A novel machine-learning framework based on early embryo morphokinetics identifies a feature signature associated with blastocyst development.

BACKGROUND: Artificial Intelligence entails the application of computer algorithms to the huge and heterogeneous amount of morphodynamic data produced by Time-Lapse Technology. In this context, Machine Learning (ML) methods were developed in order to assist embryologists with automatized and objective predictive models able to standardize human embryo assessment. In this study, we aimed at developing a novel ML-based strategy to identify relevant patterns associated with the prediction of blastocyst development stage on day 5. METHODS: We retrospectively analysed the morphokinetics of 575 embryos obtained from 80 women who underwent IVF at our Unit. Embryo morphokinetics was registered using the Geri plus® time-lapse system. Overall, 30 clinical, morphological and morphokinetic variables related to women and embryos were recorded and combined. Some embryos reached the expanded blastocyst stage on day 5 (BL Group, n = 210), some others did not (nBL Group, n = 365). RESULTS: The novel EmbryoMLSelection framework was developed following four-steps: Feature Selection, Rules Extraction, Rules Selection and Rules Evaluation. Six rules composed by a combination of 8 variables were finally selected, and provided a predictive power described by an AUC of 0.84 and an accuracy of 81%. CONCLUSIONS: We provided herein a new feature-signature able to identify with an high performance embryos with the best developmental competence to reach the expanded blastocyst stage on day 5. Clear and clinically relevant cut-offs were identified for each considered variable, providing an objective tool for early embryo developmental assessment.

The importance of rotation to teach secure half-hitch sequences in surgery.

Background: Knot security of half-knot (H) sequences varies with rotation, but half-knots risk destabilisation. Objectives: To investigate the rotation of half-hitch (S) sequences on knot security. Materials and Methods: The loop and knot security of symmetrical and asymmetrical sliding and blocking half-hitch sequences was measured using a tensiometer. Results: Loop security of symmetrical sliding half-hitch sequences is much higher than asymmetrical sequences, increasing from 6+2 to 21+2 and from 27+6 to 48+5 Newton (N) for 2 and 4 half-hitches respectively (both P<0.0001). Symmetrical sliding sequences are more compact and remain in the same plane, squeezing the passive thread, while asymmetrical sequences rotate loosely around the passive end. Blocking sequences are superior when asymmetrical since changing the passive end acts like changing rotation, transforming the asymmetrical sliding into a symmetrical blocking half-hitch on the new passive thread. The knot security of 2 sliding and 1 blocking half-hitch doubles from 52+3 to 98+2 N for the worst (asymmetric sliding and symmetric blocking, SSaSsb) or best rotation sequences (SSsSab). Adding a second asymmetric blocking half-hitch (Sab) increases security further to 105+3 N. The overall knot security of four-throw, correctly rotated, half-hitch (SSsSabSab) or half-knot (H2H1sH1s, H2H2a and H2H2s) sequences is similar for four suture diameters. Conclusion: Rotation affects the security of half-hitch sequences, which should be symmetrical when sliding, and asymmetrical when blocking. What is new?: Half-hitch sequences are clinically superior to half-knot sequences. They do not risk destabilisation, and loop security improves approximation of tissues under traction, permitting tight knots.

Serial cervical-length measurements after first episode of threatened preterm labor improve prediction of spontaneous delivery prior to 37 weeks' gestation.

