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3.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477745

RESUMO

Angiogenesis is a broad spread term of high interest in regenerative medicine and tissue engineering including the dental field. In the last two decades, researchers worldwide struggled to find the best ways to accelerate healing, stimulate soft, and hard tissue remodeling. Stem cells, growth factors, pathways, signals, receptors, genetics are just a few words that describe this area in medicine. Dental implants, bone and soft tissue regeneration using autologous grafts, or xenografts, allografts, their integration and acceptance rely on their material properties. However, the host response, through its vascularization, plays a significant role. The present paper aims to analyze and organize the latest information about the available dental stem cells, the types of growth factors with pro-angiogenic effect and the possible therapeutic effect of enhanced angiogenesis in regenerative dentistry.


Assuntos
Odontologia/tendências , Neovascularização Fisiológica/genética , Regeneração/fisiologia , Medicina Regenerativa/tendências , Autoenxertos/transplante , Humanos , Engenharia Tecidual , Transplante Homólogo/tendências
4.
Hepatology ; 73(4): 1464-1477, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32559317

RESUMO

BACKGROUND AND AIMS: There are more adults than children living with congenital heart disease (CHD) in the United States, with a growing proportion requiring heart-liver transplantation (HLT). Our aim was to ascertain the frequency, outcomes, and prognostic factors in this patient population. APPROACH AND RESULTS: United Network for Organ Sharing data on adult patients who underwent heart transplantation (HT) from 2009 through March 2020 were analyzed. The primary study outcome was patient survival. Cox proportional-hazards modeling assessed for mortality associations. There were 1,084 HT recipients: 817 (75.4%) CHD HTs only, 74 (6.8%) CHD HLTs, 179 (16.5%) non-CHD HLTs, and 14 (1.3%) heart-liver-kidney transplants. The number of CHD HLTs increased from a prior rate of 4/year to 21/year in 2019. Among patients with CHD, the 5-year survival rates were 74.1% and 73.6% in HTs only and HLTs, respectively (P = 0.865). There was a higher rate of allograft failure attributable to rejection in CHD HTs only compared with CHD HLTs (3.2% versus 0.4%; P = 0.014). Only 25 out of 115 HT-performing hospitals undertook CHD HLTs. Higher-volume centers (averaging one CHD HLT per year) had a 5-year patient survival rate of 83.0% compared with 61.3% in lower-volume centers (P = 0.079). Among HLT recipients, total bilirubin (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.12) and diabetes (HR = 2.97, 95% CI = 1.21-7.31) were independently associated with increased mortality risk, whereas CHD and age were not. CONCLUSIONS: The rate of HLT for adult CHD in the United States is rising dramatically. The survival outcomes between CHD HT only and CHD HLT groups are comparable; however, the HLT group had lower rates of acute rejection. Among HLT recipients, diabetes and elevated bilirubin are associated with increased posttransplant mortality risk. An average of one CHD HLT per year could be considered a minimum quality metric at transplant centers.


Assuntos
Cardiopatias Congênitas/cirurgia , Transplante de Coração/mortalidade , Transplante de Coração/métodos , Transplante de Fígado/mortalidade , Transplante de Fígado/métodos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Bilirrubina/sangue , Complicações do Diabetes/mortalidade , Feminino , Seguimentos , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/epidemiologia , Transplante de Coração/tendências , Humanos , Transplante de Fígado/tendências , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Doadores de Tecidos , Transplantados , Transplante Homólogo/métodos , Transplante Homólogo/mortalidade , Transplante Homólogo/tendências , Estados Unidos/epidemiologia , Adulto Jovem
5.
Ann Hematol ; 100(1): 169-180, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33159239

RESUMO

The purpose of our study is to identify the efficacy of ruxolitinib in human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients with multidrug-resistant (MDR)-graft-versus-host disease (GVHD, n = 34). MDR-GVHD was defined as GVHD showing no improvement after at least 3 types of treatments. The median number of previous GVHD-therapies was 4 for both MDR-acute GVHD (aGVHD) and MDR-chronic GVHD (cGVHD). For MDR-aGVHD (n = 15), the median time to response was 10 days (range 2 to 65), and the overall response rate (ORR) was 60.0% (9/15), including 40.0% (6/15) complete response (CR) and 20.0% (3/15) partial response (PR). The 1-year probability of overall survival after ruxolitinib was 66.7%. The rates of hematologic and infectious toxicities were 73.3% and 46.7% after ruxolitinib treatment. For MDR-cGVHD (n = 19), the median time to response was 29 days (range 6 to 175), and the ORR was 89.5% (17/19), including 26.3% (5/19) CR and 63.2% (12/19) PR. All patients remained alive until our last follow-up. The rates of hematologic and infectious toxicities were 36.8% and 47.4% after ruxolitinib treatment. Ruxolitinib is an effective salvage treatment for MDR-GVHD in haplo-HSCT recipients.


