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1.
Prostate ; 80(1): 38-50, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584209

RESUMO

BACKGROUND: Expression profiles of erythroblast transformation-specific (ETS)-related gene fusions and serine protease inhibitor Kazal-type 1 (SPINK1) in early onset prostate cancer have not been thoroughly explored. METHODS: We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55 years) and characterized the expression of ETS-related gene (ERG), SPINK1, ETS Variant 1 (ETV1), and ETV4 by dual immunohistochemistry and dual RNA in situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence, and pathological variables using whole-mount radical prostatectomy tissue were collected. RESULTS: A total of 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans were included in the analysis. Positive family history of prostate cancer was seen in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/mL (mean = 7.04). The follow-up period ranged from 1 to 123.7 months (mean = 30.3). Biochemical recurrence was encountered in 8 of 151 (5%). ERG overexpression was observed in 85 of 151 (56%) cases, followed by SPINK1 in 61 of 151 (40%), ETV1 in 9 of 149 (6%), and ETV4 in 4 of 141 (3%). There were 25 of 151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤45 years old; 76% vs 49%, P = .002), Caucasian men (71% vs 41% P = .0007), organ-confined tumors (64% vs 33%, P = .0008), and tumors of Gleason Grade groups 1 and 2 (62% vs 26%, P = .009). SPINK1 overexpression was more in African American men (68% vs 26%, P = .00008), in tumors with high tumor volume (>20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. CONCLUSION: This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.


Assuntos
Proteínas de Ligação a DNA/genética , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-ets/genética , Fatores de Transcrição/genética , Inibidor da Tripsina Pancreática de Kazal/genética , Adulto , Proteínas de Ligação a DNA/sangue , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Proto-Oncogênicas c-ets/biossíntese , Fatores de Transcrição/sangue , Regulador Transcricional ERG/biossíntese , Regulador Transcricional ERG/genética , Inibidor da Tripsina Pancreática de Kazal/biossíntese
2.
Mod Pathol ; 33(9): 1791-1801, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32238875

RESUMO

Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.


Assuntos
Próstata/metabolismo , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulador Transcricional ERG/genética , Regulador Transcricional ERG/metabolismo , Inibidor da Tripsina Pancreática de Kazal/genética , Inibidor da Tripsina Pancreática de Kazal/metabolismo
3.
Eur Respir J ; 51(4)2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29563171

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of pulmonary embolism. Its incidence following pulmonary embolism is debated. Active screening for CTEPH in patients with acute pulmonary embolism is yet to be recommended.This prospective, multicentre, observational study (Multicentre Observational Screening Survey for the Detection of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Following Pulmonary Embolism (INPUT on PE); ISRCTN61417303) included patients with acute pulmonary embolism from 11 centres in Switzerland from March 2009 to November 2016. Screening for possible CTEPH was performed at 6, 12 and 24 months using a stepwise algorithm that included a dyspnoea phone-based survey, transthoracic echocardiography, right heart catheterisation and radiological confirmation of CTEPH.Out of 1699 patients with pulmonary embolism, 508 patients were assessed for CTEPH screening over 2 years. CTEPH incidence following pulmonary embolism was 3.7 per 1000 patient-years, with a 2-year cumulative incidence of 0.79%. The Swiss pulmonary hypertension registry consulted in December 2016 did not report additional CTEPH cases in these patients. The survey yielded 100% sensitivity and 81.6% specificity. The second step echocardiography in newly dyspnoeic patients showed a negative predictive value of 100%.CTEPH is a rare but treatable disease. A simple and sensitive way for CTEPH screening in patients with acute pulmonary embolism is recommended.


Assuntos
Hipertensão Pulmonar/epidemiologia , Embolia Pulmonar/complicações , Tromboembolia/complicações , Idoso , Doença Crônica , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Suíça/epidemiologia
4.
Vasa ; 45(3): 195-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27128884

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH), an important cause of severe pulmonary hypertension, is still underdiagnosed, mainly due to the insufficient use of V/Q scannning in patients with pulmonary hypertension. This article reviews the current diagnostic approach and discusses the therapeutic options in this particular form of pulmonary hypertension. Every patient with CTEPH should undergo an evaluation in a specialised centre with experience in pulmonary arterial endarteriectomy (PEA) as the potentially curative surgical technique. Partly unresolved questions regard the status of the recently described percutaneous transluminal pulmonary angioplasty and the best medical treatment in patients with inoperable or recurrent/persistent pulmonary hypertension after PEA.


