Probability of second live birth after first natural and medically assisted reproduction-mediated live birth: A historical cohort study.

INTRODUCTION: Evidence on the role of medically assisted reproduction (MAR) in achieving the desired number of children is very limited. The aim of the current investigation was to assess the probability and the mode of conception of a second live birth according to the mode of conception of the first one. MATERIAL AND METHODS: This historical cohort study was based on administrative data from regional healthcare databases. Women hospitalized for childbirth in Lombardy between January 1, 2007 and December 31, 2017 were identified. The probability of a second live birth up to 2021 was estimated using the Kaplan-Meier method. We calculated this probability according to the mode of conception of the first birth, and the analysis was also performed in strata of maternal age at first birth. Cox proportional hazards models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between mode of conception at first live birth and the probability of having a second live birth. Mothers were right-censored if they moved out of the region, died, or did not have a second live birth by the end of follow-up. RESULTS: We identified 431 333 women who had their first live birth after a natural conception and 16 837 who had their first live birth after MAR. The probability of having a second live birth was 58.6% and 32.1%, respectively in the two groups (HR = 0.68, 95% CI: 0.66-0.70). Considering solely women who naturally conceived their first live birth, the probability to have a second child with MAR was 1.1% and to have a second child naturally 59.3%. The corresponding values were 11.5% and 25.2% in the group of women with a first MAR-mediated live birth. CONCLUSIONS: In our cohort, one woman out of 10 having a first MAR-mediated live birth underwent MAR programs again. Considering women who had a first natural live birth, this proportion was drastically reduced. In the field of MAR, more attention should be given to the capacity of a couple to achieve the number of desired children.

Neovagina creation methods in Müllerian anomalies and risk of malignancy: insights from a systematic review.

PURPOSE: This systematic review aims to provide a data synthesis about the risk of neovaginal cancer in women with Müllerian anomalies and to investigate the association between the adopted reconstructive technique and the cancer histotype. METHODS: PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov and Web of Science databases were searched from inception to March 1st, 2023. Studies were included if: (1) only women affected by Müllerian malformations were included, (2) the congenital defect and the vaginoplasty technique were clearly reported, (3) the type of malignancy was specified. RESULTS: Literature search yielded 18 cases of squamous cell carcinoma and two cases of vaginal intraepithelial neoplasia 3 (VAIN 3). Of these, 3 had been operated on according to the Wharton technique, 8 according to the McIndoe technique, 3 with a split-skin graft vaginoplasty, 2 according to the Davydov technique, 2 with a simple cleavage technique, 1 according to the Vecchietti technique and 1 with a bladder flap vaginoplasty. A total of 17 cases of adenocarcinoma and 1 case of high-grade polypoid dysplasia were also described. Of these, 15 had undergone intestinal vaginoplasty, 1 had been operated on according to the McIndoe technique and 1 had undergone non-surgical vaginoplasty. Finally, 1 case of verrucous carcinoma in a woman who had undergone a split-skin graft vaginoplasty, was reported. CONCLUSION: Although rare, neovaginal carcinoma is a definite risk after vaginal reconstruction, regardless of the adopted technique. Gynaecologic visits including the speculum examination, the HPV DNA and/or the Pap smear tests should be scheduled on an annual basis.

Current Approaches to Worsening Heart Failure: Pathophysiological and Molecular Insights.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

Forty-two normomenstruating adolescents with Müllerian obstructive anomalies: Presentation, pitfalls in the dagnosis and surgical management.

INTRODUCTION: We analyzed the frequency, presentation and pitfalls in the diagnosis and surgical management of a large group of normomenstruating adolescents with obstructive reproductive tract anomalies. MATERIAL AND METHODS: Retrospective analysis of prospectively collected data. Of the 143 outpatients referred for severe dysmenorrhea and persistent pelvic pain, 42 (29.3%) young women with obstructive Müllerian anomalies and regular menstrual flow were identified. These patients were divided into four groups: (1) patients with duplicate uterine cavities, obstructed hemivagina and ipsilateral renal agenesis (n = 34); (2) patients with unicornuate uterus and noncommunicating cavitated rudimentary horn (n = 5); (3) patients with accessory cavitated uterine mass (n = 2); (4) patients with partially obstructed transverse vaginal septum (n = 1). All 42 patients were conservatively treated via laparoscopy and 35/42 patients had also vaginal surgery. RESULTS: Of the four groups, patients in groups 2 and 3 (n = 7) were conservatively managed by laparoscopy alone; for patients in groups 1 and 4 (n = 35), laparoscopy and the vaginal approach were used. Patients of group 1 were treated by resecting the obstructed vaginal septum with drainage of retained collections. In patients in group 2, surgery consisted of the removal of the rudimentary horn. Patients of group 3 were treated by the removal of myometrial neoformations. In the patient in group 4, treatment consisted of removal of the septum. All surgical procedures were successful and no major complications were recorded. Follow-up reports highlighted the disappearance of obstruction and clear improvement in pain symptoms. CONCLUSIONS: Unilateral obstructive anomalies of the female genital tract are difficult to identify. Early diagnosis allows the preservation of reproductive activity and avoids potential complications.

Prevalence and Factors Associated With Intertwin Birth Weight Discordance Among Same-Sex Twins in Lombardy, Northern Italy.

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007-2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21-29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception.

Rokitansky Syndrome or Cervicovaginal Atresia?

STUDY OBJECTIVE: To investigate the possibility of conservative management of rudimentary uterine horns associated with vaginal agenesis. DESIGN: Observational study on cohort of consecutive cases treated with the same criteria from 2008 to 2021. SETTING: Two academic institutions and teaching hospitals in Milan, Italy. PATIENTS: Eight patients with vaginal agenesis associated with rudimentary cavitated uterine horns treated by the same team and postoperatively followed. INTERVENTIONS: All the subjects underwent the same standardized surgical procedure: laparoscopy, intraoperative ultrasound, and horn-vestibular direct anastomosis. Postoperatively vaginoscopy was performed every 6 months. MEASUREMENTS AND MAIN RESULTS: The postoperative course was generally uneventful and the mean hospital stay was 4.3 ± 2.5 (SD) days. All the patients began to menstruate a few months after the operation. Menstrual flows were light but regular. All patients had a neovaginal length > 4 cm at 1 year postoperatively, reaching approximately 6 cm at 2 years. During the follow-up period, 5 patients were sexually active without dyspareunia. In all cases, surgery restored the continuity of the neovagina and uterine horn through the creation of a "vaginal-horn fistula tract." CONCLUSION: In patients with vaginal agenesis associated with the presence of a uterine cavitary horn, it is possible to recover not only sexual activity but also menstrual function. The horn-vestibular anastomosis may be considered a valid, safe, and effective therapeutic option but requires accurate preoperative and intraoperative evaluation of rudimentary uterine structures.

Telemedicine: an Effective and Low-Cost Lesson From the COVID-19 Pandemic for the Management of Heart Failure Patients.

PURPOSE: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain.

Reconstructive surgery for congenital atresia of the uterine cervix: a systematic review.

The authors discuss the incidence, the embryological development, the classification, the presentation and the treatment options of this rare reproductive tract abnormality. In the past, the treatment proposed almost unanimously was hysterectomy and subsequent construction, when necessary, of a neovagina. In recent decades, numerous experiences of conservative therapies have accumulated that allow the restoration of menstrual function and in some rare cases even the achievement of a pregnancy. However, complications associated with recanalization of the cervix frequently resulted in the need for repeated surgery, risk of serious and sometimes fatal ascending infection. This review aims to analyze the most recent and significant experiences of conservative surgery in this field to provide an accurate picture of the various techniques and their outcomes, especially from the point of view of fertility. Conservative surgery should now be considered as the first-line treatment option. On the other hand, it is not possible to draw conclusions on the superiority of one technique over another among the various conservative options. This would require large series with adequate follow-up, which unfortunately are not available.

Protection against Ischemic Heart Disease: A Joint Role for eNOS and the KATP Channel.

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (KATP) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the KATP channel that provides a potential protective effect against IHD.

Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between the different endometrial preparation protocols for frozen embryo transfer (FET) and obstetric and perinatal outcomes? SUMMARY ANSWER: Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), post-partum hemorrhage (PPH) and cesarean section (CS) when compared with natural FET protocols. WHAT IS KNOWN ALREADY: An important and growing source of concern regarding the use of FET on a wide spectrum of women, is represented by its association with obstetric and perinatal complications. However, reasons behind these increased risks are still unknown and understudied. STUDY DESIGN, SIZE, DURATION: Systematic review with meta-analysis. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 1 November 2021. Published randomized controlled trials, cohort and case control studies were all eligible for inclusion. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The quality of evidence was also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were included only if investigators reported obstetric and/or perinatal outcomes for at least two of the following endometrial preparation protocols: programmed FET cycle (PC-FET) (i.e. treatment with hormone replacement therapy (HRT)); total natural FET cycle (tNC-FET); modified natural FET cycle (mNC-FET); stimulated FET cycle (SC-FET). MAIN RESULTS AND THE ROLE OF CHANCE: Pooled results showed a higher risk of HDP (12 studies, odds ratio (OR) 1.90; 95% CI 1.64-2.20; P < 0.00001; I2 = 50%) (very low quality), pregnancy-induced hypertension (5 studies, OR 1.46; 95% CI 1.03-2.07; P = 0.03; I2 = 0%) (very low quality), PE (8 studies, OR 2.11; 95% CI 1.87-2.39; P < 0.00001; I2 = 29%) (low quality), placenta previa (10 studies, OR 1.27; 95% CI 1.05-1.54; P = 0.01; I2 = 8%) (very low quality), PPH (6 studies, OR 2.53; 95% CI 2.19-2.93; P < 0.00001; I2 = 0%) (low quality), CS (12 studies, OR 1.62; 95% CI 1.53-1.71; P < 0.00001; I2 = 48%) (very low quality), preterm birth (15 studies, OR 1.19; 95% CI 1.09-1.29; P < 0.0001; I2 = 47%) (very low quality), very preterm birth (7 studies, OR 1.63; 95% CI 1.23-2.15; P = 0.0006; I2 = 21%) (very low quality), placenta accreta (2 studies, OR 6.29; 95% CI 2.75-14.40; P < 0.0001; I2 = 0%) (very low quality), preterm premature rupture of membranes (3 studies, OR 1.84; 95% CI 0.82-4.11; P = 0.14; I2 = 61%) (very low quality), post-term birth (OR 1.90; 95% CI 1.25-2.90; P = 0.003; I2 = 73%) (very low quality), macrosomia (10 studies, OR 1.18; 95% CI 1.05-1.32; P = 0.007; I2 = 45%) (very low quality) and large for gestational age (LGA) (14 studies, OR 1.08; 95% CI 1.01-1.16; P = 0.02; I2 = 50%) (very low quality), in PC-FET pregnancies when compared with NC (tNC + mNC)-FET pregnancies. However, after pooling of ORs adjusted for the possible confounding variables, the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP, PE, PPH (low quality) and CS (very low quality). LIMITATIONS, REASONS FOR CAUTION: The principal limitation concerns the heterogeneity across studies in: (i) timing and dosage of HRT; (ii) embryo stage at transfer; and (iii) inclusion of preimplantation genetic testing cycles. To address it, we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor. WIDER IMPLICATIONS OF THE FINDINGS: Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes. However, because of the methodological weaknesses, recommendations for clinical practice cannot be made. Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an 'a priori' high-risk profile for obstetric and perinatal complications. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: CRD42021249927.

Catheter ablation for papillary muscle arrhythmias: A systematic review.

BACKGROUND: Catheter ablation of papillary muscle ventricular arrhythmias (PM-VAs) has been associated with unsatisfactory results. Features that may affect acute and long-term procedural outcomes are not well established. OBJECTIVE: To systematically review the available data in the literature assessing efficacy and safety of PM-VAs catheter ablation. METHODS: An online search of PubMed, Cochrane Registry, Web of Science, Scopus and EMBASE libraries (from inception to March 1, 2021) was performed, in addition to manual screening. Twenty-one observational noncontrolled case-series were considered eligible for the systematic review, including 536 patients. RESULTS: Postero-medial PM harbored 60.8% of PM-VAs, while antero-lateral PM and right ventricular PMs 34.9% and 4.3% of cases, respectively. The mean acute success rate of the index ablation procedure was 88.1% (95% CI 82.8% to 91.9%, p < .001, I2 0%). After a mean follow-up period of 15.5 ± 17.4 months, pooled long-term arrhythmia-free rate was 69.2%, while the pooled long-term success rate after multiple ablation procedure was 84.9%. Overall, procedure complications occurred in nine patients (1.7%) and no procedure-related deaths were reported. The use of intracardiac echocardiography (ICE) as well as contact force sensing (CFS) and irrigated catheters during ablation was associated with higher rates of arrhythmia-freedom at long-term follow-up. CONCLUSIONS: Catheter ablation is an effective and safe strategy for PM-VAs, with an acute success rate of 88.1%, a long-term success rate of 69.2%, with a relatively low procedural complication rate. The use of ICE, irrigated catheters and catheters with CFS capability was associated with higher rates of arrhythmia-freedom at long-term follow-up.

Conservative Treatment of Didelphyc Uterus with Obstructed Hemivagina and Ipsilateral Renal Agenesis.

STUDY OBJECTIVE: To show a conservative surgical treatment for a female adolescent affected by Wunderlich syndrome with didelphys uterus and obstructed hemivagina. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: In the context of obstructive congenital müllerian anomalies, involving a stagnation of menstrual blood, the Wunderlich syndrome is the most common and constantly characterized by the duplicity of the uterine body, by the presence of an imperforate hemivagina, and by renal agenesis ipsilateral to the obstructed hemivagina. The imperforate hemivagina leads to dysmenorrhea and abdominal pain, owing to the hematocolpos and the hematometra, which arose immediately after the menarche. This is the case of a 14-year-old female adolescent affected by Wunderlich syndrome referred to the San Raffaele Hospital adolescent center (Milan, Italy) for dysmenorrhea and abdominal pain. At vaginal exploration, a right imperforated hemivagina and hematocolpos were highlighted. A diagnostic magnetic resonance imaging (MRI) found the duplicity of the uterine body, the hematometra, and the right renal agenesis. INTERVENTIONS: A combination of explorative laparoscopy and surgical vaginal time leads to the excision of the vaginal septum that allows the drainage of the hematocolpos and of the hematometra. Three surgical steps are described: 1. First laparoscopic step: exploration of the abdominal cavity with the detection of a double uterine body, an enlarged hemiuterus, and an enlarged hemivagina caused by the hematometra and the hematocolpos. Careful evaluation of adnexa for eventual presence of hematosalpinx. 2. Vaginal step divided into the following: (A) puncture of the vaginal tumescence (corresponding to the imperforated hemivagina) with a 19-gauge needle mounted on a syringe. Aspiration results in thick creamy black material (old menstrual blood). (B) In correspondence with the needle puncture, a full-thickness incision of the vaginal wall widely opening the second uterine cervix and (C) stabilization of the opening by the marsupialization of the edge of the obstructed hemivagina were performed. 3. Second laparoscopic step: having emptied the hematocolpos of the left hemiuterus, the didelphys uterus and the disappearance of the hematocolpos can be clearly seen. CONCLUSION: Here, we demonstrate a conservative surgical approach for the treatment of Wunderlich syndrome. This rare malformation is characterized by an extreme variability of the anatomic presentation, and the precise identification of the variety together with the early diagnosis is of fundamental importance for the surgical correction.

Complex connections: A young man presenting with shortness of breath, hypoxemia, right lumbar pain and left limb swelling.

A 43-year-old Caucasian man was admitted to hospital due to shortness of breath, right lumbar pain and lower left limb swelling. Arterial blood gas sample showed mild hypoxemia and respiratory alkalosis. CT scan confirmed pulmonary embolism, splenic and bilateral renal ischemic lesions. Echocardiography showed right ventricular and coronary sinus (CS) dilatation. Using contrast echocardiography, a superior sinus venous atrial septal defect and persistent left superior vena cava (PLSVC) draining in CS were suspected. Cardiac CT confirmed the diagnosis and showed overriding right superior vena cava (RSVC) draining in both atria. The patient underwent successful surgical correction.

Effects of Alcohol Consumption on Oxidative Stress in a Sample of Patients Recruited in a Dietary Center in a Southern University Hospital: A Retrospective Study.

Background and objectives: The aim of this retrospective study was to evaluate the effects of alcohol consumption on oxidative stress. Materials and Methods: The study was conducted by analyzing the increase in lipid peroxidation, the reduction of antioxidant defenses and the alteration of the oxidation/antioxidant balance after the administration of ethanol in 25% aqueous solution (v/v) at a concentration of 0.76 g/kg of body weight daily in two doses for 3 days. The changes in oxidative stress indices were investigated by standard methods previously described. Results: Ethanol administration has determined a significant increase in plasma levels of lipid hydroperoxide (LOOH), malonilaldehyde (MDA) and oxidized glutathione (GSSH), and a decrease in total antioxidant capacity (TAC), reduced glutathione (GSH) and GSH/GSSH ratio. Conclusions: In the proposed experimental condition, the excessive and repeated consumption of ethanol causes oxidative damage, as shown by the increase in lipid peroxidation, the reduction of antioxidant defenses and the alteration of the oxidation/antioxidant balance, which, at least in part, are responsible for the harmful effects of excess ethanol.

T2-mapping increase is the prevalent imaging biomarker of myocardial involvement in active COVID-19: a Cardiovascular Magnetic Resonance study.

BACKGROUND: Early detection of myocardial involvement can be relevant in coronavirus disease 2019 (COVID-19) patients to timely target symptomatic treatment and decrease the occurrence of the cardiac sequelae of the infection. The aim of the present study was to assess the clinical value of cardiovascular magnetic resonance (CMR) in characterizing myocardial damage in active COVID-19 patients, through the correlation between qualitative and quantitative imaging biomarkers with clinical and laboratory evidence of myocardial injury. METHODS: In this retrospective observational cohort study, we enrolled 27 patients with diagnosis of active COVID-19 and suspected cardiac involvement, referred to our institution for CMR between March 2020 and January 2021. Clinical and laboratory characteristics, including high sensitivity troponin T (hs-cTnT), and CMR imaging data were obtained. Relationships between CMR parameters, clinical and laboratory findings were explored. Comparisons were made with age-, sex- and risk factor-matched control group of 27 individuals, including healthy controls and patients without other signs or history of myocardial disease, who underwent CMR examination between January 2020 and January 2021. RESULTS: The median (IQR) time interval between COVID-19 diagnosis and CMR examination was 20 (13.5-31.5) days. Hs-cTnT values were collected within 24 h prior to CMR and resulted abnormally increased in 18 patients (66.6%). A total of 20 cases (74%) presented tissue signal abnormalities, including increased myocardial native T1 (n = 11), myocardial T2 (n = 14) and extracellular volume fraction (ECV) (n = 10), late gadolinium enhancement (LGE) (n = 12) or pericardial enhancement (n = 2). A CMR diagnosis of myocarditis was established in 9 (33.3%), pericarditis in 2 (7.4%) and myocardial infarction with non-obstructive coronary arteries in 3 (11.11%) patients. T2 mapping values showed a moderate positive linear correlation with Hs-cTnT (r = 0.58; p = 0.002). A high degree positive linear correlation between ECV and Hs-cTnT was also found (r 0.77; p < 0.001). CONCLUSIONS: CMR allows in vivo recognition and characterization of myocardial damage in a cohort of selected COVID-19 individuals by means of a multiparametric scanning protocol including conventional imaging and T1-T2 mapping sequences. Abnormal T2 mapping was the most commonly abnormality observed in our cohort and positively correlated with hs-cTnT values, reflecting the predominant edematous changes characterizing the active phase of disease.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. OBJECTIVE: We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. METHODS: An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. RESULTS: The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52-0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74-0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52-0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50-0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47-0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78-1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78-1.06; p 0.24). CONCLUSIONS: In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

