Optimal Timing of Inguinal Hernia Repair in Premature Infants: A NSQIP-P Study.

INTRODUCTION: Among premature infants, the incidence of inguinal hernias is reported to be as high as 30%. Despite being one of the most commonly performed procedures, the optimal setting of inguinal hernia repair (IHR) that is inpatient versus outpatient remains debatable. We sought to compare the 30-day outcomes of each approach by querying the National Surgical Quality Improvement Program-Pediatric database. MATERIALS AND METHODS: A retrospective cohort study comparing inpatient versus outpatient IHR using the National Surgical Quality Improvement Program-Pediatric database from 2013 to 2019 was performed. Demographic and clinical data were initially compared using univariate analysis. Continuous variables are presented as median and interquartile range and categorical variables are presented as n (%). Subsequently, cohorts were propensity matched using clinically and statistically significant patient characteristics. RESULTS: 928 patients underwent IHR, 634 (68.3%) while inpatient, 294 (31.7%) following hospital discharge. Inpatient IHR was associated with lower age at the time of surgery (120 versus 147 d; P < 0.0001), younger gestational age (27 versus 33 wk; P < 0.0001), decreased probability of repair in elective setting (87.2% versus 97.3%; P < 0.0001), and increased preoperative supplemental oxygen need (42% versus 4.4%; P < 0.0001). Comparison of propensity matched cohorts revealed that inpatient IHR was associated with increased procedure time (82 versus 51 min; P < 0.0001) and anesthetic duration (146 versus 102 min; P < 0.0001), wound infection rates (3.8% versus 0%; P = 0.007), blood transfusions (4.2% versus 0.5%; P = 0.036), unplanned intubations (2.8% versus 0%; P = 0.03), ventilator days (0 versus 0; range [0,30 versus 0,2]; P = 0.002), reoperation rate (5.6% versus 0%; P < 0.001), postoperative hospital length of stay (4 versus 1 d; P < 0.0001), and unplanned readmissions (8.9% versus 0.9%; P = 0.002). CONCLUSIONS: Inpatient IHR in premature neonates were associated with different postoperative outcomes than outpatient IHR. At least in the elective setting among premature infants, outpatient IHR can be considered safe in select patients while we await higher quality prospective data.

Short-term outcomes of thoracoscopic versus open lobectomy for congenital lung malformations.

PURPOSE: Thoracoscopic and open approaches for the management of congenital lung malformations (CLM) has been debated. The aim of this study is to compare 30-day outcomes for non-emergent lobectomies in children. METHODS: The National Surgical Quality Improvement Program-Pediatric database was queried for patients undergoing CLM resection from 2013 to 2020. Outcomes were compared by operative technique in an intention-to-treat model and then propensity matched. RESULTS: 2157 patients met inclusion criteria and underwent non-emergent pulmonary lobectomy for CLM. The intended operative approach was thoracoscopic in 57.7% of patients. Patients in the open group compared to the thoracoscopic were more likely to be born premature, have chronic lung disease, require preoperative oxygen support, and be ventilator dependent. After propensity matching, there was no statistically significant difference in 30-day mortality, unplanned readmission, and other complications between the thoracoscopic and open groups. Thoracoscopic approach was associated with a shorter length of stay. The proportion of cases approached via thoracoscopy increased over time from 48.8% in 2013 to 69.9% in 2020. CONCLUSIONS: This large multicenter retrospective matched analysis demonstrates thoracoscopic lobectomy in children has similar favorable 30-day outcomes and shorter length of stay for the non-emergent management of CLM, compared to open thoracotomy. LEVEL OF EVIDENCE: Level III.

Influence of denture brushing on the surface properties and color stability of CAD-CAM, thermoformed, and conventionally fabricated denture base resins.

PURPOSE: To assess the influence of denture brushing on the surface roughness, hardness, and color stability of conventional, thermoformed, and CAD-CAM denture base materials. MATERIALS AND METHODS: Seven different denture base materials were included in this study; conventional heat-polymerized acrylic resin (PMMA) served as control, polyamide, acetal, two categories of milled acrylic discs (AvaDent and IvoCad), and two categories of 3D-printed resins (NextDent and FormLabs). The specimens were constructed according to manufacturers' instructions and then subjected to simulated brushing (20,000 cycles). According to the brushing method, the specimens were split into three groups, no brushing, brushing with water, and brushing with toothpaste. Surface roughness, hardness, and color change were evaluated before and after brushing. Collected data were analyzed using ANOVA, and post-hoc Tukey's tests (α = 0.05). RESULTS: A significant difference was noted between the surface roughness of the tested materials before and after denture brushing (p < 0.05), and milled resin showed the least Ra values. Denture brushing with water significantly increased the Ra of PMMA (p = 0.004) and IvoCad (p = 0.032), while brushing using toothpaste did not show a significant increase. The brushing protocols did not alter the hardness of tested materials except that of PMMA (p = 0.001). The color stability of the tested materials showed comparable results with both brushing protocols. CONCLUSION: The tested properties showed variations between the types of denture base resins. Hardness and color stability of CAD-CAM and thermoformed denture base resins were not altered by denture brushing and showed comparable results with both brushing methods. Surface roughness was the only property that showed alteration after denture brushing.

Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems.

Genomic enhancer elements regulate gene expression programs important for neuronal fate and function and are implicated in brain disease states. Enhancers undergo bidirectional transcription to generate non-coding enhancer RNAs (eRNAs). However, eRNA function remains controversial. Here, we combined Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq) and RNA-Seq datasets from three distinct neuronal culture systems in two activity states, enabling genome-wide enhancer identification and prediction of putative enhancer-gene pairs based on correlation of transcriptional output. Notably, stimulus-dependent enhancer transcription preceded mRNA induction, and CRISPR-based activation of eRNA synthesis increased mRNA at paired genes, functionally validating enhancer-gene predictions. Focusing on enhancers surrounding the Fos gene, we report that targeted eRNA manipulation bidirectionally modulates Fos mRNA, and that Fos eRNAs directly interact with the histone acetyltransferase domain of the enhancer-linked transcriptional co-activator CREB-binding protein (CBP). Together, these results highlight the unique role of eRNAs in neuronal gene regulation and demonstrate that eRNAs can be used to identify putative target genes.

Gadd45 in Neuronal Development, Function, and Injury.

The growth arrest and DNA damage-inducible (Gadd) 45 proteins have been associated with numerous cellular mechanisms including cell cycle control, DNA damage sensation and repair, genotoxic stress, neoplasia, and molecular epigenetics. The genes were originally identified in in vitro screens of irradiation- and interleukin-induced transcription and have since been implicated in a host of normal and aberrant central nervous system processes. These include early and postnatal development, injury, cancer, memory, aging, and neurodegenerative and psychiatric disease states. The proteins act through a variety of molecular signaling cascades including the MAPK cascade, cell cycle control mechanisms, histone regulation, and epigenetic DNA demethylation. In this review, we provide a comprehensive discussion of the literature implicating each of the three members of the Gadd45 family in these processes.

Aluminum Leaching from Fluid Warmers: Regulatory Deferral to Clinicians' Decision.

Fluid-warming systems are crucial in surgical and trauma settings because of their key role in preventing or treating hypothermia and enabling proper resuscitation of blood products that are stored cold. Recently, several manufacturers have issued warnings of the possibility of aluminum leaching from their fluid warmers and cautioned about the potential for aluminum toxicity in patients who underwent fluid resuscitation with these devices. Studies suggest that one of the main factors affecting aluminum leaching in this setting is the coating of the aluminum plate itself. Coating, often with a biocompatible material, appears to reduce aluminum leaching by 100- to 200-fold compared with an uncoated plate. Nonetheless, leaching with the coating is still at a level exceeding U.S. regulations. A few aluminum-free warming systems are available on the market, but these are not carried by all providers and some clinicians may be less familiar with their use. Medical device manufacturers will likely design future warming systems with less potential for aluminum blood contact. In the meantime, the risk of inadequate resuscitation, consequent to the proper fluid warmer no longer being available, is contrasted with the risk of potential toxicity. In the situation described here, the regulators deferred the ultimate decision of which fluid warmer to use in a given situation to the risk-benefit decision of the clinician.

Single site versus conventional laparoscopic appendectomy: some pain for no gain?

INTRODUCTION: The optimal laparoscopic appendectomy approach is not clear, comparing single site laparoscopic appendectomy (SILA) to conventional 3-port appendectomy (CLA). We investigated outcomes in pediatric patients comparing SILA to CLA: length of operation, length of stay, time to resumption of regular diet, follow up, rehospitalization, and cost. METHODS: Data was collected from children 1 to 18 years with appendectomy at Loma Linda University from 2018 to 2020, operated by two surgeons. Analysis utilized two-sample T, chi-squared, and Fisher's exact tests. RESULTS: Of 173 patients, 77 underwent SILA and 96 had CLA. There was no gender, age, or race difference between groups. Mean WBC was 17.5 × 103/mL in SILA group, compared to 15.3 × 103/mL in CLA group (P = 0.004). Operative time was 47.0 SILA compared to 49.5 minutes CLA (P = 0.269). Of SILA cases, 55.8% were simple appendicitis, while 53.3% of the CLA cases were simple (P = 0.857). Regular diet was resumed after 1.7 days in the SILA group, 1.1 days in CLA (P = 0.018). Length of stay was 2.9 days for SILA, 2.4 days for CLA (P = 0.144). Seven children required hospital readmission, 5 SILA and 2 CLA (P = 0.244). Five of the children who returned had intra-abdominal abscesses, of whom 4 had SILA. There was no difference in cost. CONCLUSIONS: The operative techniques had similar outcomes and operative times. There was a trend toward more intra-abdominal abscesses in the SILA group. Further study and longer follow up is needed to determine if there is an advantage to one laparoscopic approach over another.

Permutationally Invariant Deep Learning Approach to Molecular Fingerprinting with Application to Compound Mixtures.

Recent advancements in deep learning have led to widespread applications of its algorithms to synthetic planning and reaction predictions in the field of chemistry. One major area, known as supervised learning, is being explored for predicting certain properties such as reaction yields and types. Many chemical descriptors known as fingerprints are being explored as potential candidates for reaction properties prediction. However, there are few studies that describe the permutational invariance of chemical fingerprints, which are concatenated at some stage before being fed to deep learning architecture. In this work, we show that by utilizing permutational invariance, we consistently see improved results in terms of accuracy relative to previously published studies. Furthermore, we are able to accurately predict hydrogen peroxide loss with our own dataset, which consists of more than 20 ingredients in each chemical formulation.

Inguinal hernias in premature neonates: exploring optimal timing for repair.

PURPOSE: Inguinal hernias have been reported in as many as 10-30% premature neonates, making inguinal herniorrhaphy (IHR) one of the most commonly performed surgical procedures. The timing of surgery remains controversial. The purpose of this report is to compare outcomes of IHR while in the NICU (inpatient) versus repair following discharge (outpatient) to determine optimal timing. METHODS: Premature neonates having undergone IHR over a 5-year period were identified and a retrospective case cohort analysis was performed. RESULTS: 263 patients underwent IHR during the 5-year study period with 115 (43.7%) having surgical repair inpatient (IP; prior to discharge) and 148 having outpatient herniorrhaphy (OP). Patients with IHR performed IP had significantly lower birth weight (p < 0.001), gestational age (p < 0.001), longer duration of surgery (p = 0.01) and were more likely to have post-operative ventilator dependence following repair; however, there were no differences in the rate of recurrence (p = 0.44) and incarceration (p = 0.45). CONCLUSION: Our study demonstrated no significant differences in the rates of incarceration or recurrence, following in- or out-patient IHR. These findings suggest that IHR can potentially be offered as an outpatient procedure following hospital discharge in appropriate patients. The optimal timing of IHR in premature infants remains elusive and will likely require additional multicenter investigation.

Esterified Trehalose Analogues Protect Mammalian Cells from Heat Shock.

Trehalose is a disaccharide produced by many organisms to better enable them to survive environmental stresses, including heat, cold, desiccation, and reactive oxygen species. Mammalian cells do not naturally biosynthesize trehalose; however, when introduced into mammalian cells, trehalose provides protection from damage associated with freezing and drying. One of the major difficulties in using trehalose as a cellular protectant for mammalian cells is the delivery of this disaccharide into the intracellular environment; mammalian cell membranes are impermeable to the hydrophilic sugar trehalose. A panel of cell-permeable trehalose analogues, in which the hydrophilic hydroxyl groups of trehalose are masked as esters, have been synthesized and the ability of these analogues to load trehalose into mammalian cells has been evaluated. Two of these analogues deliver millimolar concentrations of free trehalose into a variety of mammalian cells. Critically, Jurkat cells incubated with these analogues show improved survival after heat shock, relative to untreated Jurkat cells. The method reported herein thus paves the way for the use of esterified analogues of trehalose as a facile means to deliver high concentrations of trehalose into mammalian cells for use as a cellular protectant.

