High-sensitivity refractive index sensor based on strong localized surface plasmon resonance.

This study proposes two types of composite structures based on gold nano circular and nano square rings on a gold thin film for plasmonic refractive index sensing. The finite-difference time-domain method was used for simulation and analysis. The nano square ring composite structure showed superior performance, with five surface plasmon resonance modes, and a peak sensitivity and figure of merit in a liquid environment of 1600 nm/RIU and 86R I U -1, respectively. The sensing performances of localized surface plasmon resonance modes of both structures are superior to those of the propagating surface plasmon resonance modes. The proposed composite structures can provide a reference for refractive index sensing and have broad application prospects in bio-chemistry.

Does prophylactic antibiotics post pediatric pyeloplasty reduce the incidence of febrile UTIs?

PURPOSE: The use of postoperative prophylactic antibiotics in pediatric upper urinary tract reconstruction remains controversial. In this study, we examined whether low dose antibiotics administered following pediatric pyeloplasty reduce the incidence of febrile urinary tract infections at our institution. As a secondary outcome, in those patients with infection, additional analysis was performed to better quantify which patient population benefits the most from low dose prophylactic antibiotics. METHODS: Institutional review board approval (IRB) was obtained. All methods were carried out in accordance with relevant guidelines and regulations. A retrospective study was performed in patients who underwent pyeloplasty (2011-2017) at our institution. Surgical approach (laparoscopic versus robotic assisted versus open, with or without internal JJ ureteral stent) were based on surgeon preference. Patients of 8 fellowship trained pediatric urologists were included in the study period. Patients with prior history of urologic interventions or other congenital genitourinary tract abnormalities were excluded. Demographics (age, gender, ethnicity, insurance status), prior history of culture proven urinary tract infection, surgical details (administration of perioperative antibiotics), and postoperative outcomes including; 1) re-admission 30 days post-surgery, 2) any urine cultures collected due to suspected urinary tract infection. RESULTS: A total of 209 patients (149 boys, 60 girls) met our inclusion criteria with 55/209 (26%) receiving postoperative prophylactic antibiotics. The average age was 6 years (range: 2 months-18 years). Indwelling ureteral stent was used in 176 (84%) patients. Eleven patients (5%) had a culture-proven urinary tract infection within 30-days postoperatively. No significant differences were seen in postoperative complications or incidence of urinary tract infection when comparing surgical approaches, +/- ureteral stent, or the use of antibiotics. Secondary analysis noted statistically significant increase in post-operative urinary tract infection in younger children (2.8 v. 6.2 years, p = 0.02), those patients who had a positive preoperative urine culture (8/11, p = 0.01) and those with public health insurance (p = 0.038). CONCLUSION: The incidence of postoperative urinary tract infection following pyeloplasty in our cohort was relatively low. There was a higher incidence of urinary tract infection in patients less than 3 years old. The use of antibiotics in patients post pyeloplasty did not appear to affect the incidence of post-operative urinary tract infection, however, they may have a role in children who have not yet potty trained and in patients with positive preoperative urine culture.

Complications and Failure to Rescue After Inpatient Pediatric Surgery.

OBJECTIVE: To describe the frequency and patterns of postoperative complications and FTR after inpatient pediatric surgical procedures and to evaluate the association between number of complications and FTR. SUMMARY AND BACKGROUND: FTR, or a postoperative death after a complication, is currently a nationally endorsed quality measure for adults. Although it is a contributing factor to variation in mortality, relatively little is known about FTR after pediatric surgery. METHODS: Cohort study of 200,554 patients within the National Surgical Quality Improvement Program-Pediatric database (2012-2016) who underwent a high (≥ 1%) or low (< 1%) mortality risk inpatient surgical procedures. Patients were stratified based on number of postoperative complications (0, 1, 2, or ≥3) and further categorized as having undergone either a low- or high-risk procedure. The association between the number of postoperative complications and FTR was evaluated with multivariable logistic regression. RESULTS: Among patients who underwent a low- (89.4%) or high-risk (10.6%) procedures, 14.0% and 12.5% had at least 1 postoperative complication, respectively. FTR rates after low- and high-risk procedures demonstrated step-wise increases as the number of complications accrued (eg, low-risk- 9.2% in patients with ≥3 complications; high-risk-36.9% in patients with ≥ 3 complications). Relative to patients who had no complications, there was a dose-response relationship between mortality and the number of complications after low-risk [1 complication - odds ratio (OR) 3.34 (95% CI 2.62-4.27); 2 - OR 10.15 (95% CI 7.40-13.92); ≥3-27.48 (95% CI 19.06-39.62)] and high-risk operations [1 - OR 3.29 (2.61-4.16); 2-7.24 (5.14-10.19); ≥3-20.73 (12.62-34.04)]. CONCLUSIONS: There is a dose-response relationship between the number of postoperative complications after inpatient surgery and FTR, ever after common, "minor" surgical procedures. These findings suggest FTR may be a potential quality measure for pediatric surgical care.

