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Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

Grotta Bella, localizzata nella provincia di Terni, ad una altitudine di 530 m s.l.m. è stata oggetto di scavi archeologici nei primi anni ’70 da parte di G. Guerreschi. Il sito fu frequentato per un lungo arco di tempo che va dal Neolitico antico fino all’età del Bronzo finale (con successive frequentazioni nel corso dell’età del Ferro, in età romano-repubblicana ed imperiale). Parte della fauna proveniente dagli scavi è stata già oggetto di studio da parte di P. Catalani. La ripresa degli studi dei materiali archeologici provenienti dalla Grotta è stata l’occasione per una revisione anche del materiale osseo faunistico. E’ stato messo in evidenza come, dai livelli del Neolitico antico, fino a quelli del Bronzo Medio, l’economia di sussistenza fosse incentrata in prevalenza sull’allevamento del maiale. Da notare come anche per i periodi di frequentazione più tarda i dati paleoeconomici desumibili dalla fauna escludano di fatto un’economia pastorale.

Background: Since there is no available data on temporal trends of caesarean section (CS) rates in pregnant women with COVID-19 through the pandemic, we aimed to analyze the trends in caesarean section rate in a large cohort of pregnant women with COVID-19, according to the Robson Ten Group Classification System of deliveries. Methods: We prospectively enrolled pregnant women with a diagnosis of COVID-19 who delivered in our center between March 2020 and November 2021. Deliveries were classified, according to the Robson group classification, and according to three time periods: (1) deliveries from March 2020 to December 2020; (2) deliveries from January 2021 to April 2021; (3) deliveries from May 2021 to November 2021. We compared pregnancy characteristics and incidence of caesarean section, according to the Robson category in the total population, and according to the three time periods. Results: We included 457 patients matching the inclusion criteria in our analysis. We found that overall CS rate significantly decreased over time from period 1 to period 3 (152/222, 68.5% vs. 81/134, 60.4% vs. 58/101, 57.4%, χ2 = 4.261, p = 0.039). CS rate significantly decreased over time in Robson category 1 (48/80, 60% vs. 27/47,57.4% vs. 8/24, 33.3%, χ2 = 4.097, p = 0.043) and Robson category 3 (13/42, 31% vs. 6/33, 18.2% vs. 2/22, 9.1%, χ2 = 4.335, p = 0.037). We also found that the incidence of induction of labor significantly increased over time (8/222, 3.6% vs. 12/134, 9% vs. 11/101, 10.9%, χ2 = 7.245, p = 0.027). Conclusion: Our data provide an overview of the temporal changes in the management and obstetric outcome of COVID-19 pregnant women through the pandemic, confirming that standards of obstetrical assistance for pregnancies complicated by SARS-CoV-2 infection improved over time.

