Ca' Foncello Hospital

BackgroundTherapeutic hypothermia (TH) is the standard treatment for moderate to severe hypoxic–ischemic encephalopathy (HIE), yet pain assessment during TH remains challenging. This study compares two validated pain scales in asphyxiated newborns undergoing TH and receiving fentanyl analgesia.MethodsTwenty term infants with HIE treated with TH were enrolled. Pain was assessed using EDIN and N-PASS, while sedation was monitored using the N-PASS sedation subscale.ResultsN-PASS pain and sedation scores significantly decreased by day 3, whereas EDIN scores showed no significant temporal change. Effective analgesia significantly increased over time, either when defined based on EDIN (OR 3.12, p = 0.002) and on N-PASS (OR 3.06, p = 0.007), while N-PASS sedation did not show a time-dependent association. No scale showed a significant association with fentanyl dosage. A moderate positive correlation was found between EDIN and N-PASS pain scores (r = 0.409, p < 0.001). Sedation targets were achieved in only 40%–50% of assessments, with early undersedation and later oversedation observed.ConclusionsEDIN and N-PASS pain scores demonstrate moderate concordance, but capture different dimensions of neonatal pain during TH. N-PASS appears more sensitive to temporal changes, likely due to its combined behavioral and physiological components, whereas EDIN may be affected by hypothermia-related behavioral suppression.

Despite continuous improvements in neonatal resuscitation and stabilization in the last decades, thermal management immediately after birth remains an unresolved issue in preterm infants. To compare 2 strategies of thermal management (plastic wrapping with or without drying) for preventing heat loss at birth in very preterm infants. This multicenter, unblinded, randomized clinical trial was conducted among very preterm infants (birth weight <1500 g and/or gestational age ≤30 weeks 6 days) at 21 tertiary care hospitals in Italy from February 21, 2023, to July 18, 2024. Eligible neonates were randomly allocated to either drying before plastic wrapping in the delivery room (intervention arm) or plastic wrapping without drying (control arm). The primary outcome was the proportion of participants with normothermia (36.5-37.5 °C) at admission to the neonatal intensive care unit (NICU). The secondary outcomes included hypothermia (<36.5 °C), moderate to severe hypothermia (<36.0 °C), and hyperthermia (>37.5 °C) at NICU admission, temperature at 1 hour after NICU admission, intraventricular hemorrhage, respiratory distress syndrome, late-onset sepsis, bronchopulmonary dysplasia, and mortality before hospital discharge. Overall, 354 very preterm infants were randomized (180 [50.8%] female; mean [SD] gestational age, 28.6 [2.5] weeks); all received the allocated intervention and were included in the analysis. Normothermia at NICU admission was achieved in 81 of 177 dried infants (45.8%) and 82 of 177 undried infants (46.3%; risk ratio, 0.99; 95% CI, 0.79-1.24). The mean (SD) neonatal temperature at NICU admission was 36.4 °C (0.8 °C) in dried neonates and 36.5 °C (0.7 °C) in undried neonates (mean difference, -0.1 °C; 95% CI, -0.2 °C to 0.1 °C). In-hospital mortality included 26 of 177 dried neonates (14.7%) and 10 of 177 undried neonates (5.6%) (unadjusted risk ratio, 2.60; 95% CI, 1.29-5.23). The other secondary outcome measures were not different between the 2 arms. In this multicenter randomized clinical trial, drying before plastic wrapping provided no benefit to very preterm infants in maintaining normothermia at NICU admission. Most deaths could be expected due to the compromised profile of the neonates, with no pathophysiological explanation related to the trial interventions. Approximately half of the infants were outside the normal thermal range at NICU admission; hence, thermal management remains a challenge requiring further investigations. ClinicalTrials.gov Identifier: NCT05740072.

This review examines the protocols and rationale for stopping antiarrhythmic drugs (AADs) before interventional electrophysiology (EP) procedures to establish a drug-free baseline, ensuring diagnostic accuracy and procedural success. The review provided a detailed analysis of procedure-specific AADs washout requirements for supraventricular tachycardia, atrial fibrillation, and ventricular tachycardia ablation, and a comprehensive, drug-by-drug guide to calculate washout periods, based on pharmacokinetic and pharmacodynamic principles. This guide details the half-life, metabolism, and elimination pathways for all major AAD classes, and gives specific, actionable recommendations for adjusting wash-out times based on patient-specific factors, including age, renal function, and hepatic impairment. The aim is to provide clinicians with evidence-based guidance for standardizing AADs washout, thereby improving the safety and success of interventional EP procedures.

Background: Artificial intelligence (AI) is increasingly integrated into healthcare and public services, making user acceptance a key prerequisite for safe and effective implementation. The Artificially Intelligent Device Use Acceptance (AIDUA) model provides a multidimensional framework for evaluating acceptance of intelligent systems, yet no validated Italian instrument is currently available. Objectives: This study aimed to translate, culturally adapt, and preliminarily validate the Italian version of the AIDUA scale (AIDUA-IT) following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations. Methods: A two-phase cross-sectional design was used. Phase one included forward-backward translation, expert review (n = 7), and cognitive debriefing (n = 8). Phase two assessed structural validity, internal consistency, convergent and discriminant validity, and short-term test-retest reliability in a convenience sample of Italian-speaking adults (N = 140), with a subsample completing the test-retest assessment (n = 32). Results: The hypothesized eight-factor measurement model demonstrated excellent fit (Comparative Fit Index [CFI] = 0.984; Tucker-Lewis Index [TLI] = 0.981; Root Mean Square Error of Approximation [RMSEA] = 0.041; Standardized Root Mean Square Residual [SRMR] = 0.056), with strong standardized loadings (β range: 0.64-0.96) and good internal consistency (Cronbach's α and McDonald's ω range: 0.82-0.90). Convergent and discriminant validity were supported, and test-retest reliability was good to excellent across subscales (Intraclass Correlation Coefficient [ICC] range: 0.81-0.90). Conclusions: These findings provide initial evidence that the AIDUA-IT is a reliable and valid instrument for assessing acceptance of AI-enabled services in Italy. Further validation in larger and more diverse samples is recommended.

