Model-based prediction of effective target exposure for MEN1611 in combination with trastuzumab in HER2-positive advanced or metastatic breast cancer patients.

MEN1611 is a novel orally bioavailable PI3K inhibitor currently in clinical development for patients with HER2-positive (HER2+) PI3KCA mutated advanced/metastatic breast cancer (BC) in combination with trastuzumab (TZB). In this work, a translational model-based approach to determine the minimum target exposure of MEN1611 in combination with TZB was applied. First, pharmacokinetic (PK) models for MEN1611 and TZB in mice were developed.

Epicardial Dispersion of Repolarization Promotes the Onset of Reentry in Brugada Syndrome: A Numerical Simulation Study.

The Brugada syndrome (BrS) is a cardiac arrhythmic disorder responsible for sudden cardiac death associated with the onset of ventricular arrhythmias, such as reentrant ventricular tachycardia and fibrillation. The mechanisms which lead to the onset of such electrical disorders in patients affected by BrS are not completely understood, yet. The aim of the present study is to investigate by means of numerical simulations the electrophysiological mechanisms at the basis of the morphology of electrocardiogram (ECG) and the onset of reentry associated with BrS.

Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys.

Objective: COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.

Methods: The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing).

Surveillance in a Neonatal Intensive Care Unit Allowed the Isolation of a Strain of VIM-Producing .

Here, we describe the isolation of a strain of the genus encoding a VIM carbapenemase, the first to our knowledge. The strain, isolated from a rectal swab of a 10-day-old newborn admitted to a neonatal intensive care unit (NICU), was identified through whole-genome sequencing analyses as . The strain harbored the carbapenemases gene .

Closed hyperthermic intraperitoneal chemotherapy with CO recirculation system compared with the open Coliseum technique in peritoneal malignity treatment.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: first, the standard open abdominal technique (Open HIPEC); or second, the closed technique. In recent years, a new technique has been introduced to perform closed HIPEC; the Peritoneal Recirculation System (PRS-1.0 Combat) with CO recirculation technology (PRS Closed HIPEC).

Could Celiac Disease and Overweight/Obesity Coexist in School-Aged Children and Adolescents? A Systematic Review.

Celiac disease (CD) is a multifactorial, immune-mediated enteropathic disorder that may occur at any age with heterogeneous clinical presentation. In the last years, unusual manifestations have become very frequent, and currently, it is not so uncommon to diagnose CD in subjects with overweight or obesity, especially in adults; however, little is known in the pediatric population. This systematic review aims to evaluate the literature regarding the association between CD and overweight/obesity in school-age children.

RGD Cyclopeptide Equipped with a Lysine-Engaging Salicylaldehyde Showing Enhanced Integrin Affinity and Cell Detachment Potency.

Salicylaldehyde (SA) derivatives are emerging as useful fragments to obtain reversible-covalent inhibitors interacting with the lysine residues of the target protein. Here the SA installation at the C terminus of an integrin-binding cyclopeptide, leading to enhanced ligand affinity for the receptor as well as stronger biological activity in cultured glioblastoma cells is reported.

Meta-Analysis on Long-Term Outcomes of Pediatric Renal Cancer Survivors Following COG and SIOP Protocols.

Background:  Pediatric renal cancer survivors have higher rate of chronic renal disease and hypertension. These patients have similar survival rates when treated according to either Children's Oncology Group (COG) or International Society of Pediatric Oncology (SIOP) protocols. We aimed to compare the late outcome of these two approaches.

Running Away from the War in Ukraine: The Impact on Mental Health of Internally Displaced Persons (IDPs) and Refugees in Transit in Poland.

A growing body of research highlights how communities traumatized by conflict and displacement suffer from long-term mental and psychosocial illnesses. The Russian army's attack on Ukraine has resulted in an estimated 10 million people being internally or externally displaced from Ukraine, of whom more than 3.8 million have left Ukraine to seek refuge elsewhere in Europe.

[Anti-inflammatory therapies for cardiovascular diseases: novel evidence, clinical implications, and future perspectives].

Inflammation plays an important role in cardiovascular disease. Growing evidence suggests a profound involvement of the inflammatory response in the development and progression of atherosclerosis and its complications. In patients with atherosclerotic cardiovascular disease (ASCVD), residual cardiovascular risk often remains high despite optimal medical therapy and the achievement of the therapeutic targets recommended by current guidelines.

Postoperative apnea after pyloromyotomy for infantile hypertrophic pyloric stenosis.

Objective: Infantile hypertrophic pyloric stenosis (IHPS), which causes gastric outlet obstruction and hypochloremic hypokalemic metabolic alkalosis, could pose a risk of postoperative apnea in patients. The aim of this study is to evaluate the incidence of postoperative apnea in babies admitted to a tertiary-level pediatric surgical center in Milano, Italy with diagnosis of IHPS in 2010-2019. The secondary objective is to evaluate the risk factors for postoperative apnea.

Identification of genomic regions associated with total and progressive sperm motility in Italian Holstein bulls.

Sperm motility is directly related to the ability of sperm to move through the female reproductive tract to reach the ovum. Sperm motility is a complex trait that is influenced by environmental and genetic factors and is associated with male fertility, oocyte penetration rate, and reproductive success of cattle. In this study we carried out a GWAS in Italian Holstein bulls to identify candidate regions and genes associated with variations in progressive and total motility (PM and TM, respectively).

The daily swab test collection problem.

Digital Contact Tracing (DCT) has been proved to be an effective tool to counteract the new SARS-CoV-2 or Covid-19. Despite this widespread effort to adopt the DCT, less attention has been paid to the organisation of the health logistics system that should support the tracing activities. Actually, the DCT poses a challenge to the logistics of the local health system in terms of number of daily tests to be collected and evaluated, especially when the spreading of the virus is soaring.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce.

Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.

Design, Setting, And Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant).

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey.

Objectives: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs).

Methods: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included.

Should attention be paid to the cone depth in the fully visible transformation zone? Retrospective analysis of 517 patients with cervical intraepithelial neoplasia grade 3.

Objective: The predictors of positive endocervical margin (EM) and a cone-depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high-grade cervical intraepithelial neoplasia (CIN) and fully visible TZ.

Methods: The current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019.

A Nanofocused Light on Stradivari Violins: Infrared s-SNOM Reveals New Clues Behind Craftsmanship Mastery.

It is well-known that all the phases of the manufacturing influence the extraordinary aesthetic and acoustic features of Stradivari's instruments. However, these masterpieces still keep some of their secrets hidden by the lack of documentary evidence. In particular, there is not a general consensus on the use of a protein-based ground coating directly spread on the wood surface by the Cremonese Master.