ABSTRACT
Even though HIV is associated with worse prognosis in many malignancies, the clinical course of myelodysplastic syndrome (MDS) in HIV + patients has not been well studied. Determining the clinical presentation and outcomes of MDS in these patients would be important for future diagnostic strategies, as anemia and other cytopenias are commonly seen in HIV + patients. Unique data mining software was used to identify cases of MDS or AML in adult patients who were also HIV + at Albert Einstein/Montefiore Medical Center between 1 January 2003 and 1 January 2017. Using Chi-Square and Fisher's exact test, characteristics of the HIV + MDS patients were compared to 135 HIV - MDS patients from the same institution diagnosed between 1997 and 2011. Fourteen biopsy proven MDS patients were identified with concomitant HIV. HIV + MDS patients presented at a younger age (59 vs. 71 yrs, p = .001) had higher risk disease, faster progression to acute leukemia, and worse overall survival (median survival 11.2 vs. 69.1 mo, p < .001) compared to HIV - MDS controls. Additionally, there was a higher prevalence of clonal-hematopoiesis related mutations (ASXL1, DNMT3A) and a higher proportion of patients with high risk cytogenetics. Analysis of the largest single center cohort of HIV + MDS patients demonstrated that these individuals present at a significantly younger age and with higher risk disease than their HIV - counterparts.
Subject(s)
Biomarkers, Tumor/genetics , HIV Infections/complications , HIV/isolation & purification , Mutation , Myelodysplastic Syndromes/mortality , Aged , Female , Follow-Up Studies , HIV Infections/virology , Humans , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/virology , Prognosis , Retrospective Studies , Survival RateABSTRACT
: Ovarian vein thrombosis (OVT) remains poorly understood with no consensus regarding its importance or treatment. In this retrospective study, we investigated the clinical features, risk factors, treatment patterns, and prognosis of patients with OVT, including venous thromboembolism (VTE) recurrences. Adult patients who presented to our medical center with an identifiable diagnosis of OVT over a 10-year period were included in this retrospective observational study. Individual patient charts were reviewed to collect baseline and outcomes data. We identified 223 women with OVT. Median follow-up was 857 days. Only 36.6% presented with abdominal pain and 61.4% reported a history of gynecologic surgery. Overall, right or left OVT incidence was similar (44.6 and 41.4%, respectively) but peripartum patients were more likely to have right OVT (60.0%, Pâ=â0.03). VTE recurred in 22 (9.9%) women, all of which were remote from the OVT and there were no recurrences in peripartum patients. Mean (±âSD) time to recurrence was 409 (±â421) days. Only 7.6% of OVT patients were anticoagulated for OVT; these women had a 38% reduction in VTE recurrence but because of low numbers, this was not statistically significant. VTE recurrence after OVT was associated with greater mortality in all patients, including patients with cancer. OVT is associated with an increased rate of non-OVT recurrence. Peripartum OVT patients appear to constitute a different patient population as they were younger, exhibited different risk factors, and had no increased incidence of recurrence. Although only a minority of patients with OVT was anticoagulated, this group had a reduction in VTE recurrence. A prospective study is needed to determine the utility of anticoagulation for women with OVT.
Subject(s)
Ovarian Diseases , Venous Thrombosis , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Ovarian Diseases/diagnosis , Ovarian Diseases/etiology , Peripartum Period , Prognosis , Prospective Studies , Recurrence , Risk Factors , Venous Thrombosis/diagnosis , Venous Thrombosis/etiology , Young AdultABSTRACT
Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) cell lines. We demonstrated that inactivation of menin (the protein product of MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of DNMT1 mediates global DNA hypermethylation, which results in aberrant activation of the Wnt/ß-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development.