The Peritoneal Neovagina after Davydov's Laparoscopic Procedure in Mayer-Rokitansky-Küster-Hauser Syndrome: Morphology and Ultrastructure Investigation of the New Epithelium.

STUDY OBJECTIVE: To investigate the clinical appearance and morphologic and ultrastructural aspects of the mucosa of the peritoneal neovagina after laparoscopic Davydov neovaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome. DESIGN: The study group was a prospective, observational, experimental cohort of cases treated in the same institution between 2015 and 2019. Patients were followed up at 3, 6, and 12 months after surgery and then every 12 months. SETTING: Single-center academic institution and teaching hospital in Milan, Italy. PATIENTS: Fifty-one consecutive subjects with clinical and imaging diagnosis of Mayer-Rokitansky-Küster-Hauser syndrome surgically treated by the same team and postoperatively followed. INTERVENTIONS: All the subjects underwent the same standardized surgical procedure and thereafter were followed up at 3, 6, and 12 months after surgery and then every 12 months; a minimum follow-up of 12 months was achieved in all cases. Vaginoscopy and Schiller test were performed at each follow-up visit, and a biopsy specimen of the neovagina was obtained in a limited number of patients (6 out of 51) for light microscopy (LM) and scanning electron microscopy (SEM) analysis of the tissue. MEASUREMENTS AND MAIN RESULTS: In vaginoscopy, the neovaginal mucosa appeared homogeneous, smooth, and pink all along the neovaginal tract; the Schiller test detected iodine positivity at different degrees of extension upward from the hymenal ring, starting at 3 months postoperatively with almost complete positivity between 6 to 12 months in all cases. LM demonstrated adequate thickness and differentiation of the new mucosa along with the presence of glycogen storage; SEM revealed an ultrastructural surface appearance very close to normality. The main difference compared with a normal vagina was the reduced presence of vaginal mucosal folds. CONCLUSION: Under different techniques (vaginoscopy, Schiller test, LM, and SEM), a minimum of 6 months after surgery, the peritoneal neovagina epithelium showed aspects comparable to the natal mucosa of the vagina.

The evolving role of echocardiography in the assessment of patent foramen ovale in patients with left-side thromboembolism.

Patent foramen ovale (PFO) is the most common congenital cardiac abnormality found approximately in 25% of the adult population The pathophysiological role of paradoxical embolization through the PFO in ischemic stroke is well established. "Self-expanding double disk" and, more recently, suture-based "deviceless" systems are used for PFO closure in the setting of secondary prevention after ischemic stroke likely related to paradoxical embolization. Ultrasound plays a significant role in PFO assessment, indication to treatment, intra-procedural guidance, and follow-up for those undergoing PFO closure. Three different techniques are frequently used for these purposes: transesophageal echocardiography, transthoracic echocardiogram, and transcranial Doppler. In this review, advantages and limits of these techniques are discussed in detail to improve our skills in detection and treatment of this important condition by using ultrasound.

Myocardial Tissue Characterization in Heart Failure with Preserved Ejection Fraction: From Histopathology and Cardiac Magnetic Resonance Findings to Therapeutic Targets.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients' outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease's natural course.