Usefulness of double plate fixation after failed ORIF for clavicle shaft fracture.

PURPOSE: We aimed to evaluate the clinical and radiological outcomes of double plate fixation for failed clavicle shaft fracture surgery. MATERIALS AND METHODS: We analyzed 14 patients who underwent double plate fixation due to plate failure after clavicle shaft fracture surgery from March 2016 to March 2021. The study used 3.5 mm locking compression plates for superior clavicle and anterior reconstruction in all patients. In addition, moldable allograft bone was used to fill the bone defect. Clinical and radiological evaluation was performed immediately, at 2 and 4 weeks, and 3, 6, 9, and 12 months postoperatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) shoulder scale, and American Shoulder and Elbow Surgeons (ASES) scores and range of motion of the shoulder were evaluated as clinical results. For radiological evaluation, anteroposterior, caudal, and cephalad views of both clavicles were used. Successful bone union was defined as complete adjoining of the fracture site through callus formation. RESULTS: Successful bone union was achieved in all patients, and the mean time to bone union was 16.7 ± 1.2 weeks (range, 12-24 weeks). Statistically significant improvement in forward flexion and external and internal rotation was observed from 135.5° ± 6.3, 45.2° ± 5.3, and 13° ± 2.3 preoperatively to 157.0° ± 9.3, 68.7° ± 6.3, and 9.8° ± 3.1 at the final follow-up, respectively. The VAS score improved from an average of 6.2 ± 2.8 preoperatively to 1.3 ± 0.7 at the final follow-up, which was statistically significant (P = 0.018). In addition, the ASES score significantly increased from a mean of 52.1 ± 6.3 points preoperatively to 83.6 ± 7.8 points at the final follow-up (P = 0.001). The average UCLA shoulder score was 16.7 ± 1.4 and 31.4 ± 2.2 points preoperatively and at the final follow-up, respectively, which was statistically significant (P = 0.001). CONCLUSION: Double plate fixation has shown good results after failed open reduction and internal fixation (ORIF) for clavicle shaft fractures. Therefore, in complicated situations after ORIF, double plate fixation is considered a surgical treatment option.

Socioeconomic and Other Risk Factors for Retear after Arthroscopic Surgery for Nontraumatic Rotator Cuff Tear.

Background and Objectives: Few studies have investigated the socioeconomic factors associated with retear after rotator cuff repair. This study aimed to identify the risk factors, including socioeconomic factors, for rotator cuff retear in patients who underwent arthroscopic rotator cuff repair. Materials and Methods: This retrospective study included 723 patients diagnosed with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair from March 2010 to March 2021. The outcome variable was rotator cuff retear observed on postoperative magnetic resonance imaging or ultrasonography. Sex, age, obesity, diabetes, symptom duration, and tear size were the independent variables. Socioeconomic variables included occupation, educational level, type of medical insurance, and area of residence. We compared patients with and without retear and estimated the effects of the independent factors on retear risk. Results: The mean age of the patients, symptom duration, and tear size were 62.4 ± 8.0 years, 1.8 ± 1.7 years, and 21.8 ± 12.5 mm, respectively. The age, type of medical insurance, diabetes, tear size, and symptom duration differed significantly between patients with and without retearing (p < 0.05). Age, occupation, type of medical insurance, diabetes, initial tear size, and symptom duration significantly affected the risk of retear. Patients who performed manual labor had a significantly higher retear rate (p = 0.005; OR, 1.95; 95% CI, 1.23-3.11). The highest retear risk was seen in patients with Medicaid insurance (p < 0.001; OR, 4.34; 95% CI, 2.09-9.02). Conclusions: Age, initial tear size, and symptom duration significantly affect retear risk after arthroscopic rotator cuff repair. Occupation and type of medical insurance were also risk factors for retear. Socioeconomically vulnerable patients may be at a greater risk of retear. Proactive efforts are required to expand early access to medical care.

