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Currently, axillary surgery for breast cancer is considered only as staging procedure, since the risk of developing metastasis depends on the biological behavior of the primary. The postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to de-escalate surgery in patients who have a pCR. European Breast Cancer Research Association of Surgical Trialists (EUBREAST)-01 is a clinical trial in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included and type of surgery will be defined according to the response to NAST rather than on the classical T (for tumor size in the breast) and N (for axillary lymph node involvement) status. In the discussed trial, axillary surgery will be eliminated completely (no axillary sentinel lymph node biopsy) for initially clinical node-negative (cN0) patients with radiologic complete remission and a breast pCR in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (n = 267), which might give practice-changing results in a short period of time, sparing the time and the costs of a randomized comparison.
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Intestinal failure (IF) requires parenteral support (PS) substituting energy, water, and electrolytes to compensate intestinal losses and replenish deficits. Convalescence, adaptation, and reconstructive surgery facilitate PS reduction. We analyzed the effect of changes of PS on body mass index (BMI) in early adult IF. Energy, volume, and sodium content of PS and BMI were collected at the initial contact (FIRST), the time of maximal PS and BMI (MAX) and the last contact (LAST). Patients were categorized based on functional anatomy: small bowel enterostomy-group 1, jejuno-colic anastomosis-group 2. Analysis of variance was used to test the relative impact of changes in energy, volume, or sodium. Total of 50 patients were followed for 596 days. Although energy, volume, and sodium support were already high at FIRST, we increased PS to MAX, which was accompanied by a significant BMI increase. Thereafter PS could be reduced significantly, leading to a small BMI decrease in group 1, but not in group 2. Increased sodium support had a stronger impact on BMI than energy or volume. Total of 13 patients were weaned. Dynamic PS adjustments are required in the early phase of adult IF. Vigorous sodium support acts as an independent factor.
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Intestinos/patologia , Nutrição Parenteral , Sódio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Desmame , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to evaluate the impact of various factors that may influence the immunologic response to hepatitis A mono-vaccine or hepatitis A/B co-vaccine (Twinrix®) in HIV-infected patients. DESIGN: Retrospective cross-sectional study. METHODS: HIV positive patients with a full course of hepatitis A vaccine were tested for HAV antibodies. The seroconversion rates were determined, and the influence of several factors including CD4 cell counts, CD4/CD8 ratio, plasma viral load, type of vaccine, and antiretroviral therapy at the time of vaccine, was evaluated. RESULTS: After vaccination, 80.2% of the patients developed anti-HAV antibodies, 81.5% in the mono-vaccine group and 79.2% in the hepatitis A/B co-vaccine group. In the mono-vaccine group, factors significantly associated with a better response to the vaccine were higher CD4 cell count, higher CD4/CD8 ratio, and shorter time interval from vaccine to serological control. In patients who received the hepatitis A/B co-vaccine, younger age and female sex were significantly associated with better vaccine response. Multivariable logistic regression analysis revealed time interval from vaccine to serological control of more than 5â¯years vs. less than 1â¯year to be significantly associated with decrease of seroconversion after HAV vaccine. CONCLUSIONS: The response to hepatitis A vaccine is impaired in HIV positive patients. HIV patients, at least those older than 30, should be tested for seroconversion after receiving the hepatitis A vaccine. As hepatitis A titers may rapidly decline, control serology during follow-up should be proposed, possibly within two years. However, vaccine type does not play a role in vaccine response.
