Selective neck dissection of level IIB in cN0 laryngeal cancer: a systematic review and meta-analysis.

Purpose: The primary endpoint of the study was to quantitatively evaluate the presence of IIB neck level metastases in patients with laryngeal carcinoma, to provide valuable evidence to aid surgeons in the decision-making process for neck dissections. As a secondary aim this study analyzed the presence of factors that may be associated with a higher prevalence of metastasis.

Methods: Two independent authors (EE, MVV) searched for articles on PubMed, Cochrane, Embase, and Scopus databases.

Nonhealing Surgical Wounds in a Patient with Plasminogen Deficiency Type 1 Successfully Treated with Intravenous Plasminogen: A Case Report.

Intravenous plasminogen replacement therapy for patients with plasminogen deficiency type 1 (hypoplasminogenemia) was recently approved for marketing in the US. In this case report, the authors describe a 33-year-old man with hypoplasminogenemia who developed nonhealing postsurgical wounds following trauma to his right hand despite receiving standard treatment for 4 months. The patient was enrolled in a compassionate-use protocol with intravenous plasminogen replacement therapy and experienced prompt resolution of surgical wounds.

Plasminogen, human-tvmh for the treatment of children and adults with plasminogen deficiency type 1.

Aim: An open-label phase 2/3 study of plasminogen, human-tvmh administered intravenously in paediatric and adult subjects with type 1 plasminogen deficiency was conducted. Interim data was previously reported. The final data on 15 subjects who completed the study up to a maximum of 124 weeks are reported here.

Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment.

Acute respiratory distress syndrome (ARDS) is a severe complication of lung injuries, commonly associated with bacterial, fungal and viral infections, including SARS-CoV-2 viral infections. ARDS is strongly correlated with patient mortality and its clinical management is very complex, with no effective treatment presently available. ARDS involves severe respiratory failure, fibrin deposition in both airways and lung parenchyma, with the development of an obstructing hyaline membrane drastically limiting gas exchange.

A Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) for ovarian cancer.

Background: Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC).

Methods: pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence.

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas.

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines.

AXL-Receptor Targeted 14FN3 Based Single Domain Proteins (Pronectins™) from 3 Synthetic Human Libraries as Components for Exploring Novel Bispecific Constructs against Solid Tumors.

A highly specific AXL-receptor targeted family of non-immunoglobulin, single domain protein binders (Pronectins™) have been isolated from three (3) synthetic libraries that employ the human scaffold of the 14th domain of Fibronectin III (14FN3) and evolutionary CDRs diversity of over 25 billion loop sequences. The three libraries, each containing diversity in two loops, were designed to expand upon a human database of more than 6000 natural scaffold sequences and approximately 3000 human loop sequences. We used a bioinformatic-based approach to maximize "human" amino acid loop diversity and minimize or prevent altogether CDR immunogenicity created by the use of mutagenesis processes to generate diversity.

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox.

Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox (HD), containing 40-50% hydroxytyrosol, in counteracting the pain associated with FM.

Redox modulation of vitagenes via plant polyphenols and vitamin D: Novel insights for chemoprevention and therapeutic interventions based on organoid technology.

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol.

Hidrox and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, inflammation, oxidative stress, and pain. The aim of the study was to evaluate the anti-inflammatory and antioxidant effects of an oral administration of Hidrox (10 mg/kg) in the bladder and spinal cord in a rodent model of IC/BPS. The chronic animal model of cystitis was induced by repeated intraperitoneal injections of cyclophosphamide (CYP) for five consecutive days.

Hidrox Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model.

Background: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and apoptosis in the testes caused by its metabolite, acrolein.

Methods: The objective of this study was to evaluate the beneficial power of a new compound called Hidrox, containing 40-50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide.

Hidrox Roles in Neuroprotection: Biochemical Links between Traumatic Brain Injury and Alzheimer's Disease.

Traumatic brain injuries (TBI) are a serious public-health problem. Furthermore, subsequent TBI events can compromise TBI patients' quality of life. TBI is linked to a number of long- and short-term complications such as cerebral atrophy and risk of developing dementia and Alzheimer's Disease (AD).

Hidrox and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain.

Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox, an aqueous extract of olive pulp containing hydroxytyrosol, on endometriotic lesions associated with pro-oxidative alterations and pain-like behaviors.

The SARS-CoV-2-Inactivating Activity of Hydroxytyrosol-Rich Aqueous Olive Pulp Extract (HIDROX) and Its Use as a Virucidal Cream for Topical Application.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX) and evaluated its SARS-CoV-2-inactivating activity in vitro.

Repurposing of Plasminogen: An Orphan Medicinal Product Suitable for SARS-CoV-2 Inhalable Therapeutics.

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars.

Anti-inflammatory and Anti-oxidant Activity of Hidrox in Rotenone-Induced Parkinson's Disease in Mice.

Background: In developed countries, the extension of human life is increasingly accompanied by a progressive increase in neurodegenerative diseases, most of which do not yet have effective therapy but only symptomatic treatments. In recent years, plant polyphenols have aroused considerable interest in the scientific community. The mechanisms currently hypothesized for the pathogenesis of Parkinson's disease (PD) are neuroinflammation, oxidative stress and apoptosis.

Healthspan Enhancement by Olive Polyphenols in Wild Type and Parkinson's Models.

Parkinson's disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years.

Thromboembolic event rate in patients exposed to anti-inhibitor coagulant complex: a meta-analysis of 40-year published data.

Anti-inhibitor coagulant complex (AICC), an activated prothrombin complex concentrate, has been available for the treatment of patients with inhibitors since 1977, and thromboembolic events (TEEs) have been reported after infusion of AICC in patients with congenital or acquired hemophilia. With the aim of estimating the TEE incidence rate (IR) related to AICC exposure in these patients, a systematic review of the literature was carried out in Medline, according to PRISMA guidelines, from inception date to March 2017. The IR of TEEs was estimated through a meta-analytic approach by using a generalized linear mixed model based on a Poisson distribution.

Cost-effectiveness analysis of pharmacokinetic-driven prophylaxis vs. standard prophylaxis in patients with severe haemophilia A.

: The objective of this study was to assess the cost-effectiveness of pharmacokinetic-driven prophylaxis in severe haemophilia A patients. A microsimulation model was developed to evaluate the cost-effectiveness of pharmacokinetic-driven prophylaxis vs. standard prophylaxis and estimate cost, annual joint bleed rate (AJBR), and incremental cost-effectiveness ratio over a 1-year time horizon for a hypothetical population of 10 000 severe haemophilia A patients.

Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease.

Alzheimer disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline, neuropsychiatric symptoms, disability, caregiver burden, and premature death. It represents the most prevalent cause of dementia, and its incidence rates exponentially increase with increasing age. The number of Americans living with AD is rapidly increasing.

An innovative outcome-based care and procurement model of hemophilia management.

Hemophilia is a rare bleeding disorder associated with spontaneous and post-traumatic bleeding. Each hemophilia patient requires a personalized approach to episodic or prophylactic treatment, but self-management can be challenging for patients, and avoidable bleeding may occur. Patient-tailored care may provide more effective prevention of bleeding, which in turn, may decrease the likelihood of arthropathy and associated chronic pain, missed time from school or work, and progressive loss of mobility.

Immune tolerance induction in patients with haemophilia a and inhibitors: effectiveness and cost analysis in an European Cohort (The ITER Study).

Introduction: Although immune tolerance induction (ITI) is considered the first choice treatment to eradicate inhibitors in haemophilia A patients, little is known about outcomes determinants and cost magnitude.

Aim And Methods: A retrospective, multicentre study was conducted to assess the relationship between ITI outcome, clinical and treatment characteristics and cost of ITI treatment in haemophilia A patients. Data from 12 months before inhibitor diagnosis to 12 months after ITI completion were collected.

NF-κβ signaling and chronic inflammatory diseases: exploring the potential of natural products to drive new therapeutic opportunities.

Chronic inflammation has a key role in the pathogenesis of multiple diseases that represent major public health and financial concerns, including heart failure (HF), Alzheimer's disease (AD) and arthritis. Nuclear factor kappa β (NF-κβ) is a central component of inflammation; owing to its upstream signaling position, it is considered an attractive target for new anti-inflammatory therapeutics. Hydroxytyrosol is an orally bioavailable polyphenol, obtained from olives, which inhibits NF-κβ activity and has elicited promising efficacy signals in several inflammatory diseases.