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1.
Arch Orthop Trauma Surg ; 144(1): 543-550, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971511

RESUMO

INTRODUCTION: The purpose of this study is to evaluate whether using a Fracture Healing Patch (FHP) device that generates pulsed electromagnetic fields (PEMF), applied at the fracture site immediately after open reduction and internal fixation surgery, can accelerate healing of acute distal radius fractures. METHODS: In a prospective, double-blind, randomized, and sham-controlled study, thirty-two patients with DRFs treated with ORIF were included. Patients were allocated to a PEMF (active) group (n = 15) or a control (sham) group (n = 17). All patients were assessed with regard to functional Patient-Rated Wrist Evaluation (PRWE), SF12, and radiological union outcomes (X-rays and computed tomography (CT) scans) at 2, 4, 6, and 12 weeks postoperatively. RESULTS: Patients treated with the FHP demonstrated significantly bone bridging at 4 weeks as assessed by CT (70% vs 54%, p = 0.05). Mean grip strength in the active group was significantly higher as compared to control (16 ± 9 kg vs 7 ± 3.5 kg, respectively, p = 0. 02). The function subscale of the PRWE was significantly better in PEMF-treated group at 6 weeks after surgery (27.2 VS 35.5, p = 0.04). No statistically significant differences were found in SF12. CONCLUSION: PEMF application after ORIF of DRFs is safe, may accelerate bone healing which could lead to an earlier return to daily life activities and work. LEVEL OF EVIDENCE: I.


Assuntos
Fraturas do Rádio , Fraturas do Punho , Humanos , Projetos Piloto , Campos Eletromagnéticos , Estudos Prospectivos , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fraturas do Rádio/cirurgia
2.
Knee Surg Sports Traumatol Arthrosc ; 28(9): 2756-2762, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29610973

RESUMO

PURPOSE: This study was designed to (1) evaluate the clinical outcomes after arthroscopic subspinal decompression in patients with hip impingement symptoms and low AIIS, and to (2) assess the presence of low anterior inferior iliac spine on the pre-operative radiographs of patients with established subspinal impingement diagnosed intra-operatively. METHODS: Retrospective analysis of patients who underwent arthroscopic subspinal decompression has been performed. The indications for surgery were femoroacetabular impingement (FAI), or subspinal impingement. Pre-operative radiographs were assessed for anterior inferior iliac spine type. Intra-operative diagnosis of low anterior inferior iliac spine was based on the level of anterior inferior iliac spine extension relative to the acetabulum and the presence of reciprocal labral and chondral lesions. In patients where low anterior inferior iliac spine was not diagnosed on pre-operative radiographs, the pre-operative radiographs were re-read retrospectively to assess missed signs of low anterior inferior iliac spine. RESULTS: Thirty-four patients underwent arthroscopic subspinal decompression between 2012 and 2015. The patients were followed for a median of 25 months (13-37 months). Intra-operatively, grade 2 anterior inferior iliac spine was found in 27 patients and grade 3 anterior inferior iliac spine was found in 7 patients. MHHS, HOS, and HOSS scores increased from median (range) pre-operative scores of 55 (11-90), 48 (20-91) and 20 (0-80) to 95 (27-100), 94 (30-100) and 91 (5-100), respectively (p < 0.0001, p = 0.001, p < 0.0001, respectively). Pre-operative diagnosis of low AIIS was made in 6/34 patients via AP radiographs. On retrospective analysis of pre-operative radiographs, signs of low AIIS were still not observed in 21/34 (61.8%) patients. CONCLUSIONS: Arthroscopic subspinal decompression of low AIIS yielded significantly improved outcome measures and high patient satisfaction at a minimum of 13 months follow-up. Low AIIS is often under-diagnosed on AP pelvis and lateral frog radiographs and if left untreated, may result in unresolved symptoms and failed procedure. LEVEL OF EVIDENCE: IV.


Assuntos
Artroscopia/métodos , Descompressão Cirúrgica/métodos , Impacto Femoroacetabular/cirurgia , Ílio/anatomia & histologia , Acetábulo/diagnóstico por imagem , Adolescente , Adulto , Variação Anatômica , Feminino , Impacto Femoroacetabular/etiologia , Seguimentos , Articulação do Quadril/cirurgia , Humanos , Ílio/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pelve , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
Bioorg Med Chem Lett ; 27(3): 398-402, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28057420

RESUMO

The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed. The most potent compound inhibits the ASCT2 anion conductance with a Ki of 3µM, which is in the same range as that of more bulky and higher molecular weight inhibitors recently reported by others. The experimental results are consistent with computational analysis based on docking of the inhibitors against an ASCT2 homology model. The benzylproline scaffold provides a valuable tool for further improving binding potency of future ASCT2 inhibitors.


Assuntos
Sistema ASC de Transporte de Aminoácidos/antagonistas & inibidores , Prolina/análogos & derivados , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Sítios de Ligação , Células HEK293 , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Prolina/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Ratos , Relação Estrutura-Atividade
4.
J Wrist Surg ; 13(2): 151-157, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38505202

RESUMO

Background Open reduction and internal fixation of distal radius fractures is one of the most common procedures performed in wrist surgery. The use of volar locking plate has gained increasing interest in the past decade. Epiphyseal fixation can be done either with locking screws or smooth locking pegs, with no evidence supporting the use of one rather than the other. Purpose The aim of this study is to compare the stability of distal radius fixation by volar locking plate using locking screws or smooth locking pegs. Methods Adult patients with A2-A3 AO fractures treated with a volar plate with locking screws only or smooth locking pegs only were retrospectively included. Radiographic assessment was performed to evaluate extra-articular parameters in the intraoperative postreduction and fixation period and after bony healing. Forty-seven distal radius fractures were included. Results Twenty-four fractures had fixation with locking screws and 23 had fixation with smooth locking pegs. For both groups, all radiographic parameters measured showed a statistically significant difference between the intraoperative postreduction and fixation period and the remote postoperative period after union of the fracture ( p < 0.05) attesting a slight loss of reduction. Nevertheless, there were no significant differences between the groups in radiographic extra-articular parameters. Conclusion This clinical study shows that there is no difference in stability fixation between locking screws or smooth locking pegs in A2-A3 distal radius fractures. Clinical Relevance The use of smooth locking pegs only for epiphyseal fixation appears to be safe in volar plating of A2-A3 distal radius fractures in adult patients and could be an alternative to locking screws. More clinical data are needed to confirm these results. Level of Evidence Level III; retrospective comparative study.

5.
Elife ; 122023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36856089

RESUMO

Excitatory amino acid transporter 1 (EAAT1) is a glutamate transporter belonging to the SLC1 family of solute carriers. It plays a key role in the regulation of the extracellular glutamate concentration in the mammalian brain. The structure of EAAT1 was determined in complex with UCPH-101, apotent, non-competitive inhibitor of EAAT1. Alanine serine cysteine transporter 2 (ASCT2) is a neutral amino acid transporter, which regulates pools of amino acids such as glutamine between intracellular and extracellular compartments . ASCT2 also belongs to the SLC1 family and shares 58% sequence similarity with EAAT1. However, allosteric modulation of ASCT2 via non-competitive inhibitors is unknown. Here, we explore the UCPH-101 inhibitory mechanisms of EAAT1 and ASCT2 by using rapid kinetic experiments. Our results show that UCPH-101 slows substrate translocation rather than substrate or Na+ binding, confirming a non-competitive inhibitory mechanism, but only partially inhibits wild-type ASCT2. Guided by computational modeling using ligand docking and molecular dynamics simulations, we selected two residues involved in UCPH-101/EAAT1 interaction, which were mutated in ASCT2 (F136Y, I237M, F136Y/I237M) in the corresponding positions. We show that in the F136Y/I237M double-mutant transporter, 100% of the inhibitory effect of UCPH-101 could be restored, and the apparent affinity was increased (Ki = 4.3 µM), much closer to the EAAT1 value of 0.6 µM. Finally, we identify a novel non-competitive ASCT2 inhibitor, through virtual screening and experimental testing against the allosteric site, further supporting its localization. Together, these data indicate that the mechanism of allosteric modulation is conserved between EAAT1 and ASCT2. Due to the difference in binding site residues between ASCT2 and EAAT1, these results raise the possibility that more potent, and potentially selective ASCT2 allosteric inhibitors can be designed .


