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This study aimed to evaluate epilepsy outcome and antiseizure medication (ASM) discontinuation after lesionectomies as first surgical approach in pediatric population diagnosed with low‐grade epilepsy‐associated neuroepithelial tumors (LEATs). We conducted a retrospective study. Thirty‐six consecutive patients with histological diagnoses of LEATs who underwent surgery between 2018 and 2021 at our institution were included. The clinical and surgical data were retrospectively analyzed. Thirty (83.3%) of 36 patients are free of disabling seizures (Engel class I) and 19 (63,4%) of them are classified as Engel Ia. In 17 (47.2%) patients, ASM could be discontinued. The mean age at surgery was 8.6 years (±4.04) and the mean age at onset of epilepsy was 7.2 years (±3.8), whereas the mean duration of epilepsy in months at the time of surgery was 21.3 months (±23.7). The epileptogenic tumor was in the temporal lobe in 20 (55.5%) patients. Because of seizure persistence, a second or a third surgery was necessary for six patients (16.7%) and four of them had residual lesions (three in temporal and one in extratemporal site). No perioperative complications were recorded, including acute seizures, with a median hospitalization time of 7 days. Shorter epilepsy duration at time of surgery as long as a single ASM was significantly correlated with an Engel class I outcome (p‐value = .01 and p‐value = .016, respectively). Focal seizure semeiology was associated with an increased probability of antiseizure medication discontinuation (p‐value = .042). Our findings confirm that shorter epilepsy disease duration, monotherapy before surgery, and seizure semeiology are determinant factors for a positive seizure outcome and medication discontinuation, also with less invasive surgical approaches such as lesionectomies. However, considering the intrinsic multifactorial epileptogenic nature of LEATs, a tailored surgical approach should be considered to optimize clinical and seizure outcome, especially for lesions located in the temporal lobe.

In this article, we present an overview of the 2023 International Planning Competition. It featured five distinct tracks designed to assess cutting‐edge methods and explore the frontiers of planning within these settings: the classical (deterministic) track, the numeric track, the Hierarchical Task Networks (HTN) track, the learning track, and the probabilistic and reinforcement learning track. Each of these tracks evaluated planning methodologies through one or more subtracks, with the goal of pushing the boundaries of current planner performance. To achieve this objective, the competition introduced a combination of well‐established challenges and entirely novel ones. Within this article, each track offers an exploration of its historical context, justifies its relevance within the planning landscape, discusses emerging domains and trends, elucidates the evaluation methodology, and ultimately presents the results.

Primary pars plana vitrectomy with gas tamponade leads to a high single surgery anatomical success rate in uncomplicated pseudophakic retinal detachment with inferior causative breaks with no additional benefit associated with long-acting tamponade when comparing C2F6with SF6. This enables faster visual rehabilitation to patients.

Supplemental Digital Content is Available in the Text.Long-term visual recovery in patients with primary pseudophakic macula-off retinal detachments is positively correlated with the time elapsed after surgery. There is also a significant inverse association between the number of clock hours of the retinal detachment and visual acuity gain from the first follow-up to the final follow-up.

DAG1encodes for dystroglycan, a key component of the dystrophin-glycoprotein complex (DGC) with a pivotal role in skeletal muscle function and maintenance. Biallelic loss-of-function DAG1variants cause severe muscular dystrophy and muscle-eye-brain disease. A possible contribution of DAG1deficiency to milder muscular phenotypes has been suggested. We investigated the genetic background of twelve subjects with persistent mild-to-severe hyperCKemia to dissect the role of DAG1in this condition. Genetic testing was performed through exome sequencing (ES) or custom NGS panels including various genes involved in a spectrum of muscular disorders. Histopathological and Western blot analyses were performed on muscle biopsy samples obtained from three patients. We identified seven novel heterozygous truncating variants in DAG1segregating with isolated or pauci-symptomatic hyperCKemia in all families. The variants were rare and predicted to lead to nonsense-mediated mRNA decay or the formation of a truncated transcript. In four cases, DAG1variants were inherited from similarly affected parents. Histopathological analysis revealed a decreased expression of dystroglycan subunits and Western blot confirmed a significantly reduced expression of beta-dystroglycan in muscle samples. This study supports the pathogenic role of DAG1haploinsufficiency in isolated or pauci-symptomatic hyperCKemia, with implications for clinical management and genetic counseling.

