What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

BACKGROUND: Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. QUESTIONS/PURPOSES: Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? METHODS: Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). RESULTS: Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). CONCLUSION: Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. CLINICAL RELEVANCE: If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

Effect of Cabergoline Treatment on Disease Control in Acromegaly Patients.

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

OBJECTIVE: In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. METHODS: Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. RESULTS: In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. CONCLUSIONS: Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission.

BACKGROUND: Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE: To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS: A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS: A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION: Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

Clinicopathological significance of baseline T2-weighted signal intensity in functional pituitary adenomas.

PURPOSE: To assess baseline T2-weighted signal intensity (T2-WSI) of functional pituitary adenomas (FPA), and to investigate the relationship of baseline T2-WSI with clinical features, histopathological granulation patterns, and response to treatment in patients with acromegaly, prolactinoma and Cushing's disease (CD). METHODS: Somatotroph adenomas (n = 87), prolactinomas (n = 78) and corticotroph adenomas (n = 29) were included in the study. Baseline T2-WSI findings (grouped as hypo-, iso- and hyperintense) were compared with hormone levels, tumor diameter, granulation patterns and response to treatment. RESULTS: Somatotroph adenomas were mostly hypointense (53%), prolactinomas were dominantly hyperintense (55%), and corticotroph adenomas were generally hyperintense (45%). Hyperintense somatotroph adenomas were larger in size with sparsely granulated pattern and tumor shrinkage rate was lower after somatostatin analogues (SSA) (p = 0.007, p = 0.035, p = 0.029, respectively). T2 hypointensity was related with higher baseline IGF-1% ULN (upper limit of normal) levels and a better response to SSA treatment (p = 0.02, p = 0.045, respectively). In female prolactinomas, hyperintensity was correlated with a smaller adenoma diameter (p = 0.001). Hypointense female prolactinomas were related to younger age at diagnosis, higher baseline PRL levels and dopamine agonist (DA) resistance (p = 0.009, p = 0.022, p < 0.001, respectively). Hyperintense corticotroph adenomas were related to larger adenoma size and sparsely granulated pattern (p = 0.04, p = 0.017, respectively). There was no significant difference in the recurrence with T2WSI in CD. CONCLUSION: Baseline hypointense somatotroph adenomas show a better response to SSA, whereas hypointensity was related to DA resistance in female prolactinomas.

Zoledronic acid : Treatment option for Gorham-Stout disease.

Gorham-Stout disease is a rare bone resorption disease, the etiology and prognosis of which is uncertain but it is thought to be benign. It can involve one or more bones and can cause pain, swelling, deformity and fractures in affected bones. Diagnosis is made with a combination of clinical, radiological and histopathological examinations once other causes of osteolysis have been excluded. Due to its rarity, there is no standard therapeutic approach.

Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature.

Osteosarcoma as a secondary malignancy after hematopoietic stem cell transplantation (HSCT) is very rare. We present a case and review of 18 other cases reported to date. Our patient underwent HSCT for myelodysplastic syndrome at the age of 4 years. She developed osteosarcoma 13 years later. She underwent surgery after three courses of neoadjuvant chemotherapy followed by chemotherapy and mifamurtide. She has no evidence of disease 28 months after termination of chemotherapy. In 18 other cases of secondary osteosarcoma in the literature, 15 had received total body irradiation, eight had received alkylating agents, and six had received etoposide. The median interval from HSCT to the onset of osteosarcoma was 6.5 years (range 2.5-15.3), which confirms that children undergoing HSCT should be followed up for many years. In conclusion, osteosarcoma must be included in the differential diagnosis among solid tumors that may develop following HSCT.

Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis of Infection? An Experimental Animal Model.

BACKGROUND: Infection after open fractures is a common complication. Treatment options for infections developed after intramedullary nailing surgery remain a topic of controversy. We therefore used a rat fracture model to evaluate the effects of infection on osseous union when the implant was maintained. QUESTIONS/PURPOSES: In a rat model, (1) does infection alter callus strength; (2) does infection alter the radiographic appearance of callus; and (3) does infection alter the histological properties of callus? METHODS: An open femoral fracture was created and fixed with an intramedullary Kirschner wire in 72 adult male Sprague-Dawley rats, which were divided into two study groups. In the infection group, the fracture site was contaminated with Staphylococcus aureus (36 animals), whereas in the control group, there was no bacterial contamination (36 animals). No antibiotics were used either for prophylaxis or for treatment. We performed biomechanical (maximum torque causing failure and stiffness), radiographic (Lane and Sandhu scoring for callus formation), and histologic (scoring for callus maturity) assessments at 3 and 6 weeks. The number of bacteria colonies on the femur, wire, and soft tissue inside knee were compared to validate that we successfully created an infection model. The number of bacteria colonies in the soft tissue inside the knee was higher in the infection group after 6 weeks than after the third week, demonstrating the presence of locally aggressive infection. RESULTS: Infection decreased callus strength at 6 weeks. Torque to failure (299.07 ± 65.53 Nmm versus 107.20 ± 88.81, mean difference with 95% confidence interval, 192 [43-340]; p = 0.007) and stiffness at 6 weeks (11.28 ± 2.67 Nmm versus 2.03 ± 1.68, mean difference with 95% confidence interval, 9 [3-16]; p = 0.004) both were greater in the control group than in the group with infection. Radiographic analysis at 6 weeks demonstrated the fracture line was less distinct (Lane and Sandhu score of 2-3) in the infection group and complete union was observed (Lane and Sandhu score of 3-4) in the control group (p = 0.001). Semiquantitative histology scores were not different between the noninfected controls and the rats with infection (score 10 versus 9). CONCLUSIONS: Retaining an implant in the presence of an underlying infection without antibiotic treatment leads to weaker callus and impedes callus maturation compared with noninfected controls in a rat model. Future studies might evaluate whether antibiotic treatment would modify this result. CLINICAL RELEVANCE: This model sets the stage for further investigations that might study the influence of different interventions on fracture healing in implant-associated osteomyelitis. Future observational studies might also evaluate the histological properties of callus in patients with osteomyelitis.

Bilateral Multifocal Hamartoma of the Chest Wall in an Infant.

BACKGROUND: Hamartoma of the thoracic wall is a rare benign tumor that occurs in infancy and can be mistaken for a malignancy due to its clinical and imaging features. Hamartomas are extrapleural soft tissue lesions that cause rib expansion and destruction and appear on imaging as cystic areas with fluid levels and calcification. They can cause scoliosis, pressure on the neighboring lung parenchyma and mediastinal displacement. While conservative treatment is recommended in asymptomatic cases, growing lesions require surgical excision. CASE REPORT: In this report, we present the imaging findings in a 3-month-old infant that presented with a firm swelling in the chest wall and was histopathologically confirmed to have a bilateral multifocal hamartoma. CONCLUSIONS: Radiological imaging methods are important for accurate diagnosis of this very rare condition that can be confused with a malignancy.

Role of diffusion-weighted MR imaging in the differentiation of benign retroperitoneal fibrosis from malignant neoplasm: preliminary study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) features and signal intensity values at T2-weighted magnetic resonance (MR) imaging for differential diagnosis of benign retroperitoneal fibrosis (RPF) and plaque-like retroperitoneal malignant neoplasms. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this retrospective study. Fifty-one patients with plaque-like confluent retroperitoneal soft-tissue masses were divided into three groups: group I, 25 patients with malignant RPF and retroperitoneal malignant neoplasm; group II, 16 patients with chronic RPF; and group III, 10 patients with active RPF. On T1-weighted (unenhanced and contrast material-enhanced), T2-weighted, and DWI (b = 1000 sec/mm(2)) images, apparent diffusion coefficient (ADC) values and quotients of postcontrast signal intensities between lesions and psoas muscle were evaluated. The χ(2) test was used to compare categorical values; one-way analysis of variance and Kruskal-Wallis tests were used to compare groups. RESULTS: Overall sensitivity, specificity, and positive and negative predictive values of DWI findings were 92% (23 of 25 patients), 62% (16 of 26 patients), 70% (23 of 33 patients), and 89% (16 of 18 patients), respectively. Mean ADC values were 0.79 ± 0.19 in group I, 1.43 ± 0.16 in group II, and 0.91 ± 0.14 in group III. When comparing values, differences between groups I and II (ADC values, P < .0001; DWI quotients, P < .0001; postcontrast quotients, P = .001) and groups II and III (ADC values, P < .0001; DWI quotients, P = .016; postcontrast quotients, P = .04) were significant. There was no significant difference between groups I and III or between the three groups when T2-weighted values were compared. CONCLUSION: ADC of chronic RPF was higher than that for active RPF or malignant RPF and retroperitoneal malignant neoplasm. DWI can contribute to differential diagnosis of chronic RPF and malignant neoplasms with RPF morphology. Lesions in the malignant group and active RPF group had similar enhancement patterns, while those in the chronic RPF group demonstrated less enhancement. Signal intensity values on T2-weighted images were not useful for differentiating these conditions.

Minimal invasive endoscopic management of synchronous granular cell tumours in the colon and posterior mediastinum.

Granular cell tumour (GCT), which is a rare benign soft tissue neoplasm, is mostly found in the skin and soft tissue but may develop anywhere in the body. There are less than 10 reported cases of mediastinal GCTs in the current literature. Furthermore, colonic GCTs have recently gained attention due to the increased public awareness on the importance of colonoscopy screening. We report a case of a 52-year-old woman diagnosed incidentally with synchronous GCTs of the mediastinum and the hepatic flexure on her routine screening for post-operative follow-up for status-post right modified radical mastectomy due to a T2N1M0, Stage 2B breast cancer.

Subchondral curettage cement packing in the distal radius causes wrist joint degeneration: long-term evaluation of distal radius giant-cell bone tumour.

INTRODUCTION: This study investigated wrist joint degeneration after curettage and PMMA treatment for giant cell bone tumours (GCBT) at the distal radius. METHODS: We performed a retrospective single-centre study, which included 23 patients with GCBT at distal radius treated with curettage and PMMA between 2001 and 2021. The progression of wrist joint degeneration was assessed through radiographic evidence, comparing the postoperative grade with both the preoperative grade and the grade of the contralateral wrist at the latest follow-up. We also analyzed the influence of age, sex, tumour distance of the joint, subchondral bone involvement, tumour size and body mass index. RESULTS: The study included 23 patients with a mean age of 32.1 ± 13.3 years. The average duration of follow-up was 96.4 ± 69 months (range, 24-265 months). The mean tumour-cartilage distance was 1.79 ± 2.4 mm (range, 0-10 mm) and the mean BMI was 23.5 ± 3.8 kg/m2. Degeneration of the wrist joint was evident in 16 patients (69.6%) at the final assessment, however, 10 patients (43.4%) were identified as having a progression of joint degeneration secondary to the surgical procedure among the 16 patients with wrist joint degeneration at the final control view. Age, gender, dominance, tumour-cartilage distance, subchondral bone involvement, tumour size, patient height, weight, and BMI were not associated with secondary joint degeneration. CONCLUSIONS: Ten of 23 patients developed wrist joint degeneration over an average follow-up period of 8 years, and no particular factors associated with the degeneration were identified.

Malignant epignathus including a nephroblastoma component and successful management.

A male infant was born to a 24-year-old mother (gravida 1 para 1) by cesarean delivery at 33 1/7 weeks of gestation. The physical examination revealed a large mass protruding from the baby's mouth, which appeared to be attached to the palate. Tracheostomy was performed immediately in the delivery room. A partial surgical excision was performed on the second postnatal day, removing most of the teratoma (epignathus), which was attached to the back of the pharynx and protruding from the baby's mouth measuring 13×11×9 cm and weighing 545 g. The final pathological diagnosis was "malignant epignathus with nephroblastoma component." According to our knowledge, this is the first case that have malignant epignathus including nephroblastoma component in the literature.

The infragluteal sulcus: a histologic and ultrasonographic study.

UNLABELLED: The buttocks are a major component of sexual attraction, and they have their place in the concept of beauty in most cultures and ethnic groups. The infragluteal sulcus, an important part of the gluteal region, determines the attractiveness of the buttocks. For that reason, any small change in the infragluteal sulcus makes a major cosmetic difference in the morphology of the buttock. In recent years, some flaps such as the infragluteal flap, the transverse upper gracilis flap, and the transverse musculocutaneous gracilis flap have become popular because of reduced donor area morbidity and their availability for hiding incision scars. In these cases, there may be distortion of the gluteal morphology and infragluteal sulcus. In this study, the anatomic and histologic features of the tissues that form the infragluteal sulcus were analyzed for their contribution to successful reconstruction of the infragluteal sulcus. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical course and features of soft tissue sarcomas in geriatric patients: a single-center experience.

OBJECTIVE: This study was performed to examine the disease course in geriatric patients with soft tissue sarcoma and determine the risk factors for mortality. METHODS: We retrospectively analyzed patients who were treated at Istanbul University Oncology Institute from January 2000 to August 2021. RESULTS: Eighty patients were included in the study. The patients' median age was 69 years (range, 65-88 years). The median overall survival of patients diagnosed between the ages of 65 and 74 years was 70 months, and that of patients diagnosed at the age of ≤75 years was significantly lower at 46 months. The median survival of patients who did and did not undergo surgical resection was 66 and 11 months, respectively, with a significant difference. The median overall survival of patients with positive and negative surgical margins was 58 and 96 months, respectively, also with a significant difference. Age at diagnosis and recurrence/metastasis significantly affected mortality. A 1-year increase in the age at diagnosis increased mortality by 1.147 times. CONCLUSION: Age of >75 years, inability to undergo surgery, positive surgical margins, and head and neck location may be associated with a poor prognosis in geriatric patients with soft tissue sarcoma.

The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis.

OBJECTIVE: The purpose of this study was to examine the effect of prophylactic tadalafil use on a steroid-induced femoral head avascular necrosis model in terms of microscopic, imaging, and molecular biological changes. METHODS: Twenty-four New Zealand rabbits were divided into 3 equal groups. Eight rabbits were designated as the control group and did not receive treatment. Rabbits in group 1 (G1) received 0.1 mg/kg Escherichia coli lipopolysaccharide (LPS) intravenously and 40 mg/ kg methylprednisolone sodium succinate (MP) was administered intramuscularly for 3 days consecutively. Rabbits in group 2 (G2) were given 5 mg/kg tadalafil orally for 10 consecutive days. Starting on the eighth day, 0.1 mg/kg LPS was given, and following this 40 mg/kg MP injections were administered for 3 days. All animals were sacrificed 3 weeks after the final MP injection. Magnetic resonance imaging was performed, and bilateral femora were harvested. Half of the femoral head was stored for Vascular Endothelial Growth Factor (VEGF) examination with Western blot analysis. The other half was examined microscopically for the presence of osteonecrosis. RESULTS: In G1, 15 out of 16 hips (93%) of the 8 rabbits had osteonecrosis compared to 8 out of 12 hips (67%) of 6 rabbits in G2 (P > .05). The VEGF expression in G2 was significantly higher than in the control group and G1 (P < .05 and P < .001, respectively). There was no significant difference in VEGF expression between the control group and G1 (P > .05). CONCLUSION: This study has shown us that femoral head osteonecrosis can be reliably induced with LPS and corticosteroid, as described in the literature. Prophylactic tadalafil use did not decrease the occurrence of osteonecrosis significantly. However, it significantly increased VEGF expression in the femoral head independent of the effects of steroids and LPS.

Diagnosis and management of tumor-induced osteomalacia: a single center experience.

PURPOSE: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. MATERIAL METHODS: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. RESULTS: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. CONCLUSION: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment.

Vascularity and histology of fetal labrum and chondrolabral junction: its relevance to chondrolabral detachment tears.

PURPOSE: Recently, acetabular labral tears were recognized as a source of hip pain. Most of these tears were found to be localized at the chondrolabral junction. The purpose of this study was to evaluate the chondrolabral junction in reference to its collagen fiber orientation and its vascularity, which might be used to explain the preponderance of labral tears. METHODS: Eighteen formalinized fetuses with a mean gestational age of 17 weeks (range: 11-24 weeks) were examined. The acetabuli were removed en bloc with the proximal femur for ease of orientation. The acetabuli were prepared and examined in four quadrants, namely, anterior, superior, posterior, and inferior. RESULTS: The staining pattern of the posteroinferior labrum was more dense than the anterosuperior labrum, due to its high collagen content. Collagen fibers in the posteroinferior quadrants were oriented perpendicularly to the chondrolabral junction, while those in the anterosuperior quadrants had a parallel oriented. Perpendicular collagen orientation and high collagen content may explain the stronger anchorage of the labrum to the bony acetabulum in posteroinferior quadrants. All of the vessels supplying the labrum originate from the capsular connective tissue and traverse the body of the labrum to reach the articular side. None of these vessels traverse the chondrolabral junction to reach the bony acetabulum. The total number of blood vessels was significantly higher in the capsular zone than in the articular zones. The number of blood vessels did not differ between the acetabular quadrants. CONCLUSIONS: In an effort to understand the chondrolabral junction tears, we can conclude that collagen content and fiber orientation may represent the histological basis for the predominance of tears at the anterosuperior region.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

AIM: To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. MATERIAL AND METHODS: This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. RESULTS: In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. CONCLUSION: The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.