Author Correction: Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism.

Change history: In this Letter, the labels for splicing events A3SS and A5SS were swapped in column D of Supplementary Table 3a and b. This has been corrected online.

Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis.

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.

Chromosome conformation elucidates regulatory relationships in developing human brain.

Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with enhancers gained on the human lineage, many of which are under purifying selection and associated with human cognitive function. We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), highlighting multiple candidate schizophrenia risk genes and pathways, including transcription factors involved in neurogenesis, and cholinergic signalling molecules, several of which are supported by independent expression quantitative trait loci and gene expression analyses. Genome editing in human neural progenitors suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, supporting its potential role as a schizophrenia risk gene. This work provides a framework for understanding the effect of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel mechanisms underlying neuropsychiatric disorders.

Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism.

Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood. Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge, we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder.

Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification.

BACKGROUNDS: Branch retinal vein occlusion (BRVO) is one of the most important causes of visual loss in retinal vascular diseases. The aim of this study is to predict the treatment response of anti-vascular endothelial growth factor (anti-VEGF) therapy in BRVO using semi-automated quantified fluorescein angiography (FA) features. METHODS: This retrospective case-control study enrolled patients with BRVO who are receiving anti-VEGF therapy and have been followed up for > 1 year. Those receiving < 5 anti-VEGF injections in the first year were classified as the responsive group, while those receiving ≥5 injections were the refractory group. The FA images were subjected to semi-automated pre-processing. Fluorescein leakages at the 5-min image were represented by mean gray value over parafoveal and perifoveal regions. FA leakages and central retinal thickness (CRT) on optical coherence tomography (OCT) were used for predicting the treatment response and compared using area under receiver operating characteristic curve (AUC). RESULTS: Eighty-nine patients (56 males, 33 females, mean age 62.5 ± 10.9 years) with BRVO were enrolled. Of the 89 eyes, 47 (53%) were in the responsive group and 42 (47%) were in the refractory group. The refractory group had a significantly higher number of anti-VEGF injections in the first year (5.9 ± 1.6 versus 2.4 ± 1.2, p < 0.001) when compared with that of the responsive group. It had thicker pre-treatment CRT (p = 0.011), post-treatment best CRT (p < 0.001) and CRT at 1-year (p < 0.001). It also had a higher mean gray value over the parafoveal (p < 0.001) and the perifoveal (p < 0.001) regions. The mean gray value over perifoveal (AUC 0.846) and parafovel (AUC 0.818) had significantly larger AUC than that of the pre-treatment OCT (AUC 0.653; p = 0.005 and p = 0.016, respectively) when predicting treatment response. CONCLUSION: The refractory group had a more severe fluorescein leakage over the parafoveal and the perifoveal regions than the responsive group had. Semi-automated quantified FA leakage can be used as a biomarker for the prediction of anti-VEGF treatment response in macular edema due to BRVO.

Evaluation of Antegrade Intramedullary Compression Screw Fixation of Metacarpal Shaft Fractures in a Cadaver Model.

PURPOSE: Surgical options for displaced metacarpal shaft fractures include the use of Kirschner wires, plates and screws, and most recently, intramedullary headless compression screws (IMHCS), which have been reported using only retrograde insertion through the metacarpal head. We evaluated IMHCS fixation of metacarpal shaft fractures through an antegrade approach in a cadaver model. METHODS: We performed antegrade placement of IMHCS in 10 cadaver hands including all 5 digits (total of 50). Displaced transverse proximal metacarpal shaft fractures were created and reduced with a retrograde guidewire from the metacarpal head across the shaft fracture and exiting the metacarpal base. This was retrieved through a 6-mm dorsal wrist incision and overdrilled before the placement of a 4.1-mm-diameter IMHCS in the ring finger and a 4.7-mm screw in all other metacarpals. After IMHCS placement, carpometacarpal (CMC) joint violation was measured along with the optimal starting point for the guidewire on the metacarpal head relative to the dorsal cortex. RESULTS: In all 50 metacarpals, we achieved successful fracture reduction and fixation without violating the extensor mechanism at the wrist. Our retrograde guidewire entry point through the metacarpal head ranged from 4.2 to 4.7 mm volar to the dorsal cortex. The actual area of CMC joint violated by IMHCS placement was largest in the index CMC joint (4.9%), followed by the middle (3.7%), little (2.9%), ring (0.5%), and thumb joints (0.2%). CONCLUSIONS: Placement of IMHCS through an antegrade approach from the CMC joint can be performed effectively for all transverse metacarpal fractures, including the thumb, using a limited incision. There is minimal violation of the articular surfaces of the trapezium, capitate, and hamate for the thumb, middle, ring, and little metacarpals. CLINICAL RELEVANCE: Antegrade IMHCS fixation successfully avoids the potential morbidity of creating a metacarpal head articular surface or extensor mechanism defect at the metacarpophalangeal joint seen with the retrograde approaches.

