Splenomegaly impacts prognosis in essential thrombocythemia and polycythemia vera: A single center study

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019

Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function

Anti-endothelin drugs in solid tumors

Importance of the field: The endothelin (ET) axis, which includes the biological functions of ETs and their receptors, has played a physiological role in normal tissue, acting as a modulator of vasomotor tone, tissue differentiation and development, cell proliferation and hormone production. Interestingly, it also functions in the growth and progression of various tumors. Several researchers have identified the blockade of the ET-1 receptor as a promising therapeutic approach. Areas covered in this review: The clinical investigation of an orally bioavailable ET antagonist, atrasentan, in prostate cancer, is encouraging. In this neoplasia, it has shown antitumor activity, bone metastasis control and amelioration of cancer-related pain but improvement in time to progression and overall survival has still not been demonstrated. The clinical trials of other ET antagonists are reported. Literature research was performed by Pubmed and Pharmaprojects. What the reader will gain: A comprehensive view about the use of atrasentan in the treatment of castration-resistant prostate cancer (CRPC) is provided together with the scientific rationale based on the function of ET and its receptor in various cancer development mechanisms. Take home message: Atrasentan seems to be active in CRPC, although strong scientific evidence is still to be found. Interesting clinical findings regard zibotentan

Use of XR-QA2 radiochromic films for quantitative imaging of a synchrotron radiation beam

This work investigates the use of XR-QA2 radiochromic films for quantitative imaging of a synchrotron radiation (SR) beam. Pieces (200 7 30 mm2) of XR-QA2 film were irradiated in a plane transverse to the beam axis, at the SYRMEP beamline at ELETTRA (Trieste), with a monochromatic beam of size 170 7 3.94 mm2 (H 7 V) and energy of 28, 35, 38 or 40 keV. The response was calibrated in terms of average air kerma (1\uf02d20 mGy), measured with a calibrated ionization chamber. Films were digitized in reflectance mode using a flatbed scanner. The 16-bit red channel was used. The net\uf020reflectance was then converted to photon fluence per unit air kerma (mm-2 mGy-1). The SR beam profile was acquired also with a scintillator (GOS) based, fiberoptic coupled CCD camera as well as with a scintillator based flat panel detector. Horizontal profiles obtained with the two modalities were compared, evaluated in a ROI of 17.71 7 0.59 mm2, across the beam centre. Once corrected for flat field, the CCD profile was scaled in order to have the same average value as the normalized profile acquired with the gafchromic film. The same procedure was followed for the beam images acquired with the flat panel detector. Horizontal and vertical line profiles acquired with the radiochromic film show an uneven 2D distribution of the beam intensity, with variations in the order of 15\uf02d20% in the horizontal direction, while the statistical uncertainties evaluated for the radiochromic dose measurements were 6% at 28 keV. Larger variations up to 64% were observed in the vertical direction. The response of the radiochromic film is comparable to that of the other imaging detectors, within less than 5% variation

The activity of intravesical hyaluronic acid and chondroitin sulfate administration on urothelial gene expression. Preliminary results on the epidermal growth factor receptor and fibronectin gene expression evaluated in bladder washings of patients affected by non muscle-invasive bladder cancer

Introduction & Objectives Hyaluronic acid (HA) and chondroitin sulfate (CS) are two major constituents of the bladder glycosaminoglycan layer. Recent data show that Fibronectin (FN) and Epidermal Growth Factor Receptor (EGFR) gene expression can be measured in bladder washings and could represent potential biomarkers of urothelial damage and tumor aggressiveness, respectively (1,2). The aim of our study was to investigate the interference of a single intravesical instillation of HA-CS solution on the expression of FN and EGFR genes in patients affected by non-muscle-invasive bladder cancer (NMIBC). Material & Methods A prospective double-blinded study included patients undergoing adjuvant intravesical therapy for NMIBC and age matched healthy controls. For EGFR evaluation, a single HA-CS solution was administered intravesically 14 days after transurethral resection of high risk NMIBC, before the start of the adjuvant therapy. For FN evaluation, a single HA-CS instillation was administered to patients showing local toxicity secondary to intravesical adjuvant therapy. Samples of bladder washings were collected before and one week after the HA-CS instillation, obtaining a cellular pellet stored at -80 °C. Cellular RNA was isolated by a miRNeasy Mini Kit (Qiagen®) and cDNA, obtained using a “High Capacity cDNA Reverse Transcription Kit” (Life Technologies®) was used to perform a gene expression analysis by a Real Time PCR. EGFR and FN gene expression values were expressed in FOLDs of change compared to healthy controls (FN and EGFR=1). Results Thirty-eight patients and 5 controls entered the study. Seventeen and 21 patients were evaluated for FN and EGFR respectively. In 21 patients with high risk NMIBC, the median EGFR expression decreased from 2.4 folds (range: 0.1-39.0) to 1.0 fold (range: 0.05-36.8) showing a statistically significant decrease of 58.3% (p<0.02). In patients showing clinically relevant toxicity secondary to intravesical adjuvant therapy (BCG in 9 and Epirubicin in 8 patients) the median FN expression value dropped from 1.8 folds (range: 0.07-8.1) to 0.9 fold (range: 0.1-7.5) after HA-CS administration with a statistically significant decrease of 50% (p<0.05). Conclusions FN gene expression in bladder washings appears related to the intensity of the urothelial damage, reaching higher expression levels in case of severe toxicity induced by intravesical adjuvant therapy (2). In our experience the FN gene expression significantly decreases a week after the administration of HA-CS solution with contemporary symptomatic relief. Moreover the urothelial EGFR gene expression resulted significantly lowered one week after the HA-CS intravesical administration. The reduced availability of its receptor could limit the proliferative activity of EGF on the urothelium promoting recurrence and progression. Acknowledgements: GSTU Foundation References: 1. Serretta V, et al. Feasibility of EGFR evaluation in bladder washings of patients affected by non muscle-invasive bladder cancer. J Urol, 2016. 195 (4S): e327. 2. Alonge V, et al. Correlation between Fibronectin gene expression and local toxicity induced by adjuvant intravesical therapy. J Urol, 2015. 193 (4S): e53