Assuntos
Aminoácidos , Glutamina , Animais , Glutamina/metabolismo , Ácido Glutâmico , Sítios de Ligação , Alanina , Transportador 1 de Aminoácido Excitatório/metabolismo , Serina , Antígenos de Histocompatibilidade Menor/genética , Mamíferos/metabolismo
6.
J Clin Med ; 12(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36902653

RESUMO

BACKGROUND: this pilot study aimed at determining whether the application of a novel new method of generating pulsed electromagnetic field (PEMF), the Fracture Healing Patch (FHP), accelerates the healing of acute distal radius fractures (DRF) when compared to a sham treatment. METHODS: 41 patients with DRFs treated with cast immobilization were included. Patients were allocated to a PEMF group (n = 20) or a control (sham) group (n = 21). All patients were assessed with regard to functional and radiological outcomes (X-rays and CT scans) at 2, 4, 6 and 12 weeks. RESULTS: fractures treated with active PEMF demonstrated significantly higher extent of union at 4 weeks as assessed by CT (76% vs. 58%, p = 0.02). SF12 mean physical score was significantly higher in PEMF treated group (47 vs. 36, p = 0.005). Time to cast removal was significantly shorter in PEMF treated patients, 33 ± 5.9 days in PEMF vs. 39.8 ± 7.4 days in sham group (p = 0.002). CONCLUSION: early addition of PEMF treatment may accelerate bone healing which could lead to a shorter cast immobilization, thus allowing an earlier return to daily life activities and work. There were no complications related to the PEMF device (FHP).

7.
J Orthop Trauma ; 36(12): 634-638, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399675

RESUMO

OBJECTIVES: To assess outcomes and complications of conservatively managed humeral diaphyseal fractures in elderly patients, with an emphasis on the subgroup diagnosed with dementia. DESIGN: Retrospective. SETTING: Upper extremity surgery unit at an academic Level I trauma center. PATIENTS/PARTICIPANTS: Consecutive patients 65 years of age and older who were managed conservatively for humeral diaphyseal fractures between 2007 and 2015. INTERVENTION: Conservatively managed humeral diaphyseal fractures. MAIN OUTCOME MEASUREMENTS: Complications and radiographic outcomes. RESULTS: One-hundred twenty-four patients who were conservatively managed for humeral diaphyseal fractures were identified. Their mean age was 77 (65-92) years, 36 (30%) of them were male and 88 (70%) were female. Fifty-seven (46%) patients experienced complications associated with their treatment, and 33 (27%) patients were eventually treated surgically. Seventeen (14%) patients were diagnosed with dementia. This subgroup had 64% fracture-related complications, and all of them were operated (P-value <0.01 compared with age-matched patients among the other 107 participants in the study). CONCLUSION: Conservative management of humeral diaphyseal fractures seems to be associated with greater morbidity in elderly patients, especially in those diagnosed with dementia. Therefore, early surgical treatment should be considered. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Demência , Fraturas do Úmero , Humanos , Masculino , Feminino , Idoso , Tratamento Conservador , Estudos Retrospectivos , Fraturas do Úmero/terapia , Fraturas do Úmero/cirurgia , Úmero , Demência/complicações
8.
Pediatr Int ; 53(4): 426-30, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21040194

