Faculty Bibliography

INTRODUCTION/BACKGROUND:Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council guidelines. MATERIAL AND METHODS/METHODS:The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment, and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS:This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage, resuscitative endovascular balloon occlusion and resuscitative thoracotomy, pericardiocentesis, needle decompression, and thoracostomy. CONCLUSIONS:Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition, and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well-organised team using crew resource management, but also on an institutional safety culture embedded in everyday practice through continuous education, training, and multidisciplinary co-operation.

BACKGROUND:Treatment of pediatric-onset multiple sclerosis (POMS) is challenging given the lack of safety and efficacy data in the pediatric population for many of the disease-modifying treatments (DMTs) approved for use in adults with MS. Our objective was to describe the demographic features and clinical and radiologic course of patients with POMS treated with the commonly used newer DMTs within the US Network of Pediatric MS Centers (NPMSC). METHODS:This is an analysis of prospectively collected data from patients who initiated treatment before age 18 with the DMTs listed below at the 12 regional pediatric MS referral centers participating in the NPMSC. RESULTS:One hundred sixty-eight patients on dimethyl fumarate, 96 on fingolimod, 151 on natalizumab, 166 on rituximab, and 37 on ocrelizumab met criteria for analysis. Mean age at DMT initiation ranged from 15.2 to 16.5 years. Disease duration at the time of initiation of index DMT ranged from 1.1 to 1.6 years with treatment duration of 0.9-2.0 years. Mean annualized relapse rate (ARR) in the year prior to initiating index DMT ranged from 0.4 to 1.0. Mean ARR while on index DMT ranged from 0.05 to 0.20. New T2 and enhancing lesions occurred in 75%-88% and 55%-73% of the patients, respectively, during the year prior to initiating index DMT. After initiating index DMT, new T2 and enhancing lesions occurred in 0%-46% and 11%-34% patients, respectively. Rates of NEDA-2 (no evidence of disease activity) ranged from 76% to 91% at 6 months of treatment with index DMTs and 66% to 84% at 12 months of treatment with index DMTs. CONCLUSIONS:Though limited by relatively short treatment duration with the index DMTs, our data suggest clinical and MRI benefit, as well as high rates of NEDA-2, in a large number of POMS patients, which can be used to guide future studies in this population.

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = - 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health.

The cannabidiol (CBD) Expanded Access Program (EAP), initiated in 2014, provided CBD (Epidiolex) to patients with treatment-resistant epilepsy (TRE). In the final pooled analysis of 892 patients treated through January 2019 (median exposure = 694 days), CBD treatment was associated with a 46%-66% reduction in median monthly total (convulsive plus nonconvulsive) seizure frequency. CBD was well tolerated, and adverse events were consistent with previous findings. We used pooled EAP data to investigate the effectiveness of add-on CBD therapy for individual convulsive seizure types (clonic, tonic, tonic-clonic, atonic, focal to bilateral tonic-clonic), nonconvulsive seizure types (focal with and without impaired consciousness, absence [typical and atypical], myoclonic, myoclonic absence), and epileptic spasms. CBD treatment was associated with a reduction in the frequency of convulsive seizure types (median percentage reduction = 47%-100%), and nonconvulsive seizure types and epileptic spasms (median percentage reduction = 50%-100%) across visit intervals through 144 weeks of treatment. Approximately 50% of patients had ≥50% reduction in convulsive and nonconvulsive seizure types and epileptic spasms at nearly all intervals. These results show a favorable effect of long-term CBD use in patients with TRE, who may experience various convulsive and nonconvulsive seizure types. Future controlled trials are needed to confirm these findings.

Visual impairment represents a significant health and economic burden affecting 596 million globally. The incidence of visual impairment is expected to double by 2050 as our population ages. Independent navigation is challenging for persons with visual impairment, as they often rely on non-visual sensory signals to find the optimal route. In this context, electronic travel aids are promising solutions that can be used for obstacle detection and/or route guidance. However, electronic travel aids have limitations such as low uptake and limited training that restrict their widespread use. Here, we present a virtual reality platform for testing, refining, and training with electronic travel aids. We demonstrate the viability on an electronic travel aid developed in-house, consist of a wearable haptic feedback device. We designed an experiment in which participants donned the electronic travel aid and performed a virtual task while experiencing a simulation of three different visual impairments: age-related macular degeneration, diabetic retinopathy, and glaucoma. Our experiments indicate that our electronic travel aid significantly improves the completion time for all the three visual impairments and reduces the number of collisions for diabetic retinopathy and glaucoma. Overall, the combination of virtual reality and electronic travel aid may have a beneficial role on mobility rehabilitation of persons with visual impairment, by allowing early-phase testing of electronic travel aid prototypes in safe, realistic, and controllable settings.

PURPOSE OF REVIEW/OBJECTIVE:We evaluate the evolving evidence of psychiatric comorbidities associated with episodic migraine. Utilizing recent research publications, we aim to assess traditional treatment option considerations and discuss recent and evolving non-pharmacologic treatment progress for episodic migraine and related psychiatric conditions. RECENT FINDINGS/RESULTS:Recent findings indicate that episodic migraine is strongly linked to comorbid depression, anxiety, posttraumatic stress disorder, and sleep disorders. Not only do patients with episodic migraine have higher rates of psychiatric comorbidity, but a higher number of headache days reported is also strongly linked to an increased risk of developing a psychiatric disorder, indicating there may be a link between frequency and psychiatric comorbidity and that patients with high-frequency episodic migraine should be assessed for psychiatric comorbidity. Few migraine preventive medications have examined the effect of the medication on both migraine and psychiatric comorbidity though we discuss what has been reported in the literature. Non-pharmacologic-based treatments including behavioral therapies and mind-body interventions previously developed for psychiatric conditions, e.g., mindfulness-based CBT (MBCT), acceptance and commitment therapy (ACT), and mindfulness-based stress reduction (MBSR) therapy, have promising results for patients diagnosed with episodic migraine and may therefore be useful in treating migraine and comorbid psychiatric conditions. Psychiatric comorbidity may affect the efficacy of the treatment of episodic migraine. Thus, we must assess for psychiatric comorbidities to inform better treatment plans for patients. Providing patients with episodic migraine with alternate modalities of treatment may help to improve patient-centered care and increase patients' sense of self-efficacy.

Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low-grade glial-glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5' of the kinase domain, while the breakpoints in the 3' partner preserved the N-terminal kinesin-interacting domain and coiled-coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non-classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re-resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.

BACKGROUND:Human infants develop IgG responses to dietary antigens during the first 2 years of life. Yet, the source of these antibodies is unclear. In previous studies we reported on the thymus as a unique functional niche for plasma cells (PCs) specific to environmental antigens. OBJECTIVE:We sought to examine whether PCs specific to dietary antigens are detected in the infant thymus. METHODS:We tested IgG reactivity to 112 food antigens and allergens in the serum of 20 neonates and infants using microarrays. The presence of PC-secreting IgG specific to the most prominent antigens was then assessed among thymocytes in the same cohort. Using an LC-MS proteomics approach, we looked for traces of these antigens in the thymus. RESULTS:Our studies first confirmed that cow's milk proteins are prevalent targets of serum IgG in early life. Subjects with the highest serum IgG titers to cow's milk proteins also harbored IgG-producing PCs specific to the same antigens in the thymic niche. Furthermore, we detected multiple peptide fragments of cow's milk antigens in the thymus. Lastly, we verified that both serum IgG and IgG secreted by thymic PCs recognized the peptide epitopes found in the thymus. CONCLUSIONS:Our studies reveal the presence of antibody-secreting PCs specific to common dietary antigens in the infant thymus. The presence of these antigens in the thymus suggested that activation and differentiation of specific PCs occurred in this organ. Further studies are now warranted to evaluate the possible implication of these cells in tolerance to dietary antigens.