The purpose of this systematic review was to provide a comprehensive assessment of the literature on the relationship between the presence of effusion, as determined by magnetic resonance imaging (MRI), and clinical pain in patients with temporomandibular disorders (TMD). The study was performed in order to answer the following clinical question: "Can MRI-detected temporomandibular joint (TMJ) effusion be considered a marker of clinical pain?"On June 15, 2024, a systematic literature review was performed in the PubMed® and Scopus databases. The Medical Subject Headings (MeSH) terms used to initiate the search were "temporomandibular joint" AND "MRI". A PICO (Population, Intervention, Comparison, and Outcome) structured reading model was employed to identify and assess articles that evaluated the correlation between TMJ effusion visible on MRI scans and clinical pain reported by patients. The review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 539 articles were initially retrieved, of which 14 answered the research question. The review revealed a consistent pattern of results, with 12 out of the 14 articles reporting an association between effusion and pain.The findings indicate that there is a link between the occurrence of effusion and the experience of pain in individuals diagnosed with TMD.

Epidemiological and retrospective studies suggest that letrozole may improve outcomes in low-grade serous carcinoma of the ovary (LGSCO) by targeting estrogen-driven tumor progression. We designed a multicenter, randomized, open-label, phase III trial to compare letrozole versus standard chemotherapy (carboplatin plus paclitaxel) in prolonging progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), quality of life (MENQoL), and musculoskeletal pain (BPI-SF). Translational objectives explore mutational and expression profiles (NGS, RAD51/BRCA1 foci) and circulating tumor DNA (ctDNA) as markers of treatment response. Eligible patients are postmenopausal women with stage III-IV ER/PgR-positive LGSCO after primary cytoreductive surgery. Patients are randomized 1:1 to letrozole 2.5 mg daily until progression or unacceptable toxicity, or to carboplatin-paclitaxel for 6-8 cycles. Disease progression is assessed by RECIST, CA-125, and imaging every 3-6 months. As of March 2025, 46 patients have been randomized (23 per arm). Preliminary analysis shows a favorable safety profile for letrozole compared with chemotherapy. Early findings suggest letrozole is well tolerated and may represent a viable therapeutic option for hormone receptor-positive LGSCO. Ongoing molecular and clinical analyses will clarify its role in this rare subtype. ClinicalTrials.gov Identifier: NCT05601700; https://clinicaltrials.gov/study/NCT05601700.

Background and ObjectivesPatients with multiple sclerosis (MS) exhibit variability in disability progression and response to disease-modifying therapies (DMTs). Identifying those at greatest risk of disability worsening and most likely to benefit from high-efficacy DMTs remains challenging. We aimed to identify distinct disability worsening phenotypes, explore their mechanisms, and evaluate DMT impact across them.MethodsIn this multicenter cohort study, we analyzed clinical and MRI data from propensity-matched cohorts of treated and untreated patients with relapse-onset MS from the Italian MS Register. Inclusion criteria were as follows: ≥3 years of follow-up, ≤1 year between disease onset and first assessment, and complete clinical and baseline MRI data. Latent class mixture models were applied to Expanded Disability Status Scale (EDSS) scores from untreated patients to identify disability worsening phenotypes. We compared proportions of progression independent of relapse activity (PIRA) and relapse-associated worsening events across phenotypes. A random forest algorithm, trained (70%) and tested (30%) on baseline clinical and MRI features of untreated patients, was used to assign phenotypes to treated patients. Linear mixed-effects models estimated DMT impact on disability trajectories within each phenotype.ResultsWe analyzed data from 2,563 untreated (mean age 41.2 ± 10 years, 67% female) and 2,952 treated (mean age 40.8 ± 11.4 years, 66% female) patients with MS over a median follow-up of 10.1 (interquartile range: 7.0–13.0) years. Four phenotypes were identified in untreated patients: “minimal-worsening” (15%), “late-worsening” (70%), “early-worsening” (3%), and “rapid-worsening” (12%). In all phenotypes, PIRA represented the main disability accrual mechanism. “Early-worsening” and “rapid-worsening” phenotypes exhibited more brain and spinal cord T2-hyperintense and gadolinium-enhancing lesions at baseline. The classification algorithm assigned phenotypes to patients receiving DMTs with 71% accuracy: “minimal-worsening” (18%), “late-worsening” (61%), “early-worsening” (13%), and “rapid-worsening” (8%). DMT exposure significantly reduced disability accrual in all phenotypes, with high-efficacy DMTs (β = −0.16, standard error (SE) = 0.06, p < 0.001) and early escalation (β = −0.18, SE = 0.06, p < 0.001) proving especially beneficial for the “rapid-worsening” phenotype.DiscussionWe identified 4 clinically relevant disability worsening phenotypes in relapse-onset MS, primarily driven by PIRA, with greater CNS involvement linked to early and rapid progression. Despite reliance on EDSS alone, these phenotypes may inform personalized treatment and response assessment.