Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

Do All-terrain or Recreational Off-highway Vehicle Crashes Have a Higher Odds of Amputation?

BACKGROUND: Riding off-road vehicles is associated with the risk of injury to the extremities. There are two main types of four-wheel recreational off-road vehicles: quads or all-terrain vehicles (ATVs), which are essentially four-wheel off-road motorcycles, and recreational off-highway vehicles (ROVs), also colloquially referred to as utility terrain vehicles, which have side-by-side seating, higher maximum speeds, and a roll cage. There are multiple orthopaedic society position statements on ATVs, but none on ROVs. Perhaps this is because the injury patterns and differences between the two vehicles have not been elucidated. QUESTIONS/PURPOSES: (1) What patient, vehicle (ROVs versus ATVs), and injury factors are associated with amputation? (2) What are the anatomic location distributions of fractures and amputations by vehicle type? METHODS: Records of all patients in our hospital's billing system who had both a diagnostic code indicating an accident related to an off-road vehicle and one indicating an extremity or pelvic fracture between February 2014 and January 2020 were screened; this resulted in the identification of 328 patients with fractures resulting from off-road vehicle collisions. A total of 16% (51 of 328) of patients were excluded from the analysis because their injury did not involve either an ATV or an ROV; 277 patients were included in the final analysis. The following variables were collected: age at time of the injury, gender, BMI, vehicle type, Gustilo-Anderson type if applicable, amputation level if applicable, anatomic locations of injuries, ethanol level, and drug screen. ATV crashes accounted for 52% (145 of 277) of patients, and ROV crashes accounted for 48% (132 of 277). Patients from ATV crashes did not differ from those in ROV crashes in terms of mean age (24 ± 16 years versus 24 ± 13 years; p = 0.82), BMI (25 ± 7 kg/m 2 versus 26 ± 6 kg/m 2 ; p = 0.18), or gender (79% [114 of 145] men/boys versus 77% [102 of 132]; p = 0.79). Among patients who had a drug or ethanol screen, there was a higher percent of ATV riders who used marijuana (39% [19 of 49] versus 17% [7 of 42]; p = 0.04), but there were no differences in abnormal blood alcohol screen or abnormal nonmarijuana drug screen; however, these results were available in only about one-third of patients (99 of 277 for ethanol and 91 of 277 for drug screen). Statistical analysis was performed using logistic regression analysis for factors associated with amputation, with p values < 0.05 considered significant. RESULTS: After controlling for differences in demographic factors, the stepwise increase in Gustilo-Anderson grade of open fracture (OR 9.8 [95% CI 3.6 to 27.0]; p < 0.001) and ROV vehicle type (OR 15.7 [95% CI 3.6 to 68.5]; p < 0.001) were both associated with amputation. There was no increase in the odds of amputation associated with age (OR 1.0 [95% CI 0.9 to 1.1]; p = 0.81), gender (OR 1.4 [95% CI 0.3 to 5.8]; p = 0.68), or BMI (OR 1.1 [95% CI 0.9 to 1.2]; p = 0.37). The most frequent ATV fractures occurred in the forearm and wrist (22% [45 of 203]), whereas most ROV injuries occurred through the metacarpals (41% [107 of 262] of fractures and 58% [18 of 31] of amputations). CONCLUSION: ROV crashes are associated with a higher odds of amputation when compared with ATV crashes. Because most ROV injuries were in the forearm and below, this likely occurs when upper extremities are crushed and mangled under the roll cage in rollover ROV crashes. Because of this danger, we urge our orthopaedic societies to either update current ATV position statements to include ROVs or release separate statements on ROVs. LEVEL OF EVIDENCE: Level III, prognostic study.

Horizon scan: State-of-the-art therapeutics for psoriatic arthritis.

Psoriatic arthritis (PsA) is a common immune-mediated inflammatory disease (IMID) that can present with a heterogenous clinical phenotype. The advent of advanced therapies has substantially improved patient outcomes, but many patients still have suboptimal or unsustained response, resulting in morbidity, structural damage and functional impairment. There remains a need for better therapeutic options and precision medicine approaches to improve outcomes for patients with PsA. This review synthesises recently approved the state-of-the-art therapeutics for PsA, including inhibitors of IL-23, Janus kinase (JAK), tyrosine kinase 2 (TYK2) and dual-target IL-17A/F. The evidence base for emerging therapeutics, including MK-2 inhibitors, nano-IL-17 inhibitors, nanobodies and other dual-target therapies for PsA is also reviewed. Potential future therapeutic strategies and unmet research needs are discussed.

Mediation analysis to understand genetic relationships between habitual coffee intake and gout.

