Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Biallelic TUFT1 variants cause woolly hair, superficial skin fragility and desmosomal defects.

BACKGROUND: Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress. OBJECTIVES: To identify causal variants in individuals with woolly hair and skin fragility of unknown genetic cause. METHODS: This research was conducted using whole-genome sequencing, whole-exome sequencing, clinical phenotyping, haplotype analysis, single-cell RNA sequencing data analysis, immunofluorescence microscopy and transmission electron microscopy. RESULTS: We identified homozygous predicted loss-of-function tuftelin-1 (TUFT1) variants in nine individuals, from three families, with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A substitution to be a founder variant in the Irish population that likely arose approximately 20 generations ago. Human and mouse single-cell RNA sequencing data showed TUFT1 expression to be enriched in the hair dermal sheath and keratinocytes. TUFT1 expression was highly correlated with genes encoding desmosomal components implicated in diseases with phenotypes that overlap with the cohort presented here. Immunofluorescence showed tuftelin-1 to be mainly localized to the peripheral cell membranes of keratinocytes in normal skin. Skin samples from individuals with TUFT1 variants showed markedly reduced immunoreactivity for tuftelin-1, with a loss of the keratinocyte cell membrane labelling. Light microscopy revealed keratinocyte adhesion, mild hyperkeratosis and areas of superficial peeling. Transmission electron microscopy showed panepidermal acantholysis with widening of intercellular spaces throughout the epidermis and desmosomal detachment through the inner plaques. CONCLUSIONS: Biallelic loss-of-function TUFT1 variants cause a new autosomal recessive skin/hair disorder characterized by woolly hair texture and early-onset skin fragility. Tuftelin-1 has a role in desmosomal integrity and function.

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

TREXIO: A file format and library for quantum chemistry.

TREXIO is an open-source file format and library developed for the storage and manipulation of data produced by quantum chemistry calculations. It is designed with the goal of providing a reliable and efficient method of storing and exchanging wave function parameters and matrix elements, making it an important tool for researchers in the field of quantum chemistry. In this work, we present an overview of the TREXIO file format and library. The library consists of a front-end implemented in the C programming language and two different back-ends: a text back-end and a binary back-end utilizing the hierarchical data format version 5 library, which enables fast read and write operations. It is compatible with a variety of platforms and has interfaces for Fortran, Python, and OCaml programming languages. In addition, a suite of tools have been developed to facilitate the use of the TREXIO format and library, including converters for popular quantum chemistry codes and utilities for validating and manipulating data stored in TREXIO files. The simplicity, versatility, and ease of use of TREXIO make it a valuable resource for researchers working with quantum chemistry data.

Management of acute sloughing of the esophageal lining in patients with dystrophic epidermolysis bullosa-A series of six pediatric patients.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a subtype of an inherited skin disorder characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Esophageal strictures leading to chronic dysphagia and acute episodes are well recognized complications within this subtype. Sloughing of esophageal mucosa and the treatment of this emergency have heretofore received limited attention in the EB literature. METHODS: We retrospectively reviewed the electronic medical records of the patients who had an acute episode of sloughing of the esophageal lining between 2008 and 2021 and extracted the information regarding their clinical presentation and management. RESULTS: Six patients out of 210 with recessive DEB severe (RDEB-S) (n = 4), RDEB intermediate (RDEB-I) (n = 1) and dominant DEB (DDEB) (n = 1) were identified. The mean age at the time of the episode was 2.7 years. All patients had early-onset severe gastroesophageal reflux. Clinically, they presented with a coughing episode (n = 6), hematemesis (n = 6), vomiting (n = 6), and choking (n = 3), followed by coughing up a string like tissue of variable length, part of the esophageal mucosal lining. Four patients recovered with medical management only, two patients required gastrostomy insertions for feeding due to severe persistent dysphagia and one also required a Nissen's fundoplication to manage severe reflux. One patient had aspiration pneumonia. CONCLUSIONS: Sloughing of varying lengths of segments of the esophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately for urgent assessment and management. Expert multidisciplinary care is needed to manage this rare but serious condition.

The impact of using a multistrain probiotic supplement on gastrointestinal function in children and adolescents with severe recessive dystrophic epidermolysis bullosa.

