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1.
Haematologica ; 108(11): 2982-2992, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37317888

RESUMO

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.


Assuntos
Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Fluordesoxiglucose F18/uso terapêutico , Estudos Retrospectivos , Imunoterapia Adotiva , Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/tratamento farmacológico
2.
J Immunol ; 204(9): 2380-2391, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32213562

RESUMO

The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-λ1 is a key placental IFN that appeared less protective than IFN-α, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.


Assuntos
Imunidade Inata/imunologia , Macrófagos/imunologia , Placenta/imunologia , Adolescente , Antivirais/imunologia , Proteína DEAD-box 58/imunologia , Feminino , Feto/imunologia , Humanos , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Interferon-alfa/imunologia , Ligantes , Fenótipo , Gravidez
3.
BMC Pregnancy Childbirth ; 21(1): 71, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478433

RESUMO

BACKGROUND: Traditional prenatal care includes up to 13 in person office visits, and the cost of this care is not well-described. Alternative models are being explored to better meet the needs of patients and providers. OB Nest is a telemedicine-enhanced program with a reduced frequency of in-person prenatal visits. The cost implications of connected care services added to prenatal care packages are unclear. METHODS: Using data from the OB Nest randomized, controlled trial we analyzed the provider and staff time associated with prenatal care in the traditional and OB Nest models. Fewer visits were required for OB Nest, but given the compensatory increase in connected care activity and supplies, the actual cost difference is not known. Nursing and provider staff time was prospectively recorded for all patients enrolled in the OB Nest clinical trial. Published 2015 national wages for healthcare workers were used to calculate the actual labor cost of providing either traditional or OB Nest prenatal care in 2015 US dollars. Overhead expenses and opportunity costs were not considered. RESULTS: Total provider cost was decreased caring for the OB Nest participants, but nursing cost was increased. OB Nest care required an average of 160.8 (+/- 45.0) minutes provider time and 237 (+/- 25.1) minutes nursing time, compared to 215.0 (+/- 71.6) and 99.6 (+/- 29.7) minutes for traditional prenatal care (P < 0.01). This translated into decreased provider cost and increased nursing cost (P < 0.01). Supply costs increased, travel costs declined, and overhead costs declined in the OB Nest model. CONCLUSIONS: In this trial, labor cost for OB Nest prenatal care was 34% higher than for traditional prenatal care. The increased cost is largely attributable to additional nursing connected care time, and in some practice settings may be offset by decreased overhead costs and increased provider billing opportunities. Future efforts will be focused on development of digital solutions for some routine nursing tasks to decrease the overall cost of the model. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT02082275 .


Assuntos
Economia da Enfermagem , Cuidado Pré-Natal/economia , Cuidado Pré-Natal/métodos , Telemedicina/economia , Adulto , Custos e Análise de Custo , Feminino , Humanos , Minnesota , Cuidados de Enfermagem/métodos , Cuidados de Enfermagem/estatística & dados numéricos , Gravidez , Telemedicina/estatística & dados numéricos , Adulto Jovem
4.
Fetal Diagn Ther ; 48(4): 258-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33756472

RESUMO

INTRODUCTION: Congenital diaphragmatic hernia (CDH) affects 1 in 3,000 live births and is associated with significant morbidity and mortality. METHODS: A review of fetal magnetic resonance imaging (MRI) examinations was performed for fetuses with left CDH and normal lung controls. Image review and manual tracings were performed by 4 pediatric radiologists; right and left lung volumes in the coronal and axial planes as well as liver volume above and below the diaphragm in the coronal plane were measured. Intra- and interreviewer reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Excellent intra- and interreviewer reproducibility of the right and left lung volume measurements was observed in both axial planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.99; left lung: 0.97, 95% CI: 0.95-0.98) and coronal planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.98; left lung: 0.96, 95% CI: 0.93-0.98). Moderate-to-good interreviewer reproducibility was observed for liver volume above the diaphragm (ICC 0.7, 95% CI: 0.59-0.81). Liver volume below the diaphragm had a good-to-excellent interreviewer reproducibility (ICC 0.88, 95% CI: 9.82-0.93). CONCLUSIONS: The present study demonstrated an excellent intra- and interreviewer reproducibility of MRI lung volume measurements and good-to-moderate inter- and intrareviewer reproducibility of liver volume measurements after standardization of the methods at our fetal center.


Assuntos
Hérnias Diafragmáticas Congênitas , Criança , Feminino , Feto , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar , Imageamento por Ressonância Magnética , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia Pré-Natal
5.
Clin Transplant ; 34(10): e14056, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748982

RESUMO

BACKGROUND: Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). METHODS: Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. RESULTS: Participation was 55.3% (N = 199). Baseline RISC-10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing > 1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P = .01). CONCLUSION: One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.


Assuntos
Transplante de Pulmão , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários
6.
Infect Dis Obstet Gynecol ; 2020: 4365259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148387

RESUMO

Background: Sepsis is a leading cause of mortality and morbidity in neonates, with group B streptococcus (GBS) remaining the most frequent pathogen isolated from term infants. Surveillance data showed that the majority of cases of early-onset GBS disease were neonates born to women who either received no or suboptimal intrapartum antibiotic prophylaxis with a notable portion of those women having a missed opportunity to receive ≥4 hours of chemoprophylaxis. Women planning delivery by cesarean section who present in labor or rupture of membranes prior to their scheduled surgery are unlikely to receive optimal GBS chemoprophylaxis and thus their neonates are at risk of having sepsis. Materials and Methods. A retrospective cohort study of women-infant dyads was extracted from the Consortium on Safe Labor dataset. Women who had an unlabored cesarean section at ≥37 + 0 week gestation were selected and divided into four groups based on GBS status and timing of cesarean section with respect to onset of labor or rupture of membranes. The rate of neonatal sepsis and the patterns of intrapartum antibiotic chemoprophylaxis were determined. Results: The sepsis rate (4.5%) among neonates of GBS-colonized women having their unlabored cesarean section after onset of labor or rupture of membranes was significantly higher than that in any other group in this study. In this group, 9.4% of women received chemoprophylaxis for ≥4 hours, while 31% had a missed opportunity to receive ≥4 hours of chemoprophylaxis. Conclusion: This study suggests that neonates of GBS-colonized women having a planned cesarean section after onset of labor or rupture of membranes are at increased risk of having a sepsis diagnosis. This finding suggest the need for additional studies to assess the risk of sepsis among neonates of women in this group.


Assuntos
Cesárea/efeitos adversos , Ruptura Prematura de Membranas Fetais/epidemiologia , Sepse Neonatal/epidemiologia , Sepse Neonatal/etiologia , Infecções Estreptocócicas/etiologia , Streptococcus agalactiae/fisiologia , Adulto , Antibioticoprofilaxia/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Início do Trabalho de Parto , Trabalho de Parto , Sepse Neonatal/diagnóstico , Gravidez , Complicações Infecciosas na Gravidez , Estudos Retrospectivos , Fatores de Risco , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/isolamento & purificação , Adulto Jovem
7.
Liver Transpl ; 25(3): 425-435, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30615251

RESUMO

T cell-mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate-to-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Transplante de Fígado/efeitos adversos , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Humanos , Incidência , Fígado/imunologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Linfócitos T/imunologia , Fatores de Tempo , Resultado do Tratamento
8.
Clin Transplant ; 32(10): e13395, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30160337

RESUMO

BACKGROUND: Renal dysfunction occurs commonly after heart transplantation (HTx) with wide inter-individual variability but whether a genetic predisposition exists in these patients is unknown. Genomewide association studies (GWAS) have not been performed to assess the association of genetic variation with change in renal function after HTx. METHODS: Clinical and demographic data of patients who underwent HTx and provided blood samples and consent for genetic analysis were included. Genotyping was performed using Illumina Infinium Human CoreExome v1.0 analysis kit. A GWAS utilizing linear regression models was performed with estimated glomerular filtration rate (eGFR) at 1 year as the phenotype after adjusting for baseline eGFR prior to HTx and conversion from calcineurin inhibitor to sirolimus as primary immunosuppression therapy. RESULTS: A total of 251 HTx recipients were genotyped for 314,903 single nucleotide polymorphisms (SNPs). The mean (SD) age was 50 (12.5) years; most patients were of European origin (n = 243, 96.8%) and males (n = 179, 71.3%). After adjustment for potential confounders, two variants, rs17033285 (P = 4.3 × 10-7 ) and rs4917601 (P = 6.46 × 10-7 ), in a long non-coding RNA (lncRNA) gene LINC01121 and a pseudogene BTBD7P2, were identified to have a significant association with change in GFR at 1 year after HTx. CONCLUSIONS: Our first of its kind GWAS demonstrates that genetic variation affects renal function after HTx independent of other risk factors. Agnostic genetic approaches such as these may lead to identification of novel biological pathways such as the role of lncRNAs in the development of renal dysfunction post-HTx.


