Heterozygote advantage at HLA class I and II loci and reduced risk of colorectal cancer.

Objective: Reduced diversity at Human Leukocyte Antigen (HLA) loci may adversely affect the host's ability to recognize tumor neoantigens and subsequently increase disease burden. We hypothesized that increased heterozygosity at HLA loci is associated with a reduced risk of developing colorectal cancer (CRC). Methods: We imputed HLA class I and II four-digit alleles using genotype data from a population-based study of 5,406 cases and 4,635 controls from the Molecular Epidemiology of Colorectal Cancer Study (MECC). Heterozygosity at each HLA locus and the number of heterozygous genotypes at HLA class -I (A, B, and C) and HLA class -II loci (DQB1, DRB1, and DPB1) were quantified. Logistic regression analysis was used to estimate the risk of CRC associated with HLA heterozygosity. Individuals with homozygous genotypes for all loci served as the reference category, and the analyses were adjusted for sex, age, genotyping platform, and ancestry. Further, we investigated associations between HLA diversity and tumor-associated T cell repertoire features, as measured by tumor infiltrating lymphocytes (TILs; N=2,839) and immunosequencing (N=2,357). Results: Individuals with all heterozygous genotypes at all three class I genes had a reduced odds of CRC (OR: 0.74; 95% CI: 0.56-0.97, p= 0.031). A similar association was observed for class II loci, with an OR of 0.75 (95% CI: 0.60-0.95, p= 0.016). For class-I and class-II combined, individuals with all heterozygous genotypes had significantly lower odds of developing CRC (OR: 0.66, 95% CI: 0.49-0.87, p= 0.004) than those with 0 or one heterozygous genotype. HLA class I and/or II diversity was associated with higher T cell receptor (TCR) abundance and lower TCR clonality, but results were not statistically significant. Conclusion: Our findings support a heterozygote advantage for the HLA class-I and -II loci, indicating an important role for HLA genetic variability in the etiology of CRC.

Thoraco-lumbar-sacral orthoses in older people - A narrative literature review.

Fractures in the thoracolumbar region have a bimodal distribution, with an increasing number of older people presenting with acute vertebral fractures after atraumatic or low energy mechanisms of injury. In the absence of neurological compromise and significant vertebral instability, thoracolumbar fractures are often managed conservatively and bracing is widely recommended. However, in older cohorts, bracing is often ill fitting and poorly tolerated with non-compliance leading to prolonged immobilization. Systematic reviews and meta-analyses have challenged the motive of bracing, but as evidence quality is low, the role of exploratory analysis has been limited. This descriptive review summarises and examines the current evidence that underpins the use of spinal orthoses, specific to older patients, in an effort to streamline its judicious use in clinical practice and identify scope to direct further research.

Systematic review and meta-analysis of predictive factors for spontaneous regression in lumbar disc herniation.

OBJECTIVE: Relatively little evidence exists on predictive factors for the spontaneous regression of lumbar disc herniation (LDH), although it is a well-documented phenomenon. Therefore, current care is not optimized to identify those who would benefit from early surgery versus those who could avoid surgical risks and pursue nonsurgical therapy. In this study, the authors aimed to analyze and summarize all literature to date on predictive factors for spontaneous LDH regression as well as suggest future research strategies to aid in the decision-making for this cohort. METHODS: A literature search was conducted of the Cochrane, Embase, and MEDLINE databases for articles that described LDH in terms of the North American Spine Society task force definitions: bulging, protruded, extruded, and sequestered disc morphologies. All articles described a nonsurgical primary symptomatic LDH cohort with at least two MR images to assess regression. Those with concomitant spinal disease were excluded. The primary outcome was to assess the probability of disc regression for each disc morphology, with a secondary analysis for any other predictive factors identified. The authors synthesized their results with the only previous review (examining articles published before March 2014) to comprehensively describe the literature. A qualitative analysis of the wider literature was also performed for those studies with differing definitions of LDH but meeting all remaining inclusion criteria. RESULTS: Sixteen articles describing 360 cases of LDH were identified. Participants tended to be younger and male and presented with radiculopathy and L4-5 or L5-S1 LDH. The mean time to follow-up imaging was 11.5 months. The probabilities of spontaneous regression with bulging, protruded, extruded, and sequestered discs were 13.3%, 52.5%, 70.4%, and 93.0%, respectively (χ2 = 126.01, p < 0.001). Extruded and sequestered discs were also significantly more likely to completely regress than smaller morphologies. Other predictors of regression were larger baseline herniation volume (1260.16 vs 1006.71 mm3, p < 0.002), transligamentous herniation (χ2 = 13.321, p < 0.001), and higher Komori types (χ2 = 14.5132, p < 0.001). The authors also found similar trends in qualitative data as well as confirmed that symptom improvement was associated with disc regression. CONCLUSIONS: This study shows further evidence of the influence of disc morphology on predicting LDH regression as well as provides the first meta-analysis of data indicating additional predictive factors. Further investigation of predictive factors for early (< 6 months) LDH regression is suggested to optimize clinical use.

