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Maintaining sperm quality during storage is essential for optimizing reproductive efficiency in rabbit breeding. This study investigated the effects of modulating calcium metabolism and the endogenous opioid system on rabbit sperm function. Two commercial extenders (TRIS and Lepus) were supplemented with calcium chloride (CaCl2) and naloxone (Nx), either individually or in combination. Semen was collected from 20 New Zealand White (NZW) males, pooled, diluted, and assigned to eight experimental treatments. Sperm motility, kinematic parameters, vitality, and morphology were assessed after storage, and data were analyzed by two-way ANOVA. The results showed that treatment was the main factor affecting sperm quality parameters, whereas the effect of diluent was significant only for selected variables. The results revealed significant differences among experimental groups, with naloxone-treated samples (alone or combined with CaCl2) showing the highest sperm quality. In particular, total motility (MOT) increased from approximately 56-71% in control and CaCl2 groups to about 77-85% in Nx-treated groups, while progressive motility (PMOT) improved from approximately 44-57% to 73-82%. Similarly, kinetic parameters (e.g., VAP and VCL) were markedly enhanced in Nx and Nx + CaCl2 groups (reaching ~60-69 μm/s and ~150-159 μm/s, respectively), whereas CaCl2 alone consistently reduced all motility-related parameters. Sperm vitality also improved in Nx-containing treatments (up to ~0.95-0.96), compared to lower values in CaCl2-only groups (~0.77-0.92), while the percentage of abnormalities was reduced, particularly in TRIS-based and Nx-supplemented samples (down to ~2-4%). The combined Nx + CaCl2 treatments consistently showed the best overall performance across most parameters. The synergistic effect observed in the Nx + CaCl2 groups suggests that naloxone may regulate Ca2+ influx and intracellular homeostasis, preventing detrimental effects associated with calcium overload. In conclusion, pharmacological modulation of the opioid system, particularly through low concentrations of naloxone, significantly improves rabbit semen quality and, when combined with Ca2+, further enhances sperm functional parameters. These findings provide new perspectives for optimizing artificial insemination (AI) protocols in rabbit production systems.
Rare skeletal disorders (RSDs) cause lifelong functional impairment, chronic pain and reduced quality of life. Evidence-based rehabilitation strategies remain underdeveloped, particularly for adolescents and young adults. We previously demonstrated preliminary feasibility of a 5-day adapted sailing intervention but observed benefit attenuation at 3-month follow-up. This pilot trial evaluates feasibility, acceptability and safety of intensive adapted sailing therapy followed by home-based telerehabilitation maintenance versus telerehabilitation alone. This is a prospective, randomised, assessor-blinded, parallel two-arm pilot feasibility trial. 24 participants aged 12-30 years with confirmed RSDs will randomise with a 1:1 allocation ratio to: (1) 5-day adapted sailing therapy followed by 3-month telerehabilitation (n=12) or (2) 3-month telerehabilitation alone (n=12). Primary outcomes assess feasibility through recruitment efficiency (≥80% eligible patients enrolled), intervention adherence (≥75% sessions completed), participant retention (≥80% at 6-month follow-up), and safety (zero serious adverse events attributable to interventions). Secondary outcomes include sensor-based motor function (balance, gait, upper extremity mobility via inertial measurement units) and patient-reported outcomes (health-related quality of life, functional capacity, kinesiophobia, pain), measured at baseline, 3-month and 6-month follow-up. Exploratory analyses will estimate preliminary between-group effect sizes. Statistical analysis uses intention-to-treat principles with linear mixed-effects models. The study received approval from the Area Vasta Emilia Centro Ethics Committee (363/2025/Sper/IOR) on 7 July 2025. The study is ongoing, and data collection is expected to be completed by March 2026. Results will be disseminated through peer-reviewed open-access publications, conference presentations, patient organisation partnerships and plain-language summaries. NCT07102875.
