The eXtraordinarY BABIES STUDY: EARLY SOCIAL COMMUNICATION SKILLS IN INFANTS WITH SEX CHROMOSOME TRISOMY (SCT)

Purpose of Study: The eXtraordinarY Babies Study is a natural history study of health and neurodevelopment in infants with a prenatal diagnosis of SCT. Given the increased risk for social difficulties and autism in SCT in later childhood and beyond, the study explores trajectories of early social communication development to identify early predictors of outcomes, and relationship of social communication skills to developmental profiles. Methods Used: A subset of 56 participants (XXY=43, XYY=4, XXX=9) from the eXtraordinarY Babies Study completed the Autism Diagnostic Observation Schedule- 2nd edition (ADOS-2), Toddler Module as part of the 12-month visit and The Bayley-3 Scales of Infant and Toddler Development. The ADOS-2 provides ratings of 0 (typical development), 1 (mild atypicality), and 2 (atypical) for communication, social interaction, and other behavior items, and an algorithm classifies total score into categories of: Little-No Concern, Mild-Moderate Concern, Moderate-Severe Concern. Analyses were limited to those who completed the assessment prior to COVID19 mask/shield requirements. Summary of Results: High rates of delayed or atypical development of early social communication skills were identified, with >75% of the sample showing scores of 1 or 2 in frequency of babbling, spontaneous vocalizations, gesture use, and pointing. 58% of the sample showed unusual eye contact and vocalizations. Over 50% received atypical scores on items assessing the quality of eye contact. Participants showed few restricted and repetitive behaviors. Results of ADOS-2 total scores: Little-no concern 50%, Mild-Moderate concern 35.7%, Moderate-severe concern 14.3%. No one was assigned a clinical diagnosis of ASD. For this group, Bayley-3 results showed average Cognitive (scaled score 10.8 sd1.9) and Fine motor skills (9.3 sd2.3), followed by lower Receptive (8.2 sd2.4) and Expressive Language (8.9 sd3.0) and below average Gross Motor skills (7.9 sd2.6). Receptive language scores negatively correlated with ADOS-2 Social Affect (r= -.38, p = < .001) and Overall Total (r= -.41, p = < .001). Conclusion(s): Even at an early age, toddlers with SCT are at increased risk for language, communication, and social interaction delays. While no participants were diagnosed with ASD at 12 months of age, social communication deficits known to be "red flags" for later diagnosis of ASD were seen in a subset of young children with SCT. Prospective follow-up will allow us to determine the trajectory of these deficits and those that may predict higher risk for more significant clinical symptoms.

Answering the Call: Inpatient Vaccination for SARS-CoV2 Infection in an Academic Hospital

Background. While the available SARS-CoV2 vaccines are up to 94% effective at preventing COVID-19-related death or invasive mechanical ventilation, only 76% of the United States population aged >=18 years have received a primary series and 49% have received a booster. Vaccine administration has been complicated by changing schedule recommendations, packaging in multi-dose vials, and federal reporting requirements that may have limited the locations offering vaccines. We therefore implemented a pharmacy-based initiative to provide SARS-CoV2 vaccination to patients admitted to an academic health center, in order to encourage vaccination when patients had presented for other care. Methods. A pharmacy committee developed a protocol for administering the three authorized SARS-CoV2 vaccines to interested inpatients while minimizing vaccine waste, monitoring for safety events, and providing next dose education. Associated training included multidisciplinary education on requirements related to vaccine Emergency Use Authorization (EUA) status. While developing the protocol, the vaccine committee utilized a temporary procedure to administer vaccines once weekly through review by antimicrobial stewardship pharmacists during August 2021. The protocol went live in September 2021 for inpatient and emergency department sites, with subsequent tracking of the number of doses ordered (stratified by vaccine type and dose number) and number administered. Results. From August 3 2021 to March 25 2022, a total of 389 vaccine orders were placed with 302 doses (78%) administered, including 126 Moderna (48 first, 20 second, 15 third, 42 booster, and 1 undesignated), 165 Pfizer/BioNTech (80 first, 24 second, 41 third, 14 booster, and 6 undesignated), and 11 Janssen COVID-19 vaccine doses. Only 18 vaccine orders were placed on patients in the ED, with 14 (78%) of those doses administered. Of the 87 vaccine orders not administered, 6 were placed but not given, and 81 were placed and then discontinued. Conclusion. With multidisciplinary collaboration, SARS-CoV2 vaccination can be performed in inpatient and ED settings. However, orders should be monitored for protocol compliance and order discontinuation, as these may increase potential for waste.

Chronic pain through COVID

Objectives To identify good practice in the community management of chronic pain, and to understand the perspective of a group of healthcare service users towards the management of chronic pain using technology during the COVID-19 pandemic. Methods Forty-five people, recruited via social media and Pain Association Scotland, participated in three focus groups hosted over Zoom. Focus groups were conducted using semi-structured questions to guide the conversation. Data were analysed using Ritchie / Spencer's Framework Analysis. Results The participants shared observations of their experiences of remotely supported chronic pain services and insights into the potential for future chronic pain care provision. Experiences were in the majority positive with some describing their rapid engagement with technology during the COVID pandemic. Conclusion Results suggest there is strong potential for telehealth to complement and support existing provision of pain management services.

Mitigating the Inflammatory Response in Acute Pancreatitis, a Randomized Clinical Control Trial Comparing the Effects of Lactated Ringers and Normal Saline

Introduction: Data driven management strategies for acute pancreatitis (AP) in pediatrics have been limited. Adult data suggests use of lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes. The first management guideline for pediatric patients based on a standardized definition of AP severity was published in 2018;it described the need for early aggressive fluid resuscitation, but had insufficient data to recommend a specific fluid. Objective(s): To evaluate the efficacy of LR as the intravenous fluid (IVF) during the first 48 hours of an AP episode compared with NS. Study Design: A prospective multi-site randomized controlled clinical trial, started in 2016 at Children's Hospital of The King's Daughters, (Clinical Trials.gov NCT03242473), expanded to Children's National Hospital (2017), and to Cincinnati Children's Hospital Medical Center (CCHMC) (2018). Eligible patients (<19 years) diagnosed with first episode of AP were enrolled within 6 hours of presentation and were randomized to either LR or NS. A comprehensive biochemical profile was obtained at admission, and at 24 and 48 hours from time of admission. Vital signs, SIRS status, and signs of complications of AP were monitored. Clinical decisions regarding management (e.g. discharge criteria) were determined by the primary clinical team. Recruitment was stopped in the spring of 2020 due to the SARS-CoV2 pandemic. Primary outcomes were C-Reactive Protein (CRP) values at 24 and 48 hours after admission;secondary outcomes were changes in labs, SIRS status length of stay, time to initation of feeds, and development of severe AP (SAP). Result(s): There were 76 eligible patients (38 LR, 38 NS). There was no significant differences in baseline characteristics or AP etiology for either group (Table 1). There was no significant differences in initial biochemical profile except a slightly elevated anion gap in the LR group (Table 2). There was a higher proportion of patients in the LR group (32%, 12/38) discharged before 48 hours compared to NS (13%, 5/38) (Table 3). The LR group had a significantly higher rate of discharge within the first 72 hours compared to the NS group (p=0.02) (Figure 1a and 1b). In the first 48 hours, there was no difference in the primary or most of the secondary outcomes measured (Table 3). Conclusion(s): Use of LR was associated with a faster rate of discharge in the first 72 hours and had no significant negative outcomes associated with its use. No other significant differences in overall outcomes were identified with the use of LR or NS during hospitalization for AP in this study. This reduction in length of hospitalization has significant implications for patients as well as healthcare expenditures. This data suggests that early resuscitation with LR may be beneficial to recovery, particularly in patients more likely to have mild AP, who may be able to be identified early in the hospital course. Future pediatric AP studies will be required to confirm these findings. (Table Presented).

Patient-reported reasons for no-shows to screening mammogram appointments among African American women

Background: Mammography screening significantly reduces breast-cancer related mortality;however, many women fail to undergo screening as recommended by national guidelines. No-shows are responsible for a significant proportion of delayed or missed cancer screening exams. Further, no-shows disproportionately affect underserved and minority populations. We previously identified a high no-show rate for screening mammograms among patients seeking care our institution. African American (AA) women were almost three times more likely to no-show than non-Hispanic white women. The racial disparity in no-shows persisted after adjustment for socioeconomic factors. The objective of this survey study was to identify reasons for missed mammogram screening appointments among AA women. Methods: We conducted a survey (via mail or telephone) of AA women who missed their screening mammogram appointment in summer 2021. Using a structured survey instrument, we collected information on patient-specific and health service barriers. Patient-specific barriers included procedure-related concerns (e.g., concern about discomfort), cognitive-emotional factors (e.g., fear of finding cancer), and changes in health status. Health service barriers included logistical factors (e.g., transportation), cost (e.g., lack of insurance) and scheduling problems (e.g., forgot about appointment or scheduled at an inconvenient time). Here we describe the most common reasons for missed appointments and compared women who reported patient-specific versus health service barriers. Results: 255 women who no-showed for their appointment were contacted and 91 participated in the study survey (35.6% response rate). Most respondents (90%) attributed their no-show to at least one of the listed barriers. Nineteen (7.5%) attributed their no-show to COVID-19, but only 1 person reported this as their only barrier. Scheduling issues were the most commonly reported barriers (57.8%), followed by transportation (38.9%). Three-quarters of respondents reported health service barriers, while only 40.7% reported patient-related barriers. The most common patient-related barriers were cognitiveemotional (25%), changes in health status (20.9%) and procedure-related concerns (15.6%). The majority of respondents (82.6%) were interested in rescheduling their mammogram. Conclusions: Most appointment no-shows among surveyed AA women resulted from potentially preventable scheduling and transportation issues. Relatively few respondents reported cognitive-emotional or procedure-related concerns. Further, the majority of respondents were interested in rescheduling their mammogram;which suggests that these women remain motivated to undergo breast cancer screening. Programs which address preventable health-service related issues may help these women keep their appointments.

Hematopoietic Stem/Progenitor Cells and Engineering: 20-YEAR HEMATOPOIETIC PROGENITOR CELL STABILITY – THE MAYO CLINIC EXPERIENCE

Background & Aim: Hematopoietic progenitor cells (HPCs) are infused for hematopoietic reconstitution in the setting of malignancy and inherited or acquired hematological deficiencies. Given the global COVID-19 pandemic, the recommendation was made to cryopreserve all allogeneic HPCs to protect recipients by allowing for subclinical cases of infection to present prior to infusion. As such, consideration of HPC stability programs (SP) and their rigor has risen. The goal of a SP is to prove the rigor of a transplant program’s cryopreservation and storage standard operating procedures so that sufficient HPC viability and potency are maintained for engraftment. SPs are also required by accreditation agencies such as AABB and FACT. Many HPC SP have validated product expirations out to 10 years. Here we share our SP to 20 years with ongoing validation for 30-year expiration. Methods, Results & Conclusion: Program Design: Current testing frequency of our SP is within the first year, and then at three-year intervals (3, 6, 9, 12, 15, 19, 21). Our rolling SP includes 2 additional (Figure Presented) Fig. 1.Current vs proposed HPC product testing and cryopreseveration schema. samples tested at 0, 5, & 9 years, then at 3-year intervals (12, 15, 19, 21, 24, 27, 30). SP samples are collected from donors requiring additional days to reach their goal but are in excess at the conclusion of collection (e.g., Day 1 collection 4.5e6 CD34+ cells/Kg, goal 5e6 CD34+ cells/ Kg). Samples are collected on a quarterly basis with ten 1mL cryovials being drawn (Figure 1). CD3+ and CD34+ viabilities are tested after cryopreservation with an acceptable threshold set at ≥75% for both. Conclusion: We are validating our SP up to 20 years with intention to validate to 30 years. Thus far, our SP reveals product age has no to low correlation with engraftment, suggesting maintenance of potency over time in a cryopreservative of 10% DMSO, 10% plasma, and 30% PlasmaLyte-A with a final cell concentration of ≤3×108 NC/mL (Figure 2). Successful engraftment has been seen in all recipients. Transplant programs should modify testing frequency, acceptance criteria, and product expiration to meet individual need while working towards standardization in the field. Given the frequency of DLIs and 2nd/3rd transplants at the Mayo Clinic, a 30-year SP reflects the need of our transplant program.(Figure Presented)Fig. 2 . ANC and platelet engraftment dates for ≥10-year-old HPC products