Objective Hysteroscopy is considered the gold standard technique for the diagnosis and management of intrauterine pathology allowing to “see and treat” patients in 1 session if desired 1 , 2 , 3 . Pain and the inability to enter the uterine cavity are the most common limitations of hysteroscopy, especially when performed in an office setting 4 , 5 , 6 , 7 . Cervical stenosis is a common hysteroscopic finding frequently encountered in postmenopausal women, especially in patients with a history of cervical procedures such as cone biopsy [8] . It represents a challenge even for the most expert hysteroscopist. Overcoming the stenosis of the external cervical os is technically more demanding than facing the obliteration of the internal os. The aim of this video article is to illustrate the use of simple techniques that allow the hysteroscopist to safely identify the location of the external cervical os and to overcome the difficulties in entering the uterine cavity during in-office hysteroscopy in patients with severe cervical stenosis including those with complete obliteration of the external cervical os. These techniques are easy to adopt and can be used in different clinical situations in which the hysteroscopic evaluation of the uterine cavity is needed in women with severe cervical stenosis. Design A series of videos of challenging cases with severe cervical stenosis with complete obliteration of the external cervical os are presented that demonstrate maneuvers to properly identify and enter the cervical canal, unfolding key aspects of the procedure. Tips and tricks to facilitate the adoption of these useful maneuvers into clinical practice are highlighted. Setting In-office diagnostic hysteroscopy was performed using a 5-mm rigid continuous flow operative hysteroscope. Patients were placed in a dorsal lithotomy position. The vaginoscopy “no touch” technique was used [9] . No anesthesia or sedation was administered to any of the patients. Normal saline was used as distention media. Interventions Taking advantage of the magnification provided by the hysteroscope, the location of the external cervical os was determined. In cases in which the external cervical os was not clearly recognized, the cervix was gently probed with the use of the uterine palpator, grasper, or scissors ( Fig. 1 ). Recognition of the landmarks of the cervical canal provides reassurance of the adequate identification of the external cervical os and facilitates the use of the correct plane of dissection that leads into the uterine cavity ( Fig. 2 ). Additional maneuvers that are useful to navigate the endocervical canal to overcome stenosis of the internal cervical os are also illustrated. Conclusion The combination of a delicate technique and operator experience aids in overcoming the challenge of cervical stenosis in an office setting. Adopting the presented tips and tricks to enter the uterine cavity in the presence of severe cervical stenosis will reduce the rate of failed hysteroscopic procedures, decreasing the need to take patients to the operating room and the use of general anesthesia.

Surgical innovations in hysteroscopic surgery have radically changed the way of treating intrauterine pathologies, throughout the advent of the 'see-and-treat' philosophy, which transferred the advantages of inpatient surgery to the office setting. However, in-office operative hysteroscopy was mainly limited to minor pathology as a supplement to its diagnosis, whereas commonly larger abnormalities were left to be treated in the operating room. Nowadays, pre-surgical assessment of uterine pathology is based on modern ultrasound evaluation and the evolving role of in-office hysteroscopy as a well-planned treatment modality for larger lesions and more complex procedures. Office operative hysteroscopy has been accepted as a feasible, cost-effective, practical way to treat almost any intrauterine disease. Despite the growing role of other imaging tools in the proper evaluation of benign uterine diseases, especially extended beyond to direct hysteroscopic visualization, diagnostic hysteroscopy remains a valuable tool of direct endometrial sampling and may be used as the first line in the diagnosis of endometrial cancer and hyperplasia. Our aim is to describe the most recent innovations and future perspectives in the field of outpatient operative hysteroscopy: mini-resectoscopes, intrauterine morcellators, tissue retrieval systems, diode laser, new miniaturized mechanical instruments, endometrial ablation devices and portable and entry-level hysteroscopes.

Hysteroscopy is known to be the gold standard for evaluation of intrauterine pathologies, pre-menopausal and post-menopausal abnormal uterine bleeding and, in addition to this, it is a crucial examination in the infertility work-up. In-office operative hysteroscopy incorporates the outstanding possibility of seeing and treating an intracavitary pathology in the same examination, eliminating all the risk related to anesthesia and reducing procedure-related costs. By now, performing operative procedures in the office setting is recognized as feasible and safe. Over the last 20 years, many efforts have been made to implement the in-office operative approach worldwide. However, for some women, in-office hysteroscopy is still considered a painful experience, with reported discomfort at different steps of the hysteroscopic procedures. Moreover, uneventful and tedious sensations might be increased by a high level of anxiety for such examination. For this reason, despite the feasibility of the in-office approach, many clinicians are still afraid of provoking pain during the procedure and rather not to perform surgical procedures in the office, postponing the removal of the pathology in the operating room. To date, there is no consensus concerning pain management for in-office hysteroscopy and different approaches, pharmacological and non-pharmacological aids, as well as several procedural tips and tricks are utilized. Our purpose is to provide a feasible practical decalogue for the operator, to supply adequate management of pain during in-office hysteroscopic procedures, performing challenging operations, shrinking discomfort, aiming to upgrade both women's and operator's satisfaction.