Endothelial function and carotid intima media thickness in obstructive sleep apnea without comorbidity.

PURPOSE: The objective of this study was to evaluate endothelial function and carotid intima media thickness (CIMT) in moderate to severe obstructive sleep apnea (OSA) without comorbidities. METHODS: It is an observational case control study in which endothelial function was assessed using flow-mediated dilatation (FMD) and peripheral arterial tonometry (PAT), and carotid artery ultrasound was used to measure CIMT in study group subjects that included 20 normotensive, non-diabetic, treatment naïve, and moderate to severe OSA patients, and 20 normotensive, non-diabetic, and non-OSA subjects served as a control group. Study was conducted in Polysomnography Laboratory, Department of Internal Medicine, All India Institute of Medical Sciences (AIIMS) Hospital, New Delhi. RESULTS: FMD was significantly lower in the moderate to severe OSA group compared to non-OSA group (mean ± SD, 8.3 ± 2.8 vs. 13.4 ± 4.1 %; p = 0.0001). Reactive hyperemia index (RHI) was also significantly lower in the OSA group (1.55 ± 0.27 vs. 2.01 ± 0.48, p = 0.0007). CIMT was observed to be significantly higher in the OSA group compared to the non-OSA group (0.54 ± 0.09 vs. 0.48 ± 0.08 mm; p = 0.049). In the OSA group, FMD, RHI, and CIMT did not show a significant correlation with OSA disease severity indices [apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum O2 saturation]. CONCLUSION: Endothelial function in macrovascular and microvascular circulation is significantly impaired in moderate to severe OSA patients without comorbidities. These patients also show evidence of subclinical atherosclerosis, in the form of increased CIMT.

Publication Trends in Craniofacial Distraction: A Bibliometrical Analysis.

PURPOSE: The purpose of this study was to analyze the craniofacial distraction literature published over the last 50 years and to determine various trends in publications. METHODS: A literature search was conducted in November and December 2015. The date search range was 1965 to 2015. Databases searched included Medline, Web of Science, Biosis, SciELO, Data Citation, and Zoologic Records. Data were collected on distraction type, author specialty, date of publication, country, state (if United States), number of citations, journal name, journal type, and Le Fort type (for midfacial distractions). RESULTS: Total number of craniofacial distraction publications was 1729. Cranial distraction accounted for (11%), midfacial (11%), and mandibular (78%). Largest increase in publications was in the 1990s, with 48 publications from 1991 to 1995 rising to 261 publications from 1996 to 2000. Among the cranial distraction publications, Plastic and Reconstructive Surgery (PRS) (67%) were the most frequent authors but among the midfacial and mandibular distraction publications, Oral and Maxillofacial Surgery (OMFS) were the most frequent authors (68% and 64%, respectively). Total number of citations was 26,281 with OMFS (50.4%) and PRS (37%) being cited most frequently. Oral and Maxillofacial Surgery was cited most for mandibular and midfacial distraction, and PRS was cited most for cranial distraction. CONCLUSION: Research on craniofacial distraction has significantly increased since the 1970s, with mandibular distraction accounting for the majority of this rise. Among specialties, OMFS and PRS account for the majority of the literature. The United States leads the publication. Authors tend to publish distraction literature in their corresponding journal specialty, with the exception of PRS who publishes most frequently in OMFS journals.

Paget-Schroetter syndrome in 21 children: outcomes after multidisciplinary care.