Assuntos
Ciclofosfamida , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Pirazóis/uso terapêutico , Terapia de Salvação , Transplante Haploidêntico , Adolescente , Adulto , Criança , Pré-Escolar , Resistência a Múltiplos Medicamentos/fisiologia , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirimidinas , Estudos Retrospectivos , Terapia de Salvação/tendências , Transplante Haploidêntico/tendências , Transplante Homólogo/tendências , Resultado do Tratamento , Adulto Jovem
6.
Ann Hematol ; 99(9): 1979-1988, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594216

RESUMO

The FLAMSA reduced intensity (RIC) concept, also known as "sequential therapy", is a conceptual platform for the treatment of leukemia separated in several parts: induction therapy, a sequence of antileukemic and immunosuppressive conditioning for allogeneic stem cell transplantation, and immune restitution supported by donor lymphocyte transfusions. The antileukemic part consists of fludarabine, cytosine arabinoside, and amsacrine (FLAMSA); non-cross reactive agents like fludarabine and amsacrine have been successfully used in cases of refractoriness and relapse. Immunosuppressive conditioning and transplantation follow after only 3 days of rest. This way, the toxicity of allogeneic transplantation could be reduced and the anti-leukemia effects by using allogeneic immune cells could be optimized. This review summarizes available data on efficacy and toxicity of this approach. Further, possible strategies for improvements are discussed in order to provide better chances for elderly and frail patients and patients with advanced and high-risk disease. Among others, several new agents are available that target molecular changes of leukemia for induction of remission and allow for bridging the time after transplantation until adoptive immunotherapy becomes safe and effective.


Assuntos
Amsacrina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Citarabina/administração & dosagem , Leucemia/terapia , Condicionamento Pré-Transplante/tendências , Vidarabina/análogos & derivados , Antineoplásicos/administração & dosagem , Previsões , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Imunossupressores/administração & dosagem , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Leucemia/imunologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Vidarabina/administração & dosagem
7.
Ann Hematol ; 99(6): 1351-1360, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363416

RESUMO

Acute myeloid leukemia (AML) represents the most common indication for allogeneic hematopoietic cell transplantation (HCT). This study aimed to address the implementation status of allogeneic HCT for adults with AML in Japan and to provide a comprehensive overview of post-transplant outcomes. For this purpose, we analyzed data of 15,186 patients undergoing allogeneic HCT between 1992 and 2016 who were consecutively reported to the Japanese nationwide transplantation registry. The constant increase in the annual number of transplantations was clearly attributable to the growth of unrelated transplantation, and umbilical cord blood transplantation currently accounts for one-third of all allogeneic HCTs. The proportion of older patients has increased steadily since 2000, approximately, in parallel with the introduction of reduced-intensity conditioning. The probability of overall survival (OS) was estimated at 41% (95% confidence interval (CI), 40-42%) for the entire cohort, 56% (95% CI, 55-57%) for patients transplanted in complete remission (CR), and 22% (95% CI, 21-23%) for those transplanted in non-CR. Multivariate analysis identified age, sex, performance status, disease status, cytogenetic risk, donor type, graft source, sex mismatch between the donor and the recipient, and year of transplantation as factors significantly associated with OS. These findings represent the real-world data in Japan, showing the changes in transplantation practice and a detailed estimation of post-transplant outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/tendências , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Adulto Jovem
8.
Circulation ; 141(24): 1954-1967, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32363949

