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Background: Geriatric intertrochanteric fractures remain a major public health concern due to the considerable disability, morbidity, mortality, and health care costs associated with these injuries. The underlying poor bone quality and unstable nature of these fractures makes them difficult to treat. The main purpose of this study was to evaluate the outcome of hemiarthroplasty for unstable intertrochanteric hip fractures when compared to the traditional treatment options of open reduction internal fixation (ORIF)., Methods: A retrospective 1:1 matched cohort of 150 patients who had intertrochanteric fractures treated with either hemiarthroplasty or ORIF was developed using a local institutional database. Demographic, perioperative, and postoperative variables were collected with at least 1 year of patient follow-up. Statistical analyses were performed with use of Student's t-tests, chi-square tests, and analysis of variance., Results: Unstable intertrochanteric fractures treated with ORIF were associated with significantly more blood loss and an increased need for revision surgery. This effect was most pronounced in Arbeitsgemeinschaft für Osteosynthesefragen Orthopaedic Trauma Association classification type 31.A3 fractures, as patients treated with ORIF experienced significantly slower postoperative mobilization, increased blood loss, increased readmission, and revision surgery rates. Hemiarthroplasty was associated with an increased risk of greater trochanter escape, which did not appear to effect outcomes in this subset of patients., Conclusion: Hemiarthroplasty may improve outcomes for patients with unstable intertrochanteric fractures. The benefit of this technique is likely maximized in Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association type 31.A3 fractures. It remains a good option in the hands of experienced surgeons., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A number of cases of severe parkinsonism-dystonia have been recognized and reported following the illicit use of ephedrone prepared from pseudoephedrine and potassium permanganate. The pathology associated with ephedrone neurotoxicity has not been described yet in the scientific literature., Objectives: To report the first neuropathological study of ephedrone toxicity., Methods: The brain of a 33-year-old Ukrainian female ex-ephedrone addict with a long history of l-dopa-unresponsive parkinsonism with dysarthria, dystonia, profound postural instability, cock-gait, and frequent falls, and on antiretroviral treatment, was examined using routine stains and immunohistochemistry., Results: Neuropathological findings included diffuse pallidal astrogliosis without neuronal depletion. There was also widespread vascular pathology with small vessels occluded by foreign material, associated with giant cell response without any evidence of consequent focal infarction and a cerebellar abscess., Conclusions: Clinical findings of l-dopa-unresponsive parkinsonism with dystonia, caused by illicit use of ephedrone, are fully consistent with neuropathological changes in the pallidum, lack of change in the SN, and preserved tyrosine hydroxylase activity. The findings in the basal ganglia are compatible with manganese toxicity. The vascular pathology is likely a joint effect of infection and the ephedrone toxicity on the vessels. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Fibrous dysplasia (FD) results from an abnormality in lamellar bone formation and most frequently involves the proximal femur. This can lead to the development of osteoarthritis requiring total hip arthroplasty (THA). Such cases are challenging, and there is a lack of information guiding best management. As such, we devised a study assessing the outcomes and complications in patients with FD undergoing THA with modern implant technology, and we outlined our preferred surgical technique., Methods: A search of our institutional arthroplasty database was performed to identify patients who underwent THA for FD between January 2001 and July 2018 at Mount Sinai Hospital in Toronto, Canada. Data regarding implants used and the use of allograft material or metal augments or both were obtained. Complications and revision requirements were noted. Radiographic and clinical leg length discrepancies were assessed., Results: A total of 10 hips in 9 patients who underwent THA for FD were identified. Mean follow-up time was 6.0 years (range 0.5 to 10.3 yr). The majority of patients underwent THA using uncemented femoral and acetabular components with large femoral heads on highly cross-linked polyethylene liners. Most cases (80% of hips) required allograft to the proximal femur. A single complication requiring revision was noted. In 90% of hip surgeries, the patient required transfusion of packed red blood cells. Mean radiographic and clinical leg length discrepancies were 0.9 cm (range -2.4 to 2.4 cm) and 0.9 cm (range -4 to 0 cm), respectively., Conclusion: Contrary to previous reports, low complication and revision rates were observed with cementless components and routine use of allograft material. The challenging nature of such cases warrants use of an experienced arthroplasty treatment team., Competing Interests: O. Safir has served as a paid speaker and consultant for Zimmer Biomet and has been reimbursed by Zimmer Biomet for travel expenses for these activities. Gross has received educational consulting fees from Zimmer Biomet. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Total hip arthroplasty (THA) is increasingly performed in younger patients despite the lack of comprehensive assessment of long-term outcomes. We systematically reviewed the contemporary literature to assess the 1) indications, 2) implant selection and long-term survivorship, 3) complication and reoperation rates and 4) radiographic and functional outcomes of primary THA in patients younger than 55 years., Methods: We searched the Embase and MEDLINE databases for English-language articles published between 2000 and 2018 that reported outcomes of primary THA in patients younger than 55 years with a minimum follow-up duration of 10 years., Results: Thirty-two studies reporting on 3219 THA procedures performed in 2434 patients met our inclusion criteria. The most common preoperative diagnoses were avascular necrosis (1044 [32.4%]), osteoarthritis (870 [27.0%]) and developmental dysplasia of the hip (627 [19.5%]). Modular implants (3001 [93.2%]), cementless fixation (2214 [68.8%]) and metal-on-polyethylene bearings (1792 [55.7%]) were frequently used. The mean 5- and 10-year survival rates were 98.7% and 94.6%, respectively. Data on survival beyond 10 years were heterogeneous, with values of 27%–99.5% at 10–14 years, 59%–84% at 15–19 years, 70%–77% at 20–24 years and 60% at 25–30 years. Rates of dislocation, deep infection and reoperation for any reason were 2.4%, 1.2% and 16.3%, respectively. The mean Harris Hip Score improved from 43.6/100 to 91.0/100., Conclusion: Total hip arthroplasty in patients younger than 55 years provides reliable outcomes at up to 10 years. Future studies should evaluate the outcomes of THA in this population at 15–20 years’ follow-up., Competing Interests: None declared by X.Y. Mei and Y.J. Gong. O. Safir declares paid consultancies with Zimmer Biomet and DePuy Synthes, speaker fees from Zimmer Biomet, and research support from DePuy Synthes in the last 2 years. A. Gross declares speaker fees from Zimmer, and paid consultancies with Zimmer and Intellijoint within the last 2 years. P. Kuzyk declares research support from DePuy Synthes.