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Coinfecção , Infecções por HIV/imunologia , Vacinas contra Hepatite A/imunologia , Hepatite A/imunologia , Hepatite A/prevenção & controle , Imunidade , Adulto , Idoso , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos Transversais , Feminino , Vacinas contra Hepatite A/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Soroconversão , Vacinação , Carga Viral , Adulto JovemRESUMO
With a rising number of cranioplasty (CP) procedures and an increasing percentage of patients with a good clinical outcome and prolonged survival after CP, looking at the functional and aesthetic outcome of these patients becomes more and more important. The aim of our study was to evaluate a novel score, combining functional and cosmetics aspects after CP, created at our institution: the Rostock Functional and Cosmetic Cranioplasty (RFCC-) Score. A total of 27 patients were enrolled, representing all indications for a secondary CP after decompressive craniectomy or extended temporal trephination with a complete separation of the temporalis muscle. Besides the clinical evaluation, five different already established clinical rating systems were tested and compared with our score. For reasons of objectivity, the score was also tested against the patient's own rating. Our findings showed that the RFCC-Score, derived from a health professional, is superior to other scoring systems, which only display a facet of the functional state of the patient. Our score is objective and independent of a disposition for a depression of the patient. It can be obtained without the need of a verbal communication, making it applicable for nearly all patients after CP. The score is time-saving, clearly arranged, and reliable, which are inevitable requirements for the comparing and evaluation of different surgical techniques and associated complications of CP.
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Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In Sub-Saharan Africa, the prevalence of HIV-associated kidney diseases is as high as 53.3%. Combined antiretroviral treatment (cART), especially tenofovir disoproxil fumarate (TDF), is known to be nephrotoxic. We undertook this cross-sectional study conducted in 2015 at the Regional Hospital Limbe in the Southwest Region of Cameroon to determine the prevalence of renal dysfunction and its correlates among treatment-experienced HIV-infected patients on TDF and treatment-naïve patients. In April 2016, a follow-up was performed on those who had been treatment-naïve and were started on cART after enrolment in the study. We compared 119 patients on TDF-containing regimens with 47 treatment-naïve patients. Proteinuria was significantly more prevalent, and creatinine was significantly higher among treatment-naïve patients than among those on treatment (52.2% versus 26.1%; P = 0.003 and P = 0.009, respectively). The proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute was significantly higher among treatment-naïve patients than among those on TDF treatment (40.4% versus 24.4%; P = 0.041). Treatment-naïve patients displayed an improvement in creatinine levels and eGFR after 6 months of treatment. To the best of our knowledge, this is the first study to investigate the impact of TDF on renal parameters in Cameroon. TDF appears to be safe and does not appear to be a significant cause of renal impairment. However, renal parameters should be monitored regularly, as recommended by the guidelines.
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Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Nefropatias/epidemiologia , Proteinúria/epidemiologia , Tenofovir/efeitos adversos , Adolescente , Adulto , África Subsaariana , Idoso , Fármacos Anti-HIV/administração & dosagem , Camarões/epidemiologia , Creatinina/urina , Estudos Transversais , Feminino , Seguimentos , Taxa de Filtração Glomerular , Infecções por HIV/urina , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prevalência , Proteinúria/induzido quimicamente , Tenofovir/administração & dosagem , Urinálise , Adulto JovemRESUMO
AIM: To evaluate the expression and prognostic value of RARRES1 at protein level in renal cell carcinoma (RCC). MATERIALS & METHODS: Expression profile of RARRES1 was analyzed in 903 documented RCC followed by clinicopathological correlations and survival analysis. RESULTS: RARRES1 expression was seen in 72.5% of RCC. A stronger RARRES1 expression was seen in high grade compared with low grade RCC (p < 0.001). Logrank tests revealed shorter overall survival in RARRES1 positive RCC (p = 0.006) and in pT1/2 tumors with RARRES1 expression (p = 0.002). CONCLUSION: The variable expression profile in low and high grade RCC may reflect and confirm the differences of previous gene expression analysis. There was a significant prognostic value of RARRES1 expression in patients with RCC, especially in pT1/2 tumors.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteínas de Membrana/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Análise Serial de Tecidos , Adulto JovemRESUMO
BACKGROUND: Sepsis is associated with coagulation abnormalities, and a high content of intravascular tissue factor (TF) may contribute to the development of multisystem organ failure. Circulating microvesicles (MVs) are increased during sepsis and characterized by their phosphatidylserine content. It is unclear whether MVs-as a part of the host response to the infection-are beneficial or rather contribute to systemic complications in sepsis. In the present prospective clinical pilot study, we investigated whether plasma TF and MVs are associated with the risk of multiple organ failure and mortality. METHODS: Thirty patients diagnosed with sepsis, severe sepsis, or septic shock were enrolled and classified as 19 survivors and 11 non-survivors. Blood samples were collected on the day of admission and then daily for up to 2 weeks. MVs and TF were quantified in plasma by ELISA. RESULTS: Non-survivors had significantly higher TF concentrations on day 3 compared to survivors. Logistic regression analysis revealed that patients with high amounts of TF had significantly increased risk for severity of disease, according to high Simplified Acute Physiology Score II (SAPS II) scores (odds ratio 18.7). In contrast, a higher content of phosphatidylserine-rich MVs were apparently associated with a lower risk for mortality and multiple organ failure, although this was only a trend and the odds ratios were not significant. CONCLUSIONS: This study showed that a high amount of TF in septic patients is significantly associated with increased risk for disease severity, according to a high SAPS II score. Quantification of total MVs in plasma, independent from their cell origin, might be indicative for the outcome of patients in sepsis.
