Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study.

BACKGROUND: An unstable slipped capital femoral epiphysis (SCFE) is associated with a high rate of avascular necrosis (AVN). The etiology of AVN seems to be multifactorial, although it is not thoroughly known. The aims of our study were to determine the rate of AVN after an unstable SCFE and to investigate the risk factors for AVN, specifically evaluating the notion of an "unsafe window", during which medical interventions would increase the risk for AVN. METHODS: This retrospective multicenter study included 60 patients with an unstable SCFE diagnosed between 1985 and 2014. Timing of surgery was evaluated for three time periods, from acute onset of symptoms to surgery: period I, <24 h; period II, between 24 h and 7 days; and period III, >7 days. Multivariate logistic regression analysis was used to identify risk factors for AVN. RESULTS: Closed reduction and pinning was performed in 43 patients and in situ pinning in 17. Among these cases, 16 patients (27%) developed AVN. The rate of AVN was significantly higher in patients treated by closed reduction and pinning (15/43, 35%) than in those treated by in situ pinning (1/17, 5.9%) (p = 0.022). In patients treated by closed reduction and pinning, the incidence of AVN was 2/11 (18%) in period I, 10/13 (77%) in period II and 3/15 (20%) in period III, showing the significantly higher rate in period II (p = 0.002). The surgery provided in period II was identified as an independent risk factor for the development of AVN. CONCLUSIONS: Our rate of AVN was 27% using two classical treatment methods. Time-to-surgery, between 24 h and 7 days, was independently associated with AVN, supporting the possible existence of an "unsafe window" in patients with unstable SCFE treated by closed reduction and pinning.

Treatment for unstable slipped capital femoral epiphysis: Current status and future challenge in Japan.

BACKGROUND: Treatment for unstable slipped capital femoral epiphysis (SCFE) is challenging and controversial. For many years, the debate centered around closed treatments and especially the pros and cons of manual reduction and its concrete procedure. However, recent studies reported on open treatments such as open reduction through an anterior approach and modified Dunn procedure. Being in a period of such transition, we investigated the current status and future challenge of treatment for unstable SCFE. METHODS: A questionnaire survey of medical institutions specializing in pediatric hip disorders across Japan was conducted. Survey items were the accurate diagnosis of physeal stability, the pre- and intra-operative evaluation of epiphyseal hemodynamics, and current treatment strategy. RESULTS: Survey responses returned from 29 out of 40 participant institutions (response rate: 73%) revealed that 55% of the institutions evaluated physeal stability based on clinical findings of ambulation capability in accordance with the Loder classification. Another 38% diagnosed physeal stability comprehensively by combining the Loder classification and imaging findings. Epiphyseal hemodynamics was assessed preoperatively in 18% of the institutions, effectively using angiography, contrast-enhanced magnetic resonance imaging (MRI), and bone scintigraphy. Intraoperative assessment was performed in 13% based on the bleeding through a drilling hole on the articular surface and observation of the cancellous bone color during open surgeries. As a treatment strategy, 52% of the institutions used in-situ fixation, while another 38% used manual reduction and internal fixation. On the other hand, open reduction was used at 3 institutions (the remaining 10%): the modified Dunn procedure at 2 institutions and arthrotomy at 1 institution. CONCLUSION: Treatment for unstable SCFE remains controversial, but closed treatments without hemodynamic monitoring is no longer the center of the controversy. Today, the topic of the discussion is shifting toward how to correlate hemodynamic findings with treatment procedures and the indications for open treatments.

Medium-term result of Elite Plus hip arthroplasty: the second modular evolution of the original Charnley low-friction arthroplasty.

BACKGROUND: The Elite Plus total hip arthroplasty (THA) system was introduced as the second modular evolution of the original Charnley low-friction arthroplasty. However, the results of the Elite Plus THA are currently considered to be inconsistent. The aim of this study was to clarify the medium-term results and the factors affecting the results of Elite Plus THA. METHODS: The results of 97 Elite Plus THAs in 87 patients at 5 years or more postoperatively were reviewed. The patients' mean age was 65 years, and follow-up averaged 8.0 years. The Elite Plus stem was used in all hips, and three designs of socket, Hylamer Ogee in 40 hips, Wroblewski Offset Bore in 38, and Charnley Ogee in 19, were implanted. The survival rates with loosening and revision as endpoints were analyzed. To clarify the risk factors affecting the survival rates, Charnley's functional classification, Bombelli's classification, Crowe's classification, structural bone grafting of the acetabulum, cup design, stem position, and grading of the cement mantle were evaluated. CONCLUSIONS: The results of Elite Plus stem THA were excellent in the medium term. The cup design was a potential confounding factor for acetabular loosening, and the Hylamer Ogee socket was associated with a poor result.

