Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review

This systematic review focuses on the literature evidence for residual ovarian function during treatment with hormonal contraceptives. We reviewed all papers which assessed residual ovarian activity during hormonal contraceptive use, using endocrine markers such as serum anti-Müllerian hormone (AMH) concentrations, FSH, LH, oestradiol, progesterone and sonographic markers such as antral follicle count (AFC), ovarian volume and vascular indices. We considered every type (oestroprogestin or only progestin) and dosage of hormonal contraceptive and every mode of administration (oral, vaginal ring, implant, transdermal patch). We performed an electronic database search for papers published from 1 January 1990 until 30 November 2015 using PubMed and MEDLINE. We pre-selected 113 studies and judged 48 studies suitable for the review. Most studies showed that follicular development continues during treatment with hormonal contraceptives, and that during treatment there is a reduction in serum concentrations of FSH, LH and oestradiol, and also a reduction in endometrial thickness, ovarian volume and the number and size of antral follicles. The ovarian reserve parameters, namely AFC and ovarian volume, are lower among users than among non-users of hormonal contraception; regarding the effect of hormonal contraception on AMH, there are still controversies in the literature

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Clinical and molecular characterization of diffuse large B-cell lymphomas with 13q14.3 deletion.

Background: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21). Patients and methods: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years. Results: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21. Conclusions: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation

Histologic transformation in marginal zone lymphoma

Information concerning histologic transformation (HT) of marginal zone lymphomas (MZL) into aggressive entities is scant. We retrospectively analyzed the clinical variables at diagnosis and outcome, with special reference to HT, in a population of consecutive patients (pts) with confirmed diagnosis of MZL, including extranodal MZL (MALT lymphoma), splenic MZL (SMZL) and nodal MZL (NMZL). The database of the Hematology Division of the Amedeo Avogadro University of Eastern Piedmont (Novara) and of the Oncology Institute of Southern Switzerland (IOSI, Bellinzona) includes 373 cases of MZL diagnosed and treated since 1979 to 2012: 185 MALT lymphomas (50%), 88 SMZL (23%), 36 NMZL (10%). Sixty-four patients (17%) could not be properly classified (uMZL): they presented with bone marrow infiltration with or without detectable involvement of peripheral blood but without splenomegaly and with apparently no other extranodal or nodal involved site. Incidence was not significantly different according to sex (male: 47; female: 53%), median age at diagnosis was 68 years (20-94 years); 244 pts (65%) had stage III-IV disease. LDH was elevated in 55/311 (18%) tested pts, beta2-microglobulin in 108/205 (53%) tested pts. B symptoms were reported in 27/368 pts (7%). Five percent of pts had an ECOG performance status > 1. Serologic evidence of hepatitis C virus (HCV) infection was reported in 45/243 (19%) pts for whom the data was available. Among the 186 MALT lymphomas, 91 pts (49%) had a gastric localization, and 54 (29%) had multiple extranodal sites of disease involvement. Median overall survival and progression-free survival of the whole population were 15 years and 8 years, respectively. After a median follow-up of 64 months, HT was observed in 14 cases (4%, 4 95%CI:2%-6%). A diagnosis of diffuse large B cell lymphoma was documented in 12 pts (85.7% of patients undergoing HT), while in two cases the diagnosis was of classical Hodgkin lymphoma and mantle cell lymphoma, respectively. HT occurred after a median interval of 3 years (range: 1-12 years) after diagnosis. With respect to MZL type, HT occurred in 6% SMZL, 3% MALT lymphomas, 3% NMZL, and 3% uMZL (P=0.767). Risk of HT was 5% (95%CI, 3- 8%) at 5 years, 5% (95%CI:3%-8%) at 10 years and 8% (95%CI, 4-15%) at 15 years; the rate of transformation tended to plateau from that point onward. At the time of HT, most pts had high LDH serum levels (8/11, 73%) and presence of B symptoms (6/10, 60%). After transformation, ten pts received anthracycline-containing regimens, and three pts were treated with high dose cytarabine regimens; in a single patient only supportive measures were adopted. In four pts, autologous stem cell transplantation was performed after induction. At a median follow-up of 12 months after HT, five of 14 patients died, all for lymphoma-related causes, with a 2-year posttransformation survival rate of 52% (95%CI:13%-81%). The only clinical variable significantly associated with the risk of HT was elevated serum LDH level at diagnosis. No specific therapeutical approach, including watchful waiting, predicted the risk of HT. This large retrospective series documents that the risk of HT is low across all MZL types. The incidence of HT in MZL is apparently lower than that of other indolent B cell malignancies, namely follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). As also observed in FL and CLL, HT in MZL occurs relatively early during the clinical course, pointing to putative biological differences at diagnosis in MZL patients destined to transform

Le sfide per i manager sanitari tra soft skills, ICT e carriere frammentate

Institutional reforms and legislative interventions, having affected the healthcare system for years, seem to confer to the middle management an important role in managing organisational change. From the stories collected through research carried out among learners and ex-learners of the Master in Management and Innovation at Sapienza University of Rome, it has emerged the need for them to develop transversal skills indispensable for performing their role as medi-ators of top-down organisational innovations. Concerning digitalisation processes, we have collected both stories of resistance to the use of ICT and also the request for a participatory and integrated design of technological innovations. Uncertainties and cultural resistances caused by these changes fragment careers of professional women and men who narrate how they put in play different practices and skills in building their own paths and, for women only, in reconciling them with their care activity