A Potential Research Target for Scleral Remodeling: Effect of MiR-29a on Scleral Fibroblasts.

INTRODUCTION: The purpose of this study was to determine whether miR-29a regulates cell survival and apoptosis and the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MMP-2, and collagen I in scleral fibroblasts. METHODS: We transfected scleral fibroblasts with the miR-29a mimic and inhibitor. The effects of miR-29a on cell proliferation and apoptosis were determined using the CCK-8 assay and flow cytometry, respectively. Quantitative polymerase chain reaction (qPCR) was used to determine whether miR-29a regulates the mRNA levels of PTEN, MMP-2, and collagen I. The protein expression of PTEN, MMP-2, and collagen I was also assessed by western blot analysis. RESULTS: The results of CCK-8 showed that, at 0, 24, 48, and 72 h after transfection, the relative optical density values in the mimic group were 0.233 ± 0.005, 0.380 ± 0.008, 0.650 ± 0.040, and 0.906 ± 0.032, and in the inhibitor group were 0.272 ± 0.011, 0.393 ± 0.029, 0.597 ± 0.059, and 0.950 ± 0.101, respectively. The flow cytometry results showed that the apoptosis rates of each group were as follows: the mimic group (0.043 ± 0.007), the NC group (0.040 ± 0.006), the inhibitor group (0.032 ± 0.003), the inhibitor NC group (0.027 ± 0.010), the lipofectamine group (0.027 ± 0.005), and the blank group (0.031 ± 0.009). The qPCR results indicated that in the mimic group, PTEN (0.795 ± 0.182, p = 0.2783), MMP-2 (0.621 ± 0.105, p = 0.0033), and COL1A1 (0.271 ± 0.100, p = 0.0002) expression decreased, whereas in the inhibitor group, PTEN (1.211 ± 0.100, p = 0.2614), MMP-2 (1.161 ± 0.053, p = 0.1190), and COL1A1 (1.7040 ± 0.093, p = 0.0003) increased. Western blot analysis showed that in the mimic group, the expression of PTEN (0.392 ± 0.039, p < 0.0001), MMP-2 (0.577 ± 0.017, p < 0.0001), and COL1A1 (0.072 ± 0.006, p < 0.0001) protein decreased, whereas in the inhibitor group, PTEN (1.043 ± 0.042, p = 0.9413), MMP-2 (1.397 ± 0.075, p = 0.0002), and COL1A1 (1.935 ± 0.081, p < 0.0001) expression increased. CONCLUSION: MiR-29a inhibits the expression of PTEN, MMP-2, and collagen I on scleral fibroblasts, which may provide a basis studies in sclera.

Variations in analgesic, sedation, and delirium management between trauma and non-trauma critically ill children.

INTRODUCTION: Studies have shown the benefit of intensive care unit (ICU) bundled protocols; however, they are primarily derived from medical patients. We hypothesized that patients and their medication profiles are different between critically ill medical, surgical, and trauma patients. METHODS: The Pediatric Health Information System 2017 dataset was used to perform a retrospective cohort study of critically ill children. The pediatric medical, surgical, and trauma cohorts were separated based on ICD-10 codes. Data collected included demographics, secondary diagnoses, outcomes, and medication data. Medications were grouped as opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, paralytics, and "other" sedatives. A non-parametric Kolmogorov-Smirnov test (KS test) and odds ratios (reference group: medical cohort) were calculated to compare medication administration between the study cohorts for the first 30 ICU days. RESULTS: A total of 4488 critically ill children (medical 2078, surgical 1650, and trauma 760) were identified. The trauma cohort had increased incidence of delirium (medical 10.8%, surgical 11.5%, trauma 13.8%; p < 0.01) and mortality (medical 5.4%, surgical 2.4%, trauma 11.7%; p < 0.01). For all study cohorts, > 50% received GABA-agonists on ICU days 0-30. With the KS test, there was a significant difference in administration of opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, and "other" sedatives over the first 30 days in the ICU. Relative to medical patients, trauma patients had significantly higher odds of receiving anti-psychotics on ICU days 10-20 and 22-24. CONCLUSION: Critically ill pediatric trauma, medical, and surgical patients are distinctly different patient populations with differing pharmacologic profiles for analgesia, sedation, and delirium. LEVEL OF EVIDENCE: Level III (Retrospective Comparative Study).

Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR-30a to regulate COX-2/BCL9 pathway.

BACKGROUND: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric cancer. Our previous study demonstrated that H. pylori decreased the expression of micro-RNA (miRNA)-30a to promote the tumorigenesis of gastric cancer. However, the upstream regulatory molecules of miR-30a are not well elucidated. In this study, we found the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) may sponge miR-30a to regulate COX-2/BCL9 pathway. METHODS: The expression of NEAT1 was detected in gastric cancer tissues and tumor-adjacent tissues by fluorescence in situ hybridization (FISH) analysis and RT-qPCR. LncRNA-miRNA interaction networks were constructed using the RNAhybrid and starBase v.2.0. and then validated using a dual-luciferase reporter assay. The effects of NEAT1 dysregulation on the proliferative, migratory, and invasive abilities of H. pylori filtrate-infected gastric cancer cells were observed by cell counting kit-8 (CCK-8), colony formation, wound healing test, and transwell assays. Western blot and RT-qPCR were performed to detect protein and RNA expression. Immunohistochemistry (IHC) was carried out to analyze the localization and expression of COX-2 and BCL9. RESULTS: FISH and RT-qPCR demonstrated that the expression of NEAT1 was up-regulated in gastric cancer tissues, especially in H. pylori-infected gastric cancer tissues, and the expression of NEAT1 was negatively correlated with miR-30a (miR-30a-3p and miR-30a-5p). The upregulation of NEAT1 enhanced proliferation, migration, and invasion of H. pylori filtrate-infected gastric cancer cells, while the downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the effect of NEAT1 on these abilities. The dual-luciferase reporter assay identified that NEAT1 directly targeted miR-30a (miR-30a-3p and miR-30a-5p). Because miR-30a (miR-30a-3p and miR-30a-5p) negatively regulates the expression of downstream COX-2 and BCL9, NEAT1 was identified to upregulate indirectly the expression of COX-2 and BCL9. IHC showed that the expression of COX-2 and BCL9 was increased in H. pylori gastric cancer tissues. CONCLUSION: The study demonstrated that lncRNA NEAT1 may act as a promoter of tumorigenesis in H. pylori gastric cancer, by sponging miR-30a (miR-30a-3p and miR-30a-5p) to regulate the COX-2/BCL9 pathway.

Prevalence of high-risk bladder categorization with prenatal and postnatal myelomeningocele repair types.

INTRODUCTION: Urologic substudies of prenatal myelomeningocele (MMC) closure have focused primarily on continence without significant clinical benefit. Fetoscopic MMC repair (FMR) is a newer form of prenatal intervention and touts added benefits to the mother, but urological outcomes have yet to be analyzed. We set out to focus on bladder safety rather than continence and examined bladder outcomes with different prenatal MMC repairs (FMR and prenatal open [POMR]) and compared bladder-risk-categorization to traditional postnatal repair (PSTNR). METHODS: An IRB-approved retrospective analysis of all patients undergoing all forms of MMC repairs with inclusion and exclusion criteria based on the MOMS trial was performed. Bladder safety assessment required initial urodynamic studies (UDS), renal bladder ultrasound (RBUS), and/or voiding cystourethrogram (VCUG) within the 1st year of life. Follow-up analyses within the cohorts required follow-up studies within 18 months after initial evaluations. Outcomes assessed included bladder-risk-categorization based on the CDC UMPIRE study (high, intermediate, and safe), hydronephrosis (HN), and vesicoureteral reflux (VUR). A single reader evaluated each UDS. RESULTS: Initial UDS in 93 patients showed that the prevalence of high-risk bladders were 35% FMR versus 36% PSTNR and 60% POMR. Follow-up UDS showed only 8% of FMR were high-risk compared to 35% POMR and 36% PSTNR. Change from initial to follow-up bladder-risk-category did not reach significance (p = .0659); however, 10% PSTNR worsened to high-risk on follow-up, compared to none in either prenatal group. Subanalysis of follow-up UDS between the prenatal cohorts also was not significant (p = .055). Only 8% of FMR worsened or stayed high-risk compared to 35% with POMR (p = .1). HN was significantly different at initial and subsequent follow up between the groups with the least in the FMR group. CONCLUSIONS: Early outcome UDS analyses demonstrated lower incidence of high-risk bladders in FMR patients with a trend toward clinically significant improvement compared to POMR in regard to all evaluated metrics. Larger, prospective, confirmatory studies are needed to further evaluate the potential benefits on FMR on bladder safety and health.

Antiepileptic drug management in pediatric patients with brain tumor-related epilepsy.

BACKGROUND: Patients with brain tumor-related epilepsy (BTRE) are at a higher risk of significant morbidity, lower quality of life, and increased risk of mortality. We surveyed providers regarding anti-seizure medication (ASM) management in pediatric BTRE to determine if practices are standard or markedly variable. METHODS: An anonymous voluntary online survey was sent to members of the Child Neurology Society. Providers were asked specific questions regarding initiation and wean of ASMs and if this was dependent on multiple factors. Demographic information was collected. RESULTS: Fifty-one providers responded to the survey. Ninety-four percent of providers would start an ASM after a second seizure. Eighty-four percent chose levetiracetam as the preferred ASM. Management was variable when based on tumor location, extent of surgical resection, pathology, and tumor prognosis. Statistically significant differences in responses regarding management were identified when comparing neurologists and epileptologists, providers with formal neuro-oncology or epilepsy training, providers at large institutions, and years of experience. For patients who underwent a gross total resection of the tumor, neuro-oncology and epilepsy-trained providers were more likely to wean off ASMs (p < 0.049). Providers without formal training in neuro-oncology or epilepsy were more likely to get an EEG prior to making a decision about weaning off ASMs (p < 0.016). CONCLUSION: These results suggest that ASM management in BTRE varies greatly according to sub-specialty and experience. Further studies and potential development of guidelines are needed to identify the most appropriate management of ASMs for BTRE.

Role of the long noncoding RNA H19 in TGF-ß1-induced Tenon's capsule fibroblast proliferation and extracellular matrix deposition.

Glaucoma filtration surgery (GFS) is a classic surgical method used to treat glaucoma, the second leading cause of blindness. Scar formation caused by excessive Tenon's capsule fibroblast activation leads to surgical failure. However, the mechanism underlying this activation is largely unknown. In this study, we first isolated primary human Tenon's capsule fibroblasts (HTFs) and found that TGF-ß promoted the viability, proliferation and extracellular matrix (ECM) deposition of HTFs. Then, we showed that TGF-ß promoted the expression of H19 in HTFs and that suppression of H19 inhibited the effect of TGF-ß on HTFs. Furthermore, we revealed that H19 exerted its effects by interacting with miR-200a in TGF-ß-treated HTFs. Additionally, we showed that ß-catenin was a target of miR-200a in TGF-ß-treated HTFs. We also demonstrated that H19 acted by modulating the H19/miR-200a/ß-catenin regulatory axis in TGF-ß-treated HTFs. Ultimately, we found that the components of the H19/miR-200a/ß-catenin regulatory axis were aberrantly expressed in a rat model of GFS. Our results show that H19 indeed acts by modulating ß-catenin expression via miR-200a in TGF-ß-treated HTFs, thus providing a novel rationale for the development of H19-based strategies to attenuate scar formation after GFS.

Impact of a Pediatric-Focused Communication Course on Patient/Caregiver-Perceived Physician Communication Skills in a Pediatric Emergency Department.