BACKGROUND: Increased coffee intake is associated with reduced serum urate concentrations and lower risk of gout. Specific alleles of the GCKR, ABCG2, MLXIPL, and CYP1A2 genes have been associated with both reduced coffee intake and increased serum urate in separate genome-wide association studies (GWAS). The aim of this study was to determine whether these single nucleotide polymorphisms (SNPs) influence the risk of gout through their effects on coffee consumption. METHODS: This research was conducted using the UK Biobank Resource. Data were available for 130,966 European participants aged 40-69 years. Gout status and coffee intake were tested for association with four urate-associated SNPs: GCKR (rs1260326), ABCG2 (rs2231142), MLXIPL (rs1178977), and CYP1A2 (rs2472297). Multiple regression and path analysis were used to examine whether coffee consumption mediated the effect of the SNPs on gout risk. RESULTS: Coffee consumption was inversely associated with gout (multivariate adjusted odds ratio (95% confidence interval (CI)) for any coffee consumption 0.75 (0.67-0.84, P = 9 × 10-7)). There was also evidence of a dose-effect with multivariate adjusted odds ratio (95% CI) per cup consumed per day of 0.85 (0.82-0.87, P = 9 × 10-32). The urate-increasing GCKR, ABCG2, MLXIPL, and CYP1A2 alleles were associated with reduced daily coffee consumption, with the strongest associations for CYP1A2 (beta -0.30, P = 8 × 10-40), and MLXIPL (beta -0.17, P = 3 × 10-8), and weaker associations for GCKR (beta -0.07, P = 3 × 10-10) and ABCG2 (beta -0.09, P = 2 × 10-9). The urate-increasing GCKR and ABCG2 alleles were associated with gout (multivariate adjusted p < 5 × 10-8 for both), but the urate-increasing MLXIPL and CYP1A2 alleles were not. In mediation analysis, the direct effects of GCKR and ABCG2 accounted for most of the total effect on gout risk, with much smaller indirect effects mediated by coffee consumption. CONCLUSION: Coffee consumption is inversely associated with risk of gout. Although alleles at several SNPs associate with both lower coffee consumption and higher risk of gout, these SNPs largely influence gout risk directly, rather than indirectly through effects on coffee consumption.

Global Non-Potential Magnetic Models of the Solar Corona During the March 2015 Eclipse.

Seven different models are applied to the same problem of simulating the Sun's coronal magnetic field during the solar eclipse on 2015 March 20. All of the models are non-potential, allowing for free magnetic energy, but the associated electric currents are developed in significantly different ways. This is not a direct comparison of the coronal modelling techniques, in that the different models also use different photospheric boundary conditions, reflecting the range of approaches currently used in the community. Despite the significant differences, the results show broad agreement in the overall magnetic topology. Among those models with significant volume currents in much of the corona, there is general agreement that the ratio of total to potential magnetic energy should be approximately 1.4. However, there are significant differences in the electric current distributions; while static extrapolations are best able to reproduce active regions, they are unable to recover sheared magnetic fields in filament channels using currently available vector magnetogram data. By contrast, time-evolving simulations can recover the filament channel fields at the expense of not matching the observed vector magnetic fields within active regions. We suggest that, at present, the best approach may be a hybrid model using static extrapolations but with additional energization informed by simplified evolution models. This is demonstrated by one of the models.

HaNDL syndrome: transient headache and neurological deficits with cerebrospinal fluid lymphocytosis.

We report the case of a 54-year-old woman with multiple presentations to the emergency department with severe headache, transient variable neurological deficits and normal investigations aside from CSF lymphocytosis. This represents a rare but under-diagnosed condition, transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome. HaNDL is an important differential diagnosis for headache. We summarise the current knowledge about its clinical course, diagnosis and typical investigation findings.

Exercise-induced rhabdomyolysis.

We report the case of a 34 year-old man who developed exercise-induced rhabdomyolysis after unaccustomed high-intensity exercise. Subclinical rhabdomyolysis is common after heavy exercise, yet it is uncommon for patients to seek medical advice. The presentation is variable and despite potentially life-threatening complications the diagnosis may be easily missed by patients and healthcare professionals. A high-index of suspicion is critical to avoid missing the diagnosis. We summarise the current knowledge, clinical course, complications and management of exercise-induced rhabdomyolysis.

Composite paradigms in medicine: analysing Gillies' claim of reclassification of disease without paradigm shift in the case of Helicobacter pylori.

Since the publication of Kuhn's The Structure of Scientific Revolutions in 1962, the notion of paradigms has shaped the way that philosophy views scientific discovery and how changes in what is regarded as empirical fact occur. This drew heavily on examples from the history of the natural sciences to support Kuhn's hypothesis. However, some argue that medicine is different from the natural sciences. Gillies has proposed another theory of how paradigms apply to medicine; that of composite paradigms. In doing so, Gillies uses the example of Helicobacter pylori and the shift from the excess-acid theory to the current bacterial-infection theory of gastric ulcers to illustrate these fundamental differences between medicine and the natural sciences. Upon analysis of Gillies' claim, it is evident that traditional Kuhnian paradigms are also composite and that the manner in which Gillies proposes disease is classified is insufficient in describing medicine. Furthermore, new local paradigms are demonstrably introduced and the change was accompanied by many of the markers of paradigmatic change including changes in worldview, resistance, incommensurability and the introduction of new questions that could not have existed under the previous paradigm. Whilst this change may not be on the scale of the Chemical revolution, it can still be considered paradigm shift. Thagard also proposes an alternate view of discovery using the case of H. pylori. This has much in common with Kuhnian paradigms but Thagard's theory offers further elucidation and refinement. This allows it to better characterise all of the associated features of discovery relevant in the case of H. pylori, thus provides a preferable tool for examination of this important recent discovery.