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AIMS: Pulmonary vein isolation (PVI) during ablation of atrial fibrillation (Afib) may be associated with long fluoroscopy duration. Although most current publications report on fluoroscopy time (FT), the dose-area product (DAP) may be a more valuable parameter for depicting radiation exposure. The aim of our study was to describe a method to reduce DAP by simple means during ablation of Afib. METHODS: Patients undergoing Afib ablation using a three-dimensional (3D) mapping system were assigned to two fluoroscopy protocols: (1) standard settings with 7.5 pictures/s and collimation to the heart, fluoroscopy as needed for the convenience of the operator (standard group, SG); and (2) strict collimation to the left atrium, a frame rate of 4 pictures/s, shortened pulmonary vein angiography sequences, and maximal orientation by the 3D mapping system (redDAP group). The primary endpoint was DAP. RESULTS: The study comprised 206 patients, who were assigned to the SG (n = 101, 49 %) or to the redDAP group (n = 105, 51 %). Mean FT was significantly reduced from 29.9 ± 11.3 min (SG) to 13.3 ± 8.3 min (redDAP group); mean DAP was reduced by approximately 90 % from 8,690 ± 5,727 to 837 ± 647 cGycm(2). The groups did not differ significantly in body mass index (28.8 ± 4.1 vs. 29.0 ± 5.0). PVI could be achieved in 98 of 101 patients (97 %) from the SG group and in all patients (100 %) from the redDAP group. Procedure time was significantly longer in the redDAP group (160.9 ± 35.7 vs. 138.1 ± 34.3 min). CONCLUSION: Radiation exposure during Afib ablation procedures can be reduced with simple means by strict collimation to the left atrium, a frame rate of 4 pictures/s, shortened pulmonary vein angiography sequences, and maximal 3D orientation.
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Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Flebografia/métodos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Exposição à Radiação/prevenção & controle , Mapeamento Potencial de Superfície Corporal/métodos , Ablação por Cateter/métodos , Feminino , Fluoroscopia/métodos , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente/métodos , Exposição à Radiação/análise , Cirurgia Assistida por Computador/métodos , Resultado do TratamentoRESUMO
AIMS: A significant proportion of patients presenting with paroxysmal supraventricular tachycardia (PSVT) has no electrocardiogram (ECG) documentation. In these patients an electrophysiological study (EPS) may be performed to facilitate the diagnosis. METHODS AND RESULTS: In a prospective registry we compared the prevalence of inducible arrhythmias and the clinical outcome in 525 patients with and without ECG documentation. Compared with patients with a documented PSVT a smaller but substantial proportion of patients (63.7%) without ECG documentation had inducible supraventricular tachycardias (SVT). Atrio-ventricular nodal reentrant tachycardia was the most common type in both groups. Patients with an inducible SVT and no documentation were significantly younger, had a shorter episode duration and a lower hospitalization rate, which may be the cause for the lacking documentation. Similar to patients with documented PSVTs most of these patients (90.0%) were asymptomatic or clinically improved after the EPS. Even 43% of patients without an inducible tachycardia improved clinically, probably due to a placebo effect of the EPS. In particular, patients between 31 and 60 years of age seemed to benefit from an EPS because they were more likely to have inducible SVTs that could be cured by radiofrequency ablation. CONCLUSION: Our data show that a substantial proportion of patients with suspected paroxysmal tachycardia, but without ECG documentation, have inducible SVTs and obtain a clear clinical benefit from an EPS. Thus, our data provide justification for using EPS for patients in this category. To the best of our knowledge, ours is the first prospective registry that supports this approach.