DSP Gene Mutation – A Cause of Recurrent Myocarditis: A Case Series

Myocarditis has gained clinical awareness with the current COVID-19 pandemic. A recent ESC Expert Consensus document discussing management of acute myocarditis and chronic inflammatory cardiomyopathy has been published [1]. Although the document alludes to genetic predisposition, by stating that “patients with mutations responsible for arrhythmogenic cardiomyopathy may be at risk for acute myocarditis,” the growing clinical experience in this area suggests that perhaps pursuit of an inflammatory diagnosis has been at the cost of recognising an underlying genetic cause, with important implications for the patient and their family. Desmoplakin (DSP)-related arrhythmogenic cardiomyopathy (AC) is characterised by LV systolic dysfunction, subepicardial late gadolinium enhancement on cardiac magnetic resonance imaging (CMR) and frequent ventricular ectopy [2,3]. In ∼15% of DSP-related AC involving the LV, a clinical event indistinguishable from myocarditis can be the initial manifestation [4]. Myocarditis often precedes fibrosis and LV dysfunction. In this case series, we describe 3 unrelated young individuals (aged 21–28 years) diagnosed by our service with DSP pathogenic variants. In all cases the initial diagnosis was myocarditis and the diagnostic odyssey was characterised by multiple presentations with significant troponin elevations, including one in whom chronic inflammatory myocarditis was the diagnosis over many years. Since the COVID-19 pandemic, presentations for myocarditis have increased considerably [5]. This has increased the importance of the clinician considering genetic arrhythmogenic cardiomyopathy as an alternative diagnosis. Any case of myocarditis should prompt 3-generational family history, and recurrent presenters should have a CMR and be referred for consideration of genetic testing.

MITIGATING THE INFLAMMATORY RESPONSE IN ACUTE PANCREATITIS;A RANDOMIZED CLINICAL CONTROL TRIAL COMPARING THE EFFECTS OF LACTATED RINGERS AND NORMAL SALINE

