Fatebenefratelli Hospital

Macchia G., Campitelli M., Pezzulla D., Lucci S., Fodor A., Russo D., Balcet V., Bonome P., Durante S., Draghini L., Titone F., D'Agostino G.R., Tamburo M., Ferioli M., Ippolito E., et. al.

MITO-RT3/RAD (NCT04593381) is a prospective multicenter Phase II trial designed to assess the effectiveness and safety of stereotactic body radiotherapy (SBRT) in patients diagnosed with oligometastatic ovarian cancer (oligo-MPR-OC). In this report, we provide the results of the trial in the setting of lymph node disease.

Festa E., Ascione T., De Mauro D., Di Gennaro D., Baldini A., Balato G.

A 1.5-stage revision could be an alternative to a 2-stage revision for treating hip and knee chronic periprosthetic infections, guaranteeing the maintenance of joint function and infection control and preventing infection-free patients from undergoing further surgery. Our systematic review aimed to answer several questions about the indication, the infection eradication rate, and the long-term functional outcome of 1.5-stage revisions used to treat chronic periprosthetic infections of the hip and knee.

Calegari M., Zurlo I., Dell'Aquila E., Basso M., Orlandi A., Bensi M., Camarda F., Anghelone A., Pozzo C., Sperduti I., Salvatore L., Santini D., Corsi D., Bria E., Tortora G.

The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.

Evola F.R., Caldaria A., Costarella L., D’Amico A.G., D’Agata V., Vecchio M., Sessa G.

Short-stem implants offer several advantages, including the preservation of bone stock and a physiological load transfer in the subtrochanteric area. The aim of this study was to compare the radiological and functional outcomes of short stem and traditional stem during midterm follow-up. We conducted a retrospective analysis of a consecutive series of 50 patients with Fitmore and CLS stems. Clinical assessment was performed by Harris hip score; additionally, thigh pain was assessed at six months, one year, and the latest follow-up. The following radiological parameters were evaluated: stem alignment, presence of radiolucent lines and osteolysis around the stem, stem subsidence, cortical hypertrophy, femoral stress-shielding, pedestal formation at the tip of the stem, calcar resorption, heterotopic ossification, and implant loosening. The mean follow-up duration was 8.4 ± 2.1 years in the CLS group and 7.6 ± 2.2 years in the Fitmore group. The mean HHS improved from 43.0 ± 3.3 to 93.2 ± 2.5 for the CLS group and from 43.2 ± 4.4 to 93.6 ± 3.2 for the Fitmore group, without any statistical differences between the two groups. Thigh pain disappeared in all patients in the Fitmore group, while it persisted in 8% of the patients in the CLS group. There was a significant difference in the level of cortical hypertrophy between the two groups, with 28% in the Fitmore group compared to 12% in the CLS group. No statistically significant difference was observed for other radiological parameters. Both short stems and standard stems demonstrated stable fixation and satisfactory clinical and radiological outcomes.

Foschi M., D’Anna L., De Matteis E., De Santis F., Romoli M., Tassinari T., Saia V., Cenciarelli S., Bedetti C., Padiglioni C., Censori B., Puglisi V., Vinciguerra L., Guarino M., Barone V., et. al.