RESUMO

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and nonimmune factors in CAV development. METHODS: Heart transplant recipients were from 4 academic centers (Pitié-Salpêtrière and Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, and Cedars-Sinai, Los Angeles; 2004-2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological, and immunologic parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories by using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. RESULTS: A total of 1301 patients were included (815 and 486 in the European and US cohorts, respectively). The median follow-up after transplantation was 6.6 (interquartile range, 4-9.1) years with 4710 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years. The 4 trajectories were characterized by (1) patients without CAV at 1 year and nonprogression over time (56.3%), (2) patients without CAV at 1 year and late-onset slow CAV progression (7.6%), (3) patients with mild CAV at 1 year and mild progression over time (23.1%), and (4) patients with mild CAV at 1 year and accelerated progression (13.0%). This model showed good discrimination (0.92). Among candidate predictors assessed, 6 early independent predictors of these trajectories were identified: donor age (P<0.001), donor male sex (P<0.001), donor tobacco consumption (P=0.001), recipient dyslipidemia (P=0.009), class II anti-human leukocyte antigen donor-specific antibodies (P=0.004), and acute cellular rejection ≥2R (P=0.028). The 4 CAV trajectories manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios, and showed gradients for overall-cause mortality (P<0.001). CONCLUSIONS: In a large multicenter and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of patients undergoing heart transplantation for early risk stratification, patient monitoring, and clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04117152.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/cirurgia , Rejeição de Enxerto/epidemiologia , Transplante de Coração/tendências , Vigilância da População , Complicações Pós-Operatórias/epidemiologia , Adulto , Aloenxertos , Bélgica/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Transplante de Coração/efeitos adversos , Humanos , Los Angeles/epidemiologia , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Vigilância da População/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto Jovem
9.
Ann Hematol ; 99(6): 1361-1368, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32342133

RESUMO

In everyday gynecological practice, there is an unmet need to manage survivors after allogeneic hematopoietic cell transplantation (allo-HCT). The major gynecological complications include premature ovarian insufficiency (POI), chronic graft-versus-host disease (cGVHD) of the anogenital zone (cGVHDgyn), and secondary neoplasms. Aiming to assess a real-life scale of problems associated with HCT, we performed a detailed analysis of a consecutive series of females after allo-HCT who were referred for a routine gynecological evaluation. The study includes 38 females after allo-HCT in whom gynecological examination with cervical smear and USG were performed, followed by colposcopy according to NCCN guidelines. NIH scoring system was used to classify a grade of cGVHDgyn. The incidence of cGVHD was 71% whereas GVHDgyn was 29%, including 5 patients with score 3 at the time of diagnosis. The other manifestations (frequently noted) included the skin, mucosa, eyes, and liver. Menopause was diagnosed in 93% females, and in 81% of them, POI criteria were fulfilled. Ovarian function resumed in 2 cases. The rate of abnormal cytology was 26%: 4 ASCUS, 1 AGUS, 1 LSIL, 3 HSIL/ASC-H, and one cytological suspicion of cervical cancer. GVHDgyn was documented in 10 patients, and 6 of them had abnormal cervical cytology. Early topical estrogen therapy led to a significant reduction in vaginal dryness (p < 0.05), dyspareunia (p < 0.05), and less frequent cGVHDgyn (p < 0.05). GVHDgyn develops in about 30% of long-term allo-HCT survivors. Topical estrogens and hormonal replacement therapy alleviate symptoms and prevent the occurrence of severe consequences of menopause.


Assuntos
Gerenciamento Clínico , Doenças dos Genitais Femininos/etiologia , Doenças dos Genitais Femininos/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/tendências , Sobreviventes , Adolescente , Adulto , Feminino , Seguimentos , Doenças dos Genitais Femininos/diagnóstico , Humanos , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto Jovem
10.
Cancer Immunol Immunother ; 69(5): 879-899, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32130453

RESUMO

A better understanding of the complex interactions between the immune system and tumour cells from different origins has opened the possibility to design novel procedures of antitumoral immunotherapy. One of these novel approaches is based on the use of autologous or allogeneic natural killer (NK) cells to treat cancer. In the last decade, different strategies to activate NK cells and their use in adoptive NK cell-based therapy have been established. Although NK cells are often considered as a uniform cell population, several phenotypic and functionally distinct NK cells subsets exist in healthy individuals, that are differentially affected by ageing or by apparently innocuous viruses such as cytomegalovirus (CMV). In addition, further alterations in the expression of activating and inhibitory receptors are found in NK cells from cancer patients, likely because of their interaction with tumour cells. Thus, NK cells represent a promising strategy for adoptive immunotherapy of cancer already tested in phase 1/2 clinical trials. However, the existence of NK cell subpopulations expressing different patterns of activating and inhibitory receptors and different functional capacities, that can be found to be altered not only in cancer patients but also in healthy individuals stratified by age or CMV infection, makes necessary a personalized definition of the procedures used in the selection, expansion, and activation of the relevant NK cell subsets to be successfully used in NK cell-based immunotherapy.