OBJECTIVES: To evaluate the impact of a pediatric-focused, relationship-centered communication course on patient/caregiver assessment of emergency department (ED) physician communication skills. METHODS: This was a prospective study; a previously validated assessment tool (Pediatric Physician Interpersonal Communication Skills Assessment [P-PICSA]) was used to collect pediatric patient/caregiver evaluation of ED physician communication skills. Emergency department physicians were required to attend a 5.5-hour communication course. Differences in precourse/postcourse P-PICSA and top-box scores were analyzed to determine course impact on ED physician communication skills. RESULTS: From July 2016 to August 2017, 49 pediatric ED physicians participated in the course, and 24 physicians (49%) had 6-month precourse/postcourse P-PICSA data. Postcourse scores were higher for all 13 items, with 3 items achieving statistical significance: (1) the doctor used words I could understand; (2) the way the doctor involved me in making decisions about my child's care in the ED; (3) how the doctor discussed next steps and/or follow-up plans for my child's care after we leave the ED (P < 0.05). Additionally, postcourse, top-box score percentages were higher for 12 items, with 1 item achieving statistical significance (P = 0.0386). CONCLUSIONS: An organization-wide, pediatric-focused, relationship-centered communication course improved patient/caregiver-perceived ED physician communication. Further research is necessary to assess long-term sustainability.

Anesthesia-Related Factors Associated with Preterm Labor and Delivery after Open Fetal Surgery.

BACKGROUND: Fetal surgery, such as for meningomyelocele repair, has a clear clinical fetal benefit. In patients who undergo in utero repair of meningomyelocele, for example, there is reduced long-term disease morbidity. However, despite the beneficial effects of early intervention, women who undergo fetal interventions have an increased risk of preterm labor and delivery. Several surgery-related factors have been described but no specific anesthesia-related factors. OBJECTIVE: The aim of this study was to determine if any aspects of the perioperative anesthetic management influenced maternal complications following in utero surgery. METHODS: This was a retrospective chart review of the anesthetic management of mothers and fetuses who presented for open and fetoscopic myelomeningocele repair, between 2011 and 2015, at Texas Children's Fetal Center®. RESULTS: Forty-six women underwent open or fetoscopic repair of neural tube defects at our institution. We found the maternal heart rate in the postoperative period to be associated with a higher likelihood of preterm labor, but not delivery. The odds of having preterm delivery was higher for nulliparous patients and those with lower intraoperative diastolic pressure. CONCLUSIONS: Our findings confirm what has been previously reported regarding the association of nulliparity with preterm delivery. Additionally, this study highlights the importance of maintaining stable perioperative hemodynamics during the intraoperative and postoperative phases of care for patients undergoing in utero surgery.

A Multicenter Study of Nutritional Adequacy in Neonatal and Pediatric Extracorporeal Life Support.

BACKGROUND: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population. MATERIALS AND METHODS: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support. RESULTS: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%). CONCLUSIONS: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications.

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). METHODS: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. RESULTS: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. CONCLUSION: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.

Tension Band Plate (TBP)-guided Hemiepiphysiodesis in Blount Disease: 10-Year Single-center Experience With a Systematic Review of Literature.

BACKGROUND: Primary treatment for Blount disease has changed in the last decade from osteotomies or staples to tension band plate (TBP)-guided hemiepiphysiodesis. However, implant-related issues have been frequently reported with Blount cases. The purpose of our study is to evaluate the surgical failure rates of TBP in Blount disease and characterize predictors for failure. METHODS: We performed an Institutional Review Board-approved retrospective chart-review of pediatric patients with Blount disease to evaluate the results of TBP from 2008 to 2017 and a systematic literature review. Blount cases defined as pathologic tibia-vara with HKA (hip-knee-ankle) axis and MDA (metaphyseal-diaphyseal angle) deviations ≥11 degrees were included in the analysis. Surgical failure was categorized as mechanical and functional failure. We studied both patient and implant-related characteristics and compared our results with a systematic review. RESULTS: In 61 limbs of 40 patients with mean follow-up of 38 months, we found 41% (25/61) overall surgical failure rate and 11% (7/61) mechanical failure rate corresponding to 11% to 100% (range) and 0% to 50% (range) in 8 other studies. Statistical comparison between our surgical failure and nonfailure groups showed significant differences in deformity (P=0.001), plate material (P=0.042), and obesity (P=0.044) in univariate analysis. The odds of surgical failure increased by 1.2 times with severe deformity and 5.9 times with titanium TBP in the multivariate analysis after individual risk-factor adjustment. All 7 mechanical failures involved breakage of cannulated screws on the metaphyseal side. CONCLUSIONS: Most of the studies have reported high failure rates of TBP in Blount cases. Besides patient-related risk factors like obesity and deformity, titanium TBP seems to be an independent risk factor for failure. Solid screws were protective for mechanical failure, but not for functional failure. In conclusion, efficacy of TBP still needs to be proven in Blount disease and implant design may warrant reassessment. LEVEL OF EVIDENCE: Level III-retrospective comparative study with a systematic review.