A precise understanding of the national neurosurgical workforce is essential for effective healthcare planning and ensuring the long-term sustainability of the specialty. In Italy, the number of newly trained neurosurgeons is strictly limited by a competitive national residency entrance system, making accurate forecasting of workforce needs critical. Recent evidence suggests an aging neurosurgical population, highlighting the urgency of estimating retirements and training requirements to maintain adequate staffing levels. However, updated and comprehensive data on the national neurosurgical workforce have long been lacking. The Società Italiana di Neurochirurgia (SINCH) therefore promoted a national census to provide an accurate overview of all active neurosurgeons during the biennium 2022-2023. A national cross-sectional descriptive study was conducted between 2022 and 2023 to characterize the demographics and distribution of neurosurgeons within the Italian Public Health System and affiliated facilities. Three principal investigators and one supervisor coordinated the project under SINCH supervision. Data were collected through: 1) consolidation of the SINCH-PROGETKA database; 2) direct verification via personalized e-mails to all 113 neurosurgical unit directors (112 complete replies); 3) systematic web-based searches across 17 medical directory platforms; and 4) cross-matching with official medical organizations (FNOMCEO). Data were analyzed by institution type, geographic area, gender, age, and leadership role. A total of 1489 active neurosurgeons were identified, with 1055 (74.1%) confirmed as SINCH members. Most professionals worked in public institutions (AOSSN 51.1%, AOU 17.2%, IRCCS 9.7%, AOU-IRCCS 5.4%), while 235 (15.9%) operated primarily in the private sector. Workforce distribution showed marked regional disparities: Northern and Central Italy accounted for 71% of neurosurgeons, whereas the South and Islands hosted only 29%. The national average was 1 neurosurgeon per 39,523 inhabitants, one of the highest ratios in Europe. Women represented 24.1% of active neurosurgeons but only <4% of unit directors. The mean age of directors was 59 years, reflecting an aging leadership cohort. This updated census provides the most comprehensive profile to date of Italian neurosurgeons. Despite adequate overall numbers, regional and gender imbalances persist, and leadership renewal remains limited. When compared with the previous ICoNe2 study, these data confirm Italy's exceptionally high neurosurgical density and underscore the need for coordinated workforce planning, optimization of training programs, and rational redistribution of resources to ensure sustainable and equitable neurosurgical care nationwide.
Adolescence and the onset of emerging adulthood are periods of increasing autonomy; when a rare disease is present, parents may experience heightened psychological strain. Parenting self-efficacy is central to parenting competence, yet little is known about how parents' perceptions of adolescents' difficulties relate to this sense of competence in rare-disease contexts. To examine associations between parent-perceived adolescent difficulties/strengths and parenting self-efficacy and satisfaction, and whether patterns vary by family size. In this cross-sectional study, parents of adolescents and young adults with rare diseases (n = 56) and of typically developing peers (n = 56) completed the Strengths and Difficulties Questionnaire and the Parenting Sense of Competence Scale. Group differences were tested with MANOVA/MANCOVA; associations were examined with Pearson correlations and multiple regression. Compared with controls, parents in the rare-disease group reported more behavioural, emotional, hyperactivity/inattention and peer problems. Unexpectedly, they also reported higher parenting self-efficacy and satisfaction. Family size showed nuanced patterns (e.g., higher efficacy in three-child families; higher satisfaction in one-child families). Across the rare-disease group, greater perceived difficulties were associated with lower competence, whereas prosocial behaviour showed positive associations. Findings support strengths-based, family-responsive parent work and routine monitoring of parental wellbeing in clinical/psychoeducational settings. Longitudinal research is needed to evaluate directionality.