Assuntos
Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Neoplasias/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Imunoterapia Adotiva/tendências , Células Matadoras Naturais/transplante , Subpopulações de Linfócitos/transplante , Neoplasias/terapia , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Transplante Homólogo/métodos , Transplante Homólogo/tendências
11.
Ann Hematol ; 99(6): 1369-1376, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32173768

RESUMO

Allogeneic hematopoietic transplantation (allo-HCT) is still associated with significant morbidity and mortality, and risk stratification is critical. In this study, we analyzed the relationship between blood pressure control early after allo-HCT and survival outcomes. All patients who survived longer than 28 days after allo-HCT at our center between June 2007 and June 2018 (n = 353) were included, and the average systolic blood pressure (asBP) from 1 to 28 days after allo-HCT was calculated. According to the results of a ROC curve analysis, an asBP of 131 mmHg was defined as a cut-off value between high and low asBP groups. Non-relapse mortality (NRM) and OS were significantly inferior in the high asBP group (2-year-NRM 28.0% vs 11.1%, P < 0.001; 2-year-OS 46.7% vs 65.7%, P = 0.001). In addition, baseline asBP before commencement of the conditioning regimen and elevation of asBP (asBP - baseline asBP) were both associated with inferior NRM. While these results were also observed in the younger patients (≤ 50 years), no relationship was observed in the older patients (> 50 years). High blood pressure within 28 days after allo-HCT was associated with inferior survival outcomes, especially in patients younger than 50 years.


Assuntos
Pressão Sanguínea/fisiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/tendências , Hipertensão/mortalidade , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/tendências , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Resultado do Tratamento , Adulto Jovem
13.
BMC Musculoskelet Disord ; 20(1): 511, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679513

RESUMO

BACKGROUND: Proximal humeral fractures (PHFs) are the third most commonly occurring fractures in elderly patients. Most of these fractures can be treated with conservative methods, but the optimal surgical treatment strategy for unstable fractures in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes between locking compression plate (LCP) fixation and LCP fixation with fibular allograft implantation for the treatment of comminuted PHFs. METHODS: We retrospectively reviewed 60 patients (mean age, 72.75 years) with closed 3- or 4-part fractures, and a minimum of 2 years of follow-up. Fracture reduction was quantitatively determined by humeral head height (HHH) and neck-shaft angle (NSA). The clinical outcome was evaluated by Constant-Murley score (CMS) and American Shoulder and Elbow Surgeons (ASES) score. RESULT: The average radiological changes were higher in the LCP group than in the locking plate with fibular allograft group (HHH of 4.16 mm vs 1.18 mm [p < 0.001] and NSA of 9.94° versus 3.12° [p < 0.001]) . The final average outcome scores were lower in the LCP group than in the FA group (CMS of 73.00 vs 78.96 [p = 0.024] and ASES score of 72.80 vs 78.64 [p = 0.022]). The FA group showed better forward elevation (p = 0.010) and abduction (p = 0.002); however, no significant differences were observed for shoulder external rotation or internal rotation. The number of complications was higher in the LCP group (28.57%) than in the FA group (1.2%) (p < 0.001). CONCLUSION: For comminuted PHFs in elderly patients, LCP fixation combined with a fibular allograft is reasonable option to ensure satisfactory radiological and clinical outcomes. TRIAL REGISTRATION: ZDYJLY(2018)New-9 . Name of registry: IEC for clinical Research of Zhongda Hospital, Affiliated to Southeast University. Date of registration: 2018-05-17.


