Stratification of Pediatric COVID-19 Cases Using Inflammatory Biomarker Profiling and Machine Learning.

While pediatric COVID-19 is rarely severe, a small fraction of children infected with SARS-CoV-2 go on to develop multisystem inflammatory syndrome (MIS-C), with substantial morbidity. An objective method with high specificity and high sensitivity to identify current or imminent MIS-C in children infected with SARS-CoV-2 is highly desirable. The aim was to learn about an interpretable novel cytokine/chemokine assay panel providing such an objective classification. This retrospective study was conducted on four groups of pediatric patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 70 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January and May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August and October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021 andJanuary 2022 infected with delta and/or omicron variants. Group 1 was used to train an L1-regularized logistic regression model which was tested using five-fold cross validation, and then separately validated against the remaining naïve groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the cytokine/chemokine assay-based classifier. Standard laboratory markers predict MIS-C with a five-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78 ± 0.07, while the cytokine/chemokine panel predicted MIS-C with a five-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC = 0.98 and F1 = 0.93, on Group 3 it yielded AUROC = 0.89 and F1 = 0.89, and on Group 4 AUROC = 0.99 and F1 = 0.97. Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieves equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provides a highly sensitive, and specific method to identify MIS-C in patients infected with SARS-CoV-2 of all the major variants identified to date.

Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning.

An objective method to identify imminent or current Multi-Inflammatory Syndrome in Children (MIS-C) infected with SARS-CoV-2 is highly desirable. The aims was to define an algorithmically interpreted novel cytokine/chemokine assay panel providing such an objective classification. This study was conducted on 4 groups of patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 66 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January-May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August-October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021-January 2022 infected with delta and/or omicron variants. Group 1 was used to train a L1-regularized logistic regression model which was validated using 5-fold cross validation, and then separately validated against the remaining naïve groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the algorithmically interpreted cytokine/chemokine assay panel. Standard laboratory markers predict MIS-C with a 5-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78 ± 0.07, while the cytokine/chemokine panel predicted MIS-C with a 5-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC =0.98, F1=0.93, on Group 3 it yielded AUROC=0.89, F1 = 0.89, and on Group 4 AUROC= 0.99, F1= 0.97). Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieves equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provides a sensitive, specific method to identify MIS-C in patients infected with SARS-CoV-2 of all the major variants identified to date.

SARS-CoV-2 anti-spike antibodies after vaccination in pediatric heart transplantation: A first report.

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant. METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center. RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a known pre-vaccination SARS-CoV-2 viral infection had a detectable SARS-CoV-2 Anti-Spike IgG. All 12 vaccinated pre-HTx patients had a detectable antibody (median antibody level 11.6 AU/ml) including 5 patients that maintained detectable antibodies post-HTx. There were no cases of myocarditis among the total of 17 pre-HTx and 81 post-HTx patients that underwent SARS-CoV-2 vaccination. CONCLUSION: Our data suggest that a significant proportion of pediatric HTx recipients have no detectable antibody response after SARS-CoV-2 vaccination and support the recommendation to complete the vaccination series prior to HTx in those pediatric patients waiting for HTx.

Analytical and clinical performance of cPass neutralizing antibodies assay.

Serological tests for SARS-CoV-2 are a critical component of disease control strategies. SARS-CoV-2 serology tests used in clinical diagnostic should not accurately evaluate total levels the antibodies but also closely correlate with neutralizing antibodies titers. However, only limited data is available reporting correlation of neutralization antibody assays with commercial high-throughput serological assays widely used in clinical laboratories. We performed evaluation of the GenScript cPass neutralizing antibody detection assay, to assess its value for routine clinical use to measure neutralizing titers in patients who recovered from coronavirus disease 2019 (COVID-19) or have been vaccinated. We tested its clinical performance against the commonly used Ortho Vitros IgG assay. Our combined data shows that GenScript cPass neutralizing antibody assay has satisfactory analytical and clinical performance and good correlation with Ortho Vitros IgG, supporting its use as a tool for accurate SARS-COV-2 immune surveillance of recovered or vaccinated individuals.

Squamous Cell Carcinoma of a Thyroglossal Duct Cyst and the Role of a Level IA Neck Dissection.

Squamous cell carcinoma of a thyroglossal duct cyst is exceedingly rare, with less than 30 cases reported across the literature. Herein, we present a case of squamous cell carcinoma (SCC) of a thyroglossal duct cyst (TGDC) and discuss the utility of a level IA neck dissection in these cases. In 2018, a 62-year-old female presented to a university-affiliated otolaryngologist with symptoms of dysphagia and a palpable anterior midline neck mass. MRI demonstrated a 3.1 × 2.0-cm mass concerning an invasive TGDC. She was referred to our institution for further management. Preoperative imaging demonstrated an invasive TGDC but no pathological nodes. A Sistrunk procedure and a IA neck dissection were performed. Pathology demonstrated one pathological node in the neck dissection specimen. In summary, a bilateral IA neck dissection was performed on a clinically node zero (N0) patient, and a pathological node was ultimately identified. We hope that by introducing this idea of a IA neck dissection for SCC of a TGDC, we can prompt further investigation into the utility of this procedure for these uniquely rare cases.

Midterm outcomes of revisional surgery for gastric pouch and gastrojejunal anastomotic enlargement in patients with weight regain after gastric bypass for morbid obesity.

Reoperative surgery for the morbidly obese has become increasingly common due to postoperative weight regain. There are limited studies evaluating the effectiveness of revisional surgery. This study evaluates the weight loss outcomes of revisional surgery over a 2-year period at our University Hospital, USA. Of the 412 patients who underwent laparoscopic bariatric surgery between June 2009 and June 2011, we identified 25 patients who had Roux-en-Y gastric bypass (RYGB) originally, who underwent laparoscopic revisional surgery for weight regain. Preoperative and postoperative data were reviewed. Statistical analysis was performed using paired t test. This study includes 0 male and 25 female patients with an average age of 42 (range min to max: 28-58), mean original body mass index (BMI) of 54.6 kg/m(2) (r = 37.3-80.7), average lowest BMI achieved of 32.2 (r = 20.1-50.9), and average BMI at the time of revision of 41.0 kg/m(2) (r = 29.5-60.7, standard deviation (SD) = 8.5). All laparoscopic revisions consisted of resizing the gastric pouch by resection and recreating the gastrojejunostomy. Average hospital length of stay was 1.28 days (r = 1-4). Perioperative morbidity was 8 %; one patient developed a trocar site hernia which required repair, and another suffered postoperative bleeding requiring transfusion. There was no mortality. Postoperative BMI averages at 3, 6, 9, 12, and 24 months were 35.0 (SD = 7.15), 34.7 (SD = 4.26), 36.2 (SD = 7.63), 33.0 (SD = 6.58), and 44.2 (SD = 12.87), respectively. Statistically significant weight loss was achieved at 3 [t (10) = 6.74, p < 0.05], 6 [t (7) = 4.69, p < 0.05], 9 [t (9) = 2.94, p < 0.05], and 12 [t (6) = 3.78, p < 0.05] months. However, there was no statistically significant weight loss at 24 months postoperatively [t (4) = -0.16, p > 0.05]. Laparoscopic revisional bariatric surgery can be performed with significant weight loss up to 1 year postoperatively. However, additional studies are required to evaluate longer-term success.