Roles of combined femoral and acetabular anteversion in pathological changes of hip dysplasia and hip reconstructive surgery.

Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion, representing their morphological relationship in the axial plane. Along with the increasing understanding of hip dysplasia in recent years, numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip dysplasia. At present, the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation surgery. As an important surgery index, combined femoral and acetabular anteversion have a crucial role in these surgeries. Herein, we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia, total hip replacement, and redirectional hip preservation surgery.

Advances in drug resistance of osteosarcoma caused by pregnane X receptor.

Osteosarcoma (OS) is a prevalent malignancy among adolescents, commonly manifesting during childhood and adolescence. It exhibits a high degree of malignancy, propensity for metastasis, rapid progression, and poses challenges in clinical management. Chemotherapy represents an efficacious therapeutic modality for OS treatment. However, chemotherapy resistance of OS is a major problem in clinical treatment. In order to treat OS effectively, it is particularly important to explore the mechanism of chemotherapy resistance in OS.The Pregnane X receptor (PXR) is a nuclear receptor primarily involved in the metabolism, transport, and elimination of xenobiotics, including chemotherapeutic agents. PXR involves three stages of drug metabolism: stage I: drug metabolism enzymes; stage II: drug binding enzyme; stage III: drug transporter.PXR has been confirmed to be involved in the process of chemotherapy resistance in malignant tumors. The expression of PXR is increased in OS, which may be related to drug resistance of OS. Therefore, wereviewed in detail the role of PXR in chemotherapy drug resistance in OS.

Therapeutic potential of tyrosine-protein kinase MET in osteosarcoma.

Osteosarcoma, the most prevalent primary bone tumor in children and young adults, can often be successfully treated with standard chemotherapy and surgery when diagnosed at an early stage. However, patients presenting with metastases face significant challenges in achieving a cure. Despite advancements in classical therapies over the past few decades, clinical outcomes for osteosarcoma have not substantially improved. Recently, there has been increased understanding of the biology of osteosarcoma, leading to the identification of new therapeutic targets. One such target is MET, a tyrosine kinase receptor for Hepatocyte Growth Factor (HGF) encoded by the MET gene. In vitro and in vivo studies have demonstrated that the HGF/MET pathway plays a crucial role in cancer growth, invasion, metastasis, and drug resistance across various cancers. Clinical trials targeting this pathway are already underway for lung cancer and hepatocellular carcinoma. Moreover, MET has also been implicated in promoting osteosarcoma progression. This review summarizes 3 decades' worth of research on MET's involvement in osteosarcoma and further explores its potential as a therapeutic target for patients with this disease.

Comparison of midterm efficacy of Kirschner wires and elastic intramedullary nails after closed reduction of Judet type 3 radial neck fractures in children: a multicenter study.

Objective: The objective of this study was to compare the midterm efficacy of Kirschner wires and elastic intramedullary nails after the closed reduction treatment of Judet 3 radial neck fractures in children. Methods: This was a retrospective multicenter study of patients diagnosed with Judet type 3 radial neck fractures who underwent closed reduction and internal fixation at four tertiary hospitals from January 2019 to December 2021. Gender, age, fracture type, operation time, follow-up time, x-ray results and complications were collected. The recovery of elbow joint between the two internal fixation methods, elbow motion and complications at the last follow-up were compared. Results: The average operation time of EIN group was statistical significantly increased compared with KW group. There were no significant differences in MEPS score and ROM 3 months after surgery between the two groups, but the ROR Angle of EIN group was statistical significantly increased compared with KW group 3 months after surgery. There were no significant differences in MEPS score, ROM and ROR at the last follow-up. The incidence of complications in EIN group was significantly lower than that in KW group. Conclusion: The use of elastic intramedullary nails fixation or Kirschner wires fixation in the treatment of radial neck fractures in children can both achieve satisfactory fracture reduction and healing. Compared with elastic intramedullary nails, the operation time of Kirschner wires fixation is shorter, and the internal fixation does not need to be removed under anesthesia again, but the complication rate is higher.

Comparison of the midterm result between Lag-Screw fixation and K-wires treating displaced medial epicondyle fractures in children.

