The efficacy of benzodiazepines as acute anxiolytics in children: A meta-analysis.

OBJECTIVE: Current practice guidelines do not recommend benzodiazepines for acute management of anxiety disorders in pediatric patients. However, in procedural settings, benzodiazepines are commonly used to relieve acute preprocedural stress. This meta-analysis examines the efficacy and tolerability of benzodiazepines as short-term anxiolytics in children. METHOD: PubMed was searched for randomized controlled trials assessing the efficacy of benzodiazepines as short-term anxiolytics in pediatric patients. Twenty-one trials involving 1,416 participants were included. A fixed effects model was used to examine the standardized mean difference of improvement in anxiety levels compared to control conditions. In stratified subgroup and meta-regression, the effect of the specific agent, dose, timing, and setting of benzodiazepine treatment was examined. RESULTS: A significant benefit was seen for benzodiazepines compared to control (standardized mean difference = 0.71 [95% confidence interval, 0.60-0.82], k = 24, z = 12.7, P < .001). There was also funnel plot asymmetry in this meta-analysis, suggesting some evidence of publication bias. Moderator analyses found that when benzodiazepines were used in dental or nonoperating room procedures, they were more effective than when they were used in operating room procedures (test for subgroup differences Q2 = 6.34, P = .04). Tolerability analysis revealed there was no significant difference in the risk of developing irritability or behavioral changes between benzodiazepine and control groups. CONCLUSIONS: Benzodiazepines are effective and well-tolerated when used as short-term anxiolytics in procedural settings for pediatric patients. Further research is needed to determine whether benzodiazepines are effective in pediatric anxiety disorders.

Leaflet Mechanical Properties of Carpentier-Edwards Perimount Magna Pericardial Aortic Bioprostheses.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has recently been shown to be equivalent to surgical aortic valve replacement (SAVR) in intermediate-risk patients. As TAVR expands towards the traditionally SAVR population, TAVR versus SAVR durability becomes increasingly important. While the durability of TAVR is unknown, valve design - particularly with regards to leaflet stress - impacts on valve durability. Although leaflet stress cannot be measured directly, it can be determined using finite element modeling, with such models requiring the mechanical properties of the leaflets. Balloon-expandable TAVR involves the use of bovine pericardial leaflets treated in the same manner as surgical bioprosthetic leaflets. The study aim was to determine the leaflet mechanical properties of Carpentier-Edwards bioprostheses for future TAVR and SAVR computational models. METHODS: A total of 35 leaflets were excised from 12 Carpentier-Edwards Model 3000TFX Perimount Magna aortic bioprostheses (21 mm, 23 mm, and 25 mm) and subjected to displacement-controlled equibiaxial stretch testing. The stress-strain data acquired were fitted to a Fung constitutive model to describe the material properties in circumferential and radial directions. Leaflet stiffness was calculated at specified physiological stress, corresponding to zero pressure, systemic pressure, and between zero and systemic pressure. RESULTS: The 21-mm bioprostheses had significantly thinner leaflets than the larger bioprostheses. A non-linear stress-strain relationship was observed in all leaflets along the circumferential and radial directions. No significant difference in leaflet stiffness at systemic pressure, or between zero and systemic pressure, was found among the three bioprosthesis sizes. However, the leaflets from the 23 mm bioprosthesis were significantly more compliant than those of the 21 mm and 25 mm bioprostheses at zero pressure in the circumferential direction. No differences were observed in leaflet stiffness in circumferential versus radial directions. CONCLUSIONS: The bovine pericardial leaflets from Carpentier-Edwards Perimount Magna bioprostheses showed no differences in material properties among different valve sizes at systemic pressure. The thinner 21 mm leaflets did not show any corresponding differences in leaflet stiffness, which suggests that the thinner TAV leaflets may have a similar stiffness to their thicker SAV counterparts.

Biomechanics of Failed Pulmonary Autografts Compared to Native Aortic Roots.

BACKGROUND: Progressive autograft dilatation after a Ross operation suggests that remodeling does not effectively reproduce native aortic root biomechanics. In the first of this two-part series, we compared mechanical properties of explanted autografts to pulmonary roots at pulmonary pressures. The goal of this study was to compare mechanical properties of explanted autografts to native aortic roots at systemic pressures. METHODS: Autograft specimens were obtained from patients undergoing reoperation after Ross operation. For comparison, native aortic roots were obtained from unused donor hearts. Biaxial stretch testing was performed to determine tissue mechanical properties. Tissue stiffness was determined at patient-specific physiologic stresses corresponding to systemic pressures (80 and 120 mm Hg) and hypertensive state (200 mm Hg). RESULTS: Nonlinear stress-strain curves were present for both failed autografts and native aortic roots. Explanted autografts were significantly more compliant than native aortic roots at 80 mm Hg (1.53 ± 0.68 versus 2.99 ± 1.34 MPa; p = 0.011), 120 mm Hg (2.54 ± 1.18 versus 4.93 ± 2.21 MPa; p = 0.013), and 200 mm Hg (4.79 ± 2.30 versus 9.21 ± 4.16 MPa; p = 0.015). Autograft tissue stiffness at 80, 120, and 200 mm Hg was not correlated with age at the time of Ross operation (p = 0.666, p = 0.639, and p = 0.616, respectively) or time in the systemic circulation (p = 0.635, p = 0.637, and p = 0.647, respectively). CONCLUSIONS: Failed pulmonary autografts retained a nonlinear response to mechanical loading typical of healthy arterial tissue. Despite similar wall thickness between autografts and aorta, autograft stiffness in this patient population was significantly reduced compared with native aortic roots. We demonstrated that biomechanical remodeling was inadequate in these specimens to achieve native aortic mechanical properties, which may have resulted in progressive autograft root dilatation.

