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Infertility is increasing worldwide, as well as in Italy, and fallopian tube pathology represents one of the most impacting causes of infertility for multiple women. Indeed, tubal patency assessment is a crucial step in medical evaluation for women attending an in vitro fertilization (IVF) center. Currently, different methods for tubal investigation are available, such as chromosalpingoscopy, hysterosalpingography (HSG), and hysterosalpingo-contrast sonography (HyCoSy). This diagnostic exam is performed by ultrasonography and an air-water-based contrast agent represented by air-water, or foam solution (HyFoSy). An additional side benefit of these assessment tests is a fertility-enhancing effect, thanks to a positive effect defined as "tubal flushing," which in current literature is more strongly associated with HyFoSy with respect to HyCoSy. In this report, we present a case of a 34-year-old woman presented to our attention at the Reproductive and Physiopathology Unit of Sandro Pertini Hospital, Rome, in 2023, with unexplained infertility for 3.1 years of free sexual intercourse with a partner who did not report sperm abnormalities. Subsequently, in this exam, the woman spontaneously conceived in the same menstrual cycle that the 4D-HyCoSy was performed, without any additional fertility enhancement interventions. In this case report, we also include an updating review of the current literature regarding the insurgence of spontaneous pregnancy after this technique in order to explore the physiopathological and etiopathogenetic mechanisms underlying the achievement of spontaneous pregnancy and to confront our case with other recent works published. According to our clinical experience and the current literature, 4D-HyCoSy is the easiest, safest, and cheapest diagnostic exam for investigating tubal patency, which can lead to medical success in some cases of "unexplained infertility" as the achievement of a spontaneous pregnancy., Competing Interests: All authors declare no conflict of interest., (Copyright © 2024 Francesco Bisogni et al.)

Background: We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI., Methods: Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days., Results: Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 ( p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78-0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 ( p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity., Conclusions: Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.

Background: In assisted reproductive cycles (ART), the fine balance of controlling corpus luteum function is severely disrupted. To challenge this iatrogenic deficiency, clinicians aim to provide exogenous support. Several reviews have investigated progesterone route of administration, dosage and timing., Methods: A survey about luteal phase support (LPS) after ovarian stimulation was conducted among doctors in charge in Italian II-III level ART centers., Results: With regards to the general approach to LPS, 87.9% doctors declare to diversify the approach; the reasons for diversifying (69.7%) were based on the type of cycle. For all the most important administration routes (vaginal, intramuscular, subcutaneous) it appears that in frozen cycles there is a shift towards higher dosages. The 90.9% of the centers use vaginal progesterone, and when a combined approach is required, in 72.7% of cases vaginal administration is combined with injective route of administration. When Italian doctors were asked about the beginning and duration of LPS, 96% of the centers start the day of the pickup or the day after, while 80% of the centers continue LPS until week 8-12. The rate of participation of the centers confirms the low perceived importance of LPS among Italian ART centers, while may be considered quite surprising the relatively higher percentage of centers that measures P level. Tailorization to women's needs is the new objective of LPS: self-administration, good tolerability are the main aspects for Italian centers., Conclusions: In conclusion, results of Italian survey are consistent to results of main international surveys about LPS.

Background: The physical characterisation of FFF-beam profiles in the presence of a magnetic field requires a new standardization procedure and formulation., Purpose: The aim of this multicentric experience is to propose new normalisation factors to allow for the calculation of standard parameters typical of flattened beams, such as dosimetric field size and penumbra, for a 6 MV FFF beam from an MR-linac., Methods: The measurements were carried out on three ViewRay-MRIdiansystems. An equal set of measurements was acquired using the same equipment. Transverse beam profiles were acquired at seven different depthsand for six beam dimensions.The inflection point was estimated as the position of the maximum of a Gaussian fit obtained from the first derivative of the profiles. The position of the minimum and maximum points of the second derivative of the above Gaussian described the fall-off region, and the external peaks of the third derivative were considered as the in-field and out-field points. The profile normalisation was determined by imposing a 55% dose level at the inflection point and the renormalisation factors were calculated., Results: The position of the inflection point, and the second and third derivatives peaks were analysed,and the renormalisation factors as a function of field size and depth were determined. The values of the unflatness and the slope have been calculated for different depths and field sizes., Conclusion: This study represents the first multi-centric evaluation of the profiles on different low-field MR-Linac systems and theset of renormalisation parameters to analyse the FFF-beam on that system was effectively proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Evaluation of the optimal number of embryos, their quality, and the precise timing for transfer are critical determinants in reproductive success, although still remaining one of the main challenges in assisted reproduction technologies (ART). Indeed, the success of in vitro fertilization (IVF) treatments relies on a multitude of events and factors involving both the endometrium and the embryo. Despite concerted efforts on both fronts, the overall success rates of IVF techniques continue to range between 25% and 30%. The role of the endometrium in implantation has been recently recognized, leading to the hypothesis that both the "soil" and the "seed" play a central role in a successful pregnancy. In this respect, identification of the molecular signature of endometrial receptivity together with the selection of the best embryo for transfer become crucial in ART. Currently, efforts have been made to develop accurate, predictive, and personalized tests to identify the window of implantation and the best quality embryo. However, the value of these tests is still debated, as conflicting results are reported in the literature. The purpose of this review is to summarize and critically report the available criteria to optimize the success of embryo transfer and to better understand current limitations and potential areas for improvement.

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Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD ( p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days ( p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients ( p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.

Adequate iodine intake is of crucial importance in pregnancy to meet the thyroid hormone needs of both mother and fetus. In the present study, undertaken as a part of the surveillance actions following the introduction in Italy of a national salt iodination program in 2005, the iodine intake was investigated in 123 pregnant women and 49 control women living in the same area of central Italy. All the participants were screened for urinary iodine concentration (UIC), serum level of thyrotropin, free-thyroxine, free-triiodothyronine, and thyroid volume. Moreover, they were provided with a questionnaire on the use of iodine-containing salt or supplements. Control women had a median UIC of 102 µg/L, consistent with an iodine sufficiency, while in pregnant women the median UIC value was 108 µg/L, lower than the endorsed UIC of 150 µg/L. In addition, pregnant women showed a significantly increased median thyroid volume compared to controls. Interestingly, the median UIC did not differ between pregnant women not using iodine-containing salt or supplements and those regularly consuming iodized salt alone, while pregnant women with a daily intake of iodine-containing supplements had an adequate median UIC (168 µg/L). In conclusion, the data reported here showed that pregnant women and their fetuses are still exposed to the detrimental effects of iodine deficiency and that the consumption of iodine-containing supplements should be recommended in pregnancy.

