RESUMO
OBJECTIVE: C-reactive protein (CRP), a marker of systemic inflammation, has been associated with psychiatric disorders including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Some research suggests that exposure to trauma can trigger increased activity in the inflammatory system. Dissociation is associated with chronic trauma exposure and may be an important factor in understanding the risk for psychiatric outcomes associated with inflammation. The main objective of the current study was to understand how CRP was related to trauma, dissociation, PTSD and MDD in a sample of 55 traumatized African American women with type 2 diabetes mellitus recruited from an urban hospital. METHOD: High sensitivity CRP (hsCRP) was assayed through blood samples; psychiatric disorders were assessed with structured clinical interviews, dissociation was assessed with the Multiscale Dissociation Inventory, and exposure to trauma in childhood and adulthood was assessed with the Childhood Trauma Questionnaire and the Traumatic Events Inventory, respectively. RESULTS: Correlational results showed a significant association between higher concentrations of hsCRP and child abuse (pâ¯<â¯0.05), overall dissociation severity (pâ¯<â¯0.001), and PTSD symptoms (pâ¯<â¯0.01). ANOVA results showed significantly higher levels of hsCRP in those with current MDD, current PTSD, and remitted PTSD. A hierarchical linear regression model demonstrated a significant association between dissociation symptoms and greater hsCRP levels independent of childhood abuse, PTSD, and MDD (R2∆â¯=â¯0.11, pâ¯=â¯0.001) and independent of emotion dysregulation (pâ¯<â¯0.05). CONCLUSION: These findings suggest that dissociation symptoms among those with a history of trauma may be particularly associated with higher levels of inflammation.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Proteína C-Reativa/metabolismo , Maus-Tratos Infantis/tendências , Transtorno Depressivo Maior/sangue , Transtornos Dissociativos/sangue , Transtornos de Estresse Pós-Traumáticos/sangue , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Negro ou Afro-Americano/psicologia , Biomarcadores/sangue , Criança , Maus-Tratos Infantis/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Transtornos Dissociativos/epidemiologia , Transtornos Dissociativos/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e QuestionáriosAssuntos
Transfusão de Plaquetas , Raios Ultravioleta , Plaquetas , Transfusão de Sangue , Ficusina , HumanosAssuntos
Insuficiência Adrenal , Hemorragia , Leucemia Mieloide Aguda , Insuficiência Adrenal/diagnóstico por imagem , Insuficiência Adrenal/metabolismo , Insuficiência Adrenal/patologia , Idoso , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/metabolismo , Hemorragia/patologia , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologiaRESUMO
Sequencing technology, particularly next-generation sequencing, has highlighted the importance of gene mutations in myelodysplastic syndromes (MDSs). Mutations affecting DNA methylation, chromatin modification, RNA splicing, cohesin complex, and other pathways are present in most MDS cases and often have prognostic and clinical implications. Updated international diagnostic guidelines as well as the new International Prognostic Scoring System-Molecular incorporate molecular data into the diagnosis and prognostication of MDS. With whole-genome sequencing predicted to become the future standard of genetic evaluation, it is likely that MDS diagnosis and management will become increasingly personalized based on an individual's clinical and genomic profile.
Assuntos
Metilação de DNA , Síndromes Mielodisplásicas , Humanos , Mutação , Prognóstico , Splicing de RNA , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genéticaRESUMO
CEBPA-mutant acute myeloid leukemia (AML) encompasses clinically and biologically distinct subtypes of AML in both adults and children. CEBPA-mutant AML may occur with monoallelic (moCEBPA) or biallelic (biCEBPA) mutations, which can be somatic or germline, with each entity impacting prognosis in unique ways. BiCEBPA AML is broadly associated with a favorable prognosis, but differences in the type and location of CEBPA mutations as well as the presence of additional leukemogenic mutations can lead to heterogeneity in survival. Concurrent FLT3-ITD mutations have a well-documented negative effect on survival in adult biCEBPA AML, whereas support for a negative prognostic effect of mutations in TET2, DNMT3A, WT1, CSF3R, ASXL1, and KIT is mixed. NPM1 and GATA2 mutations may have a positive prognostic impact. MoCEBPA AML has similar survival outcomes compared to AML with wild-type CEBPA, and risk stratification is determined by other cytogenetic and molecular findings. Germline CEBPA mutations may lead to familial biCEBPA AML after acquisition of second somatic CEBPA mutation, with variable penetrance and age. BiCEBPA AML in children is likely a favorable-risk diagnosis as it is in adults, but the role of a single CEBPA mutation and the impact of concurrent leukemogenic mutations are not clear in this population. Laboratory evaluation of the CEBPA gene includes PCR-based fragment-length analysis, Sanger sequencing, and next-generation sequencing. Phenotypic analysis using multiparameter flow cytometry can also provide additional data in evaluating CEBPA, helping to assess for the likelihood of mutation presence.
Assuntos
Biomarcadores Tumorais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Adulto , Fatores Etários , Alelos , Biomarcadores , Proteínas Estimuladoras de Ligação a CCAAT/química , Criança , Mutação em Linhagem Germinativa , Humanos , Nucleofosmina , Ligação Proteica , Domínios e Motivos de Interação entre ProteínasRESUMO
CONTEXT.: The significance of positive immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement studies in the context of otherwise normal ancillary findings is unknown. OBJECTIVE.: To examine long-term hematologic outcomes of individuals with positive gene rearrangement studies with otherwise unremarkable blood or bone marrow studies in parallel. DESIGN.: Data from patients who underwent IG or TCR gene rearrangement testing at the authors' affiliated Veterans Affairs Hospital January 1, 2013 to July 6, 2018 were extracted from medical records. Date of testing, specimen source, and morphologic, flow cytometric, immunohistochemical, and cytogenetic characterization of the tissue source were recorded. Gene rearrangement results were categorized as test positive/phenotype positive (T+/P+), test positive/phenotype negative (T+/P-), test negative/phenotype negative (T-/P-), or test negative/phenotype positive (T-/P+) based on comparison to other studies and/or final diagnosis. Patient records were reviewed for subsequent diagnosis of hematologic malignancy for patients with positive gene rearrangements but no other evidence for a disease process. RESULTS.: A total of 136 patients with 203 gene rearrangement studies were analyzed. For TCR studies, there were 2 T+/P- and 1 T-/P+ results in 47 peripheral blood assays, as well as 7 T+/P- and 1 T-/P+ results in 54 bone marrow assays. Regarding IG studies, 3 T+/P- and 12 T-/P+ results in 99 bone marrow studies were identified. None of the 12 patients with T+/P- TCR or IG gene rearrangement studies later developed a lymphoproliferative disorder. CONCLUSIONS.: Positive IG/TCR gene rearrangement studies in the context of otherwise negative bone marrow or peripheral blood findings are not predictive of lymphoproliferative disorders.
Assuntos
Rearranjo Gênico do Linfócito B/genética , Rearranjo Gênico do Linfócito T/genética , Neoplasias Hematológicas/diagnóstico , Imunoglobulinas/genética , Transtornos Linfoproliferativos/diagnóstico , Receptores de Antígenos de Linfócitos T/genética , Idoso , Medula Óssea/patologia , Citogenética , Feminino , Citometria de Fluxo , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Imuno-Histoquímica , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/patologia , Masculino , Prontuários Médicos , FenótipoRESUMO
A hallmark of lymphoid malignancies is the presence of a monoclonal lymphocyte population. Monoclonality of B- and T-cell populations can be established through immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement analysis, respectively. The biological rationale of IG and TCR gene rearrangement analysis is that due to the extensive combinatorial repertoire made possible by V(D)J recombination in lymphocytes, it is unlikely that any substantive lymphocyte population would share the same IG or TCR gene rearrangement pattern unless there is an underlying neoplastic or reactive origin. Modern IG and TCR gene rearrangement analysis is typically performed by polymerase chain reaction (PCR) using commercially available primer sets followed by gel capillary electrophoresis. This process is highly sensitive in the detection of nearly all lymphoid malignancies. Several pitfalls and limitations, both biological and technical, apply to IG/TCR gene rearrangement analysis, but these can be minimised with high quality controls, performance of assays in duplicate, and adherence to strict criteria for interpreting and reporting results. Next generation sequencing (NGS) will likely replace PCR based methods of IG/TCR gene rearrangement analysis but is not yet widespread due to the absence of standardised protocols and multicentre validation.
Assuntos
Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Transtornos Linfoproliferativos/patologia , Subpopulações de Linfócitos B , Linfócitos B/patologia , Rearranjo Gênico , Humanos , Transtornos Linfoproliferativos/diagnóstico , Reação em Cadeia da Polimerase/métodos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Superfície Celular/genética , Subpopulações de Linfócitos T , Linfócitos T/patologiaRESUMO
OBJECTIVE: The purpose of the study was to assess demographic features, rates of trauma exposure, prevalence of post-traumatic stress and depressive symptoms in a group of urban, low-income, African-American women with type 1 or type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We conducted a survey of (n = 290) low-income, African-American women seeking care in the diabetes clinic of an urban hospital and collected data on the demographic characteristics, childhood and nonchildhood abuse trauma exposure, and the severity of post-traumatic stress and depressive symptoms using the Post-traumatic Stress Disorder (PTSD) Symptom Scale (PSS) and the Beck Depression Inventory (BDI). In a subset of women with type 2 diabetes (n = 96), we assessed haemoglobin A1c to examine the relationship between psychopathology and glycaemic control. RESULTS: Of the overall sample, 61.7% reported exposure to trauma in their lifetime, and 30.4% and 29.3% had current PTSD and MDD, respectively. Exposure to both childhood and nonchildhood abuse trauma was associated with an increased PTSD and depressive symptom severity (P's < .05). PTSD diagnosis, but not depression, was associated with increased haemoglobin A1c (P = .002). CONCLUSIONS: These data document high levels of trauma exposure, PTSD and depressive symptoms in diabetic African-American women treated in a specialty clinic of an urban hospital setting. Furthermore, these data indicate that the presence of PTSD is negatively associated with glycaemic control.