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Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia Paroxística/diagnóstico , Taquicardia Supraventricular/diagnóstico , Adulto , Idoso , Ablação por Cateter , Feminino , Alemanha/epidemiologia , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Taquicardia Paroxística/epidemiologia , Taquicardia Paroxística/fisiopatologia , Taquicardia Paroxística/cirurgia , Taquicardia Supraventricular/epidemiologia , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/cirurgiaRESUMO
BACKGROUND: The incidence of atrial fibrillation (AF) after ablation of a cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) is high. OBJECTIVE: The purpose of this study was to test the hypothesis that AFL and AF may be initiated by pulmonary vein triggers. This prospective randomized trial tested the efficacy of a standalone pulmonary vein isolation (PVI) in patients with AFL but without AF. METHODS: Patients with AFL but without documented AF were randomly assigned to 1 of 3 treatment groups: (1) antiarrhythmic drugs (AAD), (2) CTI ablation, or (3) circumferential PVI. The primary end-point was defined as any recurrent atrial tachyarrhythmia and the secondary end-point as recurrence of AFL. In case of tachyarrhythmia recurrence in the PVI group, a second PVI was performed to close gaps in the ablation lines. RESULTS: Of the 60 patients, 17 were randomized to AAD, 23 to CTI ablation, and 20 to PVI. During follow-up of 1.42 ± 0.83 years, 14 of 17 patients (82.4%) in the AAD group, 14 of 23 patients (60.9%) in the CTI group, and 2 of 20 patients (10%) in the PVI group reached the primary end-point (P <.001) after a mean of 1.4 PVI procedures per patient. AFL reoccurred in 9 patients (52.9.%) in the AAD group, in 2 patients (8.7%) in the CTI group, and after a single PVI in 3 patients (15%) in the PVI group (P = .003). After closure of gaps, 1 patient (5%) in the PVI group presented with recurrent AFL. CONCLUSION: Pulmonary vein triggers play an important role in AFL. PVI can prevent the recurrence of AFL, even without CTI ablation.
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Complicações Pós-Operatórias/diagnóstico , Veias Pulmonares , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Flutter Atrial/diagnóstico , Flutter Atrial/tratamento farmacológico , Flutter Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Eletrocardiografia Ambulatorial/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Veias Pulmonares/fisiopatologia , Veias Pulmonares/cirurgia , RecidivaRESUMO
The treatment of refractory or relapsed non-Hodgkin lymphoma (NHL) remains challenging. In this retrospective study, 88 patients with refractory or relapsed NHL received treosulfan and fludarabine as a reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of the 88 intensely pre-treated patients, 73 experienced a relapse, with 18 of the 88 patients experiencing an early relapse (ER; <6 months from the last chemotherapy). At the time of allo-HSCT, 26 patients were in complete remission (CR) and 43 in partial remission (PR), 12 patients had progressive disease (PD) and 7 had stable disease (SD). A total of 47 patients received an autologous graft followed by allo-HSCT. Following allo-HSCT, 69 of the 88 patients were in CR and 7 were in PR, resulting in an overall response rate of 86.4% (76/88). A total of 33 patients achieved a CR from PR, as did 6 patients from PD and 5 from SD. Of the 88 patients, 43 (49%) were alive at the end of the follow-up period. The patients who directly underwent allo-HSCT without prior auto-HSCT exhibited a better disease-free survival (DFS; P=0.038) with a tendency (P=0.077) for a better overall survival (OS). The patients with ER exhibited a probability of OS of 0.35±0.12 after 3 and 7 years. Chronic graft-versus-host disease (cGvHD) exerted a positive effect on OS and DFS (for limited cGvHD vs. no cGvHD, P=0.002 and 0.004, respectively). In conclusion, allogeneic stem cell transplantation following conditioning with treosufan and fludarabine constitutes a viable therapeutic option for patients with refractory or relapsed NHL and should be considered early during the course of salvage treatment.