Home monitoring with connected mobile devices for asthma attack prediction with machine learning.

Monitoring asthma is essential for self-management. However, traditional monitoring methods require high levels of active engagement, and some patients may find this tedious. Passive monitoring with mobile-health devices, especially when combined with machine-learning, provides an avenue to reduce management burden. Data for developing machine-learning algorithms are scarce, and gathering new data is expensive. A few datasets, such as the Asthma Mobile Health Study, are publicly available, but they only consist of self-reported diaries and lack any objective and passively collected data. To fill this gap, we carried out a 2-phase, 7-month AAMOS-00 observational study to monitor asthma using three smart-monitoring devices (smart-peak-flow-meter/smart-inhaler/smartwatch), and daily symptom questionnaires. Combined with localised weather, pollen, and air-quality reports, we collected a rich longitudinal dataset to explore the feasibility of passive monitoring and asthma attack prediction. This valuable anonymised dataset for phase-2 of the study (device monitoring) has been made publicly available. Between June-2021 and June-2022, in the midst of UK's COVID-19 lockdowns, 22 participants across the UK provided 2,054 unique patient-days of data.

Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study.

OBJECTIVE: Intracranial abscesses are relatively uncommon, but can result in significant mortality and morbidity. Whilst many potential causes of brain abscesses are recognised, in many cases the origin of infection remains clinically unidentified. Our objective was to investigate the role of bacteria found in the oral cavity in the development of brain abscesses. METHODS: A retrospective analysis was performed using data from 87 patients admitted to a single UK neurosurgical unit with brain abscesses over a 16-year period. Using microbiological data obtained from abscess sampling and peripheral cultures, species of bacteria were categorised in patients where no primary source of infection was identified (NSI) for their brain abscess (n = 52), or where an infective source (ISI) was identified. The microbiological data was then screened to identify common oral bacteria in each group. RESULTS: Brain abscesses from the ISI group (n = 35) demonstrated a significantly lower preponderance of oral bacteria (n = 8), than the NSI group (n = 29) (p < 0.05). Brain abscesses from the NSI group also had significantly higher counts of Streptococcus anginosus compared to ISI (p < 0.05), with brain abscesses being most common in the frontal and parietal lobes for both ISI and NSI. CONCLUSIONS: These findings suggest that the oral cavity could be considered as a source of occult infection in cases of brain abscess where no clear cause has been identified. Future studies should include oral screening and microbiome analysis to better understand the mechanisms involved and develop approaches for prevention. CLINICAL SIGNIFICANCE STATEMENT: Oral bacteria may be an under-recognised cause of brain abscesses. Careful review of oral health in brain abscess patients may help establish causation, particularly in patients with no cause for their abscess identified. Good levels of oral health may help prevent the development of brain abscesses in some individuals.

Predicting asthma attacks using connected mobile devices and machine learning: the AAMOS-00 observational study protocol.

