Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

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 <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 <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.

NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.

Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Salvage surgery for local recurrence after sublobar surgery in Stages I and II non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To examine if patients undergoing salvage surgery for local recurrence following sublobar resection (SLR) have similar perioperative complications and overall survival (OS) compared to lobectomy patients for early stage non-small cell lung cancer (NSCLC). METHODS: Patients undergoing lobectomy and SLR (segmentectomy or wedge resection) for Stages I and II NSCLC from 2010 to 2016 were reviewed. Lobectomy patients and those who underwent salvage surgery for local recurrence after SLR were compared. Salvage surgeries were curative-intent resections for recurrence. RESULTS: Cases included 634 lobectomies and 986 SLR. Fifty-nine SLR patients (6.0%) recurred at a local site compared to 11 lobectomy patients (1.7%; p < 0.001). Twenty-three locally recurrent SLR patients (39.0%) went on to salvage surgery. Peri-operative complications after salvage surgeries were similar to lobectomies (34.8% 8/23 vs. 34.7% 220/634, p = 1.00). OS at 5 years for salvage surgery patients was similar to lobectomy patients (79.6% 13/23 vs. 70.6% 227/634, p = 0.23). OS for patients who underwent salvage surgery was significantly better than those who did not have salvage surgery for recurrence (79.6% vs. 53.0%, p = 0.02). CONCLUSIONS: Patients who undergo salvage surgery for local recurrence after SLR had similar perioperative complications and OS compared to lobectomy patients but less than half underwent salvage surgery.

Risk of chyle leak after robotic versus video-assisted thoracoscopic esophagectomy.

BACKGROUND: We investigate the incidence and risk factors for post-operative outcomes including chyle leak following minimally invasive esophagectomy (MIE). METHODS: Patients undergoing MIE from May 2016 until August 2020 were prospectively followed. Outcomes of robotic and video-assisted thoracoscopic surgery (VATS) esophagectomy were analyzed. RESULTS: 347 esophagectomies were performed: 70 cases were done robotically by 2 surgeons and 277 by VATS by 14 surgeons. Patients had similar demographics, surgical technique, length of stay (LOS), and re-operation rates. Overall complication rates between robotic and VATS MIE were statistically similar (61% vs. 50%; p = 0.082). The majority of complications for either VATS (41.5%) or robotic-assisted minimally invasive esophagectomy (RAMIE) (51.4%) were grade II. Nineteen patients developed a chyle leak. Patients with a chyle leak were similar in age, gender, and hospital LOS (all p > 0.05), but were more likely to undergo a three-hole or robotic esophagectomy (both p < 0.05) as well as have higher rehabilitation requirements on discharge (26% vs. 10%; p = 0.05). Among the two surgeons who each performed > 20 robotic esophagectomies (n = 70), nine chyle leaks occurred. Rates varied by surgeon (7 vs. 2; p = 0.003). Lower leak rates occurred in the surgeon with more robotic esophagectomy experience (n = 47 vs. 23). Patients were similar in age, and gender (p > 0.05), but those with a chyle leak were more likely to undergo three-hole esophagectomies, prophylactic thoracic duction ligations, undergo the abdominal portion via laparotomy, and not have a prophylactic omental flap (all p < 0.05). CONCLUSION: Robotic and VATS esophagectomy have similar rates of re-operation, length of stay, discharge needs and complications. Differences in outcomes between VATS and Robotic esophagectomy appears to be related to surgeon experience with the robot but may also be associated with techniques such as anastomotic height, omental flap utilization and performance of laparoscopy.

Preserving NLST mortality benefits and acceptable morbidity for lung cancer surgery in a community hospital.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate whether academic thoracic surgeons could achieve morbidity and mortality rates in community hospitals equivalent to those seen in National Lung Screening Trial (NLST). METHODS: This was a retrospective review of community hospital lung cancer procedures for clinical Stage I-III non-small-cell lung cancers from 2007 through 2014. Variables include age, comorbidities, computed tomography (CT) characterization, and operative techniques. RESULTS: There were 177 patients who had lung cancers removed by a minimally invasive approach (79%), including lobectomy in 127 (72%), segmentectomy in 4 (2%), and wedge-resections in 46 (26%). The median patient age was 71 years (interquartile range [IQR], 63-76). The cohort was primarily female (58%), clinical Stage I (82%), with a median tumor size of 2.3 cm (IQR, 1.5-3.3). The median length of stay was 6 days (range: 1-35). Complications were experienced by 78 (44.1%) patients, most commonly atrial fibrillation in 20 (11.3%) followed by air-leak in 19 (10.7%). There were no in-hospital deaths. Tumor location and extent of resection were associated with complications, while larger tumor size, margin contour, and resection method were associated with air-leak (all p < 0.05). Higher clinical stage and larger tumor size were associated with occult Stage III disease (both p < 0.05). CONCLUSIONS: The low morbidity and mortality rates from the NLST were achievable in a community setting for early-stage lung cancer. Characterization of cancers using CT imaging identified factors most commonly associated with postoperative complications and the presence of occult Stage III disease.

