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AbstractObjectivesWe aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A‐related disorders.MethodsA core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified‐Delphi process. Twenty‐eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified‐Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%–79% fully or partially agree, <10% disagree.ResultsConsensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non‐seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep‐related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE.SignificanceSignificant comorbidities are present in most phenotypes of SCN8A‐related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long‐term management for patients with these comorbidities and provide the basis for future evidence‐based studies on optimal treatments of SCN8A‐related disorders. Identifying the prognosis of patients with SCN8A‐related disorders will also improve care and quality‐of‐life for patients and their caregivers.

AbstractObjectiveWe aimed to develop consensus for diagnosis/management of SCN8A‐related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A‐related disorders.MethodsA Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty‐eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%–79% fully/partially agree, <10% disagree.ResultsEarly diagnosis is important for long‐term clinical outcomes in SCN8A‐related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self‐limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first‐line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first‐line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First‐line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients.SignificanceThis is the first‐ever global consensus for the diagnosis and treatment of SCN8A‐related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence‐based care and empowers SCN8A families to advocate for their children.

Abstract Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients &lt;21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients &lt;21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Introduction: Smoking-related diseases affect 16 million Americans, causing approximately 480,000 deaths annually. The prevalence of cigarette smoking varies regionally across the United States, and previous research indicates that regional rates of smoking-related diseases demonstrate a negative association with altitude. The purpose of this study was to determine the relationship between altitude and the prevalence of cigarette smoking by county (N = 3106) in the United States. We hypothesized that smoking prevalence among adults would be negatively associated with mean county altitude. Methods: A multivariate linear regression was performed to examine the relationship between county-level mean altitude and county smoking rate. Covariates were individually correlated with 2020 smoking data, and significant associations were included in the final model. Results: The multivariate linear regression indicated that the county-level smoking rates are significantly reduced at high altitudes (p < 0.001). The model accounted for 89.5% of the variance in smoking prevalence, and for each 1000-foot increase in altitude above sea level, smoking rates decreased by 0.143%. Based on multivariate linear regression, the following variables remained independently and significantly associated: race, sex, educational attainment, socioeconomic status, unemployment, physical inactivity, drinking behavior, mental distress, and tobacco taxation. Conclusions: Our results indicate that smoking rates are negatively associated with altitude, which may suggest that altitude affects the pharmacokinetics, pharmacodynamics, and mechanistic pathways involved in cigarette use. Further research is needed to explore the relationship between altitude and smoking and how altitude may serve as a protective factor in the acquisition and maintenance of tobacco use disorders.

Background: The association of prediabetes (pDM) with stroke risk in non-diabetic geriatric patients with AF is unclear. The findings from this analysis contribute to a better understanding of the interrelation between pDM, AF, and stroke, highlighting the need for targeted interventions and risk management strategies in this vulnerable population. Methods: Utilizing the 2019 National Inpatient Sample and employing ICD-10 CM coding, we identified all non-diabetic geriatric admissions with AF. Patients were categorized into two groups: pDM+ and pDM-. The primary outcomes of interest were stroke incidence, odds and potential sex disparities in odds as a risk factor for stroke in geriatric patients with AF. Results: Of the total 218130 non-diabetic geriatric AF admissions, 3525(1.6%) had pDM. The pDM+ cohort was relatively younger (median 75 vs 77 years), and often consisted of females (57.9%; p<0.359), white (80.1%), and from the higher-income quartile (28.5%); (p<0.001). The preDM+ group had significantly higher rates of complicated HTN (50.2 vs 43.6%), hyperlipidemia (66.4 vs 53.7%), obesity (30.2 vs 13.6%), PVD (15.3 vs 9.9%), stroke (1.4 vs 0.8%). After adjusting for baseline characteristics/comorbidities, the pDM+ cohort with AF admissions showed a higher rate and significantly higher odds of stroke vs the pDM- cohort (1.4% vs. 0.8%, OR 2.00, 95%CI 1.06-3.77; p=0.033). On subgroup analyses, males had a stronger association (OR 5.48, 95%CI 1.43-21.02; p=0.013) vs. females. Conclusion: Our research revealed that geriatric patients hospitalized with AF who had concomitant pDM were twice likely to develop stroke, with male preponderance. Further research is warranted to develop tailored interventions to mitigate the risk of stroke in AF patients with pDM.

