ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration.

Defective hippocampal neurogenesis underlies cognitive impairment by carotid stenosis-induced cerebral hypoperfusion in mice.

Chronic cerebral hypoperfusion due to carotid artery stenosis is a major cause of vascular cognitive impairment and dementia (VCID). Bilateral carotid artery stenosis (BCAS) in rodents is a well-established model of VCID where most studies have focused on white matter pathology and subsequent cognitive deficit. Therefore, our aim was to study the implication of adult hippocampal neurogenesis in hypoperfusion-induced VCID in mice, and its relationship with cognitive hippocampal deficits. Mice were subjected to BCAS; 1 and 3 months later, hippocampal memory and neurogenesis/cell death were assessed, respectively, by the novel object location (NOL) and spontaneous alternation performance (SAP) tests and by immunohistology. Hypoperfusion was assessed by arterial spin labeling-magnetic resonance imaging (ASL-MRI). Hypoperfused mice displayed spatial memory deficits with decreased NOL recognition index. Along with the cognitive deficit, a reduced number of newborn neurons and their aberrant morphology indicated a remarkable impairment of the hippocampal neurogenesis. Both increased cell death in the subgranular zone (SGZ) and reduced neuroblast proliferation rate may account for newborn neurons number reduction. Our data demonstrate quantitative and qualitative impairment of adult hippocampal neurogenesis disturbances associated with cerebral hypoperfusion-cognitive deficits in mice. These findings pave the way for novel diagnostic and therapeutic targets for VCID.

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial.

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

Tailored Informational Interventions for Reducing Surplus and Waste of Fruits and Vegetables in a Food Market: A Pilot Study.

This pilot study explored the effectiveness of tailored informational interventions to reduce the surplus and waste of fruits and vegetables at the distribution level in Chile. Stalls from a fresh food market were randomized to intervention (n = 5 selling fruits, n = 5 selling vegetables) or control (n = 4 selling fruits, n = 4 selling vegetables) groups. The causes of surplus and waste were estimated by questionnaires. Surplus, avoidable waste, and unavoidable waste were measured using direct quantification before and after the intervention, and were expressed relative to the initial stock. Before the intervention, the surplus was (median [25th-75th percentile]) 46.2% [33.3-51.2] for fruits and 51.5% [41.3-55.0] for vegetables; avoidable waste was 0.1% [0.0-0.8] for fruits and 1.8% [0.7-5.3] for vegetables; and unavoidable waste was 0.0% [0.0-1.0] for fruits and 0.0% [0.0-1.3] for vegetables. Planning and storage represented the main causes explaining surplus and waste. After the intervention, the intervention group decreased the surplus of fruits compared to the control group (-17.8% [-29.0--11.0] vs. 5.8% [-0.6-7.8], respectively; p = 0.016), without other differences. In conclusion, tailored informational interventions based on the causes of surplus and waste may reduce the surplus of fruits in a fresh food market. Interventions might also include management strategies for the surplus to improve grocers' business operations.

APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke.

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo). Identification of the trial: EudraCT: 2020-002059-38 and ClinicalTrials.gov Identifier: NCT04734548 https://clinicaltrials.gov/ct2/show/NCT04734548?term=ApTOLL&cond=Stroke&draw=2&rank=1.

Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction.

Experimental evidence indicates that the control of the inflammatory response after myocardial infarction is a key strategy to reduce cardiac injury. Cellular damage after blood flow restoration in the heart promotes sterile inflammation through the release of molecules that activate pattern recognition receptors, among which TLR4 is the most prominent. Transient regulation of TLR4 activity has been considered one of the potential therapeutic interventions with greater projection towards the clinic. In this regard, the characterization of an aptamer (4FT) that acts as a selective antagonist for human TLR4 has been investigated in isolated macrophages from different species and in a rat model of cardiac ischemia/reperfusion (I/R). The binding kinetics and biological responses of murine and human macrophages treated with 4FT show great affinity and significant inhibition of TLR4 signaling including the NF-κB pathway and the LPS-dependent increase in the plasma membrane currents (Kv currents). In the rat model of I/R, administration of 4FT following reoxygenation shows amelioration of cardiac injury function and markers, a process that is significantly enhanced when the second dose of 4FT is administered 24 h after reperfusion of the heart. Parameters such as cardiac injury biomarkers, infiltration of circulating inflammatory cells, and the expression of genes associated with the inflammatory onset are significantly reduced. In addition, the expression of anti-inflammatory genes, such as IL-10, and pro-resolution molecules, such as resolvin D1 are enhanced after 4FT administration. These results indicate that targeting TLR4 with 4FT offers new therapeutic opportunities to prevent cardiac dysfunction after infarction.

Osteoporosis postmenopáusica: relevancia de la búsqueda estructurada de causas secundarias / A search for secondary causes of osteoporosis or low mineral density in postmenopausal women

BACKGROUND: A secondary cause can be found in up to one third of women with osteoporosis, potentially modifying their therapeutic approach. AIM: To determine the prevalence of secondary causes and risk factors for decreased bone mineral density (BMD) and osteoporosis. Material and Methods: We included postmenopausal women with a diagnosis of osteoporosis or low BMD who consulted for the first time in an endocrinology clinic between October 2018 and March 2020. A complete medical history, physical examination and a standardized laboratory assessment to identify secondary causes were performed. RESULTS: During the study period, 114 women were evaluated, 30 of them with low BMD and 84 with osteoporosis. After obtaining a medical history and a structured laboratory screening, at least one secondary cause was found in 50% of patients with osteoporosis and in 67% of those with low BMD. Most patients with no identified secondary cause had at least one risk factor for fragility fractures. Conclusions: A structured evaluation that includes medical history and standardized laboratory study in postmenopausal women with osteoporosis or low BMD, is a valuable tool to identify secondary causes of osteoporosis.

First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers.

ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke and myocardial infarction. The aim of this study was to characterize the safety and pharmacokinetics of ApTOLL in healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial to assess safety and pharmacokinetics of ApTOLL (30-min infusion intravenously) was performed in 46 healthy adult male volunteers. The study was divided into two parts: part A included seven single ascending dose levels, and part B had one multiple dose cohort. Safety and pharmacokinetic parameters were evaluated. No serious adverse events or biochemistry alterations were detected at any dose nor at any administration pattern studied. Maximum concentration was detected at the end of the infusion and mean half-life was 9.3 h. Interestingly, exposure increased in the first four levels receiving doses from 0.7 mg to 14 mg (AUC of 2,441.26 h∗ng/mL to 23,371.11 h∗ng/mL) but remained stable thereafter (mean of 23,184.61 h∗ng/mL after 70 mg). Consequently, the multiple dose study did not show any accumulation of ApTOLL. These results show an excellent safety and adequate pharmacokinetic profile that, together with the efficacy demonstrated in nonclinical studies, provide the basis to start clinical trials in patients.

[Post-covid syndrome after icu admission. Parameters related to a better physical recovery after 4 months.] / Síndrome pos-COVID tras ingreso en UCI. Parámetros relacionados con una mejor recuperación física a los 4 meses.

OBJECTIVE: Post-COVID syndrome can impact against every sphere of daily live. The objective of this work was to detect the factors correlated with a better or worse physical recovery four months after hospital discharge from a hospitalization in ICU due to COVID-19. METHODS: Prospective descriptive study of 125 patients valued by the Rehabilitation Service during hospitalization in ICU, from March 12th to December 31st, 2020. Data from 76 patients was analysed with clinical follow up after 1, 2 and 4 months of hospital discharge. Variables on personal, hospitalary, functional symptoms/signals and physical recovery were analysed with mean ± standard deviation, counting (percentage), T-student test and Fisher test. RESULTS: After one month, fatigue was observed in 60 (80%) patients and dyspnoea in 47 (62%). After two months, fatigue in 37 (55%), dyspnoea in 25 (33%), shoulder pain in 33 (43%), average QuickDASH was 22.7 (11.3-50), Sit-to-Stand Test in 30 seconds 11.5 (10-13) and 6-minute walk test 390 meters (326-445). In the fourth month, 25 (53%) had returned to work and had an average of the physical recovery of 79.1%±18.3%. There was no correlation between physical recovery ≥75% and the first month data, but there certainly was a correlation between some second month variables, such as fatigue (p=0.001), dyspnoea (p=0.035), QuickDASH (p=0.001) and 6-minute walk test (p=0.021). CONCLUSIONS: Symptoms (fatigue and dyspnoea) and functional scales (QuickDASH and 6-minute walk test) after 2 months predict a better/worsen physical recovery after 4 months of hospital discharge.

