All-epiphyseal versus trans-epiphyseal screw fixation for tillaux fractures: Does it matter?

BACKGROUNDTillaux fractures occur primarily in adolescents due to the pattern of physeal closure and are classified as Salter-Harris type III physeal fractures. Operative management with screw fixation is recommended for more than 2 mm of displacement or more than 1 mm of translation. However, the efficacy and complications of trans-physeal vs all-physeal screw fixation have not been investigated extensively.AIMTo compare the clinical and functional outcomes of trans-physeal (oblique) and all-epiphyseal (parallel) screw fixation in management of Tillaux fractures among pediatric patients. METHODSThis was an ethics board approved retrospective review of pediatric patients who presented to our tertiary children’s care facility with Tillaux fractures. We included patients who had surgical fixation of a Tillaux fracture over a 10 year period. Data analysis included demographics, mode of injury, management protocols, and functional outcomes. The patients were divided into group 1 (oblique fixation) and group 2 (parallel fixation). Baseline patient characteristics and functional outcomes were compared between groups. Statistical tests to evaluate differences included Fisher’s Exact or Chi-squared and independent samples t or Mann Whitney tests for categorical and continuous variables, respectively.RESULTSA total of 42 patients (28 females and 14 males) were included. There were no significant differences in body mass index, sex, age, or time to surgery between the groups [IK2]. Sports injuries accounted for 61.9% of the cases, particularly non-contact (57.1%) and skating (28.6%) injuries. Computed Tomography (CT) scan was ordered for 28 patients (66.7%), leading to diagnosis confirmation in 17 patients and change in management plan in 11 patients. [GRC3] Groups 1 and 2 consisted of 17 and 25 patients, respectively. For mid to long-term functional outcomes, there were 14 and 10 patients in groups 1 and 2, respectively. Statistical analysis revealed no significant differences in the functional outcomes, pain scores, or satisfaction between groups. No infections, non-unions, physeal arrest, or post-operative ankle deformities were reported. Two (4.8%) patients had difficulty returning to sports post-surgery due to pain. One was a dancer, and the other patient had pain while running, which led to hardware removal. Both patients had parallel fixation. Hardware removal for groups 1 and 2 were 4 (23.5%) and 5 (20.0%) patients, respectively. The reasons for removal was pain in 2 patients, and parental preference in the remaining. CONCLUSIONThis is the largest reported series of pediatric patients with Tillaux fractures comparing functional outcomes of different methods of screw fixation orientation to the physis, which showed no difference regarding functional outcomes.     

Targeting TGF-β for treatment of osteogenesis imperfecta

BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-β signaling in children with OI and conducted a phase I clinical trial of TGF-β inhibition in adults with OI.METHODSHistology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-β neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and lumbar spine areal bone mineral density (LS aBMD) were assessed.RESULTSOI bone demonstrated woven structure, increased osteocytes, high turnover, and reduced maturation. SMAD phosphorylation was the most significantly upregulated GO molecular event. GSEA identified the TGF-β pathway as the top activated signaling pathway, and IPA showed that TGF-β1 was the most significant activated upstream regulator mediating the global changes identified in OI bone. Treatment with fresolimumab was well-tolerated and associated with increases in LS aBMD in participants with OI type IV, whereas participants with OI type III and VIII had unchanged or decreased LS aBMD.CONCLUSIONIncreased TGF-β signaling is a driver pathogenic mechanism in OI. Anti–TGF-β therapy could be a potential disease-specific therapy, with dose-dependent effects on bone mass and turnover.TRIAL REGISTRATIONClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03064074","term_id":"NCT03064074"}}NCT03064074.FUNDINGBrittle Bone Disorders Consortium (U54AR068069), Clinical Translational Core of Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (P50HD103555) from National Institute of Child Health and Human Development, USDA/ARS (cooperative agreement 58-6250-6-001), and Sanofi Genzyme.     

Accumulation of mitochondrial DNA damage in keratoconus corneas

PURPOSE: To determine whether keratoconus (KC) corneas have more mitochondrial (mt)DNA damage than do normal corneas. METHODS: Thirty-three normal corneas and 34 KC corneas were studied. Immunohistochemistry for mitochondria-encoded cytochrome c oxidase (complex IV) subunit 1 (CO-Iota) and porins was performed. Total DNA was isolated and mtDNA genome amplified by either long-extension-polymerase chain reaction (LX-PCR) or short-extension-PCR (SX-PCR). LX-PCR mtDNA was digested with restriction enzymes to confirm full-length mtDNA amplicon. SX-PCR mtDNA was probed by Southern blot analysis. The T414G mutation was analyzed by peptide nucleic acid directed clamping PCR. Real-time PCR measured the ratio of mtDNA to nuclear (n)DNA. RESULTS: KC corneas had decreased CO-Iota in areas of corneal thinning. LX-PCR mtDNA digested with restriction enzymes showed expected size bands except for PstI, which showed two additional bands in some KC corneas (2/18). By both LX-PCR (7.4 +/- 3.8 vs. 4.3 +/- 2.7, P < 0.04) and SX-PCR (5.5 +/- 0.55 vs. 2.4 +/- 2.0, P < 0.006), KC corneas had an increased number of smaller-sized bands (representing mtDNA deletions/mutations) compared with normal corneas. Southern blot analysis of SX-PCR products confirmed their mtDNA origin. The T414G mutation was not detected in either KC or normal corneas. KC corneas showed a trend of lower mtDNA-to-nDNA ratio (26%, P < 0.7) than did normal corneas. CONCLUSIONS: KC corneas exhibit more mtDNA damage than do normal corneas. The previously reported increased oxidative stress and altered integrity of mtDNA may be related to each other and may be important in KC pathogenesis.     

Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts

PURPOSE: To determine whether keratoconus (KC) corneal fibroblast cultures have increased reactive oxygen species (ROS) production and are more susceptible to stress-related challenges. METHODS: Normal (n = 9) and KC (n = 10) stromal fibroblast cultures were incubated in either neutral- or low-pH conditions, with or without hydrogen peroxide. Catalase activities were measured with a fluorescent substrate assay. Superoxide and ROS/reactive nitrogen species (RNS) productions were determined with an amine-reactive green-dye assay and 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) dye assay, respectively. Cell viability was analyzed by a dye-exclusion assay. Caspase 3 activity was measured by a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was used to measure the mitochondrial membrane potential (delta psi m). RESULTS: KC fibroblasts had increased superoxide and ROS/RNS production (6.2-fold, P < 0.001 and 1.8-fold, P < 0.001, respectively) and catalase activity (P < 0.01) with higher concentrations of H2O2 compared with normal cultures (P = 0.16). After a low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3-fold, P < 0.02), showed higher caspase-3 activity (7.5-fold, P < 0.02) and decreased delta psi m (2.6-fold, P < 0.04), and had decreased cell viability (37%, P < 0.005 vs. 20%, P < 0.27) compared with normal fibroblasts. CONCLUSIONS: Under identical conditions, KC fibroblasts had increased basal generation of ROS/RNS and were more susceptible to stressful challenges (low-pH and/or H2O2 conditions) than were normal fibroblasts. In addition, the stressed KC fibroblasts possessed characteristics similar to those found in the intact KC corneas (increased catalase activity, ROS production, and apoptosis). These properties may play a role in the pathogenesis of KC.     

Double aortic arch as a source of airway obstruction in a child

Double aortic arch (DAA) is a congenital vascular anomaly. The diagnosis was difficult till the child was symptomatic, and other causes were ruled out. We present the interesting images of a child of respiratory distress because of tracheal compression from DAA.     

Multiple drug resistant,tumorigenic stem-like cells in oral cancer

An in vitro cell line model was established to exemplify tumor stem cell concept in oral cancer. We were able to identify CD147 expressing fractions in SCC172 OSCC cell line with differing Hoechst dye efflux activity and DNA content. In vivo tumorigenic assay revealed three fractions enriched with stem-like cells capable of undergoing mesenchymal transition and a non-tumorigenic fraction. The regeneration potential and transition of one fraction to other imitated the phenotypic switch and functional disparities evidenced during oral tumor progression. Knowledge of these additional stem-like subsets will improve understanding of stem cell based oral epithelial tumor progression from normal to malignant lesions.     

Aortico-right ventricular tunnel with anomalous right coronary artery

Two patients with aortic right ventricular tunnel and anomalous origin of the right coronary artery from the tunnel are reported. The literature on this condition is reviewed.     

A comparison of external and internal jugular venous pressures to monitor pulmonary artery pressure after superior cavopulmonary anastomosis

The internal jugular vein continues to be the preferred site for cannulation to monitor central venous pressure despite the reported evidence of the accuracy of external jugular venous pressure (EJVP) to reliably predict internal jugular venous pressure (IJVP). Internal jugular venous cannulation carries a risk of thrombosis that can be life-threatening in children undergoing superior cavopulmonary anastomosis and a subsequent Fontan procedure. The present study compared IJVP and EJVP in children undergoing superior cavopulmonary anastomosis and found no statistical and clinical difference between IJVP and EJVP. Thus, external jugular vein cannulation reliably predicts IJVP and pulmonary artery pressures in children undergoing superior cavopulmonary anastomosis, and may obviate the risk of life-threatening cavopulmonary thrombosis.     

The process of family management when a baby is diagnosed with a lethal congenital condition

The Family Management Style Framework (FMSF) was used as a conceptual basis for secondary data analysis of 55 previously conducted interviews with mothers and fathers of children with a lethal congenital condition from two surgical treatment eras. The directed content analysis was guided by a coding structure developed from family management dimensions identified in prior research of family response to childhood chronic conditions. Results indicated that application of the FMSF was helpful in differentiating families and their processes of family management at the onset of their infant's illness through to surviving the first surgery and going home. The dimensions of Illness View and Child Identity were central to the parents' capacity to manage their baby's illness demands within their family context. Applying a robust family framework to a complex neonatal condition at illness onset provides compelling direction for clinical interventions and their rigorous evaluation.