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Many evidences show that elevated plasma levels of uric acid (UA) are associated to the increased risk of developing athero-thrombotic cardiovascular events. Hyperuricemia is a risk factors for endothelial dysfunction (ED). ED is involved in the pathophysiology of athero-thrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the TF/TFPI balance finally changing the antithrombotic characteristics of endothelial cells.

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OBJECTIVES: Gynecological manifestation of chronic graft-versus-host disease (cGVHD) has been invariably described in association with its extensive form. We have also observed it in a patient with the limited cGVHD form. DESIGN: We here describe our experience of gynecological complications in a population of 30 women who were followed up in a single center 12-120 months after allogeneic stem cell transplant (allo-SCT) due to hematological malignancies. All of them manifested premature ovarian failure because of the received treatments. RESULTS: Three out of 14 women who were affected by cGVHD developed hematocolpometra after estrogen + progestogen therapy (EPT) introduction, due to uterine and vaginal dystrophy and synecchiae. Extensive cGVHD, including dermal and mucosal localization, was present in two women while the third had only liver involvement. None of our patients had received radiation therapy or had a posttransplant history of infection. Local application of estrogens consistently improved the gynecological complication. However, vaginal synecchiae tended to relapse when local treatment was interrupted, despite no other apparent evidence of active cGVHD. CONCLUSIONS: All women with cGVHD should undergo gynecological examination before introducing EPT, to avoid unpleasant complication as hematocolpometra. Vaginal and cervical synecchiae should be treated with prolonged local treatments, and temporary use of continuous EPT regimens may be preferable in these women. Moreover, close monitoring by pelvic exam and ultrasonography is advisable during the initial cycles to detect any complication caused by possible intrauterine adhesions undetected during the previous gynecological examination.

Comparison of the gene expression repertoire in human hematopoietic progenitors and mature leukocytes led to identification of a transcript expressed in CD34+cells and undetectable in differentiated cells. Sequencing of the cDNA (termed EHZF: early hematopoietic zinc finger) revealed 30 zinc fingers with 96% homology to mouse Evi3, a recently identified gene associated with the retroviral integration site in AKXD-27 B-cell lymphomas. EHZF and Evi3 share high homology with the transcription cofactor OAZ, implicated in the control of olfactory epithelium and B-lymphocyte differentiation and in the bone morphogenic protein (BMP) signal transduction. Here we show that (1) EHZF expression is abundant in human CD34+ progenitors and declines rapidly during cytokine-driven differentiation; (2) significant mRNA levels are found in most acute myelogenous leukemias; (3) in response to BMPs EHZF complexes SMADs 1 and 4, binds to, and enhances the transcriptional activity of, a BMP2/4 responsive element; (4) EHZF inhibits the transcriptional activity of early B-cell factor (EBF), a transcription factor essential for specification of the B-cell lineage. Taken together, our data suggest that EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies.

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) longterm survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and microarchitectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to autoHSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after autoHSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soonas abnormalities are detected.

Technetium-99m-sestaMIBI is a reliable positive tracer of skeletal lesions in multiple myeloma (MM), while bone scintigraphy by 99mTc-MDP and 67Ga scanning are considered of negligible value. We report the case of a young patient with a 5-year history of light chain MM, which was not eradicated by chemotherapy, radiotherapy, allogeneic bone marrow transplantation, α-interferon and donor lymphocyte infusion. In the final phase of the disease a CT scan showed a 14 cm mediastinal mass (Figure 1A). The neoplastic tissue took up 67Ga more avidly than 99mTc-sesta MIBI (Figures 1B-C), and focal bone lesions showed 67Ga uptake even in areas negative by MIBI scan. The patient died of disease progression in a few months. It seems that a 67Ga scan can identify patients with very aggressive MM.

Background Several evidence show that elevated plasma levels of uric acid (UA) are associated with the increased risk of developing atherothrombotic cardiovascular events. Hyperuricemia is a risk factor for endothelial dysfunction (ED). ED is involved in the pathophysiology of atherothrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the tissue factor (TF)/TF pathway inhibitor (TFPI) balance by finally changing the antithrombotic characteristics of endothelial cells. Methods Human umbilical vein endothelial cells were incubated with increasing doses of UA (up to 9 mg/dL). TF gene and protein expressions were evaluated by real-time polymerase chain reaction (PCR) and Western blot. Surface expression and procoagulant activity were assessed by FACS (fluorescence activated cell sorting) analysis and coagulation assay. The mRNA and protein levels of TFPI were measured by real-time PCR and Western blot. The roles of inflammasome and nuclear factor-κB (NF-κB) as possible mechanism(s) of action of the UA on TF/TFPI balance were also investigated. Results UA significantly increased TF gene and protein levels, surface expression, and procoagulant activity. In parallel, TFPI levels were significantly reduced. The NF-κB pathways appeared to be involved in modulating these phenomena. Additionally, inflammasome might also play a role. Conclusion The present in vitro study shows that one of the mechanisms by which high levels of UA contribute to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a nonphysiological, prothrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

Several lines of evidence have clearly indicated that inflammation plays a pivotal role in the development of atherosclerosis and of its thrombotic complications such as acute coronary syndromes or ischemic stroke. Thus, it has been postulated that the use of anti-inflammatory agents might be extremely useful to improve cardiovascular outcome. Recently, increasing attention has been reserved to one of the oldest plant-derived drugs still in use in clinical practice, colchicine that has been used as drug to treat inflammatory diseases such gout or Mediterranean fever. To date, current guidelines of the European Society of Cardiology have included colchicine as first line choice for treatment of acute and recurrent pericarditis. Moreover, several studies have investigated its role in the clinical scenarios of cardiovascular disease including chronic and acute coronary syndromes with promising results. In this review, starting from a description of the mechanism(s) involved behind its anti-inflammatory effects, we give an overview on its potential effects in atherothrombosis and finally present an updated overview of clinical evidence on the role of this drug in cardiovascular disease.

Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal component quantification; the absence of such a parameter renders difficult follow up of patients with nonsecretory MM (nsMM). In this study our aims were to determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at diagnosis and during follow up of nsMM patients. Nine nsMM patients were prospectively studied at diagnosis and during treatment for a mean time of 33 months (range: 12 - 65 þ ). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed more focal lesions than MIBI in four patients, while MIBI revealed more focal lesions than CI in two patients. During the follow up, MIBI uptake was normal in the four patients who achieved remission. Five patients did not achieve remission: CI and MIBI were concordant in three, while MIBI was falsely negative in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity (no false positive cases) and 78% specificity (2/9 false negative cases) in tracing active nsMM lesions; it should be considered complementary to CI for monitoring this rare disease.

Women undergoing stem cell transplantation (SCT) are mostly young and have more than 90% probability of ovarian failure, which is often permanent. A woman's age, use of radiotherapy and alkylating chemotherapy, and the allogeneic type of transplant are associated with a higher rate of premature ovarian failure and worse residual ovarian function. Premature ovarian failure has serious systemic and psychological effects that may need treatment and should be managed by practitioners trained to treat this particular population of women. Ultrasonographic evidence of ovarian follicles is often associated with a future resumption of cycles, but there are no serum markers to predict the return of ovarian function in these patients. In our center, the rate of ovarian function recovery was 7% after allogeneic SCT and 25% after autologous SCT (P