Azienda Ospedaliera S.Giuseppe Moscati

Pure apathy is relatively common in people with Multiple Sclerosis (PwMS), but its neural mechanisms remain unexplored. Therefore, we investigated the neural correlates of pure apathy in PwMS, differentiating it from depression. Sixty-two PwMS underwent neuropsychological assessments and Magnetic Resonance Imaging scans. Pure apathy is primarily associated with lesions in the cortical-limbic-subcortical system implicated in goal-directed behaviour and motivation. Apathy and depression arise from distinct yet partially overlapping neural mechanisms, with basal ganglia and limbic structures playing a key role.

Subclinical coronary atherosclerosis is common but its biological aggressiveness and interplay with extracoronary disease in asymptomatic individuals remain unclear. We evaluated the prevalence of high-risk coronary plaques (HRPs) and their relationship with mild carotid atherosclerosis and coronary calcium in a cardiovascular (CV) high-risk cohort in primary prevention. This retrospective multicenter study enrolled 269 asymptomatic adults with multiple CV risk factors who underwent Coronary Computed Tomography Angiography (CCTA) after prior carotid duplex ultrasound (CDUS). Coronary artery disease (CAD) was graded as absent, non-obstructive (<50% stenosis) or obstructive (≥50%), and HRPs were identified by ≥1 adverse morphological feature (low attenuation, positive remodeling, napkin-ring sign, spotty calcification). Carotid disease was classified as CDUS 0 (no plaque), CDUS 1-49% (mild), or CDUS ≥ 50% (significant). Pre-specified analyses explored prevalence of HRPs across CDUS-calcium-score strata (cut-off 100 Agatston) and independent predictors within the CDUS 1-49% subgroup. CAD was absent in 31%, non-obstructive in 41%, and obstructive in 28%. HRPs were present in 30.9% of all cases, in 26.6% of non-obstructive and in 64.6% of obstructive CAD. HRPs prevalence rose step-wise from 10.0% (CDUS 0 + Ca < 100) to 27.7% (CDUS 1-49% + Ca < 100), 41.2% (CDUS 0 + Ca ≥ 100) and 59.4% (CDUS 1-49% + Ca ≥ 100). In patients with CDUS 1-49%, current smoking independently predicted HRPs (OR 2.1, 95% CI 1.0-4.5; p = 0.049). Nearly one-third of asymptomatic adults with high CV risk already showed HRPs. Mild carotid atherosclerosis synergized with a calcium score ≥ 100 to identify a subgroup in which six of ten individuals exhibited HRPs. Smoking was the only independent clinical correlate identified of plaque vulnerability. Combined carotid ultrasound, calcium scoring and CCTA may substantially refine primary prevention risk stratification beyond traditional factors.

Real-world evidence on atogepant remains limited. GIANT2 explores the 24-week real-life effectiveness of atogepant in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) under routine clinical conditions. GIANT2 is a 24-week, prospective, multicenter, real-world, study including consecutive patients with HFEM or CM with ≥3 preventive treatment failures, treated with atogepant 60 mg once daily. Co-primary endpoints: proportions achieving ≥50% and ≥75% reductions in monthly migraine days for HFEM or monthly headache days for CM at weeks 21–24 versus baseline. Secondary endpoints: changes in migraine/headache days, analgesic intake, pain intensity, disability, patient global impression of change, 100% response rates, tolerability and safety. Response rates at weeks 21–24 were also evaluated in patients with prioranti-CGRP mAb failure. Exploratory analyses: proportion of >50% responders achieving >30% reduction in NRS scores and response rates in subgroups combining psychiatric comorbidities, CM, and medication overuse headache (MOH). Of 233 patients enrolled, 156 completed >24 weeks of treatment, with 37.2% having failed prior anti-CGRP mAbs. At weeks 21–24, 76.9% achieved a ≥ 50% response and 45.5% a ≥ 75% response, with ≥50% response more frequent in HFEM than CM (p = 0.005). A 100% response occurred in 5.1% of patients. All secondary endpoints improved significantly (p < 0.001) with greater benefits at week 24 than week 12. No difference in effectiveness was observed between mAb-naïve patients and those with prior mAb failures, who achieved ≥50% and ≥75% response rates of 70.7% and 39.7%. A combined ≥50% frequency reduction and ≥30% pain reduction was achieved by 54.5% of patients. Among patients with psychiatric comorbidities, 63.0% were ≥50% responders, while among CM patients rates were 62.1% in those with MOH and 40.0% in those with both psychiatric comorbidities and MOH (≥75% responder rates 42.4%, 37.0%, and 28.0%). Adverse events occurred in 11.2% of patients and led to discontinuation in 1.3%. GIANT2 shows that atogepant effectiveness increases from week 12 to 24 with a high proportion of responders and super-responders regardless of prior anti-CGRP mAb failure and reduces pain intensity in residual headaches in most patients. It is also effective in migraine subgroups combining psychiatric comorbidities, CM and MOH. NCT06136442.

