Endometrial evaluation with transvaginal ultrasound during hormone therapy : a prospective multicenter study

Objective To assess the value of endometrial thickness as a marker of endometrial abnormality risk during hormone therapy (HT) and to study the correlation between abnormal bleeding and abnormal endometrial histology in patients with thick endometrium. Design Prospective multicenter study. Setting University and general hospitals outpatient centers. Patient(s) Postmenopausal women (702) on HT. Intervention(s) Biendometrial thickness was measured by transvaginal sonography (TVS) between day 5 and day 10 after the last P intake and, when present, after the end of the menstrual-like bleeding. Main outcome measure(s) Hysteroscopy and biopsy were performed within 5 days from TVS on all patients with an endometrial thickness >4.5 mm (precision scale 0.5 mm). Result(s) Endometrial thickness >4.5 mm was observed in 20.5% of patients. One hundred sixteen hysteroscopies and biopsies were performed. Hyperplasia, polyps, and endocavitary fibroids were detected in 15%, 24%, and 8% of cases, respectively. The positive predictive value of TVS examination was 47%. Endometrial thickness was the only variable significantly and independently associated with histologic abnormalities and endocavitary fibroids. Abnormal bleeding occurred in 17.1% of patients. Among 17 patients detected with thick endometrium and hyperplasia, 8 cases showed abnormal bleeding. Conclusion(s): Sonographic endometrial thickness of 4.5 mm provides a sensitive tool to select HT patients who might benefit from hysteroscopy and biopsy. Abnormal bleeding is not a sensitive sign of hyperplasia in patients with thick endometrium

Endometrial evaluation with transvaginal ultrasound during hormone therapy: a prospective multicenter study.

Objective: To assess the value of endometrial thickness as a marker of endometrial abnormality risk during hormone therapy (HT) and to study the correlation between abnormal bleeding and abnormal endometrial histology in patients with thick endometrium. Design: Prospective multicenter study. Setting: University and general hospitals outpatient centers. Patient(s): Postmenopausal women (702) on HT. Intervention(s): Biendometrial thickness was measured by transvaginal sonography (TVS) between day 5 and day 10 after the last P intake and, when present, after the end of the menstrual-like bleeding. Main Outcome Measure(s): Hysteroscopy and biopsy were performed within 5 days from TVS on all patients with an endometrial thickness 4.5 mm (precision scale 0.5 mm). Result(s): Endometrial thickness 4.5 mm was observed in 20.5% of patients. One hundred sixteen hysteroscopies and biopsies were performed. Hyperplasia, polyps, and endocavitary fibroids were detected in 15%, 24%, and 8% of cases, respectively. The positive predictive value of TVS examination was 47%. Endometrial thickness was the only variable significantly and independently associated with histologic abnormalities and endocavitary fibroids. Abnormal bleeding occurred in 17.1% of patients. Among 17 patients detected with thick endometrium and hyperplasia, 8 cases showed abnormal bleeding. Conclusion(s): Sonographic endometrial thickness of 4.5 mm provides a sensitive tool to select HT patients who might benefit from hysteroscopy and biopsy. Abnormal bleeding is not a sensitive sign of hyperplasia in patients with thick endometrium

Reproductive Issues and Pregnancy Implications in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare systemic autoimmune disease that can influence reproductive health. SSc has a strong female predominance, and the disease onset can occur during fertility age in almost 50% of patients. Preconception counseling, adjustment of treatment, and close surveillance during pregnancy by a multidisciplinary team, are key points to minimize fetal and maternal risks and favor successful pregnancy outcomes. The rates of spontaneous pregnancy losses are comparable to those of the general obstetric population, except for patients with diffuse cutaneous SSc and severe internal organ involvement who may carry a higher risk of abortion. Preterm birth can frequently occur in women with SSc, as it happens in other rheumatic diseases. Overall disease activity generally remains stable during pregnancy, but particular attention should be paid to women with major organ disease, such as renal and cardiopulmonary involvement. Women with such severe involvement should be thoroughly informed about the risks during pregnancy and possibly discouraged from getting pregnant. A high frequency of sexual dysfunction has been described among SSc patients, both in females and in males, and pathogenic mechanisms of SSc may play a fundamental role in determining this impairment. Fertility is overall normal in SSc women, while no studies in the literature have investigated fertility in SSc male patients. Nevertheless, some considerations regarding the impact of some immunosuppressive drugs should be done with male patients, referring to the knowledge gained in other rheumatic diseases

