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Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding Associazione Lorenzo Risolo.

Objective: Urinary tract infections (UTI) among women form a substantial part of medical practice and both patients and medical professionals have an interest in non-antibiotic treatments and preventative measures. This research provides preliminary data on a multi-functional composition, DAPAD, which explored several biologic activities of relevance to UTI. Study Design: This formulation included D-mannose, citric acid, three prebiotic compounds, and extracts of dandelion and astragalus. Studies performed employed 4 bacterial strains that have relevance to UTI including E. coli, Proteus mirabilis, Streptococcus agalactiae and Enterococcus faecalis. Results: Key findings from in vitro studies included: DAPAD at full- and half-strength inhibited growth of all UTI bacteria. Evidence for D-mannose agglutination of E. coli was demonstrated. D-mannose also showed unexpected effects on bacterial membrane integrity with vital staining and modest growth restriction. We did not demonstrate growth inhibition by dandelion or astragalus extracts but the latter showed diminished cytokine elaboration by bladder epithelial cells. Conclusion: DAPAD is a multifunctional composition that may warrant further development as a UTI treatment or preventive if supported by clinical evaluation.

Background and Objectives: Uterine fibroids still represent the most common indication for hysterectomy for benign pathologies. In the United States, more than 479,000 hysterectomies are performed annually, 46.6% for myomas and 47.7% in women aged from 18 to 44 years. By applying appropriateness criteria to this procedure, it has been estimated that overuse ranges from 16 to 70%. One of the main reasons that induce patients and gynecologists to consider hysterectomy is represented by severe anemia. Materials and Methods: This is a retrospective cohort study of 202 patients with uterine fibroids diagnosed by transvaginal ultrasound who underwent a hysteroscopic procedure. Myoma grade, size, location, and number were assessed by transvaginal scan and office hysteroscopy and correlated to the pre-treatment hemoglobin level. Results: Univariate analysis showed that anemia does not have a statistically significant association with myoma number and with age considered as a numerical predictor. In the patients with myoma type 0, there is a possibility of 81% having anemia regardless of menorrhagia. On the contrary, in patients with myoma type 1 or type 2, the possibility of having anemia varies according to the presence or absence of menorrhagia. If there is menorrhagia, the risk of moderate anemia is only present for myomas >60 mm. Conclusions: The results of this study may contribute to defining objective criteria for the management of submucous myomas and anemia. Our data suggest that submucosal myomas type 0 >10 mm should always be treated, putting patients at risk for anemia. Myomas type 2 and 3 should be treated for the risk of anemia in the presence of menorrhagia episodes or if > of 60 mm. Adequate management of anemia and myomas could reduce the rate of unnecessary hysterectomies.

Introduction Abdominal-pelvic mass, ascites and pleural effusion are suggestive of malignant metastatic ovarian cancer. This triad is also present in a rare benign condition called Meigs syndrome. Rarely this condition is associated with an increased CA 125 level. Case report A 62-year-old woman with a history of abdominal pain underwent an ultrasound (US) examination and a chest X-ray. The imaging revealed the presence of a large pelvic mass and ascites with a monolateral pleural effusion and a high level of the tumor marker CA 125. The patient underwent a total abdominal hysterectomy, salpingoophorectomy, removal of the pelvic mass, pelvic lymphadenectomy and peritoneal biopsies. The histology showed an ovarian fibrothecoma. Discussion The US analysis according to international ovarian tumor analysis simple rules revealed "inconclusive results"; the logistic regression model LR2 and Adnex suggested a high risk of malignancy. The presence of ascites and the size of the lesion associated with a high level of CA 125 affected the correct assessment of the risk of malignancy, exposing the patient to overtreatment. Conclusions Meigs syndrome is characterized by the resolution of symptoms after surgical removal of the pelvic mass. However, it mimics the clinical picture of a malignant metastatic ovarian cancer. Clinicians have to exclude ovarian cancer and recognize the syndrome to reduce inappropriate procedures.

