A large-scale database of T-cell receptor beta sequences and binding associations from natural and synthetic exposure to SARS-CoV-2.

We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 160,000 high-confidence SARS-CoV-2-associated TCRs. This database is made freely available, and the data contained in it can be used to assist with global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.

Pathophysiology and diagnostic criteria of PCOS.

Introduction: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic syndrome mainly characterized by ovarian dysfunction, which is only one manifestation of a more complex syndrome with a significant systemic impact.

Evidence Acquisition: We review scientific literature on the pathophysiology and diagnosis of PCOS evaluating the most relevant data from original articles, reviews and meta-analyses published until June 2024.

Evidence Synthesis: From a pathophysiological point of view, the concurrence of both metabolic aspects, such as insulin resistance and obesity, and hormonal alterations, such as hyperandrogenemia, might produce the most relevant clinical signs and/symptoms of this syndrome, for instance menstrual irregularities, hair loss, acne and hirsutism.

The oral GnRH antagonists, a new class of drugs in gynecology: from pharmacokinetics to possible clinical applications.

Introduction: In ovarian steroid-dependent diseases such as uterine fibroids, endometriosis and adenomyosis, oral GnRH antagonists have emerged as new therapeutic alternatives. These oral GnRH antagonists offer key advantages, including oral administration, dose-dependent estrogen suppression and rapid reversibility.

Areas Covered: This review examines the pharmacological, clinical and therapeutic profiles of the latest non-peptide oral GnRH antagonists, through an analysis of clinical evidence and randomized clinical trials, to provide a comprehensive and up-to-date overview of their clinical applications and potential benefits.

Presurgical treatment of uterine myomas with the GnRH-antagonist relugolix in combination therapy: an observational study.

To evaluate if a preoperative medical treatment with the GnRH-antagonist relugolix in combination therapy in a series of patients with abnormal uterine bleeding associated with uterine myomas may correct the anemia before scheduled surgery for myoma-associated AUB. Thirty-one patients scheduled for surgery underwent a pre-operative three-month course with a daily oral tablet of 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.

Inhibition ratio (I.R.) and transformation index (T.I.): new indexes to compare the effectiveness and clinical behaviour of modern progestin-only pills (POP).

Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.

The Role of Different Medical Therapies in the Management of Adenomyosis: A Systematic Review and Meta-Analysis.

: Adenomyosis is a benign condition characterized by the presence of endometrial tissue within the myometrium. Despite surgery being a valuable approach, medical options are considered as the first-line approach and have been investigated in the treatment of adenomyosis, although strong evidence in favor of these is still lacking. This study aims to gather all available data and determine the effectiveness of the aforementioned medical options in patients with associated pain and not currently seeking pregnancy, both in comparison to placebo and to one another.

Fertility potential and safety assessment of residual ovarian cortex in young women diagnosed with epithelial borderline and early-stage malignant ovarian tumors.

Objective: To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool.

Methods: Multicentric retrospective study of 48 subjects (15-45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68.

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.

Use of oral GnRH antagonists combined therapy in the management of symptomatic uterine fibroids.

Uterine fibroids have an impact on women's lives due to their high prevalence, physical symptoms, their consequences on patients' emotional and psychological well-being and loss of work productivity. The choice of therapeutical approaches varies depending on several factors, and therefore should be applied individually. Currently, there is an unmet need for good, reliable, uterine-sparing options.

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

Purpose: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis.

Materials And Methods: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history.

Periodontitis, female fertility and conception (Review).

Periodontal disease (PD) has been shown to increase the risk of preterm birth, preeclampsia and low birth weight. These observations have suggested that PD may also affect the early phase of pregnancy, including conception. The present study aimed to evaluate whether an association exists between oral health status and the chance of clinical pregnancy, according to the currently published literature, by performing a systematic review.

Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias.

We investigated antibody and coronavirus disease 2019 (COVID-19)-specific T-cell mediated responses via ultra-deep immunosequencing of the T-cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike-receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ-78436735. A total of 56 patients underwent TCR immunosequencing after vaccination.

Surgery versus IVF for the treatment of infertility associated to ovarian and deep endometriosis (SVIDOE: Surgery Versus IVF for Deep and Ovarian Endometriosis). Clinical protocol for a multicenter randomized controlled trial.

The management of endometriosis-related infertility is still a challenging issue. Women can be managed with either surgery or in vitro fertilization (IVF). The decision is tailored to the patients considering pros and cons of both approaches.

COVID-19 susceptibility in endometriosis patients: A case control study.

Problem: Starting from November 2019, the world has had to face a devastating pandemic caused by SARS-CoV-2. Various studies have identified potential risk factors facilitating the infection, however it has not been demonstrated whether endometriosis might represent one of them. The purpose of this study was to evaluate if patients with endometriosis had a higher risk of contracting COVID-19 infection and, in such case, whether they developed a more severe infection than the general population.

'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.

Objectives: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis.

Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study).

Introduction: The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester.

An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A.

Background: Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target.

Methods: In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L).

An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission.

Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR).

Patients And Methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months.

Results: Eight patients (53.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

Purpose: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy.

Methods: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded.

mTOR inhibitors and risk of ovarian cysts: a systematic review and meta-analysis.

Objective: To summarise the available evidence on frequency of ovarian cyst development during mammalian target of rapamycin inhibitors (mTORi) treatment.

Methods: PubMed/Medline and EMBASE databases were searched, from 1990 up to March 2020, using the following keywords: 'tacrolimus', 'sirolimus', 'temsirolimus', 'everolimus', 'deforolimus', 'mTOR' and 'ovarian cysts' (Limit: Human, English, full article). Studies were selected for the review if they met the following criteria: clinical studies, studies reporting original data, studies reporting the number of patients using mTORi, studies reporting the number of patients with ovarian cysts.

CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes.

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to inhibitors, little is known about the immune microenvironment in relation to patient prognosis.

Methods: We performed a retrospective study of 61 patients with DDLPS.

Impact of optimizing pre-analytical phase on the diagnosis of gestational diabetes and related outcomes.

Objectives: Pre-analytical plasma glucose (PG) sampling methodology may significantly affect gestational diabetes mellitus (GDM) incidence, but no studies directly examined the impact on perinatal outcomes. We compared the effect on oral glucose tolerance test (OGTT) results of using for blood sampling the traditional sodium fluoride (NaF) tubes, batched at controlled temperature, and the more effective citrate-buffered tubes, in terms of GDM diagnosis and related outcomes.

Methods: We evaluated 578 pregnant women performing OGTT between 24- and 28-weeks' gestation.