Assuntos
Loci Gênicos , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Rejeição de Enxerto/diagnóstico , Transplante de Coração/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Insuficiência Renal/diagnóstico , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Insuficiência Renal/etiologia , Fatores de Risco
9.
Liver Transpl ; 23(1): 11-18, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27658200

RESUMO

Share 35 was implemented in 2013 to direct livers to the most urgent candidates by prioritizing Model for End-Stage Liver Disease (MELD) ≥ 35 patients. We aim to evaluate this policy's impact on costs and mortality. Our study includes 834 wait-listed patients and 338 patients who received deceased donor, solitary liver transplants at Mayo Clinic between January 2010 and December 2014. Of these patients, 101 (30%) underwent transplantation after Share 35. After Share 35, 29 (28.7%) MELD ≥ 35 patients received transplants, as opposed to 46 (19.4%) in the pre-Share 35 era (P = 0.06). No significant difference in 90-day wait-list mortality (P = 0.29) nor 365-day posttransplant mortality (P = 0.68) was found between patients transplanted before or after Share 35. Mean costs were $3,049 (P = 0.30), $5226 (P = 0.18), and $10,826 (P = 0.03) lower post-Share 35 for the 30-, 90-, and 365-day pretransplant periods, and mean costs were $5010 (P = 0.41) and $5859 (P = 0.57) higher, and $9145 (P = 0.54) lower post-Share 35 for the 30-, 90-, and 365-day posttransplant periods. In conclusion, the added cost of transplanting more MELD ≥ 35 patients may be offset by pretransplant care cost reduction. Despite shifting organs to critically ill patients, Share 35 has not impacted mortality significantly. Liver Transplantation 23:11-18 2017 AASLD.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/economia , Transplante de Fígado/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Listas de Espera/mortalidade , Adulto , Idoso , Análise Custo-Benefício , Doença Hepática Terminal/economia , Doença Hepática Terminal/mortalidade , Feminino , Custos de Cuidados de Saúde , Gastos em Saúde , Política de Saúde/economia , Política de Saúde/legislação & jurisprudência , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/economia , Resultado do Tratamento , Estados Unidos
14.
Clin Transplant ; 30(3): 247-55, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26701203

RESUMO

BACKGROUND: Frailty in non-transplant populations increases morbidity and mortality. Muscle wasting is an important frailty characteristic. Low body mass index is used to measure wasting, but can over- or underestimate muscle mass. Computed tomography (CT) software can directly measure muscle mass. It is unknown if muscle wasting is important in lung transplantation. AIM AND METHODS: The aim of this single-center, retrospective cohort study was to determine whether pre-transplant low muscle mass (as measured by CT using Slice-O-matic software at L2-L3 interspace) was associated with post-transplantation mortality, hospital and intensive care unit length of stay (LOS), duration of mechanical ventilation, or primary graft dysfunction. Lung transplant recipients from 2000 to 2012 with a CT scan less than six months prior to transplant were included. Univariate, multivariate, and Kaplan-Meier analyses were conducted. RESULTS: Thirty-six patients were included. Those with low muscle index (lower 25th percentile) had a worse survival (hazard ratio = 3.83; 95% confidence interval 1.42-10.3; p = 0.007) and longer hospital LOS by an estimated 7.2 d (p = 0.01) when adjusted for age and sex as compared to those with higher muscle index. CONCLUSION: Low muscle index at lung transplantation is associated with worse survival and increased hospital LOS.


Assuntos
Rejeição de Enxerto/diagnóstico , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Atrofia Muscular/fisiopatologia , Complicações Pós-Operatórias , Disfunção Primária do Enxerto/diagnóstico , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/diagnóstico por imagem , Disfunção Primária do Enxerto/diagnóstico por imagem , Disfunção Primária do Enxerto/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos
15.
Clin Transplant ; 29(4): 311-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25604399

RESUMO

Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single-center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15-15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58-4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.


