Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis.

Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis.

Raman imaging for monitoring deuterated squalene-gemcitabine nanomedicines in single living breast cancer cells.

We have investigated the impact of gemcitabine (Gem) and deuterated gemcitabine-squalene (GemSQ-d6) nanoparticles (NPs) on MCF7 and MDA-MB-231 breast cancer cell lines by Raman spectroscopy. Quantification of LDL expression levels in both cell lines revealed a four-fold increase in MDA-MB-231 cells compared to MCF7 cells. In in vitro antitumor assessments, Gem displayed 13.

Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double-blind placebo-controlled crossover trial.

Objective: To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure.

Methods: We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded.

A gold nanocluster/MIL-100(Fe) bimodal nanovector for the therapy of inflammatory disease through attenuation of Toll-like receptor signaling.

A better understanding of the molecular and cellular events involved in the inflammation process has opened novel perspectives in the treatment of inflammatory diseases, particularly through the development of well-designed nanomedicines. Here we describe the design of a novel class of anti-inflammatory nanomedicine (denoted as Au@MIL) synthesized through a one-pot, cost-effective and green approach by coupling a benchmark mesoporous iron(III) carboxylate metal organic framework (MOF) ( MIL-100(Fe)) and glutathionate protected gold nanoclusters ( AuSG NCs). This nano-carrier exhibits low toxicity and excellent colloidal stability combined with the high loading capacity of the glucocorticoid dexamethasone phosphate (DexP) whose pH-dependent delivery was observed.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials.

Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used.

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited.

Multicellular tumor spheroid model to study the multifaceted role of tumor-associated macrophages in PDAC.

While considerable efforts have been made to develop new therapies, progress in the treatment of pancreatic cancer has so far fallen short of patients' expectations. This is due in part to the lack of predictive in vitro models capable of accounting for the heterogeneity of this tumor and its low immunogenicity. To address this point, we have established and characterized a 3D spheroid model of pancreatic cancer composed of tumor cells, cancer-associated fibroblasts, and blood-derived monocytes.

The carbon cost of inappropriate endoscopy.

Background And Aims: Digestive endoscopy is a resource-intensive activity with a conspicuous carbon footprint and an estimated rate of inappropriateness. However, the carbon costs of inappropriate endoscopic procedures still remain obscure. Here we evaluated the environmental impact of inappropriate endoscopic examinations.

Immediate Prepectoral Implant-Based Breast Reconstruction after J-Pattern Skin-Reducing Mastectomy.

Summary: Skin-reducing mastectomy for single-stage reconstruction is an oncologically safe procedure used in women with large and ptotic breasts. This study describes a new technique, the J-pattern skin-reducing breast reconstruction with prepectoral implant and acellular dermal matrix (Braxon fast), which is indicated for patients with large and ptotic breasts who would benefit from a breast reduction and need a mastectomy for curative or prophylactic purposes. The authors present a case series of 35 breasts of 19 women who underwent this procedure from January of 2021 through December of 2022 at the Plastic and Reconstructive Surgery Department of the University Hospital Santa Maria della Misericordia, in Udine, Italy, with a median follow-up of 15 months.

Optimizing Acellular Dermal Matrix Integration in Heterologous Breast Reconstructive Surgery: Surgical Tips and Post-Operative Management.

: Prepectoral implant placement in breast reconstruction is currently a must-have in the portfolios of breast surgeons. The introduction of new tools and conservative mastectomies is a game changer in this field. The prepectoral plane usually goes hand-in-hand with the ADM wrapping of the implant.

Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies.

Background: Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant. However, this classification is largely based on expert opinion and no proper evidence exists to date to support its possible prognostic and clinical impact.

Methods: This analysis included individual patient-level data from 4 adjuvant phase III randomized trials by the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups.

Hierarchical superparamagnetic metal-organic framework nanovectors as anti-inflammatory nanomedicines.

Among a plethora of drug nanocarriers, biocompatible nanoscale metal-organic frameworks (nanoMOFs) with a large surface area and an amphiphilic internal microenvironment have emerged as promising drug delivery platforms, mainly for cancer therapy. However, their application in biomedicine still suffers from shortcomings such as a limited chemical and/or colloidal stability and/or toxicity. Here, we report the design of a hierarchically porous nano-object (denoted as USPIO@MIL) combining a benchmark nanoMOF (that is, MIL-100(Fe)) and ultra-small superparamagnetic iron oxide (USPIO) nanoparticles (that is, maghemite) that is synthesized through a one-pot, cost-effective and environmentally friendly protocol.

From Sub-Pectoral to Pre-Pectoral Implant Reconstruction: A Decisional Algorithm to Optimise Outcomes of Breast Replacement Surgery.

