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1.
BMC Psychiatry ; 24(1): 409, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816707

RESUMO

BACKGROUND: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. METHODS: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Oura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. DISCUSSION: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Adolescente , Adulto Jovem , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Estudos Prospectivos , Feminino , Masculino , Progressão da Doença , Tecnologia de Sensoriamento Remoto/métodos , Tecnologia de Sensoriamento Remoto/instrumentação , Smartphone , Estudos Longitudinais , Qualidade de Vida/psicologia
2.
J Fish Biol ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584261

RESUMO

The challenge of managing aquatic connectivity in a changing climate is exacerbated in the presence of additional anthropogenic stressors, social factors, and economic drivers. Here we discuss these issues in the context of structural and functional connectivity for aquatic biodiversity, specifically fish, in both the freshwater and marine realms. We posit that adaptive management strategies that consider shifting baselines and the socio-ecological implications of climate change will be required to achieve management objectives. The role of renewable energy expansion, particularly hydropower, is critically examined for its impact on connectivity. We advocate for strategic spatial planning that incorporates nature-positive solutions, ensuring climate mitigation efforts are harmonized with biodiversity conservation. We underscore the urgency of integrating robust scientific modelling with stakeholder values to define clear, adaptive management objectives. Finally, we call for innovative monitoring and predictive decision-making tools to navigate the uncertainties inherent in a changing climate, with the goal of ensuring the resilience and sustainability of aquatic ecosystems.

3.
J Oncol Pharm Pract ; 29(1): 130-137, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34854771

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. METHODS: In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. RESULTS: Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. CONCLUSION: Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Valaciclovir/uso terapêutico , Valaciclovir/farmacologia , Citomegalovirus , Estudos Retrospectivos , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
4.
J Fish Biol ; 103(1): 179-182, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37013794

RESUMO

The temporal effects of ethanol preservation on the δ13 C and δ15 N values of tissues excised from European eel Anguilla anguilla were assessed. Preservation significantly enriched 13 C values of fin and mucus but not dorsal muscle. The 13 C enrichment occurred in the initial 15 days of preservation and was independent of initial eel mass. Tissue preservation effects on δ15 N values were negligible. These tissue-specific isotopic shifts should be considered when ethanol-preserved eel samples are used.


Assuntos
Anguilla , Animais , Anguilla/fisiologia , Etanol , Preservação Biológica
5.
J Fish Biol ; 100(3): 847-851, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35025118

RESUMO

Ecological studies on the critically endangered European eel Anguilla anguilla often incorporate stable isotope analysis that typically uses dorsal muscle sampled from euthanised eels. To minimise the lethal sampling of imperilled populations, fin tissue and/or epidermal mucus can provide non-lethal alternatives to muscle. The results here indicate that δ13 C and δ15 N values of both eel fin and mucus are not significantly different from those of muscle and can be applied directly in comparative SI studies.


Assuntos
Anguilla , Anguilla/fisiologia , Animais , Isótopos , Muco , Músculos
6.
Genesis ; 59(7-8): e23421, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34050709

RESUMO

Congenital heart defects are a feature of several genetic haploinsufficiency syndromes, often involving transcriptional regulators. One property of haploinsufficient genes is their propensity for network interactions at the gene or protein level. In this article we took advantage of an online dataset of high throughput screening of mutations that are embryonic lethal in mice. Our aim was to identify new genes where the loss of function caused cardiovascular phenotypes resembling the 22q11.2 deletion syndrome models, that is, heterozygous and homozygous loss of Tbx1. One gene with a potentially haploinsufficient phenotype was identified, Setd5, thought to be involved in chromatin modification. We found murine Setd5 haploinsufficiency to be associated with double outlet right ventricle and perimembranous ventricular septal defect, although no genetic interaction with Tbx1 was detected. Conditional mutagenesis revealed that Setd5 was required in cardiopharyngeal mesoderm for progression of the heart tube through the ballooning stage to create a four-chambered heart.


