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Background The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia). Methods We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle–Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively. Results In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35–0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23–0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15–11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26–2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD − 0.66(− 0.93 to − 0.39)] and non-dippers [SMD − 0.35(− 0.53 to − 0.16)]. Conclusion Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications. Protocol registration PROSPERO database (ID: CRD42022310384).

Allogeneic hematopoietic cell transplantation (alloHCT) survivors have been recently recognized as patients at increased cardiovascular risk. We hypothesized that vascular function remains impaired in alloHCT survivors free of graft-versus-host-disease or relapse. We enrolled consecutive adult alloHCT survivors and non-HCT control individuals (January 2019-March 2020), matched for traditional cardiovascular risk factors. Microvascular dysfunction was dynamically assessed in real time by Laser Speckle Contrast Analysis (LASCA). Carotid-femoral pulse-wave velocity (PWV) and carotid intima media thickness (IMT) were assessed as surrogate markers of cardiovascular disease. We studied 75 patients after a median of 3.2 (range 2.1-4.9) years from alloHCT, who had suffered from grade 2 to 3 acute (20%) and/or moderate/severe chronic GVHD (42%), and 75 controls. Although traditional cardiovascular risk factors and surrogate markers of cardiovascular disease did not differ between groups, alloHCT survivors showed significantly impaired microvascular function (baseline and peak flux, time to peak, base to peak and base to occlusion change). LASCA indices were also independently associated with alloHCT. Our study shows for the first-time impaired microcirculation dynamics in alloHCT survivors, independently of cardiovascular risk factors. Additional studies are needed to address the role of novel markers in cardiovascular risk prediction, along with effects of disease type, phase, and pre-transplant treatments.

Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87–6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19–3.05). AHREs were not associated with a statistically significant increased mortality risk. The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke. Available in https://doi.org/10.17605/OSF.IO/ZRF6M .

The objective of this systematic review and meta‐analysis is to determine whether nocturnal blood pressure fall, expressed by dipping patterns according to ambulatory blood pressure monitoring (ABPM), is a risk factor for cardiovascular events (CVEs) in untreated hypertensives. Α thorough systematic literature search at MEDLINE, Embase, Cochrane Library, and gray literature was conducted through March 2020. Two reviewers screened studies and assessed dipping patterns of untreated hypertensives using ABPM with a follow‐up >6 months. Newcastle‐Ottawa scale was used for risk of bias assessment. We initially identified 463 reports; of which, seven cohort studies were eligible for meta‐analysis enrolling 10 438 untreated hypertensives. Untreated patients classified as dippers at baseline (n = 7081) had significant lower risk of CVEs and total mortality compared to non‐dippers (n = 3,357) [RR = 0.67, 95% CI (0.49, 0.92); RR = 0.71, 95% CI (0.59, 0.86)]. However, when patients were further classified into four dipping groups, only reverse dippers, yet not extreme dippers or non‐dippers, were at increased risk for CVEs compared to dippers [RR = 0.47, 95% CI (0.33, 0.66)]. Likewise, only reverse dippers had a higher stroke risk than dippers [RR = 0.39, 95% CI (0.22, 0.72)]. When compared with the whole group of dippers (including extreme dippers), non‐dipping alone (excluding reverse dipping) was not a significant risk factor for CVEs [RR = 0.84, 95% CI (0.61, 1.16)] or total mortality [RR = 0.84, 95% CI (0.61, 1.16); RR = 0.78, 95% CI (0.53, 1.13), respectively]. Untreated hypertensives may benefit more from the evaluation of reverse dipping rather than the non‐dipping phenomenon in general.

