Could a Risk-adapted Approach Support Shared Decision-making Regarding Eligibility for Adjuvant Pembrolizumab for Patients with Clear Cell Renal Cell Carcinoma at High Risk of Recurrence? A Multicentre Cohort Study.

The KEYNOTE-564 randomised controlled trial showed a disease-free survival benefit of adjuvant pembrolizumab (aPZB) in comparison to placebo for patients with clear cell renal cell carcinoma (ccRCC) at high risk of recurrence. Despite its recommendation by the European Association of Urology guidelines, the ultimate value of aPZB has recently been questioned. Arguably, patients who might benefit the most from aPZB are those whose probability of RCC recurrence outweighs their probability of dying from other causes over a reasonable timeframe after surgery.

A bioartificial and vasculomorphic bone matrix-based organoid mimicking microanatomy of flat and short bones.

We engineered an in vitro model of bioartificial 3D bone organoid consistent with an anatomical and vascular microenvironment common to mammalian flat and short bones. To achieve this, we chose the decellularized-decalcified matrix of the adult male rat scapula, implemented with the reconstruction of its intrinsic vessels, obtained through an original intravascular perfusion with polylevolactic (PLLA), followed by coating of the PLLA-fabricated vascularization with rat tail collagen. As a result, the 3D bone and vascular geometry of the native bone cortical and cancellous compartments was reproduced, and the rat tail collagen-PLLA biomaterial could in vitro act as a surrogate of the perivascular extracellular matrix (ECM) around the wall of the biomaterial-reconstituted cancellous vessels.

Male obesity: Associated effects on fertility and the outcomes of offspring.

Obesity rates are increasing globally, making it imperative to comprehend the effects of parental obesity on human reproduction. This review aims to highlight the impact of male obesity on reproductive and offspring outcomes. Male obesity has been shown to affect fertility through various mechanisms, including changes in semen quality, difficulty with natural conception, and worsened assisted reproductive technology outcomes.

Who are the superheroes? A cross-sectional study on the determinants of good health among Italian older adults.

Background: People who reach old age enjoying good physical and mental health can be defined as (health) "superheroes", given their relatively low impact on healthcare expenditure and the desirable model they represent.

Aim: To evaluate prevalence and possible determinants of being "physical superheroes" (i.e.

Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.

Background: Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION).

Aim: We investigated the risk for SRD, RVO, and ION in patients using PDE5is.

Methods: We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.

A taxonomy of early diagnosis research to guide study design and funding prioritisation.

Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis.

In Between the Psychological and Physiological Self - The Impact of Covid-19 Pandemic on the Neuro-Socio-Ecological and Inflammatory Mind-Body-Brain System.

The COVID-19 pandemic has had a profound impact on individuals' sense of self perturbating the sense of connectedness with the others, touching upon deep existential fears and deep intersubjective and cultural layers, emphasizing the importance of a neuro-socio-ecological alignment for the sense of security of psychological self. We can still observe after years how social distancing measures, quarantines, and lockdowns have disrupted social connections and routines, leading to feelings of isolation, anxiety and depressive symptomatology. Furthermore, from a physiological perspective, some people continue to experience health problems long after having COVID-19, and these ongoing health problems are sometimes called post-COVID-19 syndrome or post-COVID conditions (PASC).

Melatonin secretion patterns are associated with cognitive vulnerability and brain structure in bipolar depression.

Circadian rhythm disruption is a core symptom of bipolar disorder (BD), also reflected in altered patterns of melatonin release. Reductions of grey matter (GM) volumes are well documented in BD. We hypothesized that levels and timing of melatonin secretion in bipolar depression could be associated with depressive psychopathology and brain GM integrity.

Timing of proper introduction, optimization and maintenance of anti-TNF therapy in IBD: Results from a Delphi consensus.

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with a rapidly growing worldwide incidence. The last decades presented rapid progress in pharmacological treatment leading in many cases to clinical and endoscopic remission, including biological treatment with anti-TNF agents.

