Uterine venous malformations in the puerperium: 2 Atypical cases and literature review.

Uterine arteriovenous malformations (AVMs) is a rare but high-risk cause of uterine bleeding. The clinical management of this condition is challenging, as the ultrasound picture can sometimes be unambiguously interpreted. Moreover, in the puerperium in which acquired AVMs are most frequently formed, it is necessary to discuss the correct management in a multidisciplinary and personalized manner. We present two cases of AVMs developing in the puerperium, both with a vaginal delivery and spontaneous and complete secondment. The symptom of onset was an episode of bright red blood loss in the puerperium, on the 14th and 21st postpartum days, respectively. Transvaginal ultrasound showed a hypervascularized lesion in the myometrium with turbulent vascular flow, confirmed by transabdominal ultrasound and angiography. To date, there are no guidelines on the management of MAVs. In our cases we opted for a conservative approach, in order to preserve the fertility of the patient. These experiences reported have the purpose of enriching a literature still sparse on the subject and in the future to be able to represent a fulcrum for official recommendations.

State-of-the-Art and Upcoming Innovations in Pancreatic Cancer Care: A Step Forward to Precision Medicine.

Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in the last two decades. The incidence of pancreatic cancer is increasing, and it continues to be associated with high mortality and morbidity rates. The difficulty of early diagnosis (the lack of specific symptoms and biomarkers at early stages), the aggressiveness of the disease, and its resistance to systemic therapies are the main factors for the poor prognosis of pancreatic cancer. The only curative treatment for pancreatic cancer is surgery, but the vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. Pancreatic surgery is among the most challenging surgical procedures, but recent improvements in surgical techniques, careful patient selection, and the availability of minimally invasive techniques (e.g., robotic surgery) have dramatically reduced the morbidity and mortality associated with pancreatic surgery. Patients who are not candidates for surgery may benefit from locoregional and systemic therapy. In some cases (e.g., patients for whom marginal resection is feasible), systemic therapy may be considered a bridge to surgery to allow downstaging of the cancer; in other cases (e.g., metastatic disease), systemic therapy is considered the standard approach with the goal of prolonging patient survival. The complexity of patients with pancreatic cancer requires a personalized and multidisciplinary approach to choose the best treatment for each clinical situation. The aim of this article is to provide a literature review of the available treatments for the different stages of pancreatic cancer.

Office intrauterine morcellation for retained products of conception.

OBJECTIVE: Proposing hysteroscopic morcellation (HM) as a surgical-therapeutic approach in the treatment of retained products of conception (RPOC) to prevent intrauterine adhesions (IUAs). DESIGN: Prospective analysis. SETTING: A teaching and university hospital. PATIENTS: Women with RPOC. INTERVENTIONS: Office -HM with 'Truclear 5 C'. MATERIAL AND METHODS: Twenty-two consecutive patients presenting with trophoblastic residue retention after miscarriage and interruption of pregnancy or placenta remnants after cesarean section or delivery were enrolled. These women underwent office-HM with 'Truclear 5 C'. Primary outcomes were median time and rate of hospitalization. The quality of the specimen was also analyzed. A hysteroscopic second look for IUAs was performed. RESULTS: Mean procedure time was six minutes (SD ± 5). Tissue samples had a mean collection size 2.5 cm3+0.9. 38% of the samples had spotting or abnormal vaginal discharge. Dilatation of the cervical canal was not performed in any case. Second-look hysteroscopy did not show any de novo IUAs in any of the enrolled patients. CONCLUSIONS: In the hysteroscopic treatment of RPOC, HM is a valid choice in an office setting without the use of cervical dilatation. Removal of RPOC was uneventful in all cases, simple and carried out faster without any adverse outcomes.

Cesarean scar pregnancy: a practical overview and our series of combined double step procedure management.

BACKGROUND: Cesarean scar pregnancy (CSP), a rare iatrogenic form of ectopic pregnancy (EP), cause of severe maternal morbidity. Each subtype of CSP needs different treatment and there is no consensus about this topic. Despite improvements, the lack of universally accepted therapeutic management and discordance present in literature indicates that treatment has been mainly based on experiences reported. METHODS: A case series of our double combined approach with methotrexate (MTX) administration followed by vacuum aspiration or resectoscopic approach was reported, with an overview of literature. Eleven patients with CSP underwent a double-step treatment: systemic MTX therapy followed by vacuum aspiration or by resectoscopy, if the gestational sac was embedded deeply in myometrium. For CSP type 1, according to Delphi sonographic classification, with minor potentially risk of complications with a myometrial thickness >3.5 mm, we preferred to adopt vacuum aspiration, while type 2-3 of CSP and myometrial thickness ≤3.5mm were managed with resectoscopy. RESULTS: The average gestational age was 59.1±7.22 days. On the seventh day after MTX administration, the serum ß hCG levels decreased in 80% of all patients. After the MTX injection, the CSP mass did not disappear in any patient. MTX therapy was followed by vacuum aspiration in six and by resectoscopy in five cases. In one case bleeding was controlled by Foley balloon treated with vacuum. In type II-III, CSP was performed UAE (uterine artery embolization) followed by resectoscopy procedure. CONCLUSIONS: Compared with the results in previous studies, MTX administration followed by suction curettage was more effective than dilatation and curettage and systemic MTX in treatment of CSP. We consider very useful this procedure in case of slow absorption and when the camera was embedded deeply in myometrium (CSP2-3), because that hysteroscopy evaluation of uterine cavity under direct vision is highly accurate in identifying the real cleavage of the gestational camera. We have only used vacuum aspiration in CSP type 1 for minor risk of bleeding.

Robotic Sacrocolpopexy with Autologous Fascia Lata: A Case Series.

Objectives: Apical prolapse involves the upper vagina or vaginal vault after hysterectomy. Treatment is indicated for symptomatic women, and surgical approach is considered for women who failed or refused conservative therapy. We performed 10 pickups of autologous fascia, used for robotic sacrocolpopexy (RSCP). Materials and Methods: We included patients between 60 and 80 years old who showed a Pelvic Organ Prolapse Quantification (POP-q) over the second stage and with symptoms related to prolapse. Results: All of them underwent autologous fascia lata (AFL) pickup from the right leg and after to RSCP. One patient underwent also posterior colporrhaphy. The mean intraoperative time was 199.2 min (183-230 min). No intra-operatory complications were reported. POP-q assessment during follow-up showed improvements: C point gained on average 7.6 points (5-8) and mean values went from -0.6 to - 8.2 cm (-7 to -9 cm). The three women who had anterior compartment defects shows good anatomical reconstitution with a mean Aa and Ba value of - 2.83 cm (-2.5 to -3 cm) and gained 4 points (average gain: 3.5-4.5 cm). Total vaginal lenght (TVL). Conclusion: According to these data, in our experience, AFL employment showed a good anatomical result from the first to last follow-up.

Immune Response and Transplacental Antibody Transfer in Pregnant Women after COVID-19 Vaccination.

COVID-19 infection is associated with increased risk of pregnancy complications, making vaccination during pregnancy critical for mother-neonate dyads. Few data, often with an unrepresentative sample size, are available on SARS-CoV-2 vaccine-induced humoral and cell-mediated response. Here, we evaluated anti-S antibody and interferon-gamma (IFN-γ) production elicited by SARS-CoV-2 immunization in maternal and neonatal plasma. Pregnant women (n = 230) were prospectively enrolled and classified as unvaccinated (n = 103) and vaccinated (n = 127); after serological screening for previous infections, assays were performed on 126 dyads, 15 mothers and 17 newborns. Positive anti-S antibodies were found in most of the vaccinated subjects, regardless of timespan between immunization and delivery (range: 7-391 days). A total of 89 of 92 vaccinated women showed a broad response to COVID-19 immunization and highly effective placental transfer, as attested by anti-S positive rates (maternal = 96.7%, cord = 96.6%). Most of our subjects had indeterminate results in an IGRA assay, preventing a conclusive evaluation of IFN-γ production. Indeed, pregnancy-related hormonal changes may influence T-cell response with an impact on IFN-γ production. Positive pregnancy and perinatal outcomes reinforce the evidence that the anti-SARS-CoV-2 immunization is effective and well-tolerated in pregnant women and also protective for the fetus/neonate, even though it was not possible to define the related IFN-γ production and role.

Role of Akkermansia in Human Diseases: From Causation to Therapeutic Properties.

