10 research outputs found
Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study.
BACKGROUND: Schizophrenia (SCZ) is associated with increased risk of type 2 diabetes (T2D). The potential diabetogenic effect of concomitant application of psychotropic treatment classes in patients with SCZ has not yet been evaluated. The overarching goal of the Genetic Overlap between Metabolic and Psychiatric disease (GOMAP) study is to assess the effect of pharmacological, anthropometric, lifestyle and clinical measurements, helping elucidate the mechanisms underlying the aetiology of T2D. METHODS: The GOMAP case-control study (Genetic Overlap between Metabolic and Psychiatric disease) includes hospitalized patients with SCZ, some of whom have T2D. We enrolled 1653 patients with SCZ; 611 with T2D and 1042 patients without T2D. This is the first study of SCZ and T2D comorbidity at this scale in the Greek population. We retrieved detailed information on first- and second-generation antipsychotics (FGA, SGA), antidepressants and mood stabilizers, applied as monotherapy, 2-drug combination, or as 3- or more drug combination. We assessed the effects of psychotropic medication, body mass index, duration of schizophrenia, number of hospitalizations and physical activity on risk of T2D. Using logistic regression, we calculated crude and adjusted odds ratios (OR) to identify associations between demographic factors and the psychiatric medications. RESULTS: Patients with SCZ on a combination of at least three different classes of psychiatric drugs had a higher risk of T2D [OR 1.81 (95% CI 1.22-2.69); p = 0.003] compared to FGA alone therapy, after adjustment for age, BMI, sex, duration of SCZ and number of hospitalizations. We did not find evidence for an association of SGA use or the combination of drugs belonging to two different classes of psychiatric medications with increased risk of T2D [1.27 (0.84-1.93), p = 0.259 and 0.98 (0.71-1.35), p = 0.885, respectively] compared to FGA use. CONCLUSIONS: We find an increased risk of T2D in patients with SCZ who take a combination of at least three different psychotropic medication classes compared to patients whose medication consists only of one or two classes of drugs
MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis
MicroRNA-155-5p (miR-155-5p) is a proinflammatory, oncogenic miRNA, involved in various physiological processes, including hematopoiesis, immunity, inflammation, and cell lineage differentiation. It regulates important transcription factors, such as E2F2, hypoxia-inducible factor 1 (HIF1), and FOXO3. Recently, the dysregulation of miR-155-5p expression has been linked to chronic lymphocytic leukemia (CLL) pathogenesis. In this research study, we investigated the potential diagnostic and prognostic value of miR-155-5p in CLL. To achieve our goal, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients and 36 nonleukemic blood donors and performed polyadenylation of total RNA and reverse transcription. Next, we quantified miR-155-5p levels using an in-house-developed real-time quantitative PCR method, before proceeding to extensive biostatistical analysis. Thus, it appears that miR-155-5p is significantly overexpressed in PBMCs of CLL patients and can distinguish them from nonleukemic population. Kaplan-Meier OS analysis and bootstrap univariate Cox regression showed that high miR-155-5p expression predicts inferior OS for CLL patients (p<0.001). Interestingly, miR-155-5p overexpression retains its unfavorable prognostic role in CLL patients stratified according to established prognostic factors [CD38 expression and mutational status of the immunoglobulin heavy chain variable region (IGHV)]. Thus, miR-155-5p appears as a promising, independent molecular biomarker of unfavorable prognosis in CLL
Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis-A Case Report
Plasmablastic lymphoma (PBL) is a rare, aggressive type of B-cell
non-Hodgkin lymphoma with the vast majority of patients responding
poorly to treatment or progressing shortly thereafter.
Cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) or
CHOP-like regimens have disappointing results in this setting. We report
a case of PBL arising in a previously diagnosed
myelodysplastic/myeloproliferative (MDS/MPN) with ring sideroblasts and
thrombocytopenia (RS-T), HIV-negative patient treated with the
combination of CHOP and bortezomib. The patient achieved complete
metabolic response, which has lasted one year, longer by far than would
have been expected with the sole use of CHOP
Plasmablastic Lymphoma in an Immunocompetent Patient with MDS/MPN with Ring Sideroblasts and Thrombocytosis—A Case Report
Plasmablastic lymphoma (PBL) is a rare, aggressive type of B-cell non-Hodgkin lymphoma with the vast majority of patients responding poorly to treatment or progressing shortly thereafter. Cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) or CHOP-like regimens have disappointing results in this setting. We report a case of PBL arising in a previously diagnosed myelodysplastic/myeloproliferative (MDS/MPN) with ring sideroblasts and thrombocytopenia (RS-T), HIV-negative patient treated with the combination of CHOP and bortezomib. The patient achieved complete metabolic response, which has lasted one year, longer by far than would have been expected with the sole use of CHOP
DNA Repair Genes' Expression Abnormalities in De Novo Acute Myelogenous Leukemia (AML): Implications for Targeted Treatment
Synergistic inhibitory effects of low-dose decitabine in combination with bortezomib in the AML cell line Kasumi-1
In the present study, the ability of the proteasome inhibitor bortezomib
(BZ), an oxidative stress-inducing agent, to sensitize acute myeloid
leukemia (AML) cells to decitabine (Dacogen(R), DAC; a DNA
methyltransferase inhibitor), in terms of cell viability and
differentiation, was investigated. Kasumi-1 AML (M2) cells were treated
with low-dose DAC (10, 50, 100, 200 or 400 nM), with or without BZ (10
nM). Apoptosis and the cell cycle were evaluated after 24 h of treatment
through fluorescence-assisted cell sorting (FACS) with Annexin
V/propidium iodide and DAPI staining, respectively. The expression
levels of CD193, CD11b, CD13, CD14, CD15, CD16 and CD117 surface
differentiation markers were evaluated by FACS after 6 days of
treatment. The results indicated significant alterations in cell death
and cell cycle phases in Kasumi-1 cells following DAC and BZ combination
treatment compared to untreated cells and cells with single treatments.