Background: The aim of this study was to evaluate the efficacy of ospemifene in the Vaginal Health Index (VHI), in the vulvovaginal vascular perfusion, and to assess its impact on quality of life and sexual function., Methods: Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA), or genitourinary syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the Pulsatility Index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead, Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated., Results: The number of sexually active women significantly increased after 3 months (26 [60.46%] vs. 35 [81.39%]; P=0.01). The mean number of intercourses during the treatment increased (12.87±3.43 vs. 15.79±3.12, P=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively (PI [1.69±0.42 vs. 1.28±0.45, P=0.001] RI [0.74±0.11 vs. 0.54±0.15, P=0.001]). The FSFI, FSDS and SF-36 Questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis., Conclusions: Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Objective: To observe the real-world utilization patterns, effectiveness and safety profile of follitropin delta in women ≥18 years naïve to ovarian stimulation undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)., Design: Prospective, multinational, multicenter, observational study. All IVF/ICSI treatment protocols were conducted according to routine clinical practice, including undertaking fresh/frozen transfers. Outcomes included use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy rates and adverse drug reactions (ADRs)., Results: The first ovarian stimulation cycle using follitropin delta was initiated in 944 women. Mean baseline demographics were: age, 33.5 ± 4.7 years; bodyweight, 67.1 ± 13.6 kg; anti-Müllerian hormone, 20.3 ± 16.1 pmol/L (2.84 ± 2.25 ng/mL). The dosing algorithm was used to calculate the follitropin delta daily starting dose in 893/944 women (94.5%). The mean difference between the calculated and prescribed daily dose was small (0.2 ± 1.40 µg). The mean daily starting follitropin delta dose was 10.4 ± 2.72 µg and the mean total dose administered was 104 µg. Follitropin delta dose adjustments were reported for 57/944 (6.0%) women. The mean number of retrieved oocytes was 10.1 ± 7.03. Ongoing pregnancy at 10-11 weeks was reported for 255 women (27.0% per initiated cycle and 43.1% per fresh transfer [n=592]). Cumulative ongoing pregnancy rate after fresh and/or frozen transfer was 36.4% (344/944). Four women discontinued follitropin delta due to ADRs. Ovarian hyperstimulation syndrome (OHSS) was the most frequently reported ADR (n=37 [3.9%]); most cases of OHSS were of mild or moderate intensity (n=30 [3.2%])., Conclusions: This large real-world study of follitropin delta utilization patterns confirms its good pregnancy rates while minimizing OHSS risk during first ovarian stimulation cycle., Competing Interests: CB has received honoraria and/or non-financial support from Abbott, Ferring, Gedeon Richter, Merck, MSD, Organon and ObsEva. GG has received honoraria and/or non-financial support from Abbott, Ferring, Gedeon Richter, Guerbet, Merck, MSD, Organon, ObsEva, PregLem, ReprodWissen GmbH, Theramex, Cooper and Vifor. RR: None. PL is an employee of Ferring Pharmaceuticals. YLYS is an employee of Ferring Pharmaceuticals. SR was an employee of Ferring Pharmaceuticals at time of study conduct. JSEL has received an unrestricted research grant from Ferring Pharmaceuticals. He has also received grants and honoraria from AnshLabs, Gedeon-Richter, Ferring Pharmaceuticals, Roche Diagnostics and Titus Healthcare., (Copyright © 2022 Blockeel, Griesinger, Rago, Larsson, Sonderegger, Rivière and Laven.)

Background: The aim of this study was to evaluate the effects of breast cancer on the ovarian response and on oocyte quality following controlled ovarian hyperstimulation (COH)., Methods: This retrospective case-control study evaluated the effects of breast cancer on the ovarian response and on the oocyte quality. Oncological patients with breast cancer undergoing controlled ovarian stimulation cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male or tubal factor infertility were included in the study. Two hundred and ninety-four women were enrolled: 105 affected by breast cancer and 189 healthy women in the control group. Both groups were comparable in terms of age, BMI, and AMH value. Maximal estradiol levels on the triggering day, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, rate of metaphase 2 oocyte production, and numbers of immature and dysmorphic oocytes were analyzed., Results: Considering factors influencing the oocyte quality, such as age, BMI, AMH, duration of stimulation, E2 level on the triggering day, total FSH cumulative dose, stage, histotype, BRCA status, and hormone receptors, the univariate and multivariate analyses identified breast cancer as a risk factor for the presence of dysmorphic oocytes., Conclusions: The diagnosis of breast cancer does not seem to be associated with the impairment of the ovarian reserve, but is linked to a worsening oocyte quality.

Background: The aim of this study was to compare ovarian reserve, oocytes quality and pregnancy outcome of endometrioma treatment by laparoscopic stripping (LS) versus endometrioma ethanol sclerotherapy (EST) in infertile women awaiting in-vitro fertilization (IVF)., Methods: Retrospective analysis was performed. Twenty-three women underwent EST and 26 women LS. Intra- and postoperative complications were recorded. The women were followed-up for 36 months for cyst recurrence, oocytes quality and pregnancy outcome. Serum anti-Müllerian hormone (AMH) levels after treatment were measured to observe the impact on the ovarian reserve. Women's satisfaction was investigated with PGI-I., Results: During follow-up, there were 3 endometriomas recurrences after LS and none after EST. Six months after treatment AMH was 3.17±2.15 in EST vs. 2.22±1.97 in LS, P=0.045. Symptoms' improvement was comparable. No intraoperative complications occurred. In the LS group the postoperative complications were significantly higher. After IVF cycles, the quality of the retrieved oocytes was the same. In EST group, clinical pregnancy (48.1% vs. 19.6%) and live birth rates (36.5% vs. 14.3%) were significantly increased compared to LS. Women's satisfaction was comparable at PGI-I. Both EST and the presence of an endometrioma sized 6 cm or less proved to be independent factors of a better live birth rate in multivariate analysis., Conclusions: EST efficacy was greater than LS for endometrioma. Ovarian function was well preserved. Hospital stay was shorter, fewer complications occurred. Pregnancy outcome was better after EST.

Introduction: The number of pregnancies obtained through in vitro fertilization (IVF) techniques are increasing, and only few studies have investigated hemodynamic variations in women undergoing IVF techniques. The aim of this study was to evaluate the hemodynamic parameters in women undergoing IVF, to assess a possible correlation between hemodynamics and embryo implantation. Methods: 45 normotensive non-obese women, age ≤ 43 years, with idiopathic or tubal infertility, referred to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2020/2021, underwent IVF techniques. All women were evaluated with Ultra Sonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters at two different stages: at the mid-luteal phase, before the beginning of IVF, and at the day of embryo transfer (dET). All demographics and hormonal parameters in both groups were comparable. The hemodynamic parameters were compared between women with a positive β-HCG test vs. those testing negative. Results: 11 out of 45 (24,5%) women obtained positive β-HCG test. All demographics and hormonal parameters were comparable in both groups. Women with a positive β-HCG test showed statistically lower systemic vascular resistance (SVR) at mid-luteal phase (868.61 ± 100.1 vs. 1009 ± 168.4) and dET (818,9 ± 104.5 vs 1038.52 ± 150.82 dynes × s/cm 5 ). Conclusions: Hemodynamic assessment can identify a more favorable pre-pregnancy cardiovascular adaptation. Embryo implantation might be positively influenced by the hemodynamic parameters, e.g. lower SVR, before the beginning of IVF techniques, and during the window of implantation.

Background: Uterine fibroids are the most common benign tumor in women. According to literature, submucosal myomas have a negative effect on reproductive outcomes in women undergoing assisted reproductive techniques (ART) but there are fewer data concerning intramural fibroids. During last years, ulipristal acetate (UPA) 5 mg was widely used as medical option of fibroid's treatment, but from 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) has revoked the marketing authorization after some cases of liver toxicity., Methods: In this observational, retrospective study we collected data from a sample of 23 women affected by symptomatic uterine fibroids (from type 1 to type 7 according FIGO classification) followed in our center for assisted reproduction from 2016-2019. All patients received 5 mg/day UPA for three months, followed by two months of wash-out therapy. A group of 13 women treated with UPA, with intramural fibroid not distorting the uterine cavity, after wash-out therapy, affected by tubal or idiopathic factors of infertility too, underwent ART. We also evaluated a control group of women, not affected by fibroids, randomly selected from a general group of our ART patients, similar by age, BMI, and cause of infertility only idiopathic or tubal factors. We evaluated the impact of UPA on reduction of fibroid volume, symptomatology and distortion of the cavity in all the women treated, and the IVF (in-vitro fertilization) outcome between the fibroid group of women affected by intramural fibroids who underwent ART, and the control group., Results: In all the women treated with UPA the overall median fibroid volume pretreatment was 45.168±35.360 mm 3 , that decreased to a mean value of 22.592±22.116 mm3 post one cycle of UPA, with an overall mean decrease of -22.586 mm 3 (of 49%) statistically significant (P=0.00001). After treatment, the distortion of the uterine cavity reduced in high percentage of cases: 85,71% (type 1-2), χ 2 difference in respect to the value pretreatment of 0.3941, and 86.96% of patients subjectively referred an improvement in the symptomatology. In the group of 13 women that undergone ART, after one IVF cycle for each patient, we obtained 61% of positivity of dosage of beta human chorionic gonadotropin (hCG) after UPA treatment, and we obtained a similar value in the control group., Conclusions: In our little sample we have observed that UPA represented a valid non-invasive medical treatment strategy for fibroids in women candidate for (IVF, not only in women affected by sub-mucosal, but also by intramural fibroids not distorting uterine cavity. After a single, three months course of treatment, we obtained good results in terms of reduction of fibroid's volume and improvement of symptomatology, without side effects, preparing a more favorable environment for ART.

Hereditary cancer syndromes are a heterogeneous group of genetic conditions that are associated with an increased risk of developing cancer during lifespan. In affected women, parenthood may be accompanied by concerns for the offspring, considering the common autosomal dominant inheritance. Moreover, fertility preservation to prevent the detrimental effects of cancer treatments differs compared to other clinical contexts. The necessity to preserve gametes is indeed predictable and expected to be common. For these reasons, we advocate a personalized and early fertility counseling. Carriers should be aware of the risk of transmission. The possibility to perform elective oocytes cryopreservation, either before (previvors) or after (survivors) cancer diagnosis should be discussed. Finally, they should be informed about the options of preimplantation genetic test (PGT) and oocytes donation. In conclusion, physicians engaged in oncofertility should personalize the counseling for women with hereditary cancer syndromes, being aware of their peculiar needs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH)., Methods: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0., Results: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself., Conclusion: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation., (© 2021 International Federation of Gynecology and Obstetrics.)

Some 30% to 80% of male sub-fertility may be associated with oxidative stress that damages spermatozoa and can decrease success of in vitro fertilization (IVF) techniques. This multicenter, longitudinal, prospective study aimed to investigate whether oral antioxidant supplementation improved the reproductive competence of men who had had low fertilization rates in their previous intracytoplasmic sperm injection (ICSI) cycles without azoospermia or severe oligozoospermia or any identifiable andrological disease. Seventy-seven men from couples who had an ICSI attempt with unexplained <60% fertilization rate took an antioxidant mix of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12. Semen parameters were analyzed before (T0) and after 90 days (T90) of treatment, and outcomes of the paired T0 and T90 cycles were compared. After the treatment there was an increase in sperm concentration ( p = 0.027), total motile sperm count ( p = 0.003), progressive motility ( p < 0.0001), and a decreasing trend of DNA-fragmented spermatozoa. Embryological outcomes (fertilization, embryo quality, blastocyst development) were significantly higher in T90 than T0 cycles. No T0 cycle resulted in an evolutive pregnancy. Conversely, in T90 cycles 29 singleton clinical pregnancies were obtained. No negative neonatal outcomes were recorded in newborns after antioxidant treatment. Diet supplementation of men who have had low fertilization rates in their previous ICSI cycles with a combination of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, betaine, and vitamins may improve semen reproductive potential and ICSI clinical outcome.

