute pulmonary embolism is not associated with recurrent venous thromboembolism. BACKGROUND: There is conflicting evidence regarding the role of residual pulmonary obstruction (RPO) or persistent right ventricular dysfunction (RVD) after pulmonary embolism (PE) as a predictor of recurrent venous thromboembolism (VTE). The aim of this study was to assess whether RPO or persistent RVD after PE is associated with recurrent VTE. METHODS: MEDLINE and EMBASE were searched through December 2018. Studies reporting on (a) RPO either on computed tomography (CT) angiography or perfusion lung scan, or RVD on echocardiography or CT angiography, after therapeutic anticoagulation for the acute PE, and (b) recurrent VTE, were included in this meta-analysis. RESULTS: RPO was associated with an increased risk of recurrent VTE (16 studies; 3472 patients; odds ratio [OR] 2.22; 95% confidence interval [CI] 1.61-3.05; I2  = 26%); the association was statistically significant for lung scan-detected RPO (11 studies; 2916 patients; OR 2.21; 95% CI 1.63-3.01) but not for CT angiography-detected RPO (five studies; 556 patients; OR 2.56; 95% CI 0.82-7.94). No significant association was found between persistent RVD and recurrent VTE (four studies; 852 patients; OR 1.62; 95% CI 0.63-4.17). CONCLUSIONS: RPO is a predictor of recurrent VTE after a first acute PE, mainly when assessed by perfusion lung scan.


Assuntos
Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Disfunção Ventricular Direita/epidemiologia , Função Ventricular Direita , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão , Prevalência , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/fisiopatologia , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/fisiopatologia , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologia
15.
Nutrients ; 11(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987366

RESUMO

Intensive exercise can lead to oxidative stress, which can be particularly deleterious for lymphoid tissues. Hesperidin has demonstrated its antioxidant activity, but few studies focus on its influence on intensive training. The aim of this study was to assess the impact of hesperidin on the oxidant/antioxidant status of lymphoid tissues after an intensive training program. Wistar rats were trained for five weeks (five days per week), including two exhaustion tests plus three trainings per week. During this period, animals were orally administrated with 200 mg/kg of hesperidin or vehicle (three days per week). The oxidative status was determined before, immediately after and 24 h after an additional exhaustion test. The production of reactive oxygen species (ROS) by peritoneal macrophages, superoxide dismutase (SOD) and catalase activities in spleen, thymus and liver, and hepatic glutathione peroxidase activity (GPx) were assessed. Hesperidin prevented an increase in ROS production induced by the additional exhaustion test. Likewise, hesperidin avoided a decrease in SOD and catalase activities in the thymus and spleen that was found after the additional exhaustion test. The antioxidant effects of hesperidin were associated with a higher performance in the assessed training model. These results suggest that hesperidin, acting as an antioxidant, can prevent oxidative stress induced by exercise and improve exercise performance.


Assuntos
Antioxidantes/farmacologia , Tolerância ao Exercício/efeitos dos fármacos , Hesperidina/farmacologia , Tecido Linfoide/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Esforço Físico , Animais , Catalase/metabolismo , Células Cultivadas , Feminino , Glutationa Peroxidase/metabolismo , Tecido Linfoide/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Tempo
16.
J Clin Med ; 9(1)2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31905627

RESUMO

BACKGROUND: We aimed to describe risk factors for gastrointestinal (GI) bleeding and endoscopic findings in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: This is a prospective study from a referral HHT unit. Endoscopic tests were performed when there was suspicion of GI bleeding, and patients were divided as follows: with, without, and with unsuspected GI involvement. RESULTS: 67 (27.9%) patients with, 28 (11.7%) patients without, and 145 (60.4%) with unsuspected GI involvement were included. Age, tobacco use, endoglin (ENG) mutation, and hemoglobin were associated with GI involvement. Telangiectases were mostly in the stomach and duodenum, but 18.5% of patients with normal esophagogastroduodenoscopy (EGD) had GI involvement in video capsule endoscopy (VCE). Telangiectases ≤ 3 mm and ≤10 per location were most common. Among patients with GI disease, those with hemoglobin < 8 g/dL or transfusion requirements (65.7%) were older and had higher epistaxis severity score (ESS) and larger telangiectases (>3 mm). After a mean follow-up of 34.2 months, patients with GI involvement required more transfusions and more emergency department and hospital admissions, with no differences in mortality. CONCLUSIONS: Risk factors for GI involvement have been identified. Patients with GI involvement and severe anemia had larger telangiectases and higher ESS. VCE should be considered in patients with suspicion of GI bleeding, even if EGD is normal.

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