A Narrative Review of Multiinstitutional Data Registries of Pediatric Congenital Heart Disease in Pediatric Cardiac Anesthesia and Critical Care Medicine.

Congenital heart disease (CHD) is one of the most common birth anomalies. While the care of children with CHD has improved over recent decades, children with CHD who undergo general anesthesia remain at increased risk for morbidity and mortality. Electronic health record systems have enabled institutions to combine data on the management and outcomes of children with CHD in multicenter registries. The application of descriptive analytics methods to these data can improve clinicians' understanding and care of children with CHD. This narrative review covers efforts to leverage multicenter data registries relevant to pediatric cardiac anesthesia and critical care to improve the care of children with CHD.

Comparative evaluation of fracture resistance of endodontically treated maxillary premolars reinforced by customized glass fiber post in two different ways: An in vitro study.

Context: Endodontically treated premolars are currently restored with direct bonded techniques in conservative manner enabling them to bear functional stresses homogeneously. Aim: The study aimed to evaluate the effect of placement of compactable glass fibers in reinforcing the endodontically treated teeth in a novel conservative manner. Settings and Design: Research laboratory, in vitro study. Materials and Methods: Seventy-five extracted maxillary premolars were procured. Fifteen teeth were left untreated (Group A) and the remaining teeth were endodontically treated followed by standardized mesio-occluso-distal preparation and randomly assigned to experimental groups (n = 15) as follows: (B) no restoration, (C) restoration with composite, (D) EverStick® POST followed by composite, and (E) vertical glass fibers within 3 mm of the coronal root canal space and buccopalatal flaring of the coronal fibers followed by composite. After conditioning and thermocycling, specimens were loaded under a universal testing machine to evaluate fracture resistance and fracture pattern of specimens. Statistical Analysis Used: Obtained scores were statistically analyzed using one-way analysis of variance test for stress analysis, post hoc Tukey's test for intergroup comparison, and Chi-square test for analysis of favorable and unfavorable fracture. Results: The fracture resistance was highest to lowest as follows: Group A > E > C > D > B (P < 0.001). Conclusion: EverStick®POST used in conservative manner improved fracture strength of teeth significantly.

Efficacy of various solutions in preventing orange-brown precipitate formed during alternate use of sodium hypochlorite and chlorhexidine: An in vitro study.

AIM: The study evaluated the effectiveness of three intermediate endodontic irrigating solutions in eliminating the residual sodium hypochlorite (NaOCl), thus preventing the formation of the orange-brown precipitate when 2% chlorhexidine (CHX) is used as the final irrigant. MATERIALS AND METHODS: A total of 40 extracted human maxillary anterior teeth were selected, disinfected, and decoronated to obtain a standardized length of 10 mm. The teeth were prepared with Protaper universal rotary files until size F4 using 2.5% NaOCl as an irrigant during instrumentation. The teeth were then randomly divided into four groups of 10 samples each based on the irrigating solutions used during final wash sequence as follows: Group A - (2.5% NaOCl and 2% CHX), Group B - (2.5% NaOCl followed by 70% Isopropyl Alcohol and 2% CHX), Group C - (2.5% NaOCl followed by 6.25% sodium metabisulfite and 2% CHX), and Group D - (2.5% NaOCl followed by 3.86% sodium Thiosulfate and 2% CHX). The roots were sectioned longitudinally and the canal surface was evaluated under dental operating microscope (×16) for the presence of orange-brown precipitate. The results were tabulated as per scoring criteria and statistically analyzed. STATISTICAL ANALYSIS USED: One-way ANOVA test and post hoc Tukey's test. RESULTS: The lowest mean score was observed in Group C, followed by Group D and Group B, respectively. In comparison, there was a statistically significant (P < 0.001) difference in results between Group C and the other experimental groups. However, there was no statistically significant difference between Group B and Group D. CONCLUSION: Sodium metabisulfite was found to be very effective in preventing the formation of orange-brown precipitate.

A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia.

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry.

Prior surgery determines islet yield and insulin requirement in patients with chronic pancreatitis.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TP-IAT) is safe and effective in the management of intractable pain associated with chronic pancreatitis (CP). Prevention of pancreatogenic diabetes after TP-IAT is related to islet yield from the diseased pancreas. The purpose of this study is to compare islet yield and insulin requirement in the 76 patients who underwent different surgical procedures before TP-IAT at the Medical University of South Carolina between 2009 and 2011. METHODS: Patients were grouped into four categories based on the operation they had before TP-IAT: transduodenal sphincteroplasty/no prior surgery (n=50), Whipple or Beger procedure (n=14), distal pancreatectomy (n=8), or lateral pancreaticojejunostomy (n=4). Islets were harvested from pancreases of those patients at our current good manufacturing practice facility. Total unpurified islets were transplanted into patients via portal vein infusion. Pancreatic fibrosis, islet yield, cell viability, and insulin requirement were measured. RESULTS: The pancreases of transduodenal sphincteroplasty/no prior surgery and Whipple or Beger procedure patients were less fibrotic and had higher islet yield compared with those who had distal pancreatectomy or lateral pancreaticojejunostomy. Higher islet yield also correlated with a greater diabetes-free rate and a lesser insulin requirement at the following intervals: preoperative, postoperative, and 6 months after TP-IAT. CONCLUSIONS: Prior surgery is strongly correlated with the extent of pancreatic fibrosis, islet yield, and insulin requirements in CP patients undergoing TP-IAT. The history of prior pancreatic resection and drainage procedures may be used to predict postoperative islet function and help to determine the optimal timing for TP-IAT in CP patients.

Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models.

Rhabdomyosarcoma (RMS) is a childhood cancer originating from skeletal muscle, and patient survival is poor in the presence of metastatic disease. Few determinants that regulate metastasis development have been identified. The receptor tyrosine kinase FGFR4 is highly expressed in RMS tissue, suggesting a role in tumorigenesis, although its functional importance has not been defined. Here, we report the identification of mutations in FGFR4 in human RMS tumors that lead to its activation and present evidence that it functions as an oncogene in RMS. Higher FGFR4 expression in RMS tumors was associated with advanced-stage cancer and poor survival, while FGFR4 knockdown in a human RMS cell line reduced tumor growth and experimental lung metastases when the cells were transplanted into mice. Moreover, 6 FGFR4 tyrosine kinase domain mutations were found among 7 of 94 (7.5%) primary human RMS tumors. The mutants K535 and E550 increased autophosphorylation, Stat3 signaling, tumor proliferation, and metastatic potential when expressed in a murine RMS cell line. These mutants also transformed NIH 3T3 cells and led to an enhanced metastatic phenotype. Finally, murine RMS cell lines expressing the K535 and E550 FGFR4 mutants were substantially more susceptible to apoptosis in the presence of a pharmacologic FGFR inhibitor than the control cell lines expressing the empty vector or wild-type FGFR4. Together, our results demonstrate that mutationally activated FGFR4 acts as an oncogene, and these are what we believe to be the first known mutations in a receptor tyrosine kinase in RMS. These findings support the potential therapeutic targeting of FGFR4 in RMS.