Dickkopf-related Protein 3 as a Sensitive and Specific Marker for Cerebrospinal Fluid Leaks.

HYPOTHESIS: Cerebrospinal fluid (CSF) can be identified by using an enzyme-linked immunosorbent assay (ELISA) for Dickkopf-related protein 3 (DKK3). BACKGROUND: Cerebrospinal fluid leakage from the subarachnoid space is a potentially alarming condition that, left unrepaired, may result in increased risk of meningitis and encephalitis. Current biochemical methods of CSF leak detection involve using beta-2-transferrin-based or beta trace protein-based assays, both of which, at present, have limitations that hinder practical clinical application. This study presents the immunological detection of the CSF-enriched protein DKK3 as a method for detection of a CSF leak. METHODS: Antibodies against DKK3 were generated in rabbits and goats immunized with recombinant human DKK3. Varying dilutions and combinations of human CSF and serum were tested on immunoblots and sandwich ELISA using antibodies to DKK3. RESULTS: ELISA data show that there is a negligible amount of detectable DKK3 in serum samples compared with CSF samples. Inclusion of sera (up to 30%) in a sample containing CSF failed to produce a positive signal, whereas concentrations of CSF as low as 1% produced a positive signal. The minimum concentration required for reliable CSF detection in a sandwich ELISA was determined to be 0.5  µl. CONCLUSION: ELISA sandwich assays for DKK3 can reliably detect the presence of as little as 0.5 µl of human CSF, even in the presence of excessive serum. This study provides quantitative evidence of the utility of DKK3 immunoreactivity as an assay for the presence of CSF in samples that contain contaminating sera. The robustness of this assay has allowed for the development of a rapid, point of care test for the detection of CSF in clinical and surgical setting.

Biomechanics of Failed Pulmonary Autografts Compared With Normal Pulmonary Roots.

BACKGROUND: Progressive dilatation of pulmonary autografts after the Ross operation may reflect inadequate remodeling of the native pulmonary root to adapt to systemic circulation. Understanding the biomechanics of autograft root dilatation may aid designing strategies to prevent dilatation. We have previously characterized normal human pulmonary root material properties; however, the mechanical properties of failed autografts are unknown. In this study, failed autograft roots explanted during reoperation were acquired, and their material properties were determined. METHODS: Failed pulmonary autograft specimens were obtained from patients undergoing reoperation after the Ross operation. Fresh human native pulmonary roots were obtained from the transplant donor network as controls. Biaxial stretch testing was performed to determine tissue mechanical properties. Tissue stiffness was determined at patient-specific physiologic stresses at pulmonary pressures. RESULTS: Nonlinear stress-strain response was present in both failed autografts and normal pulmonary roots. Explanted pulmonary autografts were less stiff than were their native pulmonary root counterparts at 8 mm Hg (134 ± 42 vs 175 ± 49 kPa, respectively) (p = 0.086) and 25 mm Hg (369 ± 105 vs 919 ± 353 kPa, respectively) (p = 0.006). Autograft wall stiffness at both 8 and 25 mm Hg was not correlated with age at the Ross procedure (p = 0.898 and p = 0.813, respectively) or with time in the systemic circulation (p = 0.609 and p = 0.702, respectively). CONCLUSIONS: Failed pulmonary autografts retained nonlinear response to mechanical loading typical of healthy human arterial tissue. Remodeling increased wall thickness but decreased wall stiffness in failed autografts. Increased compliance may explain progressive autograft root dilatation in autograft failures.

Impairment of Caloric Function After Cochlear Implantation.

PURPOSE: This article seeks to review current literature on caloric function following cochlear implantation while analyzing any correlations of caloric function changes with vestibular symptoms. METHOD: This article is a systematic review of evidence-based literature. English language articles published between 1980 and 2014 that presented some form of caloric data from cochlear implant (CI) patients and that did not solely analyze overlapping data from a previous study were reviewed. Twenty-five articles met these criteria. RESULTS: Of the 439 individuals tested, 37% of patients demonstrated reduced maximum slow-phase velocity, and 34% had onset of caloric asymmetry post-CI. CONCLUSIONS: This review article found that cochlear implantation can affect caloric responses but is variable. When counseling patients preoperatively, possible effects of CI on labyrinthine function should be discussed.