Objective: To demonstrate laparoscopic surgical management of parametrial ectopic pregnancy. Design: Video presentation of laparoscopic nerve-sparing treatment of parametrial pregnancy. Setting: Tertiary university center. Patient(s): A 33-year-old patient, nullipara at 8 weeks of gestation, with no comorbidity and no previous surgery, was admitted to a spoke hospital for acute abdominal pain. During hospitalization, a transvaginal gynecologic ultrasound revealed pregnancy with ectopic localization. Free pelvic fluid was detected, and a subsequent diagnostic laparoscopy was performed because of worsening symptoms. During the procedure, hemoperitoneum drainage was instituted and American Society of Reproductive Medicine stage III pelvic endometriosis was diagnosed. A round formation approximately 3 cm in diameter was found at the left posterior parametrium (Fig. 1). Due to the pregnancy position and β-human chorionic gonadotropic (β-hCG; 820 mUI /mL) values, conservative treatment was chosen. Thus, methotrexate at 50 mg/m2 body surface area was administered. A second dose of methotrexate was administered seven days after the first one, and the β-hCG increased to 1068 mUI. On day 14 after treatment, the β-hCG was 1053 mUI/mL. Therefore, surgical treatment was chosen, and the patient was transferred to our center. An ultrasound assessment confirmed the ectopic pregnancy with a live fetus in the left posterior parametrium. Intervention(s): The patient underwent operative laparoscopy to remove the ectopic pregnancy. Surgery was performed using a 3-dimensional optical system (TIPCAM 1, S D3-LINK; Karl Storz SE & Co., Tuttlingen, Germany). After drainage of the hemoperitoneum, the gestational sac was identified in the left posterior parametrium. The uterus, tubes, and ovaries showed normal morphology. Pelvic endometriosis was confirmed. After accessing the left pelvic retroperitoneum with the medial and lateral pararectal spaces’ opening and development, ipsilateral ureterolysis was necessary to isolate the parametrial pregnancy in close contact with it. Coagulation and sectioning of the deep uterine veins were essential to control hemostasis. Identification of the left hypogastric nerve, which was partially infiltrated by the chorionic villi, and the pelvic splanchnic nerves, was required to safeguard them (Fig. 2). Subsequently, the surgeon decided to place a ureteral stent to prevent urologic complications. Main Outcome Measure(s): The laparoscopic approach proved to be safe and feasible to manage parametrial pregnancy. Result(s): The pregnancy was removed entirely. The patient was discharged 72 hours after the procedure with an uneventful postoperative course. The histologic report confirmed the diagnosis of parametrial pregnancy on decidualized endometriotic tissue. The β-hCG serum level became negative in 20 days. Conclusion(s): Extrauterine pregnancies represent one of the leading causes of maternal death in the first trimester and constitute approximately 1%–2% of total pregnancies. Of these percentages, only 5%–8.3% are nontubal. Cases of abdominal pregnancy are even rarer, estimated at

Purpose: Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is still debated. We evaluated the incidence of acute and late PV reconnection (PVR) with different AI settings and its predictors. Methods: The Ablation Index Registry is a multicenter study that included patients with paroxysmal/persistent atrial fibrillation (AF) who underwent first-time ablation. Each operator performed the ablation using his preferred ablation catheter (ThermoCool® SmartTouch or Surround Flow) and AI setting (380 posterior-500 anterior and 330 posterior-450 anterior). We divided the study population into two groups according to the AI setting used: group 1 (330–450) and group 2 (380–500). Incidence of acute PVR was validated within 30 min after PVI, whereas the incidence of late PVR was evaluated at repeat procedure. Results: Overall, 490 patients were divided into groups 1 (258) and 2 (232). There was no significant difference in the procedural time, fluoroscopy time, and rate of the first-pass PVI between the two study groups. Acute PVR was observed in 5.6% PVs. The rate of acute PVR was slightly higher in group 2 (64/943, 6.8%, PVs) than in group 1 (48/1045, 4.6% PVs, p = 0.04). Thirty patients (6%) underwent a repeat procedure and late PVR was observed in 57/116 (49%) PVs (number of reconnected PV per patient of 1.9 ± 1.6). A similar rate of late PVR was found in the two study groups. No predictors of acute and late PVR were found. Conclusion: Ablation with a lower range of AI is highly effective and is not associated with a higher rate of acute and late PVR. No predictors of PV reconnection were found.

(1) Background: This review aimed to summarize the indications for venous thromboembolic (VTE) events’ prophylaxis in a gynecological cancer population, according to the most recent guidelines. (2) Methods: A systematic review of the guidelines in PubMed, SCOPUS, Web of Science, EMBASE, and CINHAL regarding VTE prevention in gynecological cancer patients was conducted according to PRISMA criteria. We compared the recommendations given by oncological and hematological societies regarding VTE prevention in gynecological cancer patients published from January 2010 through March 2021. We searched for the following keywords: “venous thromboembolism prevention”, “cancer”, and “guidelines”. The AGREE II checklist was used to critically analyze the guidelines’ quality. (3) Results: There were 1003 documents available; 14 met the inclusion criteria, 5 were excluded and, eventually, the guidelines of 10 societies were evaluated. (4) Conclusions: The guidelines agree that low-molecular-weight heparin (LMWH) and fondaparinux achieve better results in VTE prevention in gynecological cancer patients. Direct oral anticoagulants (DOACs) can be used to prevent VTE in outpatients and high-risk medical patients after discharge. VTE risk scores should be applied to all oncological patients to identify those who would benefit from a prevention program. More attention should be paid to mechanical prophylactic methods due to the high bleeding risk of gynecological cancer patients.

True knots of the umbilical cord (UC) are a rare occurrence and are reported in 0.4–1.2% of deliveries. The compression of true knot of the UC can cause obstruction of the fetal circulation, leading to intra-uterine growth retardation or fetal death. Predisposing factors for the genesis of the true UC knot are numerous and include all the conditions, which lead to a relatively large uterine volume. This situation may predispose to free and excessive fetal movements. Although not all true knots lead to perinatal complications, they have been associated with adverse pregnancy outcomes, including fetal distress, fetal hypoxia, intra-uterine growth restriction (IUGR), long-term neurological damage, caesarean delivery and stillbirth. We present a rare case of operative delivery with vacuum in a multiparous woman at term of pregnancy with a double true knot of the UC. As in most cases, the diagnosis was made after delivery, as there were no fetal symptoms during pregnancy. Some authors assume that 3D power sonography may be useful in the diagnosis of true UC knots. However, 3D power Doppler cannot be considered as a definitive method. There are no specific prenatal indications to induce the physician to look for ultrasound signs suggestive of umbilical true knot. Some studies argue that cases of fetal death and fetal risk are directly related to the number of knots. We also support this thesis, even if further observational and retrospective studies are needed to demonstrate it.

