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.
Medieval Sicily, located at the intersection of Europe, North Africa and the Near East, experienced successive political and religious transitions under Byzantine, Aghlabid, Fatimid, Norman, and Swabian rule. While it is well established that these events led to multi-faith societies, the long-term genetic impact of regime change is unclear. To evaluate this potential impact, we applied ancient genomic analysis to 111 archaeological Sicilian individuals, leading to successful mitochondrial haplotype inferences for 67 individuals and genome-wide analyses for 32 individuals dated between the 5th and 15th centuries CE. In contrast to simple narratives of population replacement, the data indicate nuanced and unappreciated demographic shifts. Several individuals dating before the Islamic conquest of Sicily exhibit substantial North African ancestry, evidencing movement across the Mediterranean Sea before this conquest. Individuals buried in Islamic cemeteries during the 9th to 11th century were found to have diverse ancestries deriving from populations around the Mediterranean Basin, however, the same ancestry components are also found in earlier periods, limiting what can be inferred about intra-Mediterranean migrations in this dataset. Nonetheless, the Islamic period marks the appearance of individuals with distant ancestral origins, West Africa and Northern Europe. During the Norman period, Christian and Islamic burials show the same genetic diversity maintained for hundreds of years, however, by the late medieval period, the ancestry components shifted toward modern European populations. Altogether, the study demonstrates the value of examining recent periods with ancient DNA methodologies to better understand how culture, identity and mobility impacted demography in the past.
Migraine is a leading cause of disability worldwide, impairing quality of life and productivity. Preventive therapies aim to reduce attack frequency, severity and the need for acute medications. Oral atogepant (60 mg), a calcitonin gene-related peptide (CGRP) receptor antagonist, has recently expanded migraine prevention options. This study evaluated changes in triptan use after atogepant initiation using real-world data. This retrospective observational study used administrative healthcare databases from the Local Health Unit of Modena (Italy). Adults with chronic or high-frequency episodic migraine initiating atogepant between November 2023 and December 2024 were identified. Triptan use and related costs were assessed in the 6 months before and after treatment initiation (index date), measured as dispensed dosage units. Among 95 patients (86% female; mean age 53.5 years), 55 triptan users were included in the analysis. Triptan use decreased in 45 patients (82%), with ≥ 60% reduction in 27 (49%) and complete discontinuation in 10. Median consumption decreased from 76 to 24 dosage units, and mean consumption from 88.1 to 45.2. This reduction was statistically significant (Wilcoxon signed-rank test, p < 0.001). This reduction corresponded to a decrease of €2,591 in triptan-related pharmaceutical expenditure within the study cohort. Atogepant preventive treatment may substantially reduce acute migraine medication use in real-world practice, with potential clinical and economic benefits.
[This corrects the article DOI: 10.1016/j.toxrep.2026.102209.].
Lipohypertrophy, characterized by subcutaneous adipose tissue accumulation at sites of insulin administration, affects 29-76% of insulin-treated people with diabetes (PwD), yet remains underrecognized. This complication significantly impacts glycemic control through unpredictable insulin absorption, necessitating up to 25% higher insulin doses and increasing care costs. An evidence-informed consensus initiative was warranted to establish recommendations for the screening, prevention, and management of lipohypertrophy. A modified Delphi methodology was employed involving 13 international experts in endocrinology, primary care, and diabetes research. A structured literature review informed five consensus rounds, leading to fifteen statements addressing epidemiology, risk factors, clinical presentation, diagnosis, prevention, management, and education/training/systems. Inadequate injection site rotation was identified as the strongest modifiable risk factor for lipohypertrophy. The panel recommends systematic injection site examination every 6 months during the first 2 years of insulin therapy, then annually, with more frequent screening for high-risk PwD. Standardized examination protocols incorporating visual inspection and systematic palpation were endorsed, with ultrasound reserved for detecting subclinical lipohypertrophy. Prevention strategies emphasize proper education, site rotation, and single-use needle practices. Implementation of consensus recommendations presented here may improve glycemic outcomes, reduce insulin requirements and cost of care, and enhance quality of life for PwD on insulin therapy.
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.
