Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126.

Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments.

High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

RATIONALE: Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. OBJECTIVES: To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3. METHODS: We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. MEASUREMENTS AND MAIN RESULTS: The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P < 0.001) but did not influence time to sputum culture conversion overall (adjusted hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). CONCLUSIONS: Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Spinal mobilization vs conventional physiotherapy in the management of chronic low back pain due to spinal disk degeneration: a randomized controlled trial.

OBJECTIVES: The aim of the study was to examine the efficacy of spinal mobilization in subjects with low back pain (LBP) and associated spinal disk degeneration. METHODS: Seventy-five subjects suffering from chronic LBP (>3 months) were randomly allocated into 3 groups of 25 subjects each. Each group received five treatment sessions with the first group receiving manual therapy (MT) (spinal mobilization), the second a sham treatment, and the third conventional physiotherapy (CP) (stretching exercises, transcutaneous electrical nerve stimulation, and massage). Subjects were assessed for their pain intensity using the numerical pain rating scale and for their self-reported disability using the Oswestry and Roland-Morris Questionnaire at baseline and after the completion of the five treatment sessions. RESULTS: Paired t-tests showed a significant improvement for all outcome measures in the MT and CP group (p < 0.05). Analysis of covariance revealed that the MT group had significant improvement in all outcome measures in comparison with the sham and CP group (p < 0.05), whereas no significant difference was observed between the sham and CP group (p > 0.05). DISCUSSION: MT is preferable to CP in order to reduce the pain intensity and disability in subjects with chronic LBP and associated disk degeneration. The findings of this study may lead to the establishment of spinal mobilization as one of the most preferable approaches for the management of LBP due to disk degeneration. LEVEL OF EVIDENCE: 1b.

Long Term Outcomes of Total Hip Arthroplasty With Custom Made Femoral Implants in Patients With Congenital Disease of Hip.

We evaluated the outcomes of total hip arthroplasty in 67 patients (86 hips) with congenital hip disease and excessive abnormal anatomy of the proximal femur with the use of custom-made femoral stems. The design of the stem was based on CT data following the principles of CAD-CAE-CAM technique. No serious complications attributed to the femoral stem were seen. Within a median follow-up of 127.5 months the 10-year survival of any of the components was 95.4% and respective value when aseptic loosening of the stem was considered was 98.1%. Patients with high dislocations had a 10-fold risk for loosening compared to those with low dislocations. No other parameter was associated with outcomes. The clinical and radiological evaluation was in consistency with the above outcomes.

Flow cytometry as a diagnostic tool for identifying total hip arthroplasty loosening and differentiating between septic and aseptic cases.

PURPOSE: Implant loosening represents one of the major factors of total hip arthroplasty (THA) failure. The purpose of this study was to identify specific markers indicative of septic and aseptic loosening in patients that underwent THA. METHODS: Flow cytometry was performed in blood samples of 20 patients with loosening (10 septic/10 aseptic). Additional ten healthy individuals served as a control group. The expression of surface receptors and cytoplasmic molecules in patients that underwent THA was quantified. CD62L, CD18, CD11a, CD11b and CD11c expressions were evaluated and correlated with the presence of loosening. Also, a comparison between septic and aseptic THA loosening characteristics was performed. RESULTS: The mean fluorescence intensity (MFI) for CD18 was significantly decreased on all leukocytes subsets in both septic and aseptic loosening compared to control group (p < 0.005 in all occasions). Patients with aseptic loosening showed increased MFI for CD11b in granulocytes and for CD11c in monocytes and granulocytes compared to the control and aseptic group (p = 0.02 and p = 0.005, respectively). In patients with septic loosening, an increase in MFI for CD11c was observed in monocytes only compared to control group (p = 0.03). The comparison between aseptic and septic loosening showed significantly lower CD18 MFI value in granulocytes for aseptic loosening (p = 0.008). CONCLUSIONS: CD11 and CD18 MFI values appear to be indicative of loosening in THAs. Flow cytometry markers can be used to identify THA loosening, as well as to differentiate between septic and aseptic cases.

Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.

Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.

Radiotherapy for prevention of heterotopic ossification of the elbow: a systematic review of the literature.

BACKGROUND: Heterotopic ossification is a pathological process characterized by abnormal formation of bone in nonskeletal tissue. Radiotherapy for heterotopic ossification of the elbow is questionable because of possible adverse effects. METHODS: A systematic review of the literature was conducted in MEDLINE, Scopus, ISI Web of Science, National Institute for Health and Clinical Excellence, National Guideline Clearinghouse, System for Information on Grey Literature in Europe, ClinicalTrials.gov, Cochrane Central Register of Clinical Trials, and Cochrane Database of Systematic Reviews up to April 2012. All published articles assessing interventions including radiotherapy for prevention of heterotopic ossification in the elbow of adult patients were considered. Information was recorded by the first two authors, and disagreements in interpretation were resolved by consensus. RESULTS: In total, 27 studies using radiotherapy for elbow heterotopic ossification were identified (1 randomized clinical trial, 1 case-control study, and 25 case reports and case series) in the literature. Most of them used a single dose of 7.0 Gy. The randomized clinical trial was stopped early because of severe adverse effects (pseudarthrosis) caused by radiation. The case-control study showed that radiotherapy did not effectively prevent recurrence of heterotopic ossification. The case reports and case series mentioned only sparse adverse events. CONCLUSION: The use of radiation therapy for prevention of heterotopic ossification of the elbow is supported by weak evidence.

Short-Term Treatment with Rho-Associated Kinase Inhibitor Preserves Keratinocyte Stem Cell Characteristics In Vitro.

Primary keratinocytes including keratinocyte stem cells (KSCs) can be cultured as epidermal sheets in vitro and are attractive for cell and gene therapies for genetic skin disorders. However, the initial slow growth of freshly isolated keratinocytes hinders clinical applications. Rho-associated kinase inhibitor (ROCKi) has been used to overcome this obstacle, but its influence on the characteristics of KSC and its safety for clinical application remains unknown. In this study, primary keratinocytes were treated with ROCKi Y-27632 for six days (short-term). Significant increases in colony formation and cell proliferation during the six-day ROCKi treatment were observed and confirmed by related protein markers and single-cell transcriptomic analysis. In addition, short-term ROCKi-treated cells maintained their differentiation ability as examined by 3D-organotypic culture. However, these changes could be reversed and became indistinguishable between treated and untreated cells once ROCKi treatment was withdrawn. Further, the short-term ROCKi treatment did not reduce the number of KSCs. In addition, AKT and ERK pathways were rapidly activated upon ROCKi treatment. In conclusion, short-term ROCKi treatment can transiently and reversibly accelerate initial primary keratinocyte expansion while preserving the holoclone-forming cell population (KSCs), providing a safe avenue for clinical applications.

Accuracy of pedicle screw placement: a systematic review of prospective in vivo studies comparing free hand, fluoroscopy guidance and navigation techniques.

INTRODUCTION: With the advances and improvement of computer-assisted surgery devices, computer-guided pedicle screws insertion has been applied to the lumbar, thoracic and cervical spine. The purpose of the present study was to perform a systematic review of all available prospective evidence regarding pedicle screw insertion techniques in the thoracic and lumbar human spine. MATERIALS AND METHODS: We considered all prospective in vivo clinical studies in the English literature that assessed the results of different pedicle screw placement techniques (free-hand technique, fluoroscopy guided, computed tomography (CT)-based navigation, fluoro-based navigation). MEDLINE, OVID, and Springer databases were used for the literature search covering the period from January 1950 until May 2010. RESULTS: 26 prospective clinical studies were eventually included in the analysis. These studies included in total 1,105 patients in which 6,617 screws were inserted. In the studies using free-hand technique, the percentage of the screws fully contained in the pedicle ranged from 69 to 94%, with the aid of fluoroscopy from 28 to 85%, using CT navigation from 89 to 100% and using fluoroscopy-based navigation from 81 to 92%. The screws positioned with free-hand technique tended to perforate the cortex medially, whereas the screws placed with CT navigation guidance seemed to perforate more often laterally. CONCLUSIONS: In conclusion, navigation does indeed exhibit higher accuracy and increased safety in pedicle screw placement than free-hand technique and use of fluoroscopy.

Endoscopic versus open carpal tunnel release.

PURPOSE: This study compared endoscopic carpal tunnel release with the conventional open technique with respect to short- and long-term improvements in functional and clinical outcomes. METHODS: We assessed 72 outpatients diagnosed with carpal tunnel syndrome. Of these patients, 37 underwent the endoscopic method according to Chow and 35 were assigned to the open method. Improvement in symptoms, severity, and functionality were evaluated at 2 days, 1 week, 2 weeks, and 1 year postoperatively. Changes in clinical outcomes were evaluated at 1 year postoperatively. Complications were also assessed. RESULTS: Both groups showed similar improvement in all but 1 outcome 1 year after the release; increase in grip strength was significantly higher in the endoscopic group. However, the endoscopic method showed a greater improvement in symptoms and functional status compared with the open method at 2 days, 1 week, and 2 weeks postoperatively. Separate analysis of the questions referring to pain showed that the delay in improvement in the open group was because of the persistence of pain for a longer period. Paresthesias and numbness decrease immediately after the operation with comparable rates for both groups. CONCLUSIONS: Endoscopic carpal tunnel release provides a faster recovery to operated patients for the first 2 weeks, with faster relief of pain and faster improvement in functional abilities. Paresthesia and numbness subside in an identical manner with the 2 techniques. At 1 year postoperatively, both open and endoscopic techniques seem to be equivalently efficient.

Migration of the trabecular metal monoblock acetabular cup system.

Fifty-one primary total hip arthroplasties were performed using Trabecular Metal Monoblock Acetabular Cup System (Zimmer Inc, Warsaw, IN). In a 2-year prospective study, its behavior was closely monitored by clinical, radiologic, and component migration assessment by Ein-Bild-Röntgen-Analyse method. There were no complications. The mean Harris hip score was improved from 41 to 95. A polar gap at the postoperative radiograph was noted at 25% of the arthroplasties, most of which subsequently filled with bone within 6 months. The mean total absolute migration was 0.67 mm. The implant showed excellent early clinical and radiographic behavior. The 2-year migration rate study, as index of long-term survival and success, showed very good early implant stability and, in all cases except one, superior to the available studies for similar design acetabular cups.

Is TKA with computer-assisted navigation associated with less blood loss? A comparative study between computer-navigated and conventional method.

The aim of this study is to evaluate whether computer-assisted navigated TKA reduces perioperative blood loss. Patients were randomly divided into 2 groups and underwent either a conventional TKA (n = 40) or a TKA with computer-assisted navigation (n = 40). Perioperative blood loss was evaluated by laboratory parameters, postoperative drain output and number of required transfusions. Change in hemoglobin concentration and in hematocrit levels was similar. Also, there was no statistically significant difference in drain output and in the number of transfused units. The results of this study showed that TKA with computer-assisted navigation is similar to the conventional TKA regarding perioperative hemorrhage.

Is prophylaxis for heterotopic ossification with radiation therapy after THR associated with early loosening or carcinogenesis?

INTRODUCTION: Heterotopic ossification may develop after major hip surgeries, thus preventive strategies including radiation therapy and non steroid anti-inflammatory drugs are commonly employed. There are certain concerns regarding the effects of radiation therapy on implant loosening and carcinogenesis. Our study aims to evaluate whether radiation therapy results in implant loosening or radiation-induced tumours in the long term. PATIENTS AND METHODS: This was a prospective study including 97 high-risk patients for heterotopic ossification who underwent total hip arthroplasty. Patients were divided into 2 groups and received either a combination of radiation therapy and indomethacin (Group A), or indomethacin alone (Group B). Evaluated outcomes included implant loosening or development of radiation-induced tumours during the follow-up period. RESULTS: The follow-up period of the study was 10 years. Group A consisted of 50 patients, while Group B consisted of 47 patients. 3 patients died during the follow-up. There were 2 cases of implant loosening, 1 from each of the 2 groups at 9 and 10 years after surgery respectively; thus, no statistically significant difference regarding implant loosening was found (p < 0.05). During the follow-up period no cases of radiation-induced tumours were identified. CONCLUSION: Our results are consistent with those of other studies supporting the safety of radiation therapy as a preventive strategy for heterotopic ossification following major surgeries in high risk patients. Further studies with even longer follow-up may be required to definitely exclude the possibility of adverse outcomes linked with radiation therapy.

Genotype-independent association between vitamin D deficiency and polycystic ovarian syndrome in Lahore, Pakistan.

Both vitamin D deficiency and single nucleotide polymorphisms (SNPs) in the gene encoding the vitamin D receptor (VDR) have been widely reported to associate with susceptibility to polycystic ovarian syndrome (PCOS). A case-control study was conducted to study the influence of vitamin D status and genotpye for 24 SNPs in four genes in the vitamin D pathway (VDR, DBP, CYP27B1, CYP24A1) on PCOS. Statistical analyses were conducted to identify phenotypic and genotypic factors associated with risk of PCOS and to test for interactions between genotype and vitamin D status. PCOS was independently associated with lower age, higher body mass index, lower waist-hip ratio, vitamin D deficiency (serum 25-hydroxyvitamin D concentration <10 ng/mL), lack of outdoor exercise, increased fasting glucose and a family history of PCOS in at least one first degree relative. No statistically significant association was observed between the genotype of any SNP investigated and risk of PCOS, either as a main effect or in interaction with vitamin D status. We report a strong and independent association between vitamin D deficiency and risk of PCOS in Pakistan, that was not modified by genetic variation in the vitamin D pathway.

Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes.

Exposure to endocrine disrupting chemicals is an established risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the potential of glyphosate, 2, 4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE) to induce lipid accumulation in murine 3T3-L1 adipocytes. Only QpE caused a dose-dependent statistically significant triglyceride accumulation from a concentration of 5 up to 100 µM. The QpE commercial formulation Targa Super was 100 times more cytotoxic than QpE alone. Neither the estrogen receptor antagonist ICI 182, 780 nor the glucocorticoid receptor antagonist RU486 was able to block the QpE-induced lipid accumulation. RNAseq analysis of 3T3-L1 adipocytes exposed to QpE suggests that this compound exerts its lipid accumulation effects via a peroxisome proliferator-activated receptor gamma (PPARγ)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPARγ reporter gene assay at 100 µM, reaching 4% of the maximal response produced by rosiglitazone, which acts as a positive control. This indicates that lipid accumulation induced by QpE is only in part caused by PPARγ activation. The lipid accumulation capability of QpE we observe suggest that this pesticide, whose use is likely to increase in coming years may have a hitherto unsuspected obesogenic property.

Application of the Endomodel rotating hinge knee prosthesis for knee osteoarthritis.

One hundred thirty-six knees were treated with the Endomodel rotating hinge knee prosthesis as primary total knee arthroplasty (TKA). The indications for surgery included osteoarthritis (110 knees), rheumatoid arthritis (18 knees), and osteonecrosis (8 knees). Patients were divided into four study groups according to follow-up duration. Group A was followed up from 10 to 15 years, group B from 8 to 10 years, group C from 5 to 8 years, and group D from 2 to 5 years. The Hospital for Special Surgery knee score, as well as each parameter individually, showed statistically significant improvement in all groups postoperatively. A total of 88.23% were rated as excellent, 3.67% as good, and 8.08% as fair. The results suggest that the Endomodel rotating hinge prosthesis can be considered a good alternative for primary TKA in cases of serious axial deformity and collateral ligament deficiency and in rheumatoid arthritis patients.

Consistent new bone formation in 95 revisions: average 9-year follow-up.

This study evaluates the use of Wagner cementless stem for femurs with marked loss of proximal bone stock. Ninety-five hips in 89 patients were revised with a Wagner stem and prospectively studied. The indications were as follows: aseptic loosening for 84 hips, periprosthetic fracture for 5, Girdlestone for 3, mechanical loosening for 2 and recurrent dislocation for 1. The mean follow-up was 108 months (range, 84-180 months; SD, 13.5). There was only 1 re-revision, 2 months after surgery, and the survival rate at 9 years was 98.5%. The mean Merle d'Aubigné score improved from 8.8 to 16.1 (P<0.001). There were 15 (15.8%) intraoperative fractures, 5 (5.3%) dislocations, 2 (2.1%) thrombosis, and 2 (2.1%) sciatic neuropraxia. Significant bone formation occurred around the Wagner stem in 97% of the hips in these cases. No radiolucency or loosening had been diagnosed at the last follow-up.

Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line.

Use and thus exposure to quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate, which are declared as active principles in commercial formulations of herbicides, is predicted to rapidly increase in coming years in an effort to overcome the wide-spread appearance of glyphosate-resistant weeds, especially in fields where glyphosate-tolerant genetically modified crops are cultivated in the USA. Thus, there is an urgent need for an evaluation of metabolic effects of new pesticide ingredients used to replace glyphosate. As the liver is a primary target of chemical pollutant toxicity, we have used the HepaRG human liver cell line as a model system to assess the toxicological insult from quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate by determining alterations in the transcriptome caused by exposure to three concentrations of each of these compounds, including a low environmentally relevant dose. RNA-seq data were analysed with HISAT2, StringTie and Ballgown. Quizalofop-p-ethyl was found to be the most toxic of the pesticide ingredients tested, causing alterations in gene expression that are associated with pathways involved in fatty acid degradation and response to alcoholism. Isoxaflutole was less toxic, but caused detectable changes in retinol metabolism and in the PPAR signalling pathway at a concentration of 1 mM. ToxCast data analysis revealed that isoxaflutole activated PPAR gamma receptor and pregnane X responsive elements in reporter gene assays. Glyphosate and mesotrione caused subtle changes in transcriptome profiles, with too few genes altered in their function to allow a reliable pathway analysis. In order to explore the effects of glyphosate in greater depth and detail, we undertook a global metabolome profiling. This revealed a decrease in free long chain fatty acids and polyunsaturated fatty acid levels at the lowest concentration (0.06 µM) of glyphosate, although no effects were detected at the two higher concentrations tested, perhaps suggesting a non-linear dose response. This surprising result will need to be confirmed by additional studies. Overall, our findings contribute to filling the knowledge gap regarding metabolic toxicity that can potentially arise from exposure to these four herbicide active principles.

Microsurgical dissection of the carpal tunnel with respect to neurovascular structures at risk during endoscopic carpal tunnel release.

PURPOSE: The goal of this descriptive study was to investigate the anatomy of the carpal tunnel with respect to the related neurovascular structures, because a detailed knowledge of the complex anatomy of this region is essential to perform endoscopic carpal tunnel release. METHODS: Sixteen fresh-frozen cadaveric hands were used for the study. Dissection of the palmar aspect of the hand was performed by use of magnifying loupes, an operative microscope, and microsurgical instruments. All anatomic components were photographed, and dimensions were recorded by use of a micrometer. The distance from the radial aspect of the os pisiformis and the proximal and distal portals to the main structures that may be injured was measured. Topography of the transverse ligament and possible adhesions to the tendons and median nerve were also recorded. RESULTS: The mean distance from the radial aspect of the os pisiformis to the radial border of Guyon's canal and the ulnar edge of the palmaris longus tendon was 10.3 mm (range, 9 to 12 mm) and 16.1 mm (range, 12 to 22 mm), respectively. The mean distance from the distal portal to the superficial palmar arch and the ulnar artery was 10.4 mm (range, 5 to 15 mm) and 7.6 mm (range, 4.5 to 9 mm), respectively. The mean distance from the distal edge of the transverse ligament to the thenar branch of the median nerve was 2.7 mm (range, 0 to 4.1 mm). The mean length of the transverse ligament was 31 mm (range, 25 to 34.5 mm). In 14 hands we also identified the palmaris longus tendon. In 11 hands we found adhesions between the transverse ligament and the sheath of the flexor tendons. CONCLUSIONS: The palmaris longus can be used as a guide for the placement of the proximal portal. Staying at the ulnar side of the palmaris longus keeps the superficial palmar branch of the median nerve at a safe distance from the instruments. The "fat drop sign" is also a useful guide for the placement of the distal margin of the transverse carpal ligament, keeping the distal portal away from the superficial palmar arch. Synovial adhesions can usually cover the inferior surface of the transverse ligament, and they need to be removed for clear endoscopic identification of the transverse fibers before the ligament is cut. CLINICAL RELEVANCE: Detailed knowledge of the complex anatomy of the carpal tunnel is essential to perform endoscopic carpal tunnel release.

Total hip and knee arthroplasty for juvenile rheumatoid arthritis.

We performed 23 total hip and knee arthroplasties (15 total hip and 8 total knee arthroplasties) in 18 children with juvenile rheumatoid arthritis between 1984 and 2001. The mean age at surgery was 17.8 years (range 13 to 24 years). The age of presentation of the disease was from 4 to 10 years with average 7.3 years. The average length of follow-up was 9.7 years (range 7 to 16 years). All patients conformed with the American Rheumatism Association criteria for juvenile rheumatoid arthritis. All patients had complete loss of joint space and various combination of subchondral sclerosis, flattening of the femoral head, anterior inclination of the neck. Three knees were diagnosed with bony ankylosis. Follow-up was based on the Merle d'Aubigne et Postel scale modified by Charnley. One acetabular component has been revised to date. No femoral or tibial components have been revised. No patient had pain post-operatively and function was very satisfactory. Total hip and knee arthroplasties are technically difficult to execute in this age and should be performed in specialized centers. With appropriate indications pain relief,decrease of deformity and improvement of quality of life can be achieved in most patients.