Explore the vast range of titles available.

Background There is an increasing number of papers reporting the real world use of Nusinersen in different cohorts of SMA patients. Main body The aim of this paper was to critically review the literature reporting real world data on motor function in type 2 and 3 patients treated with Nusinersen, subdividing the results according to SMA type, age and type of assessment and performing a meta-analysis of the available results. We also report the available data collected in untreated patients using the same measures. Of the 400 papers identified searching for Nusinersen and spinal muscular atrophy, 19 reported motor function in types 2 and 3: 13 in adults, 4 in children and 2 included both. Twelve papers reported untreated patients’ data. All studies reported positive changes on at least one of the functional measures and at every time point while all-untreated cohorts showed negative changes. Conclusion Our review suggests that Nusinersen provides a favorable benefit in motor function across a wide range of SMA type 2 and 3 patients over a 10–14 month observation period. Although a direct comparison with studies reporting data from untreated patients cannot be made, the longitudinal changes in the treated cohorts (consistently positive) are divergent from those observed in the untreated cohorts (consistently negative). The difference could be observed both in the global cohorts and in smaller groups subdivided according to age, type or functional status.

The advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis. All patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis. The cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD±5.88) in type II, and 4.34 years (SD±4.01) in type III. The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III. Our results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available more attention should be devoted to reducing such delay as there is consistent evidence of the benefit of early treatment.

The advent of disease modifying therapies in spinal muscular atrophy (SMA) has increased life expectancy but also raising new challenges. We aimed to explore the neurobehavioral profile in SMA type I subjects and in those identified by newborn screening (NBS). Behavioral assessment included screening questionnaires (strengths and difficulties questionnaire (SDQ), social communication questionnaire (SCQ), and sensory profile 2 (SP2)), neurobehavioral observation, CARS2 and DSM-5 criteria. The cohort included thirty-one children (25 type I and 6 NBS) aged 2–10 years. On SDQ prosocial scale, 14/31 showed borderline or abnormal results. 6/14 had borderline scores at the SCQ questionnaire, while none had abnormal scores. Neurobehavioral observation suggested the presence of ASD in 3/31, confirmed by CARS2 and DSM-5 criteria. 5/31 showed other behavioral disorders. Our findings suggest that autism is present in SMA infants in a percentage slightly higher than in the general population. Other neurobehavioral difficulties are less frequent. Our study highlighted the challenges to select appropriate tools in infants with limited mobility and the need for a clear diagnostic pathway, starting with screening questionnaires followed by more appropriate diagnostic tools to reduce the number of false positive results.

Objective We report longitudinal data from 144 type III SMA pediatric and adult patients treated with nusinersen as part of an international effort. Methods Patients were assessed using Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and 6‐Minute Walk Test (6MWT) with a mean follow‐up of 1.83 years after nusinersen treatment. Results Over 75% of the 144 patients had a 12‐month follow‐up. There was an increase in the mean scores from baseline to 12 months on both HFMSE (1.18 points, p = 0.004) and RULM scores (0.58 points, p = 0.014) but not on the 6MWT (mean difference = 6.65 m, p = 0.33). When the 12‐month HFMSE changes in the treated cohort were compared to an external cohort of untreated patients, in all untreated patients older than 7 years, the mean changes were always negative, while always positive in the treated ones. To reduce a selection bias, we also used a multivariable analysis. On the HFMSE scale, age, gender, baseline value, and functional status contributed significantly to the changes, while the number of SMN2 copies did not contribute. The effect of these variables was less obvious on the RULM and 6MWT. Interpretation Our results expand the available data on the effect of Nusinersen on type III patients, so far mostly limited to data from adult type III patients.

The study reports real world data in type 2 and 3 SMA patients treated for at least 2 years with nusinersen. Increase in motor function was observed after 12 months and during the second year. The magnitude of change was variable across age and functional subgroup, with the largest changes observed in young patients with higher function at baseline. When compared to natural history data, the difference between study cohort and untreated patients swas significant on both Hammersmith Functional Motor Scale and Revised Upper Limb Module both at 12 months and at 24 months.

The natural history of spinal muscular atrophy has been radically changed by the advent of improved standards of care and the availability of disease-modifying therapies. The aim of this paper is to provide the current therapeutic scenario including new perspectives and to report the challenges related to new phenotypes a few years after the therapies have become available. The paper also includes a review of real-world data that provides information on safety and efficacy in individuals that were not included in clinical trials. Special attention is paid to future perspectives both in terms of new drugs that are currently investigated in clinical trials or providing details on current developments in the use of the available drugs, including combination therapies or new modalities of dose or administration.   Conclusion : Clinical trials and real world data support the efficacy and safety profiles of the available drugs. At the moment there is not enough published evidence about the superiority of one product compared to the others. What is Known: • Safety and efficacy results of clinical trials have led in the last 6 years to the marketing of three drugs for spinal muscular atrophy, with different mechanisms of action. What is New: • Since the drug’s approval, real-world data allow us to have data on bigger and heterogeneous groups of patients in contrast with those included in clinical trials. • In addition to the new molecules, combinations of therapies are currently being evaluated.