BACKGROUND: Sex may impact clinical outcomes in patients with stroke treated with dual antiplatelet therapy (DAPT). We aimed to investigate the sex differences in the short-term outcomes of DAPT within a real-world population of patients with noncardioembolic mild-to-moderate ischemic stroke or high-risk transient ischemic attack. METHODS: We performed a propensity score–matched analysis from a prospective multicentric cohort study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]) by including patients with noncardioembolic mild-to-moderate stroke (National Institutes of Health Stroke Scale score of 0–10) or high-risk transient ischemic attack (age, blood pressure, clinical features, duration of transient ischemic attack, presence of diabetes [ABCD 2 ] ≥4) who initiated DAPT within 48 hours of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, and 24-hour early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleeding, symptomatic intracranial hemorrhage, and 24-hour hemorrhagic transformation. Outcomes were compared between sexes using Cox and generalized ordinal logistic regression analyses, along with calculating risk differences and ratios. RESULTS: From 2278 patients in the READAPT study cohort, we included 1643 mild-to-moderate strokes or high-risk transient ischemic attacks treated with DAPT (mean age, 69.8±12.0 years; 34.3% women). We matched 531 women and men. The 90-day risk of new ischemic stroke or other vascular events was significantly lower among women than men (hazard ratio, 0.53 [95% CI, 0.28–0.99]; P =0.039). There were no significant differences in secondary effectiveness outcomes. The 90-day risk of safety outcomes was extremely low and did not differ between women and men (moderate-to-severe bleedings: 0.4% versus 0.8%; P =0.413; symptomatic intracranial hemorrhage: 0.2% versus 0.4%; P =0.563). Subgroup analysis for primary effectiveness outcome showed a lower 90-day risk of new ischemic stroke or other vascular events among women aged <50 years, baseline National Institutes of Health Stroke Scale score of 0 to 5, prestroke modified Rankin Scale score <2, large artery atherosclerosis cause, and no diabetes. CONCLUSIONS: Our findings suggest that women with noncardioembolic mild-to-moderate stroke or high-risk transient ischemic attack treated with DAPT may have lower short-term risk of recurrent ischemic events than men. Further research is needed to understand the mechanisms behind potential sex-based differences in outcomes after DAPT use. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05476081.

Manzia T.M., Trapani S., Nardi A., Ricci A., Lenci I., Sensi B., Angelico R., De Feo T.M., Agnes S., Andorno E., Baccarani U., Carraro A., Cescon M., Cillo U., Colledan M., et. al.

The challenge of transplant waiting-lists is to provide organs for all candidates while maintaining efficiency and equity.

Wierzbowska-Drabik K., Palinkas E.D., D'alfonso M.G., Mori F., Del Franco A.M., Peteiro Vazquez J., Tesic M., Djordjevic-Dikic A., Re F., Palinkas A., Aguiar Rosa S., Ciampi Q., Pellikka P., Olivotto I., Picano E.

Abstract Background The left ventricular (LV) hypercontractile phenotype (HP) plays a critical role in hypertrophic cardiomyopathy (HCM) and is usually identified with the left ventricular outflow tract gradient (LVOTG). Purpose To assess the systemic and coronary hemodynamic profile associated with HP identified with increased LV elastance (also known as force) at rest in patients with HCM. Methods We enrolled 1248 HCM patients (age 50 ± 15 years, 798 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 14 quality-controlled sites from 7 countries TTE assessment included LVOTG, EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume, mmHg/mL). Volumetric echocardiography with Simpson’s method was used to measure EF from end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), arterial elastance (AE) and ventricular-arterial coupling (VAC). We also assessed resting peak diastolic coronary flow velocity (D-CFV) in the mid-distal left anterior descending artery in a subset of 275 patients. Results EF equaled 68 ± 7%, force = 6.8 ± 5.3 mmHg/ml and LVOTG = 22 ± 28 mmHg. HP was identified as the highest quartile of force (&gt; 7.85 mmHg/ml, mean value= 13.3 ± 7.0). HP showed the lowest SV (46 ± 18 ml) and EDV (61 ± 20 ml), with the highest AE (3.19 ± 1.35 mmHg/ml) and VAC (3.46 ± 1.59) compared to other quartiles (p&lt;0.001) ( see Picture) . D-CFV was not higher in patients with HP (n = 65) compared to those (n = 210) without HP (41± 11 vs 38 ± 14 cm/s, p=ns, but higher in comparison to joint first and second Force quartile (n=122) vs 37 ±14 p =0.0472). Table displays the demografic, clinical and TTE parameters related to HP (Table). In multivariate logistic analysis 4 independent predictors of HP were identified: SBP &gt;130 mmHg with OR 2.5, female sex with OR 5.4, LV EF &gt;70% with OR 6.1 and LVOTG &gt;30 mmHg with the highest OR = 6.3. Conclusion: HCM patients with HP exhibit a distinctive systemic hemodynamic and coronary physiology profile, characterized by low SV, high VAC, and supranormal baseline D-CFV compared to non-HP patients. These findings suggest reduced cardiovascular efficiency and increased myocardial oxygen demand, possibly detrimental over time.

Wang Y., Quirino C., Zagatina A., Padang R., Kane G.C., Villarraga H.R., Cortigiani L., Vazquez J.P., Boshchenko A., Ryabova T., Manganelli F., Amor M., Yin L., Pellikka P.A., Picano E.

