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Background and Aims: Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from this disease per year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil. Esophageal squamous cell carcinomas and adenocarcinomas have proven to be inherently resistant to systemic treatments as a result of histological, molecular and etiological heterogeneity, with limited responses seen after first line therapy. Methods: We are presenting 3 case reports of 57 year old man, 53 year old man & 47 year old woman who, presented with dysphasia for solid foods, weight loss and dyspepsia since 1 month, 3 months & 1.5 months respectively. Upper gastro oesophageal endoscopy shows ulcerated friable lesion with minimal luminal compromise with biopsy showing poorly differentiated adenocarcinoma (PDAC) and PECT-CT showed FDG avid lesions in gastroesophageal junction, gastric cardia, multiple retroperitoneal lymph nodes and bilateral liver lesions. All 3 were having stage IV disease, with PDAC, squamous cell carcinoma & PDAC respectively. We have started 1st patient on DOX regimen containing Docetaxel, Oxaliplatin and Capecitabine at an interval of 2 weeks and after 4 cycles he was having stable disease in GE junction, liver and slightly increased size of retroperitoneal lymph nodes. Second & 3rd patient was put on Pclitaxel-carboplatil protocol, after 6 cycles both were having partial response & was managed with 6 cycles CAPOX as second line che otherapy. After 5th & 6th months of second line chemotherapy both patients were having progressive disease. Results: In view of radiological progression we started him on Injection, Nivolumab 240mg intravenously every 2 weekly along with low dose capecitabine 500mg twice a day. After 4 cycles of treatment his PET-CT showing complete metabolic response in GE junction, liver and retroperitoneal lesions. Now we are continuing Nivolumab and low dose capecitabine planned to complete for 2 years. Conclusion: So to conclude nivolumab along with metronomic chemotherapy with low dose capecitabine was very well tolerated and exhibited antitumor activity in extensively pretreated patient with metastatic esophageal poorly differentiated adenocarcinoma. Additional studies of Nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoin.

Background: Primary lung cancers in India were reported to be rare in earlier studies. But the trend is changing and there is increased incidence of lung cancers. Aims and Objectives: This present descriptive observational study was conducted to report the risk factor profile of the lung cancer patients from the Himalayan state of the Indian population. Materials and Methods: This descriptive epidemiological study was conducted from a single centre, in a prospective observational design, among the patients who were diagnosed as carcinoma lung histologically or cytologically over a period of one year in a tertiary care referral centre in the Himalayan state of the Northern India. The patients data was collected in detailed manner pertaining to age, sex, residence and occupation, questionnaires regarding risk factors like smoking history, Environmental tobacco smoke exposure, Indoor pollution, Alcohol history, HIV infection, Structural lung disease, Religion and Geography. Results: One hundred and one consecutive patients of primary lung cancer were recruited in the study which was confirmed either cytologically or histopathologically. Out of 101 patients, 79 (78.2%) were males and 22 (21.8%) were females, mean age was 62.65 years, 97 (96%) patients had rural background and 4 (4%) patients had urban background, 96 (95.04%) patients were active smokers, 3 (2.9%) were passive smokers and non smokers were 2 (1.9%), 25 (24.8%) were vegetarians and 76 (75.2%) were non vegetarians. 36 patients (35.6%) were from altitude of 0-1000 meters, 41 patients (40.6%) were from altitude of 1001-2000 meters, 21.8% were from altitude of 2001-3000 meters and 2% were from altitude of 3001-4000 meters. Adenocarcinoma was the most common type at all altitudes. Conclusions: Awareness about carcinoma lung in the Himalayan state especially in rural population is still lacking and are presenting at an advanced stage, which largely impact on survival of the patients. This study provides the data pertaining to risk factor profile of the lung cancer patients from the Himalayan state and can be utilised for future comparison with other Indian studies, to educate the community and to spread the awareness of the prevailing lung cancer risk factors.

The virus that causes severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the genus Beta coronavirus and the family Coronaviridae. The SARS-CoV-2 virus is a positive sense, non-segmented single-strand RNA virus that causes coronavirus disease 2019 (COVID-19), which was first reported in December 2019 in Wuhan, China. COVID-19 is now a worldwide pandemic. Globally, several newer variants have been identified; however, only a few of them are of concern (VOCs). VOCs differ in terms of infectivity, transmissibility, disease severity, drug efficacy, and neutralization efficacy by monoclonal antibodies, convalescent sera, or vaccines. VOCs reported from various parts of the world include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.529 (Omicron). These VOCs are the result of mutations, with some based on spike proteins. Mutations may also cause molecular diagnostic tests to fail to detect the few VOCs, leading to a delayed diagnosis, increased community spread, and delayed treatment. We searched PubMed, EMBASE, Covariant, Stanford variants database, and CINAHL from December 2019 to February 2022 using the following search terms: Variant of Concern, SARS-CoV-2, Omicron, etc. All types of research were chosen. All research methods were considered. This review discusses the various VOCs, as well as their mutations, infectivity, transmissibility, and neutralization efficacy.

Objective:  This study aimed to determine if treatment with IVIG of neonates with ABO incompatibility (without Rh incompatibility) results in decreased number of packed red blood cell (pRBC) transfusions and phototherapy use., Study Design:  An Institutional Review Board (IRB)-approved, single-institution retrospective study was conducted. Neonates ≥38 weeks' gestational age born between January 1, 2007, and December 31, 2016, with ABO incompatibility were included. The comparison among groups was performed using chi-square and Fisher's exact tests for categorical variables; continuous variables were assessed by Kruskal-Wallis test., Results:  Six hundred and sixty-eight neonates with ABO incompatibility met inclusion criteria, 579 were included in the analyses. From these, 431 (74%) neonates had positive Direct Antiglobulin Test (DAT); 98 (17%) received IVIG and 352 (61%) received phototherapy. Thirty-six (6%) neonates received pRBC and 6 (1%) required exchange transfusions. Only 3 (0.5%) infants received pRBC transfusions postdischarge, by 3 months of age. Neonates requiring IVIG had lower initial hemoglobin (13.6 vs. 16.0 g/dL, p  ≤ 0.0001) and higher bilirubin at start of phototherapy (9.1 vs. 8.1 mg/dL, p  = 0.0064). From the 42 (7%) neonates who received simple and exchange transfusions, IVIG use was not associated with decreased use or number of transfusions ( p  = 0.5148 and 0.3333, respectively). Newborns with A+ and B+ blood types had comparable initial hemoglobin, DAT positivity, APGAR, and bilirubin. However, infants with B+ blood group were more likely (than A + ) to require phototherapy ( p  < 0.001), receive IVIG ( p  = 0.003), and need phototherapy for a longer duration ( p  = 0.001)., Conclusion:  The results of this large retrospective study reveal that giving IVIG to neonates with ABO incompatibility was associated with increased simple or exchange transfusions. Newborns with B+ blood type required more phototherapy and IVIG. Further studies are needed to better stratify neonates who would benefit from IVIG use in order to optimize treatment strategies and avoid unnecessary risks and adverse events., Key Points: · IVIG use not associated with decreased use of pRBC or exchanges.. · Phototherapy duration associated with increased IVIG and pRBC use.. · Newborns with B+ blood type had worse hemolytic anemia.., Competing Interests: None declared., (Thieme. All rights reserved.)

Neonatal Escherichia coli (E. coli) sepsis is increasing. There is limited data on the factors contributing to increased mortality and severity of illness in neonatal E. coli sepsis. A retrospective review of neonates (<30 days) admitted to a Level IV NICU in the United States from 2008 to 2022 diagnosed with E. coli bloodstream or cerebrospinal fluid infection was conducted. Primary outcome was defined as mortality from or severe illness during E. coli infection (defined as a need for inotropic support or metabolic acidosis). E. coli neonatal sepsis rate increased from 2008 to 2022 (average of 1.12 per 1000 live births). The primary outcome, which occurred in 57.4% of cases, was independently associated with prematurity, neutropenia, and thrombocytopenia. Ampicillin resistance was not associated with the primary outcome. GA, neutropenia, and thrombocytopenia but not ampicillin resistance, are associated with mortality or severe illness from E. coli sepsis., (© 2024. The Author(s).)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded, positive-sense RNA virus. The SARS-CoV-2 virus is evolving continuously, and many variants have been detected over the last few years. SARS-CoV-2, as an RNA virus, is more prone to mutating. The continuous evolution of the SARS-CoV-2 virus is due to genetic mutation and recombination during the genomic replication process. Recombination is a naturally occurring phenomenon in which two distinct viral lineages simultaneously infect the same cellular entity in an individual. The evolution rate depends on the rate of mutation. The rate of mutation is variable among the RNA viruses, with the SARS-CoV-2 virus exhibiting a lower rate of mutation than other RNA viruses. The novel 3'-to-5' exoribonuclease proofreading machinery is responsible for a lower rate of mutation. Infection due to the SARS-CoV-2, influenza, and respiratory syncytial virus has been reported from around the world during the same period of fall and winter, resulting in a "tripledemic." The JN.1 variant, which evolved from the predecessor, the omicron variant BA.2.86, is currently the most dominant globally. The impact of the JN.1 variant on transmissibility, disease severity, immune evasion, and diagnostic and therapeutic escape will be discussed.

Objectives: Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles., Methods: We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eosinophils per high power field in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens., Results: A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian., Conclusion: Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: Cervicofacial lymphadenitis caused by non-tubercular mycobacterial (NTM) infections has the highest infection rate in children. Our objective was to assess patient demographics, treatment methods, and the impact of weather and geography on the incidence of disease in patients with NTM cervicofacial lymphadenitis., Methods: The Pediatric Health Information System (PHIS) database was queried for data on all patients diagnosed with concurrent cervicofacial lymphadenopathy and NTM infection from 2004 to 2022. We assessed the association between weather patterns and NTM cervicofacial lymphadenitis by collecting monthly weather data from the NOAA National Center for Environmental Information. Incidence rates were calculated by dividing the number of cases by the total hospital discharges during the study period., Results: Among 47 PHIS hospitals, there were 992 diagnoses of NTM cervicofacial lymphadenitis. The average age at diagnosis was 2 [IQR, 2-4], with 59 % female. Drainage of skin abscesses or lesions was performed for 93 (9.4 %) patients, while 15 (1.5 %) had an excisional procedure of the CPT codes assessed. The most common antibiotics utilized were cephalosporins (28 %), macrolides (27 %), and rifampin (12 %). The most common treatment method was surgery with antibiotics (37 %) followed by no treatment at all (35 %), surgery alone (17 %), and antibiotics alone (10 %). Of the 28 states included in the analysis, Washington (IR: 3.5) and Nebraska (IR: 3.3) had the highest incidence rates (IR) of NTM cervical lymphadenitis. The cases were relatively equally distributed across the different weather seasons within each U.S. geographic region. However, the overall average wind speed was weakly associated with increasing the risk of diagnosis when utilizing a mixed effect zero-inflated negative binomial model (Incidence Ratio: 1.07, 95 % CI: (1.01-1.14), p = 0.035)., Conclusions: Our results indicate that the most common treatment method utilized in patients within our cohort with NTM cervicofacial lymphadenitis was the concurrent use of surgery and antibiotics. Our results also indicate there may be variation in the incidence rate among different states, but additional studies are needed as our cohort only included approximately 50 % of states within the U.S., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report in the declaration of interest form., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hepatic xenobiotic metabolism and transport decline with age, while intact xenobiotic metabolism is associated with longevity. However, few studies have examined the genome-wide impact of epigenetic aging on these processes. We used reduced representation bisulfite sequencing (RRBS) to map DNA methylation changes in liver DNA from mice ages 4 and 24 months. We identified several thousand age-associated differentially methylated sites (a-DMS), many of which overlapped genes encoding Phase I and Phase II drug metabolizing enzymes, in addition to ABC and SLC classes of transporters. Notable genes harboring a-DMS were Cyp1a2, Cyp2d9, and Abcc2 that encode orthologs of the human drug metabolizing enzymes CYP1A2 and CYP2D6, and the multidrug resistance protein 2 (MRP2) transporter. Cyp2d9 hypermethylation with age was significantly associated with reduced gene expression, while Abcc2 expression was unchanged with age. Cyp1a2 lost methylation with age while, counterintuitively, its expression also reduced with age. We hypothesized that age-related dysregulation of the hepatic transcriptional machinery caused down-regulation of genes despite age-related hypomethylation. Bioinformatic analysis of hypomethylated a-DMS in our sample found them to be highly enriched for hepatic nuclear factor 4 alpha (HNF4α) binding sites. HNF4α promotes Cyp1a2 expression and is downregulated with age, which could explain the reduction in Cyp1a2 expression. Overall, our study supports the broad impact of epigenetic aging on xenobiotic metabolism and transport. Future work should evaluate the interplay between hepatic nuclear receptor function and epigenetic aging. These results may have implications for studies of longevity and healthy aging., (© 2024. The Author(s).)

The growing prevalence of cardiovascular diseases in the United States (US) has disproportionately affected minority populations more than their white counterparts. A population that is often overlooked is the Asian American population, particularly Southeastern Asian immigrants. Despite having relatively favorable socioeconomic indicators compared to the general US population, Asian Americans, specifically Southeast Asian individuals, face a significant burden of traditional cardiovascular risk factors and are considered a high cardiovascular disease risk group. In addition, most studies have aggregated Asian populations into one major racial group rather than analyzing the different ethnicities among the Asian categorization. While some studies suggest that the acculturation process has some degree of impact on cardiovascular health, there has not been a widely-used tool to measure or ascertain the totality of acculturation. Instead, multiple proxies have been used to measure acculturation, and prior studies have argued for more culturally-tailored acculturation proxies. This paper aims to assess the implications of different acculturation measures on cardiovascular health among Asian Americans, particularly Southeastern Asian immigrants. The following proxies were expanded on in this paper: English spoken at home, length of stay in the US, religiosity and spirituality, and admixed family structures. Previous studies showed that as the length of stay in the US increases, the burden of cardiovascular risk factors increases. However, the impact of English spoken at home, religiosity, and admixed family structure are still inconclusive given the extent of current studies. While most studies suggest that an increase in acculturation increases the risk of cardiovascular disease, it is critical to note that acculturation is a multifaceted process. Therefore, more studies are necessary to appropriately examine the implications of various acculturation processes on cardiovascular risk factors in Asians, specifically Southeastern Asian individuals in the US., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objectives: There are very limited data on the rate of urinary tract infections (UTI), bacteremia, and meningitis in preterm infants with fever. Many of the studies on the incidence of these infections excluded preterm infants. This study compared the rate of these infections in preterm infants born at 32-36 weeks to term infants born at 37-42 weeks., Methods: A multicenter observational cohort study was conducted to evaluate rates of UTI, bacteremia, and meningitis in term and preterm infants 8-60 days of age with a diagnosis of fever from 2016 through 2022 using encounter data from children's hospitals in the Pediatric Health Information System., Results: There were 19 507 total febrile infants identified, of which 2162 were preterm and 17 345 were term. Preterm infants had a lower rate of UTI than term infants (1.8% confidence interval [CI] [1.3-2.5] vs 3.0% CI [2.7-3.2], P = .001). Preterm and term infants did not have statistically different rates of bacteremia (1.5% CI [1.3-1.7] vs 1.2% CI [0.8-1.8], P = .44) or meningitis (0.16% CI [0.1-0.2] vs 0.05% CI [0-0.2], P = .36)., Conclusions: There was no difference in the rate of bacteremia or meningitis between term and preterm infants in a large multicenter cohort of febrile infants. Preterm infants had a lower rate of UTI than term infants. This is the first multicenter study to compare UTI, bacteremia, and meningitis between term and preterm febrile infants., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve gastrointestinal absorption of nutrients and may result in changes in body mass index (BMI), serum lipids, and fat-soluble vitamin levels. We hypothesized that serum lipids and vitamin levels would increase with CFTR modulator therapy and that greater increase in lipids and vitamin levels would be related to greater increase in BMI., Methods: A retrospective study was performed to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional parameters, serum lipids, and fat-soluble vitamin levels. Pre-ETI values (<2 years prior) and post-ETI values (>1 month after) were compared. Linear regression was used to evaluate whether change in BMI is associated with the change in lipid and/or vitamin levels and whether modulator duration is associated with the degree of rise in lipid and/or vitamin levels., Results: Adults and adolescents with CF (n = 137) were evaluated before and 31-300 days after starting ETI. Median BMI (adults 21.9 vs. 23.5 kg/m 2 ; adolescents 48 vs. 63 percentile) increased after initiation of ETI. Total cholesterol (126 vs. 154 mg/dL), low-density lipoprotein cholesterol (63 vs. 78 mg/dL), non-high-density lipoprotein cholesterol (84 vs. 102 mg/dL), and high density lipoprotein cholesterol (43 vs. 49 mg/dL) increased after ETI, while