Assuntos
Placas Ósseas , Transplante Ósseo/métodos , Fíbula/transplante , Fixação Interna de Fraturas/métodos , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Idoso , Placas Ósseas/tendências , Transplante Ósseo/tendências , Estudos de Coortes , Feminino , Fixação Interna de Fraturas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/métodos , Transplante Homólogo/tendências
14.
BMC Nephrol ; 20(1): 354, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510954

RESUMO

BACKGROUND: Although immunoglobulin A nephropathy (IgAN) is associated with an increased risk of renal allograft failure, evidences for its treatment, including renin-angiotensin-aldosterone system blockade (RAASB) usage, remain limited. METHODS: In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types, albuminuria changes, and risk of 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used. RESULTS: A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft IgAN diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 [1.09-6.98]; P = 0.03). CONCLUSIONS: In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted.


Assuntos
Aloenxertos/efeitos dos fármacos , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Aloenxertos/fisiologia , Aloenxertos/transplante , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Coortes , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Prognóstico , Sistema Renina-Angiotensina/fisiologia , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências
15.
Int J Cardiol ; 292: 166-170, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171392

RESUMO

BACKGROUND: A Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was previously developed showing that multiple comorbidities including moderate or greater valvular heart disease to be predictors of non-relapse mortality after allogeneic HCT. However, detailed description of the impact of valve disease on outcomes is lacking. METHODS: Among a large cohort of patients given allogeneic HCT between 2000 and 2017, we identified 21 patients with moderate or severe valvular disease. We also identified a cohort of 42 controls matched on age and HCT-CI score. The primary outcome was all-cause mortality, with censoring at two years of follow-up. Secondary outcomes included mortality without relapse, duration of index admission, number of readmissions, increase in creatinine and peak troponin. RESULTS: Non-myeloablative regimens were more common in the valve disease cohort compared to controls (86% vs 54% p = 0.012). Valvular disease was associated with increased all-cause mortality with adjusted hazard ratio of 2.17 (CI 1.08-4.34, p = 0.029) and for non-relapse mortality with adjusted hazard ratio of 2.53 (CI 1.16-5.52, p = 0.020). In the valve disease cohort, creatinine increased by 1.6 vs 0.9 mg/dL (p = 0.003) and peak troponin by 1.6 vs 0.3 ng/mL (p = 0.05) compared to controls. There was no difference in readmissions or length of stay when accounting for outpatient treatment. CONCLUSIONS: Despite having similar pre-procedure risk factors and undergoing less aggressive chemotherapy regimens, patients with moderate valvular disease or greater, most of whom did not meet current guideline recommendations for repair, had worse non-relapse related outcomes with higher mortality, renal and myocardial injury.


Assuntos
Doenças das Valvas Cardíacas/mortalidade , Doenças das Valvas Cardíacas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/tendências , Índice de Gravidade de Doença , Adulto , Idoso , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/tendências , Transplante Homólogo/métodos , Transplante Homólogo/mortalidade , Transplante Homólogo/tendências , Resultado do Tratamento
16.
Leuk Lymphoma ; 60(13): 3235-3243, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31185769

RESUMO

To describe temporal trends in treatment among older adult (≥66 years) patients diagnosed with diffuse large B-cell lymphoma (DLBCL), we analyzed 18,058 DLBCL patients from the Surveillance, Epidemiology, and End Results linked Medicare (SEER-Medicare) database diagnosed between 2001 and 2013. Among 65% of patients receiving treatment after diagnosis, R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) was the most common frontline therapy, increasing with more recent treatment year: 51% (2001-2003) vs. 69% (2010-2014). Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) was uncommon in these Medicare patients. As the addition of rituximab increased over time, we also observed an improved survival rate over time. It is possible there is an association, but we cannot make this inference as effectiveness was not measured in this study. Overall survival estimates indicated that survival probabilities steadily improved in more recent years; however, 5-year survival was <40%, indicating the need for improved treatment options for older adult DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/tendências , Linfoma Difuso de Grandes Células B/terapia , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Medicare/estatística & dados numéricos , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida/tendências , Fatores de Tempo , Transplante Autólogo/estatística & dados numéricos , Transplante Autólogo/tendências , Transplante Homólogo/estatística & dados numéricos , Transplante Homólogo/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia , Vincristina/uso terapêutico
17.
Blood Adv ; 3(12): 1858-1867, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31217161

RESUMO

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT01050946.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/estatística & dados numéricos , Adulto , Transplante de Medula Óssea/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Haplótipos/efeitos dos fármacos , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/radioterapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/uso terapêutico , Neutrófilos/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/estatística & dados numéricos , Transplante Homólogo/tendências , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Irradiação Corporal Total/efeitos adversos , Irradiação Corporal Total/métodos
18.
Int J Cardiol ; 290: 129-133, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31101542

