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Digital health interventions including telehealth, mobile health, artificial intelligence, big data, robotics, extended reality, computational and high-fidelity bench simulations are an integral part of the path toward precision medicine. Current applications encompass risk factor modification, chronic disease management, clinical decision support, diagnostics interpretation, preprocedural planning, evidence generation, education, and training. Despite the acknowledged potential, their development and implementation have faced several challenges and constraints, meaning few digital health tools have reached daily clinical practice. As a result, the Portuguese Society of Cardiology Study Group on Digital Health set out to outline the main digital health applications, address some of the roadblocks hampering large-scale deployment, and discuss future directions in support of cardiovascular health at large., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. Objectives : This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS., Methods: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed., Results: ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients., Discussion: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.

Introduction and Objectives: Rotational atherectomy (RA) is widely used for the management of calcified coronary stenoses. However, there is limited data on its use, trends, and outcomes. We sought to report our twelve-year experience with RA and explore the trends and outcomes of percutaneous coronary intervention (PCI) with this device., Methods: Our institutional PCI database was queried to identify all cases of RA-PCI performed between January 2009 and December 2020. We analysed peri-procedural outcomes and major adverse cardiovascular events (MACE) during follow-up: cardiovascular death, myocardial infarction, and target lesion revascularization., Results: 410 procedures (2.8% of total PCI volume) in 388 patients were included. Mean age was 72.3±9.3 years, 74.0% were male, 53.6% had diabetes, and 33.8% presented with acute coronary syndrome. There was a significant increase in median SYNTAX score (p trend =0.003) and the proportion of type B2/C lesions (p trend =0.003). Transradial access was preferred (60.0% overall) with a growing trend over time (p trend =0.003). Maximum burr size was <1.75 mm in 88.0% of cases (burr-to-artery ratio of 0.49±0.07). Angiographic success rate was consistently high (96.6% overall). Complications were recorded in 9.0% of procedures, with a temporal decline (p trend =0.029). Clinical follow-up was available for 357 patients (median time of 40 months). At one year, MACE rate was 12.1%. with no significant temporal changes., Conclusions: RA-PCI was a safe and effective procedure with a high rate of angiographic success and few complications, particularly in recent years, in line with significant technical improvements. The MACE incidence is acceptable considering the clinical risk and angiographic complexity., (Copyright © 2025 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background and Aims: Standardized definitions for outcome measures in randomized clinical trials and observational studies are essential for robust and valid evaluation of medical products, interventions, care, and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology aimed to create international data standards for cardiovascular clinical study outcome measures., Methods: The EuroHeart methods for data standard development were used. From a Global Cardiovascular Outcomes Consortium of 82 experts, five Working Groups were formed to identify and define key outcome measures for: cardiovascular disease (generic outcomes), acute coronary syndrome and percutaneous coronary intervention (ACS/PCI), atrial fibrillation (AF), heart failure (HF) and transcatheter aortic valve implantation (TAVI). A systematic review of the literature informed a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition and categorized the variable as mandatory (Level 1) or optional (Level 2) based on its clinical importance and feasibility., Results: Across the five domains, 24 Level 1 (generic: 5, ACS/PCI: 8, AF: 2; HF: 5, TAVI: 4) and 48 Level 2 (generic: 18, ACS-PCI: 7, AF: 6, HF: 2, TAVI: 15) outcome measures were defined., Conclusions: Internationally derived and endorsed definitions for outcome measures for a range of common cardiovascular diseases and interventions are presented. These may be used for data alignment to enable high-quality observational and randomized clinical research, audit, and quality improvement for patient benefit., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

ChatGPT, a language model developed by OpenAI, has been tested in several medical board examinations. This study aims to evaluate the performance of ChatGPT on the Portuguese National Residency Access Examination, a mandatory test for medical residency in Portugal. The study specifically compares the capabilities of ChatGPT versions 3.5 and 4o across five examination editions from 2019 to 2023. A total of 750 multiple-choice questions were submitted to both versions, and their answers were evaluated against the official responses. The findings revealed that ChatGPT 4o significantly outperformed ChatGPT 3.5, with a median examination score of 127 compared to 106 (p = 0.048). Notably, ChatGPT 4o achieved scores within the top 1% in two examination editions and exceeded the median performance of human candidates in all editions. Additionally, ChatGPT 4o's scores were high enough to qualify for any specialty. In conclusion, ChatGPT 4o can be a valuable tool for medical education and decision-making, but human oversight remains essential to ensure safe and accurate clinical practice.