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Overexertion and pain of the musculoskeletal system may occur partly owing to load application by the equipment. Both the weight of equipment and the duration of loading are relevant. The aim of the present study was to examine the extent of loading and resultant strain in the trunk muscles. Therefore, the trunk posture of soldiers and muscular activity in reaction to different equipment components (helmet, load-carrying equipment, gun and backpack) were evaluated. Electromyography was performed and a visual assessment of body axis was conducted based on standardised planar images. Data indicate that the activity of the trunk muscles examined (latissimus dorsi, trapezius and pectoralis major) is dependent on the weight and distribution of the equipment components. Activity in the trapezius muscle, for instance, was doubled during specific load application. Moreover, the method of carrying the rifle had a significant influence on the activity of the trapezius muscle (one-sided decrease of activity by 50%). Subjects were able to stabilise the body axis in the coronal plane through increased muscle activity, however, in the sagittal plane a compensatory ventral inclination of the body was observed. Uneven load distribution can lead to an irregular strain on the musculoskeletal system.
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Músculo Esquelético/fisiologia , Tronco/fisiologia , Adulto , Área Sob a Curva , Fenômenos Biomecânicos , Eletromiografia , Humanos , Pessoa de Meia-Idade , Ombro/anatomia & histologia , Suporte de Carga , Adulto JovemRESUMO
BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents a therapeutic concept for type B aortic dissection. Long-term outcomes and morphology after TEVAR for uncomplicated dissection are unknown. METHODS AND RESULTS: A total of 140 patients with stable type B aortic dissection previously randomized to optimal medical treatment and TEVAR (n=72) versus optimal medical treatment alone (n=68) were analyzed retrospectively for aorta-specific, all-cause outcomes, and disease progression using landmark statistical analysis of years 2 to 5 after index procedure. Cox regression was used to compare outcomes between groups; all analyses are based on intention to treat. The risk of all-cause mortality (11.1% versus 19.3%; P=0.13), aorta-specific mortality (6.9% versus 19.3%; P=0.04), and progression (27.0% versus 46.1%; P=0.04) after 5 years was lower with TEVAR than with optimal medical treatment alone. Landmark analysis suggested a benefit of TEVAR for all end points between 2 and 5 years; for example, for all-cause mortality (0% versus 16.9%; P=0.0003), aorta-specific mortality (0% versus 16.9%; P=0.0005), and for progression (4.1% versus 28.1%; P=0.004); Landmarking at 1 year and 1 month revealed consistent findings. Both improved survival and less progression of disease at 5 years after elective TEVAR were associated with stent graft induced false lumen thrombosis in 90.6% of cases (P<0.0001). CONCLUSIONS: In this study of survivors of type B aortic dissection, TEVAR in addition to optimal medical treatment is associated with improved 5-year aorta-specific survival and delayed disease progression. In stable type B dissection with suitable anatomy, preemptive TEVAR should be considered to improve late outcome. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01415804.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Stents , Adulto , Idoso , Dissecção Aórtica/mortalidade , Dissecção Aórtica/patologia , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: This study analyzed the outcome of a combined endovascular and debranching procedure for hybrid aortic arch repair (HAR) in patients with complicated type B aortic dissection. METHODS: Between February 2006 and August 2012, HAR was performed in 75 consecutive patients, with retrospective analysis of a subgroup of 45 patients who underwent HAR with complicated acute (n = 10), subacute (n = 7), or chronic (n = 28) type B dissection as the underlying disease. Descriptive statistics were computed for continuous and categoric variables. The interval to death or last follow-up was estimated using the Kaplan-Meier method. RESULTS: The patients were a mean age of 59.9 ± 10.7 years (median, 59.2; range, 35-78 years). Complete supra-aortic debranching was performed in six (13%) in zone 0 (procedure time, 200 minutes; range, 185-365 minutes) and partial debranching in 39 (87%), comprising 16 (36%) in zone 1 (procedure time, 120 minutes; range, 75-250 minutes) and 23 (51%) in zone 2 (procedure time, 91 minutes; range, 70-210 minutes). Technical success was achieved in 86.7% (39 of 45). Thirty-day mortality was 4.4% (two of 45), with an in-hospital mortality