RESUMO

BACKGROUND: Further understanding of the clinical manifestations, hospital course and treatment options of the 2009 pandemic H1N1 influenza virus (H1N1) is needed in preparation for future outbreaks. METHODS: Seventy-three children with polymerase-chain-reaction-confirmed infections with H1N1 treated in a tertiary care medical center in Israel were included in the study. Clinical data were extracted from medical records, and analyzed by hospitalization status or the presence of underlying chronic medical conditions. RESULTS: Prevalent symptoms were fever, cough and shortness of breath, with additional findings of conjunctivitis, seizures, chills, dizziness, purpuric rash and chest pain. Hospitalized patients were more likely to have shortness of breath (OR 26.7, 95%CI: 3.5-1150), abnormal lung auscultation (OR 11.6, 95%CI: 2.8-67), abnormal X-ray (OR 3.3, 95%CI: 1.1-9.6), and a chronic illness (OR 5.4, 95%CI: 1.8-17), compared with non-hospitalized ones. Disease manifestations were similar between children with or without chronic diseases. Only two (2.7%) children required intensive care, and no deaths were recorded. A high rate (18%) of thrombocytopenia was found. One child had rapid symptom resolution after intravenous immunoglobulin treatment. CONCLUSION: H1N1 infection follows a mild course, even in the presence of severe underlying diseases. Abnormal respiratory findings and the presence of a chronic disease probably contributed to the decision to hospitalize patients. A rapid resolution of H1N1 symptoms after intravenous immunoglobulin treatment warrants further study, and could be a possible therapeutic option for severe cases.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Adolescente , Criança , Pré-Escolar , Doença Crônica/epidemiologia , Comorbidade , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Influenza Humana/complicações , Influenza Humana/diagnóstico , Israel/epidemiologia , Masculino
9.
Hand (N Y) ; 15(6): 793-797, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-30880471

RESUMO

Background: The objective of the study is to evaluate clinical and radiographic outcomes in patients treated with limited-open retrograde intramedullary headless screw (IMHS) fixation for metacarpal neck and shaft fractures. Methods: Retrospective review of 91 consecutive patients (79 men; 12 women), mean age 28 (range =15-69) years, treated with IMHS fixation for acute displaced metacarpal neck (N = 56) and shaft (N = 35) fractures at a single institution. Mean follow-up was 10 (range = 1-71, median = 3) months. Preoperative mean magnitude of metacarpal neck angulation was 48° (range = 0°-90°), and mean shaft angulation was 42° (range = 0°-70°). Active motion was initiated within 5 days postoperatively. Clinical outcomes were assessed with digital goniometry, grip strength, and return to full activity. The time to radiographic union and radiographic arthrosis was assessed. Results: All 91 patients achieved full functional arc of metacarpophalangeal (MCP) motion, and all achieved full active MCP extension or hyperextension. At mean follow-up of 10 months, postoperative mean MCP joint flexion-extension arc was 88° (range = 55°-110°). Grip strength was available for 52 patients and measured 104.1% of the contralateral hand (range = 58%-230%). Radiographic union data were available for 86 patients. Seventy-six percent (65/86) achieved radiographic union by the end of week 6 (range = 2-10 weeks). Early arthrosis was noted in 1 patient at the MCP. There were 3 cases of shaft refracture after recurrent blunt trauma, following prior evidence of full osseous union. Conclusions: The IMHS fixation is safe, reliable, and durable for metacarpal neck/subcapital, axially stable shaft fractures, and select delayed unions or malunions. It allows for early postoperative motion without affecting union rates and obviates immobilization. This technique offers distinct advantages over formal open reduction and percutaneous Kirschner wire techniques.


Assuntos
Parafusos Ósseos , Fraturas Ósseas/cirurgia , Traumatismos da Mão/cirurgia , Ossos Metacarpais/lesões , Ossos Metacarpais/cirurgia , Adolescente , Adulto , Idoso , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Ossos Metacarpais/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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