INTRODUCTION: Supported self-management empowering people with asthma to detect early deterioration and take timely action reduces the risk of asthma attacks. Smartphones and smart monitoring devices coupled with machine learning could enhance self-management by predicting asthma attacks and providing tailored feedback.We aim to develop and assess the feasibility of an asthma attack predictor system based on data collected from a range of smart devices. METHODS AND ANALYSIS: A two-phase, 7-month observational study to collect data about asthma status using three smart monitoring devices, and daily symptom questionnaires. We will recruit up to 100 people via social media and from a severe asthma clinic, who are at risk of attacks and who use a pressurised metered dose relief inhaler (that fits the smart inhaler device).Following a preliminary month of daily symptom questionnaires, 30 participants able to comply with regular monitoring will complete 6 months of using smart devices (smart peak flow meter, smart inhaler and smartwatch) and daily questionnaires to monitor asthma status. The feasibility of this monitoring will be measured by the percentage of task completion. The occurrence of asthma attacks (definition: American Thoracic Society/European Respiratory Society Task Force 2009) will be detected by self-reported use (or increased use) of oral corticosteroids. Monitoring data will be analysed to identify predictors of asthma attacks. At the end of the monitoring, we will assess users' perspectives on acceptability and utility of the system with an exit questionnaire. ETHICS AND DISSEMINATION: Ethics approval was provided by the East of England - Cambridge Central Research Ethics Committee. IRAS project ID: 285 505 with governance approval from ACCORD (Academic and Clinical Central Office for Research and Development), project number: AC20145. The study sponsor is ACCORD, the University of Edinburgh.Results will be reported through peer-reviewed publications, abstracts and conference posters. Public dissemination will be centred around blogs and social media from the Asthma UK network and shared with study participants.

Relating Sound and Sight in Simulated Environments.

The auditory signals at the ear can be affected by components arriving both directly from a sound source and indirectly via environmental reverberation. Previous studies have suggested that the perceptual separation of these contributions can be aided by expectations of likely reverberant qualities. Here, we investigated whether vision can provide information about the auditory properties of physical locations that could also be used to develop such expectations. We presented participants with audiovisual stimuli derived from 10 simulated real-world locations via a head-mounted display (HMD; n = 44) or a web-based ( n = 60) delivery method. On each trial, participants viewed a first-person perspective rendering of a location before hearing a spoken utterance that was convolved with an impulse response that was from a location that was either the same as (congruent) or different to (incongruent) the visually-depicted location. We find that audiovisual congruence was associated with an increase in the probability of participants reporting an audiovisual match of about 0.22 (95% credible interval: [ 0.17 , 0.27 ]), and that participants were more likely to confuse audiovisual pairs as matching if their locations had similar reverberation times. Overall, this study suggests that human perceivers have a capacity to form expectations of reverberation from visual information. Such expectations may be useful for the perceptual challenge of separating sound sources and reverberation from within the signal available at the ear.

Application of Machine Learning Algorithms for Asthma Management with mHealth: A Clinical Review.

Background: Asthma is a variable long-term condition. Currently, there is no cure for asthma and the focus is, therefore, on long-term management. Mobile health (mHealth) is promising for chronic disease management but to be able to realize its potential, it needs to go beyond simply monitoring. mHealth therefore needs to leverage machine learning to provide tailored feedback with personalized algorithms. There is a need to understand the extent of machine learning that has been leveraged in the context of mHealth for asthma management. This review aims to fill this gap. Methods: We searched PubMed for peer-reviewed studies that applied machine learning to data derived from mHealth for asthma management in the last five years. We selected studies that included some human data other than routinely collected in primary care and used at least one machine learning algorithm. Results: Out of 90 studies, we identified 22 relevant studies that were then further reviewed. Broadly, existing research efforts can be categorized into three types: 1) technology development, 2) attack prediction, 3) patient clustering. Using data from a variety of devices (smartphones, smartwatches, peak flow meters, electronic noses, smart inhalers, and pulse oximeters), most applications used supervised learning algorithms (logistic regression, decision trees, and related algorithms) while a few used unsupervised learning algorithms. The vast majority used traditional machine learning techniques, but a few studies investigated the use of deep learning algorithms. Discussion: In the past five years, many studies have successfully applied machine learning to asthma mHealth data. However, most have been developed on small datasets with internal validation at best. Small sample sizes and lack of external validation limit the generalizability of these studies. Future research should collect data that are more representative of the wider asthma population and focus on validating the derived algorithms and technologies in a real-world setting.

Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.