An Anatomical Study of Metacarpal Morphology Utilizing CT Scans: Evaluating Parameters for Antegrade Intramedullary Compression Screw Fixation of Metacarpal Fractures.

PURPOSE: This study evaluated metacarpal morphology for antegrade placement of intramedullary headless compression screws (IMHCS) for metacarpal fracture fixation. METHODS: We analyzed 100 hand computed tomography scans to quantify cortical thickness, intramedullary diameter, and metacarpal lengths. In addition, dorsal or ulnar overhang of the metacarpals over their respective carpal bones was measured. We also predicted optimal entry points for guidewire placement at the metacarpal head. RESULTS: The ring finger metacarpal had the narrowest medullary canal width (coronal, 2.8 mm; sagittal, 3.5 mm). Not counting the thumb, the little finger metacarpal had the widest midshaft medullary width of 4.1 mm in the coronal plane and the middle metacarpal was widest in the sagittal plane with canal width of 3.9 mm. On average, there was maximal dorsal overhang at the base of the middle metacarpal (4.2 mm) and maximal ulnar overhang at the base of the small metacarpal (3.9 mm). The optimal entry point for guidewire placement over each metacarpal head was approximately 3.5 to 3.8 mm volar to the dorsal cortex. CONCLUSIONS: Minimum IMHCS diameters of 3.5 mm for the ring and 4.0 mm for the index, middle and little fingers are necessary to achieve interference fit within the medullary canal. Minimum screw lengths of 38 mm would be needed to ensure 6 mm fixation past the midshaft of the metacarpals. Antegrade IMHCS for fixation of proximal metacarpal fractures may be most feasible with thumb, middle, and little finger metacarpals because there was larger dorsal or ulnar overhang to allow screw placement without violating the carpometacarpal joints. CLINICAL RELEVANCE: Our analysis provides a reference guide for intramedullary screw sizes for each metacarpal of the hand to achieve interference fit with fracture fixation. Furthermore, the dorsal and ulnar overhangs of the metacarpal bases suggest the practicality of antegrade IMHCS fixation.

Baseline clinical features predict visual outcome in young patients with central retinal vein occlusion.

PURPOSE: To evaluate prognostic factors in young patients with central retinal vein occlusion (CRVO). METHODS: Retrospective case series. CRVO patients aged ≤ 50 and follow-up ≥ 6 months were enrolled. The best corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline, 3 months, 6 months, and last visit were documented. Severity of retinopathy was graded by comparing to standard photos. Prognostic factors associated with visual outcome at 6 months were evaluated by multiple linear regression models. RESULTS: A total of 73 eyes from 69 patients with mean age 37.6 ± 8.5 were enrolled. Forty-seven (68%) patients were male. The mean follow-up duration was 25.9 ± 23.0 months. LogMAR BCVA improved from 0.979 ± 0.785 at baseline to 0.594 ± 0.748 at the 6 months (p < 0.001) and CRT improved from 475 ± 222 µm to 299 ± 104 µm (p < 0.001). Forty-eight (66%) eyes required anti-vascular endothelial growth factor (anti-VEGF) treatment. The mean number of injections was 2.25 ± 1.41 in the first 6 months and 75% of eyes received ≦ 3 injections during the clinical course. The baseline BCVA (coefficient 0.518, p < 0.001), grade of retinal hemorrhage (coefficient 0.230, p = 0.006), grade of retinal venous engorgement (coefficient 0.238, p = 0.011), grade of optic disc edema (coefficient - 0.226, p = 0.005), and diabetes mellitus (coefficient 0.264, p = 0.047) were the independent factors associated with visual outcome at 6 months. CONCLUSIONS: Baseline clinical features are useful for the prediction of visual outcome at 6 months in young CRVO patients.

Variations in Hook of Hamate Morphology: A Cadaveric Analysis.

PURPOSE: The hook of the hamate is an anatomical structure that separates the ulnar border of the carpal tunnel from Guyon's canal and serves as a landmark for surgeons. The hook of the hamate is also subject to fracture from injury. We hypothesize that there are variations in the hook of the hamate in the general population. METHODS: One thousand pairs of hamates (2,000 hamates) from the Hamann-Todd Collection at the Cleveland Natural History Museum were analyzed. The height of the hook of the hamate and the total height of the hamate bone were measured using digital calipers. The hook height ratio was defined as the hook height divided by the total height of the hamate. Statistical analysis was performed using unpaired Student's t test to determine differences in sex and race. RESULTS: The mean hook height was 9.8 ± 1.4 mm (range, 2.5-15.9 mm), whereas the mean hook height ratio was 0.42 ± 0.04 (range, 0.15-0.56). There was a 3.1% (62/2,000) incidence of abnormally small hooks, which we classified as hypoplastic and aplastic. Of the hypoplastic hooks, 55% (24/44) were bilateral, whereas 44% (8/18) of the aplastic hooks were bilateral. The incidence of variation in size in the hook of the hamate was highest in white females (9.3%) and lowest in black males (1.4%). CONCLUSIONS: Abnormalities in hook of hamate anatomy are common in the general population, especially in white females. CLINICAL RELEVANCE: Knowledge of anatomic variation in the hook of the hamate may provide additional insight into surgeons' palpation of bony anatomy, interpretation of imaging studies, and use of the hook as a landmark during surgery.

Complications of Semiconstrained Distal Radioulnar Joint Arthroplasty.

PURPOSE: The Aptis total distal radioulnar joint (DRUJ) prosthesis is a semiconstrained implant designed for treatment of DRUJ arthritis and instability. The purpose of this study was to analyze short-term complications of this device. METHODS: We performed a retrospective chart review of patients undergoing semiconstrained DRUJ arthroplasty from 2007 to 2015 at a single institution. Records were analyzed for complications and the need for subsequent surgical procedures. RESULTS: Two senior hand surgeons at one institution performed 52 semiconstrained DRUJ arthroplasties over 8 years. Nineteen complications necessitating operative management occurred in 15 patients (29%). A total of 26 procedures were undertaken to address these complications. Complications included 4 periprosthetic fractures, 3 infections, 2 instances of aseptic loosening, 2 implant component failures, 1 instance of screw loosening, 3 neuromas requiring neurectomy, 2 instances of finger stiffness necessitating extensor tenolysis, and 2 cases of heterotopic ossification at the DRUJ. Three of the 52 implants were revised (6%) and 2 were explanted (4%); 3 of these (6%) were caused by deep infection. CONCLUSIONS: There is limited literature on outcomes of the semiconstrained DRUJ prosthesis. Prior studies reported low complication rates, with 0% to 5% revisions. In the current clinical series, 29% of patients required further surgery for complications, the most common reasons for which were periprosthetic fracture and infection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

ExPRESS miniature glaucoma shunt for intractable secondary glaucoma in superior vena cava syndrome - a case report.

BACKGROUND: The aim of this study was to clarify the pathogenic mechanism and to evaluate an intervention for intractable secondary glaucoma in superior vena cava (SVC) syndrome. CASE PRESENTATION: A 66-year-old female with underlying hypertension, diabetes mellitus, ischaemic heart disease and end-stage renal disease complained of bilateral puffy eyelids for 3 months. Over three years, the patient experienced a progressive, marked face and neck swelling, which was accompanied by dyspnoea and nocturnal coughing. The patient has been under haemodialysis for the past 5 years; there were several occurrences of vascular access re-establishment for susceptibility to vascular thrombosis, and she was also diagnosed with SVC syndrome 2 years after haemodialysis. The patient's best-corrected visual acuity (BCVA) was 20/60 in the right eye and 20/400 in the left eye. Pneumatic tonometry revealed a gradual increase in the intraocular pressure (IOP), even with the use of three types of anti-glaucoma agents. The ratio was 0.7 and bilaterally symmetric; optical coherence tomography indicated a thinning of the superior and inferior retina nerve fibre layers, and standard automated perimetry showed partial to generalized depression in both eyes. Filtering surgery for the left eye was performed, but postoperatively, the IOP increased gradually over three months. The subsequent placement of the ExPRESS miniature glaucoma device p200 effectively lowered the IOP. Postoperatively, the IOP of the left eye remained under 20 mmHg without a further decrease in visual acuity, while the right eye, which was controlled with only medication, had an IOP of greater than 30 mmHg. Because this patient refused cardiovascular intervention, conventional trabeculectomy was used to redirect the aqueous humour to the subconjunctival space to form a bleb, but failed. Fortunately, the subsequent ExPRESS implant effectively facilitated aqueous outflow through the intrascleral space, resulting in the maintenance of a normal IOP at 6 months, postoperatively. CONCLUSION: Sustained high IOP may occur after conventional filtration surgery for secondary glaucoma in SVC syndrome. To facilitate aqueous outflow, an ExPRESS glaucoma implant can be used to effectively control the IOP.

Danger zones for flexor tendons in volar plating of distal radius fractures.

PURPOSE: To define a danger zone for volar plates using magnetic resonance imaging by analyzing the position of the flexor tendons at risk around the watershed line. METHODS: We analyzed 40 wrist magnetic resonance images. The location of the flexor pollicus longus (FPL) and index flexor digitorum profundus (FDPi) tendons was recorded at 3 and 6 mm proximal to the watershed line of the distal radius. We measured the distance between the volar margin of the distal radius and the FPL and FDPi tendons, and the coronal position of the tendons. RESULTS: At a point 3 mm proximal to the watershed line, FPL and FDPi were located on average 2.6 and 2.2 mm anterior to the volar margin of the distal radius. This distance increased to 4.7 and 5.3 mm at a point 6 mm proximal to the watershed line. The FPL and FDPi were located at 57% and 42% of the total width of the distal radius from the sigmoid notch at 3 mm from the watershed, and at 66% and 46% at 6 mm from the watershed. CONCLUSIONS: Surgeons should be aware of the close proximity of the flexor tendons to the volar cortex of the distal radius proximal to the watershed line and their radial to ulnar position. Three millimeters proximal to the watershed line, plate placement more than 2 mm anterior to the volar cortex or the use of plates thicker than 2 mm poses a high risk for directly contacting flexor tendons. CLINICAL RELEVANCE: This article may prove to be helpful in avoiding flexor tendon injury during volar plate fixation.

Predicting a safe screw length for volar plate fixation of distal radius fractures: lunate depth as a marker for distal radius depth.

PURPOSE: We hypothesized that the lunate depth as measured on plain lateral radiographs can be used to predict distal radius depth radially and ulnarly and serve as a useful reference for intraoperative screw placement in volar plate fixation of distal radius fractures. METHODS: Plain radiographs and magnetic resonance imaging (MRI) of the wrists of 30 patients were reviewed. The lunate depth and the maximal depth of the distal radius were determined from plain lateral radiographs. Depth of the distal radius, measured in quartiles, was determined from axial MRI images, and the lunate depth was obtained from sagittal MRI images. The depth of the distal radius in each quartile was then calculated related to the lunate depth. RESULTS: The mean depth of the lunate on plain radiographs and MRI was 17.5 mm and 17.4 mm, respectively. The depth of the distal radius from ulnar to radial was 18.4 mm, 20.2 mm, 19.4 mm, and 15.1 mm for the 1st through 4th quartiles, respectively. The depth of the distal radius is the least radially (4th quartile), with a mean 87% of the lunate depth, and greatest in the 2nd quartile, with a mean 116% of the lunate depth. CONCLUSIONS: The depth of the lunate as measured on plain radiographs can be used as a marker for drilling and placement of safe screw lengths during volar plate fixation of distal radius fractures. We recommend that surgeons use the lunate depth as an estimate for the length of their longest screw when fixing distal radius fractures with volar plate techniques to avoid extensor tendon irritation and rupture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Functional Outcomes Following Bridge Plate Fixation for Distal Radius Fractures.

PURPOSE: To determine the functional outcomes of patients treated with dorsal spanning distraction bridge plate fixation for distal radius fractures. METHODS: All adult patients at our institution who underwent treatment of a unilateral distal radius fracture using a dorsal bridge plate from 2008 to 2012 were identified retrospectively. Patients were enrolled in clinical follow-up to assess function. Wrist range of motion, grip strength, and extension torque were measured systematically and compared with the contralateral, uninjured wrist. Patients also completed Quick-Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation outcomes questionnaires. RESULTS: Eighteen of 100 eligible patients, with a minimum of 1 year from the time of implant removal, were available for follow-up (mean, 2.7 y). All fracture patterns were comminuted and intra-articular (AO 23.C3). There were significant decreases in wrist flexion (43° vs 58°), extension (46° vs 56°), and ulnar deviation (23° vs 29°) compared with the contralateral uninjured wrist. Grip strength was 86% and extension torque was 78% of the contralateral wrist. Comparison of dominant and nondominant wrist injuries identified nearly complete recovery of grip (95%) and extension (96%) strength of dominant-sided wrist injuries, compared with grip (79%) and extension (65%) strength in those with an injured nondominant wrist. Mean Quick-Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist Evaluation scores were 16 and 14, respectively. There were 2 cases of postoperative surgical site pain and no cases of infection, tendonitis, or tendon rupture. CONCLUSIONS: Distraction bridge plate fixation for distal radius fractures is safe with minimal complications. Functional outcomes are similar to those published for other treatment methods. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Morphology of the extensor carpi ulnaris groove and tendon.

PURPOSE: Injury to the extensor carpi ulnaris (ECU) fascial supports on the distal ulna can result in ulnar-sided wrist pain, particularly when the tendon subluxates medially out of the fibroosseous groove with forearm rotation. To better understand the potential risk factors for injury and the indications for modifying the ECU groove, we have evaluated and quantified the morphology of the ECU groove and tendon. METHODS: Axial plane magnetic resonance imaging of the wrist obtained for triangular fibrocartilage complex and intercarpal pathology in 60 patients were reviewed. Mean and standard error of the mean were calculated and unpaired Student t tests performed to compare groove width and depth, radius of curvature of the groove, carrying angle, and tendon-to-groove ratio. RESULTS: There were 23 females (38%), and the mean patient age was 40 years (range, 17-71 y). The average ECU groove depth and standard error of the mean was 1.4 mm ± 0.1 mm. The radius of curvature for the ulnar ECU groove was found to be 7.0 mm ± 0.4 mm with a carrying angle of 143° ± 2°. In neutral forearm rotation, the average ratio of the width of the ECU tendon to groove was 0.7 ± 0.02. The data approximated a normal distribution. There were no statistically significant differences in these measurements between the triangular fibrocartilage complex and the intercarpal pathology subgroups. CONCLUSIONS: Variability in the relationship of the ECU groove and tendon may combine to represent risk factors for tendinosis or tendon subluxation. There may be a more normal distribution of ECU groove morphology than previously recognized. CLINICAL RELEVANCE: ECU injuries may require clinical imaging of the tendon and subsheath, in addition to potential surgical reconstruction and ulnar groove deepening. This report establishes the normative morphology and depth of the ECU groove and provides a comparative baseline when considering treatment modalities.

Radiographic evaluation of the modified Brunelli technique versus a scapholunotriquetral transosseous tenodesis technique for scapholunate dissociation.

PURPOSE: To compare reduction of the scapholunate articulation using a transosseous tenodesis through the scaphoid, lunate, and triquetrum (SLT) with the modified Brunelli technique (MBT) in a cadaver model, as measured by scapholunate (SL) angle and diastasis on radiographs. METHODS: Twelve fresh-frozen cadaveric wrists were radiographically examined in a neutral posture, ulnar deviation, and clenched fist position. The SL angle and diastasis were recorded in each position with the SL ligament intact, after sectioning the ligament and secondary restraints, and after reconstruction by either the MBT (6 wrists) or SLT technique (6 wrists). Wrists were cycled through their maximum flexion and extension arc 100 times to simulate wrist motion after ligament sectioning and reconstruction. RESULTS: After sectioning and cycling, all wrists demonstrated radiographic evidence of SL diastasis. After ligament reconstruction and cycling, there was no statistically significant difference in diastasis in the MBT reconstructions compared with the SLT reconstructions (3.0 vs 2.4 mm). The SLT group demonstrated better maintenance of the restored SL angle than the MBT reconstructions. CONCLUSIONS: In this cadaveric model, both MBT and SLT reconstructions restored anatomic parameters in the SL joint, with correction of SL diastasis and SL angle. Future studies to assess the clinical outcomes of SLT tenodesis in patients with chronic SL disruptions are important. CLINICAL RELEVANCE: The SLT tenodesis, with a central biologic tether along the SL axis and dorsal reinforcement, may prove clinically useful.