Impaired thyroid hormone availability during early pregnancy is associated with recurrent miscarriage (RM) and adverse pregnancy outcomes. The main cause of thyroid dysfunction is thyroid-related autoimmunity (TAI), characterized by a significantly higher serum level of thyroid-stimulating hormone (TSH) compared to that of women without thyroid autoimmunity. TAI is associated with a significantly increased risk of miscarriage, and the incidence of TAI in women experiencing RM is higher compared to normal fertile women. In the present study, we have performed a retrospective analysis comparing the ability to conceive, the number of miscarriages and full-term pregnancies between 227 euthyroid women with autoimmune thyroid disease affected by RM and treated with levothyroxine (LT4) as adjuvant therapy, and a control group of 230 untreated women. We have observed a significant improvement of full-term pregnancies in treated women (59%) compared to untreated women (13%, p < 0.0001). Compared to the control group, treated women had a lower percentage of miscarriages (12% vs. 30%) and improved capacity to conceive (57% vs. 29%). Using age as a variable, the outcome in women younger than 35 years was not influenced by the LT4 therapy. Whereas, in women over 35 years, supplementation with LT4 significantly reduced the miscarriage rate ( p < 0.05). We can conclude that a transient impairment of TH availability, not easily detectable before pregnancy, could be an important cause of RM in a subset of euthyroid women with autoimmune thyroid disease. This transient impairment may be reverted using adjuvant treatment with low doses of LT4.

Polycystic ovary syndrome (PCOS) is a very common endocrine and metabolic disorder with the involvement of both genetic and environmental factors. Although much has been clarified on its pathogenesis, diagnosis, clinical manifestations, and therapy, there are still areas of uncertainty. To address fundamental concepts, novel aspects and hypotheses, and future perspectives, including the possible additional benefits of treatment with nutraceuticals, an expert consensus panel formed by endocrinologists and gynecologists was established. After an independent review of the literature, the panel convened electronically on February 3, 2020, and six resolutions were created, debated, and agreed upon discussion, and finally approved in their final form in a consensus livestream meeting held on April 15. The summary of the resolutions are: (1) PCOS is a well-established medical condition that negatively affects reproduction, general health, sexual health, and quality of life; (2) the symptoms and signs of PCOS appear early in life especially in female newborns from PCOS carriers; (3) women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes mellitus; (4) a male PCOS equivalent exists, and it may impact on metabolic health and probably on reproduction; (5) the evidence supports that medical therapy for PCOS is effective, rational, and evidence-based; (6) the evidence supports a major research initiative to explore possible benefits of nutraceutical therapy for PCOS. The proposed resolutions may be regarded as points of agreement based on the current scientific evidence available., (Copyright © 2020 Aversa, La Vignera, Rago, Gambineri, Nappi, Calogero and Ferlin.)

Background: The beginning of 2020 was characterized by the COVID-19 pandemic. The world governments have adopted restrictive measures to reduce the spread of infection. These measures could affect the sexual function and quality of life of women living with their partner., Aim: The aim is to assess the impact of the social distancing measures caused by the COVID-19 pandemic on sexual function and quality of life of noninfected reproductive-age women, living with their sexual partner., Methods: Observational analysis on sexually active women, living with their partner, and without COVID-19 infection was performed. The population previously answered FSFI, FSDS, and SF-36 questionnaires. 4 weeks after the introduction of the restrictive measures, these women were invited to complete the same questionnaires by e-mail for an evaluation during the COVID-19 outbreak., Main Outcome Measures: The primary endpoint was the assessment of the women's sex function change during the social restriction period, by analyzing the FSFI and FSDS questionnaires. The secondary endpoint was the evaluation of the impact on the quality of life calculated by the SF-36 questionnaire., Results: 89 patients were considered. The median age was 39 (28-50) years. Mean sexual intercourses/month decreased from 6.3 ± 1.9 to 2.3 ± 1.8, mean difference: -3.9 ± 1.2. FSFI decreased significantly (29.2 ± 4.2 vs 19.2 ± 3.3, mean difference: -9.7 ± 2.6) and FSDS increased significantly (9.3 ± 5.5 vs 20.1 ± 5.2, mean difference: 10.8 ± 3.4). The SF-36 showed a significant change from 82.2 ± 10.2 to 64.2 ± 11.8 4 weeks after the introduction of the restrictive measures; mean difference: -17.8 ± 6.7. The univariable analysis identified working outside the home, university educational level, and parity ≥1 as predictive factors of lower FSFI. In multivariable analysis, working outside the home and combination of working outside the home + university educational level + parity ≥1 were the independent factors of a lower FSFI., Clinical Implication: The negative impact of the COVID-19 epidemic period on sexual function and quality of life in women shows how acute stress might affect the psychological state. Thus, psychological or sexual support could be useful., Strengths and Limitations: To our knowledge, this study is the first that analyzes the change in sexual activity in women during the COVID-19 outbreak period. The limitations were the low number of the analyzed participants, psychological tests were not included, and no data were collected on masturbation, self-heroism, solitary, and nonpenetrative sex., Conclusion: The COVID-19 epidemic and the restrictive social distancing measures have negatively influenced the sexual function and quality of life in not-infected reproductive-age women who live with their sexual partners. Schiavi MC, Spina V, Zullo MA, et al. Love in the Time of COVID-19: Sexual Function and Quality of Life Analysis During the Social Distancing Measures in a Group of Italian Reproductive-Age Women. J Sex Med 2020;17:1407-1413., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

There is increasing data in favour of follicle-stimulating hormone (FSH) therapy in patients with oligo-asthenozoospermia and normal-range gonadotropins in order to increase sperm count and above all sperm motility. Some studies showed an improvement in DNA fragmentation and spontaneous pregnancy. Recently, biosimilar FSH has been marketed with the same indications. We performed a retrospective multicentric case-control study involving 147 asthenozoospermic patients between 18 and 45 years of age. A total of 97 patients were treated with biosimilar FSH 150 UI three times a week for 3 months, while 50 control subjects received no treatment. Patients were evaluated at baseline and after 3 months with semen analysis including DNA fragmentation, testicular colour Doppler ultrasound, and blood tests. Spontaneous pregnancies were recorded during a further follow-up period of 6 months. Treated patients showed after treatment a statistically significant increase in sperm concentration, total sperm count, and total motile sperm, as well as improved progressive motility and non-progressive motility. DNA fragmentation showed a significant reduction. Conversely, in the control group, no significant change was found. Pregnancy rate was significantly higher in treated patients. These data suggest comparable efficacy of biosimilar FSH in the treatment of male infertility; however, larger studies are needed to confirm our results., Competing Interests: The authors declare no conflict of interest.