Superior mesenteric artery syndrome in a patient with fibrodysplasia ossificans progressiva.

An 18-year-old boy with fibrodysplasia ossificans progressiva lost weight at an accelerated rate due to gastrointestinal symptoms, resulting in a weight loss of 36 kg in 1 year. His first outpatient abdominal computed tomography (CT) result was unremarkable. Since the patient had biliary vomiting during hospitalization, his CT was reexamined, and the superior mesenteric artery syndrome diagnosis was confirmed. Thus, clinicians must consider superior mesenteric artery syndrome when presented with weight loss.

Novel RPL13 Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia.

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In vitro studies on patient-derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p < 0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p = 0.007) and attenuated global translation (p = 0.017). In line with the human phenotype, our rpl13 mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum of RPL13 mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generated rpl13 mutant zebrafish model corroborates the role of eL13 in skeletogenesis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Primarily treated patients versus referred patients in the treatment of native septic arthritis of digits: a retrospective comparative study.

BACKGROUND: Septic arthritis of digits needs urgent treatment. When treatments delayed or insufficient, patients may be referred to the upper-level hospital due to uncontrolled infection. We reviewed the treatment history of referred patients and compared the microorganisms and the clinical course of both primary and referred patients as relevant studies are rare. METHODS: In this retrospective review of consecutive case series, 45 patients (primary, n = 11; referred, n = 34) were treated with multiple irrigation and debridement. Cefazolin was used as empiric antibiotics, then changed according to microbiologic study. Previously used antibiotics, treatment delay, surgical history of the referred patients were reviewed. Identified microorganisms, required surgical intervention, hospital stay, radiologic outcome, functional outcomes were compared between both groups. RESULTS: In the referred patients, methicillin-resistant Staphylococcus aureus (MRSA) was commonly found and cefazolin was susceptible in only 15% of the cases. Longer hospital stay, prolonged antibiotic therapy, more surgical intervention including flap surgery was required to treat the referred patients. Postoperative pain was not severe in daily activities, but the final range of motion was significantly less in the referred patients compared to the primary patients. CONCLUSIONS: This study suggests that in the treatment of uncontrolled septic arthritis of the digits, antibiotic agents covering MRSA may shorten the duration of antibiotic therapy in areas of high MRSA incidence. Besides, more number of I & D including flap surgery may be required for the referred patients compared with the primary patients. These findings can help the surgeon in setting up a treatment plan or in counseling of referred patients with uncontrolled septic arthritis of the digits.

Evaluation of immune-biomarker expression in high-grade soft-tissue sarcoma: HLA-DQA1 expression as a prognostic marker.

High-grade soft-tissue sarcoma (STS) is a highly malignant neoplasm with a poor overall prognosis. Numerous prognostic factors determine tumor progression and patient outcomes. Various immune-associated cells identified in the tumor microenvironment have important roles in various tumor types. The present study was performed to evaluate the expression of immune-associated genes and to elucidate the association between these genes and the prognosis in high-grade STS. A total of 12 formalin-fixed, paraffin-embedded tissue samples of high-grade STS were subjected to gene expression analysis using the NanoString nCounter® System and another 35 samples were used for immunohistochemistry. For comparative analysis, the patients were divided into two groups according to overall survival (OS). The expression levels of 770 genes were first analyzed using the nCounter® PanCancer Immune Profiling Panel. Immunohistochemistry was then performed for the most significantly altered genes. Subsequently, the association between gene expression and prognosis of high-grade STS was evaluated. Of the 770 immune-associated genes analyzed, several genes were identified as being differentially expressed between the two groups. Based on gene expression levels and fold change, 13 representative genes were identified; 7 of the 13 candidate genes (C3, CD36, DOCK9, FCER2, FOS, HLA-DRB4 and NCAM1) were significantly overexpressed in the poor prognosis group, while the other 6 immune-associated genes (BIRC5, DUSP4, FOXP3, HLA-DQA1, HLA-DQB1 and LAG3) were increased in the good prognosis group. By immunohistochemistry, the expression of the 13 immune-associated genes was confirmed to be significantly different between the two groups. Expression of HLA-DQA1, HLA-DQB1 and HLA-DRB4 was observed in 74.3, 34.3 and 48.6% of tumors, respectively. HLA-DQA1 and HLA-DQB1 were significantly decreased, whereas HLA-DRB4 was significantly increased in the poor prognosis group. Of note, expression of HLA-DQA1 was associated with a significantly longer OS (P=0.028). In conclusion, HLA-DQA1 expression was significantly associated with long-term survival and may therefore be an immune biomarker for good prognosis in high-grade STS.

Bone density of the calcaneus correlates with radiologic and clinical outcomes after calcaneal fracture fixation.

BACKGROUND: This study aimed to determine whether bone density correlates with radiologic and clinical outcomes after screw fixation of displaced intra-articular calcaneal fractures (DIACF) with the sinus tarsi approach. MATERIALS AND METHODS: We retrospectively evaluated 43 consecutive cases of unilateral DIACF between March 2015 and December 2017. Radiologic evaluations were performed using preoperative, postoperative, and last follow-up calcaneal lateral and axial radiographs. In all patients, preoperative CT scanning of both injured and uninjured calcaneus were performed at one scanning and dual x-ray absorptiometry (DXA) scans were obtained. Hounsfield unit (HU) measurement values were determined by placing an elliptical region of interest confined to the cancellous region of the uninjured calcaneus. Clinical outcomes were assessed at a minimum of 12 months postoperatively using Foot and Ankle Outcome Scores (FAOS). RESULTS: Mean HU values of the uninjured calcaneus significantly correlated with bone mineral density scores obtained from DXA scans of the lumbar and femur (Spearman ρ = 0.656 - 0.748; p < 0.001 for both). Decreased HU values of the uninjured calcaneus significantly correlated with decreased Böhler's angle and widening of calcaneal width from postoperative to last follow-up. (Pearson r = 0.348, p = 0.022; Pearson r = -0.582, p < 0.001, respectively). Increased HU values of the uninjured calcaneus significantly correlated with improved clinical outcomes in three of five FAOS domains, including activities of daily living, sports, and quality of life (beta = 0.283 - 0.322; p < 0.05 for all). CONCLUSION: Decreased preoperative bone density significantly correlated with decreased Böhler's angle, widening of calcaneal width, and inferior short-term clinical outcomes after screw fixation of DIACF. By quantifying bone density using HU value in area where DXA cannot be performed, such foot bones, determining whether different fixation methods or systemic treatments can be tailored to bone density could help in optimizing clinical outcomes. LEVEL OF EVIDENCE: Level III, Retrospective case series.

In idiopathic cubital tunnel syndrome, ulnar nerve excursion and instability can be reduced by repairing Osborne's ligament after simple decompression.

Osborne's modified decompression involves repairing Osborne's ligament beneath the ulnar nerve after simple decompression for idiopathic cubital tunnel syndrome. In this retrospective interrupted time series, 31 patients underwent modified simple decompression and 20 patients underwent conventional simple decompression. In the modified simple decompression group, the ulnar nerve length was measured at operation in full elbow flexion and extension before and after repair of Osborne's ligament. Ulnar nerve instability during elbow motion was measured using ultrasonography before operation and at 12 months after operation. In patients treated by modified simple decompression, the ulnar nerve length in full elbow flexion reduced significantly after repair of Osborne's ligament. At 12 months after surgery, the grade of ulnar nerve instability was lower in the modified simple decompression group than in the conventional simple decompression group. The clinical outcomes did not differ significantly between the groups at 24 months after operation. Level of evidence: III.

Surgical Outcomes of Internal Fixation Using Multiple Screws in Femoral Neck Fractures with Valgus Impaction: When Should We Consider Hip Arthroplasty? A Retrospective, Multicenter Study.

PURPOSE: We analyzed the surgical outcomes at two institutions after internal fixation using multiple screws in femoral neck fractures with valgus impaction to determine independent predictors and their cut-off values for nonunion and reoperation. MATERIALS AND METHODS: Between January 2006 and December 2016, 104 femoral neck fractures with valgus impaction that underwent internal fixation using multiple screws from two institutions were enrolled. The multiple logistic regression model and receiver operating characteristics analysis were used to determine the independent predictors and cut-off values for nonunion and reoperation. RESULTS: There were 20 reoperations (19.2%) due to 11 nonunions (10.6%) and nine cases of femoral head osteonecrosis (8.7%). Multiple logistic regression analysis revealed that independent predictors of nonunion and reoperation were age and posterior tilt angle (P<0.05). The cut-off value for age and the posterior tilt angle for reoperation were 72.5 years and 12.2°, respectively. The patients with a posterior tilt angle of greater than 13° had poorer radiological and clinical outcomes compared with those with a posterior tilt angle of less than 13°, even though they did achieve bone union. CONCLUSION: Primary hip arthroplasty should be considered in patients older than 73 years of age with a posterior tilt angle greater than 13°.

The best method for evaluating anteversion of the acetabular component after total hip arthroplasty on plain radiographs.

BACKGROUND: Several radiological methods for measuring the anteversion of the acetabular component after total hip arthroplasty (THA) exist, and no single standardized method has been established. We evaluated the reliability and accuracy of six widely utilized methods (Liaw et al., Lewinnek et al., Widmer, Hassan et al., Ackland et al., and Woo and Morrey) for measuring anteversion on plain radiographs, using a reference standard in the same definition obtained from the PolyWare programme. METHODS: We reviewed 71 patients who underwent primary unilateral THA. The anteversion of the acetabular component was measured on pelvis AP radiographs using five different methods (Liaw et al., Lewinnek et al., Widmer, Hassan et al., and Ackland et al.) and on cross-table lateral radiographs using the method of Woo and Morrey. The values obtained using the PolyWare programme, which determines the anteversion of the acetabular component by edge detection, were regarded as the reference standard. RESULTS: Intra- and inter-observer reliabilities were excellent for all methods using plain radiographs, including the PolyWare programme. The method of Liaw et al. obtained values similar to those obtained using the PolyWare programme and was thus considered accurate (P = 0.447). However, values obtained using the other five methods significantly differed from those obtained using the PolyWare programme and were thus considered less accurate (P < 0.001, P < 0.001, P < 0.001, P = 0.007, and P < 0.001, respectively). CONCLUSION: The method of Liaw et al. is more accurate than other methods using plain radiographs for the measurement of the anteversion of the acetabular component after THA, with reference to the anteversion obtained from the PolyWare programme.

Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy.

A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg(-1) per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P < 0.05), whereas the levels of 3-indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2-oxoglutarate (×2.3) increased significantly (P < 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3-indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3-indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation.

MRI of the proximal femur predicts marrow cellularity and the number of mesenchymal stem cells.

PURPOSE: To determine whether the marrow conversion index (MCI) in MRI is related to the total number of mononuclear and mesenchymal stem cells (MSCs) in proximal femoral metaphysis of patients with hip osteoarthritis. MATERIALS AND METHODS: Thirty-two hips of 32 consecutive patients who underwent total hip arthroplasty (THA) for hip osteoarthritis were included in this study. MRI of the hip was performed preoperatively and MCI was subsequently calculated. Three-milliliter bone marrow samples were obtained from the proximal femur during THA and the number of total mononuclear cells was determined using a hemocytometer. Colony forming unit-fibroblasts (CFU-Fs) assays of MSCs were performed by transferring a total of 2 × 10(4) mononuclear cells to each of five 60-mm plates. One week later, the numbers of colonies were counted. RESULTS: The total number of mononuclear cells decreased with increasing MCI. Likewise, the prevalence and total number of CFU-Fs increased with increasing number of total mononuclear cells, and decreased with increasing MCI. CONCLUSION: Our results suggest that measurement of MCI in MRI can be an objective and noninvasive method to predict marrow cellularity and the number of MSCs in patients with hip osteoarthritis.

