The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis.

FoxP3 is an essential transcription factor (TF) for immunologic homeostasis, but how it utilizes the common forkhead DNA-binding domain (DBD) to perform its unique function remains poorly understood. We here demonstrated that unlike other known forkhead TFs, FoxP3 formed a head-to-head dimer using a unique linker (Runx1-binding region [RBR]) preceding the forkhead domain. Head-to-head dimerization conferred distinct DNA-binding specificity and created a docking site for the cofactor Runx1. RBR was also important for proper folding of the forkhead domain, as truncation of RBR induced domain-swap dimerization of forkhead, which was previously considered the physiological form of FoxP3. Rather, swap-dimerization impaired FoxP3 function, as demonstrated with the disease-causing mutation R337Q, whereas a swap-suppressive mutation largely rescued R337Q-mediated functional impairment. Altogether, our findings suggest that FoxP3 can fold into two distinct dimerization states: head-to-head dimerization representing functional specialization of an ancient DBD and swap dimerization associated with impaired functions.

The landscape of immune dysregulation in pediatric sepsis at a single-cell resolution.

Recognizing immune dysregulation as a hallmark of sepsis pathophysiology, leukocytes have attracted major attention of investigation. While adult and pediatric sepsis are clinically distinct, their immunological delineation remains limited. Single cell technologies facilitated the characterization of immune signatures. We tackled to delineate immunological profiles of pediatric sepsis at a single-cell level by analyzing blood samples from six septic children, at both acute and recovery phases, and four healthy children. 16 single-cell transcriptomic datasets were analyzed and compared to adult sepsis dataset. We showed a unique shift in neutrophil subpopulations and functions between acute and recovery phases, along with the regulatory role of resistin. Neutrophil signatures were comparable between adult and pediatric sepsis. Innate-like CD4 T cells were predominantly and uniquely observed in acute phase of pediatric sepsis. Our study serves as a rich source of information about the phenotypic diversity and trajectory of circulating immune cells during pediatric sepsis.

Volatile anesthetic isoflurane exposure facilitates Enterococcus biofilm infection.

Enterococcus faecalis (E. faecalis) is one of the major pathogenic bacteria responsible for surgical site infections. Biofilm infections are major hospital-acquired infections. Previous studies suggested that ions could regulate biofilm formation in microbes. Volatile anesthetics, frequently administered in surgical setting, target ion channels. Here, we investigated the role of ion channels/transporters and volatile anesthetics in the biofilm formation by E. faecalis MMH594 strain and its ion transporter mutants. We found that a chloride transporter mutant significantly reduced biofilm formation compared to the parental strain. Downregulation of teichoic acid biosynthesis in the chloride transporter mutant impaired biofilm matrix formation and cellular adhesion, leading to mitigated biofilm formation. Among anesthetics, isoflurane exposure enhanced biofilm formation in vitro and in vivo. The upregulation of de novo purine biosynthesis pathway by isoflurane exposure potentially enhanced biofilm formation, an essential process for DNA, RNA, and ATP synthesis. We also demonstrated that isoflurane exposure to E. faecalis increased cyclic-di-AMP and extracellular DNA production, consistent with the increased purine biosynthesis. We further showed that isoflurane enhanced the enzymatic activity of phosphoribosyl pyrophosphate synthetase (PRPP-S). With the hypothesis that isoflurane directly bound to PRPP-S, we predicted isoflurane binding site on it using rigid docking. Our study provides a better understanding of the underlying mechanisms of E. faecalis biofilm formation and highlights the potential impact of an ion transporter and volatile anesthetic on this process. These findings may lead to the development of novel strategies for preventing E. faecalis biofilm formation and improving patient outcomes in clinical settings.

Perioperative Factors and Radiographic Severity Scores for Predicting the Duration of Mechanical Ventilation After Arterial Switch Surgery.

OBJECTIVES: Cardiac surgery on cardiopulmonary bypass (CPB) during the neonatal period can cause perioperative organ injuries. The primary aim of this study was to determine the incidence and risk factors associated with postoperative mechanical ventilation duration and acute lung injury after the arterial switch operation (ASO). The secondary aim was to examine the utility of the Brixia score for characterizing postoperative acute lung injury (ALI). DESIGN: A retrospective study. SETTING: A single-center university hospital. PARTICIPANTS: A total of 93 neonates with transposition of great arteries with intact ventricular septum (dTGA IVS) underwent ASO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2015 to December 2022, 93 neonates with dTGA IVS were included in the study. The cohort had a median age of 4.0 (3.0-5.0) days and a mean weight of 3.3 ± 0.5 kg. About 63% of patients had ≥48 hours of postoperative mechanical ventilation after ASO. Risk factors included prematurity, post-CPB transfusion of salvaged red cells, platelets and cryoprecipitate, and postoperative fluid balance by univariate analysis. The larger transfused platelet volume was associated with the risk of ALI by multivariate analysis. The median baseline Brixia scores were 11.0 (9.0-12.0) and increased significantly in the postoperative day 1 in patients who developed moderate ALI 24 hours after admission to the intensive care unit (15.0 [13.0-16.0] v 12.0 [10.0-14.0], p = 0.046). CONCLUSIONS: Arterial switch operation results in a high incidence of ≥48-hour postoperative mechanical ventilation. Blood component transfusion is a potentially modifiable risk factor. The Brixia scores also may be used to characterize postoperative acute lung injury.

Age-dependent transcriptomic profiles of leukocytes in pediatric population.

Immunity at birth is considered immature. Following birth, our immune function is considered to grow and reach maturation over time. To obtain granular information of leukocyte functions and transcriptomic profiles in pediatric cohort, we examined leukocyte profiles in infants, preschool and school children using single cell RNA sequencing of their peripheral blood mononuclear cells (PBMCs). Monocytes and natural killer (NK) cells showed immaturity in infants. Their innate and adaptive immunity was developed by preschool age. Adaptive immune cells showed different maturation patterns. CD4, CD8 naïve T cells and plasma cells continued to mature untill school age. In CD8 naïve T cells, innate immunity was upregulated in infants, in support of our knowledge that they manifests more innate cell-like phenotype soon after birth. Many signaling pathways have been differentially up- and/or down-regulated in infants, preschool and school children. Their contribution to the development of the immune system needs to be delineated.

Perioperative prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.

OBJECTIVE: Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries. METHODS: We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). RESULTS: A total of 12 RCTs (2,209 patients) were included in our review. Corticosteroids administration was associated with a nonsignificant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I2 = 0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I2 = 41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I2 = 0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I2 = 0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use. CONCLUSIONS: The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.

Propofol directly binds to and inhibits TLR7.

Sedatives/anesthetics are important medical tools to facilitate medical care and increase patients' comfort. Increasingly, there is recognition that sedatives/anesthetics can modulate immune functions. Toll-like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single-strand RNA virus such as influenza and SARS-CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a critical anti-viral response. For example, patients with TLR7 variants including loss-of- function variants were associated with severe COVID-19. Taken together, it is important to determine if sedatives/anesthetics mitigate TLR7 function. We have previously showed that TLR7-mediated activation was not affected by volatile anesthetics. However, we found that propofol attenuated TLR7 activation among intravenous sedatives in the reporter assay. TLR7 agonist R837 stimulation increased TNF-α, IL-1ß, IL-6, IL-10, and IFN-ß mRNA levels in bone marrow-derived dendritic cells, while these levels were attenuated by propofol. Our murine lung slice experiments showed that propofol attenuated IFN production. R837 increased IFN-ß expression in the lungs, and propofol attenuated IFN-ß expression in an in vivo model of R837 intranasal instillation. We also found that propofol directly bound to and hindered its association of TLR7 with MyD88. Our analysis using fropofol, propofol derivative showed that the hydroxyl group in propofol was important for propofol-TLR7 interaction.

Isoflurane attenuates sepsis-associated lung injury.

Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of sedatives in lung injury. We examined volatile anesthetic isoflurane, which is commonly used in surgical setting, but also used as an alternative sedative in intensive care settings in European countries and Canada. We found that isoflurane exposure attenuated neutrophil recruitment to the lungs in mice suffering from experimental polymicrobial abdominal sepsis. We found that isoflurane attenuated one of major neutrophil chemoattractants LTB4 mediated response via its receptor BLT1 in neutrophils. Furthermore, we have shown that isoflurane directly bound to BLT1 by a competition assay using newly developed labeled BLT1 antagonist, suggesting that isoflurane would be a BLT1 antagonist.

Mutagenesis and homology modeling reveal a predicted pocket of lysophosphatidylcholine acyltransferase 2 to catch Acyl-CoA.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that elicits various cellular functions and promotes several pathological events, including anaphylaxis and neuropathic pain. PAF is biosynthesized by two types of lyso-PAF acetyltransferases: lysophosphatidylcholine acyltransferase 1 (LPCAT1) and LPCAT2, which are constitutive and inducible forms of lyso-PAF acetyltransferase, respectively. Because LPCAT2 mainly produces PAF under inflammatory stimuli, understanding the structure of LPCAT2 is important for developing specific drugs against PAF-related inflammatory diseases. Although the structure of LPCAT2 has not been determined, the crystal structure was reported for Thermotoga maritima PlsC, an enzyme in the same gene family as LPCAT2. Here, we identified residues in mouse LPCAT2 essential for its enzymatic activity and a potential acyl-coenzyme A (CoA)-binding pocket, based on homology modeling of mouse LPCAT2 with PlsC. We also found that Ala115 of mouse LPCAT2 was important for acyl-CoA selectivity. In conclusion, these results predict the three-dimensional (3D) structure of mouse LPCAT2. Our findings have implications for the future development of new drugs against PAF-related diseases.

Predictive Factors for Postoperative Intensive Care Unit Admission and Mechanical Ventilation After Cardiac Catheterization for Pediatric Pulmonary Vein Stenosis.

OBJECTIVE: To investigate the predictive factors for postoperative intensive care unit (ICU) admission and mechanical ventilation (MV) after cardiac catheterization for pediatric pulmonary vein stenosis (PVS). DESIGN: A retrospective observational study. SETTING: At a single tertiary academic pediatric medical center. PARTICIPANTS: Four hundred seventy-three pediatric patients diagnosed with PVS and who underwent cardiac catheterization from 2011 to 2021. MEASUREMENTS AND MAIN RESULTS: Univariate and multivariate analyses were performed for associated risk factors. The incidence of postoperative ICU admission was 46.5% (n = 220); among these, 93.4% (n = 206) required MV. Independent risk factors included male sex (odds ratio [OR] 3.93, p = 0.002 in ICU group; OR 2.89, p = 0.013 in MV group), low body weight (OR 0.80, p = 0.003 in ICU group; OR 0.79, p = 0.002 in MV group), preoperative oxygen supplement (OR 4.01, p = 0.002 in ICU group; OR 3.67, p = 0.003 in MV group), high PVS severity score (OR 1.15, p = 0.028 in ICU group), intraoperative hypotension requiring inotrope (OR 4.03, p = 0.011 in ICU group; OR 2.89, p = 0.035 in MV group), intraoperative red blood cell transfusion (OR 3.25, p = 0.023 in ICU group; OR 4.09, p = 0.005 in MV group), low preintervention PaO2/FIO2 ratio (OR 0.63, p = 0.009 in ICU group; OR 0.59, p = 0.002 in MV group), and high preintervention right ventricular systolic pressure (OR 1.39, p = 0.004 in ICU group; OR 1.27, p = 0.023 in MV group). CONCLUSION: The incidences of postoperative ICU admission and MV in this subgroup were relatively high. The identification of risk factors is useful in predicting and triaging the need for postoperative ICU admission and MV for the improvement of patient care.

Exploring Noncardiac Surgical Needs From Infancy to Adulthood in Patients With Congenital Heart Disease.

OBJECTIVES: As life expectancy for patients born with congenital heart disease (CHD) continues to rise, these patients will present increasingly for noncardiac surgery during childhood and adolescence. This study aimed to map the lifespan of noncardiac surgical needs among patients with CHD and explore how these needs may change over time. DESIGN: All patients with CHD presenting for noncardiac surgery between 2008 and 2014 were selected for review. SETTING: The study was conducted at a single urban academic tertiary pediatric hospital. PARTICIPANTS: All patients with CHD presenting for noncardiac surgery during the study period were included and grouped by cardiac diagnosis. INTERVENTIONS: Descriptive analysis included patient demographics, CHD diagnosis, procedures performed, and clinical data, including baseline saturation and underlying cardiac function. MEASUREMENTS AND MAIN RESULTS: A total of 3,011 noncardiac surgical procedures were performed on patients with CHD during the study period. The most common CHD diagnoses were patent ductus arteriosus (27.6%), ventricular septal defects (24.7%), and patent foramen ovale (24.3%). The median age was 4 years, 87% of all the patients were ≤10 years, and 41% had associated syndromes. Of the patients, 76% underwent a preoperative echocardiogram, and 10% had depressed cardiac function at the time of surgery. The most common procedures performed were ear, nose, and throat (20%), general surgery (14%), and radiology (11%). Intraoperative events were reported in 488 out of 3,010 encounters (16.2%), with the highest rates reported in patients with single-ventricle physiology (55/179; 30.7%). CONCLUSIONS: These findings suggested a greater burden of noncardiac surgery in lower age groups, with ear, nose, and throat and general surgery most common in young children and orthopedic and dental procedures increasing in adolescence.

The Characterization of Postoperative Mechanical Respiratory Requirement in Neonates and Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass in a Single Tertiary Institution.

OBJECTIVES: Although neonates and infants undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at high risk of developing perioperative morbidity and mortality, including lung injury, the intraoperative profile of lung injury in this cohort is not well-described. Given that the postoperative course of patients in the pediatric cardiac surgical arena has become increasingly expedited, the objective of this study was to characterize the profiles of postoperative mechanical ventilatory support in neonates and infants undergoing cardiac surgery on CPB and to examine the characteristics of lung mechanics and lung injury in this patient population who are potentially amendable to early postoperative recovery in a single tertiary pediatric institution. DESIGN: A retrospective data analysis of neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. SETTING: A single-center, university teaching hospital. PARTICIPANTS: The study included 328 neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. INTERVENTIONS: A subset of 128 patients were studied: 58 patients undergoing ventricular septal defect (VSD) repair, 36 patients undergoing complete atrioventricular canal (CAVC) repair, and 34 patients undergoing bidirectional Glenn (BDG) shunt surgery. MEASUREMENTS AND MAIN RESULTS: Of the entire cohort, 3.7% experienced in-hospital mortality. Among all surgical procedures, VSD repair (17.7%) was the most common, followed by CAVC repair (11.0%) and BDG shunt surgery (10.4%). Of patients who underwent VSD repair, CAVC repair, and BDG shunt surgery, 65.5%, 41.7%, and 67.6% were off mechanical ventilatory support within 24 hours postoperatively, respectively. In all three of the surgical repairs, lung compliance decreased after CPB compared to pre-CPB phase. Sixty point three percent of patients with VSD repair and 77.8% of patients with CAVC repair showed a PaO2/FIO2 (P/F) ratio of <300 after CPB. Post- CPB P/F ratios of 120 for VSD patients and 100 for CAVC patients were considered as optimal cutoff values to highly predict prolonged (>24 hours) postoperative mechanical ventilatory support. A higher volume of transfused platelets also was associated with postoperative ventilatory support ≥24 hours in patients undergoing VSD repair, CAVC repair, and BDG shunt surgery. CONCLUSIONS: There was a high incidence of lung injury after CPB in neonates and infants, even in surgeries amendable for early recovery. Given that CPB-related factors (CPB duration, crossclamp time) and volume of transfused platelet were significantly associated with prolonged postoperative ventilatory support, the underlying cause of cardiac surgery-related lung injury can be multi-factorial.

SerpinB1 controls encephalitogenic T helper cells in neuroinflammation.

SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17-expressing T cells. Here, we show that serpinB1 (Sb1) is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, Sb1-/- mice are resistant to EAE with a paucity of T helper (TH) cells that produce two or more of the cytokines, IFNγ, GM-CSF, and IL-17. These multiple cytokine-producing CD4 cells proliferate extremely rapidly; highly express the cytolytic granule proteins perforin-A, granzyme C (GzmC), and GzmA and surface receptors IL-23R, IL-7Rα, and IL-1R1; and can be identified by the surface marker CXCR6. In Sb1-/- mice, CXCR6+ TH cells are generated but fail to expand due to enhanced granule protease-mediated mitochondrial damage leading to suicidal cell death. Finally, anti-CXCR6 antibody treatment, like Sb1 deletion, dramatically reverts EAE, strongly indicating that the CXCR6+ T cells are the drivers of encephalitis.

Mechanistic consideration of the effect of perioperative volatile anesthetics on phagocytes.

A growing literature has shown that volatile anesthetics are promiscuous molecules targeting multiple molecules, some of which are critical for immunological functions. We focused on studies that delineated target molecules of volatile anesthetics on immune cells and summarized the effects of volatile anesthetics on immune functions. We also presented the perspectives of studying volatile anesthetics-mediated immunomodulation.

Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung.

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.

The effect of anesthetics on toll like receptor 9.

Toll like receptors (TLRs) are critical receptors to respond to danger signals, and their functions are relevant in the perioperative period. We previously reported that volatile anesthetics directly bound to TLR2 and TLR4 and attenuated their functions. Given that TLR9 can respond to mitochondrial DNA, a danger signal that is released upon tissue injury, we examined the role of anesthetics on TLR9 function. Our reporter assay showed that volatile anesthetics isoflurane and sevoflurane increased the activation of TLR9, while propofol attenuated it. TLR9 activation occurs via its dimerization. The dimerization is facilitated by unmethylated cytosine-phosphate-guanine (CpG) DNA as well as DNA containing cytosine at the second position from 5'-end (5'-xCx DNA). Our structural analysis using photoactivable anesthetics and rigid docking simulation showed that isoflurane and sevoflurane bound to both TLR9 dimer interface and 5'-xCx DNA binding site. Propofol bound to the TLR9 antagonist binding site. This is the first illustration that anesthetics can affect the binding of nucleic acids to their receptor. This study sets the foundation for the effect of anesthetics on TLR9 and will pave the way for future studies to determine the significance of such interactions in the clinical setting.

The Role of Anesthetic Management in Surgical Site Infections After Pediatric Intestinal Surgery.

BACKGROUND: Although surgical site infections (SSIs) remain a significant health care issue, a limited number of studies have analyzed risk factors for SSIs in children, particularly the role of intraoperative anesthetic management. Pediatric patients are less likely to have major adult risk factors for SSIs such as smoking and diabetes. Thus children may be more suitable as a cohort for examining the role of intraoperative anesthetics in SSIs. AIM: We examined an association between SSI incidence and anesthetic management in children who underwent elective intestinal surgery in a single institution. METHODS: We performed a retrospective study of 621 patients who underwent elective intestinal surgery under general anesthesia between January 2017 and September 2019, with primary outcome as the incidence of SSIs. We compared patients who were dichotomized in accordance with the median of the sevoflurane dose. We used propensity score (PS) pairwise matching of these patients to avoid selection biases. PS matching yielded 204 pairs of patients. RESULTS: We found that higher doses of sevoflurane were associated with a higher incidence of SSIs (9.8% versus 3.9%, P = 0.019). We adjusted for intraoperative factors that were not included in the PS adjustment factors, and multivariate regression analysis after PS matching showed compatible results (odds ratio: 2.58, 95% confidence interval: 1.11-6.04, P = 0.028). CONCLUSIONS: Higher doses of sevoflurane are associated with increased odds of SSIs after pediatric elective intestinal surgery. A randomized controlled study of volatile anesthetic-based versus intravenous anesthetic-based anesthesia will be needed to further determine the role of anesthetic drugs in SSI risk.

Risk factors for pediatric surgical site infection following neurosurgical procedures for hydrocephalus: a retrospective single-center cohort study.

BACKGROUND: Infection is a major complication following cerebral spinal fluid (CSF) diversion procedures for hydrocephalus. However, pediatric risk factors for surgical site infection (SSI) are currently not well defined. Because a SSI prevention bundle is increasingly introduced, the purpose of this study was to evaluate risk factors associated with SSIs following CSF diversion surgeries following a SSI bundle at a single quaternary care pediatric hospital. METHODS: We performed a retrospective cohort study of patients undergoing CSF diversion procedures from 2017 to 2019. SSIs were identified prospectively through continuous surveillance. We performed unadjusted logistic regression analyses and univariate analyses to determine an association between SSIs and patient demographics, comorbidities and perioperative factors to identify independent risk factors for SSI. RESULTS: We identified a total of 558 CSF diversion procedures with an overall SSI rate of 3.4%. The SSI rates for shunt, external ventricular drain (EVD) placement, and endoscopic third ventriculostomy (ETV) were 4.3, 6.9 and 0%, respectively. Among 323 shunt operations, receipt of clindamycin as perioperative prophylaxis and presence of cardiac disease were significantly associated with SSI (O.R. 4.99, 95% C.I. 1.27-19.70, p = 0.02 for the former, and O.R. 7.19, 95% C.I. 1.35-38.35, p = 0.02 for the latter). No risk factors for SSI were identified among 72 EVD procedures. CONCLUSION: We identified receipt of clindamycin as perioperative prophylaxis and the presence of cardiac disease as risk factors for SSI in shunt procedures. Cefazolin is recommended as a standard antibiotic for perioperative prophylaxis. Knowing that unsubstantiated beta-lactam allergy label is a significant medical problem, efforts should be made to clarify beta-lactam allergy status to maximize the number of patients who can receive cefazolin for prophylaxis before shunt placement. Further research is needed to elucidate the mechanism by which cardiac disease may increase SSI risk after shunt procedures.

Left Ventricular Outflow Tract Gradient Is Associated With Coronary Artery Obstruction in Children With Williams-Beuren Syndrome.

OBJECTIVES: Patients with Williams-Beuren syndrome are associated with a high risk of hemodynamic collapse during sedation and/or anesthesia, presumably due to occult coronary obstruction. The objective of this study was to determine the association between transthoracic echocardiogram findings and the presence of coronary obstruction to examine if coronary obstruction can be predicted by transthoracic echocardiogram before anesthesia. DESIGN: Retrospective data analysis of patients with Williams-Beuren syndrome who underwent transthoracic echocardiogram, cardiac catheterization, and/or surgical interventions to determine the correlation between echocardiogram findings and the presence of coronary obstruction determined by cardiac catheterization and/or surgery. SETTING: Single-center university teaching hospital. PARTICIPANTS: The study included 49 patients with Williams-Beuren syndrome who underwent transthoracic echocardiogram, cardiac catheterization, and/or surgical interventions. MEASUREMENTS AND MAIN RESULTS: The only variable associated with coronary artery obstruction was the maximum instantaneous gradient (MIG) across the left ventricular outflow tract (LVOT) on a transthoracic echocardiogram. LVOT MIG ≥ 75 mmHg as the optimal cutoff value was associated with coronary artery obstruction (area under the curve 0.659, odds ratio 6.71, 95% CI 1.31-34.35, p = 0.022). CONCLUSION: LVOT gradient can serve as a good predictor of the presence of coronary obstruction in patients with Williams-Beuren syndrome.

The Use of Regional Catheters in Children Undergoing Repair of Aortic Coarctation.

OBJECTIVE: The objective was to assess the effectiveness and safety of peripheral regional anesthesia in congenital cardiac surgical patients undergoing thoracotomy for aortic coarctation. DESIGN: A retrospective chart review of pediatric patients (<18 years) who underwent surgical repair of congenital heart diseases via thoracotomy between September 2013 and July 2018 was done. Among patients who underwent coarctation repair, a propensity score was used to match patients who received a regional catheter (C) versus traditional medical treatment only (M). SETTING: A single center children's hospital. PARTICIPANTS: The median age was 172 days (IQR 64-1315) in group C and 176 days (IQR 71-1146) in group M (SMD = 0.07). The median weight was 6.8 kg (IQR 4.8-13.6) in group C and 7.7 kg (4.6-17.4) in group M (SMD = 0.003). MEASUREMENTS AND MAIN RESULT: Outcomes assessed were postoperative hospital length of stay, median pain scores in the first 24 and 48 hours, and total morphine equivalent use in the first 24 and 48 hours. Complications related to the catheters were reviewed. The median oral morphine equivalent dose administered in the first 24 hours was lower in group C than group M (0.8 mg/kg, IQR 0.5-1.1 vs. 1.4 mg/kg, IQR 0.9-1.7, p = 0.019). There were no major complications related to the catheters, including hematoma. CONCLUSIONS: Peripheral regional catheters may be used to reduce opioid requirements in patients after CoA repair. Due to the low risk of these catheters, they should be considered as part of a pain management strategy for pediatric patients undergoing thoracotomy and should be incorporated into strategies to improve outcomes.