This study investigates the bio-physiological responses occurring under extreme stress conditions and the characterization of the oxy-inflammatory profile of Finishers (FRs) and NoFinishers (NFRs) athletes during the time course and following the Transpyrénéa, an 866 km extreme ultra-race across the French Pyrenees with an altitude difference of 52,900+ m ascent. Thirty-nine experienced ultra-marathon runners (age 43.5 ± 9.1 years; weight 72.1 ± 11.1 kg; BMI 23.3 ± 2.6 kg/m2) were studied using minimally invasive methods on capillary blood and urine samples obtained at baseline (T0), during (T1, 2, 3) and at the end (T4) of the race. Reactive Oxygen Species (ROS) production, total antioxidant capacity (TAC), oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG and 8-isoprostane: 8-isoPGF2α), inflammatory (IL-6), nitric oxide pathway (NOx and 3-NT), neopterin, and hematologic (lactate, and hematocrit) biomarkers were assessed. In both FR and NFR athletes a marked systemic increase in ROS, oxidative and nitrosative damage, inflammation, transient immune-renal dysfunction and lactate release were detected throughout the race. Compared to FRs, NFRs displayed significant differences concerning ROS production at T0, 8-isoPGF2-α at T0, T1 and T2, and perceived exertion (RPE score) at T2. These data potentially reflect enhanced adaptative responses to training and metabolic efficacy in FRs, allowing them to better tolerate extreme physiological stress.
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.
Population aging leads to rising chronic disease burden and healthcare costs. The metropolitan area of Genoa (Liguria), the oldest in Italy, is particularly affected. Since 2017, ASL3 has implemented a comprehensive health promotion strategy including risk-factor reduction initiatives and multidisciplinary care pathways for multimorbid patients. To evaluate the impact of the comprehensive health promotion program on the prevalence of heart failure (HF), chronic kidney disease (CKD), and chronic liver disease (CLD), and on healthcare resource use. Using the ASL3 data warehouse, we analyzed trends in HF, CKD, and CLD prevalence from 2011 to 2023 and compared yearly prevalence between 2011 and 2019 and 2020-2023. Hospitalization, outpatient activity and drug-prescription data were assessed; production and pharmaceutical costs were calculated. Regression models evaluated changes in prevalence trajectories. The resident population and average age increased slightly (from 704,355 to 711,133 people; from 49 to 51 years old). The unadjusted and standardized prevalence of HF, CKD and CLD rose significantly over the study period. However, after regression analysis, significance was confirmed only for the period 2011-2019. In 2020-2023, prevalence continued to rise, but at a substantially slower rate, suggesting an attenuation of the upward trend. A multifaceted, system-wide prevention and care model may attenuate the upward trend in chronic-disease prevalence in highly aged populations. These findings support integrated health-promotion strategies as a sustainable approach to chronic disease management and resource stewardship.
Springs represent ecotones between groundwater and surface freshwater habitats. Recent research suggested that springs can be more important than expected for stygobiont (i.e., adapted to live in groundwater) species, still information on habitat exploitation and activity of stygobionts in springs is far from complete. The aims of this study are: (i) to identify environmental factors promoting the exploitation of ecotone habitats by the stygobiont shrimp Troglocaris planinensis, commonly found in spring environments in northeastern Italy; and (ii) to experimentally evaluate whether this species exhibits differential behavioral responses to light and to subterranean and surface predator cues based on its habitat of origin (spring versus cave). From June 2020 to January 2025, we started multiple day and night surveys of T. planinensis in 64 springs of the Classic Karst (NE-Italy). Each site has been characterized with respect to abiotic and biotic features. In the laboratory, shrimps from both cave and spring populations were tested to assess behavioral differences in response to light stimuli and predatory cues, as potential adaptations to the contrasting conditions of their respective habitats. In springs, T. planinensis density reached up to 116 shrimps/m2, with significantly higher counts at night and lower densities at sites with greater fish predator abundance. Laboratory tests showed that predator cues, but not light exposure, influenced shrimp behavior regardless of their cave or spring origin. This study suggests that stygobiont crustaceans can represent a significant portion of biomass in surface waters and exploit these environments in response to changes in abiotic and biotic conditions and stimuli. However, further research is necessary to determine how stygobionts perceive surface conditions and how ecotonal pressures may drive adaptive shifts in typically groundwater-dwelling animals.
After a brief reflection on the choice of the term femicide, the discussion moves toward a psychoanalytical reading of the phenomenon, starting from the classical texts of Sigmund Freud, Melanie Klein e Jacques Lacan, and extending to contemporary theorization on gender culture and the culture of the neutral. Dynamics of possession are analyzed through the lens of Italian feminism, in an interweaving of psychoanalysis and feminism aimed at assessing the risk and preventive factors of this harrowing phenomenon.