Background/Objectives: Uterine fibroids are the most common benign neoplasms of the female genital tract, with a prevalence of 20% to 40% among women of reproductive age. Their management in the context of Assisted Reproductive Technologies (ART) represents a major clinical challenge, characterized by controversies, contrasting approaches, and a lack of shared guidelines. Indeed, the detrimental effects of fibroid treatments are not well known and may be influenced by the size, location, and number of fibroids. The impact of hysteroscopic myomectomy in women affected by submucosal myomas (FIGO classification type: G0–G2) is well documented in the current literature; however, the impact of intramural and subserosal myoma removal (FIGO types 3–8), in particular those <4/5 cm in diameter, remains controversial. The aim of the present study is to introduce and share a pragmatic surgical approach to uterine fibroid management prior to In Vitro Fertilization (IVF), to reduce the knowledge gap regarding uterine fibroid treatment. Methods: We conducted a retrospective observationally study that included 94 cases of infertile women, who underwent myomectomy at our IVF centre at Sandro Pertini Hospital, Rome, Italy, between 2020 and 2025. These patients met the inclusion criterion of having an idiopathic/tubal factor of infertility and were aged < 40. We evaluated a group of 17 women (group A) who underwent hysteroscopic myomectomy for submucosal fibroids (FIGO types 0–2) and a group of 39 women (group B) who underwent open (laparotomic) myomectomy for intramural/subserosal fibroids (FIGO types 3–8). Group B was compared with a control group of 38 women who were similar in terms of all demographic and clinical parameters and myoma features (group C) and did not want to undergo a myomectomy procedure. All surgical procedures were executed by the same expert surgeon following our proposed model: submucosal fibroids were always removed by operative hysteroscopy, while intramural/subserosal fibroids were removed if there were three or more and if they were at least 1 ≥ 3 cm in size. All enrolled patients subsequently underwent IVF treatment at our centre, which consisted of an antagonist protocol for ovarian stimulation, and all transferred embryos were of good quality according to the recent European Society of Human Reproduction and Embryology (ESHRE) classification. Results: In group A, we observed an implantation rate of 41% and a clinical pregnancy rate of 35.2%, and these results are consistent with the current literature. In group B, we obtained statistically significant differences in the implantation (31% vs. 12.9%) and pregnancy rates (28.1% vs. 7.8%) compared to group C (p = 0.02 and p = 0.03, respectively). In addition, the live birth rate was statistically higher compared to that in group C (p < 0.01). Miscarriage and preterm delivery rates were lower in group B, although the differences were not statistically significant. No severe post-surgical complications, such as uterine rupture, were observed during subsequent pregnancies. Conclusions: Despite the limited patient sample size, the monocentric experience, and the retrospective design, we emphasize the effectiveness of our proposed surgical model in women affected by myomas. Indeed, the surgical treatment of submucosal, intramural, and subserosal lesions may improve ART and pregnancy outcomes (through a higher implantation rate, pregnancy rate, and live birth rate, as well as a lower miscarriage/preterm rate).

BackgroundType II spinal muscular atrophy (SMA) often leads to scoliosis in up to 90% of cases. While pharmacological treatments have shown improvements in motor function, their impact on scoliosis progression remains unclear. This study aims to evaluate potential differences in scoliosis progression between treated and untreated SMA II patients.MethodsTreatment effect on Cobb’s angle annual changes and on reaching a 50° Cobb angle was analysed in treated and untreated type II SMA patients with a minimum 1.5-year follow-up. A sliding cut-off approach identified the optimal treatment subpopulation based on age, Cobb angle and Hammersmith Functional Motor Scale Expanded at the initial visit. Mann-Whitney U-test assessed statistical significance.ResultsThere were no significant differences in baseline characteristics between the untreated (n=46) and treated (n=39) populations. The mean Cobb angle variation did not significantly differ between the two groups (p=0.4). Optimal cut-off values for a better outcome were found to be having a Cobb angle <26° or an age <4.5 years. When using optimal cut-off, the treated group showed a lower mean Cobb variation compared with the untreated group (5.61 (SD 4.72) degrees/year vs 10.05 (SD 6.38) degrees/year; p=0.01). Cox-regression analysis indicated a protective treatment effect in reaching a 50° Cobb angle, significant in patients <4.5 years old (p=0.016).ConclusionThis study highlights that pharmacological treatment, if initiated early, may slow down the progression of scoliosis in type II SMA patients. Larger studies are warranted to further investigate the effectiveness of individual pharmacological treatment on scoliosis progression in this patient population.

ObjectiveThe aim of this study was to assess early language acquisitions in treated individuals with spinal muscular atrophy (SMA) type 1 and in infants identified by newborn screening (NBS).MethodsParents of SMA individuals aged between 8 and 36 months were asked to fill in the MacArthur-Bates Communicative Development Inventory (MB-CDI) that assesses comprehension, gesture and expressive skills. A follow-up assessment was performed in 21 of the 36.ResultsThe MB-CDI was completed by parents of 24 type 1 and 12 infants identified by NBS. Comprehension skills were preserved in 81% of the type 1 SMA and in 87% infants identified by NBS. Gesture abilities were <5th centile in 55% of the type 1 SMA and in none of those identified by NBS. Lexical expressions were <5th centile in more than 80% type 1 SMA and in 50% of infants identified by NBS. At follow-up, despite an increase in lexical expression skills, the scores remained below the fifth centile in 43% type 1 SMA and in 86% of infants identified by NBS.ConclusionsThese results suggest that language and communication development may follow a similar pattern to that observed in motor function with the possibility to develop skills (eg, ability to say clear words) that are not usually present in untreated infants but with a level of performance that does not reach that of their typically developing peers.