Assuntos
Antibioticoprofilaxia/efeitos adversos , Antifúngicos/efeitos adversos , Azóis/efeitos adversos , Pneumopatias/cirurgia , Transplante de Pulmão , Micoses/epidemiologia , Complicações Pós-Operatórias , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Humanos , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Transplantados , Estados Unidos/epidemiologia
16.
Transpl Int ; 28(12): 1383-91, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26183487

RESUMO

BACKGROUND: Survival and recurrence of cancer after liver transplant (LT) for perihilar cholangiocarcinoma (CCA) following neoadjuvant chemoradiotherapy are strongly correlated with the presence of residual CCA in the liver explant. AIM: To determine factors predicting response to neoadjuvant therapy using the presence of residual CCA on explant as a surrogate marker. METHODS: Characteristics of 109 patients having undergone LT for cholangiocarcinoma were abstracted, with attention to parameters hypothesized to influence radiation therapy efficacy. RESULTS: In the multivariable model, the presence of portal vein encasement (OR 11.8; 95% CI: 2.43-57.21; P = 0.002) and MELD score (OR 1.13; 95% CI: 1.02-1.26; P = 0.017) were predictive of residual macroscopic disease (c-statistics 0.78). Oral capecitabine in addition to standard 5-fluorouracil chemotherapy (OR 0.32, 95% CI: 0.14, 0.71; P = 0.006) was independently protective against residual cancer, independent of MELD score. CONCLUSIONS: Portal vein encasement was strongly predictive of residual macroscopic disease. Radial tumor diameter did not have greater predictive value than longitudinal diameter, confirming the appropriateness of current protocol selection criteria. No particular tumor morphology predicted better response. Maintenance oral capecitabine following 5-fluorouracil infusion was independently protective against residual disease. Portal vein encasement as a negative prognostic finding should be taken into account to optimize patient selection and management.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Tumor de Klatskin/patologia , Tumor de Klatskin/terapia , Veia Porta/patologia , Adulto , Neoplasias dos Ductos Biliares/mortalidade , Quimiorradioterapia Adjuvante , Protocolos Clínicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Tumor de Klatskin/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise Multivariada , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
17.
Health Qual Life Outcomes ; 13: 95, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-26138599

RESUMO

BACKGROUND: Deficits in health-related quality of life (HRQOL) may be associated with worse patient experiences, outcomes and even survival. While there exists evidence to identify risk factors associated with deficits in HRQOL among patients with individual medical conditions such as cancer, it is less well established in more general populations without attention to specific illnesses. This study used patients with a wide range of medical conditions to identify contributors with the greatest influence on HRQOL deficits. METHODS: Self-perceived general health and depressive symptoms were assessed using data from 21,736 Mayo Clinic Biobank (MCB) participants. Each domain was dichotomized into categories related to poor health: deficit (poor/fair for general health and ≥3 for PHQ-2 depressive symptoms) or non-deficit. Logistic regression models were used to test the association of commonly collected demographic characteristics and disease burden with each HRQOL domain, adjusting for age and gender. Gradient boosting machine (GBM) models were applied to quantify the relative influence of contributors on each HRQOL domain. RESULTS: The prevalence of participants with a deficit was 9.5 % for perception of general health and 4.6 % for depressive symptoms. For both groups, disease burden had the strongest influence for deficit in HRQOL (63 % for general health and 42 % for depressive symptoms). For depressive symptoms, age was equally influential. The prevalence of a deficit in general health increased slightly with age for males, but remained stable across age for females. Deficit in depressive symptoms was inversely associated with age. For both HRQOL domains, risk of a deficit was associated with higher disease burden, lower levels of education, no alcohol consumption, smoking, and obesity. Subjects with deficits were less likely to report that they were currently working for pay than those without a deficit; this association was stronger among males than females. CONCLUSIONS: Comorbid health burden has the strongest influence on deficits in self-perceived general health, while demographic factors show relatively minimal impact. For depressive symptoms, both age and comorbid health burden were equally important, with decreasing deficits in depressive symptoms with increasing age. For interpreting patient-reported metrics and comparison, one must account for comorbid health burden.