Background: Cerclage wires remain the current standard of care following median sternotomy, despite significant complications including dehiscence and infection. This study uses a human cadaveric model to investigate the use of glass polyalkenoate cements formulated from two glasses, A (mole fraction: SiO 2 :0.48, ZnO:0.36, CaO:0.12, SrO:0.04) and B (mole fraction: SiO 2 :0.48, ZnO:0.355, CaO:0.06, SrO:0.08, P 2 O 5 :0.02, Ta 2 O 5 :0.005), to improve wired sternal fixation., Methods: Median sternotomies were performed on fifteen cadaveric sterna. Fixation was performed with either traditional wire cerclage or adhesive-enhanced wire cerclage; the adhesive based on either Glass A or Glass B. Cyclic tensile loading of 10 N to 100 N was applied. Every 30 cycles, the maximum load was increased by 100 N up to a maximum of 500 N. Two adhered sterna were tested beyond 500 N. Mid-sternal displacement was measured to assess fixation stability., Findings: Displacement for adhesive-enhanced sternal closures were significantly less (p < 0.05) than standard wire cerclage. There was no significant difference between adhesives. Up to 500 N, no adhesive-enhanced sternum experienced a pathological sternal displacement (>2 mm), while three out of five of traditional wire fixations did. Of the two adhered samples tested beyond 500 N, one showed pathological displacement at 800 N and the other at 1100 N. Failure of adhered sterna appeared to initiate within the trabecular bone rather than in the adhesive., Interpretation: The adhesives were capable of providing immediate bone stability, significantly reducing sternal displacement. In vivo investigations are warranted to determine the effect the adhesives have on bone remodelling., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to determine if there is an anatomic relationship between pelvic geometry and acetabular depth., Materials and Methods: One hundred and fifty-one anteroposterior pelvic radiographs (157 hip joints) were selected and analyzed in a retrospective fashion. Six parameters, including iliac offset, ischial offset, acetabular offset, pelvic height, center-edge (CE) angle of Wiberg, and acetabular index (AI) angle of Tönnis were measured for each of the hip joints. Based on the defined variables, three formulas (formulas 1, 2, and 3) were calculated to represent the hemi-pelvis slope., Results: There was a strong relationship between the hemi-pelvis slope and probability of acetabular dysplasia. Wider upper pelvis was associated with deeper acetabulum and wider lower pelvis was associated with dysplastic acetabulum., Conclusions: Pelvic anatomic dimensions and the relationship between them are strongly correlated with hip dysplasia indices. Dysplastic hips tend to be found in pelvises with lower slope (low width of the upper pelvis at the level of iliac crest and high width of the lower part at the level of ischium).