Objective: To present cases of ptosis in HIV-1 patients on long-term antiretroviral therapy (ART) and review the existing literature., Methods: Five HIV-1-positive patients with slowly progressive bilateral ptosis underwent a comprehensive diagnostic evaluation, including imaging studies, neurophysiological testing, muscle biopsy, and genetic analysis. A literature review was conducted., Results: On clinical examination, all patients presented with bilateral symmetrical non-fatigable ptosis, three exhibited facial lipoatrophy and two also had mild multidirectional ophthalmoparesis and all had ocular abnormalities in Hess screen test. Additionally, one patient displayed proptosis, three had floppy lower eyelids, and four presented with exotropia. Anti-acetylcholine receptor antibodies were negative in all patients. Brain magnetic resonance imaging (MRI), motor unit potential analysis, and single-fiber electromyography were unremarkable. Orbital MRI revealed introrbital fat expansion in one patient, and limb muscle biopsies were inconclusive in two cases. Blood genetic testing for chronic progressive external ophthalmoplegia was negative in all patients. A total of 30 similar cases have been documented in the literature, with some studies reporting key findings such as muscle histology indicative of mitochondrial myopathy, MRI revealing patchy extraocular muscle hyperintensity, and muscle genetic testing identifying mitochondrial deoxyribonucleic acid (DNA) deletions. Ptosis surgical repair appears to be the most effective treatment., Conclusion: HIV patients on long-term ART may develop ocular muscle involvement due to mitochondrial dysfunction, with bilateral ptosis being the primary manifestation. Diagnosis is challenging and requires the exclusion of other conditions. Ptosis surgery can significantly improve quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction/aims: Literature on the role of gastrostomy and noninvasive ventilation (NIV) in primary lateral sclerosis (PLS) is limited. We aim to investigate whether PLS patients develop dysphagia requiring feeding tubes or respiratory failure necessitating NIV., Methods: We conducted a retrospective study of PLS patients with a definite diagnosis followed at our center (1994-2024). Patients with marked dysphagia (score < 3 on Question 3 of the ALSFRS-R) received a recommendation for gastrostomy and were divided into two groups: G1/G2 (accepted/declined gastrostomy). We investigated NIV indications due to respiratory failure and compared these patients (G3) to those without respiratory impairment (G4). Demographic, clinical, and neurophysiological data were collected and compared., Results: Forty-eight patients had a definite diagnosis of PLS. Gastrostomy was recommended to 18 (37.5%), yet only 7 patients (38.9%-G1) consented. The median time to gastrostomy was 77 months. Total survival and survival post-gastrostomy recommendation were not different between G1 and G2. Six PLS patients (12.5%-G3) developed respiratory failure and initiated NIV (median of 63 months). At 63 months, G3 had significantly lower median forced vital capacity (65% vs. 99%; p < 0.001) and phrenic nerve amplitude (0.43 vs. 0.75 mV; p = 0.039), but a greater ALSFRS-R slope (0.34 vs. 0.14; p = 0.046) and shorter survival (35 vs. 94.9 months; p = 0.009) compared to G4., Discussion: Dysphagia requiring gastrostomy was common in our PLS cohort, but survival after gastrostomy recommendation did not differ between groups. Patients who developed respiratory impairment may represent a distinct group with faster disease progression and shorter survival. Our findings may contribute to a deeper understanding and improved management of PLS., (© 2025 Wiley Periodicals LLC.)

Introduction : Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods : A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 ( C9orf72 ) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results : For the ALS group, the statistical model explained 38.8% of variance in ECAS total ( p  < 0.001), 59.4% of executive functions ( p  < 0.001), and 55% of behavioral symptoms ( p  < 0.001). For controls, it accounted for 52.8% of variance in ECAS total ( p  < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups ( p  < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls ( p  = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients ( p  = 0.009). Conclusion : This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.

