Postoperative morphologic changes of the isthmocele and clinical impact in patients treated by channel-like (360°) hysteroscopic technique.

OBJECTIVE: To evaluate the changes in (1) residual myometrial thickness (RMT), (2) cesarean scar defect (CSD) size, and (3) clinical symptoms, before and after channel-like (360°) hysteroscopic resection for the treatment of CSD. METHODS: A single-center, observational, prospective, cohort study was carried out enrolling all symptomatic patients of childbearing age, diagnosed with CSD and routinely scheduled for channel-like (360°) hysteroscopic resection from July 2020 to July 2021 at the Division of Gynecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Univeristaria di Bologna. University of Bologna, Italy. The primary outcome was the difference in mean RMT before and after the procedure. Secondary outcomes were the differences before and 4 months after the surgery in: (1) CSD size measured by transvaginal ultrasound, (2) visual analog scale (VAS) scores for the symptoms, and (3) abnormal uterine bleeding (AUB) rate. Lastly, patients' satisfaction was assessed by the global impression of improvement (PGI-I) score. RESULTS: We found a significant difference before and after the procedure in: (1) mean RMT (+2.0 mm; P < 0.001); mean size of the CSD (base: +1.6 mm; height: -2.5 mm; transverse diameter: -3.2 mm; volume: -263.7 mm3 ; P < 0.001); (2) mean VAS score for dyspareunia (-5.84; P < 0.001), dysmenorrhea (-8.94; P < 0.001), pelvic pain (-2.94; P < 0.001); (3) AUB rate (91% vs. 3%; P < 0.001). Lastly, the mean PGI-I score ± SD was 1.7 ± 0.9. CONCLUSION: Channel-like (360°) hysteroscopic resection for the treatment of patients with symptomatic CSD may lead to an increase in RMT, decrease in CSD, and improvement of symptoms after the procedure, with high patient satisfaction.

Uterine Fundus Remodeling after Hysteroscopic Metroplasty: A Prospective Pilot Study.

The septate uterus is the most common congenital uterine malformation and is treated by hysteroscopic metroplasty. There are few studies on the fundal uterine changes that occur after surgery. We designed a pilot prospective observational study to evaluate by three-dimensional transvaginal ultrasound (3D-TVS) the changes not only of the internal fundal uterine profile, but also of the external one, after hysteroscopic metroplasty. Sixty women who underwent hysteroscopic metroplasty for partial or complete uterine septum (U2a and U2b subclasses of ESHRE/ESGE classification) were enrolled. We performed 3D-TVS after surgery confirming optimal removal of the septum. However, at ultrasound follow-up after three months, we observed a significant increase (p < 0.001) in the residual septum (Zr) (3.7 mm (95% CI: 3.1-4.4)), the myometrial wall thickness (Y) (2.5 mm (95% CI: 2.0-3.0)) and the total fundal wall thickness (Y + Zr) (6.2 mm (95% CI: 5.5-6.9)). Forty-three patients (72%) required a second step of hysteroscopic metroplasty. Moreover, the shape of uterine fundus changed in 58% of cases. We actually observed a remodeling of the uterine fundus with modifications of its external and internal profiles. Therefore, we propose to always perform a second ultrasound look at least three months after the metroplasty to identify cases that require a second- step metroplasty.

Fertility Sparing Treatment of Endometrial Cancer with and without Initial Infiltration of Myometrium: A Single Center Experience.

Endometrial cancer (EC) is the fourth largest female cancer in Europe and North America. In 5% of cases, the diagnosis is made in women who wish to become pregnant. In our retrospective study, we reported our experience about fertility sparing treatment of G1 endometrioid endometrial cancer (G1 EEC) or atypical endometrial hyperplasia/endometrial intraepithelial neoplasm (AEH/EIN) in young women desiring pregnancy treated in our Center. Conservative treatment was based on operative hysteroscopy and hormone therapy with megestrol acetate (160 mg/die for 9 months). For the first time we included women with G1 EEC with minimal myometrial infiltration. The minimum follow-up period was two years and consisted of serial outpatient hysteroscopies with endometrial biopsies. Among the 36 women with G1 EEC we observed one case of disease persistence and four recurrences and four recurrences among the 46 women diagnosed with AEH/EIN. To date, 35 live births were obtained in both groups. Our results advance the hypothesis that conservative treatment can represent a safe and feasible alternative to propose to young women with desire for pregnancy. Further randomized and multicentric studies are needed to arrive at unambiguous and standardized guidelines on the surgical and medical treatment of young women with EEC or AEH/EIN.

The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis.

Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM-patients, suggesting their involvement in the pathogenesis of beta TM-osteoporosis.

Identification of alpha-thalassemia mutations in subjects from Eastern Sicily (Italy) with abnormal hematological indices and normal Hb A2.

We analyzed the prevalence of alpha-thalassemia mutations in 298 subjects from Eastern Sicily (Italy) with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal HbA2 and HbF, and normal serum iron. In 131 subjects (43.9%) we found six different genotypes of alpha-thalassemia: -alpha3.7/alphaalpha (36.6%), -alpha3.7/-alpha3.7 (27.5%), -(MED)/alphaalpha (10.0%), -alpha20.5/alphaalpha (9.1%), alphaHphIalpha/alphaalpha (8.4%), alphaHphIalpha/alphaHphIalpha (6.1%), and -alpha3.7/alphaHphIalpha (2.3%). Our data underline that in Eastern Sicily populations, the molecular screening of alpha-thalassemia mutations and/or deletions may be useful to better characterize the clinically asymptomatic subjects with a slightly reduced MCV and MCH and normal iron status.

Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin.

Reactive oxygen species play an important role in the pathogenesis of respiratory distress syndrome and its complications. This study was conducted to determine if treatment with the antioxidant melatonin would influence interleukin-6, interleukin-8, tumor necrosis factor alpha, and nitrite/nitrate levels in newborns with grade III or IV respiratory distress syndrome (radiographically confirmed) diagnosed within the first 6 hours of life. Prior to treatment, a blood sample was collected from the umbilical cord or a peripheral vein of each newborn. Second, third, and fourth blood samples were collected at 24 hours, 72 hours, and 7 days, respectively, after beginning treatment with melatonin or placebo. Compared with the melatonin-treated respiratory distress syndrome newborns, in the untreated infants the concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were significantly higher at 24 hours, 72 hours, and at 7 days after onset of the study. in addition, nitrite/nitrate levels at all time points were higher in the untreated respiratory distress syndrome newborns than in the melatonin-treated babies. Following melatonin administration, nitrite/nitrate levels decreased significantly, whereas they remained high and increased further in the respiratory distress syndrome infants not given melatonin.

Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle.

UNLABELLED: Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis. INTRODUCTION: Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. MATERIALS AND METHODS: We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin. RESULTS: Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio. CONCLUSIONS: Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients.