Multimodal prehabilitation in patients with non-small cell lung cancer: a feasibility study.

Background: Anatomic pulmonary resection is the preferred curative treatment in operable non-small cell lung cancer (NSCLC) but is associated with postoperative complications and inevitable compromise in functional capacity. Preoperative enhancement of functional capacity can be achieved with prehabilitation, yet the window of opportunity in NSCLC patients is small because patients are required to undergo surgery within 3 weeks from diagnosis. The goal of this study was to assess the feasibility of a prehabilitation programme in NSCLC within a 3-week timeframe and its effect on functional capacity-although the study was not powered to confirm improvements in functional capacity. Methods: Prehabilitation consisted of six interventions: exercise programme, nutritional support, mental support, smoking cessation, patient empowerment, and optimisation of respiratory status and was executed in two large teaching hospitals in the Netherlands. Assessments were scheduled at baseline (T0), end of program preoperatively (T1), and 6 weeks postoperatively (T2). Feasibility was defined as ≥80% of participants completing ≥80% of the programme. Functional capacity [6-minute walk test (6MWT), steep ramp test (SRT), one repetition maximum (1RM), maximal inspiratory pressure (MIP), and hand grip strength (HGS)] was evaluated on T1 and T2 compared to T0 using mixed model analyses. Results: In total, 24 patients were included. In 95.8% of patients, the program proved feasible and preoperative functional capacity significantly improved in all pre-specified tests on T1. 1RM sustained improved at T2. Conclusions: Multimodal prehabilitation for lung surgery is feasible within a timeframe of 3 weeks. Even though this study was not powered to confirm it, prehabilitation may improve preoperative functional capacity.

Reasons Patients With Primary Progressive Multiple Sclerosis Contact Their Specialist Nurses.

BACKGROUND: Questions asked by patients with primary progressive multiple sclerosis (PPMS) during patient-initiated MS nurse consultations may contain salient information that can help health care providers understand their needs, which, in turn, can help tailor counseling and treatment. METHODS: Records of all patients with PPMS visiting the MS center of a large teaching hospital in the Netherlands between January 2007 and January 2021 were studied retrospectively. Number and type (scheduled or patient initiated) of MS nurse consultations, reasons for consultations (in prespecified categories), and frequency of subsequent referrals were registered. Association between factors (living with partner, Expanded Disability Status Scale score, comorbidities, age, sex) and number of patient-initiated consultations was studied using negative binomial regression analysis. RESULTS: In total, 98 patients with PPMS were included, with 720 MS nurse consultations during follow-up (median duration, 8.1 years), of which 274 (38%) were patient initiated. Patients had a broad spectrum of reasons to contact MS nurses. The most common categories were treatment (36%) and micturition and defecation (31%). Patients living without a partner (incidence rate ratio, 2.340; 95% CI, 1.057-5.178) and male patients (incidence rate ratio, 1.890; 95% CI, 0.925-3.861) consulted MS nurses more frequently. The MS nurses made 146 referrals (20% of all contacts); 59 were after patient-initiated consultation (22%). The most frequent referrals were to neurologists, urologists, and rehabilitation specialists. CONCLUSIONS: Multiple sclerosis nurses have a pivotal role in PPMS care, especially for patients living without a partner and male patients. Recurring questions about (new) treatment options illustrate the pressing need for highly effective treatment. Micturition and defecation problems are also a considerable concern and warrant close monitoring.

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study.

BACKGROUND: The preoperative period can be used to enhance a patient's functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme. METHODS: The multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes. DISCUSSION: Since the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients. TRIAL REGISTRATION: The current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080 . Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial.

OBJECTIVES: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. METHODS: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. RESULTS: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. CONCLUSION: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition.

Good construct validity of the CT Syndesmophyte Score (CTSS) in patients with radiographic axial spondyloarthritis.

OBJECTIVES: To assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis. METHODS: Low-dose CT and conventional radiography (CR) were performed at baseline and 2 years. CT was assessed with CTSS by two readers and CR with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by three readers. Two hypotheses were tested: (1) syndesmophytes scored with CTSS are also detected with mSASSS at baseline or 2 years later; (2) CTSS is non-inferior to mSASSS in correlations with spinal mobility measures. Presence of a syndesmophyte was determined per reader per corner for all anterior cervical and lumbar corners on CT at baseline and CR at baseline and 2 years. Correlations of CTSS and mSASSS with six spinal/hip mobility measurements plus Bath Ankylosing Spondylitis Metrology Index (BASMI) were tested. RESULTS: Data from 48 patients (85% male, 85% HLA-B27+, mean age 48 years) were available for hypothesis 1 and 41/48 were available for hypothesis 2. At baseline, syndesmophytes were scored with CTSS in 348 (reader 1, 38%) and 327 (reader 2, 36%) corners out of 917. Of these, depending on reader pairs, 62%-79% were also seen on CR at baseline or after 2 years. CTSS correlated well (rs 0.46-0.73), and with higher correlation coefficients than mSASSS (rs 0.34-0.64), with all spinal mobility measures and BASMI. CONCLUSIONS: The good agreement between syndesmophytes detected by CTSS and mSASSS and the strong correlation of CTSS with spinal mobility support the construct validity of the CTSS.

Starting Home Telemonitoring and Oxygen Therapy Directly after Emergency Department Assessment Appears to Be Safe in COVID-19 Patients.

BACKGROUND: Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many advantages, we evaluated these parameters in this study. METHODS: All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups. RESULTS: 278 patients were included (n = 65 ED group, n = 213 admission group). ED group: 23.8% (n = 15) was reassessed, 15.9% (n = 10) was admitted and 7.7% (n = 5) ICU admitted. Admission group: 15.8% (n = 37) was reassessed, 6.5% (n = 14) was readmitted and 2.4% (n = 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7-13) days; the total duration of home telemonitoring was 14 (IQR 9-18) days. Admission group: duration of oxygen therapy was 10 (IQR 6-16) days; total duration of home telemonitoring was 14 (IQR 10-20) days. CONCLUSION: it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.

Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis.

OBJECTIVES: To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth. METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development. RESULTS: Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36-0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73-2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation. CONCLUSIONS: VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes.

Associations between syndesmophytes and facet joint ankylosis in radiographic axial spondyloarthritis patients on low-dose CT over 2 years.

OBJECTIVES: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion. METHODS: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects. RESULTS: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses. CONCLUSIONS: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA.

Facet joint ankylosis in r-axSpA: detection and 2-year progression on whole spine low-dose CT and comparison with syndesmophyte progression.

OBJECTIVES: To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (ldCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression of facet joint ankylosis and syndesmophytes. METHODS: Patients with r-axSpA from the Sensitive Imaging in Ankylosing Spondylitis (SIAS) cohort underwent ldCT at baseline (n = 60) and 2 years (n = 53). Facet joints (right and left, levels C2-S1) were scored as ankylosed, not ankylosed or unable to assess. Joints that were frequently poorly visible (>15% missing), were excluded. Inter-reader reliability on the patient level was assessed with intraclass correlation coefficients (ICCs) and smallest detectable change (SDC). Ankylosis was assessed at joint level and patient level for both timepoints. Syndesmophytes were assessed with CT syndesmophyte score. RESULTS: Levels C5-T2 were difficult to assess and excluded from all further analyses. Facet joint ICCs were good to excellent for status scores (0.72-0.93) and poor to excellent for progression scores (0.10-0.91). Facet joint ankylosis was detected at every level but most frequently in the thoracic joints. In total, 48% of patients showed 2-year progression. Most progression occurred in the thoracic segment. Using SDCs as cutoff, 18% of patients had progression of facet joint ankylosis only, whereas 20% of patients had progression of syndesmophytes only. CONCLUSION: This is the first study evaluating facet joints in the whole spine by ldCT in r-axSpA. Facet joint ankylosis was detected most often in the thoracic spine. Assessing facet joints in addition to syndesmophytes detected substantially more patients with damage progression over two years.

Wide Variation in Perioperative Care in Anatomical Lung Resections in the Netherlands: A National Survey.

This study aimed to describe perioperative care after anatomical lung resection in the Netherlands, before publication of Enhanced Recovery After Surgery/European Society of Thoracic Surgeons (ERAS/ESTS) guidelines in 2019. An online survey was sent to all 43 Dutch lung surgical centers in December 2017, addressing topics in the 4 phases of perioperative care (preoperative, admission, perioperative, postoperative). Respondents were requested to report care that would be delivered to a standardized patient without perioperative complications. To compare current care with ERAS/ESTS guidelines, we assigned an ERAS/ESTS score per hospital, weighted for evidence level per recommendation. Higher scores indicate higher application of recommendations. Response rate of centers was 100%, median response rate per question was 98% (interquartile range 94-100). Some perioperative recommendations are commonly applied (>85%), such as minimally invasive surgery and regional anesthesia; others, such as admission carbohydrate drinks, are not (<35%). Wide variation was observed regarding patient counselling, pre- and postoperative admission logistics, anemia correction, fluid management, pain management, and chest drain management. Median 62% (interquartile range 53%-72%) of the maximum ERAS/ESTS score was achieved. Large variation in ERAS/ESTS score between hospitals were found in all phases (preoperative: 6.0 [6.5-10.5] points, admission: 5.0 [1.0-6.0] points, perioperative: 21.5.0 [16.0-22.5] points, postoperative: 8.0 [5.0-8.5] points). Large variation exists in perioperative care after anatomical lung resection in the Netherlands. Given previously published data linking variation in perioperative care to variation in outcomes, standardization of perioperative care in lung surgery, preferably based on the ERAS/ESTS guidelines, may be warranted but requires further study.

What is the value of musculoskeletal ultrasound in patients presenting with arthralgia to predict inflammatory arthritis development? A systematic literature review.

OBJECTIVE: Musculoskeletal ultrasound (US) is frequently used in several rheumatology practices to detect subclinical inflammation in patients with joint symptoms suspected for progression to inflammatory arthritis. Evaluating the scientific basis for this specific US use, we performed this systematic literature review determining if US features of inflammation are predictive for arthritis development and which US features are of additive value to other, regularly used biomarkers. METHODS: Medical literature databases were systematically searched up to May 2017 for longitudinal studies reporting on the association between greyscale (GSUS) and Power Doppler (PDUS) abnormalities and inflammatory arthritis development in arthralgia patients. Quality of studies was assessed by two independent reviewers using a set of 18 criteria. Studies were marked high quality if scored ≥ 80.6% (which is the median score). Best-evidence synthesis was performed to determine the level of evidence (LoE). Positive and negative likelihood ratios (LR+, LR-) were determined. RESULTS: Of 3061 unique references, six fulfilled inclusion criteria (three rated high quality), of which two reported on the same cohort. Heterogeneity in arthralgia populations, various US machines and scoring systems hampered the comparability of results. LoE for GSUS as predictor was limited and moderate for PDUS; LoE for the additive value of GSUS and PDUS with other biomarkers was limited to moderate. Estimated LR+ values were mostly < 4 and LR- values > 0.5. CONCLUSIONS: Data on the value of GSUS and PDUS abnormalities for predicting inflammatory arthritis development are sparse. Although a potential benefit is not excluded, current LoE is limited to moderate. Future studies are required, preferably performed in clearly defined, well-described arthralgia populations, using standardized US acquisition protocols and scoring systems.

Increase In Il-31 Serum Levels Is Associated With Reduced Structural Damage In Early Axial Spondyloarthritis.

In spondyloarthritis, little is known about the relation between circulating cytokines and patient phenotype. We have quantified serum levels of T helper type 1 cell (Th1), Th2 and Th17 cytokines in patients with recent-onset axial spondyloarthritis (AxSpA) from the DESIR cohort, a prospective, multicenter French cohort consisting of 708 patients with recent-onset inflammatory back pain (duration >3 months but <3 years) suggestive of AxSpA. Serum levels of Th1, Th2, and Th17 cytokines were assessed at baseline in patients from the DESIR cohort fulfilling the ASAS criteria (ASAS+) and were compared with age- and sex-matched healthy controls. At baseline, ASAS+ patients (n = 443) and healthy controls (n = 79) did not differ in levels of most of the Th1, Th2 and Th17 cytokines except for IL-31, and sCD40L, which were significantly higher for ASAS+ patients than controls (p < 0.001 and p = 0.012, respectively). On multivariable analysis of ASAS+ patients, IL-31 level was associated with sCD40L level (p < 0.0001), modified Stoke AS Spine Score (mSASSS) < 1 (p = 0.035). The multivariable analyses showed that IL-31 was an independent factor associated with mSASSS < 1 (p = 0.001) and low bone mineral density (p = 0.01). Increased level of IL-31 might protect against structural damage but is also related to low BMD.

Impact of replacing radiographic sacroiliitis by magnetic resonance imaging structural lesions on the classification of patients with axial spondyloarthritis.

OBJECTIVES: To investigate in patients with chronic back pain of a short duration, the utility of adding structural MRI lesions of the SI joints to the imaging criterion of the Assessment of SpondyloArthritis International Society (ASAS) axial SpA (axSpA) criteria and the utility of replacement of radiographic sacroiliitis by structural MRI lesions. METHODS: MRI STIR (inflammation, MRI-SI), MRI T1-weighted images (structural lesions, MRI-SI-s) and radiographs of the SI joints of patients in the SPondyloArthritis Caught Early-cohort (chronic back pain: ⩾3 months, ⩽2 years; onset <45 years) were scored by two well-calibrated readers. Previously proposed cut-offs for a positive MRI-SI-s were used (based on <5% prevalence in no-SpA patients): erosions ⩾3, fatty lesions ⩾3, fatty lesions and/or erosions (erosions/fatty lesions) ⩾5. Using the definitions of MRI-SI-s, patients were classified according to the ASAS axSpA criteria. RESULTS: Twenty-nine of 294 patients were modified New York (mNY) positive and 32 were MRI-SI-s positive (erosions/fatty lesions ⩾5). Agreement between mNY and MRI-SI-s (erosions/fatty lesions ⩾5) was moderate (κ: 0.58). Using the erosions/fatty lesions ⩾5 cut-off, 3/294 additional patients were classified as axSpA (adding MRI). Using this cut-off instead of mNY (replacing mNY), classification did not change in 286 patients (97.3%), but 5 patients (1.7%) would not be classified as axSpA and 3 previously unclassified patients (1.0%) would be classified as axSpA. Similar results were seen for the other cut-offs (erosions ⩾3 and fatty lesions ⩾3). CONCLUSION: Assessment of structural lesions (fatty lesions and erosions) on MRI-SI instead of or in addition to conventional radiographs does not lead to a different ASAS axSpA classification in most of the patients with early disease onset. This suggests that structural lesions (fatty lesions and erosions) can be reliably used in the ASAS axSpA classification of patients, as both addition and replacement of radiographs of the SI joints.

Low-dose CT detects more progression of bone formation in comparison to conventional radiography in patients with ankylosing spondylitis: results from the SIAS cohort.

OBJECTIVES: To compare the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) with the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) for conventional radiographs (CR) in patients with ankylosing spondylitis (AS). METHODS: Patients with AS in the Sensitive Imaging in Ankylosing Spondylitis cohort had lateral cervical and lumbar spine CR and whole spine ldCT at baseline and 2 years. CR and ldCT images were scored by two readers, paired by patient, blinded to time order, per imaging modality. For the total score analysis, we used average scores of readers per corner on CR or quadrant on ldCT. For the syndesmophyte analysis we used individual reader and consensus scores, regarding new or growing syndesmophyte at the same corner/quadrant. RESULTS: 50 patients were included in the syndesmophyte analysis and 37 in the total score analysis. Mean (SD) status scores for mSASSS (range 0-72) and CTSS (range 0-552) at baseline were 17.9 (13.8) and 161.6 (126.6), and mean progression was 2.4 (3.8) and 17.9 (22.1). Three times as many patients showed new or growing syndesmophytes at ≥3 quadrants on ldCT compared with ≥3 corners on CR for individual readers; for consensus this increased to five times. In 50 patients, 36 new or growing syndesmophytes are seen on CR compared with 151 on ldCT, most being found in the thoracic spine. CONCLUSIONS: ldCT, covering the whole spine, detects more progression in the form of new and growing syndesmophytes in patients with AS compared with CR, which is limited to the cervical and lumbar spine. Most progression occurred in the thoracic spine.

Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort.

OBJECTIVES: To develop the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) to assess structural damage in the spine of patients with ankylosing spondylitis (AS) and test its reliability. METHODS: Patientswith AS in the SIAS cohort had whole spine ldCT at baseline and 2 years. Syndesmophytes were scored in coronal and sagittal planes in eight quadrants per vertebral unit (VU) as absent=0, <50% of the intervertebral disc space (IDS)=1, ≥50%=2 or bridging the IDS=3 (range 0-552). Images were scored by two readers, paired by patient, blinded to time order. Whole spine and spinal segment status and change scores were calculated. Inter-reader reliability was assessed by intraclass correlation coefficient (ICC), smallest detectable change (SDC) and frequency of scores per VU. RESULTS: 49 patients (mean age 50 years (SD 9.8), 84% men, 88% human leucocyte antigen B27 positive) were included. Mean (SD) scores of reader 1 were: whole spine baseline status score 163 (126) and change score 16 (21), spinal segment baseline status scores 30 (41), 97 (77) and 36 (36) and change scores 2 (7), 12 (18) and 3 (4) for the cervical, thoracic and lumbar spine, respectively. Scores of reader 2 were similar. Whole spine status score ICC was 0.99 and 0.97-0.98 for spinal segments. Whole spine change score ICC was 0.77 and 0.32-0.75 for spinal segments. Whole-spine SDC was 14.4. Score distribution pattern per VU was similar between readers. CONCLUSIONS: Using the CTSS, new bone formation in the spine of patients with AS can be assessed reliably. Most progression was seen in the thoracic spine.

Similar short-term clinical response to high-dose versus low-dose methotrexate in monotherapy and combination therapy in patients with rheumatoid arthritis.

BACKGROUND: Aiming at rapid decrease of disease activity, there has been a trend to start with higher doses of methotrexate (MTX) in patients newly diagnosed with rheumatoid arthritis (RA), both as monotherapy and in combination with other antirheumatic drugs. We aimed to study the relationship between clinical response and MTX dose as monotherapy or combination therapy in patients with early RA. METHODS: Disease-modifying anti-rheumatic drug (DMARD)-naive patients with early RA, from a large international observational database, the METEOR database, were selected if MTX was part of their initial treatment. Patients were divided into four groups: MTX monotherapy, MTX + convention synthetic (cs)DMARDs, MTX + glucocorticoids or MTX + biologic (b)DMARDs. MTX dose was dichotomized: low dose ≤10 mg/week; high dose ≥15 mg/week. Linear mixed model analyses for the Disease Activity Score (DAS), DAS in 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were performed in each medication group, with MTX dose and time as covariates. Outcomes were assessed from baseline until 3-6 months follow up. Associations were adjusted for potential confounding by indication using propensity score (PS) modelling. RESULTS: For patients starting MTX monotherapy (n = 523), MTX + csDMARDs (n = 266) or MTX + glucocorticoids (n = 615), the PS-adjusted effects of MTX dose (high versus low) on the DAS, DAS28 and HAQ were small and not clinically meaningful. Patients starting MTX + bDMARDs were disregarded due to low numbers (n =11). CONCLUSIONS: In patients newly diagnosed with RA, no clinical benefit of high compared to low initial MTX doses was found for MTX monotherapy or for MTX combination therapy with csDMARDs or glucocorticoids.

Computer-aided evaluation of inflammatory changes over time on MRI of the spine in patients with suspected axial spondyloarthritis: a feasibility study.

BACKGROUND: Evaluating inflammatory changes over time on MR images of the spine in patients with suspected axial Spondyloarthritis (axSpA) can be a labor-intensive task, requiring readers to manually search for and perceptually align a set of vertebrae between two scans. The purpose of this study was to assess the feasibility of computer-aided (CA) evaluation of such inflammatory changes in a framework where scans from two time points are fused into a single color-encoded image integrated into an interactive scoring tool. METHODS: For 30 patients from the SPondyloArthritis Caught Early (SPACