Application of Tendon With Z-Lengthening Technique.

Tendon deficiency limits repair and reconstructive options after tendon and nerve injuries of the upper extremity. Current treatment options include intercalary tendon autograft, tendon transfers, and two-stage tenodesis, with sacrifice of the flexor digitorum superficialis. These reconstructive techniques are associated with donor site morbidity and limited in the setting of multiple tendon deficiencies. The tendon with z-lengthening (TWZL) technique is presented here as an alternative treatment method for tendon injuries and tendon transfer reconstruction after nerve injuries. The TWZL technique involves splitting a tendon longitudinally, reflecting the freed tendon limb distally, and suture augmentation at the bridge site located at the distal end of the native tendon. The TWZL technique has applications throughout the upper extremity-flexor and extensor tendons injuries, biceps and triceps tendon injuries, and tendon transfers for restoration of hand function after nerve injuries. An illustrative case example is also provided. The experienced hand surgeon should consider the TWZL technique as a potential treatment option when faced with difficult clinical conditions of the hand and upper extremities.

Occult Amyloid Deposition in Older Patients Presenting With Bilateral Carpal Tunnel Syndrome or Multiple Trigger Digits.

PURPOSE: The diagnosis of amyloidosis is important for early intervention, disease monitoring, and prevention of complications and progression. Carpal tunnel syndrome (CTS) and trigger digit (TD) are two common conditions associated with early disease. The purpose of this study was to define disease prevalence among patients with bilateral CTS and multiple TDs and assess for an increased rate of diagnosis in the presence of both. METHODS: Men older than 50 years and women older than 60 years of age diagnosed with bilateral CTS, multiple TDs, or a combination of the 2 were prospectively enrolled in our study. Tenosynovial biopsy samples taken at the time of surgery were tested for the presence of amyloid using Congo red staining. Demographic and medical covariates were also collected and analyzed for differences between amyloid-positive and -negative patients. RESULTS: Fifty-six patients were enrolled in the study, and nine patients tested positive for amyloid deposition. The demographics and medical comorbidities were similar between amyloid-positive and -negative patients. Thirty patients with bilateral CTS were enrolled, and four tested positive for amyloid. For patients with multiple TDs, a total of 17 patients were enrolled, and 4 tested positive for amyloid. Among patients with multiple TDs, only men tested positive for amyloid and were, on average, younger than those who tested negative (61 and 73 years, respectively). Patients presenting with a combination of CTS and TD did not exhibit increased amyloid discovery. CONCLUSIONS: Hand surgeons should consider tenosynovial biopsy in men older than 50 years and women older than 60 years presenting with either bilateral CTS or multiple TDs. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Evidence-Based Approach to Timing of Nerve Surgery: A Review.

ABSTRACT: Events causing acute stress to the health care system, such as the COVID-19 pandemic, place clinical decisions under increased scrutiny. The priority and timing of surgical procedures are critically evaluated under these conditions, yet the optimal timing of procedures is a key consideration in any clinical setting. There is currently no single article consolidating a large body of current evidence on timing of nerve surgery. MEDLINE and EMBASE databases were systematically reviewed for clinical data on nerve repair and reconstruction to define the current understanding of timing and other factors affecting outcomes. Special attention was given to sensory, mixed/motor, nerve compression syndromes, and nerve pain. The data presented in this review may assist surgeons in making sound, evidence-based clinical decisions regarding timing of nerve surgery.

Pseudoaneurysm of the Radial Artery After CMC Arthroplasty.

Pseudoaneurysm of the radial artery is an unusual condition. Most radial artery pseudoaneurysms occur as a result of catheterization; however, any traumatic event that damages the vessel can lead to a symptomatic pseudoaneurysm. This report presents a case of an unusual late presentation of clinical symptoms associated with a pseudoaneurysm of the radial artery after arthroplasty of the thumb carpometacarpal joint.

Efficacy of a single, image-guided corticosteroid injection for glenohumeral arthritis.

