Temporal Trends of Neonatal Surgical Conditions in Texas and Accessibility to Pediatric Surgical Care.

INTRODUCTION: Texas consistently accounts for approximately 10% of annual national births, the second highest of all US states. This temporal study aimed to evaluate incidences of neonatal surgical conditions across Texas and to delineate regional pediatric surgeon accessibility. METHODS: The Texas Birth Defects Registry was queried from 1999 to 2018, based on 11 well-established regions. Nine disorders (30,476 patients) were identified as being within the operative scope of pediatric surgeons: biliary atresia (BA), pyloric stenosis (PS), Hirschsprung's disease, stenosis/atresia of large intestine/rectum/anus, stenosis/atresia of small intestine, tracheoesophageal fistula/esophageal atresia, gastroschisis, omphalocele, and congenital diaphragmatic hernia. Annual and regional incidences were compared (/10,000 births). Statewide pediatric surgeons were identified through the American Pediatric Surgical Association directory. Regional incidences of neonatal disorder per surgeon were evaluated from 2010 to 2018 as a surrogate for provider disparity. RESULTS: PS demonstrated the highest incidence (14.405/10,000), while BA had the lowest (0.707/10,000). Overall, incidences of PS and BA decreased significantly, while incidences of Hirschsprung's disease and small intestine increased. Other diagnoses remained stable. Regions 2 (48.24/10,000) and 11 (47.79/10,000) had the highest incidence of neonatal conditions; Region 6 had the lowest (34.68/10,000). Three rural regions (#2, 4, 9) lacked pediatric surgeons from 2010 to 2018. Of regions with at least one surgeon, historically underserved regions (#10, 11) along the Texas-Mexico border consistently had the highest defect per surgeon rates. CONCLUSIONS: There are temporal and regional differences in incidences of neonatal conditions treated by pediatric surgeons across Texas. Improving access to neonatal care is a complex issue that necessitates collaborative efforts between state legislatures, health systems, and providers.

Extracorporeal Membrane Oxygenation for Adult Patients With Neoplasms: Outcomes and Trend Over the Last 2 Decades.

Extracorporeal membrane oxygenation (ECMO) is utilized in the management of severe respiratory and circulatory failure. Advanced malignancy is a relative contraindication, but the indication for ECMO in the oncologic population has not been clearly established because of the wide spectrum of malignant disease and prognoses. The Extracorporeal Life Support Organization database was queried for patients older than 18 years with an International Classification of Diseases code of neoplasm over the past 2 decades (2000-2019). The data were divided into 2 decades to analyze and compare the trends with background and outcomes. One thousand six-hundred ninety-seven patients met inclusion criteria from the latest decade which is over 15 times the previous decade (n = 110). Compared with the previous decade, ECMO was used more in patients with older age (56 vs . 50.5 years old; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation (ECPR) support type ( p = 0.011), and lower oxygenation index (23.0 vs . 35.6; p < 0.001) in the latest decade. Although overall survival did not show significant improvement overall (38.9% vs . 33.6%; p = 0.312), survival in pulmonary ECMO has significantly improved in the latest decade (41.6% vs . 29.1%; p = 0.032). Compared with the previously reported data for all adult ECMO, our patients had a significantly lower survival with pulmonary (41.6% vs . 61.1%; p < 0.001) and cardiac (38.4% vs . 44.3%; p = 0.008) support while not with ECPR.

Regulation of Key Immune-Related Genes in the Heart Following Burn Injury.

Immune cascade is one of major factors leading to cardiac dysfunction after burn injury. TLRs are a class of pattern-recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen. The Rat Toll-Like Receptor (TLR) Signaling Pathway RT² Profiler PCR Array profiles the expression of 84 genes central to TLR-mediated signal transduction and innate immunity, and is a validated tool for identifying differentially expressed genes (DEGs). We employed the PCR array to identify burn-induced cardiac TLR-signaling-related DEGs. A total of 38 up-regulated DEGs and 19 down-regulated DEGs were identified. Network analysis determined that all DEGS had 10 clusters, while up-regulated DEGs had 6 clusters and down-regulated DEGs had 5 clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were involved in TLR signaling, the RIG-I-Like receptor signaling pathway, the IL-17 signaling pathway, and the NFkB signaling pathway. Function analysis indicated that DEGs were associated with Toll-like receptor 2 binding, Lipopeptide binding, Toll-like receptor binding, and NAD(P)+ nucleosidase activity. The validation of 18 up-regulated DEGs (≥10-fold change) and 6 down-regulated DEGs (≤5-fold change) demonstrated that the PCR array is a trusted method for identifying DEGs. The analysis of validated DEG-derived protein-protein interaction networks will guide our future investigations. In summary, this study not only identified the TLR-signaling-pathway-related DEGs after burn injury, but also confirmed that the burn-induced cardiac cytokine cascade plays an important role in burn-induced heart dysfunction. The results will provide the novel therapeutic targets to protect the heart after burn injury.

Reviewing ACGME Plastic Surgery Fellowship Case Logs: Is Surgical Experience Increasing?

INTRODUCTION: Over the last decade, there has been a 32% decrease in independent plastic surgery fellowships. The growing prevalence of 6-year integrated plastic surgery residencies, duty hour restrictions, and new subspecialty training fellowships for general surgeons have changed the training experience of plastic surgery fellows. METHODS: A retrospective review of the Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating fellows of independent plastic surgery fellowships in the United States was conducted from 2011 to 2019. A linear regression analysis was conducted for each case log code and category, and a 95% level of confidence was assumed (α = 0.05). RESULTS: In 2011, 141 residents from 69 programs graduated with an average of 1469.7 cases. In 2019, 84 residents from 47 programs graduated with an average of 1952 cases. Index procedures significantly increased overall during the 9 y (P < 0.001). Categorical cases increased in esthetics (P < 0.001), including facelift, browlift, blepharoplasty, and more. Categorical cases increased in reconstructive surgery (P < 0.001), including treatment of deformities of the skin, lower extremities, and trunk, nerve decompression, and hand reconstruction. In breast procedures, an increase was seen in the reduction of mammoplasty, reconstruction, and treatment of other breast deformities. In head and neck procedures, an increase was seen in resection of head and neck neoplasms and secondary cleft lip repair. Decreases in procedural numbers were seen in primary cleft lip repair and hand reconstruction by primary closure. CONCLUSIONS: Despite a 32% decline in the number of independent plastic surgery fellowships over the last 9 y, plastic surgery fellows are obtaining significantly more surgical experience, both in esthetic and reconstructive surgery.

Nuclear Factor Erythroid 2-Related Factor 2 Activation and Burn-Induced Cardiac Dysfunction.

BACKGROUND: Our previous studies have found that burn injury induces cardiac dysfunction through interruption of the antioxidant-response element (ARE) pathway in cardiac mitochondria. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator that activates many antioxidant enzymes. Oltipraz (Olti) is a Nrf2 activator and a well-known inducer of NQO1 along with other enzymes that comprise the Nrf2-associated antioxidants. We propose that Nrf2 activation will induce the ARE pathway, leading to abrogation of burn-induced cardiac dysfunction. STUDY DESIGN: In this study, we investigated the effect of Nrf2-deficiency in mice on burn-induced cardiac dysfunction. Wild-type (WT) and Nrf2-deficient mice received 30% total body surface area burn injury and were treated with or without Olti and then harvested at 3 hours and 24 hours post burn (3 hpb and 24 hpb). RESULTS: As expected, Nrf2-deficient mice exhibited exacerbated cardiac dysfunction after burn injury, as measured by Vevo 2100 echocardiography. Electron microscopy showed that Nrf2 depletion worsened burn injury-induced cardiac mitochondrial damage. In addition, Nrf2 depletion increased cardiac mitochondrial dysfunction and myocardial fibrosis after burn injury. Treatment with Olti ameliorated the heart dysfunction in burned Nrf2-/+ mice, improved cardiac mitochondrial structure and oxidative phosphorylation, as well as decreased cardiac fibrosis. These results suggest that Nrf2 and its downstream targets modulate cardiac function after burn injury. CONCLUSIONS: In summary, Nrf2 depletion worsens cardiac dysfunction after burn injury. Nrf2 activation, with a drug such as Olti, offers a promising therapeutic strategy for abrogating burn-induced cardiac dysfunction.

Outcome of Extracorporeal Membrane Oxygenation for Pediatric Patients With Neoplasm: An Extracorporeal Life Support Organization Database Study (2000-2019).

