Fatty-acid amide hydrolase inhibition mitigates Alzheimer's disease progression in mouse models of amyloidosis.

The endocannabinoid N-arachidonoylethanolamine (AEA) is a pro-homeostatic bioactive lipid known for its anti-inflammatory, anti-oxidative, immunomodulatory, and neuroprotective properties, which may contrast/mitigate Alzheimer's disease (AD) pathology. This study explores the therapeutic potential of targeting fatty acid amide hydrolase (FAAH), the major enzyme degrading AEA, in mouse models of amyloidosis (APP/PS1 and Tg2576). Enhancing AEA signaling by genetic deletion of FAAH delayed cognitive deficits in APP/PS1 mice and improved cognitive symptoms in 12-month-old AD-like mice.

Primary Peristalsis Is the Dominant Mechanism of Refluxate Clearance Following Gastroesophageal Reflux.

Background: Refluxate volume and pH drop following gastroesophageal reflux are mostly cleared by peristalsis. We evaluated the roles of primary volume clearing peristaltic wave (VCPW), secondary VCPW, post-reflux swallow-induced peristaltic wave (PSPW), and late primary peristaltic wave (LPPW) in refluxate clearance.

Methods: We retrospectively analyzed pH-impedance studies performed off therapy in 40 patients with typical esophageal symptoms.

Topical Protection of Esophageal Mucosa as a New Treatment of GERD.

Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients.

Oral selective estrogen receptor degraders for breast cancer treatment: focus on pharmacological differences.

Purpose: The management of hormone receptor-positive (HR +) breast cancer (BC) relies on endocrine therapy (ET), with a primary focus on disrupting estrogen receptor (ER) signaling due to its critical role in BC tumorigenesis and progression. While effective for both early-stage and advanced breast cancers, ET frequently encounters resistance mechanisms, including both ligand-dependent and ligand-independent trajectories, ultimately leading to disease progression.

Methods: We searched PubMed, EMBASE and Scopus databases to review the current evidence on the use of novel oral selective estrogen receptor degraders (SERDs) for the treatment of HR+ BC.

Differential expression of plasma proteins and pathway enrichments in pediatric diabetic ketoacidosis.

Background: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case-control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables.

Methods: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes.

Two-Step Surgical Strategy for Parathyroid Carcinoma: A Single-Center Experience.

Parathyroid carcinoma (PC) is a rare endocrine malignancy that poses significant diagnostic challenges due to its resemblance to benign conditions. This case series describes the clinical presentation, diagnosis, management, and short-term outcomes of four male patients (aged 54, 65, 73, and 74 years) with primary hyperparathyroidism and hypercalcemia. The preoperative diagnosis of PC remains challenging; suspicion should arise in cases of severe hypercalcemia, elevated parathyroid hormone levels, and the presence of a mass on imaging or during surgery.

The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit.

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials.

Dynamic reconfiguration of aperiodic brain activity supports cognitive functioning in epilepsy: A neural fingerprint identification.

Temporal lobe epilepsy (TLE) is characterized by alterations of brain dynamic on a large-scale associated with altered cognitive functioning. Here, we aimed at analyzing dynamic reconfiguration of brain activity, using the neural fingerprint approach, to delineate subject-specific characteristics and their cognitive correlates in TLE. We collected 10 min of resting-state scalp-electroencephalography (EEG, 128 channels), free from epileptiform activity, from 68 TLE patients and 34 controls.

Metabolomic signature of pediatric diabetic ketoacidosis: key metabolites, pathways, and panels linked to clinical variables.

Background: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case-control study utilized plasma metabolomics to explore metabolic alterations associated with DKA and to identify predictive metabolite patterns.

Histological Subtypes Might Help Risk Stratification in Different Morphological Types of IPMNs: Back to the Future?

Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated.

Concomitant Popliteomeniscal Fascicles Tears Are Found in 21% of Professional Soccer Players With Acute Anterior Cruciate Ligament Injuries.

Purpose: To investigate the incidence of popliteomeniscal fascicles (PMF) tears in anterior cruciate ligament (ACL) rupture in professional soccer players, to describe arthroscopic and magnetic resonance imaging (MRI) findings and treatment of these lesions with clinical outcomes, and to evaluate the incidence of subsequent lateral meniscus tears and ACL reinjury.