Purpose: Cognitive impairment is described in 80% of Neurofibromatosis type 1 (NF1) patients. Brain focal areas of T2w increased signal intensity on MRI, the so-called Unidentified Bright Objects (UBOs) have been hypothesized to be related to cognitive dysfunction, although conflicting results are available in literature. Here, we investigated the possible relation between UBOs’ volume, cognitive impairment, and language disability in NF1 patients. Material and methods: In this retrospective study, clinical and MRI data of 21 NF1 patients (M/F = 12/9; mean age 10.1 ± 4.5) were evaluated. Brain intellectual functioning and language abilities were assessed with specific scales, while the analyzed MRI sequences included axial 2D-T2-weighted and FLAIR sequences. These images were used independently for UBOs segmentation with a semiautomatic approach and obtained volumes were normalized for biparietal diameters to take into account for brain volume. Possible differences in terms of normalized UBOs volumes were probed between cognitively affected and preserved patients, as well as between subjects with or without language impairment. Results: Patients cognitively affected were not different in terms of UBOs volume compared to those preserved (p= 0.35 and p= 0.30, for T2-weighted and FLAIR images, respectively). Similarly, no differences were found between patients with and without language impairment (p= 0.47 and p= 0.40, for the two sequences). Conclusions: The relation between UBOs and cognition in children with NF1 has been already investigated in literature, although leading to conflicting results. Our study expands the current knowledge, showing a lack of correlation between UBOs volume and both cognitive impairment and language disability in NF1 patients.

Purpose: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). Methods: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). Results: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p= 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p< 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. Conclusions: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

Care pathways for the management of acute ophthalmic conditions have developed and transformed significantly over recent years, owing to a combination of legislative changes, policy implementation and the pressing requirement to redistribute increased demand away from traditional secondary care providers through collaboration with primary care. Following UK healthcare devolution in 1999, each nation has developed and implemented their own strategies for managing the growing demands on acute ophthalmology services. Local commissioning across England has seen Enhanced Service Pathways develop to provide acute eye care by primary care optometrists, with provision and access dependent upon locality. Northern Ireland has seen the implementation of a nationwide Primary Eyecare Acute Referral Service, whilst in Scotland and Wales, the respective Governments have redesigned primary care optometry General Ophthalmic Service contracts to incorporate provision of extended investigations and management of acute conditions by optometrists across the nation, recognising the added benefit of optometrists with higher qualifications. This narrative review summarises both peer reviewed and appropriate grey literature articles reporting on acute eye care pathways in primary care. Despite significant progress, particularly during the global COVID-19 pandemic, there is arguably still a great deal of further research and evaluation required relating to pathway innovation, the role of professionals with higher qualifications, including independent prescribing, the role of telemedicine, reassurance around clinical safety, and how digital interconnectivity could potentially add value to collaborative schemes to meet the growing demand on acute eyecare.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11Aare identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.a. Dias-Logan syndrome) ascertained through an international collaborative network, and reviewed 35 additional previously reported patients. Analysis of 77 affected individuals identified 60 unique disease-causing variants (30 frameshift, 7 missense, 6 splice-site, 17 stop-gain) and 8 unique BCL11Amicrodeletions. We define the most prevalent features of BCL11A-IDD: IDD, postnatal-onset microcephaly, hypotonia, behavioral abnormalities, autism spectrum disorder, and persistence of fetal hemoglobin (HbF), and identify autonomic dysregulation as new feature. BCL11A-IDD is distinguished from 2p16 microdeletion syndrome, which has a higher incidence of congenital anomalies. Our results underscore BCL11A as an important transcription factor in human hindbrain development, identifying a previously underrecognized phenotype of a small brainstem with a reduced pons/medulla ratio. Genotype-phenotype correlation revealed an isoform-dependent trend in severity of truncating variants: those affecting all isoforms are associated with higher frequency of hypotonia, and those affecting the long (BCL11A-L) and extra-long (-XL) isoforms, sparing the short (-S), are associated with higher frequency of postnatal microcephaly. With the largest international cohort to date, this study highlights persistence of fetal hemoglobin as a consistent biomarker and hindbrain abnormalities as a common feature. It contributes significantly to our understanding of BCL11A-IDD through an extensive unbiased multi-center assessment, providing valuable insights for diagnosis, management and counselling, and into BCL11A’s role in brain development.