Triple antiphospholipid (aPL) antibodies positivity is associated with pregnancy complications in aPL carriers: A multicenter study on 62 pregnancies

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called “aPL carriers” (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers. Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded. Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84–247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose. Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic

16siTo study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery.• In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy.• Flares were observed only in PLA and OLA-E patients.• Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.nonenoneGarcia-Fernandez A.; Gerardi M.C.; Crisafulli F.; Filippini M.; Fredi M.; Gorla R.; Lazzaroni M.G.; Lojacono A.; Nalli C.; Ramazzotto F.; Taglietti M.; Zanardini C.; Zatti S.; Franceschini F.; Tincani A.; Andreoli L.Garcia-Fernandez, A.; Gerardi, M. C.; Crisafulli, F.; Filippini, M.; Fredi, M.; Gorla, R.; Lazzaroni, M. G.; Lojacono, A.; Nalli, C.; Ramazzotto, F.; Taglietti, M.; Zanardini, C.; Zatti, S.; Franceschini, F.; Tincani, A.; Andreoli, L

A two-by-two factorial trial comparing oral with transdermal estrogen therapy and fenretinide with placebo on breast cancer biomarkers

Purpose: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. Experimental Design: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 mug/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided. Results: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39). Conclusions: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies

Confronto tra bisturi a lama fredda ed elettrobisturi nella laparotomia mediana in oncologia ginecologica: studio multicentrico collaborativo.

Confronto tra bisturi a lama fredda ed elettrobisturi nella laparotomia mediana in oncologia ginecologica: studio multicentrico collaborativo

Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial

BackgroundNeovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential. STAR aimed to assess whether stereotactic radiotherapy (SRT) reduces the number of anti-VEGF injections required, without sacrificing visual acuity.MethodsThis pivotal, randomised, double-masked, sham-controlled trial enrolled participants with pretreated chronic active nAMD from 30 UK hospitals. Participants were randomly allocated in a 2:1 ratio to 16-Gray (Gy) SRT delivered using a robotically controlled device or sham SRT, stratified by treatment centre. Eligible participants were aged 50 years or older and had chronic active nAMD, with at least three previous anti-VEGF injections, including at least one in the last 4 months. Participants and all trial and image reading centre staff were masked to treatment allocation, except one unmasked statistician. The primary outcome was the number of intravitreal ranibizumab injections required over 2 years, tested for superiority (fewer injections). The main secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at two years, tested for non-inferiority (five-letter margin). The primary analysis used the intention-to-treat principle, and safety was analysed per-protocol on participants with available data. The study is registered with ClinicalTrials.gov (NCT02243878) and is closed for recruitment.Findings411 participants enrolled between Jan 1, 2015, and Dec 27, 2019, and 274 were randomly allocated to the 16-Gy SRT group and 137 to the sham SRT group. 240 (58%) of all participants were female, and 171 (42%) of all participants were male. 241 participants in the 16-Gy SRT group and 118 participants in the sham group were included in the final analysis, and 409 patients were treated and formed the safety population, of whom two patients allocated to sham treatment erroneously received 16-Gy SRT. The SRT group received a mean of 10·7 injections (SD 6·3) over 2 years versus 13·3 injections (5·8) with sham, a reduction of 2·9 injections after adjusting for treatment centre (95% CI –4·2 to –1·6, p&lt;0·0001). The SRT group best-corrected visual acuity change was non-inferior to sham (adjusted mean letter loss difference between groups, –1·7 letters [95% CI –4·2 to 0·8]). Adverse event rates were similar across groups, but reading centre-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes. Overall, eyes with microvascular abnormalities tended to have better best-corrected visual acuity than those without. Fewer ranibizumab injections offset the cost of SRT, saving a mean of £565 per participant (95% CI –332 to 1483)