Abstract Background Heart failure and preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of reduced, normal, and supernormal left ventricular (LV) function. Objectives To assess the value of resting LV elastance 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 by 35 certified laboratories of 15 countries. HFpEF was diagnosed according to the European Society of Cardiology (ESC) guidelines. Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE, SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. In 271 (11.4%) patients, N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. Patients were divided into three groups based on rest force: low rest force group (&lt; 25% percentile, Group 1), median rest force group (≥ 25% percentile & ≤ 75% percentile, Group 2), and high rest force group (&gt; 75% percentile, Group 3). Results 330 (13.9%) patients presented with ischemic RWMA. The 3 groups showed a gradient with descending values (Group 3&gt;2&gt;1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1&gt; 2&gt; 3) for EDV, EDVi, ESV, ESVi, SV, SVi, and LAVI values (all P&lt;0.01). Patients in Group 3 have higher NTproBNP level and higher percentage of B-line compared to groups 1 and 2 (P&lt;0.05). The 3 groups were similar for values of coronary flow velocity, systolic pulmonary artery pressure, and E/e’ (see table). Univariable linear regression analysis showed that NTproBNP was correlated with force (r = 0.271, p &lt; 0.001), VAC (r = 0.194, p = 0.001), LAVI (r = 0.327, p &lt; 0.001), LVEDV (r = -0.245, p &lt; 0.001), LVEDVi (r = -0.261, p &lt; 0.001), LVESVi (r = -0.190, p = 0.002) and LVESV (r = -0.187, p = 0.002) (see figure). However, multivariable linear regression analysis showed that NTproBNP was independently associated with LAVI (β= 0.211, p &lt; 0.001) and force (β= 1.804, p = 0.002). Conclusions HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. LV force is linearly correlated with cardiac natriuretic peptide levels. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with dilation of LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. heat map

Kazukauskiene I., Sablauskas K., Ciampi Q., Cortigiani L., Wierzbowska-Drabik K., Kasprzak J.D., Lowenstein J., Karuzas A., Prota C., Gaibazzi N., Lepone A., Marconi S., Kiziela A., Arbucci R., Picano E.

Abstract Introduction The accuracy of echocardiography interpretations is crucial. However, echocardiography has varying degrees of image quality, which can impact diagnostic decision-making. Automated chamber quantification of the left ventricle (LV) and left atrium (LA) has been shown to be feasible using machine learning (ML) systems. However, the effect of image quality on the performance of these ML systems has not been investigated. Purpose To assess the effect of different echocardiographic image quality on the performance of left-sided heart quantification using an ML system. Methods A multi-center study enrolled 240 patients who underwent stress echocardiography across five centers. The acquired rest phase images were anonymized for subsequent analysis. Expert cardiologists reviewed the studies, selecting apical four-chamber (4Ch) and two-chamber (2Ch) view images. The cardiologists identified end-systolic (ES) and end-diastolic (ED) frames. They traced the endocardial borders for the LA in ES and the LV in ED and ES. The same ED and ES frames were then processed by an ML algorithm trained on a separate set of images. Subsequently, an expert cardiologist, blinded to the previous measurements, assessed the image quality of LA and LV. The image quality for each chamber in the ES or ED frame was categorized into one of four grades: poor, suboptimal, fair, and optimal. Agreement analysis between human and AI measurements was performed within each image quality group. Yield was defined as the percentage of studies where the ML system predicted an echocardiographic parameter compared to a cardiologist. Results The yield of study parameters varied significantly with image quality. The lowest yield was 45%, observed for LV end-diastolic volume in the 2Ch view when image quality was poor. In contrast, the yield of 100% was seen for LV end-diastolic volumes in both the 4Ch and 2Ch views for optimal quality images. The correlation between automated and expert cardiologist measurements of left heart volumes varied depending on image quality. For poor or suboptimal images, the Pearson correlation coefficient ranged from 0.66 to 0.91 and improved to 0.85-0.92 in fair and optimal-quality images. Additionally, there was an inverse relation between agreement metrics (bias, limits of agreement, and coefficient of variation) and improvements in image quality. However, this tendency was less pronounced or nonexistent when comparing fair and optimal-quality images. (Table 1). Conclusions Image quality affects the yield of automated analysis and the agreement between cardiologists and automated measurements in echocardiography, highlighting the need for high-quality image acquisition in use with ML systems. Table 1

Costantino C., Bonaccorso N., Mazzucco W., Balsamo F., Sciortino M., Palermo M., Maiolo K., Tina L.G., Betta P.M., Caracciolo M., Loretta C.M., Cipolla D., Vitaliti S.M., Mancuso D., Vitaliti G., et. al.

