Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as A2A Adenosine Receptor Antagonists: Exploring the Roles of Ribose at Adenosine Receptors.

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.

Comparing outcomes of plate augmentation, nail exchange, and nail exchange with plate augmentation in the treatment of atrophic femoral shaft nonunion after intramedullary nailing: a multicenter retrospective study.

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.

Usefulness of a drill stopper to prevent iatrogenic soft tissue injury in orthopedic surgery.

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.

Outcomes of Angular Stable Locking System in Femoral Diaphyseal Fractures of Elderly Patients: A Multicenter Comparative Study.

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.

A multicenter study of factors affecting nonunion by radiographic analysis after intramedullary nailing in segmental femoral shaft fractures.

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.

Surgical Outcomes of Percutaneous Pinning and Open Locking Plating in Patients With Intra-articular Fractures of the Base of the Fifth Metacarpal.

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.

Discovery of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives as novel ENPP1 inhibitors.

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).

Predictors for nonunion of unrepaired ulnar styloid fracture associated with distal radius fractures in patients treated with volar locking plate fixation and their effect on functional outcomes.

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.

Intramedullary nailing of subtrochanteric fractures in elderly patients: Comparative study of helical blade cephalomedullary nail versus reconstruction nail.

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.

Comparison of tibial plateau fracture surgical outcomes between young and elderly patients: are outcomes really poorer in the elderly?

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.

Total hip arthroplasty for failed acetabular fracture: a double-center comparative study on failed proximal femur fracture.

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.

Clinical outcomes after mini-hook plate fixation for small avulsion fractures around the interphalangeal or metacarpophalangeal joints of the hand.

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.

Excellent outcomes after double-locked plating in very low periprosthetic distal femoral fractures.

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.

Perioperative symptomatic venous thromboembolism after immediate chemoprophylaxis in patients with pelvic and lower-extremity fractures.

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.

Extraskeletal osteosarcoma misdiagnosed as heterotopic ossification after periprosthetic femoral fracture: A case report.

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.

Surgical outcomes of simple distal femur fractures in elderly patients treated with the minimally invasive plate osteosynthesis technique: can percutaneous cerclage wiring reduce the fracture healing time?

INTRODUCTION: Achieving adequate reduction is difficult when performing minimally invasive plate osteosynthesis (MIPO) in elderly patients with simple distal femur fracture. This study aimed to evaluate the elderly patients who had undergone percutaneous wiring-assisted reduction with MIPO for simple distal femur fractures to determine the effect of this technique on reduction quality and fracture union. MATERIALS AND METHODS: Between January 2009 and September 2017, 56 patients (56 femurs) with displaced simple distal femur fractures treated with MIPO at three trauma centers were finally enrolled. The MIPO technique with percutaneous cerclage wire reduction was performed in 25 patients (Group A). Among them, 12 patients had a simple spiral metaphyseal fracture (Group A*). In comparison, MIPO without percutaneous cerclage wire reduction was performed in 31 patients (Group B). Among them, seven patients had a simple spiral metaphyseal fracture (Group B*). Medical records containing surgical records were retrospectively reviewed to investigate demographic data, comorbidities, complications, operative time, and fluoroscopic time. Radiographs were evaluated for assessing the quality of the reduction and fracture union. RESULTS: The mean fracture union time of Group A* was 21.7 weeks, which was significantly shorter than that of Group B* (28.6 weeks). The mean coronal and sagittal angulation in Group A* was 0.6° and 0.7°, respectively, which were significantly lesser than those in Group B* (2.4° and 3.2°, respectively). Mean translation in Group A* was 1.43 mm, which was significantly shorter than that in Group B* (3.81 mm). Nonunion occurred in two patients in Group B. CONCLUSION: Surgical treatment of simple spiral distal femur fractures with percutaneous cerclage wiring-assisted reduction and the MIPO technique in elderly patients resulted in better reduction and faster union time. Therefore, this technique could be a good solution if used in accordance with the indication.

Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis.

Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony-forming ability, migration, invasion, and wound-healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse-docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness- and epithelial-mesenchymal transition-related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. Furthermore, ginsenoside Rd significantly decreased the number and size of tumor metastasis nodules in the livers, lungs, and kidneys of mouse model of metastasis. © 2018 IUBMB Life, 71(5):601-610, 2019.

Minimally invasive plate augmentation in the treatment of long-bone non-unions.