BACKGROUND: Children and adolescents with severe recessive dystrophic epidermolysis bullosa (RDEB-S) often have severe constipation in addition to gastrointestinal dysbiosis, due to frequent antibiotic use and reduced oral diet. Constipation is treated with long-term use of high daily doses of macrogol gel (Movicol Paediatric PlainTM or LaxidoTM). Constipation is refractory to increases in fibre and fluids, and impacts severely on quality of life. AIM: To study the initial impact and efficacy of using a multistrain probiotic supplement daily for 12 weeks in patients with RDEB-S. The authors sought to determine the impact of such a supplement on  gastrointestinal symptoms, stool consistency and the use of macrogol gel to treat constipation, as well as understanding patient reaction, palability and ease of use. METHODS: Patients were identified through the epidermolysis bullosa tertiary multidisciplinary team clinic in July 2021. Patients were included if they had a diagnosis of RDEB-S, prescribed at least one sachet of macrogol gel and provided written consent to take part. Patients were provided, proprietary liquid multistrain probiotic supplement (Symprove™) with a high bacterial count, at a dose of 1 mL kg-1 once a day. Each patient completed an anonymous, nine-question, electronic survey to document symptoms and report overall findings at the start and end of a 12-week trial period. RESULTS: Four patients with RDEB-S (two boys and two girls; age range 7-14 years) who met the inclusion criteria were approached to take part. All patients had chronic constipation requiring daily macrogol gel use (range 2-5 sachets per day). Three out of four (75%) completed the 12-week course. At baseline (before supplementation commenced), all three (100%) patients reported poor oral appetite, constipation, flatulence, abdominal bloating and pain, and frequent skin infections requiring oral antibiotics, with two of the three (66%) patients also having nausea. After 12 weeks of supplementation, all three patients (100%) reported a significant improvement in abdominal pain and bloating, nausea, stool consistency, stool frequency, flatulence and increased appetite. Two of the three patients (66%) were able to reduce their macrogol gel usage and the third patient (33%) was able to stop macrogol gel usage altogether during the study period. All three patients said they would choose to continue using the supplement if it was available. CONCLUSION: We have shown in this case series that giving a multistrain probiotic supplement in patients with RDEB-S has the potential to improve stool consistency and reduce or prevent the need for chronic macrogol gel use. Future larger-scale, placebo-controlled trials are needed to confirm these results.

Surgical Ciliated Cysts in Orthognathic Surgery.

ABSTRACT: Surgical ciliated cysts (SCC) are rare entities that were first described in the Japanese literature after treatment for chronic maxillary sinusitis. Classically associated with surgery to the maxillary sinus, they have also been reported in association with orthognathic surgery, bone grafting, and trauma. These lesions can develop from a few months up to several years after the surgical procedure. The authors report 2 new cases of SCC after a LeFort I osteotomy for class III dentofacial deformity correction. One of them presented with bilateral lesions and suffered from a recurrence after 5 years, 2 rare events associated with SCC.A review of the literature of the past 5 years was undertaken, in order to ascertain the reported time of follow-up and recurrence. A PubMed search retrieved a total of 15 articles with 17 cases reported. Nine cases were associated with orthognathic surgery, 4 with Caldwell-Luc procedures, 2 with sinus lift and 2 with trauma. The mean follow-up after removal of the SCC was of 8.6 months. Four cases did not specify the follow up time; 1 case was lost to follow-up. No relapses were reported.Like what happens with the primary lesion, a recurrence can take place several years after removal. It is the authors' opinion that adequate long-term follow-up must be granted for a timely diagnosis and treatment of relapsed SCC.

Correction to: Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).

The above article was published online with incorrect figure 1.

Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.

Surgical site infection (SSI) is a common postoperative complication and can cause avoidable morbidity and excessive costs for the health service. Novel dressings, designed specifically for postoperative wounds, can help to reduce the risk of SSI and other complications such as blistering. This study compared the use of a new polyurethane film surgical dressing (Opsite Post-Op Visible, Smith & Nephew, Hull, UK) with gauze and tape in the management of postoperative wounds. The results show that the polyurethane film dressing results in a significant reduction in SSI (1·4% versus 6·6%, P = 0·006) as well as a reduction in other postoperative wound complications (e.g. blistering and erythema). Economic analysis conducted alongside the study suggests that these improved outcomes can be achieved at a lower treatment cost than gauze and tape dressings. The modest incremental cost of the polyurethane film surgical dressing is easily offset by the reduction in the costs related to treating SSI and other wound complications associated with gauze and tape dressings.

Toward Real Chemical Accuracy on Current Quantum Hardware Through the Transcorrelated Method.

Quantum computing is emerging as a new computational paradigm with the potential to transform several research fields including quantum chemistry. However, current hardware limitations (including limited coherence times, gate infidelities, and connectivity) hamper the implementation of most quantum algorithms and call for more noise-resilient solutions. We propose an explicitly correlated Ansatz based on the transcorrelated (TC) approach to target these major roadblocks directly. This method transfers, without any approximation, correlations from the wave function directly into the Hamiltonian, thus reducing the resources needed to achieve accurate results with noisy quantum devices. We show that the TC approach allows for shallower circuits and improves the convergence toward the complete basis set limit, providing energies within chemical accuracy to experiment with smaller basis sets and, thus, fewer qubits. We demonstrate our method by computing bond lengths, dissociation energies, and vibrational frequencies close to experimental results for the hydrogen dimer and lithium hydride using two and four qubits, respectively. To demonstrate our approach's current and near-term potential, we perform hardware experiments, where our results confirm that the TC method paves the way toward accurate quantum chemistry calculations already on today's quantum hardware.

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy.

Purpose: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and Methods: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. Conclusion: Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.

Excitons and biexcitons in symmetric electron-hole bilayers.