Rotavirus disease is the world’s leading cause of severe gastroenteritis and mortality in children up to 5 years of age. Premature infants are more vulnerable to rotavirus gastroenteritis (RVGE) and its complications. International authorities strongly recommend vaccination because of the consistent reduction in infections, hospitalizations, deaths, and related costs. Background/Objectives: The objective of the present study was to evaluate the safety of anti-rotavirus vaccination in premature infants admitted and vaccinated in the main Sicilian Neonatal Intensive Care Units (NICUs) during the pandemic period. Methods: The human monovalent rotavirus vaccination (RV1) was administered to preterm infants of gestational age ≥28 weeks in the main Sicilian NICUs from January 2020 to December 2022, as a prolongation of a similar study conducted from April 2018 to December 2019. Rotavirus vaccinations were provided both to hospitalized infants and to those returning for post-discharge follow-up, beginning at six weeks of age according to the official immunization schedule. All potential adverse events—whether expected, unexpected, or serious—were recorded from the day of vaccination through 14 days (first follow-up) and 28 days (second follow-up) after each of the two scheduled doses. Results: A total of 355 preterm infants were fully vaccinated with RV in four Sicilian NICUs. The mean gestational age of newborns was 33.2 weeks (±2.7), 53% of whom were male. Vaccination was performed on average at 7 weeks of age (±2.1), and the mean weight at the time of vaccination was 3439 g (SD ± 745.2). No expected/unexpected or serious adverse events were observed either within the 14-day or within the 28-day period after administration of both two doses. Conclusions: Data confirm that vaccination in preterm infants ≥28 weeks gestational age is safe. The prolongation of this Public Health strategy, strongly recommended by the Sicilian Health Department during the pandemic period that also generally has led to a reduction of vaccination adherence and acceptance of pediatric vaccination, demonstrates the importance of multidisciplinary collaboration with neonatologists and pediatricians to continue promoting in-hospital vaccinations for fragile subjects.

Ruscitti P., Vitale A., Di Cola I., Caggiano V., Palumbo P., Di Cesare E., Hinojosa-Azaola A., Torres-Ruiz J., Guaracha-Basañez G.A., Martín-Nares E., Lopalco G., Morrone M., Iannone F., Giardini H.A., Cordeiro R.A., et. al.

Abstract Objectives To assess the lung involvement in patients with Still’s disease, an inflammatory disease assessing both children and adults. To exploit possible associated factors for parenchymal lung involvement in these patients. Methods A multicentre observational study was arranged assessing consecutive patients with Still’s disease characterized by the lung involvement among those included in the AIDA (AutoInflammatory Disease Alliance) Network Still’s Disease Registry. Still’s disease-lung involvement was defined by the presence of pleuritis, parenchymal features, acute respiratory distress syndrome (ARDS), and/or pulmonary arterial hypertension. Results In total, 90 patients with Still’s disease and lung involvement were assessed (mean age 36.3 ± 17.8 years, 35.6% male sex). Among them, 13.3% of patients were paediatrics. These patients with lung involvement mainly showed pleuritis in 72.2% of cases, parenchymal features in 34.4%, ARDS in 9.5%, and pulmonary arterial hypertension in 2.3%. After that we focused on patients characterised by parenchymal lung involvement, which is an emergent issue of clinical concern. These patients with parenchymal lung disease were significantly characterized by sore throat, pericarditis, and higher values of systemic score than others. Finally, the administration of both IL-1 or IL-6 inhibitors was not associated with the presence of parenchymal lung involvement. Conclusion The clinical characteristics of patients with Still’s disease and lung involvement were described in the AIDA network. We also provided a clinical profile of patients with parenchymal lung involvement considering its prognostic relevance. Although providing a clinical landscape of these patients, further studies are needed to fully clarify this issue.

Petrucci M., Gemma S., Carbone L., Piccioni A., Della Polla D.A., Simeoni B., Franceschi F., Covino M.