Assuntos
Síndrome da Deleção 22q11/genética , Defeitos dos Septos Cardíacos/genética , Coração/embriologia , Mesoderma/metabolismo , Metiltransferases/metabolismo , Animais , Haploinsuficiência , Mutação com Perda de Função , Mesoderma/embriologia , Metiltransferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Proteínas com Domínio T/genética
7.
J Clin Immunol ; 41(5): 1016-1030, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33651234

RESUMO

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Sixteen pediatric HSCT patients were recruited: 6 with ECP-treated aGVHD, 5 without aGVHD, and 5 with aGVHD treated with corticosteroids only. Thymopoiesis was evaluated by measuring naive T cells, TRECs, IL-7, and T cell receptor repertoire diversity. Regulatory T cell (Treg) enumeration and function and dendritic cell (DC) enumeration and phenotype were analyzed using flow cytometry. T cell transcriptome analysis was performed on ECP patients after treatment and responders pre- and post-treatment. Four ECP responders demonstrated thymic-dependent T cell recovery, and superior median naïve T cell numbers at 8 and 12 months post-HSCT compared to the aGVHD corticosteroid group. Increased Tregs and Treg suppressive function, reduced cDC/pDC and DC co-stimulatory marker expression in ECP responders suggest upregulated peripheral tolerance; these findings were not observed in partial responders. Responder post-ECP CD3+ T cell transcriptional profile demonstrated 3333 downregulated and 364 upregulated genes, with significant downregulation of ERRα and GαS pathways, and reduced expression of pro-inflammatory and adhesion proteins.Thymic function improves with successful ECP treatment. ECP reduces T cell activation and impacts peripheral tolerance via DCs and Tregs. Differences in thymic recovery, DC, and Treg cellular patterns and the T cell transcriptome were observed between ECP responders and partial responders and require further validation and investigation in additional patients.


Assuntos
Células Dendríticas/imunologia , Doença Enxerto-Hospedeiro/terapia , Fotoferese , Linfócitos T/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lactente , Interleucina-7/sangue , Masculino , Receptores de Antígenos de Linfócitos T/imunologia , Timo/citologia , Transcriptoma
8.
Transfusion ; 61(3): 894-902, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33475172

RESUMO

BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.


Assuntos
Benzilaminas/uso terapêutico , Ciclamos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Adolescente , Antígenos CD34/sangue , Remoção de Componentes Sanguíneos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Linfoma/tratamento farmacológico , Linfoma/terapia , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/radioterapia , Meduloblastoma/terapia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/radioterapia , Neuroblastoma/terapia , Células-Tronco de Sangue Periférico/metabolismo , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/terapia , Adulto Jovem
9.
Biol Blood Marrow Transplant ; 26(4): 672-682, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31676338

RESUMO

Killer immunoglobulin-like receptor (KIR) and KIR ligand (KIRL) interactions play an important role in natural killer (NK) cell-mediated graft-versus-leukemia effect following hematopoietic cell transplantation (HCT). However, there is considerable heterogeneity in the KIR gene and KIRL content in individuals, making it difficult to estimate the full clinical impact of NK cell reconstitution following HCT. Here we present a novel adaptive mathematical model designed to quantify these interactions to better assess the influence of NK cell-mediated alloreactivity on transplant outcomes. Ninety-eight HLA- matched unrelated donor (URD) HCT recipients were studied retrospectively. The KIR-KIRL interactions were quantified using a system of matrix equations. Unit values were ascribed to each KIR-KIRL interaction, and the directionality of interactions was denoted by either a positive (activating) or negative (inhibition) symbol; these interactions were then summed. The absolute values of both the missing KIRL and inhibitory KIR-KIRL interactions were significantly associated with overall survival and relapse. These score components were initially used to develop a weighted score (w-KIR score) and subsequently a simplified, nonweighted KIR-KIRL interaction score (IM-KIR score). Increased w-KIR score and IM-KIR score were predictive of all-cause mortality and relapse (w-KIR score: hazard ratio [HR], .37 [P = .001] and .44 [P = .044], respectively; IM-KIR score: HR, .5 [P = .049] and .44 [P = .002], respectively). IM-KIR score was also associated with NK cell reconstitution post-HCT. KIR-KIRL interactions as reflected by the w-KIR and IM-KIR scores influence both relapse risk and survival in recipients of HLA-matched URD HCT with hematologic malignancies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Humanos , Ligantes , Receptores KIR/genética , Estudos Retrospectivos
10.
Eur J Haematol ; 103(4): 329-334, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267566