triglycerides and very low density lipoprotein did not change. Median values for vitamin D (34.5 vs. 38.0 ng/mL) and vitamin A (40.1 vs. 47.9 µg/dL) increased, while vitamin E did not change significantly. There was no significant correlation between BMI change or duration of modulator therapy with vitamin levels or lipid changes., Conclusion: After initiation of ETI therapy, serum lipids increased in our population, but most values remained within the normal range. Vitamins A and D levels increased post-ETI and no changes were noted in vitamin E. No significant correlation between the degree of BMI change and the magnitude of increase in lipids or vitamin levels was found., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: 5-aminosalicylates (5-ASA) are used to treat mild to moderate ulcerative colitis. Despite their lack of efficacy in Crohn disease (CD), they are still used in real-world practice. Additionally, when patients have progressive disease, they may escalate to biologic therapy, at which time 5-ASA may or may not be discontinued., Objectives: The aim of this study is to assess the clinical outcomes of patients started on 5-ASA for the treatment of pediatric CD. The secondary aims were to evaluate the outcomes of those who continue 5-ASA to those who discontinue 5-ASA upon biologic escalation., Methods: We performed a single-center retrospective chart review of pediatric CD patients from 2010 to 2019 who were initially treated with 5-ASA. Demographics, medication and laboratory data, and clinical disease activity were collected., Results: Sixty-one patients were included in the study; the majority had inflammatory CD with ileocolonic involvement. Twenty-four patients were on a concomitant immunomodulator. The majority of patients (85.2%) required escalation to biologics. Thirty-two patients (61.5%) who escalated to biologic therapy continued on 5-ASA. Eighty percent of patients achieved clinical remission at 1 year, and there was no difference between those who continued 5-ASA at time of biologic initiation compared to those who did not continue the medication. Patients who discontinued 5-ASA had an average annual cost savings of $6741., Conclusion: 5-ASA is not a durable monotherapy for the treatment of pediatric CD. Patients who require escalation from 5-ASA to biologic therapy do not benefit from concomitant 5-ASA therapy. Further prospective studies are needed to confirm these findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: This study aimed to evaluate the association between desaturation <60% (severe desaturation) during intubation and a total number of intubation attempts in the first week of life in very low birth weight (VLBW) infants with adverse long-term outcomes including bronchopulmonary dysplasia (BPD) and severe periventricular/intraventricular hemorrhage grade 3 or 4 (PIVH)., Study Design: A retrospective chart review was performed on VLBW infants intubated in the neonatal intensive care unit during the first week of life between January 2017 and July 2020. Descriptive tables were generated for two outcomes including BPD and PIVH. Multivariable logistic regression was performed for each outcome including significant predictors that differed between groups with a p -value of <0.2., Results: A total of 146 patients were included. Patients with BPD or PIVH had a lower gestational age, and patients with BPD had a lower BW. Patients with BPD had a greater number of intubation attempts in the first week of life (4 vs. 3, p  < 0.001). In multivariable logistic regression controlling for confounding variables, the odds developing BPD were higher for patients with increased cumulative number of intubation attempts in the first week of life (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.03-1.62, p  = 0.029). Post hoc analyses revealed increased odds of developing BPD with increased number of intubation encounters in the first week of life (OR: 2.20, 95% CI: 1.04-4.82, p  = 0.043). In this post hoc analysis including intubation encounters in the model; desaturation <60% during intubation in the first week of life was associated with increased odds of developing BPD (OR: 2.35, 95% CI: 1.02-5.63, p  = 0.048)., Conclusion: The odds of developing BPD for VLBW infants were higher with increased intubation attempts and intubation encounters. In a post hoc analysis, the odds of developing BPD were also higher with desaturation during intubation. Further research is needed to determine mechanisms of the relationship between complicated intubations and the development of BPD., Key Points: · Neonatal intubations often require multiple attempts.. · Neonates frequently desaturate during intubation.. · Intubation attempts are positively associated with BPD.. · Severe desaturation may be positively associated with BPD.., Competing Interests: None declared., (Thieme. All rights reserved.)