BACKGROUND: Limited data are available on the efficacy of cortisone injections for glenohumeral osteoarthritis (GHOA). The amount and longevity of pain relief provided by a single cortisone injection are unclear. Additionally, it remains uncertain how the severity of radiographic GHOA and patient-reported function and pain levels impact the efficacy of an injection. Therefore, we sought to describe the relief provided by a single, image-guided glenohumeral injection in patients with GHOA. We hypothesized that patients with more severe radiographic GHOA and poorer baseline shoulder function would require earlier secondary intervention. METHODS: Patients with symptomatic GHOA who elected to receive a corticosteroid injection for pain relief were prospectively enrolled. A phone interview was conducted to record the baseline Oxford Shoulder Score (OSS) and visual analog scale (VAS) score prior to the injection, as well as the OSS and VAS score at months 1, 2, 3, 4, 6, 9, and 12 after the injection. The endpoint of the study occurred when patients required a second injection, progressed to surgery, or reached month 12. Patients were grouped by their respective baseline OSS (mild vs. moderate or severe) and Samilson-Prieto radiographic classification (mild, moderate, or severe) for analysis. RESULTS: We analyzed 30 shoulders (29 patients). Of the patients, 52% were men. The average age was 66.1 years. No significant difference in overall survival (defined as no additional intervention) was seen between groups based on either the OSS or Samilson-Prieto grade. Additionally, the OSS and VAS score at each follow-up were compared with baseline values. For the entire cohort, a clinically significant difference was seen between baseline and months 1-4 for the OSS and between baseline and months 1-4, 6, 9, and 12 for the VAS score. DISCUSSION: This study aimed to determine the efficacy of corticosteroid injections for GHOA. There were no differences in the need for secondary intervention in this population based on the severity of either the OSS or the Samilson-Prieto radiographic classification. However, patients with more severe shoulder dysfunction based on the OSS did experience statistically significantly greater symptomatic relief than patients with milder dysfunction. Additionally, following a single injection, patients in this cohort experienced statistically and clinically relevant improvements in shoulder function and pain up to 4 months after injection.

Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data.

OBJECTIVES: Tofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within. METHODS: This post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years' exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed. RESULTS: 12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the all tofacitinib cohorts' average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09-0.27) and 0.15 (0.09-0.22)); PE (0.12 (0.06-0.22) and 0.13 (0.08-0.21)); ATE (0.32 (0.22-0.46) and 0.38 (0.28-0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00-0.36) and 0.06 (0.02-0.15)); PE (0.13 (0.02-0.47) and 0.09 (0.04-0.19)); ATE (0.52 (0.22-1.02) and 0.22 (0.13-0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00-0.28) and 0.13 (0.00-0.70)); PE (0.08 (0.00-0.43) and 0.00 (0.00-0.46)); ATE (0.31 (0.08-0.79) and 0.38 (0.08-1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database. CONCLUSIONS: DVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32-0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13-0.41)).

Genetics of rheumatoid arthritis contributes to biology and drug discovery.

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Palmar Radiocarpal Artery Vascularized Bone Graft for the Unstable Humpbacked Scaphoid Nonunion With an Avascular Proximal Pole.

PURPOSE: The most challenging scaphoid nonunion is the unstable nonunion with humpbacked collapse coupled with an avascular proximal pole. Dorsal distal radius pedicled vascularized bone grafts (VBGs) are contraindicated in cases of humpback deformity. The free medial femoral condyle VBG is an excellent option but it is an extensive microsurgical procedure with lengthy operative times and dual-limb incisions. In search of a local, volar, vascularized source of bone to treat this challenging subset of scaphoid nonunions, we analyzed our results with a volar distal radius bone graft based on the pedicled palmar radiocarpal artery (PRCA). METHODS: A prospective cohort of 15 unstable nonunions with avascular proximal pole fragments was treated with the PRCA graft and open reduction internal fixation. Preoperative carpal indices revealed a high degree of instability. All 15 lacked punctate bleeding from the proximal pole. All 15 patients were treated with the PRCA VBG technique and scanned with computed tomography at approximately 6 and 12 weeks to assess for interval healing. RESULTS: All nonunions healed with an average cross-sectional trabeculation score of 70% at week 6 and 84% at week 12. Sagittal intrascaphoid angles improved from 50° to 27°, radiolunate angle improved from -20° to -7°, scapholunate angle improved from 86° to 64°, and revised carpal height ratio improved from 1.45 to 1.53, indicating correction of the humpback collapse deformity. Patients were observed an average of 22 months to have no sign of further avascular necrosis. CONCLUSIONS: Pedicled PRCA-VBG successfully addresses the dual needs of the humpbacked scaphoid nonunion with an avascular proximal pole while simultaneously limiting dissection to one limb and avoiding the additional complexities of free tissue transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Peripheral nerve repair throughout the body with processed nerve allografts: Results from a large multicenter study.

BACKGROUND: Peripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date. METHODS: This multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature. RESULTS: The study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit. CONCLUSIONS: These findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

Testing of Direct Neurorrhaphy Strain.

PURPOSE: To investigate the ideal suture material to test strain at nerve repair sites. Based on nerve strain tolerance, we aimed to determine which suture reliably failed by an average of 5% and a maximum of 8% strain when loaded to failure. METHODS: The median nerve of 19 cadavers was exposed in the distal forearm, transected proximally, and attached to a spring gauge. It was marked 5 cm on either side of its midpoint to measure strain. A laceration was created at its midpoint. We performed a tension-free end-to-end repair with a single epineural suture. Load to failure of the repair site was recorded. We recorded strain at failure and mode of failure (pullout vs breakage). Eight different sutures were tested: 6-0, 8-0, 9-0, and 10-0 nylon; and 6-0, 7-0, 8-0, and 10-0 polypropylene. RESULTS: Average strain at failure of 9-0 nylon most closely approximated 5% (4.9%). Moreover, 8-0 polypropylene and 10-0 nylon and polypropylene failed with average strains less than 5% and a maximum strain of failure less than 8%. Regardless of type, 6-0 to 8-0 caliber suture failed primarily by pullout of the suture from the epineurium whereas 9-0 and 10-0 nylon and polypropylene failed by suture breakage. Decreased precision through increased variability was seen when testing sutures failing via pullout. CONCLUSIONS: Nylon suture size 8-0 has been advocated as the suggested intraoperative aid to test strain at nerve repair sites. Our study suggests that 9-0 nylon may be a more appropriate testing suture because of its more predictable failure via breakage and its failure by a threshold of 5% to 8% strain. Although 8-0 nylon and polypropylene may also represent reasonable testing sutures, 8-0 nylon failed on average above 5% strain, with strains exceeding 8%, and both failed via the mechanism of pullout. CLINICAL RELEVANCE: This study's findings provide information for surgeons attempting to decide during surgery whether to perform direct nerve repair.

Characterization of disease burden, comorbidities, and treatment use in a large, US-based cohort: Results from the Corrona Psoriasis Registry.

BACKGROUND: Psoriasis is an immunodysregulatory inflammatory disease associated with comorbidities affecting quality of life. With the advent of new treatments, there is growing need to assess the long-term safety and efficacy of treatments in a real-world setting. OBJECTIVE: The objective of the Corrona Psoriasis Registry is to study the comparative safety and efficacy of Food and Drug Administration-approved biologic treatments. METHODS: A cross-sectional study of patients enrolled in the registry, who initiated or switched to a systemic therapy at enrollment or previous 12 months. Descriptive characteristics (demographics, clinical and patient-reported outcomes, comorbidities, and treatment history) were examined at registry enrollment. RESULTS: As of October 1, 2016, there were 1942 patients enrolled in the registry: 23% on apremilast, 4% on other nonbiologic systemic medications, 25% on interleukin (IL) 17A inhibitors, 22% on an IL-12/23 inhibitor, and 26% on tumor necrosis factor inhibitors. Overall, mean disease duration was 15.6 years, and 40% had a concurrent psoriatic arthritis diagnosis. About 66% had >3% body surface area involvement and 49% had a moderate or severe Investigator Global Assessment. LIMITATIONS: Selection and channeling bias can result in potential confounding that needs to be addressed in modeled analyses. CONCLUSION: This disease-based registry cohort represents a population exposed to multiple therapies, long disease duration, and multiple comorbidities and can be used to examine comparative safety and efficacy of various therapies.

Design characteristics of the Corrona Japan rheumatoid arthritis registry.

OBJECTIVES: The primary objective is to prospectively study the comparative safety and effectiveness of older and newer classes of nonbiologic DMARDs (Disease-modifying antirheumatic drugs), biologic DMARDs and targeted synthetic therapies approved for rheumatoid arthritis (RA) in a real-world patient population in Japan. METHODS: Prospective, multicenter, noninterventional, observational study across geographic distribution of both private and public institutions for patients with RA who are newly prescribed one of the following medications: (1) methotrexate; (2) anti-TNF biologic DMARDs; (3) non-TNF biologic DMARDs; and (4) approved JAK inhibitors at the time of enrollment into the registry. Target enrollment is currently 2000 subjects. Baseline and follow-up data on patient demographics, medical history, disease activity, laboratory results, comorbidities, hospitalizations, and targeted safety events are obtained via Physician and Patient Questionnaires. RESULTS: Fifty sites are anticipated to participate with 40 sites ethics committee (EC) approved at the time of submission consisting of 23% clinics, 21% private academic hospitals, 29% private mid-sized to large hospitals, 15% national academic hospitals, and 12% national hospitals. CONCLUSION: The Corrona Japan RA Registry will provide real-world evidence from both private and public institutions on the comparative effectiveness and safety of recently approved RA therapies in Japan.