Accumulating evidence points toward a protective role of intestinal microbiota diversity in allogeneic hematopoietic cell transplantation (allo-HCT). The purpose of this systematic review and meta-analysis is to determine the effect of antibiotic-mediated disruption of microbiota on main allo-HCT outcomes (graft-versus-host disease [GVHD], treatment-related mortality [TRM], overall survival [OS]). Following literature search, 2 reviewers screened eligible studies and assessed risk of bias (RoB). Meta-analysis was performed using Review Manager Software. Among 443 screened references, 18 were eligible for meta-analysis. In studies with genomic markers, grade II to IV acute GVHD was significantly reduced in patients not receiving gut decontamination (GD) (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.20 to 2.04). In subgroup analysis, prophylaxis with systemic antibiotics conferred an increased risk of acute GVHD (OR, 1.65; 95% CI, 1.08 to 2.53). When we incorporated RoB, we found a positive correlation of intestinal GVHD with GD (OR, 1.77; 95% CI, 1.29 to 2.44). Patients with higher microbiota diversity presented increased OS (risk ratio [RR], 1.58; 95% CI, 1.19 to 2.09) and lower TRM (RR, 0.45; 95% CI, 0.26 to 0.76). Our findings confirm that GD and prophylaxis with systemic antibiotics increase acute and intestinal GVHD. Importantly, our meta-analysis was the first to show a significant effect of microbiota diversity on TRM and OS.

Introduction:COVID-19 pandemic caused a major disruption to healthcare system. A year after COVID-19 outbreak, the question remains to what extent the lockdowns changed the volume of non-infected patients who were admitted to the Neurologic Department (ND). To determine the impact of the pandemic´s first year on a tertiary ND. Methods:non-infected patients admitted to ND between March 2020 and February 2021 were examined. A control group was generated for the same time interval starting from March 2019. Primary outcomes were the number of patients presenting with neurologic complaint who were admitted to the hospital and the diagnosis type. Secondary outcomes were hospitalization length and patients´ outcome. Results:overall, 816 patients (49.4% females) were admitted during the predetermined periods. Median age was 55 years. Median length of hospitalization was six days. We observed a 47.2% reduction in our department´s admissions during pandemic (n=282). None of the examined variables (type of neurologic diagnosis, age, gender, hospitalization length and outcome) changed significantly during pandemic. However, the number of patients admitted during the pandemic with a diagnosis categorized as “other” was statistically significant lower compared to the year before COVID-19 (p=0.007). Hospitalization length was associated only with patients´ age. Conclusion:our study examined for the first-time the consequences of the first year of COVID-19 pandemic on ND admissions. COVID-19 outbreak resulted in decreased admissions. Delays in seeking medical consultation for urgent or undiagnosed neurologic conditions require rigorous long-term monitoring to fully understand the impact of COVID-19 pandemic on patients with neurologic diseases.

Evidence for nusinersen administration in adult 5q spinal muscular atrophy (5q-SMA) patients is scarce and based on real-world observational data. The present systematic review and meta-analysis aimed to explore the efficacy and safety of nusinersen in patients older than 12 years of age with 5q-SMA. We searched MEDLINE, EMBASE, the Cochrane Library, and grey literature through April 2021. Cross-sectional studies, case reports, review articles, and studies with follow-up less than 6 months were excluded. We included 12 records (seven case-series, five cohorts) representing 11 population cohorts and enrolling 428 SMA patients. We observed statistically significant improvements on motor function Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores at the longest follow-up assessments [SMD = 0.17(95% CI 0.01–0.33), SMD = 0.22(95% CI 0.06–0.38), respectively]. HFMSE and RULM significant improvements were also detected at the subgroup analysis during 10 and 14 months. HFMSE and RULM amelioration occurred earlier in patients with SMA type 3 or 4 during short-term analysis (≤ 6 months). 6-min walk tests (6MWT) and pulmonary function tests did not change. Minimal clinically important differences in HFMSE and RULM were observed in 43.3% (95% CI 34.5–52.3) and 38.9% (95% CI 27.7–50.7), respectively. Severe adverse events were reported in 2% (95% CI 0–5.8). Treatment withdrawal rate was 3% (95% CI 0.5–6.6). Despite the low quality of evidence and the unmet need for randomized data to establish the safety and efficacy of nusinersen in adults, our meta-analysis confirms that nusinersen is a valuable treatment option for older patients with longer-disease duration. Trial registration: PROSPERO database CRD42020223109. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01200-3.