The need to understand how Community-based disparities impact morbidity and mortality in pediatric critical illness, such as traumatic brain injury. Test the hypothesis that ZIP code-based disparities in hospital utilization, including length of stay (LOS) and hospital costs, exist in a cohort of children with traumatic brain injury (TBI) admitted to a PICU using the Child Opportunity Index (COI)., Design: Multicenter retrospective cohort study., Setting: Pediatric Health Information System (PHIS) database., Patients: Children 0-18 years old admitted to a PHIS hospital with a diagnosis of TBI from January 2016 to December 2020 requiring PICU care. To identify the most severely injured children, a study-specific definition of "Complicated TBI" was created based on radiology, pharmacy, and procedure codes., Interventions: None., Main Outcomes and Measures: Using nationally normed ZIP code-level COI data, patients were categorized into COI quintiles. A low COI ZIP code has low childhood opportunity based on weighted indicators within educational, health and environmental, and social and economic domains. Population-averaged generalized estimating equation (GEE) models, adjusted for patient and clinical characteristics examined the association between COI and study outcomes, including hospital LOS and accrued hospital costs. The median age of this cohort of 8,055 children was 58 months (interquartile range [IQR], 8-145 mo). There were differences in patient demographics and rates of Complicated TBI between COI levels. The median hospital LOS was 3.0 days (IQR, 2.0-6.0 d) and in population-averaged GEE models, children living in very low COI ZIP codes were expected to have a hospital LOS 10.2% (95% CI, 4.1-16.8%; p = 0.0142) longer than children living in very high COI ZIP codes. For the 11% of children with a Complicated TBI, the relationship between COI and LOS was lost in multivariable models. COI level was not predictive of accrued hospital costs in this study., Conclusions: Children with TBI requiring PICU care living in low-opportunity ZIP codes have higher injury severity and longer hospital LOS compared with children living in higher-opportunity ZIP codes. Additional studies are needed to understand why these differences exist., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Mechanical ventilation is often used in children after cardiac surgery but can impair hemodynamics and cause lung injury. Early extubation may improve ICU length of stay and survival. We aimed to describe trends in early extubation rates and evaluate if centers that more commonly practice early extubation have better severity-adjusted outcomes., Design: Retrospective analysis was performed of admissions in the Virtual Pediatric Systems (VPS, LLC) database from 2009 to 2018. Early extubation was defined as patients extubated in the operating room or within 6 hours of PICU admission., Setting: PICUs participating in the VPS database., Patients: Children in the VPS database who underwent cardiac surgery., Interventions: None., Measurement and Main Results: Among 69,739 subjects, 20% were neonates, 47% underwent early extubation, 5.3% failed extubation, and 2.5% died. Overall, early extubation rates did not change over the study period. Centers were placed in one of four groups based on their early extubation rate in lower complexity surgeries. Centers that most commonly used early extubation had more ICU-free time among all patients in univariable analysis (lowest early extubation group, 23.8 d [interquartile range, 18.2-25.9 d]; highest early extubation group, 24.7 d [20.0-26.2 d]; p < 0.001). After adjusting for center volume, sex, age, surgical complexity, and preoperative ICU admission, increasing center-level early extubation rates were not associated with more ICU-free days. Higher center-level early extubation rate was not associated with mortality in univariable or multivariable analysis but was associated with decreased extubation failure rate (lowest early extubation group, 6.4%; highest early extubation group, 3.6%; p < 0.001)., Conclusions: In this large, multicenter database study, early extubation rates in postoperative cardiac patients did not significantly change between 2009 and 2018. Centers that performed early extubation more frequently did not have shorter ICU stays or difference in mortality rates but did have lower reintubation rates., Competing Interests: Dr. Cheifetz received funding