Background: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters., Aim: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment., Methods: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner., Results: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001)., Discussion: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events., (© 2019 American Society of Andrology and European Academy of Andrology.)

Background: Minimally-invasive video-assisted parathyroidectomy (MIVAP) can be considered as the primary treatment of choice for single parathyroid adenoma. Often, this technique is performed in a day surgery setting and is associated with regional anaesthesia (RA). Many studies have already reported the feasibility and safety of MIVAP in day surgery. Here our focus has been on the patient's personal experience with these procedures through an assessment of their recovery at home., Methods: We conducted a prospective observational study in the University Hospital of Pisa Day Surgery Unit. Forty-eight patients were enrolled and divided by personal choice of anaesthesia technique: a regional anaesthesia group (RAg) and general anaesthesia group (GAg). Data were extracted from the medical records and three questionnaires: the first was self-compiled at discharge (Q1), while the second (Q2) and the third (Q3) were administered as telephone surveys., Results: None of the patients in RAg reported pain longer than 1 day after discharge, whereas 15% of patients in GAg reported pain relief the third day after discharge (P=0.0065). Discharge in RAg was within 3 hours in 12.5% of patients, within 4 hours in 78.1%, and within 5 hours in 9.4%. Discharge in GAg was within 5 hours in 53.8% and in more than 5 hours in 46.1% (P=0.0027)., Conclusions: Patients highly appreciated day-case parathyroidectomy. Furthermore, the association of RA with MIVAP leads to better results than those of general anaesthesia (GA) and MIVAP. Finally, we point out that it is fundamental that the physicians pay attention to what the patients consider important for them; that is, the personal meaning of the hospitalization., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Implantation of the embryo into the uterine endometrium is one of the most finely-regulated processes that leads to the establishment of a successful pregnancy. A plethora of factors are released in a time-specific fashion to synchronize the differentiation program of both the embryo and the endometrium. Indeed, blastocyst implantation in the uterus occurs in a limited time frame called the "window of implantation" (WOI), during which the maternal endometrium undergoes dramatic changes, collectively called "decidualization". Decidualization is guided not just by maternal factors (e.g., estrogen, progesterone, thyroid hormone), but also by molecules secreted by the embryo, such as chorionic gonadotropin (CG) and interleukin-1β (IL-1 β), just to cite few. Once reached the uterine cavity, the embryo orients correctly toward the uterine epithelium, interacts with specialized structures, called pinopodes, and begins the process of adhesion and invasion. All these events are guided by factors secreted by both the endometrium and the embryo, such as leukemia inhibitory factor (LIF), integrins and their ligands, adhesion molecules, Notch family members, and metalloproteinases and their inhibitors. The aim of this review is to give an overview of the factors and mechanisms regulating implantation, with a focus on those involved in the complex crosstalk between the blastocyst and the endometrium.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (β-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of β-catenin ( p  = .001), E-cadherin ( p  = .001) and K-cadherin ( p  = .002), compared to the fertile ones. Furthermore, β-catenin and E-cadherin intensity gradients of expression at glandular level were found totally reversed in infertile patients. Significant lower expression levels of K-catenin ( p  = .016) and E-cadherin ( p  < .0001) at glandular level were found in RPL patients. Results showed that the low endometrial expression of β-catenin, E-cadherin and K-cadherin were associated to fertility-related problems, such as primary intertility and RPL.

Background: We conducted a retrospective study on a cohort of couples attending the Department of Andrology and Reproductive Physiopathology at Sandro Pertini Hospital in Rome for Intracytoplasmatic Sperm Injection (ICSI)-assisted reproduction programs. Some of the couples included in the study underwent more than one ICSI cycle. Between January 2015 and April 2017. Objective: To evaluate whether the advancing of the paternal age may have effect on the seminal parameters, thus negatively affecting the embryo formation, development and quality, as well as the pregnancy rate. Materials and Methods: Five hundred and forty three ICSI cycles were performed on 439 couples undergoing Assisted Reproductive Technologies (ART). Patients were subdivided into three male and three female age groups having similar size: Men: ≤38 years (M I ), 39-43 years (M II ), ≥44 years (M III ). Women: ≤35 years (F I ), 36-40 years (F II ),≥41 years (F III ). Discussion and Conclusion: Male age groups did not reveal any statistical significant differences in any age-related semen parameters. We also confirmed a statistical significant increase in the pregnancy rate of couples with older partner age difference and younger female. We found that the advanced male age increases the probability of obtaining one or no type A embryo (N A ≤1), which was almost doubled in the M III group in comparison with M I , suggesting a negative effect of male age on the efficacy of the reproductive outcome in terms of a reduced number of type A embryos. Such an effect does not seem related to semen parameters and may deserve further investigations.

Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC) resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Septic shock involves a dysregulation of the immune response to an infection. This may lead to hemodynamic dysfunction and multiple-organ failure. The main aim of this study was to evaluate the effect of coupled plasma filtration adsorption (CPFA) on the hemodynamic profile in patients with septic shock., Materials and Methods: We retrospectively analyzed data from 21 adult patients admitted to the intensive care unit with a diagnosis of septic shock, comparing data between pre-CPFA and post-CPFA treatment. They received a maximum of 5 cycles of treatment., Results: Coupled plasma filtration adsorption treatment was associated with a significant increase of mean arterial pressure (P < .001), reduction of the vasoactive/inotropic requirement (P = .007), and renal improvement. In patients with leukocytosis or leucopenia, the leukocyte count was restored to a reference range of values., Conclusion: Treatment with CPFA improves hemodynamic parameters in septic shock patients, ameliorating organ failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Today's poorer income on the one hand and the more and more unbearable costs on the other, call for solutions to maintain public health through proper and collective care. We need to think of a new dimension of health, to found a modern and innovative approach, which can combine the respect of healthcare rights with the optimization of resources. Worldwide, franchises serving millions of people every year succeed in limiting operating costs and still offer a service and a quality equal to single businesses. Let's imagine every single Day Surgery Unit (DSU), within its own hospital, as a single trade: starting a process of centralized management and subsequent affiliation with other DSUs, they would increase their healthcare offer by means of solid organization, efficiency and foresight that with a strong focus on innovation and continuous updating, thus increasing its range of consumers and containing management costs. The Short Hospitalization System (SHS) is the proposed project, which is not only a type of hospitalization which is different from the ordinary, but also an innovative clinical-organizational model, with an important economic impact, where the management and maximization of the different hospital flows (care, professional, logistical, information), as well as the ability to implement strategies to anticipate them are crucial. The expected benefits are both clinically and socially relevant. Among them: 1) best practice build up; 2) lower impact on daily habits and increased patient satisfaction; 3) reduction of social and health expenditure.

Objectives: Premature ejaculation is the most common male sexual disorder. The aim of the study was to evaluate the possible therapeutic role of pelvic floor muscle rehabilitation in patients affected by lifelong premature ejaculation., Methods: We treated 40 men with lifelong premature ejaculation, reporting, a baseline intravaginal ejaculatory latency time (IELT) ≤ 1 min, with 12-week pelvic floor muscle rehabilitation., Results: At the end of the rehabilitation, mean IELTs were calculated to evaluate the effectiveness of the therapy. At the end of the treatment, 33 (82.5%) of the 40 patients gained control of their ejaculatory reflex, with a mean IELT of 146.2 s (range: 123.6-152.4 s). A total of 13 out of 33 (39%) patients were evaluated at 6 months follow up, and they maintained a significant IELT (112.6 s) compared with their initial IELT (mean 39.8 s)., Conclusions: The results obtained in our subjects treated with pelvic floor rehabilitation are promising. This therapy represents an important cost reduction compared with the standard treatment (selective serotonin reuptake inhibitors). Based on the present data, we propose pelvic floor muscle rehabilitation as a new, viable therapeutic option for the treatment of premature ejaculation.

Background: Tubal and uterine cavity diseases commonly compromise female fertility. At the present time, hysteroscopy, laparoscopy with chromopertubation and RX-Hysterosalpingography (RX-HSG) are widely accepted screening procedures enabling the effective assessment of both tubal patency and uterine cavity. Nevertheless, consistent evidence supports the reliability of Hysterosalpingocontrast sonography (HyCoSy) in uterine cavity and tubal patency investigation, as a part of the standard infertility work-up. This prospective study was aimed at evaluating the tolerability of the technique as well as the incidence of related side effects and complications in a large series of infertile patients., Methods: Pain perception of 632 infertile women was measured by means of an 11-point numeric rating scale. Side effects and late complications were also recorded., Results: The mean numeric rating scale was 2.15 ± 2.0 SD. Most of the patients (374/632, 59.17%) rated HyCoSy as a non-painful procedure, whereas 24.36% (154/632) women reported mild pelvic pain and 9.96% (63/632) classified the discomfort as "moderate". Only 6.48% (41/632) of the patient population experienced severe pelvic pain. Fifteen (2.37%) patients required drug administration for pain relief. Twenty-six patients (4.11%) showed mild vaso-vagal reactions that resolved without atropine administration. No severe vaso-vagal reactions or late complications were observed., Conclusions: HyCoSy is a well-tolerated examination and the associated vagal effects are unusual and generally mild. Consequently, we support its introduction as a first-line procedure for tubal patency and uterine cavity investigation in infertile women.

Background/objectives: Evaluate how surgical treatment of benign thyroid disease in elderly people is prone to induce an increase of costs in the next future due to the aging process of the population., Methods: A retrospective analysis has been performed on a total of 116 patients operated between January 2007 and September 2011, divided in a group of 58 patients aged over 80 years (Group A) and 58 patients younger than 80 years (Group B). The analyzed data included age, preoperative diagnosis, severe co-morbidities, procedures other than standard needed to evaluate anaesthesiological risk, postoperative hospital stay, complications, duration of postoperative intensive care monitoring, pathologic characteristics, and costs of anaesthesiological risk assessment., Results: Statistical analysis of collected data showed that the costs related to perioperative risk assessment (p value < 0.001) and the duration of hospital stay (p value < 0.001) were higher in Group A than in Group B. Instead, surgery-related complications were not statistically different., Conclusions: Despite feasibility and safety of modern surgical techniques, indications for surgery in elderly patients affected by benign thyroid disease should be reserved mainly for those patients with severe medical necessity.

Several empirical treatments have been proposed to treat idiopathic infertility in men, including follicle-stimulating hormone (FSH). FSH administration is effective in patients with hypogonadotropic hypogonadism, which suggests it might be useful in patients with oligozoospermia who have normal FSH levels. Indeed, many studies have evaluated the efficacy of FSH administration in these patients, several of which have shown improvements in sperm parameters. By contrast, other studies have not reported any significant effect of FSH administration on conventional sperm parameters, although some of have reported the normalization of spermatozoon ultrastructural morphology, as well as reductions in DNA fragmentation, production of reactive oxygen species and aneuploidy. Contemporary studies suggest that the response to FSH treatment in oligozoospermic patients might, at least partially, reflect polymorphisms of the FSH receptor gene. Thus, FSH administration in oligozoospermic men with normal serum FSH levels might be efficacious only in selected patients. For this reason, additional studies are needed to determine the predictive factors and clinical conditions that can be used to identify patients who could benefit from FSH treatment.