Methods: ACL reconstructions on soccer players were retrospectively analyzed, and among them, a cohort of patients with PMFs tears was reviewed. The cohort was assessed with MRI examination, arthrometric testing, Lysholm score, and International Knee Documentation Committee score.

A possible role of e-FAST in the hemodynamically stable polytrauma patient: results of a single trauma center preliminary restrospective study.

Purpose: The purpose of this work is to evaluate whether EFAST can also play a role in the hemodynamically stable polytrauma patient, without delaying his arrival in the CT-scan room.

Methods: In a period of seven month, 748 polytrauma patients were retrospective valued; we analyzed the findings of the CT exams of 485 haemodynamically stable patients for whom the EFAST investigation was not requested, highlighting the possible presence of findings that, if reported during the EFAST, could have changed the patient management.

Results: 52 hemodynamically stable patients with CT examination findings potentially detectable by ultrasound examination directly in the shock room, which represent a percentage of about 11% of all the hemodynamically stable patients analyzed; about 54% of CT findings are represented by the presence of pneumothorax.

Esophageal chest pain resembles heartburn in reflux metrics and response to proton pump inhibitor therapy.

Background: Gastro-esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms.

Aims/methods: To assess whether particular patterns of impedance-pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high-resolution manometry (HRM) and impedance-pH, were included.

Autograft Choice and Jumping Performance After Anterior Cruciate Ligament Reconstruction: A Comparative Study on Professional Athletes.

Background: The extensor apparatus of the knee is of paramount importance in generating the torque needed for a countermovement jump (CMJ), especially in jumping athletes. In anterior cruciate ligament reconstruction (ACLR) procedures, graft harvesting from the extensor apparatus may dramatically affect extensor strength and jumping performance.

Hypothesis: The focused jump training of professional jumping athletes would increase the likelihood of restoring jumping performance after ACLR, despite the graft choice (autologous bone-patellar tendon-bone [BPTB] or hamstring [HS] tendon).

Machine learning-derived clinical decision algorithm for the diagnosis of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism.

Purpose: To train and validate machine learning-derived clinical decision algorithm (CDA) for the diagnosis of hyperfunctioning parathyroid glands using preoperative variables to facilitate surgical planning.

Methods: This retrospective study included 458 consecutive primary hyperparathyroidism (PHPT) patients who underwent combined 4D-CT and sestamibi SPECT/CT (MIBI) with subsequent parathyroidectomy from February 2013 to September 2016. The study cohort was divided into training (first 400 patients) and validation sets (remaining 58 patients).

An International, Expert-Based Delphi Consensus Document on Controversial Issues about TransCarotid Artery Revascularization (TCAR).

Background: Transcarotid artery revascularization (TCAR) has emerged as an alternative therapeutic modality to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) for the management of patients with carotid artery stenosis. However, certain issues regarding the indications and contraindications of TCAR remain unanswered or unresolved. The aim of this international, expert-based Delphi consensus document was to attempt to provide some guidance on these topics.

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy.

Background: Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.

Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.

ACEF vs PARIS score in Predicting Cardiovascular Events in Patients With Acute Coronary Syndrome: Insights From the START ANTIPLATELET Registry.

Several scores can predict clinical outcomes of patients with Acute Coronary Syndromes (ACS). The validated PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) score is poorly used in clinical practice because it needs items that are not always easily available. The ACEF (Age, Creatinine, and Ejection Fraction) score is more attractive because it only includes three items.

Comparison between Three Radiomics Models and Clinical Nomograms for Prediction of Lymph Node Involvement in PCa Patients Combining Clinical and Radiomic Features.

Purpose: We aim to compare the performance of three different radiomics models (logistic regression (LR), random forest (RF), and support vector machine (SVM)) and clinical nomograms (Briganti, MSKCC, Yale, and Roach) for predicting lymph node involvement (LNI) in prostate cancer (PCa) patients.

Materials And Methods: The retrospective study includes 95 patients who underwent mp-MRI and radical prostatectomy for PCa with pelvic lymphadenectomy. Imaging data (intensity in T2, DWI, ADC, and PIRADS), clinical data (age and pre-MRI PSA), histological data (Gleason score, TNM staging, histological type, capsule invasion, seminal vesicle invasion, and neurovascular bundle involvement), and clinical nomograms (Yale, Roach, MSKCC, and Briganti) were collected for each patient.