Citations

OBJECTIVEIn children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty.METHODSThe authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty.RESULTSA total of 359 patients met the inclusion criteria. The patients’ mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17–4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03–5.79), and ventilator dependence (OR 8.45, 95% CI 1.10–65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection.Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98–0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts.CONCLUSIONSThis is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.

AimsThe aim of this study was to evaluate near-infrared spectroscopy (NIRS) as a continuous, non-invasive monitor for acute compartment syndrome (ACS).Patients and MethodsNIRS sensors were placed on 86 patients with, and 23 without (controls), severe leg injury. NIRS values were recorded for up to 48 hours. Longitudinal data were analyzed using summary and graphical methods, bivariate comparisons, and multivariable multilevel modelling.ResultsMean NIRS values in the anterior, lateral, superficial posterior, and deep posterior compartments were between 72% and 78% in injured legs, between 69% and 72% in uninjured legs, and between 71% and 73% in bilaterally uninjured legs. In patients without ACS, the values were typically > 3% higher in injured compartments. All seven limbs with ACS had at least one compartment where NIRS values were 3% or more below a reference uninjured control compartment. Missing data were encountered in many instances.ConclusionNIRS oximetry might be used to aid the assessment and management of patients with ACS. Sustained hyperaemia is consistent with the absence of ACS in injured legs. Loss of the hyperaemic differential warrants heightened surveillance. NIRS values in at least one injured compartment(s) were > 3% below the uninjured contralateral compartment(s) in all seven patients with ACS. Additional interventional studies are required to validate the use of NIRS for ACS monitoring. Cite this article: Bone Joint J 2018;100-B:787–97.

Background: Anterior cruciate ligament (ACL) injuries are catastrophic events that affect athletic careers and lead to long-term degenerative knee changes. As injuries are believed to occur within the first 50 milliseconds after initial contact during a rapid deceleration task, impact simulators that rapidly deliver impulse loads to cadaveric specimens have been developed. However, no impactor has reproducibly and reliably created ACL injures in a distribution that mimics clinical observation. Purpose: To better understand ACL injury patterns through a cadaveric investigation that applied in vivo–measured external loads to the knee during simulated landings. Study Design: Controlled laboratory study. Methods: A novel mechanical impact simulator reproduced kinetics from in vivo–recorded drop landing tasks on 45 cadaveric knees. Specimens were exposed to a randomized order of variable knee abduction moment, anterior tibial shear, and internal tibial rotation loads before the introduction of an impulse load at the foot. This process was repeated until a hard or soft tissue injury was induced on the joint. Injuries were assessed by an orthopaedic surgeon, and ligament strain was recorded by implanted strain gauges. Results: The mechanical impact simulator induced ACL injuries in 87% of specimens, with medial collateral ligament (MCL) injuries in 31%. ACL tear locations were 71% femoral side, 21% midsubstance, and 9% tibial side. Peak strain before failure for ACL-injured specimens was 15.3% ± 8.7% for the ACL and 5.1% ± 5.6% for the MCL ( P < .001). Conclusion: The ACL injuries induced by the mechanical impact simulator in the present study have provided clinically relevant in vitro representations of in vivo ACL injury patterns as cited in the literature. Additionally, current ligament strains corroborate the literature to support disproportionate loading of the ACL relative to the MCL during athletic tasks. Clinical Relevance: These findings indicate that the mechanical impact simulator is an appropriate model for examining independent mechanical variables, treatment techniques, and preventive interventions during athletic tasks leading up to and including an ACL injury. Accordingly, this system can be utilized to further parse out contributing factors to an ACL injury as well as assess the shortcomings of ACL reconstruction techniques in a dynamic, simulated environment that is better representative of in vivo injury scenarios.

Summary Ketogenic dietary therapies ( KDTs ) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre‐ KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow‐up, side events, and KDT discontinuation. It has been helpful in outlining a state‐of‐the‐art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.

Purpose: To compare the outcomes of total shoulder arthroplasty (TSA) with posterior capsule plication (PCP) and reverse shoulder arthroplasty (RSA) in patients with primary osteoarthritis, posterior subluxation, and bone loss (Walch B2). Patients and methods: All shoulders undergoing anatomic TSA with PCP were retrospectively identified (group 1, G1) and compared to shoulders undergoing RSA (group 2, G2) for Walch B2 osteoarthritis. There were 15 patients in G1 (mean (SD) age and follow-up of 70.5 (7.5) years and 42.8 (18.4) months, respectively) and 16 patients in G2 (mean (SD) age and follow-up of 72.6 (5.4) years and 35.1 (14.2) months, respectively). Results: Both groups had substantial improvements in pain and function. In G1, results were excellent in 80% and satisfactory in 20%, compared to 81% and 6% in G2, respectively ( p = 0.2). The mean (SD) American Shoulder and Elbow Surgeons score was 91.2 (6.7) and 80.3 (14.3) in G1 and G2, respectively ( p = 0.08). The mean Simple Shoulder Test score was 10.6 in G1 and 8.5 in G2 ( p = 0.01). There were no reoperations in either group, but G1 had seven postoperative complications. Conclusions: The outcomes of TSA with PCP are comparable to RSA in patients with osteoarthritis and biconcave glenoids. However, TSA leads to more complications while RSA leads to lower functional outcomes.