OBJECTIVE: To review the presentation, management, and outcomes of Paget-Schroetter syndrome (PSS) in children and propose a multidisciplinary treatment algorithm involving pediatric and vascular surgery, interventional radiology, and hematology. STUDY DESIGN: Patients with PSS presenting between 2003 and 2013 were reviewed. Demographics, symptoms, therapies, and functional outcomes were noted. Data from early patients informed the development of a multidisciplinary treatment algorithm applied to later patients. RESULTS: Of 21 patients, mean ± SD age was 16 ± 1.6 years and 11 (52%) were male. Of patients with complete presentation data, common symptoms were edema (84%), discoloration (58%), and pain (58%). Thrombophilia workup revealed one heterozygote for factor V Leiden, 2 patients with factor VIII elevation and 1 patient with mildly low antithrombin. The most recent 8 patients were treated according to an algorithm developed by a multidisciplinary working group through experience with the first 13 cases. All patients underwent a venogram, endovascular intervention (including 15 receiving catheter-directed thrombolysis), and operative ipsilateral thoracic outlet decompression (first rib resection, anterior scalenectomy, and venolysis). Postoperative complications included hemothorax (2), pneumothorax (1), and recurrent thrombosis (2). Follow up duration was 12 ± 9.5 months. Symptoms recurred transiently in 1 patient. CONCLUSION: Pediatric patients with PSS can be treated successfully using a multidisciplinary treatment algorithm including anticoagulation, catheter-directed thrombolysis, and operative decompression of the thoracic outlet. Early outcomes are promising.

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

OBJECTIVES: In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. STUDY DESIGN: A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. RESULTS: A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. CONCLUSIONS: A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS: The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS: Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.

Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation During the Early Postoperative Period Following Pediatric Cardiac Surgery.

OBJECTIVE: Critical illness is associated with significant catabolism, and persistent protein loss correlates with increased morbidity and mortality. Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal muscle protein breakdown in critically ill pediatric surgical patients. However, insulin's effect on protein catabolism when given at clinically utilized doses has not been studied. The objective was to evaluate the effect of postoperative tight glycemic control and clinically dosed insulin on skeletal muscle degradation in children after cardiac surgery with cardiopulmonary bypass. DESIGN: Secondary analysis of a two-center, prospective randomized trial comparing tight glycemic control with standard care. Randomization was stratified by study center. PATIENTS: Children 0-36 months who were admitted to the ICU after cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: In the tight glycemic control arm, insulin was titrated to maintain blood glucose between 80 and 110 mg/dL. Patients in the control arm received standard care. Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine to urinary creatinine. MEASUREMENTS AND MAIN RESULTS: A total of 561 patients were included: 281 in the tight glycemic control arm and 280 receiving standard care. There was no difference in 3-methylhistidine to creatinine between groups (tight glycemic control, 249 ± 127 vs standard care, 253 ± 112, mean ± SD in µmol/g; p = 0.72). In analyses restricted to the patients in tight glycemic control arm, higher 3-methylhistidine to creatinine correlated with younger age, as well as lower weight, weight-for-age z score, length, and body surface area (p < 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p = 0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to creatinine. During urine collection, 245 patients (87%) received insulin. However, any insulin exposure did not impact 3-methylhistidine to creatinine (t test, p = 0.45), and there was no dose-dependent effect of insulin on 3-methylhistidine to creatinine (r = -0.03; p = 0.60). CONCLUSION: Although high-dose insulin has an anabolic effect in experimental conditions, at doses necessary to achieve normoglycemia, insulin appears to have no discernible impact on skeletal muscle degradation in critically ill pediatric cardiac surgical patients.

Reversibly Sticking Metals and Graphite to Hydrogels and Tissues.

We have discovered that hard, electrical conductors (e.g., metals or graphite) can be adhered to soft, aqueous materials (e.g., hydrogels, fruit, or animal tissue) without the use of an adhesive. The adhesion is induced by a low DC electric field. As an example, when 5 V DC is applied to graphite slabs spanning a tall cylindrical gel of acrylamide (AAm), a strong adhesion develops between the anode (+) and the gel in about 3 min. This adhesion endures after the field is removed, and we term it as hard-soft electroadhesion or EA[HS]. Depending on the material, adhesion occurs at the anode (+), cathode (-), or both electrodes. In many cases, EA[HS] can be reversed by reapplying the field with reversed polarity. Adhesion via EA[HS] to AAm gels follows the electrochemical series: e.g., it occurs with copper, lead, and tin but not nickel, iron, or zinc. We show that EA[HS] arises via electrochemical reactions that generate chemical bonds between the electrode and the polymers in the gel. EA[HS] can create new hybrid materials, thus enabling applications in robotics, energy storage, and biomedical implants. Interestingly, EA[HS] can even be achieved underwater, where typical adhesives cannot be used.