No Abstract. DOI: 10.52547/ijkd.6916.

Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk. We studied 554 allo-HCT recipients for 1.8 years (range, .04 to 27.75). Ten-year CI of 10.5% for iEMR was associated only with advanced disease phase at transplantation, whereas 10-year CI of 34.8% for BMR was independently associated with pretransplant disease phase, lines of treatment, and fungal infections. Most iEMR and BMR patients (75% and 81%, respectively) received systemic treatment combined with local radiation for iEMR (26%) and donor lymphocyte infusions (16% and 28%, respectively) when feasible. Extensive chronic graft-versus-host disease (GVHD) was recorded in 47% of iEMR and 48% of BMR patients. Outcomes were poor both in iEMR (10-year overall survival [OS], 18.3%) and BMR (10-year OS, 19.1%). Independent predictors of OS were disease phase, type of donor, acute and chronic GVHD, fungal infections, iEMR, and BMR. In a large population with long-term follow-up, incidence of iEMR was relatively high, developed at the late post-transplant period, and was associated only with disease phase at transplantation. Furthermore, iEMR and BMR conferred similarly poor outcomes despite systemic treatment or extensive chronic GVHD.

Since the introduction of disease modifying treatments there is an unmet need to identify biomarkers of spinal muscular atrophy (SMA) natural history. We performed a systematic review and meta-analysis to summarize available evidence. We searched MEDLINE, Embase, Cochrane Library and gray literature until February 2021. The primary outcome was biomarkers longitudinal course in adolescents and adults. The secondary outcome was the discrimination of patients from controls. We included 42 records examining 606 patients from 19 population cohorts over a maximum follow-up of 17-years. Lung function and serum biomarkers could not depict disease progression. We identified potential biomarkers of disease activity [SMA functional rating scale, MoviPlate, pinch strength, compound muscle action potential (CMAP), motor unit number estimation (MUNE)] that require further investigation. Data regarding Hammersmith functional motor scale expanded, Revised upper limb module, 6-minute walk test were contradictory impeding any pooled estimate. The pooled analysis regarding our secondary outcome revealed that upper limb CMAP amplitudes and MUNE mean values differed significantly between SMA patients and controls [mean difference -3.63(-6.2, -1.06), -119.74(-153.93, -85.56) respectively]. Given the lack of natural history data on this population, our qualitative synthesis and meta-analysis could provide valuable evidence and identify promising predictive biomarkers requiring further longitudinal examination. PROSPERO Registration: CRD42021235605.

Precision medicine has emerged as a central element of healthcare science. Complement, a component of innate immunity known for centuries, has been implicated in the pathophysiology of numerous incurable neurological diseases, emerging as a potential therapeutic target and predictive biomarker. In parallel, the innovative application of the first complement inhibitor in clinical practice as an approved treatment of myasthenia gravis (MG) and neuromyelitis optica spectrum disorders (NMOSD) related with specific antibodies raised hope for the implementation of personalized therapies in detrimental neurological diseases. A thorough literature search was conducted through May 2020 at MEDLINE, EMBASE, Cochrane Library and ClinicalTrials.gov databases based on medical terms (MeSH)” complement system proteins” and “neurologic disease”. Complement’s role in pathophysiology, monitoring of disease activity and therapy has been investigated in MG, multiple sclerosis, NMOSD, spinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson, Alzheimer, Huntington disease, Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, stroke, and epilepsy. Given the complexity of complement diagnostics and therapeutics, this state-of-the-art review aims to provide a brief description of the complement system for the neurologist, an overview of novel complement inhibitors and updates of complement studies in a wide range of neurological disorders.