Severe asthma affects a minority of patients with asthma; however, it substantially impacts morbidity, health-care use, and systemic corticosteroid-related harm. Despite the increasing use of biological treatments, achievement of severe asthma remission remains elusive. Notably, real-world data on the disease burden and remission potential of severe asthma in Europe remain limited. We aimed to close this knowledge gap, offering insights with global relevance. Using data from 13 455 adults with severe asthma enrolled in the European Severe Heterogeneous Asthma Registry, Patient-centred Clinical Research Collaboration (SHARP CRC), this cross-sectional observational study evaluated the burden of severe asthma and remission-related clinical domains (exacerbations, asthma control, airflow limitation, and maintenance oral corticosteroid use) across Europe and examined their relationship with disease duration, biological therapy, and type 2 biomarkers (blood eosinophils, fractional exhaled nitric oxide [FeNO], and total IgE). Patients with severe asthma had been enrolled in national registries according to local principles and guidelines and in accordance with the European Respiratory Society/American Thoracic Society guidelines; 3% (430 of 13 885) of patients were excluded due to no consent for the international study and/or missing medication data. Patients were predominantly female (59%; 7999 of 13 453), with adult-onset asthma (82%; 8751 of 10 711), and a median disease duration of 23 years (95% CI 20-26 years). 59% (4148 of 7006) of patients had FEV1/FVC of 0·7 or less, 62% (4680 of 7568) had FEV1 lower than 80% predicted, and 89% (3519 of 3968) had at least one active disease domain. Despite 79% (10 632 of 13 453) receiving biological therapy, more than 66% (2621 of 3968) still had at least two active domains. Elevation of type 2 biomarkers persisted (89% [2806 of 3153] with at least one elevated biomarker) despite widespread biological and maintenance oral corticosteroid treatment. A subset of biologic-naive patients (35%; 1069 of 3018) exhibited a rapid accumulation of disease burden within less than 10 years, suggesting a potentially accelerated progression trajectory. This pan-European analysis of severe asthma revealed significant clinical heterogeneity and a substantial disease burden despite advanced therapies, highlighting the enduring nature of type 2 inflammation, the potential inadequacy of current remission strategies with available therapeutic approaches, and the necessity for early identification of high-risk patients. SHARP Clinical Research Collaboration and consortium partners: European Respiratory Society, GlaxoSmithKline Research and Development, Chiesi Farmaceutici Società per Azioni, Novartis Pharma Aktiengesellschaft, Sanofi-Genzyme Corporation, and Teva Branded Pharmaceutical Products R&D.
LUCENT-URGE (NCT05767021) was a Phase 3b, multicenter, open-label, single-arm study investigating bowel urgency (BU) in patients with moderately-to-severely active ulcerative colitis (UC) and BU at baseline, treated with mirikizumab. Patients without prior mirikizumab exposure received intravenous mirikizumab 300 mg at weeks (W)0, 4, and 8, followed by subcutaneous mirikizumab 200 mg at W12, 16, 20, and 24. The primary objective was improvement in the validated BU severity measure (Urgency Numeric Rating Scale [UNRS]) at W12. Secondary objectives included improvement in BU at W28, novel measures of stool deferral time (SDT), bowel urgency frequency (BUF), and associations between BU measures. UNRS, BUF, and SDT were collected using a daily diary; the shortest weekly SDT was used for analysis. Baseline observation carried forward was used as the response for the corresponding visit for all missing observations. Missing continuous data were treated as having no change from baseline. All three BU measures at W12 were sustained or improved through W28. With mirikizumab treatment, 52.2% improved BU severity, 55.1% improved BUF, and 40.7% improved shortest weekly SDT. Patients with shortest weekly SDT ≥ 15 min or no urgency increased from 4.1% at baseline to 29.7% at W28. At W12, 36 (20.9%) achieved clinical remission and 54 (31.4%) achieved endoscopic remission, improving to 62 (36.1%) and 76 (44.2%) at W28, respectively. The safety profile was generally consistent with the known profile. In the first comprehensive approach assessing complex BU symptoms in UC, mirikizumab was associated with improvements in several BU and clinically related measures through W28. ClinicalTrials.gov, NCT05767021. Mirikizumab treatment was associated with improved bowel urgency severity, frequency, and stool deferral time in patients with moderately-to-severely active ulcerative colitis, showing better patient-reported quality of life outcomes, improved endoscopic appearance, and fewer symptoms over a 28-week trial.
Over the past two decades, adolescent psychological distress has increased markedly, with a growing number of young people experiencing intense suffering that cannot be verbalised and is instead expressed through the body, including self-harming behaviours and social withdrawal. These manifestations are frequently associated with poor therapeutic engagement and complex family dynamics characterised by emotional intrusion, overprotection, or relational absence. From a systemic and narrative perspective, symptoms are understood as meaningful communications embedded within family systems, transgenerational histories, and contemporary socio-cultural transformations. Social changes related to digital hyperconnection, altered parenting practices, and performance-oriented cultural models have reshaped adolescent subjectivity, privileging action and bodily expression over narration and mentalisation. This paper explores "shown pain" as a primary mode of communication in adolescence and examines the clinical transition from bodily enactment to narrated experience. Drawing on systemic theory, narrative psychotherapy, and neurobiological insights, the article analyses the emotional dimensions underlying self-harm and withdrawal, as well as the ambivalent regulatory functions of symptoms. A clinical case is presented to illustrate how an integrated therapeutic approach, combining individual and family therapy, can facilitate alternative narratives, support differentiation processes, and promote individual and relational change. The paper highlights the relevance of systemic psychotherapy in restoring meaning, voice, and relational listening in severe adolescent distress.
Why some tumors respond to immunotherapy ("hot" tumors) while others remain resistant ("cold" tumors) is a central challenge in oncology. Elevated RAB5A-dependent endocytosis drives tissue fluidization during the transition to invasive breast carcinoma, but its immunological consequences are unclear. Here we show that RAB5A-driven fluidization induces a mechano-metabolic stress response that disrupts the AMPK-AKAP1-DRP1 mitochondrial fission pathway, causing mitochondrial elongation. RAB5A vesicles interact with hyperfused mitochondria and promote BAX/BAK-dependent pore formation, leading to limited mitochondrial outer membrane permeabilization. This sub-lethal event is amplified by palmitoylated GASDERMIN A oligomerization on mitochondria, establishing a positive feedback loop. The resulting release of mitochondrial DNA activates the cGAS-STING innate immune pathway and drives a hyperinflammatory state. Consequently, RAB5A-expressing tumors in immunocompetent mice grow more slowly, show increased immune infiltration, and display enhanced sensitivity to immune-checkpoint blockade in a BAX/BAK-, cGAS/STING-, and mtDNA-dependent manner. These findings connect mechanical stress, mitochondrial dynamics, and innate immunity, revealing strategies to potentiate antitumor immunotherapy.
Transthoracic echocardiography (TTE) identifies a hypercontractile phenotype (HP) in chronic coronary syndromes (CCS), characterized by elevated resting left ventricular (LV) elastance (force = systolic blood pressure/end-systolic volume). To evaluate the prognostic significance and functional correlates of HP. In a prospective multicentre study, 10 677 patients with CCS underwent resting TTE to assess LV ejection fraction (EF), stroke volume, and force by quantitative volumetric echocardiography. All patients were followed for the endpoint of all-cause mortality. In a subset of 5834 patients, stress echocardiography (exercise or dobutamine) was performed for LV contractile reserve and heart rate reserve. Patients were stratified into Force quintiles (Q1-Q5). Patients with hypercontractile phenotype exhibited lower stroke volume at rest (Q5 = 34.8 ± 12.3 vs Q1-Q4 = 57.4 ± 19.1 mL; P < .01) and higher EF at rest (Q5 = 64.8 ± 6.9% vs Q1-Q4 = 58.1 ± 8.7%, P < .01). During a median follow-up of 24 months (interquartile range = 12-40 months), 509 deaths occurred. The exposure-adjusted death rate was lowest in Q3 (3.53-4.51 mmHg/mL; 1.03 per 100 person/years) and higher in Q1 (≤2.62 mmHg/mL, 2.88), Q2 (2.63-3.52 mmHg/mL, 1.86), Q4 (4.52-6.11 mmHg/mL, 1.56), and Q5 (HP, >6.11 mmHg/mL; 1.88; P < .0001 vs Q1 and Q3). Multivariable analysis identified HP (Q5; HR 1.531 vs Q3, 95% CI 1.116-2.099; P = .006) and EF (HR 0.963, 95% CI 0.953-0.972; P < .0001) as independent predictors of death. During exercise or dobutamine stress, HP showed reduced LV contractile reserve (ΔEF: Q5 = 4.3 ± 9.4% vs Q1-Q4 = 7.0 ± 9.3%; P < .001) and blunted heart rate reserve (Q5 = 1.77 ± 0.33 vs Q1-Q4 = 1.85 ± 0.39; P < .01). All patients with force-based LV contractile reserve >4.1 (present in 185, 3.2% of the population) survived. Patients with CCS with HP assessed by resting TTE demonstrate higher mortality and multilayered functional impairment, including reduced LV contractile and chronotropic reserves. Hypercontractile phenotype improved the prediction of mortality by EF. A 'stronger' heart is, in fact, functionally and prognostically weaker.
Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals' health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem cell maintenance, neuronal differentiation, and the regulation of genes involved in brain morphogenesis. Given the susceptibility of the developing nervous system to epigenetic dysregulation induced by alcohol and drugs, this narrative study aims to summarize literature evidence with the hypothesis that ING proteins may represent a critical but understudied mechanistic link between maternal substance dependence and adverse neurodevelopmental outcomes in newborns. We conducted a comprehensive literature search across three databases (PubMed, Scopus, and Web of Science) up to February 2026 to identify relevant studies. Search terms included combinations of "ING proteins", "neural development", "alcohol", "drugs", "epigenetic", "oxidative stress" and "neuroinflammation". The inclusion criteria were limited to original studies published in English that examined neural development in newborns; the exclusion criteria encompassed non-English publications, letters, editorials, and case reports, and those not directly addressing the specified topics. We identified 55 papers; six were excluded per the exclusion criteria, leaving 49 works discussed in this review. ING proteins are epigenetic regulators essential for embryonic and neural development, including neural stem cell fate and neurogenesis, while substances of abuse are disruptors of the essential pathways necessary for the right fetal brain development. Furthermore, substance abuse creates oxidative stress environments and activates pathways that require ING-mediated chromatin regulation. ING proteins likely act as mediators linking oxidative stress, neuroinflammation, and transcriptional reprogramming in the developing brain. Meanwhile, alcohol and drugs induce epigenetic reprogramming that may disrupt ING-mediated chromatin control. There is little evidence directly linking prenatal exposure (e.g., alcohol and drugs) to ING changes during fetal development. However, we hypothesize that ING proteins function as epigenetic stress response regulators whose disruption by oxidative stress, inflammation, and chromatin alterations induced by prenatal alcohol or drug exposure may contribute to impaired fetal neurodevelopment. Although direct experimental evidence remains limited, this could be a promising and relatively unexplored research area.
In January 2024, the Commissione Scientifica ed Economica (CSE) became the national body responsible for the integrated scientific and economic evaluation of medicines in Italy. This study provides the first systematic description of the CSE's activity during its initial operational year, focusing on procedural workload, timelines, and negotiation outcomes. All publicly available "Esiti CSE" documents published by the Italian Medicines Agency (AIFA) between April 2024 and April 2025 were manually extracted and validated. Each record included the negotiation typology (TN-1 to TN-8), outcome, and iter duration. Descriptive analyses summarised distributions, median and mean durations, deferral rates, and trends over time. A total of 641 procedures (523 products, 446 INNs) generated 2,145 individual outcomes. Argomento rinviato (deferral) was the most frequent outcome (55.7% of all decisions; 51% of procedures). The average procedure involved 1.9 deferrals, and 83% experienced at least one. Mean overall duration was 269 days (median 196; IQR 133-350), with the longest timelines for TN-1 and TN-4 negotiations (298 and 322 days, respectively). Oncology (L01, L04) and metabolic agents (A10) showed the greatest variability, while antivirals (J05) recorded the longest average duration (549 days) but a lower incidence of deferral. The first year of CSE activity reveals a high workload, variable timelines, and frequent deferrals, reflecting the complexity of integrating scientific and economic assessment within a single body. The results provide an empirical baseline for future monitoring and underscore the need for refinement of governance arrangements and procedural transparency in AIFA's new framework.
Increasing evidence links elevated serum uric acid levels to adverse cardiorenal outcomes. To date, limited data exist on whether the benefits of urate-lowering therapies (ULTs) depend on timely treatment initiation and sustained adherence in patients at high cardiovascular risk. An economic evaluation was conducted, based on a simulation model populated by Italian real-world patient-level data from the Uric Acid Right for Heart Health (URRAH) cohort to evaluate long-term cardiovascular, renal, and economic outcomes associated with timely allopurinol use. 10,000 patients with hyperuricemia (serum uric acid >5.6 mg/dL) and elevated cardiovascular risk were simulated over a 20-year time horizon. Timely initiation of allopurinol (before the first gout flare) was compared with treatment initiated only after symptomatic disease onset. Scenarios reflecting current and improved adherence to ULTs were assessed. Outcomes included major adverse cardiovascular events, end-stage renal disease onset, and economic outcomes from the payer's perspective. According to our model, timely initiation of allopurinol was associated with modest but consistent health gain (0.04 quality adjusted life years) including reductions in gout flares, cardiovascular- and renal endpoints. Timely allopurinol initiation was cost-saving and, from a health economic perspective, dominant over current practice. Improved ULT adherence amplified these benefits. Our hypothesis-generating research suggests that, in hyperuricemic patients at high cardiovascular risk, the potential benefits of allopurinol also depend on timely initiation and sustained adherence. While these findings do not constitute evidence of causal clinical benefit, they support a broader cardiorenal clinical approach to hyperuricemia management that extends beyond gout prevention.
Language development in early childhood varies considerably, making early detection of Developmental Language Disorders (DLDs) challenging despite their high prevalence and long-term effects on learning and mental health. In Italy, no culturally adapted, easy-to-use screening tools are currently available in primary care. To address this gap, a screening tool was developed to support the early identification of children aged 24-72 months at risk of DLD and other clinically relevant language difficulties. To evaluate the psychometric properties and accuracy of the Comunicazione e Linguaggio in Ambulatorio Pediatrico (CLAP), a brief age-specific screening tool designed for use in Italian paediatric outpatient settings. In this pilot validation study, children were recruited by primary care paediatricians during routine well-child visits and stratified into four age groups: 24-30, 36-42, 48-54, and 60-72 months. After administration of the CLAP screening tool, each child underwent a blinded speech-language pathologist (SLP) assessment. Psychometric evaluation included internal consistency, item-total correlations, confirmatory factor analysis, and item response theory indices (discrimination and difficulty). Diagnostic accuracy was assessed using ROC curves, area under the curve (AUC), sensitivity, specificity, and optimal cut-offs. Analyses were conducted separately for each age group. Fifty children were enrolled in each age group; overall, 24% of the sample fell into the pathological subgroup after the blinded SLP assessment. Internal consistency was acceptable in the 24-30-month (KR-20 = 0.695) and 36-42-month (KR-20 = 0.777) groups, but lower in older children. Factor analyses supported a mainly unidimensional structure in the younger groups. Item response theory showed good discrimination and informativeness for several items. ROC analyses indicated excellent diagnostic accuracy in the 24-30-month group (AUC = 0.93; sensitivity = 92%; specificity = 87%), fair accuracy in the 36-42- and 48-54-month groups (AUC = 0.75 and 0.74), and poor performance in the 60-72-month group (AUC = 0.46). The CLAP demonstrates promising psychometric properties and good-to-fair accuracy as a brief screening tool for identifying children aged 24-54 months at risk of clinically relevant language difficulties, including those who may need further assessment for DLD. Its age-specific design, quick administration, and non-invasive nature support its potential integration into routine primary care. For older children, an age-specific revision or an alternative tool might be required. A larger validation study is currently in progress. What is already known on this subject Developmental Language Disorder (DLD) is common in early childhood; however, early identification remains difficult due to variable developmental pathways and the absence of validated screening tools in primary care. Currently, no brief, culturally adapted instrument is available for routine use in Italian paediatric settings. What does this study add to existing knowledge This study demonstrates that the CLAP tool has promising psychometric properties, with good accuracy in the youngest age group and fair accuracy up to 54 months for identifying children at risk of clinically relevant language difficulties, including those who may later meet criteria for DLD. It provides the first evidence supporting an age-specific, feasible screening option that can be integrated into Italian primary care, while also identifying areas requiring revision for older pre-schoolers. What are the potential or actual clinical implications of this work? CLAP can assist paediatricians in the early detection of clinically relevant language difficulties in children during routine well-child visits. Its adoption could help standardize early language screening in Italy, leading to earlier referral for further diagnostic assessment and appropriate speech-language evaluation.
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The Mediterranean diet (MD) is widely recognized for its potential health benefits, yet the extent and certainty of its association with metabolic outcomes remains incompletely understood. The aim of this systematic review and meta-analysis was to evaluate the relationship between adherence to the MD and the risk or prevalence of cardiometabolic disorders in the general population, with a focus on its role in primordial and primary prevention. This review followed PRISMA 2020 and MOOSE guidelines. A systematic search of PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library was conducted through February 28, 2024. Eligible studies examined adherence to the MD in relation to the risk or prevalence of metabolic disorders. Study quality was assessed using the Newcastle-Ottawa Scale, and evidence certainty was rated with the NUTRI-GRADE framework. Pooled effect estimates were calculated using a random-effects model and reported as risk ratios (RR), hazard ratios (HR), or odds ratios (OR), as appropriate. Sixty studies comprising over 1.1 million participants were included. Higher MD adherence was consistently associated with a reduced risk of T2DM (RR: 0.96; 95% CI: 0.95-0.97), supported by moderate to high certainty of evidence. Similar inverse associations were observed for overweight (OR: 0.94; 95% CI: 0.91-0.97) and adult obesity (OR: 0.95; 95% CI: 0.93-0.97). The PREDIMED randomized trial further demonstrated a 20% reduction in diabetes incidence with MD intervention. Evidence for metabolic syndrome (RR: 0.98; 95% CI: 0.98-0.99) and hyperuricemia (OR: 0.43; 95% CI: 0.25-0.75) was suggestive of protective effects, though with lower certainty. Associations with hypercholesterolemia and hypertriglyceridemia were inconsistent and inconclusive. Adherence to the Mediterranean diet is associated with a lower risk of several metabolic disorders, particularly T2DM and obesity in adults. These findings support the inclusion of the MD in public health strategies for metabolic disease prevention. Further high-quality longitudinal and interventional studies are warranted to clarify its effects on other metabolic outcomes.
Acute type A aortic dissection (AADA) is a life-threatening cardiovascular emergency whose prognosis is closely linked to the timeliness of diagnosis and treatment. However, its low incidence and highly variable clinical presentation make early recognition challenging. In addition, poor therapeutic adherence and inadequate surveillance of predisposing factors, including hypertension and aortic aneurysm, contribute to diagnostic delays and worse clinical outcomes. A retrospective observational analysis was conducted using real-world administrative data from Italian healthcare facilities covering over 12 million individuals (2010-2024). Adult patients urgently hospitalized for AADA (ICD-9-CM 441.01) were identified. Clinical profile, comorbidities, pharmacological treatments, diagnostic procedures, and the presence of hypertension - defined as the number of annual prescriptions ≥ 9 (a proxy for diagnosis) of antihypertensive drugs - were evaluated. A total of 1625 patients were included (mean age 67.3 ± 13.4 years; 65.6% male). Diabetes was reported in 8.5% of cases, cardiovascular disease in 21.2%, and ascending aortic aneurysm or ectasia in 6%. In the year preceding hospitalization, 65.8% of patients had at least one antihypertensive prescription, but only 35% showed evidence of continuous treatment. Diagnostic procedures were infrequent: echocardiography was performed in 12.3% of patients, cardiac computed tomography/magnetic resonance angiography in 1.8%, and 24-h ambulatory blood pressure monitoring in 2.4%. This real-world analysis highlights major gaps in the pre-hospital management of AADA in Italy, characterized by suboptimal blood pressure control, poor therapeutic adherence, and limited use of diagnostic imaging in at-risk patients. These findings underscore the need for structured prevention and surveillance strategies aimed at the early recognition of predisposing conditions and the optimization of integrated care for patients at risk of acute aortic dissection.
We present a Virtual Reality application aimed at implementing a brief Acceptance and Commitment Therapy (ACT) approach targeted at older adults experiencing intrusive thoughts. The intervention combines ACT experiential exercises with purposely-developed immersive VR environments.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, mainly affecting older people. Targeted agents have reshaped first-line (1L) strategies, making real-world evidence important to complement clinical trials. To estimate the incidence of Italian patients initiating first-line CLL therapy (2019-2022) and describe demographics/clinical profile, treatment patterns, adherence, outcomes (overall survival [OS], time to next treatment [TTNT]), and healthcare costs from the perspective of the Italian National Health System (NHS). A retrospective observational study using administrative healthcare databases (~9 million residents) was conducted on CLL patients starting 1L therapy (index-date) for CLL. Baseline characteristics were assessed in the 12 months pre-index; follow-up was ≥12 months. Drug use, adherence (medication possession ratio), dose adjustments, OS, TTNT, and direct costs were analyzed with descriptive and multivariable methods. A total of 1479 patients initiated 1L therapy: 63.9% chemotherapy (CHT), 23.2% ibrutinib, 3.2% acalabrutinib, and 9.7% other regimens. CHT remained common, especially among older and more comorbid patients. Ibrutinib showed lower mortality versus CHT (HR 0.663; p=0.002) and longer TTNT (median not reached). Dose adjustments were frequent; extended refill intervals did not appear to reduce drug survival. Mean annual cost per patient was €38,573, mainly driven by drug acquisition; ibrutinib users had lower hospitalization and outpatient costs than other 1L groups. In Italian practice, ibrutinib was the main targeted 1L option and was associated with improved survival and delayed progression versus CHT. Despite higher drug costs, reduced hospital-based resource use suggests favourable overall clinical and economic impact.
High tumor burden negatively affects responses to anti-CD19 chimeric antigen receptor T-cell (CART) therapy in large B-cell lymphoma (LBCL). Therefore, bridging therapy (BT) is crucial for disease control before infusion. Here, we retrospectively compared polatuzumab vedotin (PV) combined with rituximab (PV-R) ± bendamustine (PV-BR) in a cohort of 200 patients with LBCL enrolled in the prospective, multicenter, observational CART-Società Italiana di Ematologia (SIE) study. Commercial CARTs were infused between July 2020 and January 2025. Patients received BT with either PV-BR (n = 122) or PV-R (n = 78). At median follow-up of 11.9 months, the median progression-free survival (PFS) and overall survival (OS) in the entire cohort were 10.1 and 35.1 months after CART, respectively. When comparing PV-BR- with PV-R-treated groups, patient characteristics at CART eligibility, objective response rates to BT (52.5% vs 49.4%; P = .775), median PFS (13.4 months vs 7.4 months; P = .556), and median OS (not reached vs 29.0 months; P = .954) were similar. Hematological toxicities after BT were higher with PV-BR than PV-R (36.4% vs 18.2%; P = .010; grade ≥3, 16.1% vs 6.5%; P = .048), as were rates of neurotoxicity after CART (31.1% vs 15.4%; P = .019). Rates of cytokine release syndrome and infections were comparable between the 2 groups. High tumor burden at CART infusion was independent risk factor for both PFS and OS. Our findings confirmed the role of BT and suggested that PV regimens may effectively control the disease during T-cell manufacturing. Responses and survival were similar between PV-R and PV-BR, with PV-R showing a trend toward lower toxicity, including reduced neurotoxicity, supporting its potential as a targeted, well-tolerated bridging regimen.