Chemopreventive mechanisms of methionine on inhibition of benzo(a)pyrene-DNA adducts formation in human hepatocellular carcinoma HepG2 cells.

This study was designed to investigate the molecular mechanism underlying the chemopreventive effects of methionine on benzo[a]pyrene (B[a]P)-DNA adducts formation in HepG2 cells. Methionine significantly inhibited B[a]P-DNA adduct formation in HepG2 cells. Methionine significantly decreased the cellular uptake of [(3)H] B[a]P, but increased the cellular discharge of [(3)H] B[a]P from HepG2 cells into the media. B[a]P significantly lowered total cellular glutathione (GSH) level, but co-cultured with B[a]P and methionine, gradually attenuated intracellular GSH levels in a concentration-dependent manner, which was markedly higher at 20-500µM methionine. The cellular proteins of treated cells were resolved by 2D-polyacrylamide gel electrophoresis. Proteomic profiles showed that phase II enzymes such as glutathione S-transferase (GST) omega-1, GSTM3, glyoxalase I (GLO1) and superoxide dismutase (SOD) were down-regulated by B[a]P treatment, whereas cathepsin B (CTSB), Rho GDP-dissociation inhibitor alpha (Rho-GDP-DIA), histamine N-methyltransferase (HNMT), spermidine synthase (SRM) and arginase-1 (ARG1) were up-regulated by B[a]P. B[a]P and methionine treatments, GST omega-1, GSTM3, GLO1 and SOD were significantly enhanced compared to B[a]P alone. Similarly, methionine was effective in diminishing the B[a]P-induced up-regulation of CTSB, Rho-GDP-DIA, HNMT, SRM and ARG1. Our data suggests that methionine might exert a chemoprotective effect on B[a]P-DNA adduct formation by attenuating intracellular GSH levels, blocking the uptake of B[a]P into cells, or by altering expression of proteins involved in DNA adduct formation.

Hepatotoxicity and nephrotoxicity produced by 4-hydroxy-2-nonenal (4-HNE) following 4-week oral administration to Sprague-Dawley rats.

4-Hydroxy-2-nonenal (4-HNE) is a major end product of lipid peroxidation of membrane n-6 polyunsaturated fatty acids, which are found in food products. In order to examine the toxicity attributed to 4-HNE, a subacute toxicity study was conducted in Sprague-Dawley (SD) rats. For this study, 4 groups of 10 male and 10 female rats were administered by gavage either 0 (control), 0.5, 2.5, or 12.5 mg 4-HNE/kg body weight/d for 28 d, and then sacrificed for blood and tissue sampling. No significant changes in body weight or clinical signs were observed, but biochemical analysis showed significant alterations in hepatotoxicity biomarkers, such as levels of serum albumin and total bilirubin, and aspartate aminotransferase (AST) activity, and in nephrotoxicity biomarkers, such as levels of blood urea nitrogen (BUN) and creatinine and activity of alkaline phosphatase (ALP), and urinary creatinine and protein levels at 0.5 mg/kg/d. In addition, significant increases in kidney and brain weights and a significant decrease in small intestine weight were noted at 12.5 mg/kg/d. Histologic examinations of kidneys showed hyaline droplets or accumulation of hyaline bodies in renal tubules and degeneration of tubular epithelium cells. These results demonstrate that oral daily exposure to 4-HNE for 28 d produced hepatotoxicity and nephrotoxicity. The no-observed-adverse-effect level (NOAEL) for 4-HNE was calculated to be <0.5 mg 4-HNE/kg/d.

