18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients.

BACKGROUND: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. OBJECTIVE: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. METHODS: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI)was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. RESULTS: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. CONCLUSIONS: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.

Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72. The aim of this study was to explore the pathways of phosphorylation and overexpression of the SRP72 polypeptide, using an in vitro model of Jurkat cells stimulated by recombinant human (rh)IL-1ß in the presence of MAPK inhibitors. We used Jurkat cells as a substrate stimulated with rhIL-1ß in the presence of MAPK inhibitors at different concentrations in a time course in vitro experiment by immunoprecipitation, immunoprecipitation-Western blotting, and real time PCR. Our results showed that rhIL-1ß causes up-regulation of protein expression and phosphorylation of SRP72 in Jurkat cells. Inhibitors of the MAPK pathway ERK1/2 or p38α/ß down-regulate the expression of SRP72 autoantigen in Jurkat cells stimulated by rhIL-1ß. Our results highlight the importance of studying the pathways of activation and overexpression of autoantigens. It will be necessary to perform careful research on various kinases pathways, including MAPK in dermatomyositis and other rheumatic diseases, to help to explain the routes of activation and inhibition of autoantigens. The understanding of this process may help to develop new therapies to prevent and control the loss of tolerance toward own normal proteins.

Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity.

We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.

Mismatch repair protein expression and intratumoral budding in rectal cancer are associated with an increased pathological complete response to preoperative chemoradiotherapy: A case-control study.

AIM: To determine whether the association of rectal adenocarcinoma with a defective-mismatch repair system (dMMR) was associated with a pathological complete response (pCR) to preoperative chemoradiotherapy. METHODS: A case-control study was designed with the aim of determining if patients with rectal adenocarcinoma with dMMR had an associated high pCR rate in response to neoadjuvant chemoradiotherapy (nCRT). RESULTS: Seventy-two cases with pCR were compared against 144 controls without pCR. Across 216 cases, the mean age was 56.8 years, 140 (64.8%) were men, and 63 (29.2%) demonstrated the dMMR system. The pCR was associated with G1 tumors, dMMR, the absence of vascular invasion, and low tumor budding in the pretreatment biopsy. In a multivariant analysis, the factors associated with pCR were dMMR (OR: 2.61; 95%CI: 1.355-5.040, P = 0.004) and a low degree of tumor budding (OR: 2.52; 95%CI: 1.366-4.894, P = 0.025). CONCLUSION: We found an independent association between dMMR and a low rate of tumor budding, with a higher rate of pCR, in the basal biopsies of patients with rectal carcinoma subjected to nCRT.

Splenic myeloid metaplasia in warm autoimmune hemolytic anemia (wAIHA): a retrospective study.

BACKGROUND: Splenic myeloid metaplasia (SMM) is a kind of extramedullary hematopoiesis, whereas its clinical significance in wAIHA remains unclear. The aim of this study is evaluating the frequency and clinical characteristics of SMM, compared with splenic-congestion (SC). METHODS: We included patients with wAIHA treated in a Mexican tertiary hospital between January 1992 and December 2015. All patients received steroids as first-line treatment and splenectomy as second-line treatment. RESULTS: Among the thirty-six splenectomized patients, 15 (41.6%) and 21 (58.4%) were diagnosed as SMM and SC, respectively. No differences were found in clinical characteristics between two groups. SMM patients showed lower platelet count (147×109/L vs. 240×109/L, P=0.02) and higher presence of anti-dsDNA antibodies (40% vs. 4.7%, P=0.01) than SC patients. Although the complete response (CR) rate with first-line treatment was lower in SMM patients (13.3% vs. 47.6%; P=0.04), post-splenectomy median disease-free-survival (DFS) was longer (16.2 mo vs. 5.1 mo; P=0.19). Univariate/multivariate analysis showed that achieving CR during first-line treatment (OR 0.3, 95% CI: 0.03-0.94, P=0.03) and higher platelet count (OR 0.99, 95% CI: 0.98-0.99, P=0.03) were protective factors for SMM; and anti-dsDNA titer higher than 9.6 IU/dL was a risk factor for SMM (OR 2.76, 95% CI: 1.48-5.14, P<0.001). CONCLUSION: The wAIHA patients with SMM have different biological profiles with those without SMM. This study is the first trial evaluating the significance of histopathological spleen findings and their association with rheumatologic profile.

IL-17 increased in the third trimester in healthy women with term labor.

INTRODUCTION: The function, peripheral blood expression, and physiologic importance of IL-17 is not well established. Detection of IL-17 in sera and plasma samples from patients with pre-eclampsia has been reported with inconsistent results. To establish the l levels of the IL-17 at peripheral level, we studied prospectively a cohort of 13 healthy pregnant women. OBJECTIVE: To evaluate the changes in serum levels of IL-17 in healthy pregnant women in a prospective cohort. MATERIAL AND METHODS: Thirteen healthy pregnant women were prospectively followed to evaluate serum levels of IL-17. Each patient was evaluated at each trimester. IL-17 levels were measured by ELISA. The statistical analysis was done using repeated measures anova and Bonferroni's multiple comparison test. RESULTS: IL-17 levels were significantly increased from first trimester with a mean of 14.61 up to 31.78 pg/mL at third trimester (P < 0.05), but when detectable, they were almost identical range in all trimesters. CONCLUSIONS: We propose that IL-17 levels in healthy women are present with very similar range levels during the whole pregnancy but the average is increased during the third trimester maybe as a part of the complex network of cytokines as a result of implantation, fetal development, and labor process itself.