OBJECTIVE: To assess whether repeat cervical-length (CL) measurement in women discharged from hospital after their first episode of threatened preterm labor can predict their risk of spontaneous preterm birth. METHODS: This was a secondary analysis of a randomized controlled trial of maintenance tocolysis, in which CL was measured on transvaginal ultrasound at the time of hospital discharge and after 2, 4, 8 and 12 weeks, in women who remained undelivered after their first episode of threatened preterm labor. After univariate analysis, multivariate logistic regression analysis was used to assess whether CL < 10 mm at the time of hospital discharge or at any follow-up evaluation could predict spontaneous delivery prior to 37 weeks of gestation. RESULTS: Of 226 women discharged after a diagnosis of threatened preterm labor, 57 (25.2%) delivered spontaneously prior to 37 weeks' gestation. The risk of spontaneous preterm birth was higher among women with CL < 10 mm at hospital discharge compared to those with CL ≥ 10 mm (adjusted odds ratio (aOR), 3.3; 95% CI, 1.2-9.2). Moreover, spontaneous preterm delivery was more common when CL < 10 mm was detected up to 2 weeks (aOR, 2.9; 95% CI, 1.1-7.3) or up to 4 weeks (aOR, 7.3; 95% CI, 2.3-22.8) post discharge, as compared with when CL was persistently ≥ 10 mm. The association was not significant when considering CL measurements at 8 weeks, and there was insufficient information to assess the effect of measurements obtained at 12 weeks. CONCLUSIONS: Women who remain undelivered after their first episode of threatened preterm labor continue to be at high risk of spontaneous preterm birth if their CL is below 10 mm at the time of hospital discharge or at any follow-up visit up to 4 weeks later. CL measurement could be included in the antenatal care of these women in order to stratify their risk of preterm birth, rationalize resource utilization and help clinicians improve pregnancy outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile.

OBJECTIVES: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. METHODS: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. RESULTS: Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. CONCLUSIONS: In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course.

How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?

OBJECTIVES: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time-consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI. METHODS: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated. RESULTS: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001). CONCLUSIONS: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV-associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria.

EBCOG position statement: Vaccination in pregnancy.

Maternal immunization has the potential to reduce morbidity and mortality from infectious diseases worldwide. EBCOG promotes this public health intervention supporting international recommendations about the use of vaccines during pregnancy.

Why do sub-Saharan Africans present late for HIV care in Switzerland?

OBJECTIVES: Late presentation (LP) to HIV care disproportionally affects individuals from sub-Saharan Africa (SSA). We explored the reasons for late presentation to care among this group of patients in the Swiss HIV Cohort Study. METHODS: The prevalence of LP was compared between patients from Western Europe (WE) and those from SSA enrolled between 2009 and 2012. Patients were asked about HIV testing, including access to testing and reasons for deferring it, during face-to-face interviews. RESULTS: The proportion of LP was 45.8% (435/950) among patients from WE, and 64.6% (126/195) among those from SSA (P < 0.001). Women from WE were slightly more likely to present late than men (52.6% versus 44.5%, respectively; P = 0.06), whereas there was no sex difference in patients from SSA (65.6% versus 63.2%, respectively; P = 0.73). Compared with late presenters from WE, those from SSA were more likely to be diagnosed during pregnancy (9.1% versus 0%, respectively; P < 0.001), but less likely to be tested by general practitioners (25.0% versus 44.6%, respectively; P = 0.001). Late presenters from SSA more frequently reported 'not knowing about anonymous testing possibilities' (46.4% versus 27.3%, respectively; P = 0.04) and 'fear about negative reaction in relatives' (39.3% versus 21.7%, respectively; P = 0.05) as reasons for late testing. Fear of being expelled from Switzerland was reported by 26.1% of late presenters from SSA. CONCLUSIONS: The majority of patients from SSA were late presenters, independent of sex or education level. Difficulties in accessing testing facilities, lack of knowledge about HIV testing and fear-related issues are important drivers for LP in this population.

Human recombinant FSH induces chemoresistance in human breast cancer cells via HIF-1α activation†.