Background: Female patients sustain noncontact knee ligament injuries at a greater rate compared with their male counterparts. The cause of these differences in the injury rate and the movements that load the ligaments until failure are still under dispute in the literature. Purpose/Hypotheses: This study was designed to determine differences in anterior cruciate ligament (ACL) and medial collateral ligament (MCL) strains between male and female cadaveric specimens during a simulated athletic task. The primary hypothesis tested was that female limbs would demonstrate significantly greater ACL strain compared with male limbs under similar loading conditions. A secondary hypothesis was that MCL strain would not differ between sexes. Study Design: Controlled laboratory study. Methods: Motion analysis of 67 athletes performing a drop vertical jump was conducted. Kinetic data were used to categorize injury risk according to tertiles, and these values were input into a cadaveric impact simulator to assess ligamentous strain during a simulated landing task. Uniaxial and multiaxial load cells and differential variable reluctance transducer strain sensors were utilized to collect mechanical data for analysis. Conditions of external loads applied to the cadaveric limbs (knee abduction moment, anterior tibial shear, and internal tibial rotation) were varied and randomized. Data were analyzed using 1-way analysis of variance (ANOVA), 2-way repeated-measures ANOVA, and the Fisher exact test. Results: There were no significant differences ( P = .184) in maximum ACL strain between male (13.2% ± 8.1%) and female (16.7% ± 8.3%) specimens. Two-way ANOVA demonstrated that across all controlled external load conditions, female specimens consistently attained at least 3.5% increased maximum ACL strain compared with male specimens ( F 1,100 = 4.188, P = .043); however, when normalized to initial contact, no significant difference was found. There were no significant differences in MCL strain between sexes for similar parameters. Conclusion: When compared with baseline, female specimens exhibited greater values of ACL strain at maximum, initial contact, and after impact (33, 66, and 100 milliseconds, respectively) than male specimens during similar loading conditions, with a maximum strain difference of at least 3.5%. During these same loading conditions, there were no differences in MCL loading between sexes, and only a minimal increase of MCL loading occurred during the impact forces. Our results indicate that female patients are at an increased risk for ACL strain across all similar conditions compared with male patients. Clinical Relevance: These data demonstrate that female specimens, when loaded similarly to male specimens, experience additional strain on the ACL. As the mechanical environment was similar for both sexes with these simulations, the greater ACL strain of female specimens must be attributed to ligament biology, anatomic differences, or muscular stiffness.

ABSTRACT HIV protease is known to cause cell death, which is dependent upon cleavage of procaspase 8. HIV protease cleavage of procaspase 8 generates Casp8p41, which directly binds Bak with nanomolar affinity, causing Bak activation and consequent cell death. Casp8p41 can also bind Bcl2 with nanomolar affinity, in which case cell death is averted. Central memory CD4 T cells express high levels of Bcl2, possibly explaining why those cells do not die when they reactivate HIV. Here, we determine that the Casp8p41-Bcl2 complex is polyubiquitinated and degraded by the proteasome. Ixazomib, a proteasome inhibitor in clinical use, blocks this pathway, increasing the abundance of Casp8p41 and causing more cells to die in a Casp8p41-dependent manner. IMPORTANCE The Casp8p41 pathway of cell death is unique to HIV-infected cells yet is blocked by Bcl2. Once bound by Bcl2, Casp8p41 is polyubiquitinated and degraded by the proteasome. Proteasome inhibition blocks degradation of Casp8p41, increasing Casp8p41 levels and causing more HIV-infected cells to die.

Background: Limb asymmetries, as determined through in vivo biomechanical measures, are known risk factors for anterior cruciate ligament (ACL) injury. Previous cadaveric studies have shown a lack of significant differences in ligament strain between contralateral lower extremities when identical kinematics were simulated on specimens. Recent methodological developments have applied in vivo knee kinetics to exert landing forces on cadaveric lower extremities to mimic ACL injury events, but it is unknown whether contralateral limbs fail in a consistent manner during impact simulator testing. Hypothesis: It was hypothesized that contralateral lower extremities would not exhibit side-to-side differences in ligament strains. Furthermore, it was hypothesized that failure loads and failure locations would be independent of limb dominance. Study Design: Controlled laboratory study. Methods: Fourteen pairs of cadaveric lower extremities were obtained from an anatomic donations program (8 female, 6 male; mean ± SD: age, 41.7 ± 8.1 years; mass, 86.8 ± 27.0 kg; body mass index, 29.4 ± 9.0 kg/m 2 ). A mechanical impact simulator was used to re-create the impulse ground-reaction force generated during an in vivo landing task. Ligament strains were recorded by differential variable force transducers implanted on the ACL and medial collateral ligament (MCL). Results: No significant differences were observed in peak ACL or peak MCL strain for 5 loading conditions. Fisher exact tests of independence revealed that limb dominance was independent of both load at failure and failure location. Conclusion: There were no significant differences in ACL and MCL strain values between limb sides during in vitro impact simulation testing. This finding indicates that limb dominance does not influence the failure threshold of the ACL, since there was no significant difference in failure strains. The functional mechanics of the ACL are comparable between contralateral pairs from the same healthy specimen. Clinical Relevance: Injury mechanisms and intra-articular mechanics cannot be ethically studied in an in vivo setting. The current study provides additional insight into limb asymmetry that is observed among athletes in clinical sports medicine settings.

ABSTRACTIntroduction: For sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers (ENFs), but then healthy subject reference values of HP thresholds are needed. Methods: Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. Results: In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. Discussion: For the studied somatotopic sites, we provide ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Muscle Nerve 58: 509–516, 2018