BACKGROUND: Though germline TP53 pathogenic/likely pathogenic variants (PV) are associated with Li-Fraumeni syndrome, many detected by multigene panels represent aberrant clonal expansion (ACE), most due to clonal hematopoiesis (CH). Discerning ACE/CH from germline variants and postzygotic mosaicism (PZM) is critically needed for risk assessment and management. METHODS: Participants in the Li-Fraumeni & TP53 Understanding & Progress (LiFT UP) study with a TP53 PV were eligible. Demographics, personal/family cancer history, and clinical laboratory test reports were obtained. DNA from multiple tissues was analyzed using a custom QIAseq assay (ACE panel) that included TP53 and other CH-associated genes; the ACE panel and eyebrow follicles were assessed in a workflow to discern TP53 PV clinical categories. RESULTS: Among 134 participants there was a significant difference for the age at diagnosis (P < 0.001), component cancers (P = 0.007), and clinical testing criteria (P < 0.001), comparing germline with PZM or ACE. ACE panel analysis of DNA from 55 sets of eyebrow follicles (mean 1.4 ug) and 36 formalin-fixed, paraffin imbedded tissues demonstrated low variance (SE, 3%; P = 0.993) for TP53 variant allele fraction, with no significant difference (P = 0.965) between tissue types, and detected CH gene PVs. Of 55 multi-tissue cases, germline status was confirmed for 20, PZM in seven, ACE for 25, and three were indeterminate. Additional CH variants were detected in six ACE and two germline cases. CONCLUSIONS: We demonstrated an effective approach and tools for discerning germline TP53 status. IMPACT: Discernment of PZM and TP53-driven CH increases diagnostic accuracy and enables risk-appropriate care.

Cross-sectional clinical cancer genomics community of practice survey analysis of provider attitudes and beliefs regarding the use of deceased family member tissue to guide living family member genetic cancer risk assessment.

Next-generation tumor tissue sequencing techniques may result in the detection of putative germline pathogenic variants (PVs), raising the possibility that germline cancer predisposition could be identified from archival medical tissue samples of deceased relatives. The approach, termed traceback, is designed to inform risk management recommendations for living family members. Provider perspectives regarding traceback testing have not yet been explored, so we conducted a cross-sectional survey of Clinical Cancer Genomics Community of Practice providers regarding their attitudes and beliefs toward traceback testing. Self-reported demographics, provider characteristics, attitudes and perceived barriers were collected. We evaluated responses in the context of whether providers had previous experience with traceback testing. Data were analyzed using chi-square and Fisher's exact testing. Among 207 respondents (of 816 eligible), most were women (89.4%), white (85.5%), and not Hispanic or Latino (89.7%). US-based providers represented the majority of respondents (87.4%). Relatively, few providers 32 of 207 (15.5%) had previous experience with traceback. Among the individuals without experience in traceback, 84.0% thought there would be barriers to implementation; however, only 68.8% of individuals with previous traceback experience agreed (p = .04). Respondents in both groups thought that traceback would be valuable in their practice (82.6%, p = .22) and that they would feel comfortable discussing the concept (83.6%, p = .83), interpreting the results (72.2%, p = .24), and discussing the results with their patients (80.7%, p = .38). Patient interest and cost were seen as less of a barrier by those with experience with traceback testing. Recurrent themes obtained in open-ended responses are also presented. Overall, providers believe that traceback would be a valuable tool in their practice. Individuals with previous experience identified less barriers with implementation of this testing, highlighting an area for future research and education.

Sudden perceived absence of foetal movement - a unique presentation of a vertebral haemangioma in pregnancy.

OBJECTIVE: Symptomatic vertebral haemangiomas that present during pregnancy are extremely uncommon with few cases reported in literature. Epidural haemangiomas are rarer still with few documented. METHODS: In this report, we describe the case of a 22-year-old pregnant patient who presented with apparent loss of foetal movement at 38 weeks' gestation. Clinical review demonstrated the foetus was well but neurological examination revealed lower limb paresthesia, paresis and evident uterine hypoesthesia. An MRI scan illustrated a haemangioma in the T1 vertebral body with an epidural component causing cord compression. RESULTS: The management of spinal haemangiomas that present during pregnancy is a complex clinical scenario, which requires careful multidisciplinary consideration to determine if surgical intervention is appropriate. In this case, the patient had an emergency caesarean section followed by posterior decompression and laminectomy of the T1 vertebra with excellent post-operative recovery. CONCLUSION: Gestational increase in the size of vertebral haemangiomas is well documented. We discuss a rare case in which a young pregnant patient presents with an atypical symptom of a vertebral haemangioma (uterine hypoesthesia). This case highlights the importance of prompt imaging in these scenarios and a cohesive multidisciplinary approach in order to provide optimal treatment for the patient.

Use of a modified Delphi process to develop research priorities in major trauma.

PURPOSE: The burden of major trauma within the UK is ever increasing. There is a need to establish research priorities within the field. Delphi methodology can be used to develop consensus opinion amongst a group of stakeholders. This can be used to prioritise clinically relevant, patient-centred research questions to guide future funding allocations. The aim of our study was to identify key future research priorities pertaining to the management of major trauma in the UK. METHODS: A three-phased modified Delphi process was undertaken. Phase 1 involved the submission of research questions by members of the trauma community using an online survey (Phase 1). Phases 2 and 3 involved two consecutive rounds of prioritisation after questions were subdivided into 6 subcategories: Brain Injury, Rehabilitation, Trauma in Older People, Pre-hospital, Interventional, and Miscellaneous (Phases 2 and 3). Cut-off points were agreed by consensus amongst the steering subcommittees. This established a final prioritised list of research questions. RESULTS: In phase 1, 201 questions were submitted by 65 stakeholders. After analysis and with consensus achieved, 186 questions were taken forward for prioritisation in phase 2 with 114 included in phase 3. 56 prioritised major trauma research questions across the 6 categories were identified with a clear focus on long-term patient outcomes. Research priorities across the patient pathway from roadside to rehabilitation were deemed of importance. CONCLUSIONS: Consensus within the major trauma community has identified 56 key research questions across 6 categories. Dissemination of these questions to funding bodies to allow for the development of high-quality research is now required. There is a clear indication for targeted multi-centre multi-disciplinary research in major trauma.

Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America.

The prevalence and contribution of BRCA1/2 (BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. This study aims to address this disparity. BRCA analyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel (HISPANEL) on MassARRAY; semiconductor sequencing; and copy number variant (CNV) detection. BRCA PV probability was calculated using BRCAPRO. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs; 160 BRCA1 (31% CNVs); 76 BRCA2 PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. The area under the ROC curve for BRCAPRO was 0.76. In summary, we implemented a low-cost BRCA testing strategy and documented a significant burden of non-ClinVar reported BRCA PVs among Latin Americans. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. This study helps address the gap in our understanding of BRCA-associated cancer in Latin America.

Fusion rates for conservative and surgical management of type II odontoid fractures and its impact.

BACKGROUND: Type II odontoid fractures are known to have low fusion rates following conservative management with a hard collar. However, most patients are elderly with comorbidities and are not fit for surgery. The present study identified the rates of bony fusion, complications, and clinical outcomes following conservative management of type II odontoid fractures. METHODS: We included consecutive patients referred with a suspected odontoid fracture to a Major Trauma Centre in the UK between March 2015 and December 2017. Data including patient demographics, fracture management, complications and outcomes. Bony fusion was assessed by two neurosurgeons and one neuroradiologists. Results were analysed with simple statistics and chi-squared test. RESULTS: 102 patients were included in the study (mean age = 80.4 ± 15.3). 10 (9.8%) were managed surgically and 92 (90.2%) were managed conservatively with a hard collar, for a mean of 87 days. Patients were followed up for a mean of 28.1 months (range 1-855 days) until discharge. 37% developed collar complications, namely pain, stiffness and non-tolerance. Bony union was achieved in 37.3% of patients treated with a hard collar (versus 80% in the surgical group, p = 0.0096). Increasing age was an independent risk factor for non-union (p < 0.001). Of the patients without bony union, none reported symptoms, and 90% were discharged without a collar. CONCLUSION: The management of type II odontoid fractures are difficult in an elderly, co-morbid population. With conservative management fusion rates are low, and collar complications are not insignificant. However, outcomes are good regardless of union.

Long-term cerebrovascular outcomes after bariatric surgery: A nationwide cohort study.

BACKGROUND: The proinflammatory state and metabolic changes associated with obesity contribute to cerebrovascular disease. Bariatric surgery can achieve a reliable reduction in body weight and improved metabolic profile in obese patients. However, its impact on cerebrovascular morbidity remains unexplored. This study investigates the effect of bariatric surgery on long-term risk of major cerebrovascular events. METHODS: A retrospective cohort study was designed. Data was extracted from the Clinical Practice Research Datalink. 4212 bariatric surgery patients were compared to 4212 age, sex, and BMI-matched controls. The primary composite endpoint was occurrence of any major adverse cerebrovascular event. Secondary endpoints included composite endpoints of ischaemic events, haemorrhagic events, individual components of the primary endpoint alone and all-cause mortality. An adjusted Cox proportional hazards model was implemented to analyse time to event data. RESULTS: Mean follow-up length was 11.4 years. The primary endpoint occurred in 73 patients. The bariatric surgery group had significantly lower adjusted major cerebrovascular event rates (HR 0.352, 95 %CI 0.195-0.637). Bariatric surgery was associated with lower rates of ischaemic events (HR 0.315, 95 %CI 0.156-0.635), particularly from transient ischaemic attacks (HR 0.364, 95 %CI 0.171-0.775). There was no difference in the rate of haemorrhagic events (HR 0.442, 95 %CI 0.147-1.330) or acute ischaemic stroke (HR 0.221, 95 %CI 0.046-1.054). In total 229 patients died during follow-up. Overall, all-cause mortality was significantly lower in the bariatric surgery group (HR 0.352, 95 %CI 0.195-0.637). CONCLUSIONS: This study identifies an association between bariatric surgery and lower long-term risk of major adverse cerebrovascular events in patients with obesity.

Impact of a Global Child Mental Health Observership Program: Participant Evaluation, Perceptions, and Outcomes.

OBJECTIVE: The authors describe the participant outcomes and global impact of a structured international observership program in child and adolescent mental health (CAMH) at a United States (US) pediatric academic center. METHODS: The quality improvement phase of the observership program was conducted for 2 years and included 12 participants from 9 different countries. Observers utilized a question guide to describe their clinical and academic experiences in the US in relation to their countries. Each observer completed a program evaluation at the end of the observership, and provided progress reports ranging 6-20 months following completion of the program. RESULTS: Observers valued their experience in the program with overall high evaluation ratings. Observers described major differences and similarities as well as strengths and weaknesses of the US system of care in comparison with their countries' system of care, with perspectives provided on available therapies (pharmacological and non-pharmacological), multidisciplinary treatment, and the role of culture. All observers returned to their countries upon completion of the program and demonstrated significant CAMH clinical and academic productivity with publications, leadership roles, training, education, clinical care, and advocacy in their countries after participation in the observership. CONCLUSION: The outcomes of this program demonstrate that the development and implementation of an onsite educational observership experience in an academic setting have significant potential to build international collaboration and partnerships, in order to meet the underserved mental health needs of children and adolescents globally. Such experiences promote professional growth for all involved and advance CAMH care and advocacy worldwide.

Application of Machine Learning to Support Self-Management of Asthma with mHealth.

While there have been several efforts to use mHealth technologies to support asthma management, none so far offer personalised algorithms that can provide real-time feedback and tailored advice to patients based on their monitoring. This work employed a publicly available mHealth dataset, the Asthma Mobile Health Study (AMHS), and applied machine learning techniques to develop early warning algorithms to enhance asthma self-management. The AMHS consisted of longitudinal data from 5,875 patients, including 13,614 weekly surveys and 75,795 daily surveys. We applied several well-known supervised learning algorithms (classification) to differentiate stable and unstable periods and found that both logistic regression and naïve Bayes-based classifiers provided high accuracy (AUC > 0.87). We found features related to the use of quick-relief puffs, night symptoms, frequency of data entry, and day symptoms (in descending order of importance) as the most useful features to detect early evidence of loss of control. We found no additional value of using peak flow readings to improve population level early warning algorithms.

Characterization Study of Patients Presenting to an Acute Care Pediatric Hospital Identified With Avoidant/Restrictive Food Intake Disorder.