Orthopaedic manifestations of arthrogryposis-renal dysfunction-cholestasis syndrome.

BACKGROUND: Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome (MIM♯208085) is a rare multisystem disorder, which involves the kidney, liver, skin, and central nervous and musculoskeletal systems. It is inherited as an autosomal-recessive trait, associated with germ-line mutations in the VPS33B gene. In this study, the authors reviewed the orthopaedic manifestations of ARC syndrome. MATERIALS: Ten patients diagnosed as having ARC syndrome were the subjects of this study. ARC syndrome was confirmed by mutation analysis in 8 of the 10 patients. Medical records and radiographs were retrospectively reviewed with a focus on musculoskeletal manifestations. RESULTS: Seven patients either expired at 4 to 19 months of age or were presumed to have expired. The remaining 3 patients remained alive at the time of writing this manuscript and were aged from 7 to 23 months. All patients showed musculoskeletal symptoms and/or signs, which included vertical talus (7 feet, 4 patients), pes calcaneovalgus (4 feet, 3 patients), hip dislocation (6 hips, 3 patients), pathologic fractures (5 fractures in 5 patients), and rigid kyphosis (2 patients). No surgical intervention was performed. Orthopaedic treatments, other than fracture management, were abandoned soon after diagnoses were made. CONCLUSIONS: ARC syndrome should be included in the differential diagnosis of arthrogryposis. As there is no specific effective treatment for renal dysfunction and cholestasis, orthopaedic intervention should be postponed until long-term survival is expected, though this is unlikely. LEVEL OF EVIDENCE: Level IV, diagnostic studies, case series.

Comparative nephrotoxicitiy induced by melamine, cyanuric acid, or a mixture of both chemicals in either Sprague-Dawley rats or renal cell lines.

Acute nephrotoxicities of melamine (MEL), cyanuric acid (CA), and a mixture of both melamine and cyanuric acid (MC) were comparatively investigated in male Sprague-Dawley rats at 5 doses each with 10-fold dose interval as follows: MEL at 0.0315, 0.315, 3.15, 31.5, and 315 mg/kg; CA at 0.025, 0.25, 2.5, 25, and 250 mg/kg, and MC: [1×: (0.0315 + 0.025), 10×: (0.315 + 0.25), 100×: (3.15 + 2.5), 1000×: (31.5 + 25), and (315 + 250) mg/kg]. No marked adverse effects in renal function were observed in animals treated with MEL alone or CA alone, but evidence related to nephrotoxicity was noted in rats administered MC. Renal calculi and increased kidney weights were found in rats 7 d after daily oral administration of MC. Blood urea nitrogen (BUN) and creatinine were significantly elevated in the high dose MC groups at 100× or 1000×. In addition, elevated numbers of white blood cells (WBC), neutrophils, and lymphocytes in vivo and increased levels of prostaglandin E(2) (PGE(2)) in vitro were found in the MC group. Based on these data, the NOAEL (no-observed-adverse-effect level) for nephrotoxicity for MC was estimated to be 3.15 mg/kg body weight (bw)/d (MEL) plus 2.5 mg/kg bw/d (CA). If a safety factor of 1000 or more were applied to NOAEL, tolerable daily intake (TDI) would be 0.00315 and 0.0025 mg/kg/d or less for MEL and CA, respectively, which is far below the TDI of 0.2 mg/kg/d set by World Health Organization (WHO). In addition, in vitro cytotoxicity assays showed that the ACHN human renal adenocarcinoma cell line was more sensitive to MEL, CA, and MC than the MDCK canine kidney epithelial cell line. The 24-h half maximal inhibitory concentration (IC(50)) values for MEL (4792, 2792 µg/ml) were less than those of CA (9890, 6725 µg/ml, respectively) in MDCK and ACHN cell lines, suggesting that MEL may be more cytotoxic than CA. Furthermore, the 24-h IC(50) value for MC was found to be 208 µg/ml in ACHN cells. Data suggest that NOAELs based upon acute nephrotoxic parameters for MC were low, which might require further reassessment of the current TDI.

