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1.
J Med Chem ; 67(12): 10490-10507, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38845345

RESUMEN

Building on the preceding structural analysis and a structure-activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4a demonstrated the highest selectivity for hA2AAR (Ki,hA2A = 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A = 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4a as a viable immune-oncology therapeutic candidate.


Asunto(s)
Adenina , Antagonistas del Receptor de Adenosina A2 , Nucleósidos , Receptor de Adenosina A2A , Ribosa , Humanos , Relación Estructura-Actividad , Animales , Adenina/farmacología , Adenina/química , Adenina/análogos & derivados , Antagonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/química , Antagonistas del Receptor de Adenosina A2/síntesis química , Nucleósidos/química , Nucleósidos/farmacología , Nucleósidos/síntesis química , Ribosa/química , Ribosa/metabolismo , Receptor de Adenosina A2A/metabolismo , Ratones , Estructura Molecular , Ratas , Femenino , Línea Celular Tumoral
2.
Sci Rep ; 14(1): 6059, 2024 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480840

RESUMEN

Autogenous iliac bone graft (AIBG) is the treatment of choice for managing bone defects, and favorable results have been reported for bone defects < 5 cm in length. In large bone defects ≥ 5 cm, it is difficult to obtain good results with simple bone grafting, and other management options have drawbacks, such as long immobilization periods and high complication rates. We hypothesized that AIBG in the strut form might show favorable results in large bone defects with minimal complications. This study aimed to investigate the outcomes of strut-type AIBG and evaluate its effectiveness compared to cancellous AIBG. This retrospective study included 50 patients who underwent AIBG for bone defects at a single institution between March 2011 and April 2020. We performed corticocancellous AIBG in a strut form to manage bone defects ≥ 5 cm in the lower extremities. The strut bone was harvested along the iliac crest and grafted slightly longer than the bone defect to apply a sufficient compressive force. Demographic information and radiographic and clinical results of patients who underwent strut AIBG (Group S) were analyzed. The outcomes of union, time to union, complications, and reoperation were compared with those of patients who underwent cancellous AIBG (Group C). The study population comprised 37 men (74%) and 13 women (26%), with a mean age of 50.0 (range: 19-78). The average follow-up period was 25.6 months (12-104 months). Group S included 16 patients with a mean bone defect length of 6.8 ± 1.2 cm. In Group S, union was achieved in all patients, with an average time to union of 6.7 months. Complications occurred in four cases, all related to wound problems. Group C comprised d 34 patients with a mean defect length of 2.8 ± 1.1 cm. Complications occurred in five patients in Group C, including four soft tissue problems and one implant failure. When comparing the outcomes of Groups S and C, no significant differences were observed. AIBG is an effective and safe technique for managing bone defects. Strut AIBG can be used effectively for bone defects ≥ 5 cm in the lower extremities.


Asunto(s)
Trasplante Óseo , Ilion , Masculino , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Óseo/métodos , Resultado del Tratamiento , Extremidad Inferior
3.
Arch Orthop Trauma Surg ; 144(3): 1259-1268, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38372763

RESUMEN

INTRODUCTION: Intramedullary (IM) nailing is the treatment of choice for femoral shaft fractures, but nonunion rates have been reported to be as high as 12%. Surgical interventions for nonunion involve exchange nailing or plate augmentation. Recently, a combined treatment of exchange nailing and plate augmentation has demonstrated good results, but its comparative effectiveness remains unclear. This study aimed to compare the clinical and radiographic outcomes of three different surgical interventions for atrophic femoral shaft nonunion, and investigate the factors that affect bone healing after reoperation. MATERIALS AND METHODS: A retrospective study was conducted at five university hospitals involving 149 patients with aseptic atrophic nonunion after IM nailing. These patients underwent reoperation with plate augmentation, exchange nailing, or combined treatment. Clinical and radiographic outcomes were assessed and compared according to reoperation procedure. Logistic regression analysis was performed to identify factors affecting persistent nonunion after reoperation. RESULTS: Of the cohort, 57 patients underwent plate augmentation, 64 underwent exchange nailing, and 28 received combined treatment. There were no significant differences in patient demographics among the groups. Exchange nailing produced a significantly lower union rate than did the combined treatment (82.8% vs. 100%, p = 0.016), whereas no significant difference was observed in the union rate and time to the union between plate augmentation and the combined treatment. Combined treatment showed the longest operative time and the greatest transfusion requirements. The risk factors for persistent nonunion included age, absence of autogenous bone grafts, and use of an exchange nailing technique. CONCLUSIONS: Exchange nailing as a treatment for atrophic femoral shaft nonunion after IM nailing resulted in a lower union rate. The efficacy of the combined treatment requires further study, and persistent nonunion may be influenced by age, bone grafting, and surgical techniques. A comprehensive approach targeting both biological environment and mechanical stability is crucial in the treatment of atrophic femoral shaft nonunion.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas no Consolidadas , Humanos , Fijación Intramedular de Fracturas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Clavos Ortopédicos/efectos adversos , Fracturas no Consolidadas/cirugía , Fracturas no Consolidadas/etiología , Fracturas del Fémur/cirugía , Fracturas del Fémur/etiología , Curación de Fractura
4.
J Orthop Trauma ; 38(3): 160-167, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38098139

RESUMEN

OBJECTIVES: To compare the outcomes of a minimally invasive reduction (MIR) technique using a cable and wire in spiral or oblique subtrochanteric femoral fractures (SFFs). DESIGN: Retrospective cohort study. SETTING: Two University Hospitals. PATIENT SELECTION CRITERIA: Skeletally mature patients with spiral or oblique SFFs (OTA/AO 32A1 and 32A2) treated with intramedullary nailing and MIR with a cerclage wire passer using either a single-loop cable or cerclage wire or MIR without cable or wire between May 2016 and November 2021 were included. OUTCOME MEASURES AND COMPARISONS: Coronal and sagittal interfragmentary gap, neck-shaft angle, coronal and sagittal angulation, fracture union, time to union, and Radiographic Union Score for Hip (RUSH) at 6 months post operation were compared. RESULTS: A total of 46 patients were included, with 16 each in the cable and wire groups and 14 in the non-wiring group. There were no differences in demographics ( P > 0.05), fracture classification ( P = 0.710), or operative data ( P > 0.05) between the three groups. The cable group showed significantly better coronal ( P = 0.003) and sagittal ( P = 0.003) interfragmentary gap, shorter union time ( P < 0.001), and higher 6-month RUSH score ( P < 0.001) among the three groups. There were no significant differences in outcome measures between the wire and non-wiring groups (all P > 0.05). No mechanical complications or reoperations were observed in all three groups. CONCLUSIONS: Minimally invasive reduction using a cable is more effective than wire or non-wiring reduction to improve reduction quality and promote bone union in the SFFs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Hilos Ortopédicos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Fijación Intramedular de Fracturas/métodos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Clavos Ortopédicos
5.
Heliyon ; 9(10): e20772, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37860561

RESUMEN

Objective: This study introduces a novel technique utilizing a drill stopper to limit drill penetration depth and to prevent iatrogenic injuries, specifically neurovascular damage, in orthopedic surgeries. Orthopedic surgeries frequently involve the use of drills, which are essential tools for various procedures. However, improper handling of drills can lead to iatrogenic soft tissue injuries, causing severe consequences such as permanent disability or life-threatening complications. To address this issue, we propose the use of a drill stopper as a safeguard to prevent excessive drill penetration and reduce the risk of soft tissue damage during surgery. Materials and Methods: The study involved 32 orthopedic surgeons, half of whom were experienced and the other half inexperienced. Synthetic femur bone models (Synbone) were used for drilling exercises, employing four configurations: a sharp drill bit without a stopper (SF, Sharp Free), a sharp drill bit with a stopper (SS, Sharp Stopper), a blunt drill bit without a stopper (BF, Blunt Free), and a blunt drill bit with a stopper (BS, Blunt Stopper). Each participant conducted three trials for each configuration, and the penetration depth was measured after each trial. Results: For experienced surgeons, the average penetration depths were 3.83 (±1.826)mm for SF, 11.02 (±3.461)mm for BF, 2.88 (±0.334)mm for SS, and 2.75 (±0.601)mm for BS. In contrast, inexperienced surgeons had average depths of 8.52 (±4.608)mm for SF, 18.75 (±4.305)mm for BF, 2.96 (±0.683)mm for SS, and 2.83 (±0.724)mm for BS. Conclusion: The use of a drill stopper was highly effective in controlling drill penetration depth and preventing iatrogenic injuries during orthopedic surgeries. We recommend its incorporation, particularly when using a blunt drill bit or when an inexperienced surgeon operates in an anatomically unfamiliar area. Using the drill stopper, the risk of severe injuries from excessive drill penetration can be minimized, leading to improved patient safety and better surgical outcomes.

6.
Biomedicines ; 11(10)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37893219

RESUMEN

Monoamine transporters, including dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively), are important therapeutic targets due to their essential roles in the brain. To overcome the slow action of selective monoamine reuptake inhibitors, dual- or triple-acting inhibitors have been developed. Here, to examine whether combination treatments of selective reuptake inhibitors have synergistic effects, the pharmacological properties of DAT, NET, and SERT were investigated using the selective inhibitors of each transporter, which are vanoxerine, nisoxetine, and fluoxetine, respectively. Potencies were determined via fluorescence-based substrate uptake assays in the absence and presence of other inhibitors to test the multi-drug effects on individual transporters, resulting in antagonistic effects on DAT. In detail, fluoxetine resulted in a 1.6-fold increased IC50 value of vanoxerine for DAT, and nisoxetine produced a more drastic increase in the IC50 value by six folds. Furthermore, the effects of different inhibitors, specifically monovalent ions, were tested on DAT inhibition by vanoxerine. Interestingly, these ions also reduced vanoxerine potency in a similar manner. The homology models of DAT suggested a potential secondary inhibitor binding site that affects inhibition in an allosteric manner. These findings imply that the use of combination therapy with monoamine reuptake inhibitors should be approached cautiously, as antagonistic effects may occur.

7.
Clin Orthop Surg ; 15(3): 349-357, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37274487

RESUMEN

Background: The angular stable locking system (ASLS) was developed to provide additional stability to the distal interlocking screw of the intramedullary (IM) nail. Effects of ASLS on the treatment of femoral diaphyseal fractures in the elderly remain unknown. The aim of this study was to compare radiological outcomes of IM nailing using ASLS screws to IM nails with conventional interlocking screws in elderly patients with femoral shaft fractures. Methods: A multicenter retrospective review of 129 patients (average age, 73.5 years; 98 women and 31 men) aged 65 years or older who underwent IM nail fixation for femoral diaphyseal fractures (AO/Orthopaedic Trauma Association [OTA] classification 32) was conducted. Demographic information of patients, fracture site (subtrochanteric or shaft), fracture type (traumatic or atypical), and AO/OTA fracture classification were investigated. Reduction status was evaluated by postoperative plain radiography. Presence of union and time to union were evaluated through serial plain radiograph follow-up. Reoperation due to nonunion or implant failure was also evaluated. Results: ASLS was used in 65 patients (50.3%). A total of 118 patients (91.5%) achieved union without additional surgery and the mean union time was 31.8 ± 13.0 weeks. In terms of reduction status, angulation was greater in the group using ASLS. There were no statistically significant differences of union rate, time to union, and reoperation rate according to the use of ASLS (p > 0.05). There was no difference in the outcomes according to the use of ASLS even when the analysis was divided in terms of fracture site or fracture type (p > 0.05). In further subgroup analysis, only the traumatic subtrochanteric area group showed statistically significantly shorter time to union when ASLS was used (p = 0.038). Conclusions: In geriatric patients with femoral diaphyseal fractures, the use of ASLS was not considered to have a significant effect on fracture healing. Fracture healing seemed to be more affected by surgical techniques such as minimizing the gap and fracture characteristics such as atypical femoral fractures, rather than implants.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Masculino , Anciano , Humanos , Femenino , Clavos Ortopédicos/efectos adversos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fijación Intramedular de Fracturas/métodos , Curación de Fractura , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
8.
Sci Rep ; 13(1): 7802, 2023 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-37179404

RESUMEN

The factors affecting the outcomes of segmental femoral shaft fractures are currently unknown. We evaluated the outcomes of intramedullary (IM) nail fixation and investigated factors affecting nonunion of femoral shaft segmental fractures. A total of 38 patients who underwent IM nail fixation for femoral shaft segmental fractures (AO/OTA 32C2) at three university hospitals with a minimum 1-year follow-up period were retrospectively reviewed. The patients were divided into union (n = 32) and nonunion (n = 6) groups. We analyzed smoking status, diabetes mellitus, location of the segmental fragment, segment comminution, filling of the IM nail in the medullary canal, residual gap at the fracture site, use of a cerclage wire or blocking screws as factors that may affect the surgical outcome. In the union group, the average union time was 5.4 months (4-9 months). In the nonunion group, five patients required additional surgery within an average of 7.2 months (5-10 months) postoperatively, whereas one patient remained asymptomatic and did not require further intervention. On comparing the two groups, insufficient canal filling of the IM nail (union, 25.0%; nonunion, 83.3%; p = 0.012) and the presence of a residual gap at the fracture site after reduction (union, 31.3%; nonunion, 83.3%; p = 0.027) were significantly different. In the multivariate analysis, only insufficient canal filling of the IM nail was found to be a factor affecting nonunion, with an odds ratio of 13.3 (p = 0.036). In this study, a relatively high nonunion rate (15.8%) was observed after IM nail fixation. Insufficient IM nail canal filling and a residual gap at the fracture site post reduction were factors affecting segmental femoral shaft fracture nonunion after IM nail fixation.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Humanos , Estudios Retrospectivos , Clavos Ortopédicos , Curación de Fractura , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Resultado del Tratamiento
9.
J Hand Surg Am ; 2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149801

RESUMEN

PURPOSE: The purpose of the study was to demonstrate the results of surgical treatment, including percutaneous K-wire fixation after closed reduction (CRKF) or locking plate fixation after open reduction (ORPF), in patients with intra-articular fractures of the base of the fifth metacarpal. METHODS: We retrospectively reviewed data of 29 patients who received surgical treatment for closed, intra-articular fractures of the base of the fifth metacarpal and were followed up for at least 1 year after surgery. Sixteen of the 29 patients underwent CRKF, whereas 13 patients underwent ORPF. Attempts were made to address intra-articular step-off with closed reduction in all the patients; however, if inadequate, ORPF was performed. Clinical outcomes were evaluated using Disabilities of the Arm, Shoulder, and Hand scores, visual analog scale pain scores, the total active motion (TAM) of the little finger, and grip strength. Osseous union and posttraumatic arthritis of the fifth carpometacarpal joint were also evaluated. RESULTS: K-wire fixation after closed reduction was performed for 13 simple fractures and 3 comminuted fractures; ORPF was performed for 6 simple fractures and 7 comminuted fractures. All the patients had satisfactory subjective outcomes with over 90% grip strength compared with that on the contralateral side and nearly full TAM. All the patients in both the groups achieved osseous union. There were five cases of grade 1 posttraumatic arthritis after CRKF and seven cases of grade 1 posttraumatic arthritis after ORPF. CONCLUSIONS: Surgical treatment provided satisfactory results in patients with intra-articular fractures of the base of the fifth metacarpal treated with either CRKF or ORPF. Our data showed that the patients who underwent CPKF had good results, and those who underwent ORPF after attempt failure of close reduction also had good results. Our experience suggests that ORPF can be a backup plan when CRKF cannot be accomplished in a satisfactory way. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

10.
Bioorg Med Chem Lett ; 75: 128947, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35995398

RESUMEN

Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) negatively regulates the anti-cancer Stimulator of Interferon Genes (STING) pathway. We discovered that 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives possessed inhibitory activities on ENPP1. A structure-activity relationship (SAR) study led to the identification of 46 and 23 as potent ENPP1 inhibitors. Also, compounds 46 and 23 possessed high microsomal stabilities in human, rat, and mouse liver microsome. Additionally, CYPs (1A2, 2C9, 2C19, 2D6, and 3A4) were not inhibited by 46 and 23. Molecular dynamics simulations provided an insight of binding modes between ENPP1 and compounds (46 and 23).


Asunto(s)
Hidrolasas Diéster Fosfóricas , Pirofosfatasas , Animales , Humanos , Interferones , Ratones , Microsomas Hepáticos/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Ratas , Relación Estructura-Actividad
11.
Orthop Traumatol Surg Res ; 108(5): 103322, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35577276

