Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma.

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.

Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504).

Trigger factors in patients with a patent foramen ovale-associated stroke: A case-crossover study.

Background: Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few.

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults.

Importance: Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence.

Objective: To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence.

Design, Setting, And Participants: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021.

Cognitive trajectory in the first year after first-ever ischaemic stroke in young adults: the ODYSSEY study.

Background: Limited data exists on cognitive recovery in young stroke patients. We aimed to investigate the longitudinal course of cognitive performance during the first year after stroke at young age and identify predictors for cognitive recovery.

Methods: We conducted a multicentre prospective cohort study between 2013 and 2021, enrolling patients aged 18-49 years with first-ever ischaemic stroke.

Functional brain connectivity in young adults with post-stroke epilepsy.

Approximately 1 in 10 young stroke patients (18-50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke epilepsy and their relationship with cognitive impairment. Therefore, we aimed to investigate whether young ischaemic stroke patients have altered functional networks and whether this alteration is related to cognitive impairment.

Subacute cognitive impairment after first-ever transient ischemic attack or ischemic stroke in young adults: The ODYSSEY study.

Introduction: We aimed to investigate the prevalence of cognitive impairment in the subacute phase after transient ischemic attack (TIA) and ischemic stroke (IS), factors associated with a vascular cognitive disorder, and the prevalence of subjective cognitive complaints and their relation with objective cognitive performance.

Patients And Methods: In this multicenter prospective cohort study, we recruited patients with first-ever TIA and IS, aged 18-49 years, between 2013 and 2021 for cognitive assessment up to 6 months after index event. We calculated composite Z-scores for seven cognitive domains.

Risk Factors and Causes of Ischemic Stroke in 1322 Young Adults.

Background: Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection [ASCOD]). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study).

Trigger Factors for Stroke in Young Adults: A Case-Crossover Study.

Background And Objectives: Causes of stroke in young adults differ from those in the elderly individuals, and in a larger percentage, no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke in the young population, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role.

Methods: Patients aged 18-49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17 participating centers in the Netherlands completed a questionnaire about exposure to 9 potential trigger factors in hazard periods and on a regular yearly basis.

Neuroimaging Parameters Are Not Associated With Chronic Post-stroke Fatigue in Young Stroke Patients.

Introduction: Post-stroke fatigue is frequently present in young adults, but its underlying mechanism is still unclear. The aim of the study was to investigate the association between lesion location, network efficiency and chronic post-stroke fatigue based on voxel-based lesion-symptom mapping and structural network connectivity analysis.

Patients And Methods: One hundred and thirty five young patients, aged 18-50 years, with a first-ever transient ischemic attack or cerebral infarction from the Follow-Up of Transient ischemic attack and stroke patients and Unelucidated Risk factor Evaluation (FUTURE) study, underwent 1.

Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis.

Background: The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily.

Key Clinical Adverse Events in Patients with Advanced Basal Cell Carcinoma Treated with Sonidegib or Vismodegib: A Post Hoc Analysis.

Introduction: Sonidegib is approved to treat locally advanced basal cell carcinoma (laBCC) in the USA, EU, Switzerland, and Australia and metastatic basal cell carcinoma (mBCC) in Switzerland and Australia in patients not amenable to surgery or radiotherapy. Vismodegib is approved to treat patients with mBCC, recurrent laBCC, or those not candidates for surgery or radiation. There is no head-to-head trial comparing Hedgehog inhibitors.

Increased Risk of Pregnancy Complications After Stroke: The FUTURE Study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation).

Background And Purpose: The study goal was to investigate the prevalence of pregnancy complications and pregnancy loss in women before, during, and after young ischemic stroke/transient ischemic attack.

Methods: In the FUTURE study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation), a prospective young stroke study, we assessed the occurrence of pregnancy, miscarriages, and pregnancy complications in 223 women aged 18 to 50 years with a first-ever ischemic stroke/transient ischemic attack. Pregnancy complications (gestational hypertension, diabetes mellitus, preeclampsia, and hemolysis, elevated liver enzymes, low platelet count syndrome) were assessed before, during, and after stroke using standardized questionnaires.

Prothrombotic factors do not increase the risk of recurrent ischemic events after cryptogenic stroke at young age: the FUTURE study.

Background: The role of hypercoagulable states and preceding infections in the etiology of young stroke and their role in developing recurrent ischemic events remains unclear. Our aim is to determine the prevalence of these conditions in patients with cryptogenic stroke at young age and to assess the long-term risk of recurrent ischemic events in patients with and without a hypercoagulable state or a recent pre-stroke infection with Borrelia or Syphilis.

Patients And Methods: We prospectively included patients with a first-ever transient ischemic attack or ischemic stroke, aged 18-50, admitted to our hospital between 1995 and 2010.