Angular deformity correction by asymmetrical physeal suppression in growing children: stapling versus percutaneous transphyseal screw.

PURPOSE: The aim of this study was to compare the outcomes of angular deformity correction by hemiepiphyseal stapling versus percutaneous hemiepiphysiodesis using transphyseal screw in growing children. METHODS: Forty-three physes in 19 patients underwent hemiepiphyseal stapling, and 37 physes in 23 patients underwent percutaneous transphyseal screw placement. All cases were followed up to skeletal maturity or for more than 1 year after hardware removal. Amounts and rates of angular deformity correction, physeal behaviors after hardware removal, and postoperative courses were compared between the 2 groups. RESULTS: The goal of angular correction was achieved in all except 2 patients, who reached skeletal maturity precociously. The mean rates of angular correction were not significantly different between the 2 groups, in both distal femur and proximal tibia. Hardware was removed before skeletal maturity from 56 physes. Angular change remained within 3 degrees for 43 physes (76.8%) at more than 1 year postoperatively, and the rebound phenomenon was observed in 12 (21.4%). No significant difference was observed between the 2 groups in terms of physeal behavior after hardware removal. Patients in the screw group were administered less postoperative pain medication, had shorter hospital stays, and smaller operation scars. In the stapling group, 1 case was complicated due to an extruded staple, and another case experienced premature physeal arrest at 1.5 years postoperatively. One case in the screw group experienced correction failure, probably because of a technical error during screw placement. CONCLUSIONS: Hemiepiphysiodesis using percutaneous transphyseal screw is as effective as hemiepiphyseal stapling in terms of angular deformity correction. Furthermore, hemiepiphysiodesis using transphyseal screw has the advantage of being a minimally invasive procedure, and in this series, did not cause permanent physeal arrest. LEVEL OF EVIDENCE: Level III.

Change in effective leg length after angular deformity correction by hemiepiphyseal stapling.

BACKGROUND: The hemiepiphyseal stapling has both positive and negative effects on effective leg length. The purpose of this study was to analyze change in effective leg length after angular correction by hemiepiphyseal stapling, and to validate in clinical cases. METHODS: Mathematical analysis of a hemiepiphyseal stapling model was conducted. The induced formula was validated in 6 cases fulfilling the assumptions of the model. Anatomical parameters involved in this formula were measured in additional 21 cases undergoing hemiepiphyseal stapling or hemiepiphysiodesis. RESULTS: EFFECTIVE LEG LENGTH INCREASED OR DECREASED ACCORDING TO THREE PARAMETERS IN THIS MODEL: 1) limb length distal to the operated physis (L), 2) width of the operated physis (d), and 3) the amount of angular deformity to be corrected (theta). Actual change in effective leg length of 6 cases similar to this model coincided with the predicted change at least in its direction. L/d ratio was 4.82 +/- 0.51. CONCLUSIONS: Considering the narrow range of the L/d ratio, hemiepiphyseal stapling is likely to decrease effective leg length if the amount of angular correction is less than 10 degrees , whereas to increase it if the amount of angular correction is larger than 16 degrees . This should be taken into consideration when selecting the surgical method for angular deformity correction in skeletally immature patients.

Comparison of the short term toxicity of phthalate diesters and monoesters in sprague-dawley male rats.

This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2 (ethylhexyl) phthalate (DEHP) , di (n-butyl) phthalate (DBP) , di-n-octyl phthalate (DnOP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBP) , dimethyl phthalate (DMP) , di-isodecyl phthalate (DIDP) , diundecyl phthalate (DUP) , and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP) , monobutyl phthalate (MBuP) , monobenzyl phthalate (MBeP) , monoethyl phthalate (MEP) , monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP,DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day) -treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.