Background: Innovations and advancements with implant-based breast reconstruction, such as the use of ADMs, fat grafting, NSMs, and better implants, have enabled surgeons to now place breast implants in the pre-pectoral space rather than under the pectoralis major muscle. Breast implant replacement surgery in post-mastectomy patients, with pocket conversion from retro-pectoral to pre-pectoral, is becoming increasingly common, in order to solve the drawbacks of retro-pectoral implant positioning (animation deformity, chronic pain, and poor implant positioning).

Materials And Methods: A multicentric retrospective study was conducted, considering all patients previously submitted to implant-based post-mastectomy breast reconstruction who underwent a breast implant replacement with pocket conversion procedure at the University Hospital of Udine-Plastic and Reconstructive Surgery Department-and "Centro di Riferimento Oncologico" (C.

Validation study for in vitro skin irritation test using reconstructed human skin equivalents constructed by layer-by-layer cell coating technology.

The aim of this study is to validate an in vitro skin irritation test (SIT) using three-dimensional reconstructed human epidermal (RhE) skin equivalents prepared by layer-by-layer (LbL) method (LbL-3D Skin) in a series of interlaboratory studies. The goal of these validation studies is to evaluate the ability of this in vitro test to reliably discriminate skin irritant from nonirritant chemicals, as defined by OECD and UN GHS. This me-too validation study is to assess the within- and between-laboratory reproducibility, as well as the predictive capacity, of the LbL-3D Skin SIT in accordance with performance standards for OECD TG 439.

Plasma membrane lipid bilayer is druggable: Selective delivery of gemcitabine-squalene nano-medicine to cancer cells.

Up to now the lipid bilayers were rarely considered as targets in cancer therapy despite pronounced differences in lipid composition between plasma membranes of benign and malignant cells. In this study we demonstrate that the lipid bilayer of the plasma membrane is druggable and suitable for facilitating selective delivery of amphiphilic gemcitabine-squalene nanomedicines to cancer cells. Data from radioactive assays, fluorescent membrane probes and molecular dynamics simulations provide evidence of selective accumulation of gemcitabine-squalene in the plasma membranes with disrupted lipid asymmetry and its subsequent preferential uptake by malignant cells.

Sustainability in gastroenterology and digestive endoscopy: Position Paper from the Italian Association of Hospital Gastroenterologists and Digestive Endoscopists (AIGO).

Climate crisis is dramatically changing life on earth. Environmental sustainability and waste management are rapidly gaining centrality in quality improvement strategies of healthcare, especially in procedure-dominant fields such as gastroenterology and digestive endoscopy. Therefore, healthcare interventions and endoscopic procedures must be evaluated through the 'triple bottom line' of financial, social, and environmental impact.

Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application.

Electromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth.

Before in vivo studies: In vitro screening of sphingomyelin nanosystems using a relevant 3D multicellular pancreatic tumor spheroid model.

Sphingomyelin nanosystems have already shown to be promising carriers for efficient delivery of anticancer drugs. For further application in the treatment of pancreatic tumor, the investigation on relevant in vitro models able to reproduce its physio-pathological complexity is mandatory. Accordingly, a 3D heterotype spheroid model of pancreatic tumor has been herein constructed to investigate the potential of bare and polyethylene glycol-modified lipid nanosystems in terms of their ability to penetrate the tumor mass and deliver drugs.

Patients' Question-Asking About Breast Implant-Associated Anaplastic Large Cell Lymphoma (BI-ALCL) and Breast Implant Illness (BII): Implementing Questions in BREAST-Q.

There has been recently heightened media-driven attention to BII and BI-ALCL. Nowadays the importance of receiving correct and complete evidence-based information about these diseases and the potential impact of these emerging issues on disposition to receive breast implants are not investigated on BREAST-Q. The BREAST-Q survey has the potential to create an evidence-based approach to aesthetic surgical practice.

Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial.

Background: The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2-3 years of letrozole in postmenopausal patients with breast cancer who have already received 2-3 years of tamoxifen.

Methods: This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy.

Gemcitabine lipid prodrug nanoparticles: Switching the lipid moiety and changing the fate in the bloodstream.

A simple approach to achieve a lipoprotein (LP)-mediated drug delivery is to trigger the spontaneous drug insertion into endogenous lipoproteins in the bloodstream, by means of its chemical modification. Nanoparticles (NPs) made of the squalene-gemcitabine (SQGem) conjugate were found to have a high affinity for plasma lipoproteins while free gemcitabine did not, suggesting a key role of the lipid moiety in this event. Whether the drug conjugation to cholesterol, one of the major lipoprotein-transported lipids, could also promote an analogous interaction was a matter of question.

An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study.

Background: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets.