Ageing and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19.

CD8+ T cells are critical for immune protection against severe COVID-19 during acute infection with SARS-CoV-2. However, the induction of antiviral CD8+ T cell responses varies substantially among infected people, and a better understanding of the mechanisms that underlie such immune heterogeneity is required for pandemic preparedness and risk stratification. In this study, we analyzed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in relation to age, clinical status, and inflammation among patients infected primarily during the initial wave of the pandemic in France or Japan.

Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX.

Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Design, Setting, And Participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018.

Early intervention in eating disorders: introducing the chronopathogram.

Eating disorders (EDs) pose significant challenges to mental and physical health, particularly among adolescents and young adults, with the COVID-19 pandemic exacerbating risk factors. Despite advancements in psychosocial and pharmacological treatments, improvements remain limited. Early intervention in EDs, inspired by the model developed for psychosis, emphasizes the importance of timely identification and treatment initiation to improve prognosis.

Long-term durability and temporal pattern of revisional surgery of laparoscopic large hiatal hernia repair.

Laparoscopic repair is the preferred surgical treatment for symptomatic Large Hiatal Hernia (LHH). However, data on long-term outcomes are limited. This study aims to evaluate the 20-year follow-up results of laparoscopic LHH repair in a high-volume experienced tertiary center.

Pricing for Multi-Indication Drugs in the Italian Regulatory Context.

Background: The authorization of new therapeutic indications for drugs already reimbursed by the Italian National Health Service (NHS) represents a matter of importance. This study aims to estimate the additional discount attributed to the extension of indications (EoIs) to explore the potential correlation between spending and negotiated discounts and to find specific factors (determinants) that impact on discount.

Methods: The study focused on drugs approved in Italy between 2003 and 2017 with at least four therapeutic indications, including the first approved and EoIs, with follow-up extended until 2021 to acquire all the information on the negotiation process that has been completed.

Systematic review of the needs and health-related quality of life domains relevant to people surviving cancer in Europe.

Purpose: To systematically review qualitative studies on outcomes, needs, experiences, preferences, concerns and health-related quality of life (HRQoL) of people surviving cancer in Europe in the last decade.

Methods: Protocol registered ( https://www.crd.

Painful diabetic neuropathy is associated with accelerated epigenetic aging.

About one out of two diabetic patients develop diabetic neuropathy (DN), of these 20% experience neuropathic pain (NP) leading to individual, social, and health-economic burden. Risk factors for NP are largely unknown; however, premature aging was recently associated with several chronic pain disorders. DNA methylation-based biological age (DNAm) is associated with disease risk, morbidity, and mortality in different clinical settings.

Real-Life Experience with Tildrakizumab in Plaque Psoriasis with Palmoplantar Involvement: A Multi-Center Retrospective Italian Study.

Introduction: Palmoplantar psoriasis (PPp) has a profound negative impact on patients' quality of life, and it represents a therapeutic challenge, as palms and soles are difficult to treat area. Although the efficacy profile of tildrakizumab has been well evaluated in the literature, data on its use for PPp are still limited. The objective of the study was to evaluate the efficacy and safety of tildrakizumab on moderate-to-severe plaque psoriasis with involvement of the palmoplantar area.

Cocaine and aortic dissection: the need for collaboration to overcome the underreporting bias.

The dissection of the aorta is a serious and potentially fatal consequence of cocaine use. Nonetheless, the underlying mechanisms and characteristics of this phenomenon remain to be deeply studied. The autopsy case of a 46-year-old white male found irresponsive and unconscious in his house and had a history of abusing cocaine is presented.

Fecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in South American camelids and biosecurity practices among farms in northern Italy.

South American camelids (SACs), particularly llamas (Lama glama) and alpacas (Vicugna pacos) are gaining popularity in Europe. Initially valued for their fiber and land management capabilities, these animals are now also kept for animal therapy, outdoor activities, and as companion animals. Despite their close interactions with humans and other animals, there is limited research on the transmission of microbes or antimicrobial resistance genes from SACs.

Folate metabolism in myelofibrosis: a missing key?

Folates serve as key enzyme cofactors in several biological processes. Folic acid supplementation is a cornerstone practice but may have a "dark side". Indeed, the accumulation of circulating unmetabolized folic acid (UMFA) has been associated with various chronic inflammatory conditions, including cancer.

PARP12-mediated ADP-ribosylation contributes to breast cancer cell fate by regulating AKT activation and DNA-damage response.

Breast cancer represents the primary cause of death of women under 65 in developed countries, due to the acquisition of multiple drug resistance mechanisms. The PI3K/AKT pathway is one of the major regulating mechanisms altered during the development of endocrine resistance and inhibition of steps in this signalling pathway are adopted as a key strategy to overcome this issue. ADP-ribosylation is a post-translational modification catalysed by PARP enzymes that regulates essential cellular processes, often altered in diseases.

The Brussels consensus for non-invasive ICP monitoring when invasive systems are not available in the care of TBI patients (the B-ICONIC consensus, recommendations, and management algorithm).

Background: Invasive systems are commonly used for monitoring intracranial pressure (ICP) in traumatic brain injury (TBI) and are considered the gold standard. The availability of invasive ICP monitoring is heterogeneous, and in low- and middle-income settings, these systems are not routinely employed due to high cost or limited accessibility. The aim of this consensus was to develop recommendations to guide monitoring and ICP-driven therapies in TBI using non-invasive ICP (nICP) systems.

Survey of legislative frameworks and national recommendations governing paediatric maintenance haemodialysis in Europe.

Background: The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries.

Methods: A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires.

Selenium Nucleophilicity and Electrophilicity in the Intra- and Intermolecular SN2 Reactions of Selenenyl Sulfide Probes.

Chalcogenide exchange reactions are an important class of bimolecular nucleophilic substitution reactions (SN2) involving sulfur and selenium species as nucleophile, central atom, and/or leaving group, which are fundamental throughout redox biology and metabolism. While thiol-disulfide exchange reactions have been deeply investigated, those involving selenium are less understood, especially with regards to the polarised selenenyl sulfides RSe-SR' even though the directed reactivity of selenenyl sulfides is biologically crucial for selenoenzymes such as thioredoxin reductase (TrxR) and glutathione peroxidase (GPx). Synthetic methods to create asymmetric selenenyl sulfides with high regiochemical purity only emerged over the last five years; this functional group has already demonstrated powerful applications to cell biology, through probes for molecular imaging (e.

Factors that affect alginates: a brief review.

Alginates are widely used in dentistry for various applications due to their favorable properties, including ease of use, cost-effectiveness, and patient comfort. They are commonly employed for preliminary impressions of oral structures in dental practice. This study aims to assess the impact of different factors on the performance of alginate impression materials in dentistry.

Pro-angiogenic VEGF inhibition by cadaverine and hydrocinnamic acid metabolites: impairment of periodontal regeneration due to periodontal inflammation.

Background: Cadaverine and hydrocinnamic acid are frequent metabolites in inflamed periodontal areas. Their role as a metabolite for plant growth inhibition has been established, but their relevance in humans has yet to be determined. Moreover, Vascular endothelial growth factor (VGEF) is a consistent growth factor in neo-angiogenesis in periodontal regeneration.

Ovarian clear cell carcinoma: open questions on the management and treatment algorithm.

Ovarian clear cell carcinoma (OCCC) accounts for ~10% of all epithelial ovarian cancers and is considered a different entity from the more common high-grade serous ovarian carcinoma (HGSC), with distinct clinical presentations, different risk, and prognostic factors, and specific molecular features. Most OCCCs are diagnosed at an early stage and show favorable outcomes, in contrast to those diagnosed at advanced stages, which exhibit intrinsic resistance to platinum-based chemotherapy regimens and a very poor prognosis. The standard treatment of advanced OCCC is currently based on primary debulking surgery followed by platinum-based chemotherapy according to recent international guidelines.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Digital therapeutics as a new weapon against diseases: focus on the current European legislation and possible therapeutic strategies.

Introduction: Digital therapeutics (DTx) are an emerging phenomenon within the scientific landscape which is attracting considerable international interest. This review aimed to provide an overview of the definition and classification of DTx, focusing on the contribution that DTx may provide in the treatment of a lot of diseases, compared with pharmacological treatments and highlighting it strengthens and weaknesses into the European regulatory landscape.

Areas Covered: They are software-generated therapeutic interventions directly to patients useful to prevent, manage or treat diseases.

Characterization of different clinical presentation of Merkel cell carcinomas and their potential prognostic implications.

Background: Recent studies analyzed the impact of Merkel cell polyomavirus (MCPyV) on the prognosis of Merkel cell carcinoma (MCC) patients. No data on specific morphological clinical differences of MCPyV+ or MCPyV- are currently available neither on the possible prognostic implication of different clinical presentation of MCC.

Objectives: 1) to describe clinicopathological characteristics of MCC patients and the prevalence of MCPyV infection in an Italian cohort of patients; 2) to define possible differences in clinicopathological and prognostic features among MCPyV+ and MCPyV- MCCs.

Prognostic utility of assessing ventricular-arterial coupling in arterial hypertension and cardiovascular diseases.

The assessment of myocardial function and its coupling with the arterial system, called ventricular-arterial coupling (VAC), is of paramount importance in many clinical fields, from arterial hypertension, which is the main cause of cardiovascular diseases and death, to heart failure. VAC has been the subject of studies for several decades both from an energetic cost and the impact it can exert on cardiovascular performance. Although more attention has been paid to the relationship between the left ventricle and the left arterial circuit in compromised hemodynamic stages, VAC has aroused interest in many other aspects of study, from its application in pathologies of the right sections of the heart to its clinical impact in prevention and cardiovascular risk factors.