Intensive Care Unit-Acquired Weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by profound and often prolonged muscle weakness. The complexity of its diagnosis and management requires a multidimensional approach that integrates clinical, electrophysiological, and imaging tools. This review focuses on the challenges in diagnosing ICU-AW, emphasizing the limitations of traditional methods such as manual muscle testing and electrophysiological studies, and highlights the emerging role of neuromuscular ultrasound (NMUS) as a promising, non-invasive diagnostic aid. Despite its utility, no gold standard exists for NMUS, making it an evolving area of research. The pathophysiological basis of ICU-AW involves multiple mechanisms, including critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and muscle atrophy due to disuse. Understanding these underlying mechanisms is crucial for advancing diagnostic strategies and informing therapeutic interventions. Recent insights into the molecular and cellular pathways involved, such as the role of oxidative stress, mitochondrial dysfunction, and the ubiquitin-proteasome system, have opened new avenues for targeted therapies. Management of ICU-AW remains challenging as no specific treatment has been proven fully effective. Current strategies focus on early mobilization, minimizing sedation, and optimizing nutritional support. Emerging therapies targeting molecular pathways involved in muscle degradation are under investigation, highlighting the potential to translate pathophysiological understanding into therapeutic innovations. This review underscores the need for ongoing research to establish standardized diagnostic protocols and develop targeted treatments for ICU-AW.

Cortigiani L., Gaibazzi N., Ciampi Q., Rigo F., Tuttolomondo D., Bovenzi F., Gregori D., Carerj S., Pepi M., Pellikka P.A., Picano E.

Regional wall motion abnormality (RWMA) can be absent during stress echocardiography (SE) in patients with chronic coronary syndromes (CCS) and angiographically significant coronary artery disease (CAD) despite a reduction of coronary flow velocity reserve (CFVR).

Al Khayyat S.G., Conticini E., Falsetti P., Fogliame G., Gentileschi S., Baldi C., Bardelli M., Migliore A., Cantarini L., Frediani B.

Depuis les années 1990, les traitements de fond biologiques (bDMARD) ont révolutionné le traitement des rhumatismes inflammatoires telles que la polyarthrite rhumatoïde, le rhumatisme psoriasique ou la spondyloarthrite axiale. Cependant, malgré un schéma thérapeutique complet, on observe parfois la persistance d'une synovite mono et oligoarticulaire. L'injection intra-articulaire de bDMARD pourrait résoudre l'inflammation persistante. En outre, l'administration dans l'articulation pourrait être associée à une diminution des coûts de traitement. Nous avons effectué une recherche des articles dans PubMed et Google Scholar concernant les injections intra-articulaires avec les mots-clés « etanercept », « infliximab », « adalimumab », « certolizumab », « golimumab », « tocilizumab », « ixekizumab », « secukinumab », « rituximab », chacun combiné avec l'expression « intra-articular injection ». Nous avons identifié et évalué 161 articles, dont 25, étroitement liés au sujet du présent travail, ont été sélectionnés. Ces articles ont examiné au total 310patients (97 hommes et 149 femmes, chez 64 patients le genre n'était pas précisé, âge moyen 44,7 ± 12,0 ans) et 556 articulations traitées. Cent quatre-vingt-huit patients étaient atteints de polyarthrite rhumatoïde, 47 de rhumatisme psoriasique, 27 de spondylarthrite axiale, 26 d'arthrite juvénile idiopathique, 11 d'arthrite indifférenciée, 1 d'arthrite associée à une maladie inflammatoire chronique de l'intestin et 9 présentaient un trouble articulaire inflammatoire non spécifié. Tous les patients ont reçu un inhibiteur du TNFα – adalimumab, étanercept ou infliximab – par voie intra-articulaire. Des effets indésirables ont été signalés chez neuf des 310 patients traités (2,9 %), tous d'intensité légère ou modérée. Dans certains cas, l'efficacité du traitement par bDMARD intra-articulaires se maintient pendant plusieurs mois, mais les quelques essais comparatifs randomisés publiés ont montré que les glucocorticoïdes intra-articulaires étaient plus efficaces que les bDMARD. Les bDMARD semblent peu efficaces dans la prise en charge de la synovite résistante et ne sont pas supérieurs aux infiltrations de corticoïdes. La principale limite du traitement est la mauvaise persistance du composé dans l'articulation. Since the 1990s bDMARDs have revolutionized the treatment of chronic dysimmune inflammatory arthropathies such as Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondylarthritis. Nevertheless, despite a full treatment regimen, mono- and oligoarticular persistence of the synovitis is sometimes observed. The IA use of bDMARD drugs could resolve the persistent joint inflammation and result in a reduction in the degree of immunosuppression of individuals; moreover, the use of these drugs intra-articularly could be associated with a reduction in treatment related costs. We extensively searched via PubMed and Google Scholar articles regarding IA injections using as key words "etanercept", "infliximab", "adalimumab", "certolizumab", "golimumab", "tocilizumab", "ixekizumab", "secukinumab", "rituximab" each combined with "intra-articular injection". We found and evaluated 161 papers, then we selected 25 that were highly related to the topic of the present work. The articles examined a total of 310 patients, 97 males (M), 149 females (M), in 64 patients gender was not specified, mean age 44.75 ± 12.09 years old and considered 556 treated joints. One hundred and eigthy-eight patients were affected by Rheumatoid Arthritis, 47 by Psoriatic Arthritis, 27by Axial Spondylarthritis, 26 by Juvenile Idiopathic Arthritis, 11 by Undifferentiated Arthritis, 1 by arthritis associated with inflammatory bowel disease and 9 patients by an unspecified inflammatory articular disorder. All patients were treated intra-articularly (IA) with a TNFα inhibitor among Adalimumab, Etanercept or Infliximab. Side effects were documented in 9 out of 310 (2.9 %) treated patients and all were mild or moderate. In some cases the effectiveness of IA bDMARDs treatment is maintained for several months, however in the few published RCTs the GCs appeared to act better when administered IA compared to bDMARDs. The use of bDMARDs seems to be weakly effective in the management of resistant synovitis and not superior to corticosteroids injections. The treatment's main limit appear to be the poor persistence of the compound in the joint.

