Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

A comparison of traditional and net structured intersomatic cages in the lombosacral region: A biomechanical analysis for enhancing discopathy treatment.

The vertebral column represents an essential element for support, mobility, and the protection of the central nervous system. Various pathologies can compromise these vital functions, leading to pain and a decrease in the quality of life. Within the scope of this study, a novel redesign of the Intersomatic Cage, traditionally used in the presence of discopathy, was proposed.

Treatment of peri-implant mucositis: Adjunctive effect of glycine powder air polishing to professional mechanical biofilm removal. 12 months randomized clinical study.

Introduction: To evaluate the adjunctive effect of glycine-powder air-polishing (GPAP) to full-mouth ultrasonic debridement (Fm-UD) in the treatment of peri-implant mucositis, and to determine the impact of implant and patient-level variables for disease resolution.

Methods: Individuals with a diagnosis of peri-implant mucositis were consecutively included in this randomized parallel arm clinical study. All the participants received a session of Fm-UD.

Detection of cell-free histones in the cerebrospinal fluid of pediatric central nervous system malignancies by imaging flow cytometry.

Pediatric brain tumours (PBT) are one of the most common malignancies during childhood, with variable severity according to the location and histological type. Certain types of gliomas, such a glioblastoma and diffuse intrinsic pontine glioma (DIPG), have a much higher mortality than ependymoma and medulloblastoma. Early detection of PBT is essential for diagnosis and therapeutic interventions.

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer.

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, 'real-world' data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program.

Neuropsychological Evaluation and Quantitative EEG in Patients with Frontotemporal Dementia, Alzheimer's Disease, and Mild Cognitive Impairment.

This study analyzed the efficacy of EEG resting state and neuropsychological performances in discriminating patients with different forms of dementia, or mild cognitive impairment (MCI), compared with control subjects. Forty-four patients with dementia (nineteen patients with AD, and seven with FTD), eighteen with MCI, and nineteen healthy subjects, matched for age and gender, underwent an extensive neuropsychological test battery and an EEG resting state recording. Results showed greater theta activation in posterior areas in the Alzheimer's disease (AD) and Fronto-Temporal Dementia (FTD) groups compared with the MCI and control groups.

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from , a multicentric, observational study.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available.

L1CAM expression in human gastrointestinal tract development: From tongue to colon-rectum.

Background: L1CAM (L1 cell adhesion molecule) is a member of the L1 family of neural adhesion molecules, involved in the development of multiple organs and tissues, including kidneys, the enteric nervous system, and adrenal glands. The aim of this study was to analyze, at the immunohistochemical level, the expression of L1CAM in the human tongue, parotid glands, and the different segments of the gastrointestinal tract during human development.

Design And Method: Immunohistochemical analysis for L1CAM was performed in the human tongue, parotid glands, and in the different segments of the gastrointestinal tract during development, starting from the 8th up to the 32nd week of gestation.

Primary thromboprophylaxis in not surgically treated intra-luminal gastrointestinal cancer (ILGC) treated with first-line chemotherapy: A single institution preliminary safety report.

Occurrence of venous thromboembolism in cancer patients (patients) undergoing chemotherapy is a remarkable concern for the oncologist. In addition, careful attention has to be paid to the possible major bleeding when patients carrying gastrointestinal cancer need antithrombotic therapies. To date some Cancer Associated Thrombosis (CAT) risk scores as Khorana and PROTECHT score have been developed to identify the cancer population at high-risk for venous thromboembolism (VTE).

Human centenarian-associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids.

Non-alcoholic fatty liver disease (NAFLD), encompassing fatty liver and its progression into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), is one of the rapidly rising health concerns worldwide. SIRT6 is an essential nuclear sirtuin that regulates numerous pathological processes including insulin resistance and inflammation, and recently it has been implicated in the amelioration of NAFLD progression. SIRT6 overexpression protects from formation of fibrotic lesions.

Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases.

The incidence and the burden of cardiovascular disease (CVD), coronary heart disease (CHD), type 2 diabetes mellitus (T2DM), and the metabolic syndrome are greatly increasing in our societies. Together, they account for 31% of all deaths worldwide. This chapter focuses on the role of two revolutionary discoveries that are changing the future of medicine, induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 technology, in the study, and the cure of cardiovascular and metabolic diseases.

Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and adolescents, increasing the risk of its progression toward nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. There is an urgent need for noninvasive early diagnostic and prognostic tools such as epigenetic marks (epimarks), which would replace liver biopsy in the future. We used plasma samples from 67 children with biopsy-proven NAFLD, and as controls we used samples from 20 children negative for steatosis by ultrasound.

The costs and benefits of senotherapeutics for human health.

Cellular senescence is a major contributor to age-related diseases in humans; however, it also has a beneficial role in physiological and pathological processes, including wound healing, host immunity, and tumour suppression. Reducing the burden of cell senescence in animal models of cardiometabolic disorders, inflammatory conditions, neurodegenerative diseases, and cancer using pharmaceutical approaches that selectively target senescent cells (ie, senolytics) or that suppress senescence-associated secretory phenotype (ie, senomorphics) holds great promise for the management of chronic age-associated conditions. Although studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans, the short-term and long-term side-effects of these therapies are largely unknown.

GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β-catenin and ALK5/SMAD2/3 pathways.

Objective: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue.

Methods: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines.

Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion.

Recent studies suggest that PGC1-α plays a crucial role in mitochondrial and vascular function, yet the physiological significance of PGC1α and HO expression in adipose tissues in the context of obesity-linked vascular dysfunction remains unclear. We studied three groups of six-week-old C57BL/6J male mice: (1) mice fed a normal chow diet; (2) mice fed a high-fat diet (H.F.

PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting.

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients.

Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020.

Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects.

Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC®Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics.

Bioactive Compounds from Lemon () Extract Overcome TNF-α-Induced Insulin Resistance in Cultured Adipocytes.

The consumption of plant-based food is important for health promotion, especially regarding the prevention and management of chronic diseases such as diabetes. We investigated the effects of a lemon extract (LE), containing ≥20.0% total flavanones and ≥1.

Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin.

Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death.

Milk thistle seed cold press oil attenuates markers of the metabolic syndrome in a mouse model of dietary-induced obesity.

Milk thistle cold press oil (MTO) is an herbal remedy derived from Silybum marianum which contains a low level of silymarin and mixture of polyphenols and flavonoids. The effect of MTO on the cardiovascular and metabolic complications of obesity was studied in mice that were fed a high-fat diet (HFD) for 20 weeks and treated with MTO for the final 8 weeks of the diet. MTO treatment attenuated HFD-induced obesity, fasting hyperglycemia, hypertension, and induced markers of mitochondrial fusion and browning of white adipose.

Cold Press Pomegranate Seed Oil Attenuates Dietary-Obesity Induced Hepatic Steatosis and Fibrosis through Antioxidant and Mitochondrial Pathways in Obese Mice.

Aim: Obesity is associated with metabolic syndrome, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. In this study, we investigated whether the dietary supplementation of pomegranate seed oil (PSO) exerted a protective effect on liver lipid uptake, fibrosis, and mitochondrial function in a mouse model of obesity and insulin resistance.

Method: In this in vivo study, eight-week-old C57BL/6J male mice were fed with a high fat diet (HFD) for 24 weeks and then were divided into three groups as follows: group (1) Lean; group ( = 6) (2) HF diet; group ( = 6) (3) HF diet treated with PSO (40 mL/kg food) ( = 6) for eight additional weeks starting at 24 weeks.

Senescence-like phenotype in post-mitotic cells of mice entering middle age.

Staining mice tissues for β-galactosidase activity is a fundamental tool to detect age- or disease-associated cellular senescence. However, reported analyses of positivity for senescence-associated β-galactosidase activity or for other markers of senescence in post-mitotic cells of healthy murine tissues have been fragmentary or inconclusive. Here, we attempted to independently deepen this knowledge using multiple senescence markers within the same cells of wild type mice entering middle age (9 months of age).