of 11.1% (five of 45) as a result of three additional deaths after days 33, 35, and 111. Comparing HAR for type B dissection after complete debranching in six and partial debranching in 39, the overall in-hospital mortality was 67% (four of six) and 2.6% (one of 39), respectively. After a median follow-up of 20.8 months (range, 0.3-70 months), the overall mortality was 13.3% (six of 45), with Kaplan-Meier survival estimate of 85% at 1 year. Stroke rate was 8.8% (four of 45). Paraplegia developed in one patient (2.2%), with complete recovery after spinal drainage. Cardiac complications occurred in three patients (6.7%), pulmonary complications in 10 (22.2%), and renal insufficiency requiring dialysis developed in five (11%). Retrograde dissection occurred in one patient (2.2%) 14 days after complete debranching and zone 0 thoracic endovascular aortic repair, with fatal outcome. No bypass dysfunction was seen during follow-up. The overall early and late endoleak rates were 27% (12 of 44) and 43% (13 of 30), respectively. Eight patients (18%) required reintervention, with freedom of reintervention in 91% at 1 year and 81% at 2 years. CONCLUSIONS: HAR in zone 1 and 2 appears a viable alternative to conventional aortic arch surgery in patients with complicated type B dissection. Stroke and endoleaks remain complications that need to be addressed. Treatment of type B aortic dissection with complete supra-aortic debranching and thoracic endovascular aortic repair in zone 0, however, is associated with high mortality, which might be reduced by improved technology using branched stent grafts.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Prótese Vascular , Procedimentos Endovasculares/métodos , Medição de Risco/métodos , Stents , Adulto , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aortografia , Feminino , Seguimentos , Alemanha/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.
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Esclerose Lateral Amiotrófica/patologia , Encéfalo/patologia , Imagem de Tensor de Difusão , Neurônios Motores/patologia , Fibras Nervosas Mielinizadas/patologia , Adulto , Idoso , Análise de Variância , Anisotropia , Mapeamento Encefálico , Avaliação da Deficiência , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Inhibition of signal transduction pathways has been successfully introduced into cancer treatment. The dual phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 has antitumor activity in vitro against solid tumors. Here, we examined the activity of NVP-BEZ235 in acute lymphoblastic leukemia (ALL) cells and the best modalities for combination approaches. MATERIALS AND METHODS: ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were treated with NVP-BEZ235 alone, or in combination with cytarabine (AraC), doxorubicin (Doxo) or dexamethasone (Dexa). RESULTS: NVP-BEZ235 potently inhibited the proliferation and metabolic activity of ALL cells. Antiproliferative effects were associated with G(0)/G(1) arrest and reduced levels of cyclin-dependent kinase 4 (CDK4) and cyclin D3. Inhibition of PI3K and mTOR activity was detected at 10 and 100 nM. NVP-BEZ235 combined with AraC, Doxo or Dexa synergistically enhanced the cytotoxicity compared to single-drug treatment, even in glucocorticoid-resistant cells. CONCLUSION: NVP-BEZ235 displays pronounced antiproliferative effects in ALL cells and might therefore be a useful drug in the treatment of ALL.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Imidazóis/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Quinolinas/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Imidazóis/administração & dosagem , Células Jurkat , Leucemia de Células B/tratamento farmacológico , Leucemia de Células B/enzimologia , Leucemia de Células B/metabolismo , Leucemia de Células B/patologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Quinolinas/administração & dosagem , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: Our objective was to elucidate long-term clinical and functional effects of intramyocardial stem cell transplant and to identify patients who will show sustained benefit. METHODS: Long-term outcomes of 35 patients after intramyocardial CD133(+) bone marrow stem cell transplant during coronary artery bypass grafting were compared with those of a control group of 20 patients after coronary artery bypass grafting alone. Clinical effects were assessed with the New York Heart Association classification system and the Minnesota Living With Heart Failure questionnaire. Electrocardiography, 24-hour Holter monitoring, echocardiography, myocardial perfusion scanning, magnetic resonance imaging, and computed tomography were performed. Logistic regression analyses were used to identify prognostic factors for