RESUMO
PURPOSE: Simulation-based medical education (SBME) is provided by all anesthesiology residency programs in Canada. The purpose of this study was to characterize SBME in Canadian anesthesiology residency training programs. METHODS: We administered a 21-question survey to the simulation director/coordinator for all 17 Canadian academic departments of anesthesiology from October 2019 to January 2020. The survey consisted of questions pertaining to the characteristics of the simulation centres, their faculty, learners, curriculum, and assessment processes. RESULTS: All 17 residency training programs participated in the survey and reported large variability in the number and formal training of simulation faculty and in content delivery. Five programs (29%) did not provide faculty recognition for curriculum design and running simulation sessions. Most programs offered one to four simulation sessions per academic year for each year of residency. All programs offered mannequin-based and part-task trainers for teaching technical and nontechnical skills. Fourteen programs (82%) offered interprofessional and interdisciplinary simulation sessions, and ten programs (59%) did not include in situ simulation training. Commonly reported barriers to faculty involvement were lack of protected time (12 programs, 71%), lack of financial compensation (ten programs, 59%), and lack of appreciation for SBME (seven programs, 41%). CONCLUSION: Large variability exists in the delivery of SBME in Canadian anesthesiology residency simulation programs, in part because of differences in financial/human resources and educational content. Future studies should explore whether training and patient outcomes differ between SBME programs and, if so, whether additional standardization is warranted.
RéSUMé: OBJECTIF: La formation médicale par simulation est offerte par tous les programmes de résidence en anesthésiologie au Canada. L'objectif de cette étude était de déterminer l'état actuel de la formation médicale par simulation dans les programmes canadiens de résidence en anesthésiologie. MéTHODE: D'octobre 2019 à janvier 2020, nous avons administré un sondage comportant 21 questions aux directions et équipes de coordination de la simulation des 17 départements universitaires d'anesthésiologie canadiens. L'enquête comportait des questions portant sur les caractéristiques des centres de simulation, le corps professoral, les apprenants et apprenantes, le programme d'études et les processus d'évaluation. RéSULTATS: Les 17 programmes de résidence ont tous participé à l'enquête et ont fait état d'une grande variabilité dans le nombre et la formation officielle du corps professoral en simulation ainsi que dans la prestation de contenu. Cinq programmes (29 %) n'ont pas reconnu le corps professoral en charge de la conception des programmes d'études et de l'organisation des séances de simulation. La plupart des programmes offraient une à quatre séances de simulation par année universitaire à chaque année de résidence. Tous les programmes disposaient de simulateurs d'entraînement pour tâches partielles et de mannequins pour enseigner des compétences techniques et non techniques. Quatorze programmes (82 %) offraient des séances de simulation interprofessionnelles et interdisciplinaires, et dix programmes (59 %) ne comportaient pas de formation par simulation in situ. Les obstacles les plus fréquemment signalés à la participation du corps professoral étaient le manque de temps protégé (12 programmes, 71 %), le manque de compensation financière (dix programmes, 59 %) et le manque d'appréciation de la formation médicale par simulation (sept programmes, 41 %). CONCLUSION: Il existe une grande variabilité dans la prestation de formation médicale par simulation dans les programmes de simulation pendant la résidence en anesthésiologie au Canada, causée en partie par des différences dans les ressources financières et humaines et par le contenu de la formation. Des études futures devraient déterminer si la formation et les issues pour les patient·es diffèrent d'un programme de formation médicale par simulation à l'autre et, dans l'affirmative, si une normalisation supplémentaire est justifiée.
RESUMO
Photosurfactants have shown considerable promise for enabling stimuli-responsive control of the properties and motion of fluid interfaces. Recently, a number of photoswitch chemistries have emerged to tailor the photoresponsive properties of photosurfactants. However, systematic studies investigating how photoresponsive surfactant behavior depends on the photochemical and photophysical properties of the switch remain scarce. In this work, we develop synthetic schemes and surfactant designs to produce a well-controlled library of photosurfactants to comparatively assess the behavior of photoswitch chemistry on interfacial behavior. We employ photoinduced spreading of droplets at fluid interfaces as a model for such studies. We show that although photosurfactant response is largely guided by expected trends with changes in polarity of the photoswitch, interfacial behavior also depends nontrivially and sometimes counter-intuitively on the kinetics and mechanisms of photoswitching, particularly at the interface of two solvents, as well as on complex interactions with other surfactants. Understanding these complexities enables the design of new photosurfactant systems and their optimization toward responsive functions including triggered spreading, dewetting, and destabilization of droplets on solid and fluid surfaces.
RESUMO
BACKGROUND: Status epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. METHODS: A survey was distributed to parents of patients with epilepsy aged 1â¯month to 19â¯years at British Columbia Children's Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. RESULTS: Of 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. CONCLUSIONS: There is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child's epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.
Assuntos
Epilepsia , Aplicativos Móveis , Estado Epiléptico , Criança , Epilepsia/terapia , Humanos , Masculino , Pais , ConvulsõesRESUMO
OBJECTIVES: As schools plan for re-opening, understanding the potential role children play in the coronavirus infectious disease 2019 (COVID-19) pandemic and the factors that drive severe illness in children is critical. STUDY DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository. Enrolled children provided nasopharyngeal, oropharyngeal, and/or blood specimens. SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified. RESULTS: A total of 192 children (mean age, 10.2 ± 7.0 years) were enrolled. Forty-nine children (26%) were diagnosed with acute SARS-CoV-2 infection; an additional 18 children (9%) met the criteria for MIS-C. Only 25 children (51%) with acute SARS-CoV-2 infection presented with fever; symptoms of SARS-CoV-2 infection, if present, were nonspecific. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease (P = .002). Age did not impact viral load, but younger children had lower angiotensin-converting enzyme 2 expression (P = .004). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) to the receptor binding domain of the SARS-CoV-2 spike protein were increased in severe MIS-C (P < .001), with dysregulated humoral responses observed. CONCLUSIONS: This study reveals that children may be a potential source of contagion in the SARS-CoV-2 pandemic despite having milder disease or a lack of symptoms; immune dysregulation is implicated in severe postinfectious MIS-C.
Assuntos
COVID-19 , Adolescente , Fatores Etários , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/transmissão , Teste para COVID-19 , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Massachusetts/epidemiologia , Pandemias , Índice de Gravidade de Doença , Carga Viral , Adulto JovemRESUMO
BACKGROUND: The incidence of positional plagiocephaly has increased significantly over the last two decades, which has caused a service delivery challenge for pediatric neurosurgeons. As a potential solution to the long waitlists for abnormal head shape, a plagiocephaly clinic was established at BC Children's Hospital (BCCH) in Vancouver, Canada. This clinic was supervised by an occupational therapist who had been trained by a neurosurgeon to independently assess and manage patients with a referring diagnosis of positional plagiocephaly. OBJECTIVES: To determine the efficiency of the BCCH Plagiocephaly Clinic in the management of positional plagiocephaly patients and to investigate the clinic's ability to appropriately identify and refer patients with craniosynostosis to pediatric neurosurgeons for further assessment. METHODS: A retrospective chart review was conducted to identify patients who were assessed and managed at the BCCH Plagiocephaly Clinic between 2008 and 2014. Data on patient demographics, head shape measurements, and treatment recommendations were collected, and the BC Children's neurosurgical database was cross-referenced to identify craniosynostosis cases missed by the Plagiocephaly Clinic. A descriptive analysis of the clinic's average wait times, severity of the patients' plagiocephaly, and recommended interventions was conducted. In addition, the sensitivity and specificity of the clinic's ability to appropriately refer craniosynostosis patients to pediatric neurosurgery were calculated. RESULTS: Of 1752 patients seen in the BC Children's Plagiocephaly Clinic between 2008 and 2014, 66% of patients received counseling about repositioning, 34% were referred for head banding, 19% were referred to physiotherapy for torticollis, and 1.4% were referred to the BC Children's Pediatric Neurosurgery Clinic for suspicion of craniosynostosis. The mean time from referral to first assessment by the Plagiocephaly Clinic was 41 days, and time from referral by the plagiocephaly clinic to diagnosis of craniosynostosis by a pediatric neurosurgeon was 8 days. Pediatric neurosurgeons requested imaging for 6 of the referred patients (25% ). The sensitivity and specificity of the plagiocephaly clinic for referral of craniosynostosis patients to the Pediatric Neurosurgery Clinic were 100 and 99%, respectively. CONCLUSION: The BC Children's Plagiocephaly Clinic is efficient and safe for the initial evaluation and treatment of patients with positional plagiocephaly. The clinic's model decreases wait times, appropriately manages patients with positional plagiocephaly, screens for craniosynostosis with high sensitivity and specificity, and takes pressure off outpatient neurosurgical clinics. This model for assessment of plagiocephaly could be considered in other medical centers.
Assuntos
Plagiocefalia não Sinostótica , Plagiocefalia , Canadá , Criança , Atenção à Saúde , Humanos , Lactente , Plagiocefalia não Sinostótica/diagnóstico , Plagiocefalia não Sinostótica/terapia , Estudos RetrospectivosRESUMO
The dissolution of metal sulfides, such as ZnS, is an important biogeochemical process affecting fate and transport of trace metals in the environment. However, current studies of in situ dissolution of metal sulfides and the effects of structural defects on dissolution are lacking. Here we have examined the dissolution behavior of ZnS nanoparticles synthesized via several abiotic and biological pathways. Specifically, we have examined biogenic ZnS nanoparticles produced by an anaerobic, metal-reducing bacterium Thermoanaerobacter sp. X513 in a Zn-amended, thiosulfate-containing growth medium in the presence or absence of silver (Ag), and abiogenic ZnS nanoparticles were produced by mixing an aqueous Zn solution with either H2S-rich gas or Na2S solution. The size distribution, crystal structure, aggregation behavior, and internal defects of the synthesized ZnS nanoparticles were examined using high-resolution transmission electron microscopy (TEM) coupled with X-ray energy dispersive spectroscopy. The characterization results show that both the biogenic and abiogenic samples were dominantly composed of sphalerite. In the absence of Ag, the biogenic ZnS nanoparticles were significantly larger (i.e., â¼10 nm) than the abiogenic ones (i.e., â¼3-5 nm) and contained structural defects (e.g., twins and stacking faults). The presence of trace Ag showed a restraining effect on the particle size of the biogenic ZnS, resulting in quantum-dot-sized nanoparticles (i.e., â¼3 nm). In situ dissolution experiments for the synthesized ZnS were conducted with a liquid-cell TEM (LCTEM), and the primary factors (i.e., the presence or absence structural defects) were evaluated for their effects on the dissolution behavior using the biogenic and abiogenic ZnS nanoparticle samples with the largest average particle size. Analysis of the dissolution results (i.e., change in particle radius with time) using the Kelvin equation shows that the defect-bearing biogenic ZnS nanoparticles (γ = 0.799 J/m2) have a significantly higher surface energy than the abiogenic ZnS nanoparticles (γ = 0.277 J/m2). Larger defect-bearing biogenic ZnS nanoparticles were thus more reactive than the smaller quantum-dot-sized ZnS nanoparticles. These findings provide new insight into the factors that affect the dissolution of metal sulfide nanoparticles in relevant natural and engineered scenarios, and have important implications for tracking the fate and transport of sulfide nanoparticles and associated metal ions in the environment. Moreover, our study exemplified the use of an in situ method (i.e., LCTEM) to investigate nanoparticle behavior (e.g., dissolution) in aqueous solutions.
Assuntos
Nanopartículas , Compostos de Zinco , Tamanho da Partícula , Prata , SulfetosRESUMO
We report a novel HBB: c.114G>C mutation in a Chinese family. This mutation resulted in a ß37(C3)TrpâCys amino acid substitution and was synonymous with Hb Kent, a hemoglobin (Hb) variant that was reported exclusively in patients of European descent. Though Hb Kent has a normal oxygen affinity and molecular stability, it has a characteristic dual variant appearance on cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by the posttranslational modification of cysteine. We also report the phenotypic expression of this variant when coinherited with the Southeast Asian (- -SEA) double α-globin gene deletion.
Assuntos
Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Adulto , Substituição de Aminoácidos , Povo Asiático , China , Família , Feminino , Hemoglobinas Anormais/metabolismo , Humanos , MasculinoRESUMO
The specialty of anesthesiology will soon adopt the Competence By Design (CBD) approach to residency education developed by the Royal College of Physicians and Surgeons of Canada (RCPSC). A foundational component of CBD is frequent and contextualized assessment of trainees. In 2013, the RCPSC Anesthesiology Specialty Committee assembled a group of simulation educators, representing each of the 17 Canadian anesthesiology residency programs, to form the Canadian National Anesthesiology Simulation Curriculum (CanNASC) Task Force. The goals were to develop, implement, and evaluate a set of consensus-driven standardized mannequin-based simulation scenarios that every trainee must complete satisfactorily prior to completion of anesthesiology residency and certification. Curriculum development followed Kern's principles and was accomplished via monthly teleconferences and annual face-to-face meetings. The development and implementation processes included the following key elements: 1) Curriculum needs assessment: 368 of 958 invitees (38.4%) responded to a national survey resulting in 64 suggested scenario topics. Use of a modified Delphi technique resulted in seven important and technically feasible scenarios. 2) Scenario development: All scenarios have learning objectives from the National Curriculum for Canadian Anesthesiology Residency. Standardized scenario templates were created, and the content was refined and piloted. 3) Assessment: A validated Global Rating Scale (GRS) is the primary assessment tool, informed by using scenario-specific checklists (created via a modified Delphi technique) and the Anesthesia Non-Technical Skills GRS. 4) Implementation: Standardized implementation guidelines, pre-brief/debrief documents, and rater training videos, guide, and commentary were generated. National implementation of the scenarios and program evaluation is currently underway. It is highly feasible to achieve specialty-based consensus on the elements of a national simulation-based curriculum. Our process could be adapted by any specialty interested in implementing a simulation-based curriculum incorporating competency-based assessment on a national scale.
Assuntos
Anestesiologia/educação , Competência Clínica/normas , Simulação por Computador , Currículo , Internato e Residência/normas , Canadá , Educação Baseada em CompetênciasAssuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Capacitação em Serviço/métodos , Pandemias/prevenção & controle , Simulação de Paciente , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , COVID-19 , Humanos , Equipamento de Proteção Individual , SARS-CoV-2RESUMO
BACKGROUND: The objective of this study was to compare the effect of thoracic paravertebral block (TPVB) and local anesthetic (LA) on persistent postoperative pain (PPP) 1 year following breast cancer surgery. Secondary objectives were to compare the effect on arm morbidity and quality of life. METHODS: Women scheduled for elective breast cancer surgery were randomly assigned to either TPVB or LA followed by general anesthesia. An NRS value of >3 at rest or with movement 1 year following surgery defined PPP. Blinded interim analysis suggested rates of PPP much lower than anticipated, making detection of the specified 20 % absolute reduction in the primary outcome impossible. Recruitment was stopped, and all enrolled patients were followed to 1 year. RESULTS: A total of 145 participants were recruited; 65 were randomized to TPVB and 64 to LA. Groups were similar with respect to demographic and treatment characteristics. Only 9 patients (8 %; 95 % CI 4-14 %) met criteria for PPP 1 year following surgery; 5 were in the TPVB and 4 in the LA group. Brief Pain Inventory severity and interference scores were low in both groups. Arm morbidity and quality of life were similar in both groups. The 9 patients with PPP reported shoulder-arm morbidity and reduced quality of life. CONCLUSIONS: This study reports a low incidence of chronic pain 1 year following major breast cancer surgery. Although PPP was uncommon at 1 year, it had a large impact on the affected patients' arm morbidity and quality of life.
Assuntos
Anestésicos Locais/administração & dosagem , Neoplasias da Mama/reabilitação , Neoplasias da Mama/cirurgia , Mastectomia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Vértebras Torácicas/cirurgia , Neoplasias da Mama/patologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição da Dor , PrognósticoRESUMO
PURPOSE: Stereoelectroencephalography (SEEG) is widely performed on individuals with medically refractory epilepsy for whom invasive seizure localization is desired. Despite increasing adoption in many centers across the world, no standardized electrode naming convention exists, generating confusion among both clinical and research teams. METHODS: We have developed a novel nomenclature, named the Standardized Electrode Nomenclature for SEEG Applications system. Concise, unique, informative, and unambiguous labels provide information about entry point, deep targets, and relationships between electrodes. Inter-rater agreement was evaluated by comparing original electrode names from 10 randomly sampled cases (including 136 electrodes) with those prospectively assigned by four additional blinded raters. RESULTS: The Standardized Electrode Nomenclature for SEEG Application system was prospectively implemented in 40 consecutive patients undergoing SEEG monitoring at our institution, creating unique electrode names in all cases, and facilitating implantation design, SEEG recording and mapping interpretation, and treatment planning among neurosurgeons, neurologists, and neurophysiologists. The inter-rater percent agreement for electrode names among two neurosurgeons, two epilepsy neurologists, and one neurosurgical fellow was 97.5%. CONCLUSIONS: This standardized naming convention, Standardized Electrode Nomenclature for SEEG Application, provides a simple, concise, reproducible, and informative method for specifying the target(s) and relative position of each SEEG electrode in each patient, allowing for successful sharing of information in both the clinical and research settings. General adoption of this nomenclature could pave the way for improved communication and collaboration between institutions.
Assuntos
Eletrodos Implantados , Eletroencefalografia , Técnicas Estereotáxicas , Terminologia como Assunto , Humanos , Eletroencefalografia/normas , Eletroencefalografia/métodos , Técnicas Estereotáxicas/normas , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Masculino , Encéfalo/fisiopatologia , Encéfalo/fisiologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/classificaçãoRESUMO
BACKGROUND: Focal epilepsy caused by a posterior fossa lesion is a rare phenomenon. In these cases, seizure onset typically occurs during the first few months of life, with episodes of epileptic hemifacial spasms and abnormal eye movements. Patients often present with drug-resistant epilepsy and often require resection for the best chance of seizure freedom. OBSERVATIONS: The authors present the case of a 19-month-old male with intractable epileptic hemifacial spasms and a dorsally exophytic right brainstem and middle cerebellar peduncle hamartoma, following 2 prior subtotal resections. The authors recommended a third suboccipital craniotomy with intraoperative electrocorticography, which revealed interictal spiking from an intralesional depth electrode. Near-total resection led to durable seizure freedom. LESSONS: Although posterior fossa lesions are rarely associated with epileptiform activity, this case demonstrates that pediatric patients with epileptic hemifacial spasms associated with a posterior fossa lesion may respond favorably to resection. Furthermore, this case demonstrates that intralesional electrocorticography can detect epileptic activity in posterior fossa lesions, which may predict postoperative seizure outcomes. https://thejns.org/doi/10.3171/CASE2452.
RESUMO
Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation to materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids. The resulting material self-assembles with programmable kinetics, producing macroscopic changes in material properties, via molecular assembly of KaiB-KaiC complexes. We show that colloid crosslinking depends strictly on the phosphorylation state of KaiC, with kinetics that are synced with KaiB-KaiC complexing. Our microscopic image analyses and computational models indicate that the stability of colloidal super-structures depends sensitively on the number of Kai complexes per colloid connection. Consistent with our model predictions, a high concentration stabilizes the material against dissolution after a robust self-assembly phase, while a low concentration allows circadian oscillation of material structure. This work introduces the concept of harnessing biological timers to control synthetic materials; and, more generally, opens the door to using protein-based reaction networks to endow synthetic systems with life-like functional properties.
RESUMO
Children with developmental and epileptic encephalopathies often present with co-occurring dyskinesias. Pathogenic variants in ARX cause a pleomorphic syndrome that includes infantile epilepsy with a variety of movement disorders ranging from focal hand dystonia to generalized dystonia with frequent status dystonicus. In this report, we present three patients with severe movement disorders as part of ARX-associated epilepsy-dyskinesia syndrome, including a patient with a novel pathogenic missense variant (p.R371G). These cases illustrate diagnostic and management challenges of ARX-related disorder and shed light on broader challenges concerning epilepsy-dyskinesia syndromes.
Assuntos
Proteínas de Homeodomínio , Transtornos dos Movimentos , Fatores de Transcrição , Humanos , Masculino , Feminino , Transtornos dos Movimentos/genética , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Pré-Escolar , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Lactente , Mutação de Sentido Incorreto , CriançaRESUMO
Somatic mosaic variants contribute to focal epilepsy, but genetic analysis has been limited to patients with drug-resistant epilepsy (DRE) who undergo surgical resection, as the variants are mainly brain-limited. Stereoelectroencephalography (sEEG) has become part of the evaluation for many patients with focal DRE, and sEEG electrodes provide a potential source of small amounts of brain-derived DNA. We aimed to identify, validate, and assess the distribution of potentially clinically relevant mosaic variants in DNA extracted from trace brain tissue on individual sEEG electrodes. We enrolled a prospective cohort of eleven pediatric patients with DRE who had sEEG electrodes implanted for invasive monitoring, one of whom was previously reported. We extracted unamplified DNA from the trace brain tissue on each sEEG electrode and also performed whole-genome amplification for each sample. We extracted DNA from resected brain tissue and blood/saliva samples where available. We performed deep panel and exome sequencing on a subset of samples from each case and analysis for potentially clinically relevant candidate germline and mosaic variants. We validated candidate mosaic variants using amplicon sequencing and assessed the variant allele fraction (VAF) in amplified and unamplified electrode-derived DNA and across electrodes. We extracted DNA from >150 individual electrodes from 11 individuals and obtained higher concentrations of whole-genome amplified vs unamplified DNA. Immunohistochemistry confirmed the presence of neurons in the brain tissue on electrodes. Deep sequencing and analysis demonstrated similar depth of coverage between amplified and unamplified samples but significantly more called mosaic variants in amplified samples. In addition to the mosaic PIK3CA variant detected in a previously reported case from our group, we identified and validated four potentially clinically relevant mosaic variants in electrode-derived DNA in three patients who underwent laser ablation and did not have resected brain tissue samples available. The variants were detected in both amplified and unamplified electrode-derived DNA, with higher VAFs observed in DNA from electrodes in closest proximity to the electrical seizure focus in some cases. This study demonstrates that mosaic variants can be identified and validated from DNA extracted from trace brain tissue on individual sEEG electrodes in patients with drug-resistant focal epilepsy and in both amplified and unamplified electrode-derived DNA samples. Our findings support a relationship between the extent of regional genetic abnormality and electrophysiology, and suggest that with further optimization, this minimally invasive diagnostic approach holds promise for advancing precision medicine for patients with DRE as part of the surgical evaluation.
RESUMO
Objectives: Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection. Methods: We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes. Samples were mapped based on an anatomic relationship with the presumed seizure onset zone (SOZ). We performed deep panel sequencing of amplified and unamplified DNA to identify pathogenic variants with subsequent orthogonal validation. Results: We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs. Discussion: We demonstrate regional mosaicism across epileptogenic tissue, suggesting a correlation between variant burden and SOZ. We also validate a pathogenic variant from individual amplified sEEG electrode-derived brain specimens, although further optimization of techniques is required.
RESUMO
BACKGROUND: Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. PROCEDURE: To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). RESULTS: Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). CONCLUSIONS: Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Linfoma não Hodgkin/terapia , Adolescente , Autoenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Transplante Homólogo , Adulto JovemRESUMO
INTRODUCTION: Practicing physicians have the responsibility to engage in lifelong learning. Although simulation is an effective experiential educational strategy, physicians seldom select it for continuing professional development (CPD) for reasons that are poorly understood. The objective of this study was to explore existing evidence on simulation-based CPD and the factors influencing physicians' engagement in simulation-based CPD. METHODS: A scoping review of the literature on simulation-based CPD included MEDLINE, Embase, and CINAHL databases. Studies involving the use of simulation for practicing physicians' CPD were included. Information related to motivations for participating in simulation-based CPD, study objectives, research question(s), rationale(s), reasons for using simulation, and simulation features was abstracted. RESULTS: The search yielded 8609 articles, with 6906 articles undergoing title and abstract screening after duplicate removal. Six hundred sixty-one articles underwent full-text screening. Two hundred twenty-five studies (1993-2021) were reviewed for data abstraction. Only four studies explored physicians' motivations directly, while 31 studies described incentives or strategies used to enroll physicians in studies on simulation-based CPD. Most studies focused on leveraging or demonstrating the utility of simulation for CPD. Limited evidence suggests that psychological safety, direct relevance to clinical practice, and familiarity with simulation may promote future engagement. DISCUSSION: Although simulation is an effective experiential educational method, factors explaining its uptake by physicians as a CPD strategy are unclear. Additional evidence of simulation effectiveness may fail to convince physicians to participate in simulation-based CPD unless personal, social, educational, or contextual factors that shape physicians' motivations and choices to engage in simulation-based CPD are explored.