from Philips Healthcare, Medtronic, Tim Peters, and UptoDate. Dr. Shein received funding from Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To evaluate the contribution of PICU care to increasing hospital charges for patients with bronchiolitis over a 10-year study period., Design: In this retrospective multicenter study, changes in annual hospital charges (adjusted for inflation) were analyzed using linear regression for subjects admitted to the PICU with invasive mechanical ventilation (PICU + IMV) and without IMV (PICU - IMV), and for children not requiring PICU care., Setting: Free-standing children's hospitals contributing to the Pediatric Health Information System (PHIS) database., Subjects: Children less than 2 years with bronchiolitis discharged from a PHIS hospital between July 2009 and June 2019. Subjects were categorized as high risk if they were born prematurely or had a chronic complex condition., Interventions: None., Measurements and Main Results: PICU patients were 26.5% of the 283,006 included subjects but accrued 66% of the total $14.83 billion in charges. Annual charges increased from $1.01 billion in 2009-2010 to $2.07 billion in 2018-2019, and PICU patients accounted for 83% of this increase. PICU + IMV patients were 22% of all PICU patients and accrued 64% of all PICU charges, but PICU - IMV patients without a high-risk condition had the highest relative increase in annual charges, increasing from $76.7 million in 2009-2010 to $377.9 million in 2018-2019 (374% increase, ptrend < 0.001)., Conclusions: In a multicenter cohort study of children hospitalized with bronchiolitis, PICU patients, especially low-risk children without the need for IMV, were the highest driver of increased hospital charges over a 10-year study period., Competing Interests: Dr. Shein received funding from Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Human trafficking is a global public health issue that affects pediatric patients widely. The International Labor Organization estimates children comprise approximately 25% of the identified trafficked persons globally, with domestic estimates including over 2000 children a year. Trafficked children experience a broad range of health consequences leading to interface with healthcare systems during their exploitation. In June 2018, International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) released diagnostic codes for human trafficking., Objective: To use a large, multicenter database of US pediatric hospitalizations to describe the utilization of the ICD-10-CM codes related to child trafficking, as well as the demographic and clinical characteristics of these children., Methods: This study was descriptive in nature. Encounters using data from the Pediatric Health Information System database (PHIS) with ICD-10-CM codes indicating trafficking from June 1, 2018 to March 1st, 2020 were included in the study cohort, with data collection continuing for 30 days after first hospital encounter, until March 31st, 2020. Patients 19 years old and younger were included. Condition-specific prevalence as well as demographic and clinical characteristics for patient encounters were analyzed. Study subjects were followed for 30 days after first hospital encounter to describe healthcare utilization patterns., Results: During the study period, 0.005% ( n = 293) of patient encounters in the PHIS database were identified as trafficked children. The children of our cohort were mostly female (90%), non-Hispanic Black (38%), and had public insurance (59%). Nearly two-thirds of patients ( n = 190) had a documented mental health disorder at the initial encounter, with 32.1% classified as the principal diagnosis. Our cohort had a 30-day hospital inpatient, overnight observation, or emergency department readmission rate of 16% ( n = 48)., Discussion: Our study demonstrates a low utilization of human trafficking ICD-10-CM codes in academic children's health centers, with code usage predominantly assigned to Non-Hispanic Black teenage girls. As comparison, in 2019 the National Human Trafficking Hotline identified 2,582 trafficked US children in a single year. These results suggest widespread under-recognition of child trafficking in health care settings, including the intensive care unit, in addition to racial and socioeconomic disparities amongst trafficked children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garg, Panda, Malay and Slain.)