RESUMEN

INTRODUCTION: Nonunion of ulnar styloid fractures after radius stabilisation by volar locking plate (VLP) fixation without surgical fixation on ulnar styloid fractures is quite common. However, the factors affecting the nonunion of ulnar styloid fractures and their effect on functional outcomes in patients with distal radius fractures (DRFs) treated with VLP fixation are unclear. HYPOTHESIS: The purpose of this study was to investigate the predictors affecting nonunion of unrepaired ulnar styloid fractures in patients with DRFs and the effect of nonunion and its predictors on functional outcomes. MATERIALS AND METHODS: We retrospectively reviewed data from 84 patients with DRF who underwent VLP fixation. None of the accompanying ulnar styloid fractures were manipulated during the surgery. Postoperative evaluation included the measurement of the grip strength, wrist range of motion, and Disabilities of the Arm, Shoulder, and Hand score at a minimum of one year postoperatively. Patients were divided into the nonunion and union groups according to the presence of union of ulnar styloid fracture. Demographic and radiologic parameters, including age, sex, bone mineral density, location and displacement distance of ulnar styloid fracture, and fracture pattern of DRFs, were analysed to identify predictors of nonunion. Functional outcomes were compared between the two groups and were compared according to the presence of predictors of nonunion. RESULTS: Univariate analysis revealed that the nonunion rate was higher in ulnar styloid non-base fractures, substantial displacement (≥1.9mm) of ulnar styloid fracture, and AO/OTA C-type DRF. However, multivariate logistic regression analysis showed that non-base fractures and substantial displacement were significant predictors. Accompanying ulnar styloid fracture nonunion and its predictors were found not to influence functional outcomes. DISCUSSION: Substantial displacement and non-base fracture are predictive factors for nonunion of unrepaired ulnar styloid fractures after DRF treatment with VLP fixation. However, nonunion and its predictors do not influence the overall wrist function. These findings suggest that the ulnar styloid fracture accompanying DRF should not be considered a fracture affecting the wrist function when treating with VLP fixation. LEVEL OF EVIDENCE: III, Retrospective, Case Control study.


Asunto(s)
Fracturas del Radio , Fracturas del Cúbito , Placas Óseas , Estudios de Casos y Controles , Fijación Interna de Fracturas/efectos adversos , Humanos , Radiografía , Fracturas del Radio/complicaciones , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas del Cúbito/complicaciones , Fracturas del Cúbito/diagnóstico por imagen , Fracturas del Cúbito/cirugía
12.
Sci Rep ; 12(1): 7915, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35551221

RESUMEN

The purpose of this study was to compare the fixation stability of proximal fragments and the mechanical characteristics in proximal femur models of basicervical femoral neck fracture fixed by the femoral neck system (FNS) versus the dynamic hip screw. The mean axial stiffness was 234 ± 35 N/mm in the FNS group and 253 ± 42 N/mm in the DHS group, showing no significant difference (p = 0.654). Mean values for x-axis rotation, y-axis rotation, and z-axis rotation after cycle load were 2.2 ± 0.5°, 6.5 ± 1.5°, and 2.5 ± 0.6°, respectively, in the FNS group and 2.5 ± 0.7°, 5.8 ± 2.1°, and 2.2 ± 0.9°, respectively, in the DHS group, showing no significant differences (p = 0.324, p = 0.245, and p = 0.312, respectively). The mean values of cranial and axial migration of screws within the femoral head were 1.5 ± 0.3 and 2.1 ± 0.2 mm, respectively, in the FNS group and 1.2 ± 0.3 and 2.4 ± 0.3 mm, respectively, in the DHS group, showing no significant differences (p = 0.425 and p = 0.625, respectively). The average failure load at vertical load was 1342 ± 201 N in the FNS group and 1450 ± 196 N in the DHS group, showing no significant difference (p = 0.452). FNS fixation might provide biomechanical stability comparable to that of DHS for treating displaced basicervical femoral neck fractures in young adults.


Asunto(s)
Fracturas del Cuello Femoral , Fenómenos Biomecánicos , Tornillos Óseos , Fracturas del Cuello Femoral/cirugía , Cabeza Femoral , Cuello Femoral/cirugía , Fijación Interna de Fracturas , Humanos
13.
Injury ; 53(4): 1477-1483, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35120730