Background: Spondylodiscitis can be a rare complication of gynecological surgery, typically of procedures involving the sacrum and the sacrospinous ligament. This report presents a case of spondylodiscitis arising after a laparoscopic sacrocolpopexy with a mesh. We also review the literature finding 52 cases of spondylodiscitis following sacrocolpopexy and (or) rectopexy with or without a mesh.Methods: We performed a comprehensive search from the electronic databases MEDLINE (Pubmed), Scopus, Web of Science, Embase, CINAHL, and Google Scholar from 1990 to February 2021 in order to identify case reports or case series reporting on spondylodiscitis after rectopexy or sacrocolpopexy.Results: We identified 52 total postoperative spondylodiscitis. We examined the mean age of patients, the surgical history, the time from initial surgery to spondylodiscitis, the presenting symptoms, the diagnostic tools, the medical and surgical treatment, the type of mesh used, the surgical access, and the possible causes of spondylodiscitis.Conclusions: Diagnosis of spondylodiscitis may be challenging. From our review emerges that recurrent pelvic pain and lumbosciatalgia may be signals of lumbar spondylodiscitis. Magnetic resonance is the gold standard examination for spondylodiscitis. Surgical practice needs to be improved further in order to establish the best procedure to minimize the incidence of this complication. Awareness of symptoms, timely diagnosis, and treatment are fundamental to prevent irreversible complications.

Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a debated topic. Depending on hemodynamic stability, size of pregnancy, depth of surrounding myometrium, and desires for future fertility, interstitial pregnancy can be managed medically or surgically. We reviewed the literature in December 2020 using keywords “interstitial pregnancy”, “medical treatment”, “methotrexate”, and “mifepristone”. Articles published from January 1991 until 2020 were obtained from databases EMBASE, SCOPUS, and PUBMED. We describe the case of a patient with an interstitial pregnancy that was managed with a total medical approach in August 2020 at Burlo Garofolo Hospital. The patient was asymptomatic and hemodynamically stable, with a high level of serum β-hCG (22,272 mUi/mL). We used the combination of methotrexate (MTX) and mifepristone. Medical therapy was effective leading to interstitial pregnancy resolution in 51 days without collateral effects for the patient. We found seven previous cases reported in the literature. Our purpose is to underline the efficacy of medical therapy with systemic multidose MTX associated with a single oral dose of mifepristone and also folinic acid when is present a viable fetus and a high serum β-hCG level.

Objective: to evaluate risk factors, causes, management and surgical therapy of postcoital vaginal perforation and evisceration in women with no prior pelvic surgery. Data sources: We used MEDLINE (PubMed), Scopus, Embase and Web of Science for our research. Our review includes all reports from 1980 to November 2020. The research strategy adopted included different combinations of the following terms: (intercourse) AND (coitus) AND (vaginal perforation). Methods of study selection: we report a case of vaginal evisceration after consensual intercourse in a young and healthy woman. In addition, we performed a systematic review of vaginal perforations with or without evisceration in women without prior surgery or any other predisposing disease. All studies identified were listed by citation, title, authors and abstract. Duplicates were identified by an independent manual screening, performed by one researcher and then removed. For the eligibility process, two authors independently screened the title and abstracts of all non-duplicated papers and excluded those not pertinent to the topic. Tabulation, integration and results: We have followed the PRISMA guidelines. Five manuscripts were detected through the references of the works that had been identified with the research on MEDLINE (PubMed), Scopus, Embase and Web of Science. We found 16 cases between 1980 and 2020. The young age and the virginal status represent the principal risk factors and all the lacerations occurred in the posterior vaginal fornix. The most common surgical technique was the laparotomic approach and, in the remaining cases, the laparoscopic and vaginal route was performed. Conclusions: Post-coital vaginal perforation and evisceration in women with no prior pelvic surgery is a rare condition in the clinical practice and, when it is associated with evisceration it is a surgical emergency. Usually, these injuries are not life-threatening conditions but, a delay in diagnosis, can lead to severe complications. In consideration of the high heterogeneity of the data in the literature, it is essential to define a diagnostic–therapeutic management for the patients with vaginal perforation. With our review, we try to identify the associated risk factors, the best and fastest diagnosis, and the best surgical approach. We believe that a combined vaginal and laparoscopic approach can be the best surgical treatment, useful to diagnose injuries of the abdominal organs and to improve postoperative outcome.