Background: C9orf72 gene repeat expansion (C9RE) is the most frequent gene variant associated with amyotrophic lateral sclerosis (ALS). We aimed to study the phenotype of motor neurone disease (MND) patients with C9RE in a Portuguese cohort., Methods: Demographical and clinical data of MND patients with (C9RE+) and without C9RE were compared. ALS al Rating Scale-Revised (ALSFRS-R) and Edinburgh Cognitive and Behavioural ALS Screen (ECAS) were used to evaluate functional and cognitive performance, respectively. Survival analysis was performed using Kaplan Meier log-rank test and Cox proportional hazards model., Results: We included 761 patients of whom 61 (8.0 %) were C9RE+. C9RE+ patients had a higher frequency of ALS (95.1 vs 78.4 %, p = 0.002), and lower frequency of progressive muscular atrophy (3.3 vs 16.7 %, p = 0.006). C9RE+ was associated with earlier age of onset (58.1 vs 62.6 years, p = 0.003) and more frequent MND family history (65.5 vs 11.4 %, p < 0.001). Gender, ethnicity, onset site, diagnostic delay, disease progression rate until diagnosis (ΔF), ALSFRS-R and time until non-invasive ventilation did not differ between groups. Cognitive/behavioural symptoms and ECAS did not differ between groups, except a worse visuospatial score in C9RE+ group (p = 0.035). Death rate was 1.8 and 1.6 times higher in C9RE+ patients with MND and ALS, respectively. Significant survival prognostic factors in C9RE+ group were diagnosis delay (HR = 0.96, 95 %CI 0.92-0.99, p = 0.008) and ΔF (HR = 1.93, 95 %CI 1.26-2.96, p = 0.002)., Conclusion: Our study corroborates most previous cohorts' findings, but harbours some singularities regarding onset site, phenotype, and cognitive profile, that contribute to a better understanding of C9RE epidemiology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: The lack of standardised definitions for heart failure outcome measures limits the ability to reliably assess effectiveness of heart failure therapies. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) aimed to produce a catalogue of internationally endorsed data definitions for heart failure outcome measures., Methods: Following the EuroHeart methods for the development of cardiovascular data standards, a working group was formed of representatives from the European Society of Cardiology Heart Failure Association and other leading heart failure experts. A systematic review of observational and randomised clinical trials identified current outcome measures, which was supplemented by clinical practice guidelines and existing registries for contemporary definitions. A modified Delphi process was employed to gain consensus for variable inclusion and whether collection should be mandatory (Level 1) or optional (Level 2) within EuroHeart. In addition, a set of complementary outcome measures were identified by the Working Group as of scientific and clinical importance for longitudinal monitoring for people with heart failure., Results: Five Level 1 and two Level 2 outcome measures were selected and defined, alongside five complementary monitoring outcomes for patients with heart failure., Conclusion: We present a structured, hierarchical catalogue of internationally endorsed heart failure outcome measures. This will facilitate quality improvement, high quality observational research, registry-based trials, and post market surveillance of medical devices., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Atherosclerotic plaque fluorine-18 sodium fluoride ( 18 F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18 F-NaF uptake., Methods: Subjects with high CV risk but without CV events underwent 18 F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18 F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18 F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18 F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation., Results: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL -1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18 F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003)., Conclusion: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18 F-NaF uptake was significantly reduced after six months of high-intensity statin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: Digital health (DH) is a broad concept, bringing together technology and healthcare, that is playing an increasingly important role in the daily routine of healthcare professionals (HCPs) and promises to contribute to the prevention and treatment of cardiovascular disease. There are no solid data on the position of Portuguese HCPs toward the implementation of DH in cardiovascular medicine. This national cross-sectional study aims to provide a snapshot of DH implementation in Portuguese cardiovascular HCP routines and to identify both expectations and barriers to its adoption., Methods: An 18-question survey was created specifically for this study and distributed to 1174 individuals on the Portuguese Society of Cardiology mailing list., Results: We collected 117 valid responses (response rate 10%). Almost all participants had smartphones and laptops, and two-thirds had tablets. Electronic medical information systems were the most used DH tool (84% of respondents) and were considered the most important for improving cardiovascular care. Implantable technologies (sensors and devices), telemedicine and social media were used by more than two out of three respondents and considered «very important» or «extremely important» by most of them. Most participants showed positive expectations regarding the impact of DH in cardiovascular medicine: 78% agreed that DH could improve health outcomes, 64% that it promotes health literacy and 63% that it could decrease healthcare costs. The top-rated barriers were patients' inability to use smartphones, limited access to electronic devices, and lack of legal regulation of DH., Conclusion: Most Portuguese cardiovascular HCPs had at least three electronic devices (mainly smartphones, laptops and tablets) and showed positive expectations regarding DH's current and future impact on cardiovascular medicine. Patient DH literacy, technology adoption, and DH regulation were identified as the most important barriers to increasing the adoption of DH tools in cardiovascular medicine., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction/aims: The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP)., Methods: We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients., Results: We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP., Discussion: In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Introduction and Objectives: Three-dimensional (3D) model simulation provides the opportunity to manipulate real devices and learn intervention skills in a realistic, controlled, and safe environment. To ensure that simulators provide a realistic surrogate to real procedures they must undergo scientific validation. We aimed to evaluate the 3D-printed simulator SimulHeart® for face and content validity to demonstrate its value as a training tool in interventional cardiology (IC)., Methods: Health professionals were recruited from sixteen Portuguese IC units. All participants received a 30-minute theoretical introduction, 10-minute demonstration of each task and then performed the intervention on a 3D-printed simulator (SimulHeart®). Finally, a post-training questionnaire focusing on the appearance of the simulation, simulation content, and satisfaction/self-efficacy was administered., Results: We included 56 participants: 16 "experts" (general and interventional cardiologists), 26 "novices" (cardiology residents), and 14 nurses and allied professionals. On a five-point Likert scale, the overall mean score of face validity was 4.38±0.35 and the overall mean score of content validity was 4.69±0.32. There was no statistically significant difference in the scores provided by "experts" and "novices". Participants reported a high level of satisfaction/self-efficacy with 60.7% considering it strongly improved their skills. The majority (82.1%) "agreed" or "strongly agreed" that after the simulation they felt confident to perform the procedure on a patient., Conclusion: The 3D-printed simulator (SimulHeart®) showed excellent face and content validity. 3D simulation may play an important role in future IC training programs. Further research is required to correlate simulator performance with clinical performance in real patients., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23-75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex ( p < 0.001), spinal onset ( p = 0.018), and FVC ≥ 80% ( p = 0.038). CK was 23.4% higher in spinal-onset ALS patients ( p < 0.001). High CK levels were not linked with an increased risk of death ( p = 0.334) in Cox multivariate regression analysis. CK ≥ P90 (HR = 1.001, p = 0.038), shorter disease duration (HR = 0.937, p < 0.001), lower pCMAP (HR = 0.082, p < 0.001), and higher ΔFS (HR = 1.968, p < 0.001) were risk factors for respiratory failure. The association between high CK levels and poorer respiratory outcomes could derive from cellular metabolic stress or a specific phenotype associated with faster respiratory decline. Our study suggests that CK measurement at diagnosis should be more extensively investigated as a possible marker of poor respiratory outcome in future studies, including a larger population of patients., Competing Interests: The authors declare no conflicts of interest.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in about 2% of all patients. Tofersen is a novel oligonucleotide antisense drug specifically developed to treat SOD1-ALS patients., Areas Covered: Our review covers and discusses tofersen pharmacological properties and its phase I/II and III clinical trials results. Other available drugs and their limitations are also addressed., Expert Opinion: VALOR study failed to meet the primary endpoint (change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to week 28, tofersen arm vs. placebo), but a significant reduction in plasma neurofilament light chain (NfL) levels was observed in tofersen arm (60% vs. 20%). PrefALS study has proposed plasma NfL has a potential biomarker for presymptomatic treatment, since it increases 6-12 months before phenoconversion. There is probably a delay between plasma NfL reduction and the clinical benefit. ATLAS study will allow more insights regarding tofersen clinical efficacy in disease progression rate, survival, and even disease onset delay in presymptomatic SOD1 carriers.