RESUMEN

INTRODUCTION: Intramedullary nailing (IMN), which is a common method for treating subtrochanteric fractures, is conducted as cephalomedullary (CMN) or reconstruction (RCN) nailing. Numerous studies have reported the effectiveness of CMN, which requires a shorter surgery time and provides stronger fixation strength with blade-type devices. However, the radiographic and clinical outcomes of the use of CMN and RCN in elderly patients aged ≥65 years have not been compared yet. This study aimed to investigate whether CMN offers superior outcomes over RCN in the treatment of subtrochanteric fractures in elderly patients. MATERIALS AND METHODS: This retrospective study included 60 elderly patients (17 men and 43 women; mean age: 74.9 years) diagnosed with subtrochanteric fractures and treated with IMN with helical blade CMN (CMN group: 30 patients) or RCN (RCN group: 30 patients) between January 2013 and December 2018 with at least 1 year of follow-up period. Radiologic outcomes were evaluated based on the postoperative state of alignment and the achievement and timing of bony union at the final follow-up. Clinical outcomes were evaluated using the Merle d'Aubigné-Postel score. Radiologic and clinical outcomes in the two groups were compared and analyzed, and the occurrence of complications was examined. RESULTS: The difference in malalignment between the two groups was not significant; however, the RCN group achieved more effective reduction. At the final follow-up, bony union was achieved within 18.9 weeks, on average, in 28 patients in the CMN group and within 21.6 weeks, on average, in 27 patients in the RCN group. Twenty patients in the CMN group and 26 in the RCN group showed good or better results according to the Merle d'Aubigné-Postel score. No significant differences were found for any of the parameters. CONCLUSIONS: In the treatment of difficult subtrochanteric fractures in elderly patients, RCN can provide excellent reduction and strong fixation similar to CMN and can result in outstanding clinical and radiologic outcomes.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Anciano , Clavos Ortopédicos , Femenino , Fijación Intramedular de Fracturas/métodos , Curación de Fractura , Mano , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/etiología , Fracturas de Cadera/cirugía , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
14.
Arch Orthop Trauma Surg ; 142(10): 2419-2427, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33689018

RESUMEN

INTRODUCTION: Several studies have reported that total knee arthroplasty (TKA) is a suitable solution to treat elderly patients with complex tibial plateau fractures. The purpose of the present study was to compare surgical treatment outcomes after open reduction internal fixation (ORIF) between elderly and younger patients. MATERIALS AND METHODS: We reviewed patients with plateau fracture (OTA/AO classification types 41B and 41C) who underwent ORIF at two academic trauma centers between November 2006 and October 2019. Of the 341 patients, 76 were ultimately included in the younger group (< 60 years old) and 77 in the elderly group (≥ 60 years). The average follow-up was 24 months (range 12-96 months). The primary outcome was any common complication of plateau fracture, namely post-traumatic arthritis and alignment change. Conversion to TKA, Reduction loss, coronal malalignment, non-union, union time, infection, and limb length discrepancy (LLD) were also assessed. RESULTS: The elderly group had a significantly higher prevalence of diabetes, but there were no other significant differences between the groups in terms of patient demographics, fracture characteristics, and operation characteristics. We detected no differences between the groups in terms of post-traumatic arthritis (p = 0.216), alignment change (p = 0.093), conversion to TKA (p = 0.681), reduction loss (p = 0.079), coronal malalignment (p = 0.484), non-union rate (p = 0.719), infection (p = 0.063), LLD (p = 0.154), or time to union (p = 0.513). Logistic regression analysis revealed that age > 60 years was not associated with treatment failure, defined as either post-traumatic arthritis greater than grade II or non-union (p = 0.468). OTA/AO classification type 41C2 (p = 0.019), type 41C3 (p = 0.008), and malreduction (p = 0.050) were significant risk factors for failure. CONCLUSION: Age ≥ 60 years is not an independent risk factor of poor radiographic outcome and high complication rate in tibial plateau fractures. This indicates that ORIF is still a good solution to treat elderly patients, similar to their younger counterparts.


Asunto(s)
Artritis , Fracturas de la Tibia , Anciano , Artritis/etiología , Fijación Interna de Fracturas/efectos adversos , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de la Tibia/epidemiología , Resultado del Tratamiento
15.
Eur J Trauma Emerg Surg ; 48(3): 2319-2329, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34226942