Breast cancer patients under 40 years of age who are candidate to chemotherapy with alkylating drugs may undergo controlled ovarian stimulation (COS) with recombinant human follicle-stimulating hormone (rhFSH) in order to get fertility preservation by mature oocyte cryostorage. The direct effect(s) of exogenous rhFSH on the chemosensitivity of breast cancer is currently unknown. To clarify this issue, we incubated four different breast cancer cell lines with rhFSH (10 IU/L, 24 h) and then we exposed them to doxorubicin (DOX) or cyclophosphamide (CPA). The effect(s) of rhFSH on human breast cancer cells treated with DOX or CPA was measured in terms of (1) cell viability, (2) cytotoxicity, (3) multidrug resistance (MDR) genes and proteins expression and activities, and (4) hypoxia-inducible factor 1-alpha (HIF-1α) activation. Pretreatment with rhFSH significantly increased the viability of breast cancer cells after treatment with DOX or CPA, and reduced the lactate dehydrogenase leakage and reactive oxygen species production. Moreover, after preincubation with rhFSH, the MDR proteins (Pgp, MPR1, and BCRP) expression and activity resulted upregulated and the HIF-1α pathway activated. In addition, the use of a widely used HIF-1α inhibitor, the 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), prevented the rhFSH effect on the onset of MDR. Taken together, these observations suggest that a short exposure to rhFSH induces chemoresistance to DOX and CPA in human breast cancer cells via HIF-1α activation.

Pregnancy in a woman with recurrent immunoglobulin a nephropathy: A case report.

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis and is increasingly encountered in pregnancy. The obstetric and renal outcomes of pregnancy are controversial, however. Women with IgAN are at higher risk of hypertension, preeclampsia and foetal loss; the prognosis is worse for those who have advanced chronic kidney disease and proteinuria. Here we report the case of a 32-year-old nulliparous woman with chronic hypertension who conceived during an active phase of her IgAN, which had been diagnosed 8 years earlier. Antihypertensive therapies and a low-protein diet were key to her reaching 34 weeks' gestation with acceptable kidney function. Rupture of membranes occurred at 34 weeks 3 days' gestation and a healthy boy was delivered the next day. This report aims to provide clinicians with useful information for the management of patients with IgAN during pregnancy.

Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF.

BACKGROUND: The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy. METHODS: A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5-9, 10-15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life. RESULTS: The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios. CONCLUSIONS: The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS).

Zona pellucida gene mRNA expression in human oocytes is related to oocyte maturity, zona inner layer retardance and fertilization competence.

STUDY QUESTION: Do the mRNA expression levels of zona pellucida (ZP) genes, ZP1, 2, 3 and 4 in oocyte and cumulus cells (CC) reveal relevant information on the oocyte? SUMMARY ANSWER: The ZP mRNA expression in human oocytes is related to oocyte maturity, zona inner layer (IL) retardance and fertilization capacity. WHAT IS KNOWN ALREADY: ZP structure and birefringence provide useful information on oocyte cytoplasmic maturation, developmental competence for embryonic growth, blastocyst formation and pregnancy. In order to understand the molecular basis of morphological changes in the ZP, in the current study, the polarized light microscopy (PLM) approach was combined with analysis of the expression of the genes encoding ZP1, 2, 3 and 4, both in the oocytes and in the surrounding CC. STUDY DESIGN, SIZE, DURATION: This is a retrospective study comprising 98 supernumerary human cumulus oocyte complexes (COC) [80 Metaphase II (MII), 10 Metaphase I (MI) and 8 germinal vesicle (GV)] obtained from 39 patients (median age 33.4 years, range 22-42) after controlled ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single oocytes and their corresponding CC were analysed. Oocytes were examined using PLM, and quantitative RT-PCR was performed for ZP1, 2, 3 and 4 in these individual oocytes and their CC. Ephrin-B2 (EFNB2) mRNA was measured in CC as a control. Presence of ZP3 protein in CC and oocytes was investigated using immunocytochemistry. Data were analysed using one-parametric and multivariate analysis and were corrected for the potential impact of patient and cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Oocytes contained ZP1/2/3 and 4 mRNA while in CC only ZP3 was quantifiable. Also ZP3 protein was detected in human CC. When comparing mature (MII) and immature oocytes (MI/GV) or their corresponding CC, ZP1/2 and 4 expression was lower in mature oocytes compared to the expression in immature oocytes (all P < 0.05) and ZP3 expression was lower in the CC of mature oocytes compared to the expression in CC of immature oocytes (P < 0.05). This coincided with a significantly smaller IL-ZP area and thickness in mature oocytes than in immature oocytes (all P < 0.05). In mature oocytes, IL-ZP retardance was significantly correlated with the expression of all four ZP mRNAs (all P < 0.05). The oocyte ZP3 expression was the main predictor of the fertilization capacity, next to IL-retardance and IL-thickness. Using stepwise regression analysis, IL-thickness combined with EFNB2 expression in CC and the patient's ovarian response resulted in a noninvasive oocyte fertilization prediction model. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study and the relation of oocyte mRNA levels to fertilization capacity is indirect as oocyte gene expression analysis required lysis of the oocyte. WIDER IMPLICATIONS OF THE FINDINGS: Overall relations between PLM observations, mRNA expression changes and intrinsic oocyte competence were successfully documented. As such PLM and CC gene expression are confirmed as valuable noninvasive techniques to evaluate oocyte competence. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by University of Torino, Italy, WFWG UZ-Brussel and Agentschap voor Innovatie door Wetenschap en Technologie IWT 110680, Belgium. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis.