Tendon patch grafting using the long head of the biceps for irreparable massive rotator cuff tears.

BACKGROUND: Surgical treatment of massive rotator cuff tears is challenging for shoulder surgeons. The purpose of this study was to investigate both clinical outcomes and cuff integrity after tendon patch grafting using the long head of the biceps (LHB) tendon for irreparable massive rotator cuff tears. METHODS: A short deltoid splitting approach was used to expose the torn cuff tendon stump. After tenodesis of the LHB tendon, its intraarticular portion was resected. If the size of the harvested tendon was smaller than that of the cuff defect, it was split into two layers. Then, the LHB tendon was sutured to the remnant cuff tendons and fixed to the footprint using the transosseous suture technique. A total of 14 patients (12 men, 2 women; average age 64 years) underwent this procedure. The average postoperative follow-up period was 28 months (range 12-51 months). Active elevation angle of the shoulder as well as the Japanese Orthopaedic Association (JOA) score were assessed before surgery and at the time of follow-up. Postoperative cuff integrity was assessed using T2-weighted magnetic resonance imaging (MRI). RESULTS: All cuff defects were successfully closed with this technique. Average active elevation angle improved from 69 degrees to 149 degrees . Total JOA score also improved from 54.7 points to 83.1 points. Thirteen shoulders showed no re-tearing on T2-weighted MRI; a minor discontinuity of the repaired cuff tendon was observed in the other shoulder. CONCLUSIONS: The LHB tendon is available in case tenodesis or tenotomy is needed. The resected tendon may be used as a graft for rotator cuff repair without any additional skin incision, which could reduce both the surgical invasion and the risk of infection. The LHB tendon patch grafting may be one of the useful options for surgical treatment of irreparable massive rotator cuff tears.

A patient with focal fibrocartilaginous dysplasia in the distal femur and review of the literature.

Focal fibrocartilaginous dysplasia (FFCD) is a rare and benign bone lesion that induces bowing deformity of the long bones in young children. Excessive production of fibrocartilage by abnormal differentiation in the metaphysis or by trauma during delivery or after birth is thought to cause growth disturbance. Radiologically, the lesion is characterized by a lucent defect with marginal sclerosis in the medial metaphysis of the long bone. However, there have been few reports about the initial radiological changes of FFCD before bowing started. We report a patient with FFCD in the left distal femur in whom the radiological changes were serially observed during the course of the disorder. A 2-week-old boy first visited our hospital because of left thigh pain. Plain radiographs did not show any abnormal findings at that time. At 10 weeks, a well-defined lucent defect with bony fragment inside was observed in the distal femoral medial cortex. At 1 year, this bony fragment gradually vanished but varus deformity progressed and reached approximately 40 degrees at the age of 2. After removal of the lesion, osteotomy and immobilization was performed with Ilizarov external fixator comprising rings, rods and wires. Complete bone union was achieved 3 months after operation. It is noteworthy that we could observe the initial radiological changes of FFCD before varus deformity occurred. As far as we know, there have been no descriptions of the bony fragment inside a lucent defect of the lesion. Radiological features may vary in the early phase of FFCD.

Measurement of soft tissue elasticity in the congenital clubfoot using scanning acoustic microscope.

To compare the soft-tissue elasticity between the medial, lateral, and posterior aspects, the deltoid and calcaneofibular ligaments, and the medial, lateral, and posterior capsular tissues were collected from 27 feet of 16 congenital-clubfoot patients. The tissue sound speed, which closely correlates to the Young's modulus, was measured using a scanning acoustic microscope. Contrary to our expectations, lateral ligament showed a significantly higher sound speed than medial ligament (P=0.0023). Lateral capsule also showed a higher sound speed than the medial one (P=0.0338). The results of the study indicated that the lateral soft tissues including the ligaments and capsule underwent severe contracture in congenital clubfoot.

Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset.

This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to or clinical presentation of type 1 diabetes. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 128 Japanese patients with type 1 diabetes and in 107 healthy control subjects in a case-controlled study. The allelic and haplotypic frequencies of the IL-10 gene promoter region polymorphisms were similar in patients with type 1 diabetes and in control subjects. However, the -819T and -592A allele were associated with adult-onset (>18 years) of the disease (p = 0.037). Furthermore, the frequency of ATA haplotype was increased in adult-onset patients than that in early-onset patients (< or =18 years; p = 0.037). Among the genotypes comprising ATA haplotype, the frequency of ATA/ATA was significantly higher in adult-onset patients than in early-onset patients (p = 0.004). These results suggest that the IL-10 gene promoter polymorphisms are associated with the age-at-onset in Japanese patients with type 1 diabetes.

Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population.

Stromal-cell derived factor-1 (SDF-1) is a powerful chemokine that upregulates T-cell migration and activation. The gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10, suggesting a contribution by SDF-1 to the induction of diabetes. Recently the role of SDF-1 gene polymorphism in the clinical presentation of type 1 diabetes in French population has been reported. To test the putative involvement of SDF-1 gene polymorphism in predisposition to or clinical heterogeneity of type 1 diabetes in Japanese population, we conducted the case-control study. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the polymerase chain reaction-restriction fragment length polymorphism technique in 184 patients with abrupt-onset type 1 diabetes and 106 healthy control subjects. No significant difference in allele and genotype frequencies of SDF1-3'A variant was found between type 1 diabetic patients and healthy controls. However, the SDF1-3'A variant was strongly associated with early-onset diabetes in a recessive model (AA versus AG + GG, p = 0.017). The mean age-at-onset in patients carrying SDF1-3'AA genotype was significantly younger than that in patients with SDF1-3' AG or GG genotype (p = 0.028). The frequencies of SDF1-3' A variant were significantly increased in HLA-DR4/9 patients compared with non-DR4/9 patients (p = 0.008). These results suggest that the SDF-1 gene polymorphism is associated with the age-at-onset of type 1 diabetes in Japanese population.

Insulin attenuates leptin-induced STAT3 tyrosine-phosphorylation in a hepatoma cell line.

Leptin, the 16 kDa protein product of the ob gene, is secreted by adipocytes. The long form leptin receptor (ObRb) is expressed at high levels in the hypothalamus, and regulates appetite and energy expenditure. The fact that serum concentration of leptin is correlated with body mass index (BMI) suggests reduced sensitivity to leptin. Even though hyperinsulinemia and hyperleptinemia could coexist in obese humans, little is known about the interaction of insulin and leptin. In this study, we examined the effect of insulin on leptin signaling using Huh 7 cells transiently transfected with ObRb cDNA. Insulin inhibits leptin-induced STAT3 phosphorylation in a time- and dose-dependent manner without affecting Janus tyrosine kinases (JAKs) JAK2 phosphorylation. Okadaic acid prevents the inhibitory effect of insulin on leptin-induced STAT3 activation.

Stromal cell-derived factor-1 chemokine gene variant in patients with type 1 diabetes and autoimmune thyroid disease.

Type 1 diabetes is a heterogenous autoimmune disease and is frequently associated with other organ-specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to have clinical and immunological features distinct from patients without AITD. This study investigated whether stromal cell-derived factor (SDF)-1 gene polymorphism is associated with susceptibility to type 1 diabetes and AITD. SDF-1 is a powerful chemokine that upregulates T-cell migration and activation, and the gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the PCR-RFLP technique in 54 type 1 diabetic patients with AITD, 75 type 1 diabetic patients without AITD, 137 nondiabetic patients with AITD, and 106 healthy subjects in a case-control study. No significant differences on the allele and genotype frequencies of the SDF1 gene polymorphism were found, not only in type 1 diabetic patients with AITD compared with normal controls but also between nondiabetic patients with AITD and healthy control subjects. These results suggest that the SDF1-3'A variant is not associated with genetic susceptibility to type 1 diabetic patients and AITD.

Epitope analysis of GAD65 autoantibodies in Japanese patients with autoimmune diabetes.

Type 1 diabetes is an organ-specific autoimmune disease characterized by T cell-mediated destruction of pancreatic beta cells. In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA-2 are the important immunological features of type 1 diabetes. The prevalences of anti-islet autoantibodies in patients with Japanese type 1 diabetes are 60-70% for GAD autoantibodies, 45-50% for insulin autoantibodies (IAA), and 60-65% for IA-2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosis-prone, there are a number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset called LADA. These patients with LADA often progress toward an insulin-deficient state within several years after diagnosis. High levels of GAD autoantibodies have a high predictive value for future insulin deficiency in LADA. Further, epitope analysis of GAD65 autoantibodies may be helpful to predict future insulin dependency in LADA patients. In conclusion, Japanese patients with type 1 diabetes are clinically heterogeneous and the determination of immunological features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.

Interleukin-10 gene promoter region polymorphisms in patients with type 1 diabetes and autoimmune thyroid disease.

Type 1 diabetes is a heterogeneous autoimmune disease and is frequently associated with other organ-specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to show distinct clinical and immunological features from patients without AITD. This study investigated whether interleukin-10 (IL-10) gene promoter region polymorphisms are associated with susceptibility to type 1 diabetes and AITD. The frequency of -1082G/A, -819C/T, and -592C/A polymorphisms was analyzed in 54 type 1 diabetic patients with AITD, 74 type 1 diabetic patients without AITD, 124 nondiabetic patients with AITD, and 107 healthy subjects in a case-control study. No significant differences on the allele and genotype frequencies of three polymorphisms were found not only in type 1 diabetic patients with AITD compared with normal controls, but also between nondiabetic patients with AITD and healthy controls. The distribution of IL-10 gene haplotypes was also similar between both patient groups and normal controls. These results suggest that IL-10 gene promoter region polymorphisms are not associated with genetic susceptibility to type 1 diabetes and AITD.

Association of interleukin-18 gene promoter polymorphisms in type 1 diabetes and autoimmune thyroid disease.

Type 1 diabetes is a heterogeneous autoimmune disease and is often associated with other organ-specific autoimmune diseases, including autoimmune thyroid disease (AITD). IL-18 is a potent proinflammatory cytokine capable of inducing IFN-gamma production that is associated with the development of type 1 diabetes and AITD. The gene for IL-18 is located near Idd2 and has been reported to be associated with a susceptibility to type 1 diabetes. To test the putative involvement of IL-18 gene polymorphism in predisposition to type 1 diabetes and AITD, we conducted a case-control study in Japanese population. The SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of the IL-18 gene were analyzed by sequence-specific PCR in 74 nondiabetic patients with AITD, 47 type 1 diabetic patients with AITD, and 114 normal controls. There was no significant increase in the genotype and allele frequencies not only in nondiabetic patients with AITD compared with normal controls, but also in type 1 diabetic patients with AITD compared with normal controls. The distribution of IL-18 gene haplotypes was also similar between both patient groups and normal controls. These results suggest that polymorphisms of the IL-18 gene are not associated with a susceptibility to AITD and type 1 diabetes coexistent with AITD in Japanese population.

Intracerebroventricular administration of insulin and glucose inhibits the anorectic action of leptin in rats.

Obese individuals with glucose intolerance present with high serum levels of glucose, insulin, and leptin. These substances are potent inhibitors of feeding in the brain. Obese subjects still present with over-feeding despite elevation of the above factors. To elucidate the mechanism of this paradox, the effects of insulin and glucose on the anorectic action of leptin in the hypothalamus were examined. Adult male Sprague-Dawley rats (weighing 285-320 g) were pretreated with intracerebroventricular injection of insulin, glucose, or saline, followed by leptin (7.5 microg) or phosphate-buffered saline (PBS) injection into the third cerebral ventricle (icv). The cumulative food intakes were measured 24 hr after leptin icv. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was determined by Western blotting. In rats pretreated with saline and stimulated with leptin (saline/LEPTIN group), food intake diminished to about 50% of that of the saline/PBS group (P < 0.005). Food intake in the insulin/LEPTIN group was significantly higher compared with the saline/LEPTIN group (P < 0.005) and reached the level seen in the saline/PBS group. Similar data were obtained in glucose pretreatment experiments. Insulin and glucose icv resulted in reduction of leptin-induced STAT3 tyrosine phosphorylation compared with saline. Infusion of insulin and glucose icv did not alter peripheral blood glucose levels in all groups. High insulin or glucose levels in the brain could result in leptin resistance as manifested by food intake, which is probably due to the attenuation of STAT3 phosphorylation downstream the leptin receptor.