Recent studies of the privacy-preserving consensus guarantee the initial-value privacy but leave real-time running values of consensus states unprotected with respect to external eavesdroppers. In this article, a novel real-time privacy-preserving average consensus algorithm is proposed to fill this gap by utilizing the quasi-resonance (QR) algorithm and the mask function with real-time privacy-preserving property based on the multifrequency (MF) sinusoids. Several kinds of sinusoids are included in the mask function to achieve the privacy preservation of the initial value and real-time values simultaneously, such as nondecaying and exponentially-decaying MF sinusoids. The QR algorithm can achieve the exact consensus because of its high control gain on a specific resonant frequency in MF sinusoids. The designed privacy-preserving average consensus algorithm will not increase the communication pressure since the single signal of the sum of MF sinusoids is transmitted to evade increasing information amount. As an application of the developed consensus algorithm, the privacy-preserving distributed secondary control of the islanded ac microgrid is obtained to achieve active power sharing and frequency restoration.

Introduction: The growing demographic presence of the transgender (TGD) population has sparked an increase in clinical investigations focusing on the impacts of gender-affirming hormone therapy (GAHT) in adults with gender dysphoria. Despite this surge in studies, there remains a significant gap in the literature regarding the health status of older TGD individuals. This review aims to assess prevalent pathological conditions within the TGD population, specifically concentrating on aging-related diseases investigated to date. Methods: A systematic search across Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science databases was conducted to identify articles reporting on the aging process in TGD individuals. Methodological quality was evaluated using Newcastle–Ottawa Scale (NOS) scores. Results: Initial database searches yielded 12,688 studies, which were refined to 18 through elimination of duplicates and title/abstract review. Following a comprehensive appraisal, nine studies were included in the systematic review. These articles, published between 2017 and 2023, involved a total of 5403 participants. The evidence indicates a noteworthy percentage of the TGD population being at risk for cardiovascular diseases, experiencing depression or disability, and demonstrating hesitancy toward major recommended screening programs. Conclusions: Limited studies on older TGD individuals highlight not only an organic risk of chronic diseases but also a cognitive/psychiatric risk that should not be underestimated. Further research is imperative to deepen our understanding of the pathophysiological mechanisms involved in the health challenges faced by older TGD individuals.

To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR ≥ 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR ≥ 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR < 0.90, TSG = 0 (n = 37, 4.9%); G4: QFR < 0.90, TSG > 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p < 0.01). ROC analysis showed an AUC of 0.74 (95% CI: 0.67 to 0.80; p < 0.001). TSG > 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77–4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90).

Growing concern surrounds the impact of social media platforms on public discourse1–4and their influence on social dynamics5–9, especially in the context of toxicity10–12. Here, to better understand these phenomena, we use a comparative approach to isolate human behavioural patterns across multiple social media platforms. In particular, we analyse conversations in different online communities, focusing on identifying consistent patterns of toxic content. Drawing from an extensive dataset that spans eight platforms over 34 years—from Usenet to contemporary social media—our findings show consistent conversation patterns and user behaviour, irrespective of the platform, topic or time. Notably, although long conversations consistently exhibit higher toxicity, toxic language does not invariably discourage people from participating in a conversation, and toxicity does not necessarily escalate as discussions evolve. Our analysis suggests that debates and contrasting sentiments among users significantly contribute to more intense and hostile discussions. Moreover, the persistence of these patterns across three decades, despite changes in platforms and societal norms, underscores the pivotal role of human behaviour in shaping online discourse.

In this article, we develop a general open multiagent systems (OMAS) framework over undirected graphs where the agents' interaction is, in general, nonlinear, time-varying, and heterogeneous, in that the agents interact with different pairwise interaction rules for each link, possibly nonlinear, which may change over time. In particular, assuming the agents interact by exchanging flows, which modify their states, our framework guarantees that the sum of the states of agents participating in the network is preserved. To this end, agents maintain a state variable for each of their neighbors. Upon the disconnection of a neighbor, such a variable is used to completely eliminate the effect of previous interaction with disconnected agents from the overall system. In order to demonstrate the effectiveness of the proposed OMAS framework, we provide a case study focused on average consensus, and, specifically, we develop a sufficient condition on the structure of the agents' interaction guaranteeing asymptotic convergence under the assumption that the network becomes fixed. The article is complemented by simulation results that numerically demonstrate the effectiveness of the proposed method.