Introduction: Data driven management strategies for acute pancreatitis (AP) in pediatrics have been limited. Adult data suggests use of lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes. The first management guideline for pediatric patients based on a standardized definition of AP severity was published in 2018;it described the need for early aggressive fluid resuscitation, but had insufficient data to recommend a specific fluid. Objective: To evaluate the efficacy of LR as the intravenous fluid (IVF) during the first 48 hours of an AP episode compared with NS. Study Design: A prospective multisite randomized controlled clinical trial, started in 2016 at Children's Hospital of The King's Daughters, (Clinical Trials.gov NCT03242473), expanded to Children's National Hospital (2017), and to Cincinnati Children's Hospital Medical Center (CCHMC) (2018). Eligible patients (<19 years) diagnosed with first episode of AP were enrolled within 6 hours of presentation and were randomized to either LR or NS. A comprehensive biochemical profile was obtained at admission, and at 24 and 48 hours from time of admission. Vital signs, SIRS status, and signs of complications of AP were monitored. Clinical decisions regarding management (e.g. discharge criteria) were determined by the primary clinical team. Recruitment was stopped in the spring of 2020 due to the SARS-CoV2 pandemic. Primary outcomes were C-Reactive Protein (CRP) values or changes in CRP and SIRS;secondary outcomes were changes in labs, length of stay, and development of severe AP (SAP). Results: There were 76 eligible patients (38 LR, 38 NS). There was no significant differences in baseline characteristics or AP etiology for either group (Table 1). There were no significant differences in initial biochemical profiles except a slightly elevated anion gap in the LR group (Table 2). There was a higher proportion of patients in the LR group (32%, 12/38) discharged before 48 hours compared to NS (13%, 5/38) (Table 3). The LR group had a significantly higher rate of discharge within the first 72 hours compared to the NS group (p=0.02) (Figure 1). In the first 48 hours, there was no difference in the primary or most of the secondary outcomes measured (Table 3). Conclusion: Use of LR was associated with a faster rate of discharge in the first 72 hours. This reduction in length of hospitalization has significant implications for patients as well as healthcare expenditures. This data suggests that early resuscitation with LR may be beneficial to recovery, particularly in patients more likely to have mild AP, who may be able to be identified early in the hospital course. No other significant differences in overall outcomes were identified with the use of LR or NS during hospitalization for AP in this study. Future pediatric AP studies will be required to confirm these findings.(Table Presented)(Table Presented)(Table Presented) (Figure Presented)

Characteristics and Outcomes of COVID-19 in Hospitalized Native American Patients: A Single-Site Retrospective Analysis

Background. COVID-19 continues to threaten public health, particularly in Native American (NA) communities, which experienced some of the highest rates of COVID-19 infection and mortality in the US. Although the risk factors and clinical characteristics of COVID-19 are well documented in the general population, there has been little research on NA patients. Methods. We present descriptive data based on chart reviews of COVID-19 patients hospitalized between April 1 and July 31, 2020 at the Whiteriver Service Unit (WRSU), an Indian Health Service site on the Fort Apache Reservation. Results. Of the 2,262 COVID-19 cases during the observation period, 490 (22%) were hospitalized and 35 (1.6%) died within 28 days. Compared to previous reports, hospitalized patients at WRSU were younger (median age 54), more likely to be female (55% female), and more likely to have comorbidities (92% at least 1, median 2). Patients under 50 (n=200) often had a history of alcohol abuse (51%) or polysubstance abuse (20%). One third of hospitalized patients (34%) were monitored at home and referred for treatment through a high-risk outreach program. Patients were admitted much earlier at WRSU than in other locations, with a median interval of 4 days from symptom onset to hospitalization compared to 7 days reported elsewhere, but over half were still transferred to higher care. Although WRSU patients had higher rates of comorbidities, the 28-day hospital mortality rate from COVID-19 was nearly half of what has been previously reported (35/490, 7% vs 15-20% reported elsewhere, p < 0.001). This trend persisted after controlling for age. Multivariate logistic regression showed that increasing age, male sex, and high BMI were significantly associated with higher risk of death from COVID-19 (overall model p < 0.001). Characteristics and outcomes of hospitalized COVID-19 patients at WRSU Conclusion. Hospitalized patients at WRSU tended to be younger but with more comorbidities than previous studies. This may reflect the fact that NAs tend to acquire comorbidities at younger ages than the general population. This may also reflect the high rates of substance abuse in younger patients, which could be an additional risk factor for severe COVID-19. We believe that the low mortality rates at WRSU are a result of our outreach program, which likely decreased the interval between symptom onset and medical treatment.