OBJETIVO: El síndrome pos-COVID puede impactar en todas las esferas de la vida diaria. El objetivo de este trabajo fue detectar qué factores se relacionan con una mejor/peor recuperación física a los 4 meses del alta hospitalaria tras ingreso en UCI por la COVID-19. METODOS: Estudio prospectivo de una cohorte de 125 pacientes valorados por Rehabilitación durante su ingreso en UCI, del 12 marzo al 31 diciembre del 2020. Las variables personales, hospitalarias, síntomas/signos funcionales y de recuperación física de los 76 pacientes que continuaron seguimiento al mes, 2 y 4 meses del alta hospitalaria fueron analizadas mediante media ± desviación estándar, contaje (porcentaje), test t-student y test de Fisher. RESULTADOS: En el primer mes, aquejaban fatiga 60 (80%) pacientes y disnea 47 (62%). En el segundo mes referían fatiga 37 (55%), disnea 25 (33%), dolor de hombro 33 (43%), la media de QuickDASH fue 22,7 (11,3-50), de sit to stand test en 30 segundos 11,5 (10-13) y de test 6 minutos marcha 390 metros (326-445). En el cuarto mes, se habían reincorporado laboralmente 25 (53%) y la media de recuperación física fue 79,1%±18,3%. No hay relación entre una recuperación física ≥75% y variables del primer mes, pero sí con variables del segundo mes, como la fatiga (p=0,001), disnea (p=0,035), QuickDASH (p=0,001) y Test 6 minutos marcha (p=0,021). CONCLUSIONES: Los síntomas (fatiga y disnea) y el QuickDASH y test 6 minutos marcha a los 2 meses predicen una mejor/peor recuperación física a los 4 meses tras el alta hospitalaria.

Síndrome pos-COVID tras ingreso en UCI. Parámetros relacionados con una mejor recuperación física a los 4 meses / Post-COVID syndrome after ICU admission. Parameters related to a better physical recovery after 4 months

Fundamentos: El síndrome pos-COVID puede impactar en todas las esferas de la vida diaria. El objetivo de este trabajo fue detectar qué factores se relacionan con una mejor/peor recuperación física a los 4 meses del alta hospitalaria tras ingreso en UCI por la COVID-19. Métodos: Estudio prospectivo de una cohorte de 125 pacientes valorados por Rehabilitación durante su ingreso en UCI, del 12 marzo al 31 diciembre del 2020. Las variables personales, hospitalarias, síntomas/signos funcionales y de recuperación física de los 76 pacientes que continuaron seguimiento al mes, 2 y 4 meses del alta hospitalaria fueron analizadas mediante media ± desviación estándar, contaje (porcentaje), test t-student y test de Fisher. Resultados: En el primer mes, aquejaban fatiga 60 (80%) pacientes y disnea 47 (62%). En el segundo mes referían fatiga 37 (55%), disnea 25 (33%), dolor de hombro 33 (43%), la media de QuickDASH fue 22,7 (11,3-50), de sit to stand test en 30 segundos 11,5 (10-13) y de test 6 minutos marcha 390 metros (326-445). En el cuarto mes, se habían reincorporado laboralmente 25 (53%) y la media de recuperación física fue 79,1%±18,3%. No hay relación entre una recuperación física ≥75% y variables del primer mes, pero sí con variables del segundo mes, como la fatiga (p=0,001), disnea (p=0,035), QuickDASH (p=0,001) y Test 6 minutos marcha (p=0,021). Conclusiones: Los síntomas (fatiga y disnea) y el QuickDASH y test 6 minutos marcha a los 2 meses predicen una mejor/peor recuperación física a los 4 meses tras el alta hospitalaria.(AU)

