Morphometric and clinical comparison of MRI-based synthetic CT to conventional CT of the hip in children.

BACKGROUND: MRI-based synthetic CT (sCT) generates CT-like images from MRI data. OBJECTIVE: To evaluate equivalence, inter- and intraobserver reliability, and image quality of sCT compared to conventional (cCT) for assessing hip morphology and maturity in pediatric patients. MATERIALS AND METHODS: We prospectively enrolled patients <21 years old with cCT and 3T MRI of the hips/pelvis. A dual-echo gradient-echo sequence was used to generate sCT via a commercially available post-processing software (BoneMRI v1.5 research version, MRIguidance BV, Utrecht, NL). Two pediatric musculoskeletal radiologists measured seven morphologic hip parameters. 3D surface distances between cCT and sCT were computed. Physeal status was established at seven locations with cCT as reference standard. Images were qualitatively scored on a 5-point Likert scale regarding diagnostic quality, signal-to-noise ratio, clarity of bony margin, corticomedullary differentiation, and presence and severity of artifacts. Quantitative evaluation of Hounsfield units (HU) was performed in bone, muscle, and fat tissue. Inter- and intraobserver reliability were measured by intraclass correlation coefficients. The cCT-to-sCT intermodal agreement was assessed via Bland-Altman analysis. The equivalence between modalities was tested using paired two one-sided tests. The quality parameter scores of each imaging modality were compared via Wilcoxon signed-rank test. For tissue-specific HU measurements, mean absolute error and mean percentage error values were calculated using the cCT as the reference standard. RESULTS: Thirty-eight hips in 19 patients were included (16.6 ± 3 years, range 9.9-20.9; male = 5). cCT- and sCT-based morphologic measurements demonstrated good to excellent inter- and intraobserver correlation (0.77

Maintaining independence in individuals with dementia at home after a fall: a protocol for the UK pilot cluster randomised controlled trial MAINTAIN.

INTRODUCTION: Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual's overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia. METHOD AND ANALYSIS: This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes. ETHICS AND DISSEMINATION: The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN16413728.

A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study.

BACKGROUND: Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible. METHODS: The study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants' own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals. DISCUSSION: Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care. TRIAL REGISTRATION: The feasibility study was registered: ISRCTN15676570.

Novel Extramedullary Fixation Device for Hammertoe Correction: A Retrospective Review of 100 patients.

Classically, one of the more common treatment options for rigid hammertoe correction consists of end-to-end arthrodesis stabilized by temporary Kirschner wire (K-wire) fixation maintained until osseous consolidation or complication necessitating premature removal. However, single K-wire fixation allows for axial rotation which results in loss of compression at the arthrodesis site. To counteract this, intramedullary implants were designed to provide fusion site stability in all planes negating extra-skeletal extension of the wire. Nevertheless, manual pressfit implants arguably offer less reliable positioning of the fusion site in a true end to end orientation due to variation in intramedullary stem placement compared to direct visualization with dorsal plating. Larger diameter implants create an osseous void at the bony interface reducing the potential of true bony union. Hammertoe implant failure poses a unique and challenging salvage scenario which can ultimately end in amputation. Extramedullary fixation is uniquely designed to merge both benefits of K-wires and intramedullary implants while eliminating inadequacies of each. A total of 100 patients who underwent 150 rigid hammertoe corrections with an extramedullary implant were retrospectively reviewed. The mean postoperative follow-up was 12.6 months (range 12-18 months). Overall, 94 of 100 patients (94%) achieved radiographic union, defined by 2 or more bridged cortices at the arthrodesis site without signs of hardware breakage or signs of lucency across one or more fusion sites at a mean 8.8 weeks (range 7-10 weeks). This study demonstrated excellent results in regards to postoperative arthrodesis when utilizing an extramedullary implant for hammertoe deformity correction. This device minimizes osseous deficit by extramedullary application, all while augmenting intramedullary K-wire fixation.

Manifestation of Nonuremic Calciphylaxis in the Extremities: Case Report and Review.

Nonuremic calciphylaxis is a rare condition presenting with peripheral ischemic ulcerations. Calciphylaxis is the deposition of calcium and phosphate into arteriolar walls caused by exceeding their solubility range in the blood. It is most commonly seen in patients with end-stage renal disease; however, nonuremic calciphylaxis occurs in patients with normal or mildly impaired renal function. Risk factors for nonuremic calciphylaxis include Coumadin therapy, obesity, and diabetes mellitus. Histopathologic examination of deep skin biopsy containing subcutaneous adipose tissue reveals medial calcification of dermal and subcutaneous arterioles. This diagnosis must be managed locally with wound care and systemically by control of blood calcium solubility. Avoidance of infection is critical to survival. Here we report a case of calciphylaxis in a patient with normal renal function and serum levels of calcium and phosphorus who presented with gangrene of the extremities. Increased awareness of this debilitating disease will lead to earlier diagnosis, proper treatment and improved patient outcomes.

The Lapidus Arthrodesis: Examining the Effect of the Metatarsal Base Transfixion Screw.

The modified Lapidus bunionectomy is a useful and highly powerful procedure for correcting hallux abducto valgus. Traditionally reserved for "severe" deformities, this procedure has seen a recent resurgence in the podiatric community for its unique ability to achieve tri-planar correction of this challenging deformity. Although this procedure has been extensively studied in both biomechanical labs and the clinical arenas, no clear consensus has been achieved regarding optimal fixation for this thought-provoking procedure. The current study examined the differences in strength between commercially available 5-hole locking plates with interfragmentary compression vs a crossed-screw with a third "transfixation" screw construct in a controlled setting. Ten fresh-frozen cadaveric match pair limbs (20 total limbs) were used to complete this study. Ten limbs were randomly assigned to a 3-screw construct. The other 10 contralateral limbs were assigned to a commercially available 5-hole locking plate (5 stainless steel and 5 titanium alloy) with an interfragmentary lag screw construct. The first rays were then isolated and potted into a 4-point bending device. The specimens were loaded to failure in a servohydraulic load frame at a controlled rate. Failure was defined as catastrophic or 3 mm of plantar gapping at the arthrodesis site. The mean maximal load to failure was 310.9 ± 109.4 N for the 3-screw construct. The mean maximal load to failure for the locking plate constructs was 264.1 ± 100.9 N. This difference was not statistically significant (p = .328). These results suggest that a 3-screw construct for Lapidus arthrodesis is as strong as commercially available locking plate constructs.

Radiofrequency Ablation for the Treatment of Painful Neuroma.

Mechanical compression of interdigital nerves beneath the deep transverse intermetatarsal ligament and between the metatarsal heads leads to painful irritation and possible fibrosis. Conservative measures of padding and injections often fail to provide long-term relief. Surgical excision provides definitive relief, but the procedure is not without risk. Incomplete excision and stump neuroma formation are a few of the possible complications associate with open excision. This retrospective cohort study was performed to provide a review of the available literature on the identification and treatment of interdigital neuromas and to examine the overall incidence of patient satisfaction after radiofrequency ablation as definitive treatment for interdigital neuroma formation. This study population consisted of 32 patients (25 females and 7 males with 1 patient having bilateral procedures) with a mean age of 46.3 ± 17 (range 31 to 65) years. For all procedures, the median patient satisfaction score was 92.5 (interquartile range 50 to 100) of 100, with a mean follow-up period of > 2.5 years. Only 1 patient in the study population reported no relief after 3 total procedures. Radiofrequency ablation offers a minimally invasive alternative with a short postoperative recovery course and considerably fewer complications compared with surgical excision of the intermetatarsal neuroma as described in prior reports.

Syndesmotic Ligament Allograft Reconstruction for Treatment of Chronic Diastasis.

Chronic diastasis after a syndesmotic injury can lead to ankle joint instability and loss of joint congruence. Failure to restore the fibula into the proper anatomic position within the incisura increases the focal stress on the talus and can accelerate degenerative joint destruction. In the case of failed syndesmotic repair, fixation options are limited. If promptly diagnosed, the syndesmosis may be amenable to open debridement and subsequent fixation with 2 interosseous screws. If latent diastasis is found, however, syndesmotic fusion by bone block arthrodesis is recommended. We present a syndesmotic allograft repair technique for surgical reconstruction of chronic unstable syndesmotic ruptures.

Intrinsic Fixation of the Tibial Sesamoid in First Metatarsophalangeal Joint Arthrodesis: A Cadaveric Study.

Nonunion rate of first metatarsophalangeal joint (MTP) joint arthrodesis is reportedly less than 6%, regardless of fixation type. Robust modern plating constructs aim to decrease incidence of nonunion while also allowing early postoperative weight-bearing. Quicker transition to weight-bearing postoperatively increases patient adherence, decreases adjacent joint stiffness, and reduces risk of deep vein thrombosis in the postoperative period. The purpose of this study was to investigate the effect tibial sesamoid fixation has on first MTP joint arthrodesis.

Acute Deltoid Ligament Repair in Ankle Fractures: Five-year Follow-up.