An experimental model of dryness on vaginal mucosa is proposed to assess the efficacy of a new vaginal gel (Respecta® Hydragel Ref 17031). The dryness model was induced on reconstituted human vaginal epithelium (HVE) by incubating the tissues in modified environmental conditions (R.H. &lt, 50% and T = 40 °C) for 48 h. The products were applied on the ‘Dry’ HVE models for 24 h (series 48 h + 24 h) in standard culture conditions (37 °C 5% CO2). Their efficacy in counteracting vaginal dryness was assessed and compared to tissues treated with saline solution and cultured in standard culture conditions (negative control) and to untreated tissues incubated in dryness conditions for 48 h and then recovered after 24 h in standard culture conditions (positive control). The products’ efficacy was quantified by measuring the following parameters: (1) water flux and direct moisturization by AQP3 immunohistochemical staining, and (2) maintenance of moisturization and elasticity of the mucosa by hyaluronic acid (CD44) immunofluorescence staining. Respecta® Hydragel demonstrated efficacy in regulating the water flux by inducing AQP3 expression thus determining a positive water balance within the vaginal epithelium. It induced a remodelling of the epithelium morphology with restored trophism compared to the dry HVE control. Furthermore, it demonstrated a significant increase of the expression of CD44, related to hyaluronic acid (HA) distribution in the extracellular matrix. HA has the ability to act on the cellular matrix composition and its renewal compared to the dry HVE control. Through these mechanisms it induces a deep hydration and elasticity of the vaginal mucosa.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy which represents a consequence of a previous cesarean section. It is associated with major maternal morbidity and mortality and has potential implications on future fertility. Because of possible serious complications, CSP should be swiftly diagnosed and treated. There is no management protocol for this rare, life-threatening condition, and each patient should be evaluated individually. Several types of conservative treatment have been used to treat cesarean scar pregnancy: dilation and curettage (D&C), excision of trophoblastic tissues, local or systemic administration of methotrexate, bilateral hypogastric artery ligation, and selective uterine artery embolization with curettage and/or methotrexate administration. In our study we present a cesarean scar pregnancy of a 40-year-old woman who was treated with angiographic uterine artery embolization (UAE) followed by hysteroscopic diode laser resection. Our combined UAE–hysteroscopic laser surgery appears to offer an effective, safe, and minimally invasive surgical treatment.

Introduction: A high level of surgical ability is required to perform endoscopic knot tying. Barbed sutures help in avoiding this procedure, thus reducing intraoperative time and lowering blood loss and hospitalization time when compared to traditional sutures. Some cases of bowel occlusion following the use of barbed sutures have been described in literature. All of them are characterized by the entanglement of an intestinal loop in wire barbs with bowel occlusion symptoms.Case Presentation: We report two more cases which occurred in our Institute in 2020 and review those which have been reported in the literature by searching on Pubmed, Scopus, and Embase. We used the search terms: “Barbed,” ”Suture,” “Bowel,” and ”Obstruction.” We examined in the literature the surgical procedures, the type of complications, the time to onset of the complications, and the type of barbed suture.Discussion: Twenty-two cases in total were reported in the literature from 2011 to 2020, and bowel complications were largely subsequent to interventions such as hernia surgical repair and myomectomy. In order to take advantage of barbed sutures while minimizing the risk of adverse events, such as intestinal occlusion, some precautions may be considered, such as the shortening of thread tails and use of antiadhesive barriers. Moreover, performing a few stitches backwards when ending the suture might be a useful suggestion. Further studies in this field may be useful in order to assess whether it might be better avoiding barbed suture application on serosal tissues to prevent bowel damage.

Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40–50% of these will experience further episodes. The high incidence of vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen® Microbio+, a new product containing Saccharomyces cerevisiae, melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen® Microbio+ group. Conclusions: Unilen® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.

Background: Placental chorioangioma is the most common benign non-trophoblastic neoplasm of the placenta. Its clinical relevance lies in the size of the tumor since larger masses cause pregnancy complications, including an unfavorable neonatal outcome. Case presentation: We report the case of a 34-year-old second gravida and nullipara at the 35th week of gestation, admitted to the gynecological department for antibiotic-resistant fever. The cardiotocography performed during hospitalization showed an abnormal fetal pattern. A 2250 g newborn was delivered by cesarean section. No complications were observed during childbirth and postpartum was insignificant. On gross inspection a white fleshy intraparenchymal mass blooming on the maternal surface was noted; routinely stained sections revealed features consistent with chorioangioma with vascular channels lined by inconspicuous endothelial cells immunoreactive for CD31 and CD133. Focal expression of CD133 was also observed in placental villi. Discussion: CD133 expression indicated the presence of stem cells in chorioangioma, suggesting their possible role in the development of mesenchymal lesions including chorioangioma.

Uterine leiomyomas are a common finding in medical practice, but their frequency changes drastically when contextualized in a syndrome, as in the following case. A 50-year-old woman with a known Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome presented at our clinic with abdominal pain located in the lower quadrants and scarcely responsive to analgesic therapy. A twisted gynecological pelvic mass was diagnosed, and management for prompt resolution was adopted. Histologically the mass was described as a leiomyoma. The aim of the present study is to share our experience and to review the literature to compare different manifestation of the disease and different approach used in the various centers. The additional novelty of the paper is the immunohistochemical study we carried out on the leiomyoma that is contrasted with the current etiopathogenetic theories.

Background: The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. Aim: To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. Methods: In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. Results: A total of 2675 patients (64.3% male, age 78 (70–84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38–12.08) and diabetes (OR: 2.22, 95% CI: 1.02–4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60–3.55 for each point), with a c-index = 0.64 (0.52–0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63−0.71) p < 0.001. Conclusions: In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status.

Background Ablation index (AI) is a new lesion quality marker that has been demonstrated to allow a high single-procedure arrhythmia-free survival in single-center studies. This prospective, multi-center study was designed to evaluate the reproducibility of pulmonary vein (PV) isolation guided by the AI. Methods A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV isolation and were divided in four study groups according to operator's preference in choosing the ablation catheter (a contact force (ST) or contact force surround flow (STSF) catheter) and the AI setting (330-450 or 380-500 at anterior wall or posterior wall, respectively). Results At 12 months a high rate of freedom from AF recurrences was observed in patients with both paroxysmal and persistent AF (91% vs 83.3%; P = .039). There was no difference in the rate of AF recurrence among the four study groups (4.5% in group ST330-450, 12.2% in group ST 380-500, 14.9% in group STSF330-450, 9.4% in group STSF380-500; P = .083). Recurrence was also similar between patients treated with a ST (8%) or STSF catheter (12.1%; P = .2), and within patients targeting an AI settings of 330 to 450 (10.9%) or 380 to 500 (10.3%; P = .64). In patients with paroxysmal AF, there was no difference (P = .12) in the 1-year freedom from AF recurrence among 14 operators that performed ≥10 ablation procedure. Conclusions An ablation protocol respecting strict criteria for contiguity and quality lesion resulted in high rate of 1-year freedom from AF recurrence, irrespective of the ablation catheters, AI settings, and operator.

AIM: To report the Italian data deriving from the European Society of Cardiology-EURObservational Research Program atrial fibrillation ablation long-term registry. METHODS AND RESULTS: Ten Italian centers enrolled up to 50 consecutive patients undergoing atrial fibrillation ablation. Of the 318 patients included, 5 (1.6%) did not undergo catheter ablation, 1 had ablation partially done and 62 were lost at 1-year follow-up. Women were less represented (23.6%) and the median age was 60.0 years. A total of 195 patients (62.3%) suffered paroxysmal atrial fibrillation, whereas only 9 (2.9%) had long-standing persistent atrial fibrillation. Most Italian patients (92.3%) were symptomatic but suffering fewer symptomatic events than patients enrolled in other countries (median of two events in the month preceding the ablation vs. three, respectively; P

Background and objectives: Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Early diagnosis is essential in order to allow conservative medical and surgical treatments. Although many treatment approaches are disponible, the most effective is still unclear. The aim of this study is to evaluate the efficacy of hysteroscopic management in early CP in order to preserve future fertility. Materials and Methods: This is a retrospective observational case series. Five patients with a diagnosis of CP, hemodynamically stables and managed conservatively between 2014 and 2019 at the Institute of Child and Maternal Health Burlo Garofolo in Trieste, Italy, were included. Four patients, with &beta, hCG levels &gt, 5000 mUi/mL were managed by hysteroscopy, with or without a previous systemic Methotrexate (MTX). One case with &beta, hCG levels &lt, 5000 mUi/mL was treated using MTX combined to Mifepristone and Misoprostol. Results: In one patient treated by hysteroscopy alone it occurred a profuse vaginal bleeding with necessity for blood transfusion. Haemorrhage was controlled by a second hysteroscopic procedure. No complications, such as vaginal bleeding, were recorded in the other cases. Serum &beta, hCG levels become undetectable in a range of 15&ndash, 40 days after hysteroscopic management, after medical treatment it become undetectable after 35 days. Serum &beta, hCG levels had a faster drop the day after hysteroscopy than post medical management. The onset of a spontaneous pregnancy at the normal implantation site occurred after five months in one case treated by hysteroscopy. Conclusions: Many therapeutic approaches are effective for CP treatment. Hysteroscopy, alone or in combination with MTX, may provide a greater effect on the descent of &beta, hCG, leading to a reduction of the hospitalization stay, decreasing costs and period for attempt pregnancy. Further prospective studies on larger samples are needed to define therapeutic protocols for CP management