Background: Cardiovascular disease is the leading cause of death worldwide, with a notable impact on postmenopausal women. However, contemporary large-scale population-based data for the burden and disparities of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) in this population remains limited. Methods: The National Inpatient Sample (2020, ICD10 codes, age>55 years) was queried to identify postmenopausal women's hospitalizations. Socio-demographics, racial subgroups, comorbidities, and MACCE rates were retrieved with a more granular comparative analysis in postmenopausal women. A p<0.05 was considered statistically significant. Results: Of the total 8435195 postmenopausal women hospitalizations (median age 75 years), 1021375 (12.1%) were identified with MACCE. MACCE cohort, in comparison to non-MACCE cohort, had significantly higher prevalence of hypertension (77.1% vs 71.3), diabetes (39.8% vs 34.0%), hyperlipidemia (53.7% vs 48.4%), PVD (9.8% vs 7.1%), prior MI (8.3 vs 5.7%), prior TIA/stroke (10.5 vs 9%) and CKD (29.4 vs 23.4%). Significant clinical predictors for all-cause mortality were found to be race Asian/PI vs white ( 1.31 [1.09-1.18]), median household income national quartile (1.16 [1.13-1.20]), hypertension (1.18[1.16-1.20]) diabetes (1.20 [1.19-1.22]), hyperlipidemia (1.12[1.11-1.14]), prior MI (1.37[1.34-1.40]) and prior TIA stroke (1.0 5 [1.03-1.07] (all p<0.05). Conclusion: Among hospitalizations, Asian/Pacific Islanders, patients from the lowermost income quartile with co-existent hypertension, diabetes, hyperlipidemia, CKD, and cardiovascular comorbidities independently revealed the highest MACCE rates. Special emphasis needs to be laid on socio-demographics, comorbidities, and racial differences for CVD disease prevention, and risk factor modification in postmenopausal women.

Abstract Background Impella is an advanced ventricular assist device frequently used as a bridge to heart transplantation. The association of Impella with increased rates of gout flares has not been studied. Our primary aim is to determine the rates of gout flares in patients on Impella support. Methodology A retrospective study was conducted between January 2017 and September 2022 involving all patients who underwent heart transplantation. The cohort was divided into groups based on Impella support for statistical analysis. In patients receiving Impella support, outcome measures were compared based on the development of gout flares. Results 213 patients were analyzed, with 19.71% supported by Impella. Impella and non-Impella groups had similar age, race, and BMI, but more males were in the Impella group. Gout and chronic kidney disease were more prevalent in Impella-supported patients, while coronary artery disease was less common. The incidence of gout flare was significantly higher in Impella patients (31% vs. 5.3%). The Impella group had an adjusted odds ratio for in-hospital gout flare of 8.069 (95% CI = 2.13–35.08, P = 0.003). Impella-supported patients with gout flares had longer intensive care unit and hospital stays but no difference in mortality or other outcomes. Conclusion Our study is the first to identify the potential association between Impella support and increased rates of gout flares in hospitalized patients. Future studies are required to confirm this association and further elucidate the biological pathways. It is imperative to consider introducing appropriate measures to prevent and promptly manage gout flares in Impella-supported patients.

Abstract Background Depression has emerged as a critical risk factor for development and progression of various cardiovascular diseases; however, the association between depression and Hypertrophic Cardiomyopathy (HCM) outcomes is less clear. We aimed to determine the impact of comorbid depression on patients hospitalized with HCM. Methods The National Inpatient Sample (2020) was assessed to identify patients hospitalized with HCM using relevant ICD-10 codes. Propensity score matching of 1:1 was performed and the cohort was divided into two - those with comorbid depression (HCM-D+) and those without (HCM-D-). Baseline characteristics and comorbidities were compared between the two cohorts. Impact of comorbid depression on hospitalized HCM patients was evaluated using a multivariate regression analysis adjusting for confounders. Results We identified a cohort of 15530 in-hospital HCM patients with a median age of 67 years (66.9% females, 33.1% males, 74.6% whites, 19.1% blacks, 4.3% hispanics, 1.7% Asians). Amongst 15530, 85.5% admissions were non-elective. The HCM-D+ cohort had significantly higher rates of comorbidities such as hypertension (76.4% vs 71.4%), hyperlipidemia (62.5% vs 52.4%), obesity (27.9% vs 24.9%), smoking (28.1% vs 25.7%), dementia (8.2% vs 4.4%) and cancer (7.5% vs 5.8%) (p&lt;0.001). When in-hospital outcomes were compared, HCM-D+ cohort paradoxically appeared to have 44% lower risk of all-cause mortality (OR-0.56; 95%CI: 0.37- 0.84), 22% lower risk of composite end points (all-cause mortality, heart failure, atrial fibrillation, cardiac arrest including ventricular fibrillation, acute ischemic stroke) (OR-0.78; 95%CI:0.66-0.91), 21% lower risk of atrial fibrillation alone (OR-0.79; 95%CI:0.67-0.92) (p&lt;0.001). Conclusion Despite having higher rates of comorbidities, comorbid depression in HCM patients appeared to improve in-hospital outcomes. Further studies are needed to uncover the paradoxical protection provided by underlying depression.