Risk factors and mechanisms of stroke in young adults: The FUTURE study.

Incidence of ischemic stroke and transient ischemic attack in young adults is rising. However, etiology remains unknown in 30-40% of these patients when current classification systems designed for the elderly are used. Our aim was to identify risk factors according to a pediatric approach, which might lead to both better identification of risk factors and provide a stepping stone for the understanding of disease mechanism, particularly in patients currently classified as "unknown etiology".

Effect of Formal Education on Vascular Cognitive Impairment after Stroke: A Meta-analysis and Study in Young-Stroke Patients.

Objectives: The extent of vascular cognitive impairment (VCI) after stroke varies greatly across individuals, even when the same amount of brain damage is present. Education level is a potentially protective factor explaining these differences, but results on its effects on VCI are inconclusive.

Methods: First, we performed a meta-analysis on formal education and VCI, identifying 21 studies (N=7770).

The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study.

Introduction: Patients who suffer a stroke at a young age, remain at a substantial risk of developing recurrent vascular events and information on very long-term prognosis and its risk factors is indispensable. Our aim is to investigate this very long-term risk and associated risk factors up to 35 years after stroke.

Patients And Methods: Prospective cohort study among 656 patients with a first-ever ischaemic stroke or transient ischaemic stroke (TIA), aged 18-50, who visited our hospital (1980-2010).

Remote Lower White Matter Integrity Increases the Risk of Long-Term Cognitive Impairment After Ischemic Stroke in Young Adults.

Background And Purpose: Poststroke cognitive impairment occurs frequently in young patients with ischemic stroke (18 through 50 years of age). Accumulating data suggest that stroke is associated with lower white matter integrity remote from the stroke impact area, which might explain why some patients have good long-term cognitive outcome and others do not. Given the life expectancy of decades in young patients, we therefore investigated remote white matter in relation to long-term cognitive function.

Accelerated development of cerebral small vessel disease in young stroke patients.

Objective: To study the long-term prevalence of small vessel disease after young stroke and to compare this to healthy controls.

Methods: This prospective cohort study comprises 337 patients with an ischemic stroke or TIA, aged 18-50 years, without a history of TIA or stroke. In addition, 90 age- and sex-matched controls were included.

Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study.

Background: In about 30% of young stroke patients, no cause can be identified. In elderly patients, kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke. There are hypotheses that novel non-traditional risk factors, like chronic inflammation and oxidative stress, are involved in chronic kidney disease, affecting the cerebral microvasculature that would in turn lead to stroke.

Long-term depressive symptoms and anxiety after transient ischaemic attack or ischaemic stroke in young adults.

Background And Purpose: Few studies exist on long-term post-stroke depressive symptoms and anxiety in young adults, although these young patients have a particular interest in their long-term prognosis, given their usually long life expectancy and being in the midst of an active social, working and family life. The aims of this study were to investigate the prevalence of depressive symptoms and anxiety and their association with clinical and demographic variables and with functional outcome after stroke in young adults.

Methods And Results: Long-term prevalence of depressive symptoms and anxiety was calculated in 511 patients with a transient ischaemic attack or ischaemic stroke, aged 18-50 years, using the Hospital Anxiety and Depression scale, compared with 147 controls.

Women have a poorer very long-term functional outcome after stroke among adults aged 18-50 years: the FUTURE study.

Due to their young age young stroke survivors have to cope with a dramatic impact on their life for the decades to come. We investigated the sex-specific very long-term functional outcome after transient ischemic attack (TIA) and ischemic stroke (IS) in adults aged 18-50 years. This study is part of a cohort study among 619 first-ever young ischemic stroke patients, admitted to our department between January 1, 1980 and November 1, 2010.

Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study.

Background And Purpose: Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first occurrence of structural damage and are preceded by microscopic changes that may already be associated with a worse memory function.

Cognitive performance and poor long-term functional outcome after young stroke.

Objective: To investigate the influence of cognitive performance on long-term functional outcome after ischemic stroke (IS) in young adults aged 18 through 50 years (young IS).

Methods: This study is part of a prospective cohort study among 277 stroke survivors with a young IS admitted to our department between January 1, 1980, and November 1, 2010. Functional outcome was assessed during follow-up between 2009 and 2012 with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living scale (IADL).

Poststroke Epilepsy Is Associated With a High Mortality After a Stroke at Young Age: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation Study.

Background And Purpose: Poststroke epilepsy is a common complication after a young stroke. We investigated the association between poststroke epilepsy and mortality.

Methods: We performed a prospective cohort study among 631 patients with a first-ever transient ischemic attack or ischemic stroke, aged 18 to 50 years.