Introduction: Nusinersen was approved for 5q spinal muscular atrophy (SMA), irrespective of age, SMA type or functional status. Nonetheless, long-term data on adults with milder phenotypes are scarce. We aimed to characterize evolution on motor and respiratory function in our cohort of adults with type 3 SMA., Methods: We conducted a longitudinal retrospective single-center study, including adults (≥18 years) with type 3 SMA under nusinersen for > 22 months. We reported on motor scores and spirometry parameters., Results: Ten patients were included, with a median follow-up of 34 months (range = 22-46). Four patients (40%) were walkers. None used non-invasive ventilation. In Revised Upper Limb Module (RULM) and Expanded Hammersmith Functional Motor Scale (HFMSE), difference of medians increased at 6, 22 and 46 months comparing to baseline (-0.5 vs. + 1.5 vs. + 2.5 in RULM; + 4.0 vs. + 7.5 vs. + 6.0 in HFMSE). Two (50%) walkers presented a clinically meaningful improvement in 6-min walk distance. We did not report any clinically meaningful decrement in motor scores. Spirometry parameters showed an increasing difference of medians in maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (-3 vs. + 13.4 vs. + 28.7 percentage points of predicted value for MIP; + 11.8 vs. + 13.1 vs. 13.3 percentage points of predicted value for MEP)., Discussion: Our cohort supports a sustained benefit of nusinersen in adults with type 3 SMA, in motor and respiratory function. Multicentric studies are still warranted., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients., Material and Methods: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed., Results: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited., Conclusions: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier., Competing Interests: Declaration of competing interest Miguel Oliveira Santos and Mamede de Carvalho received support from Sanofi. The other authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clinical practice guidelines recommend oral anticoagulation (OAC) for stroke prevention in selected patients with atrial fibrillation (AF). However, some patients still experience thrombo-embolic events despite adequate anticoagulation. The optimal management of these cases remains uncertain, leading to practice pattern variability. We present a series of three cases illustrating the use of left atrial appendage occlusion (LAAO) as an adjunctive stroke prevention strategy in AF patients with recurrent thrombo-embolic events despite adequate anticoagulation., Case Summary: Case one describes an 89-year-old female on apixaban who presented with a thrombus and underwent successful mechanical thrombectomy. Left atrial appendage occlusion was performed, and no subsequent thrombo-embolic events were reported. Case 2 involves a 72-year-old female on full-dose apixaban who experienced recurrent strokes despite adequate anticoagulation. Thrombectomy was performed twice, and complications arose during LAAO. The patient was discharged on warfarin + clopidogrel and remained event-free at the six-month follow-up. Case 3 features an 88-year-old female on rivaroxaban who experienced recurrent cerebral ischaemic events and gastrointestinal bleeding. Left atrial appendage occlusion using an Amplatzer Amulet™ device was successful, and the patient remained event-free at the one-year follow-up., Discussion: This case series emphasizes the complexity of stroke prevention in AF patients and underscores the need for an individualized approach. Incorporating LAAO alongside OAC can provide additional stroke protection for patients with inadequate response to anticoagulation. Further randomized controlled trials are needed to evaluate the efficacy and safety of this approach. In light of the limited evidence available, these cases contribute to the growing body of knowledge on the potential role of LAAO in secondary stroke prevention in AF patients with recurrent thrombo-embolic events despite appropriate anticoagulation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dermatomyositis (DM) is an inflammatory myopathy often paraneoplastic in nature. Patients have characteristic cutaneous findings and possible muscle involvement. In the latter, muscle enzymes are elevated, and the electromyogram shows varied changes. Muscle or skin biopsy and myositis-specific antibodies confirm the diagnosis. Here, we report the case of an 86-year-old woman with cutaneous lesions, proximal weakness, and sicca symptoms. Muscle enzymes and electromyogram were normal. Antinuclear antibodies were elevated, and anti-TIF1γ and anti-Ro52 antibodies were positive. Muscle biopsy was compatible with the diagnosis of DM, and salivary gland biopsy confirmed Sjögren's syndrome. Malignancy investigation identified a rectal cancer, which was resected. This case illustrates a rare form of cancer presentation - anti-TIF1γ DM with normal muscle enzymes and electromyogram and concomitant secondary Sjögren's syndrome. Malignancy screening and multidisciplinary management were crucial to a successful approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Oliveira Santos et al.)

