The Magnitude of Postconvulsive Leukocytosis Mirrors the Severity of Periconvulsive Respiratory Compromise: A Single Center Retrospective Study.

Background: Generalized epileptic convulsions frequently exhibit transient respiratory symptoms and non-infectious leukocytosis. While these peri-ictal effects appear to arise independently from one another, the possibility that they stem from a common ictal pathophysiological response has yet to be explored. We aimed to investigate whether peri-ictal respiratory symptoms and postictal leukocytosis coexist. Methods: We performed a single center retrospective chart review of 446 patients brought to our emergency department between January 1, 2017 and August 23, 2018 for the care of generalized epileptic convulsions with or without status epilepticus. We included 152 patients who were stratified based on the presence (PeCRC+) or absence (PeCRC-) of overt periconvulsive respiratory compromise (PeCRC). In addition, patients were stratified based on the presence or absence of postconvulsive leukocytosis (PoCL), defined as an initial postconvulsive white blood cell (WBC) count ≥ 11,000 cells/mm3. Triage vital signs, and chest x ray (CXR) abnormalities were also examined. Results: Overt PeCRC was observed in 31.6% of patients, 43% of whom required emergent endotracheal intubations. PoCL was observed in 37.5% of patients, and was more likely to occur in PeCRC+ than in PeCRC- patients (79.2 vs. 18.2%; OR = 17.0; 95% CI = 7.2-40.9; p < 0.001). Notably, the magnitude of PoCL was proportional to the severity of PeCRC, as the postconvulsive WBC count demonstrated a negative correlation with triage hemoglobin oxygen saturation (R = -0.22; p < 0.01; CI = -0.48 to -0.07). Moreover, a receiver operating characteristic analysis of the WBC count's performance as predictor of endotracheal intubation reached a significant area under the curve value of 0.81 (95% CI = 0.71-0.90; p < 0.001). Finally, PeCRC+ patients demonstrated frequent CXR abnormalities, and their postconvulsive WBC counts correlated directly with triage heart rate (R = 0.53; p < 0.001). Conclusion: Our data support the existence of an ictal pathophysiological response, which induces proportional degrees of PoCL and PeCRC. We suggest this response is at least partially propelled by systemic catecholamines.

Plasma Free Fatty Acids Metabolic Profile with LC-MS and Appetite-Related Hormones in South Asian and White European Men in Relation to Adiposity, Physical Activity and Cardiorespiratory Fitness: A Cross-Sectional Study.

South Asians have a greater cardiovascular disease (CVD) and type 2 diabetes (T2D) risk than white Europeans, but the mechanisms are poorly understood. This study examined ethnic differences in free fatty acids (FFAs) metabolic profile (assessed using liquid chromatography-mass spectrometry), appetite-related hormones and traditional CVD and T2D risk markers in blood samples collected from 16 South Asian and 16 white European men and explored associations with body composition, objectively-measured physical activity and cardiorespiratory fitness. South Asians exhibited higher concentrations of five FFAs (laurate, myristate, palmitate, linolenic, linoleate; p ≤ 0.040), lower acylated ghrelin (ES = 1.00, p = 0.008) and higher leptin (ES = 1.11, p = 0.004) than white Europeans; total peptide YY was similar between groups (p = 0.381). South Asians exhibited elevated fasting insulin, C-reactive protein, interleukin-6, triacylglycerol and ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) and lower fasting HDL-C (all ES ≥ 0.74, p ≤ 0.053). Controlling for body fat percentage (assessed using air displacement plethysmography) attenuated these differences. Despite similar habitual moderate-to-vigorous physical activity (ES = 0.18, p = 0.675), V ˙ O2max was lower in South Asians (ES = 1.36, p = 0.001). Circulating FFAs in South Asians were positively correlated with body fat percentage (r2 = 0.92), body mass (r2 = 0.86) and AUC glucose (r2 = 0.89) whereas in white Europeans FFAs were negatively correlated with total step counts (r2 = 0.96). In conclusion, South Asians exhibited a different FFA profile, lower ghrelin, higher leptin, impaired CVD and T2D risk markers and lower cardiorespiratory fitness than white Europeans.

Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis.

OBJECTIVE: To evaluate the frequency of HLA class I and II alleles associated with traditional forms of inflammatory arthritis in patients with immune checkpoint inhibitor (ICI)-induced inflammatory arthritis as compared with population controls. METHODS: High-resolution HLA typing was performed on 27 patients with ICI-induced inflammatory arthritis and 726 healthy controls. Genotyping at the shared epitope (SE) locus (HLA DRB1) was performed on 220 RA cases. Allele-positivity rates and frequency of having at least one SE allele were compared using Fisher's exact test between ICI-induced inflammatory arthritis and healthy controls. Frequency of having at least one SE allele was also compared between ICI-induced inflammatory arthritis and RA cases. RESULTS: Twenty-six patients with ICI-induced inflammatory arthritis were of European descent, and one was African American. In those 26 patients, 16 (61.5%) had at least one SE allele, significantly different from healthy controls of European descent, in whom 299 (41.2%) had at least one SE allele (odds ratio 2.3, P = 0.04). The allele-positivity rate of DRB1*04: 05 was also higher in the ICI-induced inflammatory arthritis group. The ICI-induced inflammatory arthritis population and RA patients of European descent did not differ in frequency of having at least one SE allele, but ICI-induced inflammatory arthritis patients were more likely to be autoantibody-negative for RF and anti-CCP antibodies. CONCLUSION: Patients with ICI-induced inflammatory arthritis of European descent were more likely to have at least one SE allele than healthy controls. Further studies are needed to validate these findings and investigate whether a unique immunogenetic framework increases risk for different immune-related adverse events.

Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic Markers.

Birth characteristics such as birth order, birth weight, birth defects, and Down syndrome showed some of the first risk associations with childhood leukemia. Examinations of correlations between birth characteristics and leukemia risk markers have been limited to birth weight-related genetic polymorphisms. We integrated information on nongenetic and genetic markers by evaluating the relationship of birth characteristics, genetic markers for childhood acute lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The multiethnic study consisted of cases with childhood ALL (n=161) and healthy controls (n=261). Birth characteristic data were collected through questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93; 95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI, 1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse correlation with a birth characteristic, gestational age, with a gene-dosage effect (P=0.005), and in interaction with a transferrin receptor rs3817672 genotype (Pinteraction=0.05). This correlation translated into a strong association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our study provides evidence for the involvement of prenatal events in the development of childhood ALL. The inverse correlation of rs9366637 with gestational age has implications on the design of HFE association studies in birth weight and childhood conditions using full-term newborns as controls.

Genetic Associations of PPARGC1A with Type 2 Diabetes: Differences among Populations with African Origins.

The aim of this study was to assess the differences in correlation of PPARGC1A polymorphisms with type 2 diabetes (T2D) risk in adults of African origins: African Americans and Haitian Americans. The case-control study consisted of >30 years old, self-identified Haitian Americans (n = 110 cases and n = 116 controls) and African Americans (n = 124 cases and n = 122 controls) living in South Florida with and without T2D. Adjusted logistic regression indicated that both SNP rs7656250 (OR = 0.22, P = 0.005) and rs4235308 (OR = 0.42, P = 0.026) showed protective association with T2D in Haitian Americans. In African Americans, however, rs4235308 showed significant risk association with T2D (OR = 2.53, P = 0.028). After stratification with sex, in Haitian Americans, both rs4235308 (OR = 0.38, P = 0.026) and rs7656250 (OR = 0.23, P = 0.006) showed protective association with T2D in females whereas in African American males rs7656250 had statistically significant protective effect on T2D (OR = 0.37, P = 0.043). The trends observed for genetic association of PPARGC1A SNPs, rs4235308, and rs7656250 for T2D between Haitian Americans and African Americans point out differences in Black race and warrant replicative study with larger sample size.