Assuntos
Doença Crônica/epidemiologia , Doença Crônica/psicologia , Depressão/epidemiologia , Depressão/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Adulto , Idoso , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Perfil de Impacto da Doença , Inquéritos e Questionários , Estados Unidos/epidemiologia
18.
J Hepatol ; 61(1): 124-31, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24607625

RESUMO

BACKGROUND & AIMS: Though hepatic involvement is common in patients with hereditary haemorrhagic telangiectasia (HHT), symptomatic liver disease is rare but potentially fatal without liver transplantation. Factors associated with clinically significant liver disease in patients with HHT are unknown. METHODS: In this prospective cohort study, we included consecutive patients from 2001 to 2011 with definite HHT, who underwent systematic protocol screening including contrast-enhanced hepatic CT and/or abdominal ultrasound. Using a multivariable logistic regression model, we developed a simple clinical scoring index to identify the presence of symptomatic liver disease (cardiac failure, portal hypertension, or biliary disease) or 'at-risk' liver disease (asymptomatic patients, with hepatic bruit, abnormal liver biochemistry, or elevated cardiac index). RESULTS: Of 316 patients with definite HHT, 171 patients (54.1%; age 53.4 ± 15.2 y, 101 females) had hepatic involvement on imaging. Twenty-nine patients had symptomatic liver disease (22 patients with high-output heart failure); 45 patients were 'at-risk' for liver disease. Using multivariable logistic regression analysis, we derived a score using age, gender, hemoglobin and alkaline phosphatase at presentation which could accurately distinguish patients with clinically significant liver involvement from patients with no or incidental liver lesions (c-statistic=0.80). A score <3 indicated low risk (<5%) and score >6 indicated high risk (>80%) of harboring clinically significant liver disease in HHT. CONCLUSIONS: A simple scoring system can distinguish patients at low, moderate, and high risk of harboring clinically significant liver disease. With validation, this score may be used to identify patients for individualized screening and enrollment in clinical trials.


Assuntos
Hepatopatias/etiologia , Hepatopatias/patologia , Telangiectasia Hemorrágica Hereditária/complicações , Adulto , Idoso , Fosfatase Alcalina/sangue , Malformações Arteriovenosas/etiologia , Malformações Arteriovenosas/patologia , Estudos de Coortes , Feminino , Hemoglobinas/metabolismo , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Hepatopatias/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia
19.
Transplant Cell Ther ; 30(4): 455.e1-455.e7, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38346643

RESUMO

Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester. In our cohort of 95 CAR-T recipients, almost one-half had low CD4 T and B cell counts prior to CAR-T that remained persistently low post-CAR-T. Prior to CAR-T, the seronegative rate was lowest for tetanus and highest for pneumococcus irrespective of prior transplantation status (within 2 years of CAR-T). At 3 months post-CAR-T, overall seronegativity rates were similar to pre-CAR-T rates for the prior transplantation and no prior transplantation groups. For patients who received IVIG, loss of seropositivity was seen for hepatitis A (1 of 7; 14%). No seroconversion was noted for pneumococcus. For patients who did not receive IVIG, loss of seropositivity was seen for pneumococcus (2 of 5; 40%) and hepatitis A (1 of 4; 25%). CAR-T recipients commonly experience T cell and B cell lymphopenia and might not have adequate antibody titers against vaccine-preventable diseases despite IVIG supplementation. Loss of antibody titers post-CAR-T is possible, highlighting the need for revaccination. Additional studies with long-term follow-up are needed to inform the optimal timing of immunization post-CAR-T.


Assuntos
Hepatite A , Linfoma , Receptores de Antígenos Quiméricos , Humanos , Estudos Retrospectivos , Imunoglobulinas Intravenosas , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos
20.
Blood Adv ; 8(18): 4877-4885, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39028948

RESUMO

ABSTRACT: Unirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study end points included relapse-free survival (RFS), event-free survival (EFS), and overall survival. Before CART infusion, 48 patients (32%) received bridging radiotherapy (BRT), and 102 (68%) did not. The median follow-up was 21 months. After CART infusion, BRT patients had higher objective response (92% vs 78%; P = .046) and sustained complete response rates (54% vs 33%; P = .015). Local relapse in sites present before CART was lower in the BRT group (21% vs 46%; P = .003). BRT patients had improved 2-year RFS (53% vs 44%; P = .023) and 2-year EFS (37% vs 34%; P = .039) compared with patients who did not receive BRT. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared with 42% in those who did not (P = .002). BRT before CART for patients with limited (<5 involved disease sites) R/R NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.


Assuntos
Linfoma de Células B , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Linfoma de Células B/radioterapia , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Imunoterapia Adotiva/métodos , Adulto Jovem
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