Introduction/aims: In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS., Methods: We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H' RI ) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H' Pre ) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H' Pos )., Results: Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H' RI 0.35 vs. 0.11, p = .036; H' Pre 1.0 vs. 5.0, p = .001; H' Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition., Discussion: Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS., (© 2024 Wiley Periodicals LLC.)

Background and Purpose: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function of ALS patients is uncertain., Methods: A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO 2 mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t-test, χ 2 , or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan-Meier analysis assessed survival. p < 0.05 was considered significant., Results: We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS-R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO 2 mean (p = 0.014)., Conclusions: ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Stroke is a significant public health problem, with non-valvular atrial fibrillation (NVAF) being one of its main causes. This cardiovascular arrhythmia predisposes to the production of intracardiac thrombi, mostly formed in the left atrial appendage (LAA). When there are contraindications to treatment with oral anticoagulants, another therapeutic option to reduce the possibility of thrombus formation in the LAA is the implantation of an occlusion device by cardiac catheterization. The effectiveness of LAA occlusion is dependent on accurate preprocedural device sizing and proper device positioning at the LAA ostium, to ensure sufficient device anchoring and avoid peri-device leaks. Additive manufacturing, commonly known as three-dimensional printing (3DP), of LAA models is beginning to emerge in the scientific literature to address these challenges through procedural simulation. This review aims at clarifying the impact of 3DP on preprocedural planning of LAA occlusion, specifically in the training of cardiac surgeons and in the assessment of the perfect adjustment between the LAA and the biomedical implant., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Introduction: Primary lateral sclerosis (PLS) is a rare, adult-onset and slowly progressive motor neuron disorder whose clinical core is characterized by upper motor neuron (UMN) dysfunction. Its formal diagnosis is clinically based and disease duration-dependent. Differentiating PLS from other disorders involving UMN can be challenging, particularly in the early stages., Areas Covered: Our review covers and discusses different aspects of the PLS field, including the diagnostic criteria and its limitations, its differential diagnosis and their major pitfalls, and the actual role of neurophysiology, neuroimaging, genetics, and molecular biomarkers. Symptomatic treatment of the different manifestations is also addressed. The authors searched MEDLINE and Scopus. They also searched the reference lists of articles identified by our search strategy and reviewed and selected those deemed relevant. They selected papers and studies based on the quality of the report, significance of the findings, and on the author's critical appraise and expertise., Expert Opinion: It is important to investigate novel molecular biomarkers and plan multicenter clinical trials for PLS. However, this will require a large international project to recruit enough patients, particularly given the diagnostic uncertainty of the current clinical criteria. A better understanding of PLS pathophysiology is crucial for designing disease-targeted therapies.

Background: Visual assessment of the percentage diameter stenosis (%DS VE ) of lesions is essential in coronary angiography (CAG) interpretation. We have previously developed an artificial intelligence (AI) model capable of accurate CAG segmentation. We aim to compare operators' %DS VE in angiography versus AI-segmented images., Methods: Quantitative coronary analysis (QCA) %DS (%DS QCA ) was previously performed in our published validation dataset. Operators were asked to estimate %DS VE of lesions in angiography versus AI-segmented images in separate sessions and differences were assessed using angiography %DS QCA as reference., Results: A total of 123 lesions were included. %DS VE was significantly higher in both the angiography (77% ± 20% vs. 56% ± 13%, p < 0.001) and segmentation groups (59% ± 20% vs. 56% ± 13%, p < 0.001), with a much smaller absolute %DS difference in the latter. For lesions with %DS QCA of 50%-70% (60% ± 5%), an even higher discrepancy was found (angiography: 83% ± 13% vs. 60% ± 5%, p < 0.001; segmentation: 63% ± 15% vs. 60% ± 5%, p < 0.001). Similar, less pronounced, findings were observed for %DS QCA  < 50% lesions, but not %DS QCA  > 70% lesions. Agreement between %DS QCA /%DS VE across %DS QCA strata (<50%, 50%-70%, >70%) was approximately twice in the segmentation group (60.4% vs. 30.1%; p < 0.001). %DS VE inter-operator differences were smaller with segmentation., Conclusion: %DS VE was much less discrepant with segmentation versus angiography. Overestimation of %DS QCA  < 70% lesions with angiography was especially common. Segmentation may reduce %DS VE overestimation and thus unwarranted revascularization., (© 2023 Wiley Periodicals LLC.)

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1 -positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1 -related patients., Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test., Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems., Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

Objective : Motor Neuron Diseases (MND) have a large clinical spectrum, being the most common amyotrophic lateral sclerosis (ALS) but there is significant clinical heterogeneity. Our goal was to investigate this heterogeneity and any potential changes during a long period. Methods : We performed a retrospective cohort study among a large Portuguese cohort of MND patients ( n  = 1550) and investigated changing patterns in clinical and demographic characteristics over the 27-year period of our database. With that aim, patients were divided into three 9-year groups according to the date of their first visit to our unit: P1, 1994-2002; P2, 2003-2011; P3, 2012-2020. Results : The overall cohort's clinical and demographic characteristics are consistent with clinical experience, but our findings point to gradual changes over time. Time pattern analysis revealed statistically significant differences in the distribution of clinical phenotypes, the average age of onset, diagnostic delay, the proportin of patients using respiratory support with noninvasive ventilation (NIV), time to NIV, and survival. Across time, in the overall cohort, we found an increasing age at onset ( p  = 0.029), a decrease of two months in diagnostic delay ( p <  0.001) and a higher relative frequency of progressive muscular atrophy patients. For ALS patients with spinal onset, from P1 to P2, there was a more widespread (54.8% vs 69.4%, p  = 0.005) and earlier (36.9 vs 27.2 months, p =  0.05) use of NIV and a noteworthy 13-month increase in median survival ( p  = 0.041). Conclusions : Our results probably reflect better comprehensive care, and they are relevant for future studies exploring the impact of new treatments on ALS patients.

Background and Purpose: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear., Methods: Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO 2 mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors., Results: We included 276 patients (153 men, onset age = 62.6 ± 11.0 years, disease duration = 13.0 ± 9.6 months, spinal onset in 182) with mean survival of 40.1 ± 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1 > G2 > G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO 2 mean. Independent predictors for G2 were MIP and SpO 2 mean; for G3, the only independent predictor was PhrenAmpl., Conclusions: These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro . LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer., Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Introduction and Objectives: Social media (SoMe) has a flourishing role in cardiovascular (CV) medicine as a facilitator of academic communication not only during conferences and congresses, but also by scientific societies and journals. However, there is no solid data illustrating the use of SoMe by CV healthcare professionals (CVHP) in Portugal. Hence, the main goal of this national cross-sectional survey was to accurately characterize SoMe use by Portuguese CVHPs., Methods: A 35-item questionnaire was specifically developed for this study, approved by the Digital Health Study Group of the Portuguese Society of Cardiology (SPC), and sent, by e-mail, to the mailing list of the SPC (including 1293 potential recipients)., Results and Conclusion: There were 206 valid answers. Fifty-two percent of respondents were female and 58% were younger than 44 years of age with almost two out of three participants being physicians. Ninety-two percent of the survey participants reported that they are currently using SoMe; LinkedIn was the most common platform used for professional purposes. Sixty-four percent believed SoMe had had a positive impact on their clinical practice; 77% and 49% had used SoMe for acquiring and sharing information related to COVID-19, respectively. In conclusion, the majority of Portuguese CVHPs that participated in this survey are actively using SoMe, with a greater participation of those <45 years of age; its clinical impact is positive, with a leading role in the dissemination of evidence during the COVID pandemic., (Copyright © 2023 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Declaration of Competing Interest None.

Collateral development in chronic total occlusions (CTO) is crucial to perfuse the distal myocardium and its angiographic evaluation is frequently used to assess the need for revascularization. We aimed to analyse the association between the presence of ischemia and hibernating myocardium, evaluated by cardiac [ 13  N]NH3/2-[ 18  F]FDG PET-CT, and the angiographic characterization of the collateral circulation. Prospective study including patients with a CTO who underwent a [ 13  N]NH3 and, when deemed necessary, 2-[ 18  F]FDG PET-CT. Well developed (WD) collaterals were defined as a concomitant angiographic Rentrop grade 3 and Werner collateral connection score 2 or 3, whereas the remaining as poorly developed (PD). 2% thresholds used to identify prognostic benefit of revascularization were applied: ischemia > 10% and hibernating myocardium > 7%. Fifty-nine patients (age 62.9±9.1 years, 58 male) were recruited, WD collaterals were present in 28 (47.5%). No significant differences were found in ischemia (WD 6.4±4.3 vs. PD 7.0±4.1, p = 0.64) and hibernation (WD 1.8±1.9 vs. PD 3.1±3.3, p = 0.18) scores. Most CTO territories demonstrated ischemia, but only 19 (46.3%) were associated with an area > 10% (WD 47.6% vs. PD 45.0%, p = 0.58). Scared non-viable myocardium was limited to 9 (15.3%) patients and was not associated with PD collaterals. Hibernating myocardium was frequent (54.2%), but just 6 (10.2%) CTO patients had an area of > 7% (WD 3.6% vs. PD 16.1%, p = 0.20). Collateral assessment by angiography has a poor association with the ischemic burden and hibernation state of CTO territories. Myocardial viability was present even in most CTO with angiographic PD collaterals., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE., Methods: This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6 weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 μg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs., Results: Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination., Conclusion: The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.

Amyotrophic lateral sclerosis (ALS) and myopathy have been already described as part of a common genetic syndrome called multisystem proteinopathy. They may occur together or not, and can be associated with other clinical features such as frontotemporal dementia and Paget's bone disease. In addition, primary skeletal muscle involvement has been also reported in inherited forms of lower motor neuron disease, in spinal-bulbar muscular atrophy and in spinal muscular atrophy. We aim to characterize three sporadic, spinal-onset ALS patients, one with a concurrent non-specific myopathy, and two with a previous diagnosis of myopathy before upper and lower motor neuron signs emerged. Perhaps our sporadic ALS cases associated with myopathy share a common, but still unknown, pathogenic background. These cases raise the paradigm of a possible interplay between skeletal muscle degeneration and motor neuron damage.