Low-dose DAC/BZ combinations significantly enhanced apoptosis and
decreased the population of live Kasumi-1 cells, with 100 and 200 nM of
DAC and 10 nM BZ appearing to have the most potent synergistic effect
according to a combination index. Furthermore, cell cycle profiling
revealed that DAC/BZ treatment synergistically led to G0/G1- and
G2/M-phase arrest. By contrast, DAC appeared to promote monocytic and
granulocytic differentiation of Kasumi-1 cells more effectively alone
than in combination with BZ. BZ acted synergistically with low-dose DAC
in vitro, leading to enhanced apoptosis and G0/G1- and G2/M-phase arrest
in AML cells, hence prohibiting either DNA synthesis or mitosis.
Although further in vivo investigation is necessary, these results
provide a strong rationale for the implementation of a combination
treatment with DAC and bortezomib in AML therapy, followed by DAC alone,
which may achieve better clinical responses and possibly partially
overcome the frequently encountered DAC resistance of patients with AML
Discontinuation of the renin-angiotensin system inhibitors improves erythropoiesis in patients with lower-risk myelodysplastic syndromes
Renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme
inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) has been
related to anemia in various situations. We aimed to investigate whether
discontinuation of RAS inhibitors improves erythropoiesis in patients
with lower-risk myelodysplastic syndromes (LR-MDSs). Seventy-four
patients with LR-MDS were divided into three groups matched for gender
and age. Group A consisted of 20 hypertensive patients who discontinued
RAS inhibitors and received alternative medications. Group B consisted
of 26 patients who continued to receive ACEi/ARB and Group C included 28
patients (50% hypertensive) never exposed to ACEi/ARB. Half of the
patients in each group were under treatment with recombinant human
erythropoietin (rHuEPO). Data were collected at baseline and after 3, 6
and 12 months. Group A showed a significant increase in hemoglobin from
10.4 +/- 1g/dL at baseline to 12.6 +/- 1.2 g/dL after 12 months (p =
0.035) and in hematocrit (31.4 +/- 3% versus 37.9 +/- 4%, p = 0.002).
Incident anemia decreased from 100% at baseline to 60% at 12 months (p
= 0.043) despite a concomitant dose reduction in rHuEPO by 18% (p =
0.035). No changes in hemoglobin and hematocrit were observed in both
Group B and Group C. In the subset of patients not treated with rHuEPO,
improvement of erythropoiesis was found only in Group A, as measured by
changes in hemoglobin (11.5 +/- 1 g/dL versus 12.4 +/- 1.3 g/dL, p =
0.041) and hematocrit (34.5 +/- 3% versus 37.1 +/- 4%, p = 0.038)
after 12 months. In contrast, Group B and Group C decreased hemoglobin
and hematocrit after 12 months (p < 0.05). In conclusion,
discontinuation of ACEi/ARB in LR-MDS patients is followed by a
significant recovery of erythropoiesis after 12 months
Coexistence of Myeloid and Lymphoid Neoplasms: A Single-Center Experience
The coexistence of a myeloid and a lymphoid neoplasm in the same patient is a rare finding. We retrospectively searched the records of the Hematology Division of the Second Department of Internal Medicine and Research Institute at Attikon University General Hospital of Athens from 2003 to 2018. Nine cases have been identified in a total of 244 BCR-/ABL1- negative MPN and 25 MDS/MPN patients and 1062 LPD patients referred to our institution between 2003 and 2018. Each case is distinct in the diversity of myeloid and lymphoid entities, the chronological occurrence of the two neoplasms, and the patient clinical course. All of them exhibit myeloproliferative (6 JAK2 V617F-positive cases) and lymphoproliferative features, with 1 monoclonal B-cell lymphocytosis (MBL), 3 B-chronic lymphocytic leukemias (B-CLL), 3 B-non-Hodgkin lymphomas (B-NHL), 1 multiple myeloma (MM), and 1 light and heavy deposition disease (LHCDD), while in three cases myelodysplasia is also present. The challenges in identifying and dealing with these rare situations in everyday clinical practice are depicted in this article
Additional file 1: of Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study
Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study. Description of survey flow. Diagnostic assessment of T2D and psychiatric disease. Physical assessments. Table S1. T2D occurrence based on simple logistic regression modelling among patients with SCZ. Figure S1. Manhattan plot of association results from a GWAS on T2D in individuals receiving a combination of three or more psychotropic drugs, including one FGA and one SGA. For each of the 9,565,382 analysed variants the –log10 of the p-value is plotted against its chromosomal position. Blue and red lines indicate suggestive (p < 5*10− 6) and genome-wide (p < 5*10− 8) significance. Figure S2. Quantile-quantile plot of association results from a GWAS on T2D in individuals receiving a combination of three or more psychotropic drugs, including one FGA and one SGA. For each SNP the –log10 of the p-value is plotted against its expected value under the null distribution. (DOCX 219 kb