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A community of practice (CoP) is a group of people who share a concern or a passion for something they do and learn how to do it better as they interact regularly. While the field of hematology/oncology has historically prioritized clinical care and biomedical research, medical education has received increasing attention within hematology/oncology in recent years. In 2018, ASCO launched the Education Scholars Program to train hematology/oncology clinicians in the science of teaching and learning. However, the number of hematology/oncology educators nationally and internationally far exceeds the capacity of the Education Scholars Program to train them. In addition, hematology/oncology educators often lack sufficient mentorship and guidance at their own institutions to pursue their chosen career path effectively. To ensure high-quality clinical care and research for generations to come, attention must be paid to improving support for hematology/oncology educators. Therefore, supported by ASCO, we developed an international medical education (Med Ed) CoP for hematology/oncology educators with the purpose of providing them with support, community, mentorship, resources, and scholarly opportunities in medical education. In this article, we describe the development of the Med Ed CoP using a three-stage framework (Establish-Grow-Sustain) including successes, challenges, and reflections. By supporting the needs of hematology/oncology educators, the Med Ed CoP will serve as a home for all who contribute to the field of hematology/oncology.
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Educação Médica , Hematologia , Oncologia , Humanos , Oncologia/educação , Hematologia/educação , Mentores , Comunidade de PráticaRESUMO
Background and Objectives: Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy. Methods: In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector. Results: Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute). Discussion: Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.
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A woman in her late 60s with severe chronic obstructive pulmonary disease (COPD) and emphysema underwent bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) to address hyperinflation. The initial EBV placement has led to partial lobar atelectasis of the left lower lobe and resulted in significant improvement in the patient's symptoms and lung function. However, valve migration occurred later due to pneumothorax unrelated to valves, leading to suboptimal clinical improvement. The patient achieved delayed full lobar atelectasis 21 months after EBV placement, which led to a significant clinical improvement. The patient decided to be delisted from the lung transplant list due to the improvement. This case highlights the importance of considering delayed atelectasis as a possible outcome of EBV placement and suggests the need for further exploration of the long-term implications and associations of this procedure.
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Broncoscopia , Pneumonectomia , Atelectasia Pulmonar , Doença Pulmonar Obstrutiva Crônica , Humanos , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/diagnóstico por imagem , Feminino , Broncoscopia/métodos , Pneumonectomia/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/diagnóstico por imagem , Pessoa de Meia-Idade , Próteses e Implantes , Resultado do TratamentoRESUMO
Objective: Interictal epileptiform spikes, high-frequency ripple oscillations, and their co-occurrence (spike ripples) in human scalp or intracranial voltage recordings are well-established epileptic biomarkers. While clinically significant, the neural mechanisms generating these electrographic biomarkers remain unclear. To reduce this knowledge gap, we introduce a novel photothrombotic stroke model in mice that reproduces focal interictal electrographic biomarkers observed in human epilepsy. Methods: We induced a stroke in the motor cortex of C57BL/6 mice unilaterally (N=7) using a photothrombotic procedure previously established in rats. We then implanted intracranial electrodes (2 ipsilateral and 2 contralateral) and obtained intermittent local field potential (LFP) recordings over several weeks in awake, behaving mice. We evaluated the LFP for focal slowing and epileptic biomarkers - spikes, ripples, and spike ripples - using both automated and semi-automated procedures. Results: Delta power (1-4 Hz) was higher in the stroke hemisphere than the non-stroke hemisphere in all mice ( p <0.001). Automated detection procedures indicated that compared to the non-stroke hemisphere, the stroke hemisphere had an increased spike ripple ( p =0.006) and spike rates ( p =0.039), but no change in ripple rate ( p =0.98). Expert validation confirmed the observation of elevated spike ripple rates ( p =0.008) and a trend of elevated spike rate ( p =0.055) in the stroke hemisphere. Interestingly, the validated ripple rate in the stroke hemisphere was higher than the non-stroke hemisphere ( p =0.031), highlighting the difficulty of automatically detecting ripples. Finally, using optimal performance thresholds, automatically detected spike ripples classified the stroke hemisphere with the best accuracy (sensitivity 0.94, specificity 0.94). Significance: Cortical photothrombosis-induced stroke in commonly used C57BL/6 mice produces electrographic biomarkers as observed in human epilepsy. This model represents a new translational cortical epilepsy model with a defined irritative zone, which can be broadly applied in transgenic mice for cell type specific analysis of the cellular and circuit mechanisms of pathologic interictal activity. Key Points: Cortical photothrombosis in mice produces stroke with characteristic intermittent focal delta slowing.Cortical photothrombosis stroke in mice produces the epileptic biomarkers spikes, ripples, and spike ripples.All biomarkers share morphological features with the corresponding human correlate.Spike ripples better lateralize to the lesional cortex than spikes or ripples.This cortical model can be applied in transgenic mice for mechanistic studies.
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We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500â Hz), ripple (80-250â Hz) and fast ripple (250-500â Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.
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Eletrocorticografia , Humanos , Masculino , Feminino , Adulto , Eletrocorticografia/métodos , Adulto Jovem , Adolescente , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Criança , Ondas Encefálicas/fisiologia , Encéfalo/fisiopatologiaRESUMO
Expiratory Central Airway Collapse (ECAC) is a multifactorial, underdiagnosed entity that poses unique challenges. Airway stenting is used as a predictor for successful outcomes after central airway stabilization surgery via tracheobronchoplasty (TBP). This approach may pose suboptimal performance in certain ECAC variants. We hypothesize that Continuous Positive Airway Pressure (CPAP), used as a pneumatic stent, could be a non-invasive alternative to evaluate surgical candidacy in cough-predominant ECAC presentations. We report on a 67-year-old female with a history of chronic cough and confirmed ECAC. After optimization of medical therapy without significant relief and unsuccessful stent trial. We opted to perform CPAP trial during exercise, the patient exercised on a treadmill, and CPAP was applied at two levels (9 cmH2O, 11 cmH2O). The use of CPAP was associated with resolution of cough and a decrease in exercise-related perceived exertion. Applying CPAP during exercise may be a promising alternative to stent trials to determine patients' candidacy for surgical management of cough-predominant ECAC.
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Short trinucleotide expansions at the FMR1 locus are associated with the late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from fragile X syndrome (associated with longer expansions), with no clear molecular explanation for these marked differences. One prevailing theory posits that the shorter, premutation expansion uniquely causes extreme neurotoxic increases in FMR1 mRNA (i.e., four to eightfold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single-nucleus RNA sequencing to postmortem frontal cortex and cerebellum from 7 individuals with premutation and matched controls (n = 6) to assess cell type-specific molecular neuropathology. We found only modest upregulation (~1.3-fold) of FMR1 in some glial populations associated with premutation expansions. In premutation cases, we also identified decreased astrocyte proportions in the cortex. Differential expression and gene ontology analysis demonstrated altered neuroregulatory roles of glia. Using network analyses, we identified cell type-specific and region-specific patterns of FMR1 protein target gene dysregulation unique to premutation cases, with notable network dysregulation in the cortical oligodendrocyte lineage. We used pseudotime trajectory analysis to determine how oligodendrocyte development was altered and identified differences in early gene expression in oligodendrocyte trajectories in premutation cases specifically, implicating early cortical glial developmental perturbations. These findings challenge dogma regarding extremely elevated FMR1 increases in FXTAS and implicate glial dysregulation as a critical facet of premutation pathophysiology, representing potential unique therapeutic targets directly derived from the human condition.
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Síndrome do Cromossomo X Frágil , Humanos , Síndrome do Cromossomo X Frágil/patologia , Tremor/genética , Expansão das Repetições de Trinucleotídeos , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Ataxia/genética , Ataxia/patologia , Encéfalo/metabolismo , Astrócitos/metabolismoRESUMO
The practice of oncology continues to evolve over time. Educators find themselves in a position where they are no longer able to teach a topic in its entirety. Moreover, the rapid expansion of information available through research and discovery in the field of oncology makes it difficult for learners to process the constant barrage of new content. Lecturers continue to impart knowledge using didactic techniques, often trying to include as much material as possible in the time permitted. The question becomes: In the face of an impossibly large field, how can one assist learners in learning, and retaining, what is most important? The science of learning continues to develop, and we now recognize that there are ways to teach that optimally facilitate the retention and application of knowledge. By using these strategies, educators can make it easier for learners to absorb and retain key information. This article will touch upon several such techniques: cognitive load optimization, analogy, contrasting cases, elaboration, and just-in-time telling. By applying these methods to didactic presentations, educators can ensure that their lessons are heard, understood, and ultimately transformed into something unforgettable.
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Educação Médica , Aprendizagem , HumanosRESUMO
Pleural effusion is a common condition related to various diseases such as heart failure, malignancies, and pneumonia. Ovarian hemangioma is a rare type of female genital tumour and can rarely cause pleural effusion. In this case, we present a 48-year-old female with repeated episodes of recurrent right-sided pleural effusion over 1 year with no clear aetiology. Abdominal computed tomography revealed a large left ovarian mass. After surgical removal of the mass, the repeated pleural effusion episodes ceased, and histopathology analysis reported a rare ovarian hemangioma. Pseudo Meigs' syndrome is a triad of an ovarian tumour, ascites, and hydrothorax that rarely presents with ovarian hemangioma; both effusions are eradicated after removing the tumour.
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A mixture of valine (Val) and isoleucine (Ile) not only decreases the negative impact of very low protein (VLP) diets on the growth of pigs, but also influences the nitrogen (N) balance and lipid metabolism; however, the underlying pathways are not well understood. This study aimed to investigate the effect of dietary Val and Ile on lipogenesis, lipolysis, and ureagenesis under protein restriction. After one week of acclimation, forty three-week-old pigs were randomly assigned to following dietary treatments (n = 8/group) for 5 weeks: positive control (PC): normal protein diet; negative control (NC): VLP diet; HV: NC supplemented with Val; HI: NC supplemented with Ile; and HVI: NC supplemented with both Val and Ile. HVI partially improved the body weight and completely recovered the feed intake (FI) of pigs fed with NC. HVI increased thermal radiation and improved the glucose clearance. HVI had a lower blood triglyceride than PC and blood urea N than NC. NC and HV promoted lipogenesis by increasing the transcript of fatty acid synthase (FAS) in the liver and lipoprotein lipase (LPL) in adipose tissue but reducing hormone-sensitive lipase (HSL) in the liver. HVI reduced the increased rate of lipogenesis induced by the NC group through normalizing the mRNA abundance of hepatic FAS, sterol regulatory element binding transcription factor 1, and HSL and LPL in adipose tissue. NC, HV, HI, and HVI reduced the ureagenesis by decreasing the protein abundance of carbamoyl phosphate synthetase I, ornithine transcarboxylase, and arginosuccinate lyase in the liver. Overall, HVI improved the growth, FI, and glucose clearance, and decreased the rate of lipogenesis induced by VLP diets.
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STUDY OBJECTIVE: Sleep spindles are present from birth and reflect cognitive functions across the lifespan, but normative values for this cognitive biomarker across development are lacking. This study aims to establish normative spindle features over development. METHODS: All available normal 19-channel electroencephalograms from developmentally normal children between February 2002 and June 2021 in the MGH EEG lab were analyzed. Approximately, 20 000 spindles were hand-marked to train and validate an automated spindle detector across ages. Normative values for spindle rate, duration, frequency, refractory period, and interhemispheric lag are provided for each channel and each age. RESULTS: Sleep EEGs from 567 developmentally normal children (range 0 days to 18 years) were included. The detector had excellent performance (F1 = 0.47). Maximal spindle activity is seen over central regions during infancy and adolescence and frontopolar regions during childhood. Spindle rate and duration increase nonlinearly, with the most rapid changes during the first 4 months of life and between ages 3 and 14 years. Peak spindle frequency follows a U-shaped curve and discrete frontal slow and central fast spindles are evident by 18 months. Spindle refractory periods decrease between ages 1 and 14 years while interhemispheric asynchrony decreases over the first 3 months of life and between ages 1 and 14 years. CONCLUSIONS: These data provide age- and region-specific normative values for sleep spindles across development, where measures that deviate from these values can be considered pathological. As spindles provide a noninvasive biomarker for cognitive function across the lifespan, these normative measures can accelerate the discovery and diagnosis in neurodevelopmental disorders.
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Fases do Sono , Sono , Criança , Adolescente , Humanos , Pré-Escolar , Lactente , Encéfalo , Eletroencefalografia , CogniçãoRESUMO
Little is known whether a combination Ile and added Val improves the growth of pigs offered very low protein (VLP) diets through changes in nutrients digestibility and gut microbiota. The objective of this study was to investigate the effect of a mixture of Val above and Ile at NRC levels on growth, nutrient digestibility and gut microbiota in pigs fed with VLP diets. Forty, weaned piglets were assigned to: positive control: normal-protein-diet; negative control (NC): VLP diet supplemented with first four limiting amino acids; VA: NC with Val above NRC; IL: NC with Ile at NRC level; VAIL: NC with Val above and Ile at NRC levels. While both VAIL and VA groups completely recovered the inhibitory effects of VLP diets on feed intake, only VAIL partially recovered the negative effects of VLP diets on growth performance. VAIL and VA increased the thermal radiation and decreased the digestibility of nitrogen. NC increased the relative abundance of Pasteurellaceae and Enterobacteriaceae in the colon. VAIL had a higher abundance of colonic Actinobacteria, Enterococcus, and Brevibacillus and the colon content of VA was more enriched with Mogibacterium. Overall, VAIL partially improved the growth performance which is likely linked with alterations in gut microbiota composition.
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Dieta com Restrição de Proteínas , Isoleucina , Suínos , Animais , Ração Animal/análise , Valina/farmacologia , Dieta , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição Animal , DigestãoRESUMO
Trauma in older people leads to substantial morbidity and mortality. The National Hip Fracture Database (NHFD) has driven improved practice with units compared to identify outliers. In 2013, our unit was an outlier for mortality post hip fracture (30-day mortality 12.2% vs. 8.3% nationally). This triggered external review. In 2019 the unit was highlighted as an exemplar in the UK. We describe the process that moved us from outlier to outstanding. After the initial review process, we made changes to our healthcare system, with regular reassessment of progress and care quality. Examples include a dedicated hip fracture unit, strong leadership (Nursing, Orthopaedic, Geriatrician, Anaesthetic), consultant-led in-depth monthly mortality reviews, changes to admission pathways and delirium prevention. Improvements were seen in all aspects of hip fracture care in 2019 compared with 2012. Thirty-day case-mixed adjusted mortality halved (12.2-6.1%), with substantial reductions in reoperations and pressure sores. Length of stay reduced by 5.9 days. In 2019 our unit's performance was significantly above the national average for all six indicators assessed by NHFD: prompt orthogeriatric review (97% vs. 91% national average), prompt surgery (85% vs. 68%); NICE compliant surgery (85% vs. 74%); prompt mobilisation (93% vs. 81%); not delirious postoperatively (77% vs. 69%); return to original residence (78% vs. 71%). The NHFD highlighted our Unit as one of nine (from 175 total) highly performing UK trusts. We summarise our service development and improvement work undertaken to achieve 'outstanding' status, which provides a valuable template to units managing trauma in older people.
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Serviços Médicos de Emergência , Fraturas do Quadril , Ortopedia , Idoso , Geriatras , Fraturas do Quadril/cirurgia , Humanos , Tempo de Internação , Qualidade da Assistência à SaúdeRESUMO
Rolandic epilepsy (RE) is the most common focal, idiopathic, developmental epilepsy, characterized by a transient period of sleep-potentiated seizures and epileptiform discharges in the inferior Rolandic cortex during childhood. The cause of RE remains unknown but converging evidence has identified abnormalities in the Rolandic thalamocortical circuit. To better localize this transient disease, we evaluated Rolandic thalamocortical functional and structural connectivity in the sensory and motor circuits separately during the symptomatic and asymptomatic phases of this disease. We collected high resolution structural, diffusion, and resting state functional MRI data in a prospective cohort of children with active RE (n = 17), resolved RE (n = 21), and controls (n = 33). We then computed the functional and structural connectivity between the inferior Rolandic cortex and the ventrolateral (VL) nucleus of the thalamus (efferent pathway) and the ventroposterolateral (VPL) nucleus of the thalamus (afferent pathway) across development in children with active, resolved RE and controls. We compared connectivity with age in each group using linear mixed-effects models. We found that children with active RE have increasing thalamocortical functional connectivity between the VL thalamus and inferior motor cortex with age (p = 0.022) that is not observed in controls or resolved RE. In contrast, children with resolved RE have increasing thalamocortical structural connectivity between the VL nucleus and the inferior motor cortex with age (p = 0.025) that is not observed in controls or active RE. No relationships were identified between VPL nuclei and the inferior sensory cortex with age in any group. These findings localize the functional and structural thalamocortical circuit disruption in RE to the efferent thalamocortical motor pathway. Further work is required to determine how these circuit abnormalities contribute to the emergence and resolution of symptoms in this developmental disease.
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Epilepsia Rolândica , Córtex Cerebral/diagnóstico por imagem , Criança , Epilepsia Rolândica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Estudos Prospectivos , Tálamo/diagnóstico por imagemRESUMO
BACKGROUND: COVID-19 disrupted undergraduate clinical education when medical schools removed students from clinical rotations following AAMC recommendations. Clerkship directors (CDs) had to adapt rapidly and modify clerkship curricula. However, the scope and effects of these modifications are unknown. OBJECTIVE: To examine the effects of the initial phase of COVID-19 on the internal medicine (IM) undergraduate clinical education. DESIGN: A nationally representative web survey. PARTICIPANTS: IM CDs from 137 LCME-accredited US medical schools in 2020. MAIN MEASURES: Items (80) assessed clerkship structure and curriculum, assessment in clerkships, post-clerkship IM clinical experiences, and CD roles and support. The framework of Understanding Crisis Response (Royal Society for Encouragement of Arts, Manufactures, and Commerce) was used to determine whether curricular modifications were "amplified," "restarted," "let go," or "ended." KEY RESULTS: Response rate was 74%. In response to COVID-19, 32% (32/101) of clerkships suspended all clinical activities and 66% (67/101) only in-person. Prior to clinical disruption, students spent a median of 8.0 weeks (IQR: 2) on inpatient and 2.0 weeks (IQR: 4) on ambulatory rotations; during clinical re-entry, students were spending 5.0 (IQR: 3) and 1.0 (IQR: 2) weeks, respectively. Bedside teaching and physical exam instruction were "let go" during the early phase. Students were removed from direct patient care for a median of 85.5 days. The sub-internship curriculum remained largely unaffected. Before the pandemic, 11% of schools were using a pass/fail grading system; at clinical re-entry 47% and during the survey period 23% were using it. Due to the pandemic, 78.2% of CDs assumed new roles or had expanded responsibilities; 51% reported decreased scholarly productivity. CONCLUSIONS: Curricular adaptations occurred in IM clerkships across US medical schools as a result of COVID-19. More research is needed to explore the long-term implications of these changes on medical student education and clinical learning environments.
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COVID-19 , Estágio Clínico , Educação de Graduação em Medicina , Estudantes de Medicina , Currículo , Educação de Graduação em Medicina/métodos , Humanos , Medicina Interna/educaçãoRESUMO
Alzheimer's Disease (AD) is a neurodegenerative disorder that can cause life-altering and debilitating cognitive decline. AD's etiology is poorly understood, and no disease-modifying therapeutics exist. Here, we describe the use of 2D and 3D tissue culture models of herpesvirus-induced AD, which recapitulate hallmark disease features of plaque formation, gliosis, neuroinflammation, and impaired neuronal signaling, to screen a panel of 21 medications, supplements, and nutraceuticals with purported neuroprotective benefits. This screen identified green tea catechins and resveratrol as having strong anti-plaque properties, functional neuroprotective benefits, and minimal neurotoxicity, providing support for their further investigation as AD preventives and therapies. Two other candidates, citicoline and metformin, reduced plaque formation and were minimally toxic, but did not protect against virus-induced impairments in neuronal signaling. This study establishes a simple platform for rapidly screening and characterizing AD compounds of interest in 2D and 3D human cortical tissue models representing physiologically relevant disease features.