Osteonecrosis of the jaw after adjuvant endocrine therapy plus alendronate in a breast cancer patient

Background. Bisphosphonates-associated osteonecrosis of the jaws (BRONJ) is a serious complication, which has been defined by Bedogni et al. (1) as an adverse drug reaction consisting of progressive destruction and death of bone that affects the mandible and/or maxilla of patients exposed to the treatment with nitrogen-containing bisphosphonates (NBPs) in absence of a previous radiation treatment. Generally, IV NBPs have a strong association with BRONJ than oral NBPs as evidenced by the higher incidence of BRONJ (0-10%) in patients treated with IV drugs than in patients in oral therapy (<1%). Objectives. The aim of this study was to report a clinical case of BRONJ in an oncologic patient who has been treated with anastrozole and oral NBPs for secondary osteoporosis. Case report. In February 2014 a 75-year-old woman was referred because of history of pain in the left posterior mandibular region and hypoesthesia/anesthesia of the homolateral inferior lip and chin. In the anamnesis, she had referred to be in therapy with alendronate since 2004, for a history of severe osteoporosis and, in multimodal chemotherapy and anastrazole since 2010 for a diagnosis of breast cancer. Furthermore, left lower molar extraction was performed on March 2013. Clinical examination revealed swelling of the extraoral soft tissue in the left emimandible; intraorally, the presence of a mucosal fistula on the left mandibular angle was identified. CT was performed and BRONJ diagnosis was defined with a stage 2A according to Bedogni et al. Conclusions. Administration of NBP is indicated to treat also osteoporosis anastrazole-induced in oncological patients, showing that patients with hormone receptor-positive early-stage breast cancer taking oral BP could represent a subset in which it would be useful to apply BRONJ prevention protocols

Lines on projective varieties and applications

The first part of this note contains a review of basic properties of the variety of lines contained in an embedded projective variety and passing through a general point. In particular we provide a detailed proof that for varieties defined by quadratic equations the base locus of the projective second fundamental form at a general point coincides, as a scheme, with the variety of lines. The second part concerns the problem of extending embedded projective manifolds, using the geometry of the variety of lines. Some applications to the case of homogeneous manifolds are included.Comment: 15 pages. One example removed; one remark and some references added; typos correcte

Energy response of GR-200A thermoluminescence dosemeters to CO-60 and to monoenergetic synchrotron radiation in the energy range 28-40 KEV

7noThe response of LiF:Mg,Cu,P thermoluminescence dosemeters (type GR-200A) to monoenergetic radiation of energy 28, 35, 38 and 40 keV was evaluated with respect to irradiation with a calibrated 60Co gamma-ray source. High-precision measurements of the relative air kerma response performed at the SYRMEP beamline of the ELETTRA synchrotron radiation facility (Trieste, Italy) showed a significant deviation of the average response to low-energy X-rays from that to 60Co, with an over-response from 6 % (at 28 keV) to 22 % (at 40 keV). These data are not consistent with literature data for these dosemeters, where model predictions gave deviation from unity of the relative air kerma response of about 10 %. The authors conclude for the need of additional determinations of the low-energy relative response of GR-200A dosemeters, covering a wider range of monoenergetic energies sampled at a fine energy step, as planned in future experiments by their group at the ELETTRA facility.Published online first 02 March 2015partially_openembargoed_20160302F. Emiro; F. Di Lillo; G. Mettivier; C. Fedon; R. Longo; G. Tromba; P. RussoF., Emiro; F., Di Lillo; G., Mettivier; Fedon, Christian; Longo, Renata; G., Tromba; P., Russ

Clinical implications of discordant early molecular responses in CML patients treated with imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt;10% after 3 months or &lt;1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3-and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values &gt;10% at 3 months but &lt;1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (event-free survival 68.2% vs. 32.7%; p &lt; 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months &gt;10% but &lt;1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS &lt;10% at 3 months but &gt;1% at 6 months (75% vs. 18.2%; p &lt; 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values &lt;1% at 6 months (p &lt; 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points