Adjuvant therapy following induction therapy and surgery improves survival in N2-positive non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate treatment strategies and factors influencing overall survival (OS) and disease-free survival (DFS) in resectable, non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node metastasis. METHODS: All patients undergoing surgery for NSCLC with N2 disease between 2006 and 2016 were included. Treatment approaches included surgery only, neoadjuvant therapy followed by surgery, surgery followed by adjuvant therapy, and neoadjuvant therapy followed by surgery and adjuvant therapy (triple therapy). Patient clinical and pathologic data were retrospectively collected. RESULTS: A total of 281 patients were included in the study. In total, 209 patients had neoadjuvant therapy, 47.4% of which went on to received additional adjuvant therapy. The pathologic complete response rate was 12.9%. The treatment strategy which included triple therapy was isolated as a significant contributor to improved OS and DFS. Nodal downstaging (N0) after induction therapy conferred an OS benefit (38.3% vs. 15.6%, p = .03). Patients with single-station N2 disease experienced higher DFS. Video-assisted thoracic surgery (VATS) lobectomy completion rates were higher at the end of the study period compared to the beginning (p < .001). CONCLUSIONS: Patients who undergo neoadjuvant therapy for N2-positive NSCLC may benefit from additional adjuvant therapy. Single-station N2 disease confers higher DFS. VATS completion rates for lobectomy increase as experience increases.

Outcomes of superior segmentectomy versus lower lobectomy for superior segment Stage I non-small-cell lung cancer are equivalent: An analysis of 196 patients at a single, high volume institution.

OBJECTIVES: To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment. METHODS: We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS. RESULTS: Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences. CONCLUSIONS: In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.

Early thoracic surgery consultation and location of therapy impact time to esophagectomy.

Background: Neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy is the standard treatment for resectable, locally advanced esophageal cancer. The ideal timing between neoadjuvant therapy and esophagectomy is unclear. Delayed esophagectomy is associated with worse outcomes. We investigated which factors impacted time to esophagectomy in our patients. Methods: We conducted a retrospective analysis of prospectively collected data of patients with pT0-3N0-2 esophageal cancers who underwent CROSS trimodality therapy from May 2016 to January 2020. Sociodemographic factors, comorbidities, and neoadjuvant factors (location of CRT, treatment toxicity, discontinuation of treatment) were compared between patients who underwent surgery within 60 days and those after 60 days. Results: In total, 197 patients were analyzed of whom 137 underwent esophagectomy within 60 days (early surgery, ES) and 60 were outside that window (delayed surgery, DS). More DS patients had a history of myocardial infarction (MI) or stroke (both 11.67% vs. 3.65%, P=0.05) and required CRT dose reduction (16.67% vs. 6.57%, P=0.04). Fewer DS patients received CRT at Dana-Farber Cancer Institute (DFCI) or a DFCI satellite site (33.33% vs. 58.4%, P=0.01) and saw our surgeons before CRT completion (68.33% vs. 89.78%, P=0.001). CRT at DFCI [odds ratio (OR) 2.63, P=0.01] or a satellite site (OR 3.07, P=0.01) and evaluation by a thoracic surgeon (OR 4.07, P=0.001) shortened time to esophagectomy. History of MI (OR 0.29, P=0.04), stroke (OR 0.29, P=0.04), and CRT dose reduction (OR 0.35, P=0.03) delayed time to esophagectomy. Conclusions: Improving access to multispecialty cancer centers and increasing satellite sites may improve time to esophagectomy.

Early adoption of robotic lung resection in an established video assisted thoracic surgery practice.

Background: Reported advantages to robotic thoracic surgery include shorter length of stay (LOS), improved lymphadenectomy, and decreased complications. It is uncertain if these benefits occur when introducing robotics into a well-established video-assisted thoracoscopy (VATS) practice. We compared the two approaches to investigate these advantages. Materials and methods: IRB approval was obtained for this project. Patients who underwent segmentectomy or lobectomy from May 2016-December 2018 were propensity-matched 2: 1 (VATS: robotic) and compared using weighted logistic regression with age, gender, Charlson Comorbidity Index, surgery type, stage, Exparel, and epidural as covariates. Complication rates, operation times, number of sampled lymph nodes, pain level, disposition, and LOS were compared using Wilcoxon rank-sum and with Rao-Scott Chi-squared tests. Results: 213 patients (142 VATS and 71 robot) were matched. Duration of robotic cases was longer than VATS (median 186 min (IQR 78) vs. 164 min (IQR 78.75); p < 0.001). Significantly more lymph nodes (median 11 (IQR 7.50) vs. 8 (IQR 7.00); p = 0.004) and stations were sampled (median 4 (IQR 2.00) vs. 3 (IQR 1.00); p < 0.001) with the robot. Interestingly, robotic resections had higher 72-hour pain scores (median 3 (IQR 3.25) vs. 2 (IQR 3.50); p = 0.04) and 48-hour opioid usage (median 37.50 morphine milligram equivalents (MME) (IQR 45.50) vs. 22.50 MME (IQR 37.50); p = 0.01). Morbidity, LOS, and disposition were similar (all p > 0.05). Conclusions: The robotic approach facilitates better lymph node sampling, even in an established VATS practice.

Liposomal bupivacaine intercostal block placed under direct vision reduces morphine use in thoracic surgery.

Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.

Perioperative Esophagectomy Outcomes in Older Esophageal Cancer Patients in Two Different Time Eras.

To investigate perioperative outcomes of esophagectomies by age groups. Retrospective analysis of esophageal cancer patients undergoing esophagectomy from 2005 to 2020 at a single academic institution. Baseline characteristics and outcomes were analyzed by 3 age groups: <70, 70-79, and ≥80 years-old. Sub-analysis was done for 2 time periods: 2005-2012 and 2013-2020. Of 1135 patients, 789 patients were <70, 294 were 70-79, and 52 were ≥80 years-old. Tumor characteristics, and operative technique were similar, except positive longitudinal margins rates (all <3%) (P = 0.008). Older adults experienced increased complications (53.6% vs 69.7% vs 65.4% respectively; P < 0.001) attributable to grade II complications (41.4% vs 62.2% vs 63.5% respectively; P < 0.001). Hospital length of stay (LOS) and rehabilitation requirements were higher in older adults (both P < 0.05). 30-day readmissions, reoperation, and 30-day mortality rates (all <2%) showed no association with age group. Overall complications, LOS, discharge disposition and re-operative rates improved from 2005 to 2012 to 2013-2020 for all (P < 0.05). Increasing age was an independent risk factor for cardiovascular complications (OR 1.7, 95% CI 1.23-2.46 for ages 70-79 and OR 2.7, 95% CI 1.37-5.10 for ages ≥80 ), inpatient rehabilitation (OR 3.3, 95% CI 2.26-5.05 for ages 70-79 and OR 12.1 95% CI 5.83-25.04 for ages ≥80), and prolonged LOS (OR 1.64 95% CI 1.16-2.31 for ages 70-79 and OR 3.6 95% CI 1.71-7.67 for ≥80. After adjusting for time period, older age remained associated with complications (P < 0.05). Highly selected older adults at a large volume esophagectomy center can undergoesophagectomy with increased minor complication and rehabilitation needs.

Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children.

Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C. Design, Setting, and Participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. Exposure: Diagnosis of MIS-C. Main Outcomes and Measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. Conclusions and Relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. METHODS: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3. RESULTS: Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction. CONCLUSION: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.

Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-control Investigation.

BACKGROUND: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. METHODS: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. RESULTS: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. CONCLUSIONS: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C.

Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C.

Objective: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: Across 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments. Discussion: Among patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020.

Importance: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. Objective: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. Design, Setting, and Participants: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). Results: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. Conclusions and Relevance: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.

Esophagectomy for Esophageal Cancer Performed During the Early Phase of the COVID-19 Pandemic.

Delay in time to esophagectomy for esophageal cancer has been shown to have worse peri-operative and long-term outcomes. We hypothesized that COVID-19 would cause a delay to surgery, with worse perioperative outcomes, compared to standard operations. All esophagectomies for esophageal cancer at a single institution from March-June 2020, COVID-19 group, and from 2019 were reviewed and peri-operative details were compared between groups. Ninety-six esophagectomies were performed in 2019 vs 37 during March-June 2020 (COVID-19 group). No differences between groups were found for preoperative comorbidities. Wait-time to surgery from final neoadjuvant treatment was similar, median 50 days in 2019 vs 53 days during COVID-19 p = 0.601. There was no increased upstaging, from clinical stage to pathologic stage, 9.4% in 2019 vs 7.5% in COVID-19 p = 0.841. Fewer overall complications occurred during COVID-19 vs 2019, 43.2% vs 64.6% p = 0.031, but complications were similar by specific grades. Readmission rates were not statistically different during COVID-19 than 2019, 16.2% vs 10.4% p = 0.38. No peri-operative mortalities or COVID-19 infections were seen in the COVID-19 group. Esophagectomy for esophageal cancer was not associated with worse outcomes during the COVID-19 pandemic with minimal risk of infection when careful COVID-19 guidelines are followed. Prioritization is recommended to ensure no delays to surgery.

Internal Staging Discordance in National Cancer Databases for Non-Small Cell Lung Cancer.

BACKGROUND: The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer. METHODS: NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed. RESULTS: Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P < .001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P < .001). The NCDB misclassified 0.99% tumors >5 cm as stage I vs 0.04% in SEER (P < .001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stage