Aim: Control of postoperative pain is one of the most important concerns for both the patients and the surgical team. In this regard the efficacy of wound infiltration with local analgesia and the most proper drugs to be used are not settled. We conducted our study trying to investigate this point in a prospective randomized double blinded manner., Methods: With inclusion criteria of: age (18-65 y), volume <90 mL, first time, no lymph node enlargement and exclusion criteria of: duration >90 min, incision length >10 cm, neck dissection decided during surgery and a postoperative complication within the first 24 hours. Sixty patients planned for total thyroidectomy under general anesthesia were enrolled in the study in three groups with twenty patients assigned randomly to each one: group (A) a control group in which no wound infiltration was done, group (B) in which preoperative wound infiltration with 10 mL bupivacaine 0.5% was done, and group (C) in which preoperative wound infiltration with 10 mL ropivacaine 0.75% was done. Postoperative pain was evaluated by Visual Analogue Score (VAS) with a scale of (0-10) at 1 hour, 4 hours, 8 hours and 16 hours., Results: The postoperative pain experienced by all the patients reached a maximum point at 1 hour postoperatively then started to decrease to be minimal at 8 hours and almost negligible at 16 hours. Ropivacaine group showed a statistically significant decrease in pain perception at 1 hour postoperatively (P=0.028), bupivacaine group showed also a decrease in pain perception at 1 hour but it was not statistically significant. At 4 hours of operation and after; neither ropivacaine nor bupivacaine showed an effect on pain perception., Conclusion: The benefit of local wound infiltration with local analgesia in decreasing postoperative pain is limited to a short period after surgery in which the use of ropivacaine 0.75% is recommended over pubivaccaine 0.5%.

Background: Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection., Methods: One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n=50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment., Results: Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups., Conclusions: Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Background: This prospective, randomized study was designed to objectively demonstrate that minimally invasive video-assisted thyroidectomy (MIVAT) improves postoperative pain compared with standard thyroidectomy, via the dosage of biochemical mediators measured before and after surgery., Methods: Forty-nine patients undergoing total thyroidectomy were allotted to MIVAT (n = 23) or traditional thyroidectomy (OPEN) (n = 26) groups. At hospitalization (T0), interleukin (IL)-1, -2, -4, -6, -10, -3, tumor necrosis factor (TNF)-α, TGF-β, and MCP-1 were measured. The basal pain tolerance also was evaluated by VAS. Blood samples for interleukin measurement and VAS evaluations were obtained from all patients in the recovery room (T1) and 24 h after surgery (T2)., Results: At T0, the MIVAT and the OPEN groups were not different in terms of basal pain tolerance and biochemical profile. At T1, VAS scores were significantly higher (p = 0.04), whereas TGF-β (p = 0.03) and MCP-1 (p = 0.03) levels were significantly lower in the OPEN than in the MIVAT group. No significant difference was demonstrated for other interleukins. A significant inverse relationship between VAS and TGF-β was demonstrated and confirmed through the correlation (p = 0.003) and regression (p = 0.003, p < 0.0001, R (2) = 0.172) coefficients; the stepwise regression also demonstrated that TGF was the most predictive factor of postoperative pain (p = 0.0038) through an inverse relationship. No statistically significant difference has been demonstrated at T2., Conclusions: TGF-β serum levels immediately after surgery seem to correlate with pain evaluation, confirming that reduced postoperative distress is an objective outcome of MIVAT. This result confirms the results of studies based only on subjective pain evaluations.

Background: Responses to monotherapy corticosteroid or thalidomide have been described in prostate cancer, in chemotherapy naïve subjects., Methods: A total of 39 men with hormone refractory, metastatic prostate cancer who had progression during or after at least 1 conventional cytotoxic drug were treated on a single-arm Phase II trial with dexamethasone, 0.75 mg twice a day plus thalidomide, 100-400 mg/day., Results: Best-observed responses included >50% prostate-specific antigen (PSA) reduction with no radiologic progression: 10 of 39 (26%; 95% confidence interval 13% to 42%). An additional 14 of 39 had decreased PSA but then with radiologic or other progression by 12 weeks. Median progression-free survival was 84 days. Toxicity appeared treatable; there were 5 nonfatal thromboses. There was 1 subject who had complete PSA and radiologic response; 4 responders tolerated treatment without progression for more than 1 year., Conclusions: PSA responses were frequent. Mostly, these were not durable, but some lasted more than a year. Further investigation on determinants of response durability for these or related compounds should be considered. The response rate of the present data does not support Phase III testing of this regimen for this population.

Development of reliable procedures to assess fitness to safe driving after traumatic brain injury (TBI) is a crucial step in rehabilitation. However, prior studies are highly inconsistent in the choice of measures recommended for predicting driving fitness from different pre-driving measures. In the present paper the relevant literature is reviewed with the aim of shedding light on the reasons for these inconsistencies. The discrepant results reflect investigative choices which differ in five aspects: (1) the type of predictors used as pre-driving screening; (2) the type of measures considered as the criterion for the determination of fitness to drive after TBI; (3) the severity of the TBI in the sample of patients studied; (4) the extent of the neural structures damaged by TBI and the overlap of these areas with those involved in driving tasks; (5) the length of the follow-up considered. The strengths and weaknesses of the different methods and measures are discussed with their implications for future research and clinical rehabilitation. Encouraging findings come from recent studies that combined together medical, psychosocial, and personality measures, thereby improving the explanatory power of the predictors used. The use of post-injury driving fitness measures with great ecological and external validity seems equally promising in assessing actual driving in the real world.

Primary Objective: The present study explored the possibility of predicting post-injury fitness to safe driving in patients with severe traumatic brain injury (TBI) (n = 66)., Methods and Procedure: Sixteen different measures, derived from four domains (demo/biographic, medico-functional, neuropsychological, and psychosocial) were used as predictor variables, whereas driving outcomes were assessed in terms of driving status (post-TBI drivers versus non-drivers) and driving safety (number of post-TBI car accidents and violations)., Main Outcomes and Results: About 50% of the patients resumed driving after TBI. Compared to post-TBI non-drivers, post-injury drivers had shorter coma duration. With regard to driving safety, the final multiple regression model combined four predictors (years post-injury, accidents and violations before TBI, pre-TBI-risky-personality-index, and pre-TBI-risky-driving-style-index) and explained 72.5% of variance in the outcome measure., Conclusions: Since the best three predictors of post-injury driving safety addressed patients' premorbid factors, the results suggest that in order to evaluate the actual possibility of safe driving after TBI, it would be advisable to consider carefully patients' pre-TBI histories.

