Potential Alzheimer's early biomarkers in a transgenic rat model and benefits of diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology.

Alzheimer's disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer's model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aß plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings.

Interstitial Brachytherapy for Lip Cancer: Technical Aspects to Individualize Treatment Approach and Optimize Outcomes.

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip. Catheters are inserted across the length of tumor entering and exiting approximately 5 mm beyond the palpable tumor extent. A custom mouthpiece is fabricated to facilitate normal tissue sparing. Patients undergo computed tomography imaging, the gross tumor volume is contoured based on physical examination and computed tomography findings, and an individualized brachytherapy plan is generated with the goals of achieving gross tumor volume D90% ≥ 90% and minimizing V150%. Ten patients with primary (n = 8) or recurrent (n = 2) cancers of the lip who received high-dose-rate lip IBT using 2.0- to 2.5-week treatment regimens are described (median prescription: 47.6 Gy in 14 fractions of 3.4 Gy). Local tumor control was 100%. There were no cases of acute grade ≥4 or late grade ≥2 toxicity, and cosmesis scores were graded as good to excellent in all patients. IBT represents an excellent treatment option for patients with lip squamous cell carcinoma. With careful attention to technical considerations furthered described in the present report, high rates of tumor control, low rates of toxicity, and favorable esthetic and functional outcomes can be achieved with IBT for lip cancer.

Repurposing ibudilast to mitigate Alzheimer's disease by targeting inflammation.

Alzheimer's disease is a multifactorial disease that exhibits cognitive deficits, neuronal loss, amyloid plaques, neurofibrillary tangles and neuroinflammation in the brain. Hence, a multi-target drug would improve treatment efficacy. We applied a new multi-scale predictive modelling framework that integrates machine learning with biophysics and systems pharmacology to screen drugs for Alzheimer's disease using patients' tissue samples. Our predictive modelling framework identified ibudilast as a drug with repurposing potential to treat Alzheimer's disease. Ibudilast is a multi-target drug, as it is a phosphodiesterase inhibitor and toll-like receptor 4 (TLR4) antagonist. In addition, we predict that ibudilast inhibits off-target kinases (e.g. IRAK1 and GSG2). In Japan and other Asian countries, ibudilast is approved for treating asthma and stroke due to its anti-inflammatory potential. Based on these previous studies and on our predictions, we tested for the first time the efficacy of ibudilast in Fisher transgenic 344-AD rats. This transgenic rat model is unique as it exhibits hippocampal-dependent spatial learning and memory deficits and Alzheimer's disease pathology, including hippocampal amyloid plaques, tau paired-helical filaments, neuronal loss and microgliosis, in a progressive age-dependent manner that mimics the pathology observed in Alzheimer's disease patients. Following long-term treatment with ibudilast, transgenic rats were evaluated at 11 months of age for spatial memory performance and Alzheimer's disease pathology. We demonstrate that ibudilast-treatment of transgenic rats mitigated hippocampal-dependent spatial memory deficits, as well as hippocampal (hilar subregion) amyloid plaque and tau paired-helical filament load, and microgliosis compared to untreated transgenic rat. Neuronal density analysed across all hippocampal regions was similar in ibudilast-treated transgenic compared to untreated transgenic rats. Interestingly, RNA sequencing analysis of hippocampal tissue showed that ibudilast-treatment affects gene expression levels of the TLR and ubiquitin-proteasome pathways differentially in male and female transgenic rats. Based on the TLR4 signalling pathway, our RNA sequencing data suggest that ibudilast-treatment inhibits IRAK1 activity by increasing expression of its negative regulator IRAK3, and/or by altering TRAF6 and other TLR-related ubiquitin ligase and conjugase levels. Our results support that ibudilast can serve as a repurposed drug that targets multiple pathways including TLR signalling and the ubiquitin/proteasome pathway to reduce cognitive deficits and pathology relevant to Alzheimer's disease.

Timapiprant, a prostaglandin D2 receptor antagonist, ameliorates pathology in a rat Alzheimer's model.

We investigated the relevance of the prostaglandin D2 pathway in Alzheimer's disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer's disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer's disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer's disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer's disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer's disease.

Targeting the GTV in medically inoperable endometrial cancer using brachytherapy.

PURPOSE: We aimed to determine the relationship between gross tumor volume (GTV) dose and tumor control in women with medically inoperable endometrial cancer, and to demonstrate the feasibility of targeting a GTV-focused volume using imaged-guided brachytherapy. METHODS AND MATERIALS: An endometrial cancer database was used to identify patients. Treatment plans were reviewed to determine doses to GTV, clinical target volume (CTV), and OARs. Uterine recurrence-free survival was evaluated as a function of CTV and GTV doses. Brachytherapy was replanned with a goal of GTV D98 EQD2 ≥ 80 Gy, without regard for coverage of the uninvolved uterus and while respecting OAR dose constraints. RESULTS: Fifty-four patients were identified. In the delivered plans, GTV D90 EQD2 ≥ 80 Gy was achieved in 36 (81.8%) patients. Uterine recurrence-free survival was 100% in patients with GTV D90 EQD2 ≥ 80 Gy and 66.7% in patients with EQD2 < 80 Gy (p = 0.001). On GTV-only replans, GTV D98 EQD2 ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D2cc was lower for bladder (47.1 Gy vs. 73.0 Gy, p < 0.001), and sigmoid (47.0 Gy vs. 58.0 Gy, p = 0.007) on GTV-only replans compared to delivered plans. Bladder D2cc was ≥ 80 Gy in 11 (25.0%) delivered plans and four (9.1%) GTV-only replans (p = 0.043). Sigmoid D2cc was ≥ 65 Gy in 20 (45.4%) delivered plans and 10 (22.7%) GTV-only replans (p = 0.021). CONCLUSIONS: OAR dose constraints should be prioritized over CTV coverage if GTV coverage is sufficient. Prospective evaluation of image-guided brachytherapy to a reduced, GTV-focused volume is warranted.

Gentamicin pre-soaking of hamstring autografts decreases infection rates in anterior cruciate ligament reconstruction.

AIMS: Graft infection following anterior cruciate ligament reconstruction (ACLR) may lead to septic arthritis requiring multiple irrigation and debridement procedures, staged revision operations, and prolonged courses of antibiotics. To our knowledge, there are no previous studies reporting on how gentamicin pre-soaking of hamstring grafts influences infection rates following ACLR. We set out to examine this in our study accordingly. METHODS: This retrospective study included 2,000 patients (1,156 males and 844 females) who underwent primary ACLR with hamstring autografts between 2007 to 2017. This included 1,063 patients who received pre-soaked saline hamstring grafts for ACLR followed by 937 patients who received pre-soaked gentamicin hamstring grafts for ACLR. All operative procedures were completed by a single surgeon using a standardized surgical technique. Medical notes were reviewed and data relating to the following outcomes recorded: postoperative infection, clinical progress, causative organisms, management received, and outcomes. RESULTS: Superficial wound infection developed in 14 patients (1.31 %) receiving pre-saline soaked hamstring grafts compared to 13 patients (1.38 %) receiving pre-gentamicin soaked hamstring grafts, and this finding was not statistically significant (p = 0.692). All superficial wound infections were treated with oral antibiotics with no further complications. There were no recorded cases of septic arthritis in patients receiving pre-gentamicin soaked grafts compared to nine patients (0.85%) receiving pre-saline soaked grafts, which was statistically significant (p = 0.004). CONCLUSION: Pre-soaking hamstring autographs in gentamicin does not affect superficial infection rates but does reduce deep intra-articular infection rates compared to pre-soaking hamstring grafts in saline alone. These findings suggest that pre-soaking hamstring autografts in gentamicin provides an effective surgical technique for reducing intra-articular infection rates following ACLR.Cite this article: Bone Jt Open 2021;2(1):66-71.

Functional alignment achieves soft-tissue balance in total knee arthroplasty as measured with quantitative sensor-guided technology.

AIMS: Total knee arthroplasty (TKA) using functional alignment aims to implant the components with minimal compromise of the soft-tissue envelope by restoring the plane and obliquity of the non-arthritic joint. The objective of this study was to determine the effect of TKA with functional alignment on mediolateral soft-tissue balance as assessed using intraoperative sensor-guided technology. METHODS: This prospective study included 30 consecutive patients undergoing robotic-assisted TKA using the Stryker PS Triathlon implant with functional alignment. Intraoperative soft-tissue balance was assessed using sensor-guided technology after definitive component implantation; soft-tissue balance was defined as intercompartmental pressure difference (ICPD) of < 15 psi. Medial and lateral compartment pressures were recorded at 10°, 45°, and 90° of knee flexion. This study included 18 females (60%) and 12 males (40%) with a mean age of 65.2 years (SD 9.3). Mean preoperative hip-knee-ankle deformity was 6.3° varus (SD 2.7°). RESULTS: TKA with functional alignment achieved balanced medial and lateral compartment pressures at 10° (25.0 psi (SD 6.1) vs 23.1 psi (SD 6.7), respectively; p = 0.140), 45° (21.4 psi (SD 5.9) vs 20.6 psi (SD 5.9), respectively; p = 0.510), and 90° (21.2 psi (SD 7.1) vs 21.6 psi (SD 9.0), respectively; p = 0.800) of knee flexion. Mean ICPD was 6.1 psi (SD 4.5; 0 to 14) at 10°, 5.4 psi (SD 3.9; 0 to 12) at 45°, and 4.9 psi (SD 4.45; 0 to 15) at 90° of knee flexion. Mean postoperative limb alignment was 2.2° varus (SD 1.0°). CONCLUSION: TKA using the functional alignment achieves balanced mediolateral soft-tissue tension through the arc of knee flexion as assessed using intraoperative pressure-sensor technology. Further clinical trials are required to determine if TKA with functional alignment translates to improvements in patient satisfaction and outcomes compared to conventional alignment techniques. Cite this article: Bone Joint J 2021;103-B(3):507-514.

The impact of COVID-19 on trauma and orthopaedic surgery in the United Kingdom.

The coronavirus 2019 (COVID-19) global pandemic has had a significant impact on trauma and orthopaedic (T&O) departments worldwide. To manage the peak of the epidemic, orthopaedic staff were redeployed to frontline medical care; these roles included managing minor injury units, forming a "proning" team, and assisting in the intensive care unit (ICU). In addition, outpatient clinics were restructured to facilitate virtual consultations, elective procedures were cancelled, and inpatient hospital admissions minimized to reduce nosocomial COVID-19 infections. Urgent operations for fractures, infection and tumours went ahead but required strict planning to ensure patient safety. Orthopaedic training has also been significantly impacted during this period. This article discusses the impact of COVID-19 on T&O in the UK and highlights key lessons learned that may help to proactively prepare for the next global pandemic. Cite this article: Bone Joint Open 2020;1-7:420-423.

Long-Term Results of Revision Total Hip Arthroplasty Using a Modern Extensively Porous-Coated Femoral Stem.

BACKGROUND: The use of an extensively porous-coated uncemented cobalt-chrome monoblock femoral stem for revision total hip arthroplasty (THA) is well established with excellent mid-term results. The aim of this study is to report the long-term survivorship of these implants in femoral stem revisions. METHODS: This is a long-term retrospective review of prospectively collected data of 55 femoral stem revisions in 55 patients using a contemporary, cementless extensively porous-coated cobalt-chrome monoblock stem. All patients between 2001 and 2006 who underwent first time femoral stem revision with a contemporary, cementless extensively porous-coated cobalt-chrome monoblock stem were included. Harris Hip Score, Western Ontario and McMaster Universities Index, and University of California Los Angeles activity scores were recorded preoperatively and at latest follow-up. Radiographs were analyzed for evidence of loosening, subsidence, osteolysis, and bony union. This study included 55 patients, comprising of 36 females (66%) and 19 males (34%) with a mean age of 66.4 ± 9.3 years at the time of surgery. The mean time interval from index procedure was 9.8 ± 2.9 years. Mean time from revision THA to final follow-up was 13.2 ± 2.17 years with a minimum of 10 years of follow-up. RESULTS: Indications for revision included aseptic loosening (33), prosthetic joint infection (13), and periprosthetic fracture (10). Significant improvement in Harris Hip Score (85.1 ± 1.77 vs 51.8 ± 2.3, P < .001), Western Ontario and McMaster Universities Index (17.6 ± 0.77 vs 33.3 ± 0.8, P < .001), and University of California Los Angeles (5.25 ± 0.2 vs 2.7 ± 0.36, P < .001) scores were found at latest follow-up compared to preoperative. Fifty-four patients (98%) achieved stable bony ingrowth on radiographic analysis. All 10 patients treated for periprosthetic fractures achieved bony union of their fractures. Two patients suffered intraoperative periprosthetic fractures and were treated with a cable-plating system. There were no mechanical failures and no femoral stem re-revisions. One patient was diagnosed with a deep infection and was treated with chronic suppressive antibiotic therapy due to significant medical comorbidities. CONCLUSION: Revision of the femoral component with a contemporary extensively porous-coated cobalt-chrome femoral stem has excellent functional outcomes, radiographic outcomes, and long-term survivorship with minimal complications.

Maternal periconceptional and first trimester protein restriction in beef heifers: effects on maternal performance and early fetal growth.

This study evaluated the effect of protein restriction during the periconception (PERI) and first trimester (POST) periods on maternal performance, physiology and early fetal growth. Yearling nulliparous heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri respectively) beginning 60 days before conception. From 24 to 98 days post-conception (dpc), half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost respectively), yielding four groups in a 2×2 factorial design with a common diet until parturition. Protein restriction was associated with lower bodyweight subsequent to reduced (but positive) average daily weight gain (ADG) during the PERI and POST periods. During the POST period, ADG was greater in LPeri than HPeri heifers and tended to be greater in LPost than HPost heifers during the second and third trimester. Bodyweight was similar at term. The pregnancy rate did not differ, but embryo loss between 23 and 36 dpc tended to be greater in LPeri than HPeri heifers. Overall, a greater proportion of male fetuses was detected (at 60 dpc 63.3% male vs 36.7% female). Protein restriction altered maternal plasma urea, non-esterified fatty acids, progesterone, leptin and insulin-like growth factor 1 at critical stages of fetal development. However, profiles varied depending on the sex of the conceptus.

Enhancing return to work or school after a first episode of schizophrenia: the UCLA RCT of Individual Placement and Support and Workplace Fundamentals Module training.

BACKGROUND: This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling. METHODS: Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication. RESULTS: The IPS-WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS-WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS-WFM intervention (45 v. 26 weeks, p < 0.004). CONCLUSIONS: The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

Low cardiac and left anterior descending coronary artery dose achieved with left-sided multicatheter interstitial-accelerated partial breast irradiation.

PURPOSE: Studies have shown that an additional mean dose of 1 Gy to the heart can increase the relative risk of cardiac events. The purpose of this study was to quantify the dose delivered to the heart and left anterior descending artery (LAD) in a series of patients with left-sided breast cancer (BC) or ductal carcinoma in situ treated with multicatheter-accelerated partial breast irradiation (MC-APBI) at a single institution. METHODS AND MATERIALS: Patients with left-sided BC or ductal carcinoma in situ treated consecutively from 2005 to 2011 with MC-APBI were retrospectively identified. Cardiac and LAD contours were generated for each patient. Cardiac dosimetry and distance to the planning target volume were recorded. Patient health records were reviewed and cardiac events were recorded based on Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty consecutive patients with left-sided BC treated with MC-APBI were retrospectively identified. Median followup was 41.4 months. Mean equivalent dose in 2 Gy fractions delivered to the heart and LAD were 1.3 (standard deviation: 0.7, range: 0.2-2.9) and 3.8 (standard deviation: 3.0, range: 0.4-11.3) Gy, respectively. There was an inverse linear relationship (R2 = 0.52) between heart-to-lumpectomy cavity distance and mean heart equivalent dose in 2 Gy fractions. One patient (5%) experienced symptomatic cardiac toxicity. CONCLUSIONS: MC-APBI consistently delivers average doses to the heart and LAD that are similar to those achieved in most series with deep inspiration breath-hold and lower than free-breathing radiotherapy techniques. Distance from the heart to the lumpectomy cavity and the availability of other heart-sparing technologies should be considered to minimize the risk of cardiac toxicity.

Novel use of ViewRay MRI guidance for high-dose-rate brachytherapy in the treatment of cervical cancer.

PURPOSE: To characterize image quality and feasibility of using ViewRay MRI (VR)-guided brachytherapy planning for cervical cancer. METHODS AND MATERIALS: Cervical cancer patients receiving intracavitary brachytherapy with tandem and ovoids, planned using 0.35T VR MRI at our institution, were included in this series. The high-risk clinical target volume (HR-CTV), visible gross tumor volume, bladder, sigmoid, bowel, and rectum contours for each fraction of brachytherapy were evaluated for dosimetric parameters. Typically, five brachytherapy treatments were planned using the T2 sequence on diagnostic MRI for the first and third fractions, and a noncontrast true fast imaging with steady-state precession sequence on VR or CT scan for the remaining fractions. Most patients received 5.5 Gy × 5 fractions using high-dose-rate Ir-192 following 45 Gy of whole-pelvis radiotherapy. The plan was initiated at 5.5 Gy to point A and subsequently optimized and prescribed to the HR-CTV. The goal equivalent dose in 2 Gy fractions for the combined external beam and brachytherapy dose was 85 Gy. Soft-tissue visualization using contrast-to-noise ratios to distinguish normal tissues from tumor at their interface was compared between diagnostic MRI, CT, and VR. RESULTS: One hundred and forty-two fractions of intracavitary brachytherapy were performed from April 2015 to January 2017 on 29 cervical cancer patients, ranging from stages IB1 to IVA. The median HR-CTV was 27.78 cc, with median D90 HR-CTV of 6.1 Gy. The median time from instrument placement to start of treatment using VR was 65 min (scan time 2 min), compared to 105 min using diagnostic MRI (scan time 11 min) (t-test, p < 0.01). The contrast-to-noise ratio of tumor to cervix in both diagnostic MRI and VR had significantly higher values compared to CT (ANOVA and t-tests, p < 0.01). CONCLUSIONS: We report the first clinical use of VR-guided brachytherapy. Time to treatment using this approach was shorter compared to diagnostic MRI. VR also provided significant advantage in visualizing the tumor and cervix compared to CT. This presents a feasible and reliable manner to image and plan gynecologic brachytherapy.

Clinical implementation of a novel Double-Balloon single-entry breast brachytherapy applicator.

PURPOSE: The purpose of the study was to describe the clinical utilization of a novel Double-Balloon applicator for accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: The Double-Balloon single-entry breast applicator contains a single central treatment catheter, as well as four peripheral catheters that can be differentially loaded to customize radiation dose coverage. An inner balloon is filled with up to 7-30 cm3 of saline to increase separation between the peripheral catheters, and an outer balloon is filled with up to 37-115 cm3 of saline to displace breast tissue from the peripheral catheters. Treatment planning objectives include coverage of the breast planning target volume to a minimum of V90 > 90%, limiting dose heterogeneity such that V200 < 10 cm3 and V150 < 50 cm3, and limiting maximum dose to skin (<100% of prescription dose) and ribs (<145% of prescription dose). RESULTS: High-dose-rate APBI was delivered to 11 women using this device (34 Gy in 10 twice daily fractions). The mean V90 was 98.2% (range 94.2-99.4%). The mean skin Dmax with the Double-Balloon applicator was 83.3% (range 75.6-99.5%). The mean breast V200 was 5.8 cm3 (range 2.3-10.2 cm3), and the mean breast V150 was 32.9 cm3 (range 25.0-41.7 cm3). Pretreatment quality assurance was performed using CT prior to each morning fraction and ultrasound prior to each afternoon fraction. CONCLUSIONS: The Double-Balloon applicator can be easily introduced into a previously existing brachytherapy program. APBI plans created with this applicator achieve excellent planning target volume coverage, while limiting skin dose and maintaining breast V200 < 10 cm3.

Acute Pediatric Monteggia Fractures: A Conservative Approach to Stabilization.

BACKGROUND: In 2015, a multicenter study group proposed a treatment algorithm for pediatric Monteggia fractures based upon the ulnar fracture pattern. This strategy recommends surgical stabilization for all complete ulna fractures. The purpose of this study was to evaluate whether an initial nonoperative approach to pediatric Monteggia fractures resulted in poorer outcomes and a higher rate of complications. METHODS: This institutional review board approved retrospective study evaluated all Monteggia fractures presenting to a level 1 pediatric trauma center between 2008 and 2014. Chart and radiographic reviews were performed on 94 patients who met inclusion criteria. The mean age was 5.5 years (range, 1 to 13 y). The mean clinical follow-up was 18 weeks. Major complications were defined as those requiring an unplanned second procedure (other than implant removal) or that may result in long-term disability (residual radial head subluxation/dislocation). Univariate (P<0.05) and Multivariate Classification and Regression Tree (CART) (P<0.05) analyses were used to identify variables associated with the need for surgical stabilization. RESULTS: At final follow-up, there were no cases of residual radiocapitellar joint subluxation or dislocation and all fractures had healed. The majority (83%) of patients were successfully managed with a cast. Univariate analysis found Bado type and maximum ulna angulation as significant predictors (P<0.05), whereas the CART analysis found ulna angulation >36.5 degrees as the only primary predictor of requiring surgical stabilization. Overall, good outcomes were achieved in all patients with few major complications. CONCLUSIONS: Although treatment algorithms are intended to minimize complications and maximize good outcomes, we believe that an unintentional consequence of the recently proposed pediatric Monteggia fracture treatment guideline may be the overtreatment of these injuries. In our cohort, the majority of patients were able to avoid the operating room and surgical implants without compromising outcomes or complications. This more conservative approach, however, requires close monitoring of patients in the first 3 weeks during which most reductions were lost. LEVEL OF EVIDENCE: Level IV-therapeutic studies, case series.

Technical Note: Confirming the prescribed angle of CT localizer radiographs and c-arm projection acquisitions.

PURPOSE: Accurate CT radiograph angle is not usually important in diagnostic CT. However, there are applications in radiation oncology and interventional radiology in which the orientation of the x-ray source and detector with respect to the patient is clinically important. The authors present a method for measuring the accuracy of the tube/detector assembly with respect to the prescribed tube/detector position for CT localizer, fluoroscopic, and general radiograph imaging using diagnostic, mobile, and c-arm based CT systems. METHODS: A mathematical expression relating the x-ray projection of two metal BBs is related to gantry angle. Measurement of the BBs at a prescribed gantry (i.e., c-arm) angle can be obtained and using this relation the prescribed versus actual gantry angle compared. No special service mode or proprietary information is required, only access to projection images is required. Projection images are available in CT via CT localizer radiographs and in the interventional setting via fluorography. RESULTS: The technique was demonstrated on two systems, a mobile CT scanner and a diagnostic CT scanner. The results confirmed a known issue with the mobile scanner and accurately described the CT localizer angle of the diagnostic system tested. CONCLUSIONS: This method can be used to quantify gantry angle, which is important when projection images are used for procedure guidance, such as in brachytherapy and interventional radiology applications.

A retrospective review to assess whether spinal fusion and scoliosis correction improved activity and participation for children with Angelman syndrome.