Objectives: Injuries are the leading cause of morbidity and mortality in children ages 1 to 18 years. There are limited studies about pediatric thoracolumbar (TL) spinal injuries; the purpose of this study was to characterize TL spinal injuries among pediatric patients evaluated in US trauma centers., Methods: This was a retrospective cohort study of the National Trauma Data Bank. Patients aged 1 to 18 years with a thoracic or lumbar spinal injury sustained by blunt trauma during calendar years 2011 through 2016 were included. Cervical spinal injuries, death before arrival, or penetrating trauma were excluded. The data was abstracted, and missing data was addressed by imputations. Data was analyzed using descriptive statistics and multinomial logistic regressions., Results: A total of 20,062 patients were included in the study. Thoracolumbar spinal injuries were more commonly sustained by 16- to 17-year-olds (45.7%), boys (56.6%), and White (74.8%). The injuries were often from a motor vehicle collision (MVC) (55.2%) and resulted in a bone injury (82.3%). Mechanism of injury and age were significant in predicting injury type. A fall was more likely than MVC to result in disc injury (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.24-2.33), strain injury (OR, 1.18; 95% CI, 1.05-1.34), or cord injury (OR, 1.27; 95% CI, 1.12-1.45). Younger children were more likely than adolescents to present with disc injury (OR, 2.79; 95% CI, 1.75-4.45), cord injury (OR, 1.46; 95% CI, 1.18-1.81), or strain injury (OR, 1.37; 95% CI, 1.09-1.72)., Conclusions: To our knowledge, this is the largest pediatric TL spinal study. Clinicians should consider TL spinal injuries when adolescents present after an MVC, and specifically, TL spinal cord injuries when young children present after a fall. Additionally, pediatric TL spinal injury prevention should highlight motor vehicle and fall safety., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The use of 16S rRNA sequencing in culture-negative infections has improved identification of bacterial pathogens in select scenarios, but its clinical impact requires further elucidation, especially in the pediatric population. This retrospective study aims to determine the clinical utility of 16S rRNA sequencing on the clinical management of pediatric culture-negative infections in our institution. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples ( p < 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility ( n = 9, 30%), followed equally by joint fluid ( n = 6, 20%) and bone ( n = 6, 20%), with no difference between fluid and fresh tissue specimens ( p = 0.346). Although the difference was not statistically significant ( p = 0.4111), the overall use of broad-spectrum coverage was decreased. The median number of antibiotics was decreased from two to one ( p < 0.0001) based on 16S rRNA sequencing results. The results suggest that 16S rRNA sequencing has a significant impact on decreasing the number of antibiotics used in the treatment of pediatric culture-negative infections. 16S rRNA sequencing performed on pulmonary specimens has the highest likelihood of identifying a pathogen compared to other specimen types. Additional cost-benefit analysis needs to be completed to further determine clinical benefit.

Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity., Methods: We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution. IBD patients were graded using the simple endoscopic score for Crohn's disease or Mayo endoscopic score for ulcerative colitis. Histologic slides were graded using the Geboes method., Results: Three-hundred thirty-one patients were included in the study and 107 had IBD. For endoscopy, median FC was lowest for all IBD patients with no disease (181 μg/g) and highest in severe disease (921 μg/g), with significant difference between no disease and moderate and severe disease ( P = 0.019, 0.003), and between mild and severe disease ( P = 0.012). For histology, median FC was lowest with no disease (328 μg/g) and highest in severe disease (895 μg/g), with significant difference between no disease and moderate and severe disease ( P = 0.021, 0.018). The control population had a significantly lower median FC than the IBD population in endoscopic remission (35.5 versus 181 μg/g; P = 0.018)., Conclusions: There was a linear increase in FC values associated with increasing disease severity in the undifferentiated IBD cohort. Values for IBD patients in endoscopic remission were significantly different from our control population. FC may be a useful noninvasive marker to assess disease severity., Competing Interests: Dr Sferra is a member of a scientific advisory committee for a research study sponsored by Merck & Co., Inc. Dr. Moses is on the speaker’s bureau for AbbVie, Inc. The remaining authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)