Introduction. Interstitial pregnancy (IP) is an ectopic pregnancy (EP) located in the portion of the fallopian tube that penetrates the uterine muscular layer. Incidence increased in the last two decades with the widespread use of the assisted reproductive techniques. It is estimated in 1-6% of all the EPs, with a maternal mortality rate of 2.0-2.5%. Clinical presentation, gestational age at diagnosis, beta-human chorionic gonadotropin (β-hCG) levels, ultrasound features, and patient preference, should be considered to determine the best management: surgical, medical treatment, or close observation. We report two cases of IP successfully managed with systemic MTX and Mifepristone: in one case β-hCG was >10.000 mIU/mL and a vital embryo was present. Materials and Methods. A literature search was carried out on MEDLINE, EMBASE, and PUBMED. We identified two cases of IP referred to the Institute for Maternal and Child Burlo Garofolo, Trieste. Data related to clinical presentation, β-hCG, and ultrasound scan at the moment of the diagnosis were recorded. In one of the cases, the β-hCG level was >10.000 mIU/mL, and a vital embryo was testified at an ultrasound scan. The patient was asymptomatic and she was treated using multidose systemic Methotrexate (MTX) combined with Mifepristone. In the second case, in the presence of a clinically stable patient with β−hCG>10.000 mIU/mL, it was chosen that the administration of Mifepristone combined with a double dose of MTX. β-hCG levels and ultrasound examinations were performed weekly until a complete resolution of the IP. Results. In the first case, β-hCG dropped down in 5 days and became undetachable in 30 days. In the second case, β-hCG became undetectable in 47 days. The first-line therapy in asymptomatic women could be addressed to a combined protocol, consisting of a systemic multidose MTX regimen with a single oral dose of Mifepristone. Conclusions. Clinical management of IP remains a debated topic. In selected cases, a systemic multidose MTX regimen combined with a single oral dose of Mifepristone could be considered also in the presence of high serum β-hCG.

Objectives Aim of this study is to refer a single center experience of laparoscopic or laparotomic assisted ureteral stenting without the use of imaging guidance. Study design We recruited 19 patients in the Institute for Maternal and Child Health in Trieste (Italy) who underwent ureteral stenting between June 2017 and December 2018 for suspicious ureteral injury during gynecological surgery. Ureteral stents insertions were performed in all cases using rigid cystoscopes, hybrid guidewire with a hydrophilic coating, and double loop ureteral stents; the ureters were skeletonized during surgery and stents were used to permit better visualization of the ureteral whole and to prevent complications connected with the ureteral devascularization and minor not recognized ureteral injuries. All the procedures were performed under a laparoscopic or laparotomic guide. Results No sign of acute kidney failure was reported during the post-operative kidney functions evaluation. The right position of the stents was confirmed in the first postoperative day by ultrasonographic imaging. No major complications related to the urinary tract have been detected. Ten patients stated stent related symptoms well controlled by analgesic therapies. All stents were removed by office cystoscopies one month later without reporting any complication. Conclusions Introducing fluoroscopy or ultrasonographic imaging into the operative field could be difficult and time-consuming. Instead, the laparoscopic and laparotomic guided ureteral stenting without the use of imaging currently used in the standard clinical practice of many institutions even without an official standardization in order to treat or prevent ureteral injuries after the surgery, seems to be safe and feasible.

Objective: To identify the possible causes of spontaneous bladder rupture after normal vaginal delivery and to propose a diagnostic and therapeutic algorithm. Material and Methods: MEDLINE (PubMed), Web of Science and Scopus databases were searched up to August 2020. Manuscripts considered were published from 1990 and only English articles were included. The research strategy adopted included the following terms: (bladder rupture) AND (spontaneous) AND (delivery). 103 studies were identified. Duplicates were found through an independent manual screening. Subsequently, two authors independently screened the full text of articles and excluded those not pertinent to the topic. Discrepancies were resolved by consensus. Finally, thirteen studies were included. Results: PRISMA guidelines were followed. For each study, fetal weight, catheterization during labor, parity, maternal age, occurrence time, previous abdominal or pelvic surgery, symptoms complained of, diagnostic methods, and treatment were considered. Median age was 26.0 (range 20–34 years); median presentation time was 3.0 days after delivery (range 1–20 days); and median newborn weight was 3227.0 g (range 2685–3600 g). Catheterization during labor was reported only in four of the thirteen cases (30.8%) identified. The symptoms most frequently complained of were abdominal pain and distension, fever, oliguria, haematuria and vomiting. Instrumental diagnosis was performed using X-rays in five cases and computerized tomography in six cases. Ultrasound was chosen in five cases as a first diagnostic tool. In two cases, cystography was performed. Treatment was always laparotomic repair of the visceral defect. Conclusion: Abdominal pain, increased creatinine and other signs of kidney failure on blood tests should lead to suspicion of this complication. Cystourethrography is regarded as a procedure of choice, but a first ultrasound approach is recommended. The main factor for the therapeutic choice is the intraperitoneal or extraperitoneal rupture of the bladder. Classical management for intraperitoneal rupture of the bladder is surgical repair and urinary rest.

Uterine leiomyoma presents the highest incidence among benign tumors of the female reproductive tract. The present study compared the proteome of leiomyoma treated with ulipristal acetate with that of untreated leiomyoma to investigate protein expression patterns in relation to oxidative stress. Paired tissue samples from seven treated and untreated leiomyomas were collected and the proteome was analyzed by two‑dimensional gel electrophoresis (2‑DE). Western blotting was used to validate the results of 2‑DE, and mass spectrom‑ etry was used to identify proteins. The tissue expression of 30 proteins was markedly affected by treatment with ulipristal acetate. Bioinformatics analysis revealed that several of the differentially expressed proteins were involved in the degrada‑ tion of hydrogen peroxide and the synthesis of reactive oxygen species. The present study suggested the involvement of oxida‑ tive stress as a novel mechanism of action of ulipristal acetate. These findings require further investigations to understand the role of ulipristal acetate in the treatment of the leiomyoma.