Purpose: To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent., Patients and Methods: Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m(2), respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated., Results: Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P =.49). The objective response rate was 9%, 7%, and 15%, respectively (P =.10). PSA response rates were 24%, 28%, and 34%, respectively (P =.082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity., Conclusion: Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.

Background: Mitoxantrone in combination with a low-dose glucocorticoid has been shown to produce more favorable outcomes among men with hormone-refractory prostate carcinoma than glucocorticoid alone. Therefore, the authors sought to determine the safety and activity of higher doses of mitoxantrone in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) and a glucocorticoid in preparation for a possible Phase III trial comparing standard to dose-escalated mitoxantrone., Methods: This Phase II trial enrolled 45 patients from October 1996 to March 1998. Twenty-one patients without pelvic irradiation (Arm I) received 21 mg/m(2) of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m(2) on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM-CSF at 500 microg/daily for a minimum of 10 days per cycle beginning on the third day of the cycle., Results: In Arm I, 33% of assessable patients achieved a partial response, 50% had a > or = 50% decline in their PSA, and 35% had a > or = 75% decline in PSA values. The comparable numbers in Arm II were 24%, 48%, and 35%, respectively. The median survival times were 12 months in Arm I and 14 months in Arm II. Treatment had to be discontinued in 13% of patients because of thrombocytopenia. No other significant toxicities were encountered., Conclusions: Higher doses of mitoxantrone (17 and 21 mg/m(2)) were associated with activity comparable to many estramustine combinations and generally were well tolerated. However, because the degree and frequency of thrombocytopenia were greater than that observed with standard dose mitoxantrone (12-14 mg/m(2)), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing., (Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10217)

In order to investigate phamacotherapeutic responsiveness of major depression and other behavioural disturbances associated with traumatic brain injury (TBI), 20 post-TBI patients were diagnosed as being depressed by two independent neuropsychiatrist observers, out of 37 consecutive TBI subjects sent to psychiatric counselling for poor compliance during rehabilitation programmes or psychiatric/behavioural disturbances after return to society. They were subsequently divided into two subgroups, depending on time elapsed from trauma (A: within 6 months; B: at 24-36 months post-trauma) and were enrolled in an open informed pharmachological study. Rating at baseline included Glasgow Coma Score on hospital admission, length of coma, length of hospitalization, Functional Independence Measure (FIM), Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression scale (CGI). BPRS and CGI were repeated after 12 weeks of oral administration of citalopram (20 mg a day) and carbamazepine (600 mg a day). At baseline, psychiatric symptoms in group B were worse than in group A (particularly somatic overconcern, anxiety, depressed mood, psychomotor slowness, inappropriate and labile affect). At T1, the global (group A and B combined) CGI and BPRS scores showed a statistically significant improvement when compared with T0, even if group B scores remained higher than group A. The results of this study suggest that: (a) citalopram combined with carbamazepine is effective in reducing depression and behavioural disorders following TBI, and (b) these disturbances should be addressed as soon as possible during the acute rehabilitation period.

Dispersal and vicariance are often contrasted as competing processes primarily responsible for spatial and temporal patterns of biotic diversity. Recent methods of biogeographical reconstruction recognize the potential of both processes, and the emerging question is about discovering their relative frequencies. Relatively few empirical studies, especially those employing molecular phylogenies that allow a temporal perspective, have attempted to estimate the relative roles of dispersal and vicariance. In this study, the frequencies of vicariance and dispersal were estimated in six lineages of birds that occur mostly in the aridlands of North America. Phylogenetic trees derived from mitochondrial DNA sequence data were compared for towhees (genus Pipilo), gnatcatchers (genus Polioptila), quail (genus Callipepla), warblers (genus Vermivora) and two groups of thrashers (genus Toxostoma). Different area cladograms were obtained depending on how widespread and missing taxa were coded. Nonetheless, no cladogram was obtained for which all lineages were congruent. Although vicariance was the dominant mode of evolution in these birds, approximately 25% of speciation events could have been derived from dispersal across a preexisting barrier. An expanded database is now needed to estimate the relative roles of each process. Applying a molecular clock calibration, nearly all speciation events are of the order of a million or more years old, much older than typically presumed.

Purpose: Toward developing a model to study the mechanism of action of suramin against prostate cancer, we identified the effect of suramin on the growth of xenografts of the androgen-independent human prostate carcinoma DU145 cell line and our subline of suramin-resistant (SR) DU145 cells which are less responsive to suramin in vitro., Methods: Athymic nude mice bearing DU145 or SR DU145 xenografts were treated intraperitoneally (IP) once weekly with normal saline (vehicle control) or suramin in normal saline. For data analysis mice were grouped as follows: 0 mg/kg (controls), < 210 mg/kg, 210 to 260 mg/kg, or >260 mg/kg suramin., Results: The growth of DU 145 xenografts was slowed by treatment with 210 to 260 mg/kg suramin IP once weekly: differences in tumor volume for the 210 to 260 mg/kg group compared with the control group on days 29 and 57 showed growth inhibited by 43% and 55%, respectively. At the same time, growth of SR DU 145 xenografts generally was not slowed by suramin treatment at any dose, but appeared to be enhanced to some degree by all doses of suramin during the typical slower initial growth phase of xenografts of this cell line: differences in tumor volume compared with control on day 29 showed growth enhanced by 100% to 342%. Mice treated with 210 to 260 mg/kg maintained nadir suramin plasma levels near our clinically relevant target of 1 x 10(-4) M., Conclusions: Suramin, without concomitant corticosteroid therapy, was effective in slowing the growth of DU145 xenografts in nude mice at clinically relevant plasma suramin levels. The data showing efficacy for DU145 xenografts was supported by the lack of efficacy at the same time for xenografts of cells known to be less responsive to suramin in vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels. In discussions on the utility of suramin our data should be considered as support for continuing the study of suramin in the treatment of advanced, androgen-independent prostate cancer.