Borrowing Strength and Borrowing Index for Bayesian Hierarchical Models.

A novel borrowing strength measure and an overall borrowing index to characterize the strength of borrowing behaviors among subgroups are proposed for a given Bayesian hierarchical model. The constructions of the proposed indexes are based on the Mallow's distance and can be easily computed using MCMC samples for univariate or multivariate posterior distributions. Consequently, the proposed indexes can serve as meaningful and useful exploratory tools to better understand the roles played by the priors in a hierarchical model, including their influences on the posteriors that are used to make statistical inferences. These relationships are otherwise ambiguous. The proposed methods can be applied to both the continuous and binary outcome variables. Furthermore, the proposed approach can be easily adapted to various settings of clinical trials, where Bayesian hierarchical models are deem appropriate. The effectiveness of the proposed method is illustrated using extensive simulation studies and a real data example.

A High Ratio of Plasma: RBC Improves Survival in Massively Transfused Injured Children.

BACKGROUND: Massive transfusion protocols with balanced blood product ratios have been associated with improved outcomes in adult trauma. The impact on pediatric trauma is unclear. MATERIAL AND METHODS: A retrospective review of the Pediatric Trauma Quality Improvement Program data set was performed using data from January 2015 to December 2016. Trauma patient's ≤ 18 y of age, who received red blood cells (RBCs) and were massively transfused were included. Children with burns, dead on arrival, and nonsurvivable injuries were excluded. Outcome data and mortality were assessed based on low (<1:2), medium (≥1:2, <1:1), and high (≥1:1) plasma and platelet to RBC ratios. RESULTS: There were 465 children included in the study (median age, 8 [2-16] y; median injury severity score, 34 [29-34]; mortality rate, 38%). Those transfused a medium plasma:RBC ratio received the greatest blood product volume in 24 h (90 [56-164] mL/kg; P < 0.01). Those in the low plasma:RBC group underwent fewer hemorrhage control procedures [56 (34%); P < 0.01], but ratio was not significant when controlling for age and other variables. Survival was improved for those who received a high plasma:RBC ratio (P = 0.02). Platelet transfusions were skewed toward lower ratios (95%) with no difference in clinical outcomes between the groups. CONCLUSIONS: A high ratio of plasma:RBC may result in decreased mortality in severely injured children receiving a massive transfusion. Prospective, multicenter studies are needed to determine optimal resuscitation strategies for these critically ill children.

Reoperation after isolated subaortic membrane resection.

BACKGROUND: The resection of a subaortic membrane remains far from a curative operation. We sought to examine factors associated with reoperation and the degree of aortic valve regurgitation as a potential long-term source for reoperation. METHODS: All patients who underwent resection of an isolated subaortic membrane between 1995 and 2018 were included. Patients who underwent other procedures were excluded. Paired categorical data were compared using McNemar's test. Univariate time-to-event analyses were performed using Kaplan-Meier methods with log-rank tests for categorical variables and univariate Cox models for continuous variables. RESULTS: A total of 84 patients (median age 6.6, 31% females) underwent resection of isolated subaortic membrane. At a median follow-up of 9.3 years (interquartile range 0.6-22.5), 12 (14%) patients required one reoperation and 1 patient required two reoperations. Median time to first reoperation was 4.6 years. The degree of aortic valve regurgitation improved post-operatively from pre-operatively (p = 0.0007); however, the degree of aortic valve regurgitation worsened over the course of follow-up (p = 0.010) to equivalence with pre-operative aortic valve regurgitation (p = 0.18). Performance of a septal myectomy was associated with longer freedom from reoperation (p = 0.004). CONCLUSIONS: In patients with isolated subaortic membranes, performance of a septal myectomy can minimise risk for reoperation. Patients should be serially monitored for degradation of the aortic valve, even if aortic regurgitation is not present post-operatively.