Treating obesity in children and adolescents is complex, given the dynamic nature of growth and development during this life stage. The role of pharmacological treatments in the management of pediatric obesity remains uncertain, particularly with respect to outcomes beyond weight reduction, including quality of life and long-term adverse events. To assess the benefits and harms of pharmacological interventions for the treatment of obesity in children and adolescents. We searched CENTRAL, MEDLINE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov on 3 July 2023 without language restrictions. In June 2025, we checked the status of ongoing studies and updated results accordingly. We included randomized controlled trials (RCTs) evaluating pharmacological interventions in children (0 to 9 years) and adolescents (10 to 19 years) with essential obesity. Eligible studies administered any medication, at any dose, as monotherapy or in combination, for at least three months and reported outcomes after a minimum follow-up of six months. Critical outcomes were change in body mass index (BMI), change in weight, any adverse events, discontinuation due to adverse events, and incidence or severity of obesity-related outcomes. Important outcomes were health-related quality of life, mental and physical well-being, and obesity-related disability. We used the RoB 2 tool to assess bias in the included RCTs. We calculated mean differences (MDs) and standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, with their corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for critical outcomes and quality of life. We included 37 RCTs with a total of 4218 participants. Two were cross-over trials; 35 were parallel-group trials. We identified seven ongoing studies and six studies as awaiting classification. Of the included studies, 25 involved adolescents only. Eleven studies planned to include both children and adolescents, but only eight actually did. One study intended to include children but did not specify participants' age at inclusion. Trials randomized participants to pharmacological interventions or control alongside common baseline treatments (e.g. behavioral or lifestyle approaches, diet, and physical activity). Of the 37 included studies, 31 used placebo and six used no intervention (baseline treatment alone) as the comparator. The studies were conducted across 17 high-income, six middle-income, and three low-income countries. Length of follow-up ranged from six to 31 months, with a median of 11 months. Pharmacological interventions versus placebo Compared to placebo, pharmacological interventions (glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, orlistat, sibutramine, topiramate, phentermine plus topiramate) may reduce BMI (change from baseline) by 1.80 kg/m2 (95% CI -2.36 to -1.24; I2 = 87%; 25 studies, 3091 participants; low-certainty evidence) and weight (change from baseline) by 5.47 kg (95% CI -7.45 to -3.50; I2 = 89%; 20 studies, 2380 participants; low-certainty evidence). Adverse events were frequent. Pharmacological interventions (GLP-1 agonists, sibutramine, phentermine, topiramate) likely make little to no difference in the risk of any adverse events compared to placebo (RR 1.03, 95% CI 1.00 to 1.07; I2 = 0%; 8 studies, 1877 participants; moderate-certainty evidence). Pharmacological interventions (GLP-1 agonists, metformin, orlistat, sibutramine, phentermine, topiramate) may make little to no difference in the risk of discontinuation due to adverse events, although the risk was slightly higher with the medications (RR 1.50, 95% CI 0.82 to 2.75; I2 = 17%; 13 studies, 2213 participants; low-certainty evidence). One study (46 participants), comparing sibutramine to placebo, found that there may be little to no difference in the incidence of obesity-related outcomes for adolescents with comorbidities (assessed as changes in glycemia, blood pressure, total cholesterol, and triglycerides). We were unable to pool other data on incidence or severity of obesity-related outcomes. Compared to placebo, pharmacological interventions (GLP-1 agonists, phentermine plus topiramate) likely result in little to no difference in quality of life, assessed with the Impact of Weight on Quality of Life-Kids (IWQOL) questionnaire (MD 1.02, 95% CI -1.94 to 3.98; I2 = 48%; 4 studies, 741 participants; moderate-certainty evidence). Pharmacological interventions versus no intervention Compared to no intervention, metformin may reduce BMI (change from baseline) by 1.51 kg/m2 (95% CI -2.29 to -0.73; I2 = 0%; 3 studies, 151 participants) and weight (change from baseline) by 3.20 kg (95% CI -6.12 to -0.28; 1 study, 42 participants), but the evidence for both outcomes is very uncertain. Compared to no intervention, pharmacological interventions (metformin and orlistat) may increase the risk of discontinuations due to adverse events, but the evidence is very uncertain (RR 13.70, 95% CI 0.83 to 225.43; 2 studies, 84 participants). None of the studies comparing pharmacological interventions to no intervention reported data on adverse events, obesity-related outcomes, and quality of life that could be pooled in meta-analysis. Only eight of the 37 included studies enrolled children, and data were seldom disaggregated by age, limiting the ability to draw conclusions about benefits or harms in children. This review includes clinical trials assessing the benefits and harms of pharmacological treatments - including GLP-1 agonists, metformin, orlistat, phentermine, sibutramine, and topiramate - for weight management in adolescents with obesity. Evidence suggests that pharmacological treatments may result in small reductions in BMI and weight, which could be clinically important, although effects vary by medication. Evidence on desirable and undesirable effects in children is scant. Uncertainties remain about the optimal duration of treatment, consequences of treatment discontinuation, and long-term benefits and harms, particularly considering the physiology of children and impact on growth. Studies with longer follow-up are needed to evaluate outcomes beyond BMI and weight change, including the potential effects of treatment discontinuation. The Department of Nutrition and Food Safety at the WHO commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation (NORAD), the Swedish International Development Cooperation Agency (SIDA), the Government of the Grand Duchy of Luxembourg, the Government of Germany (BMG), and the Government of Greece to the WHO Department of Nutrition and Food Safety. Our protocol is registered in PROSPERO: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433123.