Assuntos
Angioplastia com Balão , Anti-Hipertensivos/uso terapêutico , Endarterectomia , Hipertensão Pulmonar/terapia , Artéria Pulmonar , Embolia Pulmonar/terapia , Idoso , Pressão Sanguínea/efeitos dos fármacos , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Valor Preditivo dos Testes , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Respiration ; 89(2): 127-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25661477

RESUMO

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.


Assuntos
Hipertensão Pulmonar/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suíça/epidemiologia , Adulto Jovem
7.
Eur Heart J ; 35(17): 1112-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24595865

RESUMO

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.


Assuntos
Aterosclerose/terapia , Doenças Vasculares Periféricas/terapia , Aorta Abdominal , Aorta Torácica , Doenças da Aorta/diagnóstico , Doenças da Aorta/terapia , Aterosclerose/diagnóstico , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/terapia , Diagnóstico Precoce , Humanos , Extremidade Inferior/irrigação sanguínea , Artérias Mesentéricas , Doenças Vasculares Periféricas/diagnóstico , Artéria Renal , Extremidade Superior/irrigação sanguínea
8.
BJU Int ; 114(6): 824-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24053586

RESUMO

OBJECTIVE: To evaluate oncological outcomes in patients undergoing robot-assisted radical prostatectomy (RARP) at a high-volume tertiary centre with focus on biochemical recurrence (BCR); previous studies on oncological outcomes for patients undergoing RARP for prostate cancer are limited to small series. PATIENTS AND METHODS: In all, 5152 consecutive patients underwent RARP from 2001 to 2010; 4803 patients comprised the study cohort after exclusions. BCR was defined as a serum prostate-specific antigen (PSA) level of ≥0.2 ng/mL with a confirmatory value. BCR-free survival (BCRFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method and Cox hazards regression models were generated. RESULTS: The mean preoperative PSA level was 6.1 ng/mL, pathological Gleason grade and stage were ≥7 in 68% and ≥pT3 in 34% of patients. There was BCR in 470 patients (9.8%), 31 patients developed metastatic disease (0.7%) and 13 patients died from prostate cancer (0.3%) during a mean (range) follow-up of 34.6 (1-116.7) months. Actuarial 8-year BCRFS, MFS and CSS were 81%, 98.5% and 99.1%, respectively. In patients with node-positive disease, actuarial 5-year BCRFS, MFS, and CSS were 26%, 82%, and 97%. For organ-confined disease, predictors of BCR included pathology Gleason grade (primary Gleason 5 vs 3, hazard ratio [HR] 5.52, P = 0.018; Gleason 4 vs 3, HR 1.97, P = 0.001), preoperative PSA level (10-20 vs ≤10 ng/mL, HR 2.38, P = 0.001), and surgical margin status (positive vs negative, HR 3.84, P < 0.001) CONCLUSIONS: RARP appears to confer effective long-term biochemical control. To our knowledge, this is the largest report of oncological outcomes in a RARP series to date.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Neoplasias da Próstata/mortalidade , Recidiva , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
9.
Vasa ; 43(4): 239-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25007901

RESUMO

A relationship between tumor and thrombosis is well known. This review covers the aspect of incidence and pathophysiology of cancer-related thromboembolism. Cancer patients have an up to 7 % risk of developing venous thrombosis, partly because they are subject to various circumstantial risk factors such as surgical interventions, immobilization or drugs during their illness. On the other hand, tumors frequently generate a prothrombotic state, which may remain without clinical manifestation or result in anticoagulant-resistent venous thromboembolism. Recently discovered thrombosis-generating mechanisms could help to classify patients in categories with high and low thrombotic risk, which will allow tailored prophylactic and therapeutic interventions.


Assuntos
Neoplasias/epidemiologia , Neoplasias/fisiopatologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/fisiopatologia , Animais , Coagulação Sanguínea , Humanos , Incidência , Neoplasias/sangue , Prognóstico , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/sangue
10.
Thromb J ; 11(1): 6, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-23496906

RESUMO

BACKGROUND: While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS: Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS: The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS: Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.

11.
Z Gesundh Wiss ; 31(4): 539-552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34026423

RESUMO

Aim: To use a Delphi-panel-based assessment of the effectiveness of different non-pharmaceutical interventions (NPI) in order to retrospectively approximate and to prospectively predict the SARS-CoV-2 pandemic progression via a SEIR model (susceptible, exposed, infectious, removed). Methods: We applied an evidence-educated Delphi-panel approach to elicit the impact of NPIs on the SARS-CoV-2 transmission rate R0 in Germany. Effectiveness was defined as the product of efficacy and compliance. A discrete, deterministic SEIR model with time step of 1 day, a latency period of 1.8 days, duration of infectiousness of 5 days, and a share of the total population of 15% assumed to be protected by immunity was developed in order to estimate the impact of selected NPI measures on the course of the pandemic. The model was populated with the Delphi-panel results and varied in sensitivity analyses. Results: Efficacy and compliance estimates for the three most effective NPIs were as follows: test and isolate 49% (efficacy)/78% (compliance), keeping distance 42%/74%, personal protection masks (cloth masks or other face masks) 33%/79%. Applying all NPI effectiveness estimates to the SEIR model resulted in a valid replication of reported occurrence of the German SARS-CoV-2 pandemic. A combination of four NPIs at consented compliance rates might curb the CoViD-19 pandemic. Conclusion: Employing an evidence-educated Delphi-panel approach can support SARS-CoV-2 modelling. Future curbing scenarios require a combination of NPIs. A Delphi-panel-based NPI assessment and modelling might support public health policy decision making by informing sequence and number of needed public health measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01566-2.

12.
PLoS One ; 18(9): e0291315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37713401

RESUMO

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.


Assuntos
Adenocarcinoma , Terapia Viral Oncolítica , Neoplasias da Próstata , Humanos , Masculino , Adenocarcinoma/terapia , Adenoviridae , Terapia Genética/efeitos adversos , Interleucina-12/genética , Leucócitos Mononucleares , Próstata , Neoplasias da Próstata/terapia , Genes Transgênicos Suicidas
13.
Eur Heart J Open ; 3(4): oead069, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37528902

RESUMO

Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.

14.
Mol Ther ; 19(7): 1353-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21587209

RESUMO

We have developed a replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-hNIS) armed with two suicide genes and the human sodium iodide symporter (hNIS) gene. In this context, hNIS can be used as a reporter gene in conjunction with nuclear imaging and as a potentially therapeutic gene when combined with (131)I radioiodine therapy. Here, we quantified the volume and magnitude of hNIS gene expression in the human prostate following injection of a high Ad5-yCD/mutTK(SR39)rep-hNIS dose using a standardized injection algorithm, and estimated the radiation dose that would be delivered to the prostate had men been administered (131)I with curative intent. Six men with clinically localized prostate cancer received an intraprostatic injection of Ad5-yCD/mutTK(SR39)rep-hNIS under transrectal ultrasound guidance. All men received 2 × 0.5 ml deposits (5 × 10(11) vp/deposit) in each of the four base and midgland sextants and 2 × 0.25 ml deposits (2.5 × 10(11) vp/deposit) in each of the two apex sextants for a total of 12 deposits (5 × 10(12) vp) in 5 ml. On multiple days after the adenovirus injection, men were administered sodium pertechnetate (Na(99m)TcO(4)) and hNIS gene expression in the prostate was quantified by single photon emission computed tomography (SPECT). hNIS gene expression was detected in the prostate of six of six (100%) men. On average, 45% (range 18-83%) of the prostate volume was covered with gene expression. Had men been administered 200 mCi (131)I, we estimate that the mean absorbed dose to the prostate would be 7.2 ± 4.8 Gy (range 2.1-13.3 Gy), well below that needed to sterilize the prostate. We discuss the obstacles that must be overcome before adenovirus-mediated hNIS gene transfer and (131)I radioiodine therapy can be used as a definitive treatment for localized prostate cancer.


Assuntos
Adenoviridae/genética , Vetores Genéticos/genética , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/terapia , Simportadores/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Simportadores/genética
15.
Pulm Circ ; 12(1): e12001, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35506112

RESUMO

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival.

16.
Res Pract Thromb Haemost ; 6(4): e12712, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35599701

RESUMO

Background: Hospitalized patients with COVID-19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective: To test whether therapeutic anticoagulation improves clinical outcomes in severe COVID-19. Patients/Methods: In this multicenter, open-label, randomized controlled trial, we recruited acutely ill medical COVID-19 patients with D-dimer >1000 ng/ml or critically ill COVID-19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30-day follow-up. Participants were randomized to in-hospital therapeutic anticoagulation versus low-dose anticoagulation in acutely ill participants/intermediate-dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30-day all-cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. Results: Among 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18-3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. Conclusions: Among patients with severe COVID-19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.

17.
BJU Int ; 107(4): 642-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20575975

RESUMO

OBJECTIVE: To evaluate the incidence of, and predictors for, lymphadenectomy in patients undergoing robot-assisted radical cystectomy (RARC) for bladder cancer. PATIENTS AND METHODS: Utilizing the International Robotic Cystectomy Consortium (IRCC) database, 527 patients were identified who underwent RARC at 15 institutions from 2003 to 2009. After stratification by age group, sex, pathological T stage, nodal status, sequential case number, institutional volume and surgeon volume, logistic regression was used to correlate variables to the likelihood of undergoing lymphadenectomy (defined as ≥ 10 nodes removed). RESULTS: Of the 527 patients, 437 (82.9%) underwent lymphadenectomy. A mean of 17.8 (range 0-68) lymph nodes were examined. Tumour stage, sequential case number, institution volume and surgeon volume were significantly associated with the likelihood of undergoing lymphadenectomy. Surgeon volume was most significantly associated with lymphadenectomy on multivariate analysis. High-volume surgeons (> 20 cases) were almost three times more likely to perform lymphadenectomy than lower-volume surgeons, all other variables being constant [odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.39-4.05; P = 0.002]. CONCLUSION: The rates of lymphadenectomy at RARC for advanced bladder cancer are similar to those of open cystectomy series using a large, multi-institutional cohort. There does, however, appear to be a learning curve associated with the performance of lymphadenectomy at RARC.


Assuntos
Cistectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Robótica , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cistectomia/estatística & dados numéricos , Métodos Epidemiológicos , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
18.
Can J Urol ; 18(2): 5592-600, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21504646

RESUMO

INTRODUCTION: Prostate cancer is the second most common cause of cancer death in American men. For patients with adverse pathologic features, postoperative radiotherapy to prostate bed after radical prostatectomy has been shown in randomized studies to improve many important clinical endpoints including overall survival. In this review article, we distinguish adjuvant radiation treatment (ART) from salvage radiation treatment (SRT), discuss the evidences for ART and its potential side effects focusing on the debate concerning the optimal timing of post prostatectomy radiation treatment (RT). MATERIAL AND METHODS: A comprehensive literature search was conducted in MEDLINE including pre-MEDLINE. CONCLUSION: for patients with adverse pathologic factors, adjuvant radiation treatment after prostatectomy reduces the rate of PSA failure with the potential for significantly improving metastases-free and overall survival. Whether an equivalent survival benefit can be attained with early salvage radiation treatment after biochemical recurrence, is still an area of debate.


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação , Análise de Sobrevida
19.
Microsurgery ; 31(3): 246-50, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21400581

RESUMO

False aneurysms in the hand are rare. A false aneurysm of the common digital artery in the palm for the second and third finger is reported, illustrating our experience with arterial graft reconstruction after excision as a valid alternative surgical therapy to a vein graft, when ligation or end-to-end anastomosis are not indicated or feasible. The superficial palmar branch of the radial artery was chosen as donor vessel based on the similarity in vessel diameter and wall thickness to the common digital arteries. Ease of harvesting and performing the microvascular anastomosis using an arterial graft allows for a viable reconstruction after false aneurysm excision in the palm.


Assuntos
Falso Aneurisma/cirurgia , Mãos/cirurgia , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Artéria Radial/transplante , Enxerto Vascular/métodos , Adulto , Falso Aneurisma/diagnóstico , Artérias/cirurgia , Artérias/transplante , Dedos/irrigação sanguínea , Traumatismos da Mão/complicações , Humanos , Masculino , Resultado do Tratamento
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