Structural variants (SVs), including large deletions, duplications, inversions, translocations, and more complex events have the potential to disrupt gene function resulting in rare disease. Nevertheless, current pipelines and clinical decision support systems for exome sequencing (ES) tend to focus on small alterations such as single nucleotide variants (SNVs) and insertions-deletions shorter than 50 base pairs (indels). Additionally, detection and interpretation of large copy-number variants (CNVs) are frequently performed. However, detection of other types of SVs in ES data is hampered by the difficulty of identifying breakpoints in off-target (intergenic or intronic) regions, which makes robust identification of SVs challenging. In this paper, we demonstrate the utility of SV calling in ES resulting in a diagnostic yield of 0.4% (23 out of 5825 probands) for a large cohort of unsolved patients collected by the Solve-RD consortium. Remarkably, 8 out of 23 pathogenic SV were not found by comprehensive read-depth-based CNV analysis, resulting in a 0.13% increased diagnostic value.

Abstract.Pregnancy can influence the development and progression of congenital arteriovenous malformations (AVM) and thus lead to life-threatening complications for the mother and fetus like high output cardiac failure and premature delivery. The simultaneous presence of a capillary malformation and AVM strongly suggests a RASA1 related disorder.Keywords:Arteriovenous malformations, capillary malformation-arteriovenous malformation, capillaries/abnormalities, port-wine stain, pregnancy, RASA1 protein

BackgroundPatients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END.MethodsPatients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0–1 or 0–2, and occurrence of END.ResultsAmong 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406).ConclusionPatients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

The MYT1Lgene plays a critical role in brain development, promoting the differentiation and proliferation of cells, important for the formation of brain connections. MYT1Lis also involved in regulating the development of the hypothalamus, which is a crucial actor in weight regulation. Genetic variants in the MYT1Lare associated with a range of developmental disorders, including intellectual disability, autism spectrum disorder, facial dysmorphisms, and epilepsy. The specific role of MYT1Lin epilepsy remains elusive and no patients with developmental and epileptic encephalopathy (DEE) have been described so far. In this study, we report a patient with DEE presenting with severe refractory epilepsy, obesity, and behavioral abnormalities. Exome sequencing led to the identification of the heterozygous variant NM_001303052.2: c.1717G>A, p.(Gly573Arg) (chr2‐1910340‐C‐T; GRCh38.p14) in the MYT1Lgene. This variant was found to be inherited by the father, who was a mosaic and did not suffer from any neuropsychiatric disorders. Our observations expand the molecular and phenotype spectrum of MYT1L‐related disorders, suggesting that affected individuals may present with severe epileptic phenotype leading to neurocognitive deterioration. Furthermore, we show that mosaic parents may not display the disease phenotype, with relevant implications for genetic counseling.

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

ABSTRACTAutomated planning is a prominent Artificial Intelligence (AI) challenge that has been extensively studied for decades, which has led to the development of powerful domain-independent planning systems. The performance of domain-independent planning systems are strongly affected by the structure of the search space, that is dependent on the application domain and on its encoding.This paper proposes and investigates a novel way of combining machine learning and heuristic search to improve domain-independent planning. On the learning side, we use learning to predict the plan cost of a good solution for a given instance. On the planning side, we propose a bound-sensitive heuristic function that exploits such a prediction in a state-space planner. Our function combines the input prediction (derived inductively) with some pieces of information gathered during search (derived deductively). As the prediction can sometimes be grossly inaccurate, the function also provides means to recognise when the provided information is actually misguiding the search. Our experimental analysis demonstrates the usefulness of the proposed approach in a standard heuristic best-first search schema.