Pulmonary endothelial nedd9 and the prothrombotic pathophenotype of acute respiratory distress syndrome due to sars-cov-2 infection

Background: The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia upregulates expression of a pro-thrombotic NEDD9 peptide (N9 ) on the extracellular plasma membrane surface. We hypothesized that increased pulmonary endothelial N9 is a novel feature of the SARS-CoV-2 pathophenotype. Methods: Paraffin-embedded autopsy lung specimens were acquired from patients with ARDS due to SARS-CoV-2 infection (n=13), ARDS of other causes (n=10), and non-disease controls (n=5). Immunofluorescence characterized expression of N9 , fibrin, and TCF12, a putative binding target of SARS-CoV-2 and known transcriptional regulator of NEDD9. We performed RNA-Seq on mRNA isolated from control HPAECs treated with normoxia or hypoxia (0.2% O2 ) for 24 hr. Immunoprecipitation-liquid chromatography-mass spectrometry (IP-LC-MS) profiled protein-protein interactions involving N9 relevant to thrombus stabilization. Results: Compared to non-SARS-CoV-2-ARDS lungs, pulmonary endothelial N9 expression and N9-fibrin colocalization was increased by 174% (P<0.002) and 212% (P<0.001) in SARS-CoV-2-ARDS, respectively. Compared to normoxia, hypoxia increased TCF12 mRNA quantity significantly in HPAECs in vitro [+1.19-fold, P=0.001;false discovery rate (FDR)=0.005]. Pulmonary endothelial nuclear TCF12 expression was also increased by 370% in SARS-CoV-2-ARDS vs. controls. In HPAEC plasma membranes, IP-LC-MS identified a novel protein-protein interaction between NEDD9 and the β3 subunit of the αvβ3 integrin, which regulates fibrin anchoring to endothelial cells. Conclusions: Compared to non-SARS-CoV-2-ARDS, SARS-CoV-2-ARDS is associated with increased pulmonary endothelial N9 expression and N9-fibrin colocalization in microthrombi in situ. Increased hypoxia signaling or SARS-CoV-2-mediated regulation of TCF12 are potential mechanisms by which to explain these findings. Identifying N9 in the pulmonary microthrombi of SARS-CoV-2 lungs may have important pathobiological and, potentially, therapeutic implications for ARDS patients.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Aging Online: Characterizing Attention, Reward Function, and Mental Health in Older Online Workers

Background: Identifying predictors of healthy aging is extremely timely, as older adults will soon outnumber younger. In this preregistered study of adults age 30+ we tested whether attention and reward function predict depression and anxiety, drawing on socioemotional selectivity theory. Methods: Participants (N=265, 102 male, 163 female, mean age=53.28, sd=11.3) were recruited using Amazon Mechanical Turk. Participants completed online versions of the PHQ9, GAD7, and a behavioral battery including: Delay Discount task, selective visual attention (Flanker, Visual Search, and Simons), and Willingness to Pay. Generalized linear models and linear mixed effects models were used for hypothesis testing. Results: We replicated a relationship between older age and lower depression (r=-.17, FDRp<.0001) and anxiety (r= -.16, FDRp<.0001), and canonical congruent-incongruent RT differences for all three attention tasks (p>.001). Relative to a pre-COVID sample (N=799), the COVID-era participants did not show a significant change in depression (PHQ9) or anxiety (GAD7, p>.05), disconfirming hypotheses. Reaction time significantly increased with age for the Visual Search (p<.001) and Simons tasks (p<.001) but not the Flanker (p>.05). Reward function did not change significantly with age (p>.05). Exploratory analyses identified a relationship between response time to incongruent stimuli and symptoms of anxiety (significant with age included as a potential confound, p<.05). Conclusions: Mental health of older online workers remained stable despite the COVID19 pandemic. Attention functions change with age, but reward function remains stable. Response to incongruent stimuli was predictive of anxiety scores on the GAD7. Supported By: VA Career Development Award, Kaggle Open Data Research Grant, Gorilla Grant Keywords: Cognition, Aging, Depression, Reward, Attention