Study Question: Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? Summary Answer: E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. What is Known Already: E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis. Study Design, Size, Duration: This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9). Participants/Materials, Setting, Methods: E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline. Main Results and the Role of Chance: A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P < 0.05). On the other hand, the expression of mesenchymal genes such as c-Myc, Vimentin, neuronal-Cadherin and sushi domain containing 2 remained unchanged. Cabergoline treatment induced a significant reduction of the E-MSC angiogenic potential (P < 0.05 versus control). Large Scale Data: Not applicable. Limitations, Reasons for Caution: Further studies are necessary to investigate the cellular and molecular mechanisms underlying the endothelial cell differentiation. Wider Implications of the Findings: E-MSCs may undergo endothelial differentiation, and be potentially involved in the development of endometriotic implants. Cell culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment. Study Funding/Competing Interest(s): This study was supported by the 'Research Fund ex-60%', University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

Large randomized trial comparing transabdominal ultrasound-guided embryo transfer with a technique based on uterine length measurement before embryo transfer.

OBJECTIVE: To compare in a randomized, non-inferiority trial the embryo transfer (ET) technique based on uterine length measurement before transfer (ULMbET) with transabdominal ultrasound-guided embryo transfer (TA-UGET) in a large population of patients undergoing in-vitro fertilization (IVF). METHODS: Patients undergoing IVF with ET with cleaving fresh embryos were randomized to receive ULMbET or TA-UGET. The transfer of one to three embryos on day 2-3 of culture was performed using a soft catheter either under transabdominal ultrasound guidance (TA-UGET group) or after measurement of the uterine cavity by transvaginal ultrasound and calculation of the discharge site (ULMbET group). The primary outcome measures were clinical pregnancy rate, ongoing pregnancy rate and implantation rate, and secondary outcomes included patient discomfort during ET. RESULTS: A total of 1648 patients undergoing IVF were randomized to receive ULMbET (n = 828) or TA-UGET (n = 820) and were included in the analysis. Comparable clinical pregnancy rate (38.2% vs 38.9%), implantation rate (24.8% vs 25.2%) and ongoing pregnancy rate (33.1% vs 34.8%) were observed in ULMbET and TA-UGET groups. The discomfort intensity score and the proportion of patients with moderate-to-severe discomfort during ET were significantly higher in the TA-UGET group (2.6 vs 1.5 visual analog scale points and 19.8% vs 1.2%; P = 0.045 and P = 0.003, respectively). CONCLUSION: The ULMbET technique leads to IVF results comparable to those obtained with UGET, but is better tolerated than is TA-UGET and is technically easier to perform for a single operator. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Migraine in perimenopausal women.

Hormonal changes during the reproductive cycle are thought to account for the variation in migraine occurrence and intensity. Although the majority of women and the specialists treating them do not consider migraine as a component of the climacteric syndrome, many women, in fact, do experience migraine during perimenopause. If a woman already suffers from migraine, the attacks often worsen during menopausal transition. Initial onset of the condition during this period is relatively rare. Women with the premenstrual syndrome (PMS) prior to entering menopause are more likely to experience, during late menopausal transition, an increased prevalence of migraine attacks. Hormone replacement therapy (HRT) can be initiated during the late premenopausal phase and the first years of postmenopause to relieve climacteric symptoms. The effect of HRT on migraine, either as a secondary effect of the therapy or as a preventive measure against perimenopausal migraine, has been variously investigated. HRT preparations should be administered continuously, without intervals, to prevent sudden estrogen deprivation and the migraine attacks that will ensue. Wide varieties of formulations, both systemic and topical, are available. Treatment with transdermal patches and estradiol-based gels is preferable to oral formulations as they maintain constant blood hormone levels. Natural menopause is associated with a lower incidence of migraine as compared with surgical menopause; data on the role of hysterectomy alone or associated with ovariectomy in changing the occurrence of migraine are till now unclear.

Migraine attacks in the pharmacy: a gender subanalysis on treatment preferences.

In 2014 our group published the results of a survey conducted in Piedmont, Italy, on the patterns of use and dispensing of drugs in patients requesting assistance from pharmacists for relief of a migraine attack. Epidemiological studies on migraine have consistently shown that migraine is far more common among women than men. This gender difference is also reflected in the higher percentage of women visiting a pharmacy to obtain treatment or advice for headache attacks. In this study, we further explored gender differences in healthcare-seeking behavior and use of migraine medications. The aim of the study was to determine whether women made better selective use of migraine medications and whether visiting a headache center for consultation and treatment reflected awareness of how best to manage their condition. Among the drugs usually taken for relieving head pain, there was no statistically significant difference between men and women in the routine use of NSAIDs (55.6 vs. 51.6 %) or ergot derivatives (8.7 vs. 9.3 %). Statistically significant differences emerged between men and women (27.9 vs. 35.4 %) in the use of triptans (p = 0.003; OR 1.41, 95 % CI 1.12-1.78) and in the use of combined medications (8.5 vs. 12.2 %) (p = 0.029; OR 1.49, 95 % CI 1.04-2.14) but not in the use of simple OTC non-NSAIDs. Less men than women sought professional medical care for managing migraine (65.7 vs. 72.4 %) (p = 0.003; OR 0.71, 95 % CI 0.57-0.89); more women than men sought treatment at a headache center (21.7 vs. 17.4 %) (p = 0.044; OR 1.31, 95 % CI 1.07-1.72).

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

The first case of breast cancer in thalassemic patient: case report and review of literature.

Thalassemias are genetic disorders characterized by decreased synthesis of one of the globin chains. Beta-thalassemia is caused by impairment in the production of beta-globin chains leaving the excess alpha chains unstable. With better treatment approaches and improvement in chelation therapy, thalassemic patients are living longer. As a consequence, new complications and associations with other conditions including malignancy have emerged. The occurrence of malignancies in thalassemia has rarely been reported, and our review of the literature revealed only few cases. We report the first case of a thalassemic patient developing breast cancer and discuss the possibility of a link between the two disease entities. This case is intended to alert physicians of the possibility of a malignancy in thalassemia patients.

Frovatriptan 2.5 mg plus dexketoprofen (25 mg or 37.5 mg) in menstrually related migraine. Subanalysis from a double-blind, randomized trial.