INTRODUCTION: Exchange nailing is most acceptable for treating hypertrophic non-union of the long bones, requiring the removal of previously fixed implant. However, its main effect of mechanical stabilization is controversial in non-isthmal area. We hypothesized that minimally invasive plate augmentation over the non-union site may have a better option, without the need of bone grafting or removing pre-existing implants. MATERIALS AND METHODS: Seventeen patients with hypertrophic non-union of the long bones between 2010 and 2014 on radiography who previously underwent intramedullary (IM) nailing or plate osteosynthesis for long-bone fractures were included. A locking compression plate was inserted with at least three mono- or bicortical screws at each proximal and distal segment. Broken or loosened interlocking screws of IM nail were simultaneously re-fixed. Fracture site exposure, pre-fixed implant removal, and bone grafting were not performed. We investigated whether union occurred and analyzed functional outcomes and complications. RESULTS: Eleven femoral and six tibial non-unions were prospectively included. In the pre-existing implants, 13 nails and 4 plates were found. All cases achieved union at a mean 22.7 weeks. One case of superficial infection was managed with oral antibiotics. Deep infection or implant failure did not occur. CONCLUSIONS: Minimally invasive plate augmentation can achieve additional stability and promote healing of hypertrophic non-union of the long bones. When indicated, this technique is the least invasive alternative to exchange nailing and reduces surgical risks in the treatment of diaphyseal non-union.

Comparison of outcomes according to fixation technique following the modified Ludloff osteotomy for hallux valgus in patients with rheumatoid arthritis.

BACKGROUND: Clinical and radiological outcomes including fixation stability of osteotomy site were compared in rheumatoid arthritis (RA) patients who underwent modified Ludloff osteotomy to correct hallux valgus with osteotomy site fixation using two screws versus those who underwent additional fixation using a plate. METHODS: The fixation technique performed with two screws was used to fix the osteotomy sites following modified Ludloff osteotomy in 15 patients (15 feet, Group S), while the augmented plate fixation technique was used in 14 patients (16 feet, Group P). Surgical outcomes were analysed using the American Orthopedic Foot and Ankle Society (AOFAS) scores, and radiologic parameters measured before surgery and during follow-up examinations. To evaluate the stability of each osteotomy site fixation technique, the 1-2 inter-metatarsal angle (IMA) and angle of the altered margin of the lateral cortex (AMLC) were measured immediately and 6 weeks after surgery, and variations in the angles were compared. In addition, bone mineral density (BMD) values were compared between patients with correction loss at the osteotomy site and those with no loss of correction. RESULTS: No significant differences between groups were found for total AOFAS scores before surgery and at the final follow-up. However, significant differences were observed in the 1-2 IMA, beginning at 6 weeks postoperatively and continuing through the final follow-up. The 1-2 IMA and angle of AMLC measured immediately after and 6 weeks after surgery showed significantly greater variation in Group S than in Group P. In Group S, patients with correction loss (5 feet) at osteotomy site showed significantly lower BMD values than those with no loss of correction (10 feet). Despite the lower BMD values of patients in Group P than in Group S, a loss of correction did not occur in these patients. CONCLUSIONS: Correction loss occurred at the osteotomy site within 6 weeks postoperatively in patients who underwent fixation using only the two-screw fixation technique following modified Ludloff osteotomy; such loss could be reduced using the augmented plate fixation technique even in patients with osteoporosis.

Percutaneous cerclage wiring followed by intramedullary nailing for subtrochanteric femoral fractures: a technical note with clinical results.

BACKGROUND: Although intramedullary nailing is an ideal treatment for subtrochanteric femoral fractures, it is technically challenging in fractures extending into the nail entry area and/or involving the lesser trochanter. Although the application of circumferential wire may facilitate reduction in these situations, its use remains controversial due to possible blood supply disturbances to underlying bone. In the present study, we evaluated complex subtrochanteric fractures treated by percutaneous cerclage wiring followed by intramedullary (IM) nailing for anatomical fracture reduction and union. METHODS: Twelve patients (mean age 48.3 years) with an unstable subtrochanteric fracture were prospectively treated. Indications of percutaneous cerclage wiring followed by IM nailing were a fracture extending proximally into the nail entry area deemed difficult to treat by anatomical reconstruction by IM nailing or a fracture with long oblique or spiral component. One or two cerclage wires were percutaneously applied for the temporary reduction of main fragments, and then, a cephalo-medullary or a reconstruction nail was fixed. We assessed radiologic results (union time, alignment), functional results, and complications. RESULTS: All 12 cases healed, without a bone graft, at an average of 19.1 weeks after surgery (range 16-24). In 11 cases, acceptable alignment was achieved (mean, valgus 0.3° extension 0.6°) with minimal leg-length discrepancy; the other exhibited 1 cm of shortening. All patients were able to return to pre-injury activity levels, and median Merle d'Aubigne score was 16.9 (15-18). No infection or implant-related complication was encountered to latest follow-up (minimum 12 months postoperatively). CONCLUSION: Temporary reduction by percutaneous wiring offers a means of satisfactory nailing in difficult subtrochanteric femoral fractures, and affords anatomical reconstruction and favorable bony union.