Protective effect of a peptide derived from the endogenous PKC inhibitor PKI55 on the neurosecretory function in ischemic brain slices

We have recently identified the PKI55 protein, coding for 55 amino acids, that is normally poorly translated in vivo and acts as a specific modulator of either cPKC-α and nPKC-δ isozymes. PKI55 remains relatively inactive until PKC attains an active conformation and reaches a critical concentration in the cell; it is not modified by the enzyme but irreversibly associates with its target, thus behaving as a suicidal inhibitor. The inhibition and degradation of over-activated PKC isozymes may prevent unfavorable changes in cellular phenotypes, resulting from PKC overexpression (Selvatici, J Mol Evol 2003 57:131). In the present work we compared the in vitro biochemical activity of the PKI55 protein, of its 39-amino acids N-terminal fragment (G39) and of its 16 amino acids C-terminal fragment (G16) on specific PKC recombinant isozymes, by measuring the initial rate of phosphate incorporation from 32P-ATP into saturating amounts of histone IIIS. PKI55 concentration-dependently inhibited PKC activity, provided that calcium ions were present in the assay medium (IC50=6μM). The inhibitory activity was retained by G16 (IC50=50μM), but not by G39. The active fragment G16 was tested in an in vitro model of brain ischemia: superfused guinea pig cerebral cortex slices, continuously electrically (10 Hz) stimulated, were exposed to 20 min of oxygen-glucose deprivation (OGD, Badini, Neurochem Int 1997 31:817), and then reperfused for 1 hour (REP). PKC activity was increased to 244±36% at the end of OGD, while acetylcholine (ACh) release, taken as an index of the neurosecretory function, was reduced to 35±2% of the controls. Following REP, a reduction in PKC activity to 54±7% was displayed, indicating a down regulation of previously activated PKC (Selvatici, J Neurosci Res 2003 71:64). ACh release only partially recovered (REP=69±6% of the controls), suggesting persistence of neuronal suffering. PKC activation during OGD was attenuated by 50µM G16 and the consequent down regulation following REP was prevented. Moreover, ACh release fully recovered to normal values (REP+G16=91±4% of the controls). These data suggest a neuroprotective action for G16, the active fragment of the endogenous PKC inhibitor PKI55

Management of hydrosalpinx before IVF: A literature review.

Hydrosalpinx has a detrimental effect on the outcome of in vitro fertilization (IVF). Surgical intervention such as salpingectomy or tubal occlusion before IVF improves the outcome of IVF, but these procedures are often contraindicated in women with dense pelvic adhesions. Thus, it is worthwhile to search minimally invasive alternative therapies. The main objective of this review is to assess and compare the value of all the therapeutic options for hydrosalpinx before IVF. The results of the following procedures were compared: the laparoscopic treatments (salpingectomy/proximal tubal occlusion), the hysteroscopic insertion of device achieving tubal occlusion, the tuberous sclerosis and the aspiration of hydrosalpingeal fluid at the time of IVF procedure. Laparoscopic surgical treatment should be considered for all women with hydrosalpinx before IVF. Whenever laparoscopy is not recommended, hysteroscopic insertion of device seems the most effective option for management of hydrosalpinx before IVF

Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia

Background and objectives: aberrant promoter methylation targets CpG islands causing gene silencing. We explored aberrant promoter methylation of genes potentially involved in B-cell malignancies and encoding proteins implicated in DNA repair (O6-methylguanine-DNA methyltransferase, MGMT), detoxification of environmental xenobiotics (glutathione S-transferase P1, GSTP1), apoptosis regulation (death associated protein kinase, DAP-k and caspase 8, CASP8) and cell cycle control (p73). Design and methods: three hundred and seventeen B-cell malignancies were investigated by methylation-specific polymerase chain reaction (MSP) of MGMT, GSTP1, DAP-k, CASP8 and p73 genes. In selected cases, MSP results were matched to protein expression studies by immunohistochemistry or Western blotting. Results: DAP-k promoter methylation occurred at highest frequency in follicular lymphoma (85.0%) and MALT-lymphoma (72.2%). MGMT methylation targeted both precursor B-cell neoplasia (23.8%) and mature B-cell tumors (27.6%). GSTP1 methylation was commonest in hairy cell leukemia (75.0%), follicular lymphoma (55.5%), Burkitt s lymphoma (52.0%), and MALT lymphoma (50.0%). Methylation of p73 and CASP8 was rare or absent. DAP-k and MGMT methylation caused absent protein expression. Interpretation and conclusions: methylation of MGMT, DAP-k and GSTP1 represents a major pathogenetic event in several B-cell malignancies. In follicular lymphoma and MALT lymphoma, frequent inactivation of the apoptosis extrinsic pathway through DAP-k methylation may reinforce the survival advantage already conferred by deregulation of the intrinsic apoptotic pathway. Inactivation of GSTP1 in gastric MALT lymphoma represents an additional mechanism favoring accumulation of reactive oxygen species and lymphomagenesis. Finally, the frequency of GSTP1 aberrant methylation in diffuse large B-cell lymphoma prompts studies aimed at verifying the prognostic impact of this epigenetic lesion in these lymphomas