RESUMO

Hematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11 allogeneic and four autologous HCT). Ascorbate levels declined postconditioning to 27.3 µMol/L (±14.1) by day 0 (P = .03 compared with pretransplant baseline), reaching a nadir level of 21.5 (±13.8) on day 14 (P = .003) post-transplant. Patients undergoing allogeneic HCT continued to have low AA levels to day 60 post-transplant. The role of AA in maintaining endothelial function and hematopoietic as well as T-cell recovery is provided, developing the rationale for repletion of vitamin C following HCT.


Assuntos
Ácido Ascórbico/sangue , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adulto , Idoso , Biomarcadores , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo
11.
J Anim Ecol ; 88(7): 1066-1078, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30982964

RESUMO

Ecological theory on the trophic impacts of invasive fauna on native competitors is equivocal. Whilst increased interspecific competition can result in coexisting species having constricted and diverged trophic niches, the competing species might instead increase their niche sizes to maintain energy intakes. Empirical experiments can test invasion theory on competitive interactions and niche sizes across different spatial scales and complexity. The consequences of increased interspecific competition from a model alien fish Leuciscus idus were tested on two taxonomically and trophically similar native fishes, Squalius cephalus and Barbus barbus. Competitive interactions were tested in tank aquaria using comparative functional responses (CFRs) and cohabitation trials. The consequences of these competitive interactions for the trophic niche sizes and positions of the fishes were tested in pond mesocosms. Comparative functional responses revealed that compared to B. barbus, L. idus had significantly higher attack and consumption rates; cohabitation trials revealed B. barbus growth rates were depressed in sympatry with L. idus. For L. idus and S. cephalus, differences in their functional response parameters and growth rates were not significant. Pond mesocosms used stable isotope metrics to quantify shifts in the trophic niche sizes of the fishes between allopatry and sympatry using a substitutive experimental design. Isotopic niches were smaller and more divergent in sympatric paired species than predicted by their allopatric treatments, suggesting trophic impacts from interspecific competition. However, an all-species sympatric treatment revealed similar niche sizes with allopatry. This maintenance of niche sizes in the presence of all species potentially resulted from the buffering of direct competitive effects of the species pairs by indirect effects. Experimental predictions from tank aquaria assisted the interpretation of the constricted and diverged trophic niches detected in the paired-species sympatric treatments of the pond mesocosms. However, the all-species sympatric treatment of this experiment revealed greater complexity in the outcomes of the competitive interactions within and between the species. These results have important implications for understanding how alien species integrate into food webs and influence the trophic relationships between native species.


Assuntos
Ecologia , Espécies Introduzidas , Animais , Cadeia Alimentar , Estado Nutricional , Simpatria
12.
Analyst ; 143(11): 2479-2485, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29589850

RESUMO

In this study, we used a rapid, highly-sensitive, single-cell biomass measurement method, Live Cell Interferometry (LCI), to measure biomass in populations of CD3 + T cells isolated from hematopoietic stem cell transplant (SCT) patients at various times pre- and post-transplant (days 0-100). CD3 + T cell 'mass spectra' were obtained from five autologous and 20 allogenic transplant recipients. We found a pronounced rise in median T cell biomass (+25%; p <0.001) shortly after transplant (day 14), which moderated by day 60. Further, the inter-patient and intra-patient cell masses were most variable at days 14 and 30 post-transplant. T cell biomass trends were similar in both autologous and allogenic transplant recipients. These data suggest that T cell biomass changes are associated with immune reconstitution occurring in the first few weeks post-transplant. To our knowledge, this is the first time single-cell biomass measurements have been studied in human clinical trials. With refinement, these data may prove useful in guiding the withdrawal of immunosuppression following SCT, reducing the likelihood of Graft-Versus-Host Disease or cancer relapse occurring.