Objective To investigate the diagnostic accuracy of endometrial biopsy performed with hysteroscopic direct visualization using the “grasp technique” for the detection of endometrial carcinoma (EC) histology type and tumor grade. Methods A cross-sectional study including the clinical and pathology records of patients with confirmed EC who underwent definitive surgery at University of Naples was performed. The preoperative diagnosis of endometrial tumor type and grade obtained using the hysteroscopy grasp technique was correlated with the final pathology specimens. Those results were compared to the diagnostic accuracy of the biopsies collected in a cohort of patients who underwent preoperative diagnostic hysteroscopy followed by blind endometrial biopsy using the Novak curette with subsequent surgical definitive treatment at University of Pisa. Statistical analysis was based on frequency data and diagnostic agreement of the pathology results. Results A total of 129 patients were included in the final analysis. An agreement rate of 104/106 (98.1%) for endometrioid type and 15/23 (65.2%) for non-endometrioid type was obtained between preoperative hysteroscopic grasp endometrial biopsy specimens and the final pathology with a coefficient k for G1, G2 and G3 tumors of 0.928, 0.925 and 0.974, respectively. When compared to 121 patients undergoing preoperative blind Novak endometrial biopsy, the hysteroscopic grasp technique was superior in agreement rates for tumor histotype [diagnostic accuracy (0.922 vs 0.890); K value (0.705 vs 0.642)] and grade when in presence of endometrioid type EC (K Cohen 0.354 for G1, 0.263 for G2 and 0.488 for G3). Conclusions Preoperative hysteroscopic guided “grasp” endometrial biopsy provides a more accurate diagnosis of EC histology type and tumor grade when in presence of endometrioid type tumor compared to blind endometrial biopsy obtained using the Novak curette.

Today the rate of unexpected pregnancy is still unacceptably high; long-acting reversible contraceptives, (LARC) seem to be an effective and modern solution. Intrauterine contraception (IUC) is the main exponent of the LARC and it is living a new exponential spread in the last years. Today IUC is the most widely used reversible contraceptive method and it is recommended by the major scientific gynecological societies. This review of the literature aims to retrace the history of intrauterine contraception and to focus attention on intrauterine systems (IUS), its last and most modern form. The three systems (LNG-IUS 52 mg; LNG-IUS 13.5 mg; LNG-IUS 19.5 mg) base their extraordinary effectiveness on the same mechanism of action, however they present some important differences that can be used to enhance and customize the treatment, not just contraceptive, based on the woman's needs.

Acute coronary syndromes (ACS) may represent an intriguing clinical scenario for implantation of bioresorbable vascular scaffold (BRS). Nevertheless, the knowledge about the performance of these devices in patients with ACS is limited. Therefore, we performed a meta-analysis of clinical studies aiming to assess the safety and efficacy of everolimus-eluting-BRS versus everolimus-eluting-metallic stents (EES) in ACS patients undergoing percutaneous coronary intervention. Six studies enrolling 2,318 patients were included and analyzed for the risk of primary safety outcome (stent or scaffold thrombosis [ST/ScT]), primary efficacy outcome (target lesion revascularisation [TLR]), and secondary outcomes (myocardial infarction, cardiac death, all-cause death). Median follow-up was 9.5 (6 to 19.5) months. Patients treated with BRS had a significantly higher risk of definite ST/ScT compared with those receiving EES (2.3% vs 1.08%, odds ratio [OR] 2.22, 95% confidence interval [CI] 1.10 to 4.45, p = 0.03, I2 = 0%). Similarly, the risk of TLR was significantly higher in the BRS compared with EES group (3.5% vs 2.5%, OR 1.79, 95% CI 1.02 to 3.16, p = 0.04, I2 = 0%). When TLRs due to thrombosis were excluded, the difference in risk estimates between the 2 groups was no longer significant (OR 1.19, 95% CI 0.48 to 2.98, p = 0.71, I2 = 25%). Risk for secondary endpoints did not differ between the 2 groups. Results were confirmed when clinical and procedural variables were tested as potential effect modifiers in the meta-regression analysis for both primary endpoints. In conclusion, compared with those receiving EES, patients with ACS treated with BRS had increased risk of definite device thrombosis and TLR at mid-term follow-up.

Bioresorbable vascular scaffolds (BRS) represent the latest innovation in the field of interventional cardiology. BRS have recently been introduced in routine clinical practice and their use has progressively extended in everyday clinical practice. The BRS use appears theoretically attractive in patients presenting with acute coronary syndromes (ACS) as they are generally young with long life expectancy, thus possibly benefiting more of the so-called vascular reparative therapy. Furthermore, "culprit" lesions are usually softer and more easily expandable by current BRS compared to stable chronic lesions. However an increased risk of BRS thrombosis has been reported in clinical trials excluding ACS patients. Therefore, concerns have been raised on the safety of BRS implantation in the ACS setting in which the risk of thrombotic recurrences is definitely higher (compared to stable lesions) independently by the device implanted. Aim of this review is to provide an overview of the available data on the BRS performance in ACS patients.

Background— The sphingosine-1-phosphate receptor 1 (S1PR1) and β 1 -adrenergic receptor (β1AR) are G-protein–coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein–coupled receptor kinase-2, which triggers desensitization and downregulation processes. Although classic signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply result in opposing action on cAMP production, in this report we have uncovered a direct interaction between these 2 receptors, with regulatory involvement of G-protein–coupled receptor kinase-2. Methods and Results— In HEK (human embryonic kidney) 293 cells overexpressing both β1AR and S1PR1, we demonstrated that β1AR downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1 agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a β-adrenergic receptor agonist) treatment. This cross talk between these 2 distinct G-protein–coupled receptors appears to have physiological significance, because they interact and show reciprocal regulation in mouse hearts undergoing chronic β-adrenergic receptor stimulation and in a rat model of postischemic heart failure. Conclusions— We demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious β1AR overstimulation in heart failure.

A 70-year-old man was admitted because of a 6-month history of progressive dyspnoea on exertion. The medical history showed that he suffered from patent ductus arteriosus (PDA) that was closed at 35 years of age by surgical ligation. Subsequently, up to year 1992, no evidence of residual left-to-right shunt was found. When he first came to our attention, we performed an echocardiographic test evidencing left ventricular dilation and contractile dysfunction and a recurrence of PDA. To exclude other possible causes of congestive heart failure, we performed several tests, including a coronary angiogram that showed coronary atherosclerosis without significant lesions. The haemodynamic study confirmed that the PDA was associated with a mild pulmonary hypertension with a QP: QS of 2: 1. The patient did not report any cardiovascular risk factor. Therefore, we concluded that PDA was responsible for congestive heart failure in this patient. We performed percutaneous closure of PDA, which was able to reverse left ventricular dilation and dysfunction, improving the patient's symptoms, at 1 month as well as 4 months after the interventional procedure. Although this kind of device is frequently used in the paediatric population, adult patients may present different challenges in proper management, such as poor visualization, calcification and pulmonary hypertension. In the description of the case reported here, we show that a PDA can present as congestive heart failure in the elderly. Percutaneous closure can be very effective in ameliorating left ventricular performance as well as symptoms.

OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms leads to variable changes in cardiac function. Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown. METHODS: To address this issue, we performed load-independent measurements of cardiac systolic and diastolic function by pressure-volume (PV) loop analysis in intact wild-type mice (WT) and transgenic mice overexpressing the AC isoforms 5 or 8. RESULTS: Here we show that cardiac overexpression of either AC5 or AC8 transgenic mice determined an increase in intrinsic cardiac contractility. Interestingly, AC8 transgenic mice displayed a significantly greater increase in cardiac contractility and improved active phase of relaxation. Despite these differences detected by PV loop analysis, both AC5 and AC8 mice showed a marked increase in exercise capacity on treadmill testing. CONCLUSIONS: Our results demonstrate that load-independent measurements of cardiac function are needed to compare different groups of genetically-modified mouse models and to detect subtle AC isoform-specific changes in cardiac performance.