Evaluation of calcaneal malposition by magnetic resonance imaging in the infantile clubfoot.

Magnetic resonance imaging (MRI) can clearly visualize both the ossification centers and surrounding cartilage of growing bones and enable a three-dimensional analysis of their positional relationships by using overlapping images. The calcaneal position was evaluated based on five newly proposed parameters of magnetic resonance images in 30 clubfeet of 18 infants with the bimalleolar and lower leg axes as reference lines. Sixteen unaffected feet in the unilateral cases were analyzed as normal feet. MRI showed that the calcaneus in clubfoot rotated internally, medially and posteriorly with reference to the bimallelar axis and that it took an equinus and a varus position with reference to the lower leg axis as compared with the normal foot. These five parameters and their normal values on the calcaneal position should be useful for the evaluation of infantile clubfeet.

Eosinophilic granuloma arising from the pelvis in children: A report of three cases.

Eosinophilic granuloma (EG) is a benign tumor-like condition which is characterized by a clonal proliferation of Langerhans-type histiocytes and defined as a local form of Langerhans cell histiocytosis (LCH). The radiographic appearances of EG are quite different depending on the phase of the disease and the site of involvement. A status of EG in the bone is divided into acute and chronic phases. Radiologically acute phase of EG is difficult to differentiate from a malignant bone tumor such as Ewing's sarcoma or acute osteomyelitis. Chronic phase of EG may mimic a chronic osteomyelitis or a benign bone tumor. We report 3 children's cases of EG in the pelvis which showed quite different radiological features and clinical courses. A 6-year-old boy (Case 1) had an osteolytic lesion with slightly defined margins in the right acetabulum. A 4-year-old boy (Case 2) had a radiologically similar-looking lesion in the left acetabulum. These lesions resembled radiologically chronic osteomyelitis (Brodie's abscess) or a benign bone tumor and healed spontaneously after biopsy. A 2-year-old boy (Case 3) had an osteolytic lesion with ill-defined margin in the ilium. It was difficult to differentiate from a malignant tumor such as Ewing's sarcoma, or acute osteomyelitis. The lesion became enlarged after needle biopsy. In spite of an additional curettage, the osteolytic lesion remained in the left pelvis in 1 year. Treatment for EG is controversial. Curettage of the affected site and bone grafting is usually accomplished. However, some EG heal spontaneously. It is of great importance to understand the natural course of EG and this knowledge will give us the opportunity to avoid unnecessary treatment. EG with poor osteolytic margins may progress further after biopsy. EG with well-defined margins may heal spontaneously after biopsy only.

Poor results of the cementless total hip arthroplasty with a nonporous coated acetabular component: AcSys Shearer Cup.

BACKGROUND: This study followed patients for a minimum of 7 years after primary total hip arthroplasty using cementless acetabular components and evaluated their outcomes. METHODS: We followed 73 patients (75 hips), who had undergone total hip arthroplasty with cementless nonporous coated acetabular components (3M AcSys Shearer Cup) for a mean of 9.8 years (range 7-13 years). There were 61 women and 12 men with a mean age of 53 years (range 27-69 years) at surgery. The diagnosis was primary osteoarthritis in 9 hips, osteoarthritis secondary to developmental dysplasia in 58 hips, osteonecrosis of the femoral head in 6 hips, and rheumatoid arthritis in 2 hips. RESULTS: Three cups were revised because of aseptic loosening, and one cup was revised following removal of the prosthesis due to deep infection. Radiographic loosening was observed in 22 hips at the latest follow-up. The survival rate at 10 years was 94.7% with revision as the endpoint and 72% with radiographic loosening as the endpoint. The Merle d'Aubigné and Postel hip score showed significant improvement postoperatively and was maintained well even in cases showing radiographic loosening. CONCLUSIONS: The intermediate radiological results with the AcSys Shearer Cup were unsatisfactory because of the high loosening rate, although the revision rate was low. The nonporous outer surface and the poor fixation mechanism between the metal shell and liner may have contributed to the high failure rate. Regular radiological review is recommended when this cup is used because early loosening is often painless.

Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-gamma activation.

Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-gamma, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-gamma.