Background: There are several different techniques commonly used to perform intramedullary (IM) nailing of the femur to fix femoral fractures. We sought to identify significant differences in outcomes of studies comparing 1) trochanteric and piriformis entry and 2) antegrade and retrograde entry in IM nailing of the femur., Methods: We searched MEDLINE, Cochrane and Embase databases and the Orthopaedic Trauma Association and American Academy of Orthopaedic Surgeons websites for comparative studies published from inception to November 2015. Criteria used to select articles for detailed review included use of antegrade and retrograde entry point or use of trochanteric and piriformis entry point for IM nailing of the femur in adult patients. Functional and technical outcomes were extracted from accepted studies., Results: We identified 483 potential studies, of which 52 were eligible. Of these, we included 13 publications and 2 abstracts (2 level I, 7 level II and 6 level III studies). Trochanteric entry significantly reduced operative duration by 14 min compared with piriformis entry ( p = 0.030). Retrograde nailing had a greater risk of postoperative knee pain than antegrade nailing ( p = 0.05). On the other hand, antegrade nailing had significantly more postoperative hip pain ( p = 0.003) and heterotopic ossification ( p < 0.001) than retrograde nailing. No significant differences in functional outcomes were observed., Conclusion: Although some significant differences were found, the varying quality of studies made recommendation difficult. Our meta-analysis did not confirm superiority of either antegrade over retrograde or trochanteric over piriformis entry for IM nailing of the femur., Level of Evidence: Level III therapeutic.

Objectives: To evaluate longitudinal trends in the use of total hip arthroplasty (THA), hemiarthroplasty (HA), internal fixation (IF), and nonoperative management and to identify individual-level factors associated with nonoperative treatment of hip fracture (HF)., Design: Longitudinal analysis of administrative data., Setting: Manitoba, Canada., Participants: All adults who experienced nontraumatic hip fractures between 1990 and 2014 (N = 19,626; mean age 80.6, 72.3% female)., Measurements: Billing codes were used to identify surgical treatment, and trends in treatment over time were examined. Regression models were developed to identify individual factors associated with receiving nonoperative management., Results: Use of THA increased from 0.6% for all HFs in 1990-94 to 5.3% in 2010-14, use of HA increased from 19.3% to 29.7%, and use of IF declined from 71.8% to 59.9% (P < .001 for all); increase in THA and HA were largest in individuals with femoral neck fracture. Nonoperative management declined from 8.3% in 1990-94 to 5.1% in 2010-14 (P < .001). Factors associated with nonoperative management included aged 90 and older, male sex, residing in a care facility before fracture, and rural residence., Conclusion: HF is increasingly treated with THA and HA, whereas rates of nonoperative management and IF are declining. Future efforts should focus on ensuring that all individuals are optimally triaged to the best procedure for them, with nonoperative management considered for individuals with extremely poor prefracture health., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

➤ The outcome of acetabular revision is heavily influenced by the degree of associated bone loss.➤ Uncemented hemispherical acetabular components can be used in the majority of acetabular revisions, although occasionally the degree of bone loss precludes the stability of the hemispherical component at the correct anatomic level or there is minimal bleeding host bone left for biologic fixation.➤ Massive acetabular bone loss resulting in the need for bone grafts or highly porous augments involving more than half of the acetabulum is one of the main indications for the use of cages.➤ The cup-cage reconstruction is based on bone-grafting the deficient acetabulum and securing a hemispherical, highly porous metal component with multiple screws to bridge the discontinuity and off-loading the hemispherical component with a titanium cage spanning from ischium to ilium.➤ In addition to managing pelvic discontinuities, the cup-cage construct can also be used in hips without discontinuity as the hemispherical, highly porous metal component is used to restore bone stock.➤ In situations in which there is not enough bleeding host bone to secure a hemispherical component, a highly porous metal augment can be used to address the osseous deficiency. The augment is also protected with a cage to assist bone ingrowth., (Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.)

Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are critical regulators of neuronal excitability, but less is known about their possible roles in synaptic plasticity and memory circuits. Here, we characterized the HCN gene organization, channel properties, distribution, and involvement in associative and nonassociative forms of learning in Aplysia californica. Aplysia has only one HCN gene, which codes for a channel that has many similarities to the mammalian HCN channel. The cloned acHCN gene was expressed in Xenopus oocytes, which displayed a hyperpolarization-induced inward current that was enhanced by cGMP as well as cAMP. Similarly to its homologs in other animals, acHCN is permeable to K(+) and Na(+) ions, and is selectively blocked by Cs(+) and ZD7288. We found that acHCN is predominantly expressed in inter- and motor neurons, including LFS siphon motor neurons, and therefore tested whether HCN channels are involved in simple forms of learning of the siphon-withdrawal reflex in a semiintact preparation. ZD7288 (100 μM) significantly reduced an associative form of learning (classical conditioning) but had no effect on two nonassociative forms of learning (intermediate-term sensitization and unpaired training) or baseline responses. The HCN current is enhanced by nitric oxide (NO), which may explain the postsynaptic role of NO during conditioning. HCN current in turn enhances the NMDA-like current in the motor neurons, suggesting that HCN channels contribute to conditioning through this pathway.

Case: A forty-three-year-old woman on bisphosphonate therapy sustained an atypical femoral fracture that was successfully treated with an intramedullary nail. After she developed radiographic and clinical signs of an impending stress fracture of the contralateral femur, prophylactic nailing was performed. However, seven months postoperatively, she sustained a spontaneous, complete fracture of the prophylactically nailed femur at the site of the lateral cortical stress lesion., Conclusion: To our knowledge, progression of a bisphosphonate-associated stress lesion to a complete fracture months after initially successful prophylactic intramedullary nailing has not been previously reported. Implications regarding treatment and prognosis are discussed.