Direct repair of deep deltoid ruptures after traumatic ankle fracture is not commonly performed. Previous studies overlook the contributions of the medial deltoid to overall ankle stability and long-term patient satisfaction. Historically, deep deltoid injuries have been addressed indirectly through syndesmotic ligament repair. This technique fails to restore, however, the anatomic function of the primary medial stabilizing structure. The oversight of direct deltoid repair may be one contributing factor to the less than optimal outcomes after ankle fractures with syndesmotic injuries. This article reports a positive response with direct deep deltoid repair, at average 5-year follow-up, with 93% positive return to normal function.

Cryopreserved Amniotic Membrane and Autogenous Adipose Tissue as an Interpositional Spacer After Resection of a Cubonavicular Coalition: A Case Report and Review of the Literature.

Coalitions of the hindfoot are a relatively rare but challenging condition encountered by foot and ankle surgeons. Those that manifest between the cuboid and navicular (cubonavicular coalitions) are seen even more infrequently and are estimated to comprise ∼1% of all tarsal coalitions. Treatment for cubonavicular coalitions parallels protocols for more common hindfoot coalitions. Typically, resection versus hindfoot arthrodesis procedures are used. The present study describes the case of a 34-year-old male with a painful cubonavicular coalition and early secondary signs of arthrosis. Despite the recommended guidelines of hindfoot arthrodesis, he elected for surgical resection. Autogenous adipose tissue and cryopreserved amniotic membrane were used for interposition at the resection site. This case demonstrates that surgical resection with interpositional grafting can be successful even in advanced disease states.

Charcot Pathogenesis: A Study of In Vivo Gene Expression.

Charcot neuroarthropathy is a rare but often difficult to manage disease in the neuropathic patient. Early signs such as unremarkable edema, marginal trauma, or minor infection can activate a cascade of bony destruction and lead to gross prominence or deformity, with dire consequences. The exact molecular mechanism is poorly understood. Current theory states that an inflammatory reaction leads to the activation of osteoclasts mediated by specific cytokines. Our study sought to test the genetic expression of certain biomarkers in diabetic patients with and without Charcot neuroarthropathy compared with patients with and without diabetes or neuropathy. A total of 30 patients participated in the study, 17 (57%) males and 13 (43%) females. Peripheral blood samples were drawn, and gene expression was measured using real-time polymerase chain reaction. The expression levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin showed no significant increase in the Charcot neuroarthropathy group compared with the healthy control group. We determined that the levels of receptor activator of nuclear factor kappa-B ligand and osteoprotegerin were not significantly increased in Charcot neuroarthropathy patients compared with healthy control patients. These results demonstrate a need for further investigation into alternative molecular pathways to determine the exact mechanism of the disease process.

The Use of Pediatric Flexible Intramedullary Nails for Minimally Invasive Fibular Fracture Fixation.

Fibular fractures in the setting of an unstable ankle joint require surgical fixation; however, several factors contradict open surgical correction. Severe soft tissue compromise can delay adequate fracture reduction and preclude the standard incisional approach. The soft tissue envelope in the setting of obesity, diabetes, and/or peripheral vascular disease further complicates definitive treatment. Poorly timed open fixation can lead to delayed healing of the incision site, with wound breakdown and the potential for hardware failure. Proximal fibular fractures are also at unique risk of neurovascular compromise with open reduction and internal fixation. Surgical fixation has now focused on minimizing the soft tissue insult using percutaneous techniques in the comorbid patient. We present a case that highlights a minimally invasive technique that provides dynamic stable internal fixation of fibular fractures with the use of flexible pediatric intramedullary nails, typically used in long bone fractures of children.

Irreducible Ankle Fracture Dislocation Due to Tibialis Posterior Tendon Interposition: A Case Report.

Traumatic ankle fractures and dislocations that fail closed reduction present a challenging set of circumstances that can potentially lead to unnecessary complications and require surgical intervention. Interposition of adjacent tendons occurs rarely and can obstruct the anatomic realignment. Because of the potential for neurovascular compromise and possible skin tension necrosis, an irreducible fracture dislocation must be addressed with open reduction and internal fixation. The present case details an unusual, low-energy, external rotation ankle fracture and dislocation that was incapable of skeletal traction relocation. The present report also details the intraoperative finding of a complex injury pattern.

Long-Term Follow-Up of the Cheilectomy for Degenerative Joint Disease of the First Metatarsophalangeal Joint.

Cheilectomy is the surgical resection of 20% to 30% of the dorsal metatarsal head and proximal phalanx. The present retrospective study evaluated the long-term efficacy of aggressive cheilectomy to address degenerative joint disease of the first metatarsophalangeal joint. To our knowledge, this is the second longest duration study to date to evaluate the long-term efficacy of the cheilectomy procedure, with a mean follow-up period of 7.14 years (range 39 weeks to 14.87 years). The mean patient age was 55.71 ± 9.51 years, and 37 (65%) of the patients were female. Age, sex, foot type, and preoperative radiographic parameters of hallux rigidus were also evaluated and correlated. The mean percentage of success with this operation was 87.69%. Of the 58 patients, 51 (87.93%) experienced no limitations in their daily activities. Only 2 patients (3.33%) subsequently required subsequent arthrodesis. The results of the present study suggest that cheilectomy offers long-term satisfaction for patients with hallux rigidus and is an acceptable alternative to the joint destructive procedure of first metatarsophalangeal arthrodesis.

Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer.

UNLABELLED: Gastrin-releasing peptide receptors (GRPr) and prostate-specific membrane antigen (PSMA) are two identifying biomarkers expressed in very high numbers on prostate cancer cells and could serve as a useful tool for molecular targeting and diagnosis of disease via positron-emission tomography (PET). The aim of this study was to produce the multipurpose, bivalent [DUPA-6-Ahx-((64)Cu-NODAGA)-5-Ava-BBN(7-14)NH2] radioligand for prostate cancer imaging, where DUPA = (2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid), a small-molecule, PSMA-targeting probe, 6Ahx = 6-aminohexanoic acid, 5-Ava = 5-aminovaleric acid, NODAGA = [2-(4,7-biscarboxymethyl)-1,4,7-(triazonan-1-yl)pentanedioic acid] (a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)), and BBN(7-14)NH2 = bombesin, a GRPr-specific peptide targeting probe. METHODS: The PSMA/GRPr dual targeting ligand precursor [DUPA-6-Ahx-K-5-Ava-BBN(7-14)NH2], was synthesized by solid-phase and manual peptide synthesis, after which NODAGA was added via manual conjugation to the ε-amine of lysine (K). The new bivalent GRPr/PSMA targeting vector was purified by reversed-phase high performance liquid chromatography (RP-HPLC), characterized by electrospray-ionization mass spectrometry (ESI-MS), and metallated with (64)CuCl2 and (nat)CuCl2. The receptor binding affinity was evaluated in human, prostate, PC-3 (GRPr-positive) and LNCaP (PSMA-positive) cells and the tumor-targeting efficacy determined in severe combined immunodeficient (SCID) and athymic nude mice bearing PC-3 and LNCaP tumors. Whole-body maximum intensity microPET/CT images of PC-3/LNCaP tumor-bearing mice were obtained 18 h post-injection (p.i.). RESULTS: Competitive binding assays in PC-3 and LNCaP cells indicated high receptor binding affinity for the [DUPA-6-Ahx-((nat)Cu-NODAGA)-5-Ava-BBN(7-14)NH2] conjugate. MicroPET scintigraphy in PC-3/LNCaP tumor-bearing mice indicated that xenografted tumors were visible at 18h p.i. with collateral, background radiation also being observed in non-target tissue. CONCLUSIONS: DUPA-6-Ahx-((64)Cu-NODAGA)-5-Ava-BBN(7-14)NH2] targeting vector, as described herein, is the first example of a dual GRPr-/PSMA-targeting radioligand for molecular of imaging prostate tumors. Detailed in vitro studies and microPET molecular imaging investigations of [DUPA-6-Ahx-((64)Cu-NODAGA)-5-Ava-BBN(7-14)NH2 in tumor-bearing mice indicate that further studies are necessary to optimize uptake and retention of tracer in GRPr- and PSMA-positive tissues.

Altered expression of circadian rhythm genes among individuals with a history of depression.

BACKGROUND: Depression has been associated with several circadian rhythm perturbations, suggesting a disruption of the circadian clock system in affective disorders. The interaction of several circadian clock genes generates these daily circadian rhythms. METHODS: This cross-sectional study evaluated whether circadian gene expression differed between individuals with a history of depression and participants without a similar history. The participants were 60 healthy older adults. Half of the participants had a history of depression. Real-time quantitative polymerase chain reaction was used to measure the circadian gene Clock, BMAL1, Period1, and Period2 messenger RNA levels in peripheral blood leukocytes. RESULTS: Individuals with a history of depression had higher Clock, Period1, and Bmal1 mRNA levels, compared to non-depressed participants. LIMITATIONS: Although circadian gene expression fluctuates throughout the day, clock gene mRNA levels were evaluated only in the morning. CONCLUSIONS: These results suggest that disruptions of the molecular mechanisms underlying the circadian clock system may be associated with depression.