improvement in long-term left ventricular ejection fraction after stem cell treatment. RESULTS: The stem cell group revealed similar New York Heart Association and life quality scores to the control group. Myocardial perfusion score at the area of risk was significantly increased in the stem cell group after 36-month follow-up (P = .024 vs control). Multivariate logistic regression analysis revealed a 44-fold higher probability of at least 5% improvement in left ventricular ejection fraction for patients with preoperative left ventricular ejection fraction not greater than 40% than for patients with preoperative ejection fraction greater than 40% (P = .018). Furthermore, patients operated on between 7 and 12 weeks after myocardial infarction had a 56-fold higher chance of at least 5% improvement in left ventricular ejection fraction than patients treated later than 12 weeks after infarction (P = .023). CONCLUSIONS: Intramyocardial stem cell therapy was safe but lacked significant lasting benefits beyond 6 months in our study cohort with a limited number of patients. Preoperative left ventricular ejection fraction and time since myocardial infarction may be critical parameters for selection of patients who can benefit most from intramyocardial stem cell treatment during coronary artery bypass grafting.
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Antígenos CD/análise , Terapia Baseada em Transplante de Células e Tecidos , Ponte de Artéria Coronária , Glicoproteínas/análise , Transplante de Células-Tronco Hematopoéticas , Infarto do Miocárdio/fisiopatologia , Peptídeos/análise , Células-Tronco/imunologia , Função Ventricular Esquerda , Antígeno AC133 , Idoso , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Injeções , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Imagem de Perfusão do Miocárdio , Miocárdio , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Experimental and clinical studies have suggested that intramyocardial bone marrow stem cell transplantation combined with coronary artery bypass grafting might improve left ventricular function in the setting of chronic ischemic heart disease. We therefore conducted a systematic review and meta-analysis of available publications regarding the efficacy and safety of intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting. METHODS: The databases PUBMED, MEDLINE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (all from their inception to May 2009) were searched for randomized controlled trials and cohort studies of intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting to treat ischemic heart disease. Six studies were included. RESULTS: Compared with control groups, the bone marrow stem cell transplantation group showed a significant improvement of left ventricular ejection fraction from baseline to follow-up (5.40%; 95% confidence interval, 1.36-9.44; P = .009). Moreover, the overall change of left ventricular end-diastolic volume from baseline to follow-up favored the bone marrow stem cell therapy group (9.55 mL; 95% confidence interval, -2.82 to 21.92; P = .13). Major adverse cardiovascular events, including ventricular arrhythmia and the composite of other cardiovascular events, were not significantly different between the bone marrow stem cell therapy group and controls (relative risk for ventricular arrhythmia = 0.951; 95% confidence interval, 0.389-2.325; P = .913; relative risk for cardiovascular event = 1.134; 95% confidence interval, 0.28-4.6; P = .86). CONCLUSIONS: Clinical evidence suggests that intramyocardial bone marrow stem cell transplantation in combination with coronary artery bypass grafting is associated with improvements of functional parameters in patients with chronic ischemic heart disease. Furthermore, surgical intramyocardial bone marrow stem cell transplantation seems to be safe.
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Transplante de Medula Óssea , Ponte de Artéria Coronária , Isquemia Miocárdica/cirurgia , Miocárdio/patologia , Transplante de Células-Tronco , Função Ventricular Esquerda , Adulto , Transplante de Medula Óssea/efeitos adversos , Distribuição de Qui-Quadrado , Ponte de Artéria Coronária/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Recuperação de Função Fisiológica , Análise de Regressão , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Volume Sistólico , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133(+)-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient. METHODS: CD133(+)-SC (1 × 10(6) cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days. RESULTS: Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133(+) stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed. CONCLUSION: SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.