OBJECTIVES: This study update in usage and outcomes of pediatric extracorporeal membrane oxygenation (ECMO) for patients with neoplasm analyzed according to demographics, clinical variables, and complications. DESIGN: Retrospective database review of the Extracorporeal Life Support Organization registry from the last 2 decades (2000-2019). The data were divided between two decades in order to compare patients' backgrounds and outcomes over time. SETTING: ECMO centers reporting to Extracorporeal Life Support Organization. PATIENTS: Patients equal to or younger than 18 years old with International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes that referred to neoplasms who were managed with ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, cancer subtype, clinical variables, and ECMO complications were assessed in relation to the primary study outcome of survival to hospital discharge. Nine-hundred two patients met inclusion criteria; 699 patients were in the latest decade, which is more than three times the number from the previous decade (203 patients). On univariate analysis, compared with the previous decade, in the later decade, ECMO was more frequently applied in patients with pre-ECMO cardiac arrest (31.3% vs 17.1%; p < 0.001), and/or lower oxygenation index (38.0 vs 48.1; p < 0.001). We failed to identify a difference in survival between the 2 decades (42.8% vs 37.9%; p = 0.218). On multivariable analysis, diagnosis of hematologic malignancy, post-cardiopulmonary resuscitation support type, hematopoietic stem cell transplant, and age older than seven were each associated with greater odds of mortality. CONCLUSIONS: The use of ECMO in children with neoplasm has expanded over the latest decade with changes in patient selection. Mortality remains unchanged. Hence, although the clinician still should stay cautious in its application, ECMO can be considered as an option to rescue pediatric oncologic patients in the setting of worsening cardiopulmonary status in the PICU.

CVP and echo Measurements are Associated with Improved Outcomes in Patients with Gastrointestinal (GI) Hemorrhage: A Retrospective Analysis of the MIMIC- IV Database.

Purpose: Mortality associated with acute Gastrointestinal (GI) hemorrhage in intensive care units (ICU) has remained high in patients suffering from hemodynamic instability. Prompt recognition and rapid assessment of bleeding severity are crucial to improve survival. Central venous pressure (CVP) monitoring is commonly used for early recognition of intravascular imbalances, but its effectiveness in predicting fluid responsiveness is often questioned. Echocardiography (echo) is a rapid, noninvasive method to repeatedly assess cardiac function and fluid responsiveness. This study investigated the impact of CVP and echo measurements on the outcomes of critically ill patients with GI hemorrhage. Methods: The study was based on the Medical Information Mart for Intensive Care IV (MIMIC- IV) database. Patients were divided into four groups according to the usage of CVP and/or echo. The primary outcomes were 7-day, 14-day, 28-day, and overall mortalities after ICU admission. Cox Proportional-Hazards Models were used to elucidate the relationship between CVP/ Echo monitoring and mortality. The severity of illness of patients were adjusted by qSOFA score, SOFA score and base deficit level at admission. Results: Among 1705 eligible patients, 82 patients had both CVP and echo, 85 had CVP only, and 116 had Echo only. The results of survival analysis indicated that, comparing with those without either CVP or echo, the echo utilization was associated with improved mortalities at all time points during ICU stay for patients with moderate GI hemorrhage, and the combined use of CVP and echo was associated with lower 7-day,14-day and overall mortalities for patients with severe GI hemorrhage. Conclusion: Early usage of CVP and echo monitoring or echo alone are associated with lower mortality in the short and long-term when compared to patients without either measurement. Clinicians should consider goal-directed resuscitation guided by echo with/without CVP in patients with GI hemorrhage early after admission to ICU.

Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies.

Systemic chemotherapeutics remain the standard of care for most malignancies even though they frequently suffer from narrow therapeutic index, poor serum solubility, and off-target effects. In this study, we have encapsulated etoposide, a topoisomerase inhibitor effective against a wide range of cancers, in surface-modified liposomes decorated with anti-GD2 antibodies. We characterized the properties of the liposomes using a variety of methods including dynamic light scattering, electron microscopy, and Fourier transformed infrared spectroscopy. We examined whether these immunoliposomes were able to target cell lines expressing varying levels of surface GD2 and affect cellular proliferation. Anti-GD2 liposomes were generally targeted in a manner that correlated with GD2 expression and inhibited proliferation in cell lines to which they were efficiently targeted. The mechanism by which the immunoliposomes entered targeted cells appeared to be via clathrin-dependent uptake as demonstrated using flow cytometry and confocal microscopy. These studies suggest that anti-GD2-targeted, etoposide-loaded liposomes represent a potential strategy for more effective delivery of anti-cancer drugs that could be used for GD2 positive tumors.