RESUMEN

PURPOSE: This study aimed to compare the clinical and radiological outcomes of patients who underwent total hip arthroplasty (THA) after failed osteosynthesis of acetabular fractures vs. fractures of the proximal femur. METHODS: This is a retrospective comparative study in two centers. A total of 110 patients who underwent THA after osteosynthesis of acetabular or proximal femur fractures were categorized into groups: group 1 (53 patients with acetabular fracture) and group 2 (57 patients with proximal femur fracture). The mean follow-up period was 6.3 (range 2-16.5) years. The Harris hip scores (HHSs), complications, radiological results, and Kaplan-Meier survival curves were evaluated. RESULTS: The mean preoperative HHSs of 39.4 (group 1) and 41.2 (group 2) were improved to 83.6 and 84.7 at the final follow-up (p < 0.001 and p < 0.001, respectively). There were two cases of aseptic cup loosening, two cases of septic cup loosening, two cases of deep infection, two cases of dislocation, two cases of sciatic nerve palsy, and one case of periprosthetic fracture in group 1, and one case of dislocation and two cases of infection in group 2, which showed a statistical difference in complication rate (p = 0.021). Total cup migration was significantly higher in group 1 (p = 0.015). After a mean follow-up period of 6.3 years, the survival rate was significantly lower in group 1 (69.4% vs. 97.1%, p = 0.015). CONCLUSION: THA following osteosynthesis of acetabular fracture showed poorer survival, higher complication rate, and higher migration of the acetabular cup than THA following osteosynthesis of proximal femur fracture.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Fracturas de Cadera , Fracturas de la Columna Vertebral , Acetábulo/lesiones , Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/métodos , Fracturas del Fémur/cirugía , Fémur/cirugía , Estudios de Seguimiento , Fracturas de Cadera/cirugía , Humanos , Reoperación , Estudios Retrospectivos , Fracturas de la Columna Vertebral/cirugía , Resultado del Tratamiento
16.
J Orthop Surg Res ; 16(1): 186, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33706801

RESUMEN

BACKGROUND: Mini-hook plate has been described for the treatment of various small avulsion fragments in the hand. This retrospective study aimed to evaluate clinical outcomes after mini-hook plate fixation in patients with an avulsion fracture around the interphalangeal or metacarpophalangeal joints of the hand. METHODS: Nineteen patients with avulsion fractures around the interphalangeal or metacarpophalangeal joints of the hand were included in this study. Seven patients had a mallet fracture, and 12 patients had other phalangeal avulsion fractures including central slip, collateral ligament, volar plate, and flexor avulsion fractures. The osseous union and functional outcomes, including finger joint motion, joint stability, pinching strength, and the disabilities of the arm, shoulder, and hand score, were evaluated. RESULTS: The mean duration of follow-up was 33.8 months. All patients in mallet and other phalangeal avulsion fractures achieved osseous union between the avulsion fragment and phalangeal bone, and there was no joint subluxation. There were no significant differences in the disabilities of the arm, shoulder, and hand scores. However, the patients with mallet fracture have lower mean percentage values of the total active range of motion and pinching strength than other phalangeal avulsion fractures. We abandoned this procedure in mallet fractures because the early results after mini-hook plate fixation in mallet fractures appeared unfavorable. CONCLUSION: These results suggest that the mini-hook plate fixation can provide sufficient stability and good clinical outcomes in those with phalangeal avulsion fractures. However, the outcomes for mallet fractures were not as good as those for other phalangeal avulsion fractures.


Asunto(s)
Placas Óseas , Articulaciones de los Dedos/cirugía , Fijación Interna de Fracturas/métodos , Fracturas por Avulsión/cirugía , Articulación Metacarpofalángica/cirugía , Evaluación de la Discapacidad , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
17.
J Chem Inf Model ; 61(1): 36-45, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33252229

RESUMEN

Following identification of a target protein, hit identification, which finds small organic molecules that bind to the target, is an important first step of a structure-based drug design project. In this study, we demonstrate a target-specific drug design method that can autonomously generate a series of target-favorable compounds. This method utilizes the seq2seq model based on a deep learning algorithm and a water pharmacophore. Water pharmacophore models are used to screen compounds that are favorable to a given target in a large compound database, and seq2seq compound generators are used to train the screened compounds and generate entirely new compounds based on the training model. Our method was tested through binding energy calculation studies of six pharmaceutically relevant targets in the directory of useful decoys (DUD) set with docking. The compounds generated by our method had lower average binding energies than decoy compounds in five out of six cases and included a number of compounds that had lower binding energies than the average binding energies of the active compounds in four cases. The generated compound lists for these four cases featured compounds with lower binding energies than even the most active compounds.


Asunto(s)
Aprendizaje Profundo , Diseño de Fármacos , Algoritmos , Ligandos , Simulación del Acoplamiento Molecular , Proteínas , Agua
18.
Arch Orthop Trauma Surg ; 141(2): 207-214, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33128096

RESUMEN

INTRODUCTION: Very low periprosthetic distal femur fractures (PPDFFs) are rare injuries and often have a relatively high failure rate after single lateral locked plating. The double plating technique yields good outcomes in osteoporotic fractures of the distal femur. To date, there is limited information on double-locked plate fixation of very low PPDFFs. This study aimed to evaluate the outcomes and complications of surgically treated very low PPDFFs using double-locked plate fixation. MATERIALS AND METHODS: Between January 2013 and December 2018, sixty-one consecutive patients with PPDFFs have been conducted. Only Su type III PPDFFs with double-locked plate fixation through a lateral minimally invasive approach and a medial subvastus approach to the distal femur were analyzed. Patients were encouraged to perform straight leg raising exercises and active knee motion on the second postoperative day. Assisted weight bearing from the early postoperative days was supported, and full weight-bearing was allowed after healing the fracture site. All patients were evaluated according to the time to union, limb alignment, range of knee motion, Knee Society Score, and presence of complications. RESULTS: Twenty one patients (17 females and 4 males, mean age 76 years, range 56-90) were included in the study. There were 10 of 33-A1, 6 of 33-A2 and 5 of 33 A3 fractures, according to the AO classification. Of 21 patients, 20 achieved union at an average of 14 weeks postoperatively. Postoperative limb alignment was satisfactory in all cases, with an average mechanical distal lateral femur angle of 89° and average mechanical posterior distal femur angle of 86°. All patients recovered the knee joint motion similar to that of the contralateral side, and daily life pre-injury. The average knee and function scores were 94 and 89, respectively. There were one case of non-union and three cases of superficial wound infection, which resolved after intravenous antibiotic therapy. CONCLUSIONS: Double locked plating showed excellent radiographic and functional outcomes with few complications in patients with very low PPDFFs. Based on these promising results, we propose the consideration of double-locked plate fixation in the treatment of very low PPDFFs.


Asunto(s)
Placas Óseas , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas , Fracturas Periprotésicas/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Resultado del Tratamiento
19.
Sci Rep ; 10(1): 5431, 2020 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-32214183

RESUMEN

The purpose of this study was to investigate the incidence of symptomatic venous thromboembolism (VTE) after chemoprophylaxis in patients with pelvic and lower-extremity fractures, and to identify risk factors for VTEs in this subgroup of patients. To detect VTE, multi-detector computed tomography (CT) angiography was performed. Of 363 patients assessed, the incidence of symptomatic VTE was 12.4% (45 patients), and the incidence of symptomatic PE was 5.2% (19 patients). For the risk-factor analysis, a higher Charlson comorbidity index (p = 0.037), and a history of external fixator application (p = 0.007) were associated with increased VTE risk. Among patients who had VTE, male sex (p = 0.017), and above-the-knee fractures (p = 0.035) were associated with increased pulmonary embolism (PE) risk. In conclusions, the incidence of VTE in post-traumatic patients is not low after chemoprophylaxis. Risk factors for VTE and PE are different among patients with pelvic and lower-extremity fractures.


Asunto(s)
Anticoagulantes/administración & dosificación , Huesos de la Extremidad Inferior/lesiones , Dabigatrán/administración & dosificación , Enoxaparina/administración & dosificación , Fracturas Óseas/complicaciones , Huesos Pélvicos/lesiones , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Anticoagulantes/uso terapéutico , Quimioprevención , Dabigatrán/uso terapéutico , Enoxaparina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Embolia Pulmonar/prevención & control , Factores de Riesgo , Factores Sexuales , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & control , Adulto Joven
20.
Acta Orthop Traumatol Turc ; 54(1): 118-123, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32175906

RESUMEN

Extraskeletal osteosarcoma is a malignant tumor of soft tissue characterized by osteoid production and has a very low prevalence, comprising approximately 4% of all osteosarcomas and about 1% of all soft tissue sarcomas, and a total of about 350 cases have been reported until now. Heterotopic ossification is a pathological finding of bony tissue in soft tissue regions such as muscle, skin and subcutaneous tissue. We report a case of an 86-year-old woman with a history of total hip arthroplasty (THA), in which open reduction and internal fixation were done for periprosthetic femoral Fracture. The ossified lesion misdiagnosed as heterotopic ossification initially was diagnosed as extraskeletal osteosarcoma at 6 months after the surgery. Both extraskeletal osteosarcoma and heterotopic ossification have no definite symptoms, but show radiopaque shadows on simple radiograph. Therefore, careful attention and thorough evaluation with multiple imaging tests may be necessary for the differential diagnosis of these entities.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur/cirugía , Osificación Heterotópica/diagnóstico , Osteosarcoma , Fracturas Periprotésicas/diagnóstico , Radiografía/métodos , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Femenino , Humanos , Osteosarcoma/diagnóstico , Osteosarcoma/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología
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