Symmetric electron-hole bilayer systems have been studied at zero temperature using the diffusion quantum Monte Carlo method. A flexible trial wave function is used that can describe fluid, excitonic, and biexcitonic phases. We calculate condensate fractions and pair correlation functions for a large number of densities r(s) and layer separations d. At small d we find a one-component fluid phase, an excitonic fluid phase, and a biexcitonic fluid phase, and the transitions among them appear to be continuous. At d=0, excitons appear to survive down to about r(s)=0.5 a.u., and biexcitons form at r(s)>2.5 a.u.

Congenital Zika syndrome.

In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.

En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.

Density Matrix Renormalization Group for Transcorrelated Hamiltonians: Ground and Excited States in Molecules.

We present the theory of a density matrix renormalization group (DMRG) algorithm which can solve for both the ground and excited states of non-Hermitian transcorrelated Hamiltonians and show applications in molecular systems. Transcorrelation (TC) accelerates the basis set convergence rate by including known physics (such as, but not limited to, the electron-electron cusp) in the Jastrow factor used for the similarity transformation. It also improves the accuracy of approximate methods such as coupled cluster singles and doubles (CCSD) as shown by recent studies. However, the non-Hermiticity of the TC Hamiltonians poses challenges for variational methods like DMRG. Imaginary-time evolution on the matrix product state (MPS) in the DMRG framework has been proposed to circumvent this problem, but this is currently limited to treating the ground state and has lower efficiency than the time-independent DMRG (TI-DMRG) due to the need to eliminate Trotter errors. In this work, we show that with minimal changes to the existing TI-DMRG algorithm, namely, replacing the original Davidson solver with the general Davidson solver to solve the non-Hermitian effective Hamiltonians at each site for a few low-lying right eigenstates, and following the rest of the original DMRG recipe, one can find the ground and excited states with improved efficiency compared to the original DMRG when extrapolating to the infinite bond dimension limit in the same basis set. An accelerated basis set convergence rate is also observed, as expected, within the TC framework.

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer.

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC. Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase chain reaction (RT-PCR) using a customized pre-selected panel of 20 genes. Results: At least 1 CTC was detected by enumeration in 53.8% of samples. Most patients had fewer than 5 CTCs (91%) and the highest observed count was 35 CTCs. Enumeration of single CTCs was not prognostic, although detection of CTC clusters at any time point was associated with increased risk of progression [hazard ratio (HR) 3.00, 95% confidence interval (CI): 1.1-8.2, P=0.0318]. In contrast, 124 (97.6%) patients with samples interrogated for gene expression had at least 1 gene detectable in at least 1 sample, and 101 (79.5%) had at least one elevated epithelial gene in at least one timepoint. High expression of BCL2, CD274 [programmed death-ligand 1 (PD-L1)], CDH1, EPCAM, FGFR1, FN1, KRT18, MET and MUC1 were associated with poor prognosis. Patients with CTCs positive for at least 3 epithelial genes at baseline all progressed within 10 months (HR 8.2, P<0.001, 95% CI: 3.2-21.1). BCL2, CD274 (PD-L1), EPCAM and MUC1 remained significant independent prognostic factors in multivariate, time-dependent analyses of progression and death. Conclusions: The selective profile of CTC genes and identification of CTC clusters better correlated with prognosis than enumeration of enriched CTC in NSCLC patients in this study.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Evaluation of the use of high-efficacy treatments (HETs) in patients with relapsing-remitting multiple sclerosis in Argentina.

BACKGROUND: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years. METHODS: A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included. RESULTS: Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0-1 year) and in treatment-experienced patients it was 5 years (IQR: 3-9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2. CONCLUSION: The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS.

Disease activity after discontinuation of disease-modifying therapies in patients with multiple sclerosis in Argentina: data from the nationwide registry RelevarEM.

INTRODUCTION: The discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is commonly seen in real-world settings due to several factors. AREA COVER: The aim of this study is to describe the frequency of disease activity after discontinuation of DMTs in MS patients included in the Argentinean MS and NMOSD registry. DISCUSION: Patients with relapsing remitting MS (RRMS) and active secondary progressive MS (SPMS) were included based on the following criteria: they discontinued treatment for more than 6 months, they had been treated with a DMT for ≥2 years, and they had at least 6 months of follow-up in the registry after discontinuation. Demographic and clinical data were collected. Disease activity during follow-up was defined as the presence of a clinical relapse or a new magnetic resonance (MRI) lesion (either new lesions on T2-weighted sequence and/or contrast enhancement). Bivariate analysis was applied to identify clinical and demographic factors related to disease activity. CONCLUSION: We included 377 patients (75.5% RRMS, 22.5% SPMS) who had discontinued DMTs. The mean (SD) follow-up after discontinuation was 15.7 (7.9) months. After discontinuation, the presence of relapse was detected in 18.8% and 3.5% in RRMS and SPMS, respectively; and new MRI activity in 22% and 3.5%, respectively. We found that higher risk of relapse and MRI activity was associated with younger age (p < 0.001), shorter disease duration (p < 0.001), and RRMS phenotype (p = 0.006). Males showed higher MRI activity (p 0.011). This study provides real-world data that can guide physicians when considering discontinuation of DMTs.