OBJECTIVE: This study investigates outcome of scoliosis treatment for 11 children with Angelman syndrome (AS), with particular focus on activity, participation and the musculoskeletal factors that may affect these outcomes. METHODS: Retrospective review of medical records, radiographs and questionnaires administered to caregivers of 11 children (8M:3F) with AS and scoliosis. Six underwent observational treatment during childhood and five underwent spinal fusion. The Activities Scale for Kids (ASKp) questionnaire was used to measure activity and participation. Questionnaire and radiographic data were recorded over a 2 year period. RESULTS: In the observational group, scoliosis increased from 31° to 46°. Mean ASKp decreased from 13.8 to 11.9 (p = 0.06). In the operative group, scoliosis decreased from 68° to 29°. Mean ASKp increased from 11.4 to 15.9 (p < 0.01). There was also a reduction in spinal-related pain and mean number of hospital admissions for chest infection. However, there was a 60% major complication rate. There was no difference in mobility, GMFCS level, feeding or communication in either group before or after treatment. CONCLUSION: In children with significant scoliosis and AS, spinal fusion was associated with a small improvement in activity and participation, reduction in pain and a decrease in frequency of severe chest infections. Non-operative treatment resulted in progression of scoliosis during childhood and decrease in activity.

Using the theory of planned behavior to improve treatment adherence in Mexican Americans with schizophrenia.

OBJECTIVE: Failure to adhere to treatment with antipsychotic medication is the most common cause of relapse among patients with schizophrenia. A novel multifamily group (MFG) intervention, informed by the Theory of Planned Behavior (TPB), demonstrated efficacy in increasing medication adherence and decreasing rehospitalizations in schizophrenia patients. This report explores the hypothesis that the improved outcomes obtained through the MFG approach were mediated by changes in the patients' attitudes toward medications, subjective norms-social influences, and perceived behavioral control of resources. METHOD: Data from a recently completed, randomized controlled trial of MFG was used to test the hypothesis that the improvement in adherence was mediated by the 3 TPB factors. Subjects were 174 Mexican American adults with schizophrenia-spectrum disorder who had participated in a study of MFG focused on improving medication adherence. Assessments occurred at baseline and at 4, 8, 12, 18, and 24 months. RESULTS: Path analysis revealed that the increased adherence associated with MFG was mediated by improvements in subjective norms but not attitudes toward medications nor perceived behavioral control. CONCLUSION: An MFG treatment specifically tailored to increase medication adherence among Mexican Americans with schizophrenia achieved its benefits by leveraging social influences through teaching family members how to support medication adherence in their ill relatives.

Shoulder linked arthroplasty in patients with obstetric brachial plexus palsy can improve quality of life and function at short-term follow-up.

BACKGROUND: Patients with obstetric brachial plexus palsy (OBPP) are prone to develop degenerative shoulder disease at a younger age than the general population. To date, no reports have been published on the complexities or outcome of shoulder arthroplasty (SA) in this unique patient group. METHODS: We reviewed of 9 SAs in 9 patients (3 men and 6 women) with OBPP with mean follow-up 5.1 years (range, 2.6-7.6 years). Patients were a mean age of 29 years (range, 16-56 years). Patients had undergone a mean of 3 previous operations (range, 2-6). All patients underwent linked constrained SA. RESULTS: The mean Oxford Shoulder Score increased from 8 (range, 3-10) preoperatively to 21 (range, 12-32) at the final follow-up (P < .001) predominantly due to pain relief. Mean range of active forward elevation and abduction improved from 35° and 39° to 46° and 45°, respectively. Patients improved significantly in 2 of 8 Short-Form 36-Item health-related quality of life domains, bodily pain (P = .013) and mental health (P = .035), and the overall physical component summary score (P = .006). Range of motion had mild improvements. Three required reoperation (33%), comprising 1 excision of heterotopic ossification, 1 trimming of a prominent screw, and 1 deltoid rupture repair. CONCLUSIONS: SA is effective at relieving pain and health-related quality of life for young patients with OBPP; however, compared with the general population, the complication rate is high and functional gains are small.