RESUMO

BACKGROUND: In patients having undergone orthotopic heart transplantation, a number of complications exist that are known to be connected to both telomerase activity and telomere length. The aim of this study was to determine how telomere length in aortic DNA correlates with the subsequent post-transplantation development of the patients. MATERIALS AND METHODS: Between 2005 and 2015, we collected aortic samples from 376 heart recipients (age 50.8 ±â€¯11.8 years) and 383 donors (age 38.6 ±â€¯12.2 years). Relative telomere length in aortic tissue DNA was determined using quantitative PCR. RESULTS: Shorter telomere length was detected in heart allograft recipients compared to donors (P < 0.0001). Patients suffering acute cellular rejection had significantly shorter telomere length (P < 0.01) than patients without rejection. Shorter telomere length was observed in patients with implanted mechanical circulatory support before heart transplantation (P < 0.03), as well as in subjects with cardiac allograft vasculopathy (P < 0.05). Overall survival time after heart transplantation was associated with shorter donor telomeres (P < 0.004). CONCLUSIONS: Telomere length differed between donors and recipients independent of the sex and age of the patients. Our findings suggest a potential new linkage between the aortic telomere length of recipients and post-heart transplant complications. Further studies focusing on epigenetic modifications and gene regulation involved in telomere maintenance in transplanted patients should verify our results.


Assuntos
Aorta/fisiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Transplante de Coração/tendências , Encurtamento do Telômero/fisiologia , Transplante Homólogo/tendências , Adulto , Feminino , Rejeição de Enxerto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Telômero/fisiologia , Doadores de Tecidos
19.
J Neurol ; 266(8): 1960-1972, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087160

RESUMO

BACKGROUND: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. METHODS: We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. RESULTS: Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. CONCLUSIONS: Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/mortalidade , Adulto , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade/tendências , Doenças do Sistema Nervoso/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendências , Adulto Jovem
20.
J Orthop Surg Res ; 14(1): 85, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898115

RESUMO

OBJECTIVE: We compared autografts and allograft using partial and complete transphyseal anterior cruciate ligament (ACL) reconstruction techniques among skeletally immature individuals. METHODS: Male and females younger than 18 and 16 years old, respectively, diagnosed with ACL tear from April 2006 to March 2012 entered the study. One group had four-strand hamstring autograft, and the other had tibialis posterior allograft reconstruction. Those who had allografts either had hyper-laxity or recurvatum. RESULTS: Achieved mean (± SD) 2000 International Knee Documentation Committee subjective score was not statistically different (P = 0.385) between allograft (n = 13) (84.3 ± 3.2) and autograft groups (n = 18) (85.6 ± 4.4). Mean Knee injury and Osteoarthritis Outcome Score (KOOS) subscale Knee-Related Quality of Life at 2 years was 78.0 ± 7.2 and 75 ± 7.4 for allograft and autograft groups, respectively (p = 0.261). Mean 2-year KOOS subscale Sports and Recreation was 82.1 ± 5.8 and 84.8 ± 6.6 for allograft and autograft groups, respectively (p = 0.244). No patient reported instability, giving way, or locking of the knee. Pivot shift test was negative in all patients; however, a minor positive Lachman test was found in six cases (46%) within the allograft group and seven cases (39%) in the autograft group. One postoperative septic arthritis was documented in the autograft group. CONCLUSION: Considering existing concern that joint laxity and recurvatum are among the precursors of non-contact ACL injury in adolescents, bone-patellar-bone autografts are not applicable in this age group because of the open physis; furthermore, considering that hamstring autografts are insufficient (size thickness and stretchability), we recommend soft tissue allografts for ACL reconstruction in skeletally immature patients.


Assuntos
Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Autoenxertos/transplante , Instabilidade Articular/diagnóstico por imagem , Adolescente , Lesões do Ligamento Cruzado Anterior/epidemiologia , Reconstrução do Ligamento Cruzado Anterior/tendências , Autoenxertos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Instabilidade Articular/epidemiologia , Masculino , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/tendências , Estudos Prospectivos , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Transplante Homólogo/métodos , Transplante Homólogo/tendências
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