AbstractThe Critical Path Method (CPM), the Last Planner System (LPS) and location-based methods, such as the Line of Balance (LB), are discussed extensively in the technical literature about schedules. However, no discussion exists focusing on the differences and similarities of these methods in terms of their use in different countries. Using chi-squared and Fisher’s exact tests, this research compared three countries (Brazil, Finland, and United States) and the methods to evaluate both intra- and inter-country implementation to gain additional insights about their use. Results suggest statistically significant intra- and inter-country differences regarding how these methods are used, with a specific focus on mechanics in the countries, offering important information to address their various scheduling needs. The results reflect the current state of practice; engineering and construction managers should understand different ways of understanding scheduling. Such understanding can lead to more efficient communication with collaborators and when incorporating foreign teams in projects. The study identifies the need for further scientific explanation as to why these methods are used in the manner they are intra-country as well as adaptions made in inter-country relationships.

Loss-of-function variants in CHAMP1were recently described as cause of a neurodevelopmental disorder characterized by intellectual disability (ID), autism, and distinctive facial characteristics. By exome sequencing (ES), we identified a truncating variant in CHAMP1, c.1858A > T (p.Lys620*), in a patient who exhibited a similar phenotype of severe ID and dysmorphisms. Whether haploinsufficiency or a dominant negative effect is the underlying pathomechanism in these cases is a question that still needs to be addressed. By array-CGH, we detected a 194 kb deletion in 13q34 encompassing CHAMP1, CDC16and UPF3, in another patient who presented with borderline neurodevelopmental impairment and with no dysmorphisms. In a further patient suffering from early onset refractory seizures, we detected by ES a missense variant in CHAMP1, c.67 G > A (p.Gly23Ser). Genomic abnormalities were all de novo in our patients. We reviewed the clinical and the genetic data of patients reported in the literature with: loss-of-function variants in CHAMP1(total 40); chromosome 13q34 deletions ranging from 1.1 to 4 Mb (total 7) and of the unique patient with a missense variant. We could infer that loss-of-function variants in CHAMP1cause a homogeneous phenotype with severe ID, autism spectrum disorders (ASD) and highly distinctive facial characteristics through a dominant negative effect. CHAMP1haploinsufficiency results in borderline ID with negligible consequences on the quality of life. Missense variants give rise to a severe epileptic encephalopathy through gain-of-function mechanism, most likely. We tentatively define for the first time distinct categories among the CHAMP1-related disorder on the basis of pathomechanisms.

The growing clinical success of hematopoietic stem/progenitor cell (HSPC) gene therapy (GT) relies on the development of viral vectors as portable “Trojan horses” for safe and efficient gene transfer. The recent advent of novel technologies enabling site-specific gene editing is broadening the scope and means of GT, paving the way to more precise genetic engineering and expanding the spectrum of diseases amenable to HSPC-GT. Here, we provide an overview of state-of-the-art and prospective developments of the HSPC-GT field, highlighting how advances in biological characterization and manipulation of HSPCs will enable the design of the next generation of these transforming therapeutics.

Background: Traditional cardiac rehabilitation (CR) is effective in improving physical performance and prognosis after myocardial infarction (MI). Anyway, it is not consistently recommended to older adults, and its attendance rate is low. Previous studies suggested that alternative, early and tailored exercise interventions are feasible and effective in improving physical performance in older MI patients. Anyway, the demonstration that they are associated also with a significant reduction of hard endpoints is lacking. Aim: To describe rationale and design of the “Physical activity Intervention in Elderly patients with myocardial Infarction” (PIpELINe) trial. Methods: The PIpELINe trial is a prospective, randomized, multicentre study with a blinded adjudicated evaluation of the outcomes. Patients aged ≥ 65 years, admitted to hospital for MI and with a low physical performance one month after discharge, as defined as short physical performance battery (SPPB) value between 4 and 9, will be randomized to a multi-domain lifestyle intervention (including dietary counselling, strict management of cardiovascular and metabolic risk factors, and exercise training) or health education. The primary endpoint is the one-year occurrence of the composite of cardiovascular death or re-hospitalization for cardiovascular causes. Results: The recruitment started in March 2020. The estimated sample size is 456 patients. The conclusion of the enrolment is planned for mid-2023. The primary endpoint analysis will be available for the end of 2024. Conclusions: The PIpELINe trial will show if a multi-domain lifestyle intervention is able to reduce adverse events in older patients with reduced physical performance after hospitalization for MI. Trial registration: ClinicalTrials.gov NCT04183465.