Aim: The exact timing of introduction, optimization and maintenance of anti-TNF therapy in IBDs is not thoroughly covered in current guidelines.

Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

Background And Aims: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD.

Dissociative Dimensions and Their Implications for Emotional Dysregulation Underlying Borderline Personality Disorder Features.

Emotion dysregulation is considered a core feature of borderline personality disorder (BPD). The role of dissociation in BPD has been discussed from different perspectives. Nevertheless, implications of dissociation for BPD features are not clear.

Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin.

Background: Disordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine -metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive.

Results: Monolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies.

The Association Between Insomnia, Insomnia Medications, and Erectile Dysfunction.

Background: Sleep quality and duration have been investigated for their association with health. Insomnia affects up to one-third of adults and may impact male erectile function. In addition, medical treatments for insomnia (many of which are sedatives) may also affect erectile quality.

Comparing Liver Venous Deprivation and Portal Vein Embolization for Perihilar Cholangiocarcinoma: Is It Time to Shift the Focus to Hepatic Functional Reserve Rather than Hypertrophy?

: Among liver hypertrophy technics, liver venous deprivation (LVD) has been recently introduced as an effective procedure to combine simultaneous portal inflow and hepatic outflow abrogation, raising growing clinical interest. The aim of this study is to investigate the role of LVD for preoperative optimization of future liver remnant (FLR) in perihilar cholangiocarcinoma (PHC), especially when compared with portal vein embolization (PVE). : Between January 2013 and July 2022, all patients diagnosed with PHC and scheduled for preoperative optimization of FTR, through radiological hypertrophy techniques, prior to liver resection, were included.

Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study.

Background: Upadacitinib is an oral, selective, and reversible JAK inhibitor with demonstrated efficacy in patients with moderately to severely active ulcerative colitis in a phase 2b induction trial, two phase 3 induction trials (U-ACHIEVE Induction and U-ACCOMPLISH), and a primary analysis of the first 451 patients entering a subsequent maintenance trial (U-ACHIEVE Maintenance). Here, we present overall results from the entire U-ACHIEVE Maintenance population.

Methods: In this randomised, placebo-controlled, double-blind, phase 3 maintenance study done across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 251 clinical centres in 44 countries, patients aged 16-75 years with moderately to severely active ulcerative colitis (adapted Mayo score 5-9, centrally assessed endoscopic subscore of 2 or 3) for 90 days or more were randomly assigned (2:1) to double-blind upadacitinib 45 mg once daily or placebo induction therapy in the phase 2b induction trial or two phase 3 induction trials.

What to expect from the novel pulsed thulium:YAG laser? A systematic review of endourological applications.

Introduction: Several preclinical studies about a novel pulsed-thulium:yttrium-aluminum-garnet (p-Tm:YAG) device have been published, demonstrating its possible clinical relevance.

Methods: We systematically reviewed the reality and expectations for this new p-Tm:YAG technology. A PubMed, Scopus and Embase search were performed.

Gene Therapy for Hemoglobinopathies.

β-Thalassemia and sickle cell disease are autosomal recessive disorders of red blood cells due to mutations in the adult β-globin gene, with a worldwide diffusion. The severe forms of hemoglobinopathies are fatal if untreated, and allogeneic bone marrow transplantation can be offered to a limited proportion of patients. The unmet clinical need and the disease incidence have promoted the development of new genetic therapies based on the engineering of autologous hematopoietic stem cells.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

Backgrounds And Aims: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis.

Methods: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses.

A "cui prodest" evaluation on the development of a minimally invasive liver surgery program: a differential benefit analysis of open and laparoscopic approach for left and right hemihepatectomies.

Background: The correlation between technical feasibility and short-term clinical advantage provided by laparoscopic over open technique for major hepatectomies is unclear. This monocentric retrospective study investigates the possible differences in the benefit provided by minimally invasive approach between left and right hepatectomy, deepening the concept of differential benefit in the setting of anatomical major resections.

Methods: All hemihepatectomies performed from January 2004 to December 2021 were identified in the institutional database.