OBJECTIVES: Nearly one-quarter of individuals diagnosed with avoidant/restrictive food intake disorder (ARFID) require medical admission. There have been efforts to characterize ARFID in outpatient and intensive day treatment settings; however, authors of few studies have examined this presentation in the inpatient pediatric hospital setting. In this study, we aim to further characterize patients presenting to the hospital with concerns for ARFID. METHODS: This study involved a retrospective chart review of medically admitted patients with ARFID seen by the psychiatry consultation service at a tertiary care New England pediatric hospital from 2015 to 2016. RESULTS: The typical hospitalized patient with ARFID was a 12.9-year-old, white girl with previous history of outpatient mental health treatment, anxiety disorder, and gastrointestinal-related diagnoses admitted to adolescent medicine or pediatric hospitalist services with >1 year of feeding difficulties often triggered by a precipitating event. Despite >80% of subjects receiving evaluations as outpatients for feeding-related concerns, including 60.5% seeing their primary care provider, <20% were diagnosed with ARFID before hospitalization. The average length of admission was 8 days. All imaging, scopes, and swallow studies conducted during the admission were nonrevealing. Almost half of patients required enteral tube feeds, and 63.2% required psychiatric medications during the admission. Only 31.6% of patients had the ARFID diagnosis documented in their discharge notes. CONCLUSIONS: Consistent identification of ARFID remains variable, underrecognized by community providers, and underdocumented by hospital providers. Accurate recognition of ARFID and additional study into contributory factors and treatment approaches may help improve effective health care use and treatment outcomes.

Association between Clonal Hematopoiesis and Late Nonrelapse Mortality after Autologous Hematopoietic Cell Transplantation.

Clonal hematopoiesis (CH), characterized by the accumulation of acquired somatic mutations in the blood, is associated with an elevated risk of aging-related diseases and premature mortality in non-cancer populations. Patients who undergo autologous hematopoietic cell transplantation (HCT) are also at high risk of premature onset of aging-related conditions. Therefore, we examined the association between pretreatment CH and late-occurring (≥1 year) nonrelapse mortality (NRM) after HCT. We evaluated pathogenic and likely pathogenic CH variants (PVs) in 10 patients who developed NRM after HCT and in 29 HCT recipient controls matched by age at HCT ± 2 years (median, 64.6 years; range, 38.5 to 74.7 years), sex (79.5% male), diagnosis (61.5% with non-Hodgkin lymphoma, 18.0% with Hodgkin lymphoma, and 20.5% with multiple myeloma), and duration of follow-up. We analyzed mobilized hematopoietic stem cell DNA in samples collected before HCT using a custom panel of amplicons covering the coding exons of 79 myeloid-related genes associated with CH. PVs with allele fractions >2% were used for analyses. Cases were significantly more likely than controls to have CH (70% versus 24.1%; P = .002), to have ≥2 unique PVs (60% versus 6.9%; P < .001), and to have PVs with allelic fractions ≥10% (40% versus 3.4%; P = .003). Here we provide preliminary evidence of an association between pre-HCT CH and NRM after HCT independent of chronologic age. Integration of CH analyses may improve the accuracy of existing pre-HCT risk prediction models, setting the stage for personalized risk assessment strategies and targeted treatments to optimally prevent or manage late complications associated with HCT.

Vestibular dysfunction in acute traumatic brain injury.

Traumatic brain injury (TBI) is the commonest cause of disability in under-40-year-olds. Vestibular features of dizziness (illusory self-motion) or imbalance which affects 50% of TBI patients at 5 years, increases unemployment threefold in TBI survivors. Unfortunately, vestibular diagnoses are cryptogenic in 25% of chronic TBI cases, impeding therapy. We hypothesized that chronic adaptive brain mechanisms uncouple vestibular symptoms from signs. This predicts a masking of vestibular diagnoses chronically but not acutely. Hence, defining the spectrum of vestibular diagnoses in acute TBI should clarify vestibular diagnoses in chronic TBI. There are, however, no relevant acute TBI data. Of 111 Major Trauma Ward adult admissions screened (median 38-years-old), 96 patients (87%) had subjective dizziness (illusory self-motion) and/or objective imbalance were referred to the senior author (BMS). Symptoms included: feeling unbalanced (58%), headache (50%) and dizziness (40%). In the 47 cases assessed by BMS, gait ataxia was the commonest sign (62%) with half of these cases denying imbalance when asked. Diagnoses included BPPV (38%), acute peripheral unilateral vestibular loss (19%), and migraine phenotype headache (34%), another potential source of vestibular symptoms. In acute TBI, vestibular signs are common, with gait ataxia being the most frequent one. However, patients underreport symptoms. The uncoupling of symptoms from signs likely arises from TBI affecting perceptual mechanisms. Hence, the cryptogenic nature of vestibular symptoms in TBI (acute or chronic) relates to a complex interaction between injury (to peripheral and central vestibular structures and perceptual mechanisms) and brain-adaptation, emphasizing the need for acute prospective, mechanistic studies.