Purpose of Review To review current literature on endothelial dysfunction with previous coronaviruses, and present available data on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology and clinical phenotype Recent Findings Recent evidence suggests that signs and symptoms of severe COVID-19 infection resemble the clinical phenotype of endothelial dysfunction, implicating mutual pathophysiological pathways. Dysfunction of endothelial cells is believed to mediate a variety of viral infections, including those caused by previous coronaviruses. Experience from previous coronaviruses has triggered hypotheses on the role of endothelial dysfunction in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which are currently being tested in preclinical and clinical studies. Summary Endothelial dysfunction is the common denominator of multiple clinical aspects of severe COVID-19 infection that have been problematic for treating physicians. Given the global impact of this pandemic, better understanding of the pathophysiology could significantly affect management of patients.

Drug-induced thrombotic microangiopathy (DITMA) is a life-threatening complication that is often under-recognized and under-reported (1). Despite recent systematic reviews published in 2015 (2) and 2018 (3), the list of drugs implicated in TMA continues to expand (4–9). In addition, novel reports have unraveled potential new mechanisms that might contribute to a targeted therapy of this syndrome. In this opinion article, we aimed to summarize recent data on DITMA, categorizing drugs based on mechanisms of actions and specialties.

Immunotherapy with chimeric antigen receptor T (CAR-T cells) has been recently approved for patients with relapsed/refractory B-lymphoproliferative neoplasms. Along with great efficacy in patients with poor prognosis, CAR-T cells have been also linked with novel toxicities in a significant portion of patients. Cytokine release syndrome (CRS) and neurotoxicity present with unique clinical phenotypes that have not been previously observed. Nevertheless, they share similar characteristics with endothelial injury syndromes developing post hematopoietic cell transplantation (HCT). Evolution in complement therapeutics has attracted renewed interest in these life-threatening syndromes, primarily concerning transplant-associated thrombotic microangiopathy (TA-TMA). The immune system emerges as a key player not only mediating cytokine responses but potentially contributing to endothelial injury in CAR-T cell toxicity. The interplay between complement, endothelial dysfunction, hypercoagulability, and inflammation seems to be a common denominator in these syndromes. As the indications for CAR-T cells and patient populations expand, there in an unmet clinical need of better understanding of the pathophysiology of CAR-T cell toxicity. Therefore, this review aims to provide state-of-the-art knowledge on cellular therapies in clinical practice (indications and toxicities), endothelial injury syndromes and immunity, as well as potential therapeutic targets.

Autologous hematopoietic stem cell transplantation (AHSCT) is established as a standard of care for diseases ranging from hematological malignancies to other neoplastic pathologies and severe immunological deficiencies. In April 1995, our group performed the first AHSCT in progressive multiple sclerosis (MS). Since then, a plethora of studies have been published with encouraging but controversial results. Major challenges in the field include appropriate patient selection, improvements in AHSCT procedure, and timing of this treatment modality. Beyond AHSCT, several new intravenous or oral agents have been developed and approved over the last 20 years in MS. The emergence of multiple effective therapies for MS has created a challenging scenario for both treating physicians and patients. Novel cell-based therapies other than AHSCT are also currently investigated in MS patients with promising results. Our review is aimed at summarizing state-of-the-art knowledge on basic principles and results of AHSCT in MS and its role compared to novel agents.

Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4 months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.