Assuntos
Tamanho Celular , Transplante de Células-Tronco Hematopoéticas , Linfócitos T/citologia , Doença Enxerto-Hospedeiro , Humanos , Transplante Homólogo
13.
Am J Med Genet A ; 173(6): 1566-1574, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28425213

RESUMO

Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity. In this study, we evaluated genotype-phenotype associations in 34 individuals with CdLS. Participants with NIPBL mutations had significantly lower self help skills and were less likely to have verbal skills relative to those who were negative for the NIPBL mutation. No significant differences were identified between the groups in relation to repetitive behavior, mood, interest and pleasure, challenging behavior, activity, impulsivity, and characteristics of autism spectrum disorder whilst controlling differences in self help skills. Significant correlations indicating lower mood, interest and pleasure, and increased insistence on sameness with older age were identified for those who were NIPBL mutation positive. The findings suggest similarities in the behavioral phenotype between those with and without the NIPBL mutation once differences in self help skills are controlled for. However, there may be subtle differences in the developmental trajectory of these behaviors according to genetic mutation status in CdLS.


Assuntos
Transtorno do Espectro Autista/genética , Síndrome de Cornélia de Lange/genética , Estudos de Associação Genética , Proteínas/genética , Transtorno do Espectro Autista/fisiopatologia , Proteínas de Ciclo Celular , Síndrome de Cornélia de Lange/fisiopatologia , Exoma/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Fenótipo
14.
Biol Blood Marrow Transplant ; 22(5): 850-61, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26688192

RESUMO

Immune reconstitution kinetics and subsequent clinical outcomes in HLA-matched recipients of allogeneic stem cell transplantation (SCT) are variable and difficult to predict. Considering SCT as a dynamical system may allow sequence differences across the exomes of the transplant donors and recipients to be used to simulate an alloreactive T cell response, which may allow better clinical outcome prediction. To accomplish this, whole exome sequencing was performed on 34 HLA-matched SCT donor-recipient pairs (DRPs) and the nucleotide sequence differences translated to peptides. The binding affinity of the peptides to the relevant HLA in each DRP was determined. The resulting array of peptide-HLA binding affinity values in each patient was considered as an operator modifying a hypothetical T cell repertoire vector, in which each T cell clone proliferates in accordance with the logistic equation of growth. Using an iterating system of matrices, each simulated T cell clone's growth was calculated with the steady-state population being proportional to the magnitude of the binding affinity of the driving HLA-peptide complex. Incorporating competition between T cell clones responding to different HLA-peptide complexes reproduces a number of features of clinically observed T cell clonal repertoire in the simulated repertoire, including sigmoidal growth kinetics of individual T cell clones and overall repertoire, Power Law clonal frequency distribution, increase in repertoire complexity over time with increasing clonal diversity, and alteration of clonal dominance when a different antigen array is encountered, such as in SCT. The simulated, alloreactive T cell repertoire was markedly different in HLA-matched DRPs. The patterns were differentiated by rate of growth and steady-state magnitude of the simulated T cell repertoire and demonstrate a possible correlation with survival. In conclusion, exome wide sequence differences in DRPs may allow simulation of donor alloreactive T cell response to recipient antigens and may provide a quantitative basis for refining donor selection and titration of immunosuppression after SCT.


Assuntos
Exoma , Modelos Genéticos , Receptores de Antígenos de Linfócitos T/genética , Transplante de Células-Tronco , Linfócitos T , Doadores de Tecidos , Adulto , Aloenxertos , Feminino , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade
15.
Biol Blood Marrow Transplant ; 21(7): 1237-45, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25849208

RESUMO

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Modelos Imunológicos , Condicionamento Pré-Transplante , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Imunossupressores/uso terapêutico , Transfusão de Linfócitos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Prognóstico , Estudos Prospectivos , Recidiva , Risco , Irmãos , Análise de Sobrevida , Transplante Homólogo , Doadores não Relacionados , Irradiação Corporal Total
16.
Skeletal Radiol ; 44(5): 673-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25626524

RESUMO

PURPOSE: Analysis of joint fluid remains a key factor in the diagnosis of periprosthetic infection. Recent reports have shown that neutrophils in infected joint fluid release esterase, an enzyme that is a reliable marker for infection. Testing for leukocyte esterase is routinely done in the analysis of urine for the presence of urinary tract infection, by a simple "dipstick" method. We report our experience with this technique in the evaluation of patients suspected of having septic arthritis or periprosthetic joint infection (PJI) by comparing results of leukocyte esterase positivity with confirmed joint infection as defined by the American Academy of Orthopaedic Surgeons (AAOS). MATERIALS AND METHODS: We retrospectively reviewed leukocyte esterase test results performed on synovial fluid aspirated from 57 patients with prosthetic (52) and native (5) joints. Patients either presented with unexplained painful arthroplasties, routine testing of PROSTALAC (PROSthesis with Antibiotic-Loaded Acrylic Cement) orthopedic implants, or clinical suspicion of periprosthetic infection or septic arthritis. Synovial fluid was percutaneously aspirated using a standard technique. The patient age range was 31-91 years with a mean age of 69.1 years, consisting of 30 women (52.6 %) and 27 men (47.4 %). The "gold standard" for the presence or absence of infection at our institution and in the study group was based on the most recent recommendations of the AAOS. Positive culture remained the "gold standard" for native joint infection. RESULTS: Of the total 57 joints aspirated and included in the study, 20 (35.1 %) were read as positive (2+) on the leukocyte test strip and 37 (64.9 %) were read as negative (negative, trace, or 1+). PJI was diagnosed in 19 patients and native joint septic arthritis was identified in one patient. Sensitivities were excellent at 100 % with no false negatives in the entire cohort. There was one false positive in the periprosthetic group yielding a specificity, positive predictive value and negative predictive value of 97, 95, and 100 %, respectively. The results for the native joints showed markedly less specificity and positive predictive value at 50 and 33 %; however, its negative predictive value remained at 100 %. CONCLUSIONS: Our test results confirm that the leukocyte esterase test can accurately detect PJI and that it can be used as a part of the traditional PJI workup. In the assessment of native joints, its high negative predictive value suggests that it is a valuable tool in excluding native joint septic arthritis.


Assuntos
Artrite Infecciosa/diagnóstico , Hidrolases de Éster Carboxílico/análise , Infecções Relacionadas à Prótese/diagnóstico , Fitas Reagentes , Líquido Sinovial/química , Urinálise/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Infecciosa/enzimologia , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/enzimologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Br J Haematol ; 166(4): 566-70, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24749631

RESUMO

Whole exome sequencing (WES) was performed on stem cell transplant donor-recipient (D-R) pairs to determine the extent of potential antigenic variation at a molecular level. In a small cohort of D-R pairs, a high frequency of sequence variation was observed between the donor and recipient exomes independent of human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in HLA-matched unrelated, compared with related D-R pairs. When mapped to individual chromosomes, these polymorphic nucleotides were uniformly distributed across the entire exome. In conclusion, WES reveals extensive nucleotide sequence variation in the exomes of HLA-matched donors and recipients.


Assuntos
Exoma/genética , Polimorfismo de Nucleotídeo Único/genética , Transplante de Células-Tronco , Tolerância ao Transplante/genética , Biblioteca Gênica , Variação Genética/genética , Rejeição de Enxerto/genética , Doença Enxerto-Hospedeiro/genética , Humanos , Análise de Sequência de DNA , Transplante Homólogo
18.
J Clin Microbiol ; 52(6): 2186-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24696023

RESUMO

The Viper HSV-Q(x) assay was evaluated for the detection of herpes simplex virus 1 (HSV-1) and HSV-2 in specimens from oral, anogenital, and other miscellaneous sites. The HSV-Q(x) assay was found to be highly sensitive and accurate; however, a gray zone may be required for specimens with values falling between 50 and 800 maximum relative fluorescence units.