Background: Both synovial chondromatosis and femoroacetabular impingement present with hip pain and may lead to hip osteoarthritis. We present a small case series and describe the clinical presentation, investigation, and treatment of patients with synovial chondromatosis who also had cam-type femoroacetabular impingement involving the same hip., Methods: Five patients (four men and one woman with a mean age of thirty-four years [range, thirty to thirty-seven years]) with unilateral synovial chondromatosis of the hip presented with clinical and radiographic features of ipsilateral cam-type femoroacetabular impingement. The diagnosis of associated synovial chondromatosis was made on the basis of preoperative imaging in four of the cases. All patients were treated with surgical hip dislocation, excision of the synovial chondromatosis loose bodies, and reshaping of the femoral head-neck junction., Results: These hips exhibited radiographic features that are not typically seen with idiopathic cam-type femoroacetabular impingement, including femoral head hypertrophy, lateralization of the femoral head, and haziness in the acetabular fossa. None of the hips showed signs of advanced osteoarthritis intraoperatively. The alpha angle improved from a mean of 72.4° preoperatively to 42.6° postoperatively. At a mean of twenty-two months of follow-up, the patients had a mean Harris hip score of 80.6, substantially improved from the preoperative value of 39., Conclusions: Hips with synovial chondromatosis may present with clinical and radiographic features resembling those of cam-type femoroacetabular impingement. As simultaneous treatment of both conditions is best accomplished with surgical hip dislocation rather than other, less-extensive surgical approaches, we recommend preoperative consideration of synovial chondromatosis in patients presenting with unilateral cam-type femoroacetabular impingement.

The binding of ATP to trimeric P2X receptors (P2XR) causes an enlargement of the receptor extracellular vestibule, leading to opening of the cation-selective transmembrane pore, but specific roles of vestibule amino acid residues in receptor activation have not been evaluated systematically. In this study, alanine or cysteine scanning mutagenesis of V47-V61 and F324-N338 sequences of rat P2X4R revealed that V49, Y54, Q55, F324, and G325 mutants were poorly responsive to ATP and trafficking was only affected by the V49 mutation. The Y54F and Y54W mutations, but not the Y54L mutation, rescued receptor function, suggesting that an aromatic residue is important at this position. Furthermore, the Y54A and Y54C receptor function was partially rescued by ivermectin, a positive allosteric modulator of P2X4R, suggesting a rightward shift in the potency of ATP to activate P2X4R. The Q55T, Q55N, Q55E, and Q55K mutations resulted in non-responsive receptors and only the Q55E mutant was ivermectin-sensitive. The F324L, F324Y, and F324W mutations also rescued receptor function partially or completely, ivermectin action on channel gating was preserved in all mutants, and changes in ATP responsiveness correlated with the hydrophobicity and side chain volume of the substituent. The G325P mutant had a normal response to ATP, suggesting that G325 is a flexible hinge. A topological analysis revealed that the G325 and F324 residues disrupt a β-sheet upon ATP binding. These results indicate multiple roles of the extracellular vestibule amino acid residues in the P2X4R function: the V49 residue is important for receptor trafficking to plasma membrane, the Y54 and Q55 residues play a critical role in channel gating and the F324 and G325 residues are critical for vestibule widening.

To address the general problem of intersegmental coordination of oscillatory neuronal networks, we have studied the leech heartbeat central pattern generator. The core of this pattern generator is a timing network that consists of two segmental oscillators, each of which comprises two identified, reciprocally inhibitory oscillator interneurons. Intersegmental coordination between the segmental oscillators is mediated by synaptic interactions between the oscillator interneurons and identified coordinating interneurons. The small number of neurons (8) and the distributed structure of the timing network have made the experimental analysis of the segmental oscillators as discrete, independent units possible. On the basis of this experimental work, we have made conductance-based models to explore how intersegmental phase and cycle period are determined. We show that although a previous simple model, which ignored many details of the living system, replicated some essential features of the living system, the incorporation of specific cellular and network properties is necessary to capture the behavior of the system seen under different experimental conditions. For example, spike frequency adaptation in the coordinating interneurons and details of asymmetries in intersegmental connectivity are necessary for replicating driving experiments in which one segmental oscillator was injected with periodic current pulses to entrain the activity of the entire network. Nevertheless, the basic mechanisms of phase and period control demonstrated here appear to be very general and could be used by other networks that produce coordinated segmental motor outflow.