Medial epicondyle fractures a prevalent injury, constituting 11% to 20% of all elbow fractures in children and adolescents. Common fixation strategies for displaced medial epicondylar fractures involve the use of K-wires and Lag-Screw fixation. The aim of this retrospective study was to compare 2 methods for treating medial epicondylar fractures in children. In this retrospective study, 26 children with displaced medial epicondyle fractures were included. Patients were divided into 2 groups after reduction: Lag-Screw (LS) group and K-wires group. We compared the operation time, range of motion (ROM), range of rotation (ROR), and Mayo elbow performance score (MEPS). A total of 26 patients were available for a long-term follow-up, with a mean age of 11.6 ±â€…2.5 years, follow up by 35.7 ±â€…5.7 months. The average operation time in K-wires group was shorter than the Lag-Screw group. The average ROM, ROR, and MEPS of the 2 groups are excellent in 3 months follow up after operation and maintained excellent results during the final follow-up. Regarding MEPS, ROM, and ROR, there was no significant difference between LS group and KW group. However, the LS group experienced fewer complications than the KW group. Both Lag-Screw and K-wires fixation for medial epicondyle fractures in pediatric patients yield favorable mid-term results when assessed in terms of ROM,ROR, MEPS. K-wires fixation, while having a shorter operation time and saving an additional anesthesia and surgery to remove the implants compare to fixed by Lag-Screw fixation, does come with a higher complication rate.

A modified method for reconstruction of posterior tibial tendon after resection of juvenile painful type II accessory navicular.

BACKGROUND: The surgical treatment of accessory navicular (AN) is divided into simple resection of AN and Kidner surgery used to reconstruct posterior tibial tendon (PTT) after AN resection. However, both of these procedures have certain disadvantages. Herein, we proposed a modified method to reconstruct PTT and compared the short-term clinical effect of our method with the modified Kidner procedure. METHODS: We collected data from 23 adolescent children with painful type II AN treated in our department between January 2015 and June 2020. The American Orthopedic Foot and Ankle Society Ankle-Hind foot (AOFAS-AH) Scores, the Meary Angle, and Pitch Angle of the lateral weight-bearing plain radiographs status were recorded before and after the operation to evaluate the treatment outcomes. RESULTS: In the modified Kidner surgery (MK) group, the median AOFAS-AH increased from 61 (59-68) to 87 (83-91) (P < 0.05); the Pitch angle of the lateral weight-bearing plain radiographs increased from 13.0 (8-18) to 17.4 (14-22), and the Meary angle decreased from 18.3 (14-24) to 14.2 (8-20) (P < 0.05). In the PTT preservation folded suture (FS) group, the median AOFAS-AH increased from 61 (59-68) to 87 (85-91) (P < 0.05); the Pitch angle of the lateral weight-bearing plain radiographs increased from 12.3 (7-18) to 18.4 (15-26), and the Meary angle decreased from 17.8 (13-23) to 5.7 (3-8) (P < 0.05). There was no significant difference in AOFAS-AH postoperative scores between the FS group and MK group; however, the improvement on Pitch and Meary angle of the lateral weight-bearing plain radiographs was significantly better in the FS group than in MK group (P < 0.05). CONCLUSIONS: For painful type II AN in juvenile patients, the insertion-preserving folding suture procedure had similar short-term results on AOFAS-AH scores but greater improvement in the Meary angle and the Pitch Angle than the modified Kidner method. LEVEL OF EVIDENCE: III.

Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor.

Breast cancer is the most common malignancy in women worldwide. Triple-negative breast cancer (TNBC), refers breast cancer negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, characterized by high drug resistance, high metastasis and high recurrence, treatment of which is a difficult problem in the clinical treatment of breast cancer. In order to better treat TNBC clinically, it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research. Pregnane X receptor (PXR) is a nuclear receptor whose main biological function is to participate in the metabolism, transport and clearance of allobiological agents in PXR. PXR plays an important role in drug metabolism and clearance, and PXR is highly expressed in tumor tissues of TNBC patients, which is related to the prognosis of breast cancer patients. This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress.

Effects of different pelvic osteotomy surgeries on acetabular center and pelvic morphology.

OBJECTIVE: To compare the effects of Salter pelvic osteotomy, Pemberton pelvic osteotomy, and triple pelvic osteotomy on the center of acetabulum and pelvic morphology in children with hip joint disease. METHODS: The data of children treated with Salter pelvic osteotomy (2 males and 14 females with an average age of 2.49 years), Pemberton pelvic osteotomy (4 males and 11 females with an average age of 6.11 years), and triple pelvic osteotomy(4 males and 8 females with an average age of 9.59 years) between January 2011 and December 2020 were collected. After discharge, the outpatient review was followed up for at least 1 year. All patients underwent anterior-posterior pelvic X-ray scanning before surgery, three months after surgery in the first year and every six months after the first year. The following X-ray features were analyzed: bilateral pelvic height (PH), iliac crest inclination (ICI), a horizontal distance of the acetabulum center (HD), and vertical distance of the acetabulum center (VD). RESULTS: The mean follow-up time was 16.9 ± 4.9 months in the Salter group, 20.7 ± 5.1 months in the Pemberton group, and 18.0 ± 5.4 months in the triple group (all P > 0.05). No significant differences between PH, HD, and VD of both sides on the preoperative AP pelvic x-ray were found. However, at the last follow-up, PH, HD,VD, and ICI increased in the Salter group (all P < 0.05), PH and VD increased in the Pemberton group (all P < 0.05), and VD decreased in the Triple group (P < 0.05). CONCLUSION: Salter pelvic osteotomy may cause pelvic height to increase and the center of acetabulum to move outward and downward. In contrast, Pemberton pelvic osteotomy may cause pelvic height to increase and the center of acetabulum to move downward. Triple pelvic osteotomy only causes the center of acetabulum to move downward.

Modified ulnar lengthening for correction of the Masada type 2 forearm deformity in hereditary multiple exostosis.

Few articles have reported on the treatment of Masada type 2 forearm deformities in hereditary multiple exostosis, possibly because of the high redislocation rate and other complications. This study precisely declares the use of modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities. 20 children with Masada type 2 forearm deformities were admitted for surgical treatment at our hospital from February 2014 to February 2021. There were 13 girls and 7 boys, ranging in age from 3.5 to 15 years (mean: 9 years) at the time of operation. We removed the prominent osteochondromas of the distal ulna and the proximal radius, positioned a classic Ilizarov external fixator on the forearm and then performed ulnar transverse one-third proximal diaphyseal subperiosteal osteotomy. We adopted modified ulnar lengthening postoperatively. The effects of surgical correction of deformity and functional improvement of the limb were assessed via regular follow-up and X-ray. The patients were followed up for 36 months, and the ulna was lengthened 26.99 mm on average; all radial heads remained relocated. The radiographic evaluations, including relative ulnar shortening, radial articular angle, and carpal slip, were improved. The functions of the elbow and forearm were all improved after surgery. Modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities in hereditary multiple exostoses has been proven to be an effective and reliable technique in the early stage.

Post-traumatic heterotopic ossification in front of the ankle joint for 23 years: A case report and review of literature.

BACKGROUND: Heterotopic ossification (HO) refers to the formation of new bone in non-skeletal tissues such as muscles, tendons or other soft tissues. Severe muscle and soft tissue injury often lead to the formation of HO. However, anterior HO of the ankle is rarely reported. CASE SUMMARY: We report a patient with massive HO in front of the ankle joint for 23 years. In 1998, the patient was injured by a falling object on the right lower extremity, which gradually formed a massive heterotopic bone change in the right calf and dorsum of the foot. The patient did not develop gradual ankle function limitations until nearly 36 mo ago, and underwent resection of HO. Even after 23 years and resection of HO, the ankle joint was still able to move. CONCLUSION: It is recommended that the orthopedist should be aware of HO and distinguish it from bone tumor.

Percutaneous calcium sulfate injection versus localized scrape bone grafting: clinical effect comparison in titanium elastic nail treatment of pathological fracture of proximal humerus caused by unicameral bone cysts in children.

Objective: A retrospective study was conducted to compare the mid-term clinical efficacy between percutaneous calcium sulfate injection (PCSI) and localized scrape bone grafting (LSBG) in using titanium elastic nails treat humerus pathologic fractures caused by unicameral bone cysts in children. Methods: Humerus pathologic fracture patients with unicameral bone cysts in our pediatric orthopedic department from January 2015 to January 2020 were retrospectively analyzed. Patients were divided into two groups, namely the PCSI group and the LSBG group, based on the type of bone grafting material they received. Preoperative assessments were made in both groups using the Cyst Index and Cyst activity. During the perioperative phase, assessments were made regarding operative time, bleeding, postoperative VAS scores, and the frequency of reoperation within 2 years. Clinical outcomes were evaluated using the Capanna scale at the last follow-up, and the occurrence of re-fractures during the follow-up period. Results: A total of 22 patients were included, with a mean follow-up duration of 33.5 ± 5.8 months. No significant differences were found between the two groups in terms of Cyst Index and Cyst activity before the operation. The operative time, bleeding, and postoperative VAS scores in the PCSI group were found to be lower than those in the LSBG group (P < 0.05). The PCSI group also showed a higher frequency of reoperation within 2 years compared to the LSBG group (P < 0.05). However, no significant differences were observed between the two groups in terms of Capanna scale scores at the last follow-up and the incidence of re-fractures during follow-up. Conclusions: Both titanium elastic nails (TEN) combined with PCSI or LSBG were found to be safe and effective treatments for humerus pathologic fractures caused by unicameral bone cysts in children. PCSI is considered as a less invasive option with shorter operative times, less bleeding, and reduced postoperative pain, although it comes with the risk of multiple injections. On the other hand, LSBG is considered as a more invasive option for the treatment of active bone cysts but is associated with a lower recurrence rate.

Comparison of the midterm result between locking plate and elastic intramedullary nail treating oblique ulnar fracture Bado type I acute monteggia fracture in pediatric patients.

BACKGROUND: Acute Monteggia fracture (AMF) is defined as a fracture of the proximal ulna combined with a dislocation of the radial head, with less than 1 percent prevalence in pediatric patients with an elbow injury. This retrospective study aimed to compare the efficacy of two treatment methods for oblique ulnar fracture AMF Bado type I in children. METHODS: In this retrospective study, 28 children with oblique ulnar fracture acute Monteggia injury Bado I were included. Patients was divided into two groups: In the EIN group 16 patients were fixed with elastic intramedullary nail after reduction, and in the LCP group 12 patients were fixed with locking compression plate after reduction. Operation time and blood loss were recorded and the patients were assessed clinically by the Mayo Elbow Performance Score (MEPS), range of movement(ROM) and range of rotation(ROR). RESULTS: Twenty-eight patients were accessible for durable follow-up, with a mean age of 7.7 ± 1.3 years, follow up by 33.7 ± 5.1 months. The average operation time was 48.1 ± 9.2 min for the EIN group and 67.1 ± 7.2 min for the LCP group. The average blood loss was 8.2 ± 2.3 ml for the EIN group and 18.8 ± 3.8 ml for the LCP group. The average operation time and average blood loss in the EIN group are significant less than the LCP group. Mean MEPS, ROM, ROR in both group improved significantly before sugery to three months after surgery, and maintained very good results at last follow up. There is no significant difference between the EIN group and the LCP group in MEPS, ROM and ROR. CONCLUSIONS: Oblique ulnar fracture Bado type I acute monteggia fracture in pediatric patients fixed by EIN and LCP can both get good mid-term results measured by MEPS, ROM and ROR, Fixed by EIN have shorter operation time and less blood loss than fixed by LCP.

Comparison of mid-term clinical results between lag screw fixation and Kirschner wire fixation after close reduction in adolescent triplane distal tibia epiphyseal fracture.

OBJECTIVE: To compare the mid-term clinical results of lag screw and Kirschner wire fixation(KWF) for close reduction in triplane distal tibia epiphyseal fracture. METHODS: A retrospective analysis of 25 cases of triplane fractures of the distal tibia treated in our department from Jan 2017 to Dec 2019 was performed, Lag screw fixation(LSF) was used in 14 cases and Kirschner wire fixation in 11 cases, the clinical results were evaluated by premature epiphyseal closure(PPC) rate, the American Orthopaedic Foot and Ankle Score (AOFAS) Ankle-hindfoot foot scoring system, the lateral distal tibial angle (LDTA) from X-ray. RESULTS: All the 25 children were followed up for a mean of 34(ranging 26-52) months. AOFAS scores improved from a mean of 33(ranging 29-43) pre-op, to 82(ranging 77-88) at three month follow up, to 92 (ranging 88-98) at last follow-up in all 25 cases. Till last follow up there was no cases premature physeal closure in LSF group but 4 cases in KWF group, LDTA in both groups at last follow up shows no ankle varus or valgus deformity, and the ankle joint function was not limited in all cases. CONCLUSION: Lag screw and Kirschner wire fixation methods can both achieve good clinical effects for triplane distal tibia epiphyseal fracture. Lag screw fixation provide lower PPC rate but Kirschner wire fixation save one anesthesia and surgery.

Synovial chondromatosis of the hip joint in a 6 year-old child: A case report.

BACKGROUND: Synovial chondromatosis (SC) is a rare benign lesion first reported by Ambrose Pare in 1558. It is most common in the knee joint, followed by the hip joint and elbow joint. It is characterized by the presence of multiple pearl-like osteochondral bodies in the joint. The incidence in children is extremely low. CASE SUMMARY: We report a 6-year-old Chinese boy who presented to our hospital with left hip joint pain and claudication for more than one year. We performed total surgical resection of SC tissue in the left hip. A good prognosis was confirmed at the 6-wk follow-up. Pain and swelling symptoms were totally relieved, range of motion of his left hip returned to normal, and there was no clinical evidence of lesion recurrence at last follow-up. Our case is the youngest reported patient with SC occurring in the hip. CONCLUSION: SC is a rare disease and can be easily misdiagnosed. When we encounter children with hip pain and claudication, increased vigilance and a comprehensive physical examination and imaging examination should be considered, in order to avoid misdiagnosis and delayed treatment in patients.

Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Mid-term clinical result of femoral varus osteotomy combined with Pemberton osteotomy in treating spastic hip subluxation.

Hip subluxation in ambulant children with cerebral palsy may lead to limited walking and pain. This study aimed to introduce the indications and methods of femoral varus osteotomy combined with Pemberton osteotomy in treating spastic hip subluxation to evaluate the interim clinical result and outcome and to discuss its corrective mechanism and orthopedic effect. A total of 23 children with spastic hip subluxation, who underwent femoral varus osteotomy combined with Pemberton osteotomy were selected. The clinical effects were evaluated according to the migration percentage, acetabular index, proximal femur neck shaft angle (NSA), and Melbourne Cerebral Palsy Hip Classification System (MCPHCS). The median migration percentage was 55 (50, 75) before operation, 20 (0, 30) at postoperative 1 year, and 22 (5, 32) at last follow-up. The median acetabular index was 30° (25°, 40°) before operation, 20°(15°, 26°) at postoperative 1 year, and 20° (15°, 25°) at last follow-up. The median NSA was 145 (138, 153) before operation, 117 (107, 126) at postoperative 1 year, and 118 (110, 125) at last follow-up. The MCPHCS grade 4 counts 23 (100%) before operation, grade 3 counts 20 (87.0%), grade 2 counts 2 (8.7%) and grade 1 counts 1 (4.3%) at postoperative 1 year, and grade 4 counts 1 (4.3%), grade 3 counts 21 (91.3%) and grade 1 counts 1 (4.3%) at last follow-up. Femoral varus osteotomy combined with Pemberton osteotomy is a good surgical treatment for children with Gross Motor Function Classification System levels I and II and migration percentage greater than 50%.

Dysplasia epiphysealis hemimelica combined with contralateral accessory scaphoid bone: A case report and literature review.

RATIONALE: Dysplasia epiphysealis hemimelica (DEH), also known as Trevor disease, is a rare, developmental bone disorder of childhood. PATIENT CONCERNS: A 9-year-old girl was admitted due to pain in front of the medial malleolus of her right foot after a long walk or distance movement, in which the pain could be relieved after rest, while it was repeated and lasted for several months. DIAGNOSIS: Dysplasia epiphysealis hemimelica INTERVENTIONS:: The patient underwent an open resection surgery. After operation, the pain was totally relieved. Postoperative pathological diagnosis showed DEH. OUTCOMES: At the 6-month follow-up, pain and claudication symptoms fully disappeared, and range of motion of the right foot returned to normal level. CONCLUSIONS: Dysplasia epiphysealis hemimelica is an uncommon disease which can cause pain of foot in children. LESSONS: When the pediatric orthopedic surgeon treated the children suffered with foot pain should be aware of this rare disease, especially accessory scaphoid bone was found in another foot.

Synovial chondromatosis of the hip joint in childhood: A case report and literature review.

RATIONALE: Pain in the hip joint is a common symptom in children. The common diseases leading to pain in the hip joint in children include transient synovitis of the hip, septic arthritis of the hip, and Legg-Calve-Perthes disease. PATIENT CONCERNS: A 7-year-old boy was admitted due to pain in the right hip joint and limping for more than 1 month. DIAGNOSIS: Synovial chondromatosis. INTERVENTIONS: The patient underwent a hip open surgery, all the loose bodies in articular capsule were removed. OUTCOMES: At the 6-month follow-up, pain and limping disappeared, and the range of activity of the hip joint was restored to a normal level. CONCLUSIONS: Synovial chondromatosis is an uncommon disease which can cause pain of hip joint in children. LESSONS: When the pediatric orthopedic surgeon treats the children suffered with hip pain the surgeon should be aware of this rare disease.

A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status.

To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis. RAF265 has a serum half-life of approximately 200 h. The MTD was 48 mg once daily given continuously. Among 77 patients, most common treatment-related adverse effects were fatigue (52%), diarrhea (34%), weight loss (31%) and vitreous floaters (27%). Eight of 66 evaluable patients (12.1%) had an objective response, including seven partial and one complete response. Responses occurred in BRAF-mutant and BRAF wild-type (WT) patients. Twelve of 58 (20.7%) evaluable patients had a partial metabolic response. On-treatment versus pretreatment IHC staining in 23 patients showed dose-dependent p-ERK inhibition. We observed a significant temporal increase in placental growth factor levels and decrease in soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) levels in all dose levels. RAF265 is an oral RAF/VEGFR-2 inhibitor that produced antitumor responses, metabolic responses, and modulated angiogenic growth factor levels. Antitumor activity occurred in patients with BRAF-mutant and BRAF-WT disease. Despite low activity at tolerable doses, this study provides a framework for the development of pan-RAF inhibitors and modulators of angiogenesis for the treatment of melanoma.

Comparison of mid-term efficacy of spastic flatfoot in ambulant children with cerebral palsy by 2 different methods.

To compare the treatment efficacy of spastic flatfoot surgery by 2 different surgical methods: nonfusion subtalar arthroereisis using subtalar joint stabilizer (SJS) and Dennyson-Fulford subtalar arthrodesis (D-FSA).A total of 26 cases of ambulant children with cerebral palsy diagnosed as spastic flatfoot were surgically treated from January 2011 to December 2014. Preoperative and postoperative American Orthopedic Foot and Ankle Society-Ankle and Hindfoot (AOFAS-AH) scores, anteroposterior-talocalcaneal angles (ATAs), and lateral talar-first metatarsal angles (Meary angles) of the affected foot were recorded.Among 12 children in the SJS group, the AOFAS-AH scores were median preoperative score of 61 (58-64) versus median postoperative score of 83 (75-92), with significant difference (P < .05). Of the 20 feet treated, only 1 foot developed occasional pain. Postoperative ATA was decreased from preoperative 35° (20°-50°) to 19° (12°-25°); lateral X-ray films showed that the Meary angle was decreased from preoperative 20° (15°-40°) to postoperative 0° (0°-3°). The differences in both findings were statistically significant (P < .05). Fourteen children (22 treated feet) formed the D-FSA group; all demonstrated fusion of the talocalcaneal joint; AOFAS-AH scores were median preoperative score of 61 (58-64) versus median postoperative score of 83 (75-92), with significant difference (P < .05). Only 1 foot had occasional pain. Postoperative ATA was decreased from preoperative 35° (20°-45°) to 16° (12°-25°); lateral X-ray films showed that the Meary angle was decreased from preoperative 19° (10°-40°) to postoperative 2° (0°-5°); the differences in both findings were statistically significant (P < .05).Both nonfusion subtalar arthroereisis using SJS and D-FSA were effective for the surgical treatment of spastic flatfoot, with similar clinical outcomes.