PURPOSE: The purpose of this article is to investigate the efficacy and safety of frovatriptan plus dexketoprofen 25 or 37.5 mg (FroDex25 or FroDex37.5, respectively) compared to that of frovatriptan 2.5 mg (Frova) in menstrually related migraine (MRM). AIM: The aim of this article is to analyze a subgroup of 76 women who treated an MRM attack in this multicenter, randomized, double-blind, parallel-group study. METHODS: The primary end-point was the proportion of patients who were pain free (PF) at two hours. Secondary end-points included pain-relief (PR) at two hours and 48 hours sustained pain free (SPF). RESULTS: PF rates at two hours were 29% under Frova, 48% under FroDex25 and 64% under FroDex37.5 (p < 0.05). PR at two hours was Frova 52%, FroDex25 81% and FroDex37.5 88%, while 48 hours SPF was 18% under Frova, 30% under FroDex25 and 44% under FroDex37.5. CONCLUSION: Combining frovatriptan+dexketoprofen produced higher PF rates at two hours compared to Frova while maintaining efficacy at 48 hours. Tolerability profiles were comparable.

Migraine attacks in the pharmacy: a survey in Piedmont, Italy.

Headache patients often consult a pharmacist in an attempt to obtain momentary pain relief without having been given any previous expert advice. A specific questionnaire was distributed to the pharmacies in order to assess the patterns of use and dispensing of analgesic medications to the headache patient who turns to the pharmacist for relief of a painful attack. This study aimed at identifying migraine patients who self-medicated, with further end points including whether these patients shared any particular clinical characteristics, the most common type of analgesic medications used, and what, if anything, was recommended by the pharmacist; lastly, which health care professional, if any, routinely managed the patient's headaches. A total of 9,100 questionnaires were distributed to the pharmacies and the complete 3,065 were included in the database. The ID Migraine Screener Test was used to classify subjects into 4 groups: "Definite migraine" (3/3 positive answers: n = 1,042; 34 %), "Probable migraine" (2/3: n = 969; 31.6 %), "Unlikely migraine" (1/3: n = 630; 20.5 %), and "Other headaches" (0/3: n = 424; 13.8 %). Only Definite and Probable migraines (n = 2,011) are considered in this paper. Amongst the drugs usually taken by the patients, NSAIDs were more common in the Probable migraine group (60.7 %) than in the Definite migraine (44.7 %) group (p < 0.001). On the contrary, triptans were more commonly used by the Definite migraine group (42.9 %) than the Probable migraine (23.7 %) group (p < 0.001), and combination drugs were preferentially (p < 0.001) chosen by the Definite (13.8 %) rather than the Probable migraine group (8.7 %). A total of 29.2 % of respondents reported that for the management of their headaches, they did not avail themselves of any type of professional healthcare, such as their general practitioner, a headache specialist, or a Headache Center.

Endonasal mucosal contact points in chronic migraine.

Some anatomo-functional alterations of the nose may be considered as possible causes of headache: deviations of the nasal septum, abnormal turbinates, especially middle or superior, with consequent areas of mucosal contact with the septum. This study was performed on 100 subjects, 27 chronic migraine (CM) sufferers and 73 subjects who never suffered from migraine as control group. In the CM group, a direct endoscopic assessment was carried out in order to search for mucosal points of contact. Following the endoscopy, the patients underwent a computerized tomography (CT) in order to confirm the mucosal contact and for a better evaluation of its localization. The control group (C group) consisted of subjects who underwent a CT of the skull for various reasons. In CM group, a mucosal contact was highlighted in 14 patients (51.8 %); it was unilateral in 50 % of cases. In C group, the contact was present in 27 cases (36.9 %); in 81.5 % of them (n = 22), it was unilateral. A single site of contact was present in 6 (22 %) patients in CM group and 20 (27.3 %) patients in C group; more sites, in 8 (29.6 %) CM group patients and in 7 (9.5 %) patients of the C group. The connection between subjects and the number of single or multiple contacts in the two groups was statistically significant (p = 0.049). Furthermore, the frequency of the septum-middle turbinate was significantly (p = 0.0013) more frequent in CM sufferers (13/14) compared with control subjects (11/27). This study suggests, although with extremely early data, the need to select carefully patients for a possible surgical approach, using various parameters: in particular, the site of the mucosal contact, favoring the cases with multiple areas of contact, mainly between septum-middle turbinate and septum-superior turbinate.