Non-tubal ectopic pregnancies (NT-EPs) are rare but potentially life-threatening conditions. The incidence ranges are between 5&ndash, 8.3% of all ectopic pregnancies. For this retrospective observational study, 16 patients with NT-EP and treated from January 2014 to May 2020 were recruited. Demographic details, symptoms, Beta human chorionic gonadotrophin (&beta, hCG) levels, ultrasound findings, management and treatment outcomes were presented. In hemodynamically stable patients, diagnosis was made using ultrasounds and &beta, hCG levels. Laparoscopy was essential to identify and remove the ectopic pregnancy in clinical unstable patients. A radical laparoscopic approach was chosen in one case of cervical pregnancy diagnosed late in the first trimester. Medical treatment and minimally invasive procedure, alone or combined, resulted in effective strategies in asymptomatic women with an early diagnosis of NT-EP. We report cases of cervical pregnancies successfully treated by hysteroscopy alone or combined with medical treatment, the first case of scar pregnancy treated by mini-reseptoscope and curettage and the fifth case of interstitial pregnancy treated with Methotrexate and Mifepristone. In this manuscript we report a single center experience in the management of NT-EPs with the aim of outlining the importance of the early diagnosis for a minimally invasive treatment in order to reduce maternal morbidity and mortality and preserve future fertility.

Aims Despite catheter ablation (CA) has become an accepted treatment option for symptomatic, drug-resistant atrial fibrillation (AF), the safety of this procedure continues to be cause for concern. The aim of the present study was to assess the incidence of complications with permanent sequelae of CA for AF using open-irrigated catheters in a contemporary, unselected population of consecutive patients. Methods and results From 1 January 2011 to 31 December 2011, data from 2167 consecutive patients who underwent CA for AF using an open-irrigated catheter in 29 Italian centres were collected. All the complications occurring to the patient from admission to the 30th post-procedural day were recorded. No procedure-related death was observed. Complications occurred in 81 patients (3.7%): 46 patients (2.1%) suffered vascular access complications; 13 patients (0.6%) cardiac tamponade, successfully drained in all the cases; six patients (0.3%) arterial thromboembolism (four transient ischaemic attack and two ischaemic strokes); five (0.2%) patients conservatively treated pericardial effusion; three patients (0.1%) phrenic nerve paralysis; three patients (0.1%) pericarditis; three patients (0.1%) haemothorax, and two patients (0.1%) other isolated adverse events. At multivariate analysis, only female sex [odds ratio (OR) 2.5, confidence interval (CI): 1.5-3.7, P < 001] and the operator experience (OR 0.5, CI: 0.4-0.7, P < 001) related to the complications. Only five (0.2%) patients developed permanent sequelae from their complications. Conclusion Catheter ablation for AF with the use of open-irrigated catheters is currently affected by a very low rate of complications leading to permanent sequelae. © 2014 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014.

Objectives.We compared the efficacy of two different mapping techniques in identifying the ablation site for atrial tachycardia. Moreover, we evaluated the additive positive predictive value of mechanical interruption of atrial tachycardia to reduce the number of ineffective radiofrequency applications.Background.Radiofrequency catheter ablation has been suggested as a highly effective technique to treat drug-resistant atrial tachycardia. However, irrespective of the mapping technique utilized, success was most often achieved with a large number of radiofrequency applications.Methods.Forty-five patients with atrial tachycardia underwent radiofrequency catheter ablation. Mapping techniques included identification of earliest atrial activation and pace-mapping concordant sequence.Results.Atrial tachycardia was successfully treated in 42 (93.3%) of 45 patients with a mean of 3.9 radiofrequency pulses/ patient. An interval between the onset of the intracavitary atrial deflection and the onset of the P wave during atrial tachycardia (AP interval) ≥30 ms (p < 0.001) and pace-mapping concordant sequence (p = 0.01) were all significant predictors of outcome. An AP interval ≥30 ms and a pace-mapping concordant sequence were highly sensitive (92.8%, 95% confidence interval [CI] 80.5% to 98.5%; 85.7%, 95% CI 71.5% to 94.6%, respectively) but less specific (47.8%, 95% CI 37.9% to 58.2%; 36.8%, 95% CI 27.6% to 47.2%, respectively) in identifying the site of ablation. By using atrial tachycardia mechanical interruption combined with the AP interval >30 ms or the pace-mapping concordant sequence, we obtained a specificity of 76.5% (95% CI 66.4% to 84.0%) and 73.5% (95% CI 63.2% to 81.4%), respectively, and a positive predictive value of 49.2% and 44.6%, respectively.Conclusions.An AP interval ≥30 ms and a pace-mapping concordant sequence were reliable mapping features for predicting the outcome of the ablation procedure. Mechanical interruption of atrial tachycardia improved the specificity and positive predictive value of these two mapping techniques.

Background— Pulmonary veins (PVs) play a pivotal role in initiating and perpetuating atrial fibrillation (AF). We investigated if PV electrical isolation from the left atrium is required for curing AF. Methods and Result— Fifty-one patients with paroxysmal or persistent AF underwent circumferential radiofrequency ablation of PV ostia performed with an anatomic approach. The end point of the ablation procedure was the recording of low peak-to-peak bipolar potentials ( Conclusions— Our findings show that with the use of a pure anatomic approach, it is possible to prevent AF in >80% of patients undergoing catheter ablation. Moreover, the isolation of PVs is not crucial for curing AF.