The gut microbiota plays a critical role in the modulation of host metabolism and immune response, and its impairment has been implicated in many gastrointestinal and extraintestinal diseases. Current evidence shows the well-documented role of A. muciniphila in maintaining the integrity of the intestinal barrier, modulating the host immune response, and improving several metabolic pathways, making it a key element in the pathogenesis of several human diseases. In this scenario, A. muciniphila is the most promising next-generation probiotic and one of the first microbial species suitable for specific clinical use when compared with traditional probiotics. Further studies are needed to provide more accurate insight into its mechanisms of action and to better elucidate its properties in several major areas, paving the way for a more integrated and personalized therapeutic approach that finally makes the most of our knowledge of the gut microbiota.

Nutrition in Acute Pancreatitis: From the Old Paradigm to the New Evidence.

The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The "pancreatic rest" was the cornerstone of the old paradigm, and nutritional support was not even included in AP management. Traditional management of AP was based on intestinal rest, with or without complete parenteral feeding. Recently, evidence-based data underlined the superiority of early oral or enteral feeding with significantly decreased multiple-organ failure, systemic infections, surgery need, and mortality rate. Despite the current recommendations, experts still debate the best route for enteral nutritional support and the best enteral formula. The aim of this work is to collect and analyze evidence over the nutritional aspects of AP management to investigate its impact. Moreover, the role of immunonutrition and probiotics in modulating inflammatory response and gut dysbiosis during AP was extensively studied. However, we have no significant data for their use in clinical practice. This is the first work to move beyond the mere opposition between the old and the new paradigm, including an analysis of several topics still under debate in order to provide a comprehensive overview of nutritional management of AP.

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls.

Polyneuropathies (PNP) are the most common type of disorder of the peripheral nervous system in adults. However, information on microRNA expression in PNP is lacking. Following microRNA sequencing, we compared the expression of microRNAs in the serum of patients experiencing chronic painful PNP with healthy age-matched controls. We have been able to identify four microRNAs (hsa-miR-3135b, hsa-miR-584-5p, hsa-miR-12136, and hsa-miR-550a-3p) that provide possible molecular links between degenerative processes, blood flow regulation, and signal transduction, that eventually lead to PNP. In addition, these microRNAs are discussed regarding the targeting of proteins that are involved in high blood flow/pressure and neural activity dysregulations/disbalances, presumably resulting in PNP-typical symptoms such as chronical numbness/pain. Within our study, we have identified four microRNAs that may serve as potential novel biomarkers of chronic painful PNP, and that may potentially bear therapeutic implications.

Cellular therapies in liver and pancreatic diseases.

Over the past two decades, developments in regenerative medicine in gastroenterology have been greatly enhanced by the application of stem cells, which can self-replicate and differentiate into any somatic cell. The discovery of induced pluripotent stem cells has opened remarkable perspectives on tissue regeneration, including their use as a bridge to transplantation or as supportive therapy in patients with organ failure. The improvements in DNA manipulation and gene editing strategies have also allowed to clarify the physiopathology and to correct the phenotype of several monogenic diseases, both in vivo and in vitro. Further progress has been made with the development of three-dimensional cultures, known as organoids, which have demonstrated morphological and functional complexity comparable to that of a miniature organ. Hence, owing to its protean applications and potential benefits, cell and organoid transplantation has become a hot topic for the management of gastrointestinal diseases. In this review, we describe current knowledge on cell therapies in hepatology and pancreatology, providing insight into their future applications in regenerative medicine.

A strategy to formulate data-driven constitutive models from random multiaxial experiments.

We present a test technique and an accompanying computational framework to obtain data-driven, surrogate constitutive models that capture the response of isotropic, elastic-plastic materials loaded in-plane stress by combined normal and shear stresses. The surrogate models are based on feed-forward neural networks (NNs) predicting the evolution of state variables over arbitrary increments of strain. The feasibility of the approach is assessed by conducting virtual experiments, i.e. Finite Element (FE) simulations of the response of a hollow, cylindrical, thin-walled test specimen to random histories of imposed axial displacement and rotation. In these simulations, the specimen's material is modelled as an isotropic, rate-independent elastic-plastic solid obeying J2 plasticity with isotropic hardening. The virtual experiments allow assembling a training dataset for the surrogate models. The accuracy of two different surrogate models is evaluated by performing predictions of the response of the material to the application of random multiaxial strain histories. Both models are found to be effective and to have comparable accuracy.

Exaggerated Placental Site as a Cause of Hysterectomy for Massive Bleeding After First Trimester Voluntary Abortion.

Objectives: Placental implantation anomalies in first-trimester abortions may determine severe bleeding leading to hysterectomy. There are very few cases of urgent hysterectomy post-abortion reported in the literature, related to placenta accreta spectrum, but in any of them is considered association with benign trophoblastic lesions. Methods: We report the case of a woman, who underwent surgical voluntary abortion by vacuum aspiration during first trimester, without any apparent surgical complications. Immediately, after this procedure, the patient had massive vaginal bleeding; an emergency hysterectomy was performed. Histological examination showed an exaggerated placental site (EPS). Results: Morphological findings describe a trophoblastic tumor-like lesion, which differs from placenta accreta and often considered an asymptomatic occasional feature. Proliferative index, evaluated by double immunostain for CK8-18 and Ki-67, was unremarkable (<1%). Conclusions: Only a single report in the literature describes a case of symptomatic EPS 65 after first-trimester abortion. Major attention should be paid to trophoblastic pathology in order to understand a possible relationship with uterine bleeding and to find a clinical, ultrasound or chemical indicator.

A Surgical Technique to Preserve the Subvalvular Apparatus in Patients Undergoing Mitral Valve Replacement for Severe Ischemic Regurgitation

ABSTRACT Severe functional mitral valve regurgitation should be treated in patients undergoing myocardial revascularization. When replacement is considered the best therapeutic option, preservation of the mitral subvalvular apparatus is crucial, especially in the emergency setting, because of its primary role in preserving geometry and function of left and right ventricles. Here we present a simple and quick technique, where subvalvular apparatus is preserved in toto in patients undergoing mitral valve replacement with a bioprosthesis.

Transient Receptor Potential Vanilloid 1 Signaling Is Independent on Protein Kinase A Phosphorylation of Ankyrin-Rich Membrane Spanning Protein.

The sensory ion channel transient receptor potential vanilloid 1 (TRPV1) is mainly expressed in small to medium sized dorsal root ganglion neurons, which are involved in the transfer of acute noxious thermal and chemical stimuli. The Ankyrin-rich membrane spanning protein (ARMS) interaction with TRPV1 is modulated by protein kinase A (PKA) mediating sensitization. Here, we hypothesize that PKA phosphorylation sites of ARMS are crucial for the modulation of TRPV1 function, and that the phosphorylation of ARMS is facilitated by the A-kinase anchoring protein 79 (AKAP79). We used transfected HEK293 cells, immunoprecipitation, calcium flux, and patch clamp experiments to investigate potential PKA phosphorylation sites in ARMS and in ARMS-related peptides. Additionally, experiments were done to discriminate between PKA and protein kinase D (PKD) phosphorylation. We found different interaction ratios for TRPV1 and ARMS mutants lacking PKA phosphorylation sites. The degree of TRPV1 sensitization by ARMS mutants is independent on PKA phosphorylation. AKAP79 was also involved in the TRPV1/ARMS/PKA signaling complex. These data show that ARMS is a PKA substrate via AKAP79 in the TRPV1 signaling complex and that all four proteins interact physically, regulating TRPV1 sensitization in transfected HEK293 cells. To assess the physiological and/or therapeutic significance of these findings, similar investigations need to be performed in native neurons and/or in vivo.

Clinical Implications of Helicobacter pylori Antibiotic Resistance in Italy: A Review of the Literature.

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a "high priority" pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment.

Autoimmune Pancreatitis: From Pathogenesis to Treatment.

Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.

A Surgical Technique to Preserve the Subvalvular Apparatus in Patients Undergoing Mitral Valve Replacement for Severe Ischemic Regurgitation.

Severe functional mitral valve regurgitation should be treated in patients undergoing myocardial revascularization. When replacement is considered the best therapeutic option, preservation of the mitral subvalvular apparatus is crucial, especially in the emergency setting, because of its primary role in preserving geometry and function of left and right ventricles. Here we present a simple and quick technique, where subvalvular apparatus is preserved in toto in patients undergoing mitral valve replacement with a bioprosthesis.

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. METHODS: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. RESULTS: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). CONCLUSION: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.