tbuckley/cabot-search huggingface dataset:
Abstract 126: ’Tick Tock’ it’s Time to Shock; Increased Shock Latency is Associated With Intra-Arrest Transport and Reduced Survival From Out-Of-Hospital Cardiac Arrest
Authors: Andrew Pugh, Hill Stoecklein, Michael Stroud, Scott T Youngquist
Journal: Circulation (2019)

Introduction: Timely defibrillation of shockable rhythms during out of hospital cardiac arrest (OHCA) is an important link in the chain of survival. In 2011 the Salt Lake City Fire Department (SLCFD) adopted ECG filtering technology to allow rhythm interpretation during CPR and a protocol to defibrillate shockable rhythms immediately upon identification. Hypothesis: We hypothesized that, under the new protocol, time from observing VF to defibrillation would, on average, be less than the 2 minutes expected by guidelines. We also hypothesized that increased shock latency would be associated with intra-arrest transport and decreased survival. Methods: Prospectively collected and abstracted defibrillator data from non-traumatic cardiac arrest cases treated by ALS providers from SLCFD between Dec 2011 and June 2019 were analyzed along with Utstein variables and outcomes. Using the defibrillator manufacturer’s review software, the timing of observed rhythm changes and defibrillation events was manually abstracted based on post-incident physician interpretation. Generalized linear and Poisson mixed models were used for analysis. Results: A total of 696 cardiac arrests with 965 shocks delivered to shockable rhythms were analyzed after excluding pediatric cases, non-ALS cases, and cases in which the defibrillator file was lost or corrupted. Median time to defibrillation was 67 sec (IQR 30-143 sec) with mixed-effects grand mean of 106 sec (95% CI 96-117 sec). Delayed defibrillation (&gt; 2 min) occurred in 293/965 (30%) of shocks. Transport of patients in arrest was associated with an increase in shock latency of 42 sec (95% CI 21-63 sec) compared to patients treated on scene. Among patients with an initial shockable rhythm, time from VF appearance to defibrillation was, on average, 40 sec (95% CI 15-66 sec) shorter among survivors than non-survivors. Conclusions: Use of an aggressive defibrillation protocol enabled by ECG filtering software resulted in a median time to defibrillation of under 2 minutes. Increasing shock latency was associated with intra-arrest transport providing a causal hypothesis for the poor outcomes observed in this population. We observed a negative association between survival and average time to defibrillation of shockable rhythms.
A Phase 3 Trial of Ganitumab with Gemcitabine as First-Line Treatment of Metastatic Pancreatic Cancer: A Safety Update from the Gamma Trial
Authors: C. Fuchs, M. Ikeda, T. Okusaka, S. Ohkawa, N. Mizuno, V. Haddad, J. McGreivy, D. Chang
Journal: Annals of Oncology (2012)
The promise and reality of therapeutic discovery from large cohorts
Authors: Eugene Melamud, D. Leland Taylor, Anurag Sethi, Madeleine Cule, Anastasia Baryshnikova, Danish Saleheen, Nick van Bruggen, Garret A. FitzGerald
Journal: Journal of Clinical Investigation (2020)

Technological advances in rapid data acquisition have transformed medical biology into a data mining field, where new data sets are routinely dissected and analyzed by statistical models of ever-increasing complexity. Many hypotheses can be generated and tested within a single large data set, and even small effects can be statistically discriminated from a sea of noise. On the other hand, the development of therapeutic interventions moves at a much slower pace. They are determined from carefully randomized and well-controlled experiments with explicitly stated outcomes as the principal mechanism by which a single hypothesis is tested. In this paradigm, only a small fraction of interventions can be tested, and an even smaller fraction are ultimately deemed therapeutically successful. In this Review, we propose strategies to leverage large-cohort data to inform the selection of targets and the design of randomized trials of novel therapeutics. Ultimately, the incorporation of big data and experimental medicine approaches should aim to reduce the failure rate of clinical trials as well as expedite and lower the cost of drug development.
HER2 Status in advanced Gastric Carcinoma Patients Treated with Trastuzumab
Authors: C. Gomez-Martin, J.C. Plaza, E. Del Valle, F. Pons Valladares, P. Jimenez Fonseca, A. Salud, A. Leon, F. Rivera, E. Garralda, F. Lopez-Rios
Journal: Annals of Oncology (2012)
Partnerships, Processes, and Outcomes: A Health Equity–Focused Scoping Meta-Review of Community-Engaged Scholarship
Authors: Kasim Ortiz, Jacob Nash, Logan Shea, John Oetzel, Justin Garoutte, Shannon Sanchez-Youngman, Nina Wallerstein
Journal: Annual Review of Public Health (2020)

In recent decades, there has been remarkable growth in scholarship examining the usefulness of community-engaged research (CEnR) and community-based participatory research (CBPR) for eliminating health inequities.This article seeks to synthesize the extant literature of systematic reviews, scoping reviews, and other related reviews regarding the context, processes, and research designs and interventions underlying CEnR that optimize its effectiveness. Through a scoping review, we have utilized an empirically derived framework of CBPR to map this literature and identify key findings and priorities for future research. Our study found 100 reviews of CEnR that largely support the CBPR conceptual framework.
P-0042 Preliminary Safety Analysis From PAC-C Study of Capecitabine+Paclitaxel→Capecitabine Maintenance (PX-X) vs Capecitabine+Cisplatin (XP) As First-Line Chemotherapy for Recurrent/Metastatic Gastric Cancer
Authors: Lin Shen, Xiaotian Zhang, Zhihao Lu, Bing Hu, Qingxia Fan, Wei Li, Wei Liu, Tianshu Liu, Yueyin Pan, Nong Xu
Journal: Annals of Oncology (2012)
Development of digital biomarkers for resting tremor and bradykinesia using a wrist-worn wearable device
Authors: Nikhil Mahadevan, Charmaine Demanuele, Hao Zhang, Dmitri Volfson, Bryan Ho, Michael Kelley Erb, Shyamal Patel
Journal: npj Digital Medicine (2020)

Abstract Objective assessment of Parkinson’s disease symptoms during daily life can help improve disease management and accelerate the development of new therapies. However, many current approaches require the use of multiple devices, or performance of prescribed motor activities, which makes them ill-suited for free-living conditions. Furthermore, there is a lack of open methods that have demonstrated both criterion and discriminative validity for continuous objective assessment of motor symptoms in this population. Hence, there is a need for systems that can reduce patient burden by using a minimal sensor setup while continuously capturing clinically meaningful measures of motor symptom severity under free-living conditions. We propose a method that sequentially processes epochs of raw sensor data from a single wrist-worn accelerometer by using heuristic and machine learning models in a hierarchical framework to provide continuous monitoring of tremor and bradykinesia. Results show that sensor derived continuous measures of resting tremor and bradykinesia achieve good to strong agreement with clinical assessment of symptom severity and are able to discriminate between treatment-related changes in motor states.
Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIS) Erlotinib and Gefitinib in the Treatment of Patients with Brain Metastases from Non-Small Cell Lung Cancer (NSCLC)
Authors: D.R. Naskhletashvili, V. Gorbounova
Journal: Annals of Oncology (2012)
Radiological Evaluation of Newly Diagnosed Non-Brainstem Pediatric High-Grade Glioma in the HERBY Phase II Trial
Authors: Daniel Rodriguez Gutierrez, Chris Jones, Pascale Varlet, Alan Mackay, Daniel Warren, Monika Warmuth-Metz, Esther Sánchez Aliaga, Raphael Calmon, Darren R. Hargrave, Adela Cañete, Maura Massimino, Amedeo A. Azizi, Marie-Cécile Le Deley, Frank Saran, Raphael F. Rousseau, Gudrun Zahlmann, Josep Garcia, Gilles Vassal, Jacques Grill, Paul S. Morgan, Tim Jaspan
Journal: Clinical Cancer Research (2020)

The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data.
Abstract 347: Sudden Cardiac Arrest Caused by Coronary Artery Disease in School Students
Authors: Mamoru Ayusawa, Masataka Kato, Akiko Komori, Yuriko Abe, Rie Ichikawa
Journal: Circulation (2019)

Background: To disclose coronary artery disease (CAD) in the young is difficult by electrocardiogram screening for school students before their first events. Methods: By reviewing all reports submitted to the Mutual Aid System for Schools between 1989 and 2015, we listed all cases of sudden cardiac arrest which were considered to be caused by CAD. Kawasaki disease sequela was excluded. Epidemiology, type of CAD, symptom before onset, the intensity of the exercise at onset were investigated. Results: Thirty cases were enrolled and 26 resulted in sudden deaths, 4 were resuscitated without unfavorable sequelae. Cardioverter-defibrillator were implanted in 2 cases. Twenty-eight were male. One student was in 6th grader of primary, 11 in junior high, 15 cases in high, and 3 cases in nursing schools. Before onset, 12 cases were diagnosed as normal by ECG screening, 1 case for each was diagnosed as premature ventricular contraction, Wolff-Parkinson-White syndrome, and past history of atrial flutter. Diagnosis of 15 cases was unknown. Types based on hospital or post-mortem records: Left coronary artery (LCA); LCA of two cases were originated from the pulmonary artery, 4 cases from right coronary cuspid (RCC), and 1 from an unknown site. Two cases with LCA malformation without detail description, 3 with left ostium stenosis, and 1 with a myocardial bridge. Right coronary artery (RCA); RCA of a student was from left coronary cuspid (LCC), 1 from unknown site, 4 cases were diagnosed as hypoplastic RCA. Three cases complicated with atherosclerotic stenosis, 2 with hypoplastic CA, a case with single CA, and 4 with vasospastic angina.The school grader at onset: All of 4 cases with LCA from RCC, 2/3 with the LCA ostium stenosis and 3/4 with RCA hypoplasia were junior high school cases. Exercise intensity (level 1 to 5: most strenuous): At the onset, 19 cases were at level 5, 7 at level 4, 1 at level 3, 3 at an unknown level. Exercise at onset; soccer in 6 cases, basketball in 5, long distance running in 4, swimming, baseball, tennis, rugby, kendo, and on the way to school were in 2 for each. Conclusion: Anomalous ostium and origin of CA from the opposite side cusp tend to cause cardiac arrest in younger cases. CA evaluation by CT angiogram, MRI, or myocardial perfusion imaging is desirable.
Gideon (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma [HCC] and of Its Treatment with Sorafenib [SOR]) 2nd Interim Analysis (IA): Subgroup Analysis by Disease Etiology
Authors: J. Bronowicki, S. Ye, M. Kudo, J. Marrero, A. Venook, K. Nakajima, R. Lencioni
Journal: Annals of Oncology (2012)
Phase 2 Results from a Phase 1/2 Study of Tak-700 (ORTERONEL), An Oral, Investigational, Nonsteroidal 17,20-Lyase Inhibitor, with Docetaxel and Prednisone (DP) in Metastatic Castration-Resistant Prostate Cancer (MCRPC)
Authors: D.P. Petrylak, J.G. Gandhi, W.R. Clark, E.I. Heath, J. Lin, W.K. Oh, D.B. Agus, B. Carthon, S. Moran, G. Liu
Journal: Annals of Oncology (2012)
Engineered Protein Scaffolds as Next-Generation Therapeutics
Authors: Michaela Gebauer, Arne Skerra
Journal: The Annual Review of Pharmacology and Toxicology (2020)

The concept of engineering robust protein scaffolds for novel binding functions emerged 20 years ago, one decade after the advent of recombinant antibody technology. Early examples were the Affibody, Monobody (Adnectin), and Anticalin proteins, which were derived from fragments of streptococcal protein A, from the tenth type III domain of human fibronectin, and from natural lipocalin proteins, respectively. Since then, this concept has expanded considerably, including many other protein templates. In fact, engineered protein scaffolds with useful binding specificities, mostly directed against targets of biomedical relevance, constitute an area of active research today, which has yielded versatile reagents as laboratory tools. However, despite strong interest from basic science, only a handful of those protein scaffolds have undergone biopharmaceutical development up to the clinical stage. This includes the abovementioned pioneering examples as well as designed ankyrin repeat proteins (DARPins). Here we review the current state and clinical validation of these next-generation therapeutics.
An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates
Authors: Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena-Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P.M.H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa García-Caballero, Yingfeng Zheng, Junbin Qian, Laure-Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwé, Paul De Leyn, Johan Vansteenkiste, Birgit Weynand, Xavier Sagaert, Erik Verbeken, Albert Wolthuis, Baki Topal, Wouter Everaerts, Hanibal Bohnenberger, Alexander Emmert, Dena Panovska, Frederik De Smet, Frank J.T. Staal, Rene J. Mclaughlin, Francis Impens, Vincenzo Lagani, Stefan Vinckier, Massimiliano Mazzone, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Tobias K. Karakach, Huanming Yang, Jian Wang, Lars Bolund, Lin Lin, Bernard Thienpont, Xuri Li, Diether Lambrechts, Yonglun Luo, Peter Carmeliet
Journal: Cancer Cell (2020)
Efficacy of Chemotherapy (CHT) Beyond Tyrosine Kinases Inhibitors (TKI) in Advanced Non Small Cell Lung Cancer (NSCLC) Patients (PTS) Unselected for Epidermal Growth Factor Receptor (EGFR) Mutation
Authors: P. Trenta, R. Iacovelli, A. Palazzo, D. Pellegrino, C. Mosillo, F. Rubini, A. Prete, V. Magri, A. De Benedetto, E. Cortesi
Journal: Annals of Oncology (2012)
P-0039 Irinotecan as a Second/Third Line Chemotherapy in Gastric Cancer Patients who Failed S-1-Based Treatment
Authors: Yasuhiro Kodera, Norifumi Ohashi, Yoshinari Mochizuki, Kiyoshi Ishigure, Chie Tanaka, Suguru Yamada, Daisuke Kobayashi, Tsutomu Fujii, Michitaka Fujiwara, Seiji Ito
Journal: Annals of Oncology (2012)
P-0242 Xelox and Bevacizumab as First-Line Treatment in fit Elderly Patients with Metastatic Colorectal Cancer: The Boxe Study
Authors: Gerardo Rosati, Antonio Avallone, Giuseppe Aprile, Alfredo Butera, Federica De Pauli, Giorgio Reggiardo, Domenico Bilancia
Journal: Annals of Oncology (2012)
5-FU Induced Encephalopathy During 5-FU Containing Regimen for Esophageal Squamous Cell Carcinoma
Authors: K. Kato, N. Hokamura, K. Akiyoshi, Y. Honma, S. Iwasa, T. Hamaguchi, Y. Yamada, Y. Shimada
Journal: Annals of Oncology (2012)
Expression of excision repair cross-complementation group 1 protein and outcome in patients with nasopharyngeal cancer
Authors: H. Lee, Y. Hwang, J. Han, J. Choi, S. Kang, S. Jeong, M. Ann, Y. Oh, J. Kim, C. Kim
Journal: Journal of Clinical Oncology (2009)

6085 Background: We evaluated the prognostic significance of thymidylate synthase (TS), and Excision Repair Cross-Complementation Group 1 protein (ERCC1) in patients (pts) with nasopharyngeal cancer (NPC) treated with concurrent chemoradiotherapy (CCRT). Methods: Pretreatment tumor biopsy specimens from 41 pts with locally advanced NPC were analyzed for TS and ERCC1 expression by immunohistochemistry. All patients were treated with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m 2 /day and cisplatin 20 mg/m 2 /day, days 1–4) followed by CCRT starting on day 22. CCRT consisted of radiotherapy (70Gy/35 fractions for 7 weeks) with cisplatin 20mg/m 2 /day for 4 days on weeks 1, 4, 7 of radiotherapy. Results: Complete response and partial response were achieved in 34 pts (83%) and 6 pts (15%), respectively. Within median follow up duration of 101 months (26–147months) in survivors, 5-years overall survival (OS) of all pts was 50%. High expression of TS and ERCC1 was observed in 21 (51%) and 25 (60%) pts, respectively. High expression of ERCC1 was associated with WHO type 1 or 2 histology (p = 0.045). In univariate analysis, high expression of ERCC1 was associated with poor OS (5-year: 73% versus 35%; p = 0.005), while high expression of TS was not correlated with pts outcome (p = 0.867). In multivariate analysis, high expression of ERCC1 was a significant independent predictor of poor OS (p = 0.041) along with WHO type 1 or 2 histology (p = 0.004). Conclusions: High expression of ERCC1 protein may be useful for prediction of poor outcome in pts with NPC treated with CCRT. No significant financial relationships to disclose.
P-0228 The CEA Biochemical Response of Metastatic Colorectal Cancer Treated with Bevacizumab
Authors: Beatriz Gonzalez-Astorga, Encarnación González-Flores, Javier Garcia Garcia, Aranzazu Gonzalez-Vicente, Jesus Soberino, Cynthia Gonzalez, Julia Ruiz, Verónica Conde, Juan Ramón Delgado
Journal: Annals of Oncology (2012)
P-0078 Reversing Drug Resistance of Bel-7402/5fu to 5-Fluorouracil Via Suppression of Nrf2 by the Noncytotoxic Dose of Sorafenib
Authors: Suna Zhou, Mingxin Zhang, Jinxiang Zhu, Ermek Tangsakar, Jiansheng Wang
Journal: Annals of Oncology (2012)
Colorectal Cancer Screening: Factors Associated With Not Undergoing an Early Colonoscopy After a Positive Fecal Occult Blood Test
Authors: E. Ferrat, J. Lebreton, S. Bercier, K. Veerabudun, Z. Brixi, E. Paillaud, C. Attali, S. Bastuji-Garin
Journal: Annals of Oncology (2012)
Pharmacokinetics (PK) and Safety of Tesetaxel, a Novel Oral Taxane, in Japanese Patients (PTS) with Advanced Solid Tumors
Authors: K. Tanaka, T. Kurata, Y. Fujisaka, H. Kawakami, H. Hayashi, T. Cousin, W. Okamoto, T. Kudoh, T. Satoh, K. Nakagawa
Journal: Annals of Oncology (2012)
Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension
Authors: Jason H. Karnes, Howard W. Wiener, Tae-Hwi Schwantes-An, Balaji Natarajan, Andrew J. Sweatt, Abhishek Chaturvedi, Amit Arora, Ken Batai, Vineet Nair, Heidi E. Steiner, Jason B. Giles, Jeffrey Yu, Maryam Hosseini, Michael W. Pauciulo, Katie A. Lutz, Anna W. Coleman, Jeremy Feldman, Rebecca Vanderpool, Haiyang Tang, Joe G. N. Garcia, Jason X.-J. Yuan, Rick Kittles, Vinicio de Jesus Perez, Roham T. Zamanian, Franz Rischard, Hemant K. Tiwari, William C. Nichols, Raymond L. Benza, Ankit A. Desai
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis.Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50-0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034).Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.
Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation
Authors: Hans Helmut Niller, Klemens Angstwurm, Dennis Rubbenstroth, Kore Schlottau, Arnt Ebinger, Sebastian Giese, Silke Wunderlich, Bernhard Banas, Leonie F Forth, Donata Hoffmann, Dirk Höper, Martin Schwemmle, Dennis Tappe, Jonas Schmidt-Chanasit, Daniel Nobach, Christiane Herden, Christoph Brochhausen, Natalia Velez-Char, Andreas Mamilos, Kirsten Utpatel, Matthias Evert, Saida Zoubaa, Markus J Riemenschneider, Viktoria Ruf, Jochen Herms, Georg Rieder, Mario Errath, Kaspar Matiasek, Jürgen Schlegel, Friederike Liesche-Starnecker, Bernhard Neumann, Kornelius Fuchs, Ralf A Linker, Bernd Salzberger, Tobias Freilinger, Lisa Gartner, Jürgen J Wenzel, Udo Reischl, Wolfgang Jilg, André Gessner, Jonathan Jantsch, Martin Beer, Barbara Schmidt
Journal: The Lancet Infectious Diseases (2020)
MLN8237 (ALISERTIB), An Investigational Aurora a Kinase (AAK) Inhibitor, in Patients with Advanced Solid Tumors Including Castration-Resistant Prostate Cancer (CRPC) Receiving a Standard Docetaxel Regimen: Preliminary Phase 1 Results
Authors: N.M. Hahn, J. Sarantopoulos, C. Higano, X. Zhou, B. Zhang, E.J. Leonard, E. Benaim, J. Graff
Journal: Annals of Oncology (2012)
Plasmatic Epstein-Barr Virus MICRO-RNA -BART-17 in Nasopharyngeal Carcinomas Patients: High Potential as a Tumor Biomarker Associated to EBV DNA Concentration
Authors: F.R. Ferrand, C. Gourzones, B. Verillaud, E. Saada, P. Lang, V. Schneider, C. Amiel, J. Guigay, P. Busson
Journal: Annals of Oncology (2012)
Intellectual Disability in KATP Channel Neonatal Diabetes
Authors: Pernille Svalastoga, Åsta Sulen, Jarle R. Fehn, Stein M. Aukland, Henrik Irgens, Eivind Sirnes, Silje K.E. Fevang, Eivind Valen, Irene B. Elgen, Pål R. Njølstad
Journal: Diabetes Care (2020)

OBJECTIVE Neonatal diabetes has been shown to be associated with high neuropsychiatric morbidity in a genotype-phenotype–dependent manner. However, the specific impact of different mutations on intellectual functioning is still insufficiently characterized. Specifically, only a small number of subjects with developmental delay have been comprehensively assessed, creating a knowledge gap about patients carrying the heaviest burden. RESEARCH DESIGN AND METHODS We assessed the intellectual functioning and mental health of the complete Norwegian population with KATP channel neonatal diabetes. Eight sulfonylurea-treated children (five with the p.V59M genotype [KCNJ11]) were assessed using age-matched control subjects with type 1 diabetes. The investigations included a physical and motor developmental examination, cerebral MRI, psychometrical examination, and questionnaires assessing intellectual capabilities and psychiatric morbidity. RESULTS A strong genotype-phenotype correlation was found, revealing the p.V59M genotype as highly associated with substantial intellectual disability, with no significant correlation with the time of sulfonylurea initiation. Consistent with previous studies, other genotypes were associated with minor cognitive impairment. Cerebral MRI verified normal brain anatomy in all but one child. CONCLUSIONS We here presented a comprehensive assessment of intellectual functioning in the largest cohort of p.V59M subjects to date. The level of intellectual disability revealed not only changes the interpretation of other psychological measures but downplays a strong protective effect of sulfonylurea. Within the scope of this study, we could not find evidence supporting an early treatment start to be beneficial, although a weaker effect cannot be ruled out.