Abstract Background Patients with Inflammatory Bowel Disease (IBD), i.e. Ulcerative colitis (UC) and Crohn’s Disease (CD), may suffer from genito-urinary tract-related disturbances. Whether lower urinary tract symptoms (LUTS) are more frequent in IBD patients is unclear. Objectives: 1) to assess the prevalence of LUTS in patients with IBD compared to controls (HC); 2) to define the role of clinical-demographic variables in this clinical setting. Methods Real-life, cross-sectional, multi-center study. LUTS were assessed in males and females through the International Prostatic Symptoms Score (IPSS) and the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaires, respectively. IBD activity was assessed in CD by the CDAI, and in UC by PMS and TMS. Significance of differences was assessed by chi2 or Fisher’s exact test or Mann–Whitney or Kruskal–Wallis test, as appropriate. Correlation was tested by Spearman’s analysis. The level of statistical significance, corrected by the Bonferroni method for multiple testing, was set at p &amp;lt; 0.017. Results 1) Two hundred forty-five IBD patients [(35.5% CD, 64.5% UC), 152 males and 93 females, median age 47 yrs (34-61 yrs)] and 142 HC [64 males and 78 females, median age 46 yrs (35-58 yrs)] were included; 2) IPSS total score was higher in IBD patients than in HC [7 (3-12) vs 4 (1-8), respectively, p = 0.002], with no significant differences between CD and UC; 3) IPSS subscores of incomplete emptying and intermittency were significantly higher in IBD patients than in HC (p = 0.001 and p = 0.004, respectively); 4) A significantly higher percentage of IBD patients had moderate to severe IPSS total score compared to HC (28.5% vs 11.2%, p = 0.003); 5) BFLUTS total score, was higher in IBD patients, particularly in UC, than in HC [7 (3–12) vs. 4.5 (2–11.3), p = 0.044); 6) IBD activity showed a weak (i.e. r = 0.2-0.29) to moderate (r = 0.3-0.39) correlation with IPSS or BFLUTS. Conclusion 1) Prevalence of LUTS is higher in IBD patients than in controls with no differences between CD and UC; 2) IPSS moderate to severe total scores are more frequent in IBD patients than in controls; 3) Male IBD patients have significantly higher incomplete emptying and frequency IPSS subscores than controls; 4) IBD patients should be assessed for LUTS through validated questionnaires for prompt diagnosis and treatment.

The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1years, range 65.1-94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56-0.73, p<0.001). At 12months, the discontinuation rate was significantly higher among patients with a CFS >3 (29.2%) compared with those with a CFS ≤3 (8.8%) (p<0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