The quality of upper extremity orthopedic care in liability claims filed and claims paid.

PURPOSE: To review a series of closed liability claims for upper extremity conditions to guide improvements for upper extremity care and thereby reduce the frequency of paid claims. METHODS: The authors, a team of 3 orthopedic surgeons and 3 nonphysician investigators experienced in closed claims research, investigated 108 closed upper extremity liability claims from a large United States-wide insurer for events that occurred between 1996 and 2009. We sought to determine the types of conditions, treatments, and surgeon factors common to claims made and claims paid. RESULTS: Liability claims were primarily for the care of common problems, such as fractures (n = 52; 48%) or degenerative conditions (n = 24; 26%), rather than complex challenging conditions or disorders, such as deficiencies treated with replantations or tissue transfers. The most common adverse outcomes in these claims were nonunion or malunion of fractures (n = 29; 27%), nerve injury (n = 20; 19%), and infection (n = 13; 12%). Most claims (n = 57; 53%) involved a permanent injury. The surgeon's operative skills were more commonly an issue in paid claims (n = 13; 45%) than in claims without payment (n = 14; 19%). Claims for mismanagement of fractures (n = 52; 48% of all claims) were more likely to result in payment (n = 20; 38%) than nonfracture claims (n = 10; 18%). CONCLUSIONS: This analysis suggests that the incidence of upper extremity claims made and claims paid may be reduced if surgeons acquire and maintain the knowledge and skills necessary for the care of the common conditions they encounter, including fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Prospective randomized controlled trial comparing 1- versus 7-day manipulation following collagenase injection for dupuytren contracture.

PURPOSE: To compare the efficacy, tolerance, and safety of manual manipulation at day 7 to day 1 following collagenase Clostridium histolyticum (CCH) injection for Dupuytren contracture. METHODS: Eligible patients were randomized to manipulation at day 1 versus day 7 following CCH injection. Preinjection, premanipulation, postmanipulation, and 30-day follow-up metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joint contractures were measured. Pain scores were recorded at each time point. Data were stratified per cohort based on primary joint treated (MCP vs PIP). Means were compared using paired and unpaired t-tests. RESULTS: Forty-three patients with 46 digits were eligible and were randomized to 1-day (22 digits) and 7-day (24 digits) manipulation. For MCP joints, there were no significant differences in flexion contractures between 1- and 7-day cohorts for initial (47° vs 46°), postmanipulation (0° vs 2°), or 30-day follow-up (1° vs 2°) measurements. Premanipulation, the residual contracture was significantly lower in the 7-day group (23° vs 40°). For PIP joints, there were no significant differences between 1- and 7-day cohorts for initial (63° vs 62°), premanipulation (56° vs 52°), postmanipulation (13° vs 15°), or 30-day (14° vs 16°) measurements. There were no significant differences in pain or skin tears between the 2 groups. No flexor tendon ruptures were observed. CONCLUSIONS: The effectiveness of CCH in achieving correction of Dupuytren contractures was preserved when manipulation was performed on day 7, with no differences in correction, pain, or skin tears. These data suggest that manipulation can be scheduled at the convenience of the patient and surgeon within the first 7 days after injection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Characterization of autoimmune eye disease in association with Down's syndrome.

BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Measurement scales in clinical research of the upper extremity, part 1: general principles, measures of general health, pain, and patient satisfaction.

Measurement is a fundamental cornerstone in all aspects of scientific discovery, including clinical research. To be useful, measurement instruments must meet several key criteria, the most important of which are satisfactory reliability, validity, and responsiveness. Part 1 of this article reviews the general concepts of measurement instruments and describes the measurement of general health, pain, and patient satisfaction.