Objectives: In ST-segment elevation myocardial infarction (STEMI), time delay between symptom onset and treatment is critical to improve outcome. The expected transport delay between patient location and percutaneous coronary intervention (PCI) centre is paramount for choosing the adequate reperfusion therapy. The "Centro" region of Portugal has heterogeneity in PCI assess due to geographical reasons. We aimed to explore time delays between regions using process mining tools., Methods: Retrospective observational analysis of patients with STEMI from the Portuguese Registry of Acute Coronary Syndromes. We collected information on geographical area of symptom onset, reperfusion option, and in-hospital mortality. We built a national and a regional patient's flow models by using a process mining methodology based on parallel activity-based log inference algorithm., Results: Totally, 8956 patients (75% male, 48% from 51 to 70 years) were included in the national model. Most patients (73%) had primary PCI, with the median time between admission and treatment <120 minutes in every region; "Centro" had the longest delay. In the regional model corresponding to the "Centro" region of Portugal divided by districts, only 61% had primary PCI, with "Guarda" (05:04) and "Castelo Branco" (06:50) showing longer delays between diagnosis and reperfusion than "Coimbra" (01:19). For both models, in-hospital mortality was higher for those without reperfusion therapy compared to PCI and fibrinolysis., Conclusion: Process mining tools help to understand referencing networks visually, easily highlighting its inefficiencies and potential needs for improvement. A new PCI centre in the "Centro" region is critical to offer timely first-line treatment to their population., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a median survival of 2-5 years. An early diagnosis is essential for providing ALS patients the finest management possible. Studies from different countries report a similar median diagnostic delay of around 12 months, which is still far from desirable. We analyzed the diagnostic pathway in different countries in order to identify the major challenges., Methods: We studied a cohort of 1,405 ALS patients from five different centers, in four different countries (Turkey, Germany, Poland, and Portugal), which collaborated in a common database. Demographic, disease and sociocultural factors were collected. Time from first symptom onset to first medical evaluation and to diagnosis, the specialist assessment and investigations requested were analyzed. Factors contributing to diagnostic delay were evaluated by multivariate linear regression., Results: The median diagnostic delay from first symptom onset was 11 months and was similar between centers. Major differences were seen in the time from symptom onset to first medical evaluation. An earlier first medical evaluation was associated with a longer time to diagnosis, highlighting that ALS diagnosis is not straightforward in the early stages of the disease. The odds for ALS diagnosis were superior when evaluated by a neurologist and increased over time. Electromyography was decisive in establishing the diagnosis., Conclusions: We suggest that a specific diagnostic test for ALS-a specific biomarker-will be needed to achieve early diagnosis. Early referral to a neurologist and to electromyography is important for early ALS diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Falcão de Campos, Gromicho, Uysal, Grosskreutz, Kuzma-Kozakiewicz, Oliveira Santos, Pinto, Petri, Swash and de Carvalho.)

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The clinical epidemiology of inherited myopathies in sub-Saharan Africa (SSA) is unknown but likely underdiagnosed due to problems of scientific research and social issues. We report a case series of patients born in SSA, evacuated to Portugal through an international health protocol and seen at a single neuromuscular disorders centre, between January/2004 and August/2021. We identified 9 patients (5 males), 35.6 ± 19.3 years-old (10-64), from Cape Verde (n = 4), Angola (n = 2), Sao Tome and Principe (n = 2) and Guinea-Bissau (n = 1), with a delay in diagnosis of 19.7 ± 14.3 years. Seven patients (77.8 %) had positive family history. Most patients had significant morbidity, requiring wheelchair (55.6 %), and nocturnal non-invasive ventilation (55.6 %). The diagnosis included Bethlem myopathy (n = 2), Duchenne muscular dystrophy (n = 2), Emery-Dreifuss muscular dystrophy (n = 1), LGMDR1 (n = 2), LGMDR2 (n = 1), and type-1 myotonic dystrophy (n = 1). Genetic testing was remarkable for 3 mutations previously not described. Despite the small sample, the spectrum of hereditary myopathies in our cohort is like western studies. Further studies are needed to better understand the epidemiology of muscle diseases in SSA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Some amyotrophic lateral sclerosis (ALS) patients on continuous non-invasive ventilation (NIV) develop dysphagia demanding a clinical decision regarding gastrostomy., Material and Methods: We have analyzed a cohort of seventy-four ALS patients dependent on continuous NIV (>22 h/day) and without feeding tube., Results: Three patients underwent to gastrostomy due to dysphagia progression. The other patients were categorized in two groups according to question 3 ("swallowing") of the ALSFRS-R scale: group 1 (G1), score = 4 (normal), and group 2 (G2), score = 3 or 2 (mild-moderate dysphagia). G2 included 29 (40.8%) patients. Survival was similar in G1 and G2 (p = 0.12). Disease duration (p < 0.0001) and ALSFRS-R progression rate (p = 0.008) at NIV >22 h/day were predictors for survival in G1, but not for G2. Gender, onset-region, and age at NIV >22 h/day did not influence survival., Conclusions: Our findings are relevant when discussing gastrostomy with these patients., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We describe three unrelated patients with sporadic motor neuron disease (MND) and hereditary amyloid transthyretin (ATTRv) amyloidosis family history, who were asymptomatic carriers of the pVal50Met mutation of transthyretin (TTR) gene. Patients 1 and 2 were a 43-year-old man with a spinal-onset of ALS and a 37-year-old woman with a bulbar-onset of ALS, who died due to respiratory complications five and two years after disease onset, respectively. Patient 3 is a 52-year-old woman, with a two-year history of a probable primary lateral sclerosis, and a frontotemporal dysfunction. Imaging, cerebrospinal fluid (CSF) and nerve conduction and small fiber tests were normal in all. Genetic testing for ALS was negative in the two patients tested. Previous studies in MND patients have identified reduced TTR levels in CSF and neuronal gene overexpression, suggesting a neuroprotective role of TTR. The association of MND in patients with TTR gene mutations has not yet been described.