Assuntos
Herpes Genital/diagnóstico , Herpes Genital/virologia , Herpes Simples/diagnóstico , Herpes Simples/virologia , Técnicas de Diagnóstico Molecular/métodos , Simplexvirus/classificação , Simplexvirus/isolamento & purificação , Fluorescência , Genitália/virologia , Humanos , Técnicas de Diagnóstico Molecular/normas , Boca/virologia , Sensibilidade e Especificidade
19.
Skeletal Radiol ; 43(8): 1079-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24781818

RESUMO

OBJECTIVE: To re-assess the accuracy of chemical shift imaging in diagnosing indeterminate bone marrow lesions as benign or malignant. MATERIALS AND METHODS: We retrospectively reviewed our experience with MR imaging of the pelvis to assess the accuracy of chemical shift imaging in distinguishing benign from malignant bone lesions. Two musculoskeletal radiologists retrospectively reviewed all osseous lesions biopsied since 2006, when chemical shift imaging was added to our routine pelvic imaging protocol. Study inclusion criteria required (1) MR imaging of an indeterminate bone marrow lesion about the pelvis and (2) subsequent histologic confirmation. The study group included 50 patients (29 male, 21 female) with an average age of 67 years (range, 41-89 years). MR imaging results were evaluated using biopsy results as the "gold standard." RESULTS: There were 27 malignant and 23 benign lesions. Chemical shift imaging using an opposed-phase signal loss criteria of less than 20 % to indicate a malignant lesion, correctly diagnosed 27/27 malignant lesions and 14/23 benign lesions, yielding a 100 % sensitivity, 61 % specificity, 75 % PPV, 100 % NPV, and 82 % accuracy. The area under the receiver operator characteristic (ROC) curve was 0.88. The inter-rater and intra-rater agreement K values were both 1.0. CONCLUSIONS: Chemical shift imaging is a useful adjunct MR technique to characterize focal and diffuse marrow abnormalities on routine non-contrast pelvic imaging. It is highly sensitive in identifying malignant disease. Despite its lower specificity, the need for biopsy could be eliminated in more than 60 % of patients with benign disease.


Assuntos
Neoplasias da Medula Óssea/diagnóstico , Medula Óssea/patologia , Imageamento por Ressonância Magnética/métodos , Pelve/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Skeletal Radiol ; 43(2): 165-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24270975

RESUMO

PURPOSE: Percutaneous synovial biopsy has recently been reported to have a high diagnostic value in the preoperative identification of periprosthetic infection of the hip. We report our experience with this technique in the evaluation of patients undergoing revision hip arthroplasty, comparing results of preoperative synovial biopsy with joint aspiration in identifying an infected hip arthroplasty by bacteriological analysis. MATERIALS AND METHODS: We retrospectively reviewed the results of the 110 most recent revision hip arthroplasties in which preoperative synovial biopsy and joint aspiration were both performed. Revision surgery for these patients occurred during the period from September 2005 to March 2012. Using this study group, results from preoperative cultures were compared with preoperative laboratory studies and the results of intraoperative cultures. Synovial aspiration was done using an 18- or 20-gauge spinal needle. Synovial biopsy was done coaxially following aspiration using a 22-gauge Chiba needle or 21-gauge Sure-Cut needle. Standard microbiological analysis was performed on preoperative synovial fluid aspirate and synovial biopsy. Intraoperative tissue biopsy bacteriological analysis results at surgical revision were accepted as the "gold standard" for the presence or absence of infection. RESULTS: Seventeen of 110 (15 %) of patients had intraoperative culture-positive periprosthetic infection. Of these 17 cases, there were ten cases where either the synovial fluid aspiration and/or the synovial biopsy were true positive (sensitivity of 59 %, specificity of 100 %, positive predictive value of 100 % and accuracy of 94 %). There were seven cases where aspiration and biopsy results were both falsely negative, but no false-positive results. Similar results were found for synovial fluid aspiration alone. The results of synovial biopsy alone resulted in the identification of seven infected joints with no false-positive result (sensitivity of 41 %, specificity of 100 %, positive predictive value of 100 %, and accuracy of 91 %). CONCLUSIONS: Standard microbiological analyses performed on percutaneous synovial biopsy specimen during the preoperative evaluation of patients undergoing revision hip arthroplasty did not improve detection of culture-positive periprosthetic infection as compared to synovial fluid aspiration alone.


Assuntos
Infecções Bacterianas/patologia , Biópsia por Agulha/métodos , Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/patologia , Membrana Sinovial/patologia , Infecções Bacterianas/microbiologia , Prótese de Quadril/microbiologia , Humanos , Infecções Relacionadas à Prótese/microbiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Membrana Sinovial/microbiologia
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