Risk factors for infection after pediatric lung transplantation.

Although infection is the leading cause of death in the first year following pediatric lung transplantation, there are limited data on risk factors for early infection. Sepsis remains under-recognized and under-reported in the early post-operative period for lung transplant recipients (LTR). We evaluated the incidence of infection and sepsis, and identified risk factors for infection in the early post-operative period in pediatric LTRs. A retrospective review of medical records of LTRs at a large quaternary-care hospital from January 2009 to March 2016 was conducted. Microbiology results on days 0-7 after transplant were obtained. Sepsis was defined using the 2005 International Pediatric Consensus Conferencecriteria. Risk factors included history of recipient and donor infection, history of multi-drug resistant (MDR) infection, nutritional status, and surgical times. Among the 98 LTRs, there were 22 (22%) with post-operative infection. Prolonged donor ischemic time ≥7 hours, cardiopulmonary bypass(CPB) time ≥340 minutes, history of MDR infection and diagnosis of cystic fibrosis were significantly associated with infection. With multivariable regression analysis, only prolonged donor ischemic time remained significant (OR 4.4, 95% CI: 1.34-14.48). Further research is needed to determine whether processes to reduce donor ischemic time could result in decreased post-transplant morbidity.

LncRNA HOTAIR mediates TGF-ß2-induced cell growth and epithelial-mesenchymal transition in human lens epithelial cells.

Posterior capsule opacification (PCO) results from the proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) and fibers in the capsular bag. Previous reports have demonstrated that transforming growth factor ß2 (TGF-ß2) affects the cellular processes via modulation of EMT in LECs. However, the mechanisms that underlie the TGF-ß2-induced EMT in LECs are still largely unknown. In this study, we confirmed that TGF-ß2 induces EMT in SRA01/04 cells via the up-regulation of the long non-coding RNA (lncRNA) HOTAIR. To study the effects of HOTAIR on the proliferation, migration and EMT of SRA01/04 cells as well as the underlying mechanism, we used small interfering RNA (siRNA) to specifically attenuate HOTAIR expression in SRA01/04 cells. CCK8 cell-counting kit was used to examine SRA01/04 cell viability; EdU cell proliferation kit was used to examine SRA01/04 cell proliferation; Transwell system and scratch assays were used to observe cell migration; and qPCR and western blot analysis were used to evaluate EMT progression. We found that inhibition of HOTAIR expression repressed SRA01/04 cell viability, proliferation, migration and prevented the TGF-ß2-induced changes in cellular processes via modulation of EMT. Ultimately, we found that HOTAIR affected the TGF-ß/Smad signaling pathway. In summary, we elucidated that HOTAIR affected the cell viability, proliferation, and migration in the TGF-ß2-induced EMT in SRA01/04 cells and suggested that modulation of HOTAIR may be helpful in PCO prevention and therapy.

Evodiamine Suppresses ABCG2 Mediated Drug Resistance by Inhibiting p50/p65 NF-κB Pathway in Colorectal Cancer.

Evodiamine (Evo), extracted from the Chinese herbal medicine Evodia rutaecarpa, has cytotoxic effects on different types of human cancer cells. However, its effects on drug resistance and their molecular mechanism and therapeutic target in colorectal cancer are not well understood. In the present study, we observed that Evo inhibited cell growth and induced apoptosis in adose-and time-dependent manner in HCT-116/L-OHP cells. Moreover, Evo treatment reduced Rhodamine 123 accumulation and ATPase activity in HCT-116/L-OHP cells, indicating that Evo decreased the efflux function in HCT-116/L-OHP cells. Interestingly, phosphorylation of NF-κB pathway, particularly p50/p65, was also inhibited by Evo treatment. Furthermore the effect of Evo in reversing drug resistance and suppressing phosphorylation of NF-κB pathway were attenuated after treatment with the NF-κB activator (LPS). Additionally, Evo inhibited the tumor growth in a colorectal MDR cancer xenograft model and down regulated p-NF-κB level in vivo. Our study provided the first direct evidence that Evo can attenuate multidrug resistance by blocking p-NF-κB signaling pathway in human colorectal cancer. Evo could be a potential candidate for cancer chemotherapy.