Boncristiano A., Balestrini S., Doccini V., Specchio N., Pietrafusa N., Trivisano M., Darra F., Cossu A., Battaglia D., Quintiliani M., Gambardella M.L., Parente E., Monni R., Matricardi S., Marini C., et. al.

AbstractObjectiveFenfluramine (FFA), stiripentol (STP), and cannabidiol (CBD) are approved add‐on therapies for seizures in Dravet syndrome (DS). We report on the long‐term safety and health care resource utilization (HCRU) of patients with DS treated with FFA under an expanded access program (EAP).MethodsA cohort of 124 patients received FFA for a median of 2.8 years (34.4 months). We compared data on safety and HCRU during FFA treatment with those from a same pre‐treatment period. Echocardiography was conducted every 6 months. Information collected included gender, age, and auxological parameters (height, weight, and body mass index [BMI]) at the start (T0) and follow‐up (T1); FFA treatment details (start, withdrawal, dosage); adverse events (AEs); and HCRU data including hospital admissions, status epilepticus (SE) episodes, and rescue medication use. We grouped patients by weight: ≤37.4 kg (n = 68, 54.8%) and ≥37.5 kg (n = 56; 45.1%), with FFA dosing adjusted accordingly. Statistical analyses included paired t test, Wilcoxon signed‐rank test, Kaplan–Meier analysis, and Bonferroni correction to adjust for multiple testing.ResultsMean age was 47 months at clinical diagnosis and 81 months at T0. The last follow‐up average FFA dose was .5 mg/kg/day, with a median of .4 mg/kg/day. FFA led to a 9.5% reduction in prior treatment load. At last follow‐up, 118 of 124 (91.5%) remained on FFA. Rescue medication use decreased significantly from 4.5 to 1, hospitalizations from 1 to 0, and SE episodes from 0–240 to 0–180 (p < .001 for all). Seizure freedom was achieved in 9 of 118 patients (7.6%). AEs occurred in 39 of 124 patients (31.5%), with no cardiac issues or deaths. There was an overall mean reduction in BMI, with no statistical significance, and never requiring FFA withdrawal.SignificanceFFA is well tolerated, without cardiac toxicity, and reduces treatment load and HCRU, suggesting improved patient management. BMI reduction in young children highlights the need for growth and nutritional monitoring.