Evaluation of apple pomace based reconstituted feed in rats after solid state fermentation and ethanol recovery

To utilize apple pomace in an economical and effective way, a feed was developed by solid state fermentation (SSF) using sequential interactive co-culture of Candida utilis and Kloeckera. Removal of ethanol and drying of the left - over residue. Feeding trial was conducted in white albino rats before and after reconstitution of apple pomace feed in the choice and no choice study. Feeding of apple pomace feed in the rats before reconstitution indicated that neither in fermented nor in unfermented form it was acceptable. In the no choice study both in 100% fermented and unfermented apple pomace group feed intake decreased continuously resulting in death of rats apparently due to decreased digestibility owing to high fibre content. Further, fermented or unfermented apple pomace based feed had lower digestibility and efficiency of conversion than the standard rat feed. Compared to the standard feed group, growth rates in all the feed groups were negative. The results of choice study of different feeds corroborated with the no-choice study mentioned earlier. Incorporation of fermented apple pomace into standard rat feed in the ratio of 1:1 gave better acceptability and digestibility. Reconstituted feed with 10% jaggery, 2% groundnut oil, 0.01% mixed flavour and 1% salt was the most acceptable. The post-mortem examination of the rats that died during the feeding trial revealed generalized oedema, probably due to some hepatotoxin in the feed. The blood glucose level in the apple pomace feed group except that was reconstituted with jaggery, showed a general hypoglycemia, though falling in the range. The increased ALT and AST levels in the serum also suggest damage to the liver. The mortality rate, post-mortem examination of the rats that died during the feeding trial and blood biochemical analysis of rat serum suggest a more elaborative study for extended period of time.<br>Para utilizar bagaço de maçã de uma maneira econômica e eficaz, foi desenvolvido um processo por fermentação no estado sólido (SSF) que utiliza uma co-cultura interativa seqüencial de Cândida utilis e Kloechera. Remoção do etanol foi realizado através da secagem do bagaço de maçã. Os testes com o bagaço de maçã fermentado ou não foram feitos em ratos brancos em um experimento delineado. Os resultados mostraram que o bagaço de maçã fermentado ou não se mostraram aceitáveis sendo que os mesmos apresentaram uma digestibilidade inferior a ração comum. Quando o estudo alimentando os ratos utilizando 100% de bagaço de maçã fermentado e não fermentado e alterando a concentração progressivamente, observou-se a morte dos ratos aparentemente devido a uma redução da digestibilidade em razão da alta concentração em fibras. Em comparação com o grupo padrão, as taxas de crescimento foram negativas em todos os grupos estudados. A mistura da ração padrão com o bagaço de maçã fermentado na proporção 1:1, proporcionou maior aceitabilidade e digestibilidade. A mistura do bagaço de maçã fermentado com 10% de 'jagerry', 2% de óleo de 'groundnut', 0,01% de aromas e 1% de sal foi o mais aceitável. O exame pós-morte dos ratos que receberam a dieta durante sua alimentação apresentou edema generalizado, provavelmente devido a alguma hepatotoxina na alimentação. O nível de glicose no sangue do grupo alimentado com bagaço de maçã, exceto misturado com 'jagerry', mostrou uma hypoglicemia geral. A taxa de mortalidade, o exame pós-morte dos ratos que morreram durante o experimento e a análise bioquímica do sangue e do soro sugerem um estudo mais elaborativo e mais prolongado