Background: Post-COVID syndrome can impact against every sphere of daily live. The objective of this work was to detect the factors correlated with a better or worse physical recovery four months after hospital discharge from a hospitalization in ICU due to COVID-19. Methods: Prospective descriptive study of 125 patients valued by the Rehabilitation Service during hospitalization in ICU, from March 12th to December 31st, 2020. Data from 76 patients was analysed with clinical follow up after 1, 2 and 4 months of hospital discharge. Variables on personal, hospitalary, functional symptoms/signals and physical recovery were analysed with mean ± standard deviation, counting (percentage), T-student test and Fisher test. Results: After one month, fatigue was observed in 60 (80%) patients and dyspnoea in 47 (62%). After two months, fatigue in 37 (55%), dyspnoea in 25 (33%), shoulder pain in 33 (43%), average QuickDASH was 22.7 (11.3-50), Sit-to-Stand Test in 30 seconds 11.5 (10-13) and 6-minute walk test 390 meters (326-445). In the fourth month, 25 (53%) had returned to work and had an average of the physical recovery of 79.1%±18.3%. There was no correlation between physical recovery ≥75% and the first month data, but there certainly was a correlation between some second month variables, such as fatigue (p=0.001), dyspnoea (p=0.035), QuickDASH (p=0.001) and 6-minute walk test (p=0.021). Conclusions: Symptoms (fatigue and dyspnoea) and functional scales (QuickDASH and 6-minute walk test) after 2 months predict a better/worsen physical recovery after 4 months of hospital discharge.(AU)

[A search for secondary causes of osteoporosis or low mineral density in postmenopausal women]. / Osteoporosis postmenopáusica: relevancia de la búsqueda estructurada de causas secundarias.

BACKGROUND: A secondary cause can be found in up to one third of women with osteoporosis, potentially modifying their therapeutic approach. AIM: To determine the prevalence of secondary causes and risk factors for decreased bone mineral density (BMD) and osteoporosis. MATERIAL AND METHODS: We included postmenopausal women with a diagnosis of osteoporosis or low BMD who consulted for the first time in an endocrinology clinic between October 2018 and March 2020. A complete medical history, physical examination and a standardized laboratory assessment to identify secondary causes were performed. RESULTS: During the study period, 114 women were evaluated, 30 of them with low BMD and 84 with osteoporosis. After obtaining a medical history and a structured laboratory screening, at least one secondary cause was found in 50% of patients with osteoporosis and in 67% of those with low BMD. Most patients with no identified secondary cause had at least one risk factor for fragility fractures. CONCLUSIONS: A structured evaluation that includes medical history and standardized laboratory study in postmenopausal women with osteoporosis or low BMD, is a valuable tool to identify secondary causes of osteoporosis.

Influence of metabolic syndrome on post-stroke outcome, angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI.

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.

Characterization of Oral Health Status in Chilean Patients with X-Linked Hypophosphatemia.

X-Linked Hypophosphatemia (XLH) is the most common cause of inherited hypophosphatemic rickets. Dental involvement, including spontaneous abscesses and/or fistulae, is an important part of the disease and has not been completely defined, especially in cohorts from developing countries. To describe oral health status in a cohort of Chilean patients with XLH and explore its correlation with biochemical presentation and treatment, we conducted a cross-sectional observational study of patients with PHEX mutation-confirmed XLH. All patients had an oral clinical exam, radiographic evaluation; clinical and biochemical data were obtained to determine their association with oral features. Twenty-six patients were included, 77% adults and 23% children. Most adults (89%) had past or current dental pulp pathology (abscesses and/or fistulae). Pulpal chamber enlargement and radiolucent apical lesions were common radiological features (94 and 74%, respectively). In children, abscess and/or fistulae were also common (33%). Caries index, which was determined by dmft/DMFT, was higher than the Chilean national average. Early and long-term therapy with phosphate and activated vitamin D was associated with lower carious index and attachment loss. XLH patients frequently present with high pulpal involvement and carious index. Conventional therapy was associated with lower carious index and attachment loss. These data highlight the importance of early and periodical dental care in order to prevent dental damage and assure a good quality of oral health for XLH patients.