Introduction: Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (alloHCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence and impact on survival. Methods: We searched MEDLINE, COCHRANE, EMBASE through March 2019 for studies published in English. We deemed eligible all types of primary studies including randomized controlled trials (RCTs), controlled observational studies (both cohort and case control), case series and case reports. The eligibility criteria were: (a) adult population specified as patients fifteen years old or older, (b) alloHCT for hematologic diseases, (c) neurologic disorders' diagnosis. Two independent reviewers screened, extracted data and assessed risk of bias (RoB). The primary outcome being the incidence of neurologic complications was assessed in a form of a proportion of adult patients with the neurologic manifestation (n) from the total group of patients that received alloHCT for hematologic diseases (N). We performed a random-effects meta-analysis of proportions using the Freeman-Tukey double arcsine transformation, including only cohort studies. Secondary outcome was impact of neurologic complications on overall survival of patients presented with symptoms after allo-HCT. Pre-planned sensitivity analysis integrating the risk of bias assessment by excluding studies evaluated as high risk was performed as well as prespecified subgroup analyses according to the type of neurologic event. Results: We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case-series and 425 case-reports (PRISMA flow diagram). RoB ranged from fair to high although case-series were of low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Incidence rates of neurologic complications varied, according to type of complications and studies, from 0.6% for immune-mediated disorders in retrospective cohorts to 13% for drug-related events in prospective cohorts. In meta-analysis of proportions, we included only cohort studies, retrospective or prospective, with homogenous population to estimate a proportion. Neurologic clinical signs or symptoms were detected in 1415 out of 37450 [6.2% (95%CI 4.8-7.7), Ι2= 96.1% (p Regarding the severity of neurologic complications and death rate in patients with outcome of interest, data were too diverse to provide any safe conclusion. Neurologic complications had a detrimental impact on survival depending on type of complication in various studies. Based on study type, high RoB in most of the included studies, as well as significant heterogeneity in results from observational data, high imprecision and suspected publication bias, quality of evidence was very low applying the GRADE tool. Conclusion: Our study highlights the wide spectrum and significant impact of neurologic complications on survival post alloHCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients. Disclosures No relevant conflicts of interest to declare.

Introduction: Despite advances in the field, diagnosis and management of the wide spectrum of neurological events as sequelae of allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated the incidence, diagnosis, management and long-term prognosis of neurological complications in alloHCT recipients. Methods: We enrolled consecutive allogeneic HCT recipients transplanted in our center (7/1990-9/2017). We performed a retrospective review of data in our prospectively acquired database. Results: Among 758 alloHCT recipients, 127 (16.8%) patients presented with neurological complications. Interestingly, neurological complications were more common in unrelated or alternative donors (p Neurological adverse events presented late post-transplant (median +140day, interquartile range/IR 232). Timing of neurological complications was associated only with acute and chronic graft-versus-host-disease/GVHD (p=0.001 and p1 episodes (median 10.4 months, IR 25.1). Based on symptoms, timing and additional testing, neurological complications were classified into: CNS relapse (24), thrombotic microangiopathy (12), CNS hemorrhage (7), posterior reversible encephalopathy (6), drug-associated polyneuropathy (7) and seizure (6), other leukoencephalopathy (8), thromboembolic events (5), neuralgia (4), myopathy (3), sinusoidal obstruction syndrome (1), Guillain-Barre syndrome (1), Wernicke encephalopathy (1), myelitis (1) and multiple sclerosis (1). Opportunistic CNS infections were attributed to aspergillosis (12), mucormycosis (3), Cytomegalovirus (9), Epstein-Barr encephalitis (3) or lymphoproliferative disease (4), Human herpesvirus 6 (5), Human herpesvirus 7 (2), toxoplasmosis (3); while others could not be otherwise specified (10). Resolution of neurological complications was achieved in only 37 (29%) patients. With a median follow-up of 11.4 months (IR 30.3) in patients with neurological complications, incidence of chronic GVHD was 52.8%, relapse mortality 48.6%, treatment-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. In the multivariate analysis, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In the whole cohort, acute, chronic GVHD and relapse rates did not differ between patients with or without neurological complications. However, bacterial, viral and fungal infections were significantly increased in patients with neurological complications (p Conclusions: Our large retrospective study highlights the wide spectrum of manifestations and etiologies of neurological complications in alloHCT recipients. Prompt diagnosis is required for adequate management, a major of determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted to improve patient outcomes. Figure. Figure. Disclosures Gavriilaki: European Hematology Association: Research Funding. Vardi:Janssen: Honoraria; Gilead: Research Funding.

We read with interest the innovative study by Bustamante et al.1 that focuses on the prognostic role of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in recanalization of acute ischemic stroke. Beyond limitations already noted by the authors, important issues need to be further discussed.