Robot-assisted retroperitoneal lymph node dissection (R-RPLND) is an increasingly adopted minimally invasive option for carefully selected patients with testicular germ-cell tumours. We performed a narrative (non-systematic) review of retrospective single- and multicentre cohorts from high-volume programmes to appraise peri-operative safety, functional preservation, and oncologic control in primary and post-chemotherapy settings. In primary disease (typically clinical stage I–IIA/B), representative medians across series from expert centres include estimated blood loss of ~ 50 to 200 mL, hospital stay of 1–2 days, and nodal yields of ~ 19 to 32; major complications (Clavien–Dindo ≥ III) are uncommon (~ 0 to 10%), and antegrade ejaculation is usually preserved (often ≥ 85 to 100%) when nerve-sparing templates are applied. In post-chemotherapy cohorts—generally limited to smaller, peripherally located residual masses with favourable biology—robotic RPLND is feasible but technically demanding, with reported conversion rates of ~ 0 to 13% and major complication rates of ~ 10 to 20%; chylous complications remain a notable risk. Across available retrospective comparative series, including propensity-matched cohorts, R-RPLND has been associated with lower estimated blood loss and shorter hospitalisation than open RPLND (for example, ~ 200 vs 300 mL and 1 vs 5 days in a matched primary cohort; ~ 235 vs 825 mL and 2 vs 7 days in post-chemotherapy series), at the cost of longer operative time, while nodal yields and short-term oncologic outcomes appear comparable; these non-randomised data are descriptive and subject to selection and centre bias rather than proof of causality. For carefully staged seminoma IIA/B (≤ 3 cm nodes), contemporary guidelines permit RPLND as a chemotherapy-sparing option (Moderate recommendation; Evidence Level B), consistent with phase II data showing high 2–3-year disease control after primary RPLND. Centralisation and experience are critical: population-based analyses suggest fewer in-hospital complications and shorter hospital stays with robotic cases, and learning-curve data show improving efficiency and safety as programmes mature. Overall, when undertaken by experienced teams in high-volume centres, R-RPLND offers low blood loss, short hospitalisation, favourable ejaculatory outcomes, and low in-field recurrence for appropriately selected patients, while requiring judicious case selection and a low threshold for conversion in technically demanding post-chemotherapy disease.

This study aims to compare and organize recommendations from the most eminent international guidelines on the staging and treatment of lymph node (LN) involvement in penile cancer (PC). Early recognition and appropriate management of nodal disease remain the cornerstone of care, influencing both survival and treatment-related morbidity. This study compares and organize recommendations form the most eminent international guidelines-including NCCN, ESMO-EURACAN, and EAU-ASCO-on the staging and treatment of lymph node involvement in penile cancer. Open inguinal LN dissection (ILND) remains the standard treatment for not superficial cancers and its morbidity has driven interest in minimally invasive surgical approaches, such as video-endoscopic inguinal lymphadenectomy (VEIL), including its robot-assisted variant (RA-VEIL). Their role is well defined in clinically node-negative (cN0) patients but remains investigational in node-positive (cN+) cases. For cN3 disease and pelvic node involvement, multimodal strategies including chemotherapy, surgery, and radiotherapy are required. The variability among guidelines underscores the need for collaborative efforts and high-quality prospective trials to refine and standardize treatment recommendations.

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of near normal, normal, and supernormal left ventricular (LV) function. Objectives To assess the value of resting LV elastance (also known as force) with transthoracic echocardiography (TTE) to identify HFpEF phenotypes. Methods In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024. Systolic blood pressure (SBP) was measured. We assessed LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE), ventricular-arterial coupling (VAC), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. 680 patients finished follow-up with a composite end-point of major adverse cardiac events (MACEs). Patients were divided into three groups: low force (&amp;lt; 25th percentile, Group 1, &amp;lt; 3.24 mmHg/ml), intermediate force (≥ 25th percentile and ≤ 75 thpercentile, Group 2, 3.24-5.48 mmHg/ml), and high force (&amp;gt; 75 th percentile, Group 3, &amp;gt;5.48 mmHg/ml). Results The 3 groups showed a gradient with descending values (Group 3&amp;gt;2&amp;gt;1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1&amp;gt; 2&amp;gt; 3) for EDV, ESV, SV, and LAVI values (all P&amp;lt;0.01). After a median follow-up of 16 months, 205 MACEs occurred in 138 patients. Cumulative MACEs rate was lowest in group 2 (14.7% person-year), higher in group 1 (16.1% person-year) and 3 (22.9% person-year, log rank p = 0.036). Conclusions HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with larger LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. The hypercontractile and hypocontractile phenotypes are associated with a higher risk of subsequent events.