Autoreactivity to malondialdehyde-modifications in rheumatoid arthritis is linked to disease activity and synovial pathogenesis.

Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA antibodies are associated with inflammatory and autoimmune conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA). While RA is primarily associated with autoreactivity to citrullinated antigens, we also observed increases in serum IgG anti-MDA in RA patients compared to controls. IgG anti-MDA levels significantly correlated with disease activity by DAS28-ESR and serum TNF-alpha, IL-6, and CRP. Mass spectrometry analysis of RA synovial tissue identified MDA-modified proteins and revealed shared peptides between MDA-modified and citrullinated actin and vimentin. Furthermore, anti-MDA autoreactivity among synovial B cells was discovered when investigating recombinant monoclonal antibodies (mAbs) cloned from single B cells, and 3.5% of memory B cells and 2.3% of plasma cells were found to be anti-MDA positive. Several clones were highly specific for MDA-modification with no cross-reactivity to other antigen modifications such as citrullination, carbamylation or 4-HNE-carbonylation. The mAbs recognized MDA-adducts in a variety of proteins including albumin, histone 2B, fibrinogen and vimentin. Interestingly, the most reactive clone, originated from an IgG1-bearing memory B cell, was encoded by near germline variable genes, and showed similarity to previously reported natural IgM. Other anti-MDA clones display somatic hypermutations and lower reactivity. Importantly, these anti-MDA antibodies had significant in vitro functional properties and induced enhanced osteoclastogenesis, while the natural antibody related high-reactivity clone did not. We postulate that these may represent distinctly different facets of anti-MDA autoreactive responses.

Benefit of biologics initiation in moderate versus severe rheumatoid arthritis: evidence from a United States registry.

Objectives: To compare clinical outcomes and treatment patterns among patients with moderate vs severe RA following biologic DMARD initiation. Methods: Biologics-naive patients with moderate to severe RA [Clinical Disease Activity Index (CDAI) >10] who initiated a biologic DMARD were selected from the Corrona registry (2001-13). CDAI, functional status [modified HAQ (mHAQ)] and patterns of drug use were compared at 1 and 2 years post-initiation between patients with moderate (CDAI >10⩽22) vs severe (CDAI >22) baseline disease activity. Results: A total of 1596 patients (817 severe, 779 moderate) had ⩾1 year of follow-up and 1269 (635 severe, 634 moderate) had ⩾2 years of follow-up. Patients with severe vs moderate baseline disease activity experienced greater improvements in disease activity [mean change in CDAI -18.9 vs -6.0 at year 1; -21.0 vs -7.1 at year 2 ( P < 0.0001)] and physical function [mean change in mHAQ -0.2 vs -0.1 ( P < 0.0001) at year 1; -0.2 vs -0.1 ( P = 0.0013) at year 2]. Greater proportions of patients with moderate vs severe disease activity achieved remission (CDAI ⩽2.8) [22.7 vs 15.8% ( P = 0.0003) at year 1; 25.9 vs 20.9% ( P = 0.0396) at year 2] or low disease activity (CDAI <10) [60.1 vs 41.2% at year 1; 66.7 vs 49.4% at year 2 ( P < 0.0001)]. Most patients remained on the original biologic drug (>70% at year 1; >62% at year 2). Conclusion: With biologic therapy, RA patients with higher baseline disease activity achieved greater improvements in measures of disease activity than those with lower levels of disease, but less often achieved the common targets of remission or low disease activity.

The clinical status and economic savings associated with remission among patients with rheumatoid arthritis: leveraging linked registry and claims data for synergistic insights.

INTRODUCTION: Treat to target guidelines recommend achieving remission or low disease activity in rheumatoid arthritis (RA). However, the reduction in adverse events and costs associated with lower disease activity is unclear. METHODS: We used Corrona linked to Medicare data to identify RA patients. Time varying disease activity was measured using Clinical Disease Activity Index (CDAI); outcomes included all-cause hospitalization, a composite of hospitalization or emergency department (ED) visits, mortality, and medical costs. Outcome-specific Cox proportional models evaluated the adjusted hazard ratios between disease activity and outcomes, controlling for potential confounders including comorbidities grouped into four patient phenotypes. Costs were analyzed with mixed models using a Gaussian distribution with log transformation. RESULTS: Depending on outcome, 4593 RA patients contributed up to 12 001 person years. Median age was 71 years, 75% women. At baseline, approximately 50-60% of patients were in remission or low disease activity. There was a dose-response relationship between RA disease activity (remission, low, moderate, and high) and the incidence of hospitalizations (13.1, 17.8, 21.2, 27.5 per 100 py, respectively); all adjusted hazard ratios were significant: 0.68 (remission), 0.87 (low), and 1.24 (high) compared with moderate disease activity. Similar trends were observed for ED visits and mortality. The crude difference in annual medical costs between remission ($11 145) and moderate disease activity ($17 646) was $-6 500; the adjusted difference (95%CI) was $-3133 (-4737.72, -1528.43). CONCLUSION: Leveraging the benefits of linking registry and administrative data together, lower disease activity in RA was associated with incrementally reduced risks of all-cause hospitalization, ED visits, mortality, and medical costs in a dose-dependent fashion. Copyright © 2016 John Wiley & Sons, Ltd.

Sex differences in gout characteristics: tailoring care for women and men.

BACKGROUND: To characterize the differences between women and men with gout. METHODS: We analyzed a US national cohort of gout patients cared for by rheumatologists. RESULTS: Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05). CONCLUSIONS: The profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Use of Processed Nerve Allografts to Repair Nerve Injuries Greater Than 25 mm in the Hand.

Processed nerve allografts (PNAs) have been demonstrated to have improved clinical results compared with hollow conduits for reconstruction of digital nerve gaps less than 25 mm; however, the use of PNAs for longer gaps warrants further clinical investigation. Long nerve gaps have been traditionally hard to study because of low incidence. The advent of the RANGER registry, a large, institutional review board-approved, active database for PNA (Avance Nerve Graft; AxoGen, Inc, Alachua, FL) has allowed evaluation of lower incidence subsets. The RANGER database was queried for digital nerve repairs of 25 mm or greater. Demographics, injury, treatment, and functional outcomes were recorded on standardized forms. Patients younger than 18 and those lacking quantitative follow-up data were excluded. Recovery was graded according to the Medical Research Council Classification for sensory function, with meaningful recovery defined as S3 or greater level. Fifty digital nerve injuries in 28 subjects were included. There were 22 male and 6 female subjects, and the mean age was 45. Three patients gave a previous history of diabetes, and there were 6 active smokers. The most commonly reported mechanisms of injury were saw injuries (n = 13), crushing injuries (n = 9), resection of neuroma (n = 9), amputation/avulsions (n = 8), sharp lacerations (n = 7), and blast/gunshots (n = 4). The average gap length was 35 ± 8 mm (range, 25-50 mm). Recovery to the S3 or greater level was reported in 86% of repairs. Static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament (SWF) were the most common completed assessments. Mean s2PD in 24 repairs reporting 2PD data was 9 ± 4 mm. For the 38 repairs with SWF data, protective sensation was reported in 33 repairs, deep pressure in 2, and no recovery in 3. These data compared favorably with historical data for nerve autograft repairs, with reported levels of meaningful recovery of 60% to 88%. There were no reported adverse effects. Processed nerve allograft can be used to reconstruct long gap nerve defects in the hand with consistently high rates of meaningful recovery. Results for PNA repairs of digital nerve injuries with gaps longer than 25 mm compare favorably with historical reports for nerve autograft repair but without donor site morbidity.

Rare, low-frequency, and common variants in the protein-coding sequence of biological candidate genes from GWASs contribute to risk of rheumatoid arthritis.

The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association studies (GWASs). First, we assessed the contribution of rare coding variants in the 25 genes to the risk of RA in a pooled sequencing study of 500 RA cases and 650 controls of European ancestry. We observed an accumulation of rare nonsynonymous variants exclusive to RA cases in IL2RA and IL2RB (burden test: p = 0.007 and p = 0.018, respectively). Next, we assessed the aggregate contribution of low-frequency and common coding variants to the risk of RA by dense genotyping of the 25 gene loci in 10,609 RA cases and 35,605 controls. We observed a strong enrichment of coding variants with a nominal signal of association with RA (p < 0.05) after adjusting for the best signal of association at the loci (p(enrichment) = 6.4 × 10(-4)). For one locus containing CD2, we found that a missense variant, rs699738 (c.798C>A [p.His266Gln]), and a noncoding variant, rs624988, reside on distinct haplotypes and independently contribute to the risk of RA (p = 4.6 × 10(-6)). Overall, our results indicate that variants (distributed across the allele-frequency spectrum) within the protein-coding portion of a subset of biological candidate genes identified by GWASs contribute to the risk of RA. Further, we have demonstrated that very large sample sizes will be required for comprehensively identifying the independent alleles contributing to the missing heritability of RA.

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.

BACKGROUND: We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. METHODS: Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. RESULTS: The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. CONCLUSIONS: This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.