OBJECTIVESWe tested the hypothesis that the response to flecainide infusion can identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic and ablation therapy reduces the recurrences of AF.BACKGROUNDInfusion of class IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter. Catheter ablation of atrial flutter has been demonstrated to be highly effective in preventing recurrences of atrial flutter.METHODSSeventy-one consecutive patients with paroxysmal or chronic AF, in whom flecainide infusion (2 mg/kg body weight, intravenously) determined the transformation of AF into common atrial flutter (positive response), were randomized to receive one of the following treatments: oral pharmacologic treatment with flecainide (group A, n = 23); the hybrid treatment (catheter ablation of the inferior vena cava-tricuspid annulus isthmus, plus oral flecainide) (group B, n = 24); or catheter ablation of the isthmus only (group C, n = 24). Thirty-seven patients with a negative response to flecainide, who chose to be submitted to the hybrid treatment, were selected as the control group (group D).RESULTSDuring a mean follow-up period of 24 ± 7.2 months, the recurrences of AF and atrial flutter in group B (42%) were significantly lower than those in group A (78%, p < 0.001), group C (92%, p < 0.001) and group D (92%, p < 0.001).CONCLUSIONSThe creation of a complete bi-directional conduction block at the inferior vena cava-tricuspid annulus isthmus, plus flecainide administration, reduces the recurrences of both AF and atrial flutter in patients with class IC atrial flutter. Moreover, the early response to flecainide is safe and reliable in identifying patients who may benefit from this therapy.

Inappropriate Sinus Tachycardia After Catheter Ablation. Introduction: Inappropriate sinus tachycardia (IST) has been observed following radiofrequency ablation (RFA) of the AV nodal fast pathway. This study was aimed to prospectively analyze the incidence and clinical significance of IST following RFA of para-Hisian accessory pathways (APs). Methods and Results: Twenty-eight patients (pts) with para-Hisian APs underwent RFA. An AP was defined as para-Hisian whenever its atrial and ventricular insertions were associated with a His-bundle potential ≥ 0.1 mV. RF current was always delivered at the atrial aspect of the tricuspid annulus. to a site where the His-bundle potential was < 0.15 mV. Time- and frequency-domain analysis of heart rate variability was performed in 22 patients, before and after RFA. Abolition of AP conduction was obtained in all pts, and no AV conduction alteration occurred. Six pts (21.4%) presented with IST 45 to 240 minutes after the ablation procedure. In 5 of them, IST disappeared spontaneously within 72 hours, whereas in 1 pt β-blockers were required for 2 months. The atrial potential amplitude (1.217 ± 0.264 mV vs 0.882 ± 0.173 mV, P = 0.009) and A/V potential amplitude ratio (2.633 vs 1.686, P = 0.05) were significantly higher in pts who developed IST than in those who did not. A marked decrease in heart rate variability was observed only in pts who developed IST. Conclusion: IST is a relatively frequent complication after RFA of para-Hisian APs: it is generally short-lasting and usually does not require any treatment. IST after catheter ablation is likely to depend upon transient parasympathetic denervation of the sinus node.

Otitis media (OM) affects the middle ear and is typically characterized by earache. OM may be classified as acute (AOM) or chronic (COM), based on symptom duration. OM may be clinically suspected, but the diagnosis is usually confirmed by the otoscopy. Antibiotic therapy is frequently used in clinical practice. However, antibiotics often induce intestinal and respiratory dysbiosis associated with some clinical problems. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3).

In this work, Dynamic Mode Decomposition (DMD) and Proper Orthogonal Decomposition (POD) methodologies are applied to hydroacoustic dataset computed using Large Eddy Simulation (LES) coupled with Ffowcs Williams and Hawkings (FWH) analogy. First, a low-dimensional description of the flow fields is presented with modal decomposition analysis. Sensitivity towards the DMD and POD bases truncation rank is discussed, and extensive dataset is provided to demonstrate the ability of both algorithms to reconstruct the flow fields with all the spatial and temporal frequencies necessary to support accurate noise evaluation. Results show that while DMD is capable to capture finer coherent structures in the wake region for the same amount of employed modes, reconstructed flow fields using POD exhibit smaller magnitudes of global spatiotemporal errors compared with DMD counterparts. Second, a separate set of DMD and POD modes generated using half the snapshots is employed into two data-driven reduced models respectively, based on DMD mid cast and POD with Interpolation (PODI). In that regard, results confirm that the predictive character of both reduced approaches on the flow fields is sufficiently accurate, with a relative superiority of PODI results over DMD ones. This infers that, discrepancies induced due to interpolation errors in PODI is relatively low compared with errors induced by integration and linear regression operations in DMD, for the present setup. Finally, a post processing analysis on the evaluation of FWH acoustic signals utilizing reduced fluid dynamic fields as input demonstrates that both DMD and PODI data-driven reduced models are efficient and sufficiently accurate in predicting acoustic noises.