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.
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.
Mild cognitive impairment (MCI) may precede dementia, and safe nutritional strategies able to support cognitive function are of clinical interest. Dietary nucleotides may contribute to membrane phospholipid synthesis, synaptic function, and neuroprotective pathways; however, clinical evidence in older adults with MCI remains limited. This randomized placebo-controlled trial evaluated the efficacy and tolerability of nucleotide-rich yeast extracts from Kluyveromyces fragilis and Saccharomyces cerevisiae. Seventy-two participants (mean age 73.5 ± 7.7 years; range 60-85) were randomly assigned (1:1:1) to receive K. fragilis extract, S. cerevisiae extract, or placebo once daily for 180 days. Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) at baseline (T0), 90 days (T1), and 180 days (T2); quality of life was assessed using the SF-12 questionnaire at T0 and T2. Treatment effects were analyzed using linear mixed-effects models adjusted for age and sex. After 180 days, MoCA scores increased by 4.42 points in the K. fragilis group and 3.92 points in the S. cerevisiae group, compared with 0.58 points in the placebo group (time × treatment p < 0.001; T0-T2 within-group p < 0.001 for both active groups and p = 0.14 for placebo). MMSE scores increased by 1.62 and 3.11 points in the K. fragilis and S. cerevisiae groups, respectively, compared with 0.25 points in the placebo group (time × treatment p < 0.001; T0-T2 within-group p < 0.001 for both active groups and p = 0.57 for placebo). The SF-12 mental component score increased by 7.50 and 9.16 points in the two active groups, respectively (time × treatment p = 0.022; T0-T2 p = 0.0013 and p < 0.001, respectively), while physical quality-of-life scores did not change significantly (PCS time × treatment p = 0.11). No adverse events were reported. Nucleotide-rich K. fragilis and S. cerevisiae yeast extracts were well tolerated and were associated with improved cognitive scores over six months in older adults with MCI. Larger multicenter trials are needed to confirm these findings.
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.
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Primary immunodeficiencies, also known as inborn errors of immunity (IEIs), and secondary immunodeficiencies (SIDs) present a multitude of challenges for clinicians due to their overlapping clinical features and diverse underlying aetiologies. IEIs mainly arise from inherited genetic defects, while SIDs are acquired conditions. IEIs are associated with an increased risk of cancer, particularly haematological malignancies, which have been linked to SID, highlighting an area of overlap. It is being increasingly recognised that in the context of cancer, immune deficiencies initially attributed to secondary causes were in fact due to an underlying IEI. This article aims to provide a comprehensive guide for recognising the subtle, yet pivotal clues that may help identify an underlying IEI in patients with haematological malignancies. Combinations of clinical features aligned to the manifestations of IEI, laboratory markers, functional studies, IEI experienced histological assessment, and genetic studies, alongside recognition of atypical responses to therapy for autoimmune and inflammatory features of IEI, and atypical features of the malignancy and its response to therapy and recurrence, can help unmask the IEI hidden within SID. This distinction is of critical importance for patients and their families, as it alters both the treatment of the underlying IEI as well as potentially the approach to the treatment of malignancy.
The present study aimed to analyze systemic antibiotic prescription patterns in the Salerno Local Health Authority (ASL Salerno) during 2024. The objective was to describe territorial antibiotic consumption and monitor prescribing appropriateness from epidemiological, pharmacological, and antimicrobial stewardship perspectives, using the World Health Organization (WHO) AWaRe classification system as a reference. A retrospective analysis of antibiotic prescriptions was conducted across ASL Salerno in 2024. Total prescription and associated expenditures were assessed, along with distribution across districts and pharmacological classes. Antibiotics were categorized according to the Anatomical Therapeutic Chemical (ATC) system and further classified using the WHO AWaRe framework (Access, Watch, Reserve) to evaluate prescribing appropriateness and potential patterns of antimicrobial resistance. More than 1 million antibiotic prescriptions were recorded, totaling approximately €15 million in expenditure. Prescribing patterns showed a predominance of penicillins and cephalosporins, followed by macrolides, fluoroquinolones, and J01X class. A substantial proportion of prescriptions belonged to the Watch category, particularly third-generation cephalosporins, fluoroquinolones, and fosfomycin. Some districts demonstrated a higher reliance on Watch antibiotics, while others showed increased use of Access agents such as amoxicillin, doxycycline, and amikacin. The surveillance analysis highlights significant variability in antibiotic prescribing practices within ASL Salerno and a substantial use of Watch-group antibiotics. These findings suggest the need for strengthened antimicrobial stewardship interventions, such as targeted education, auditing, and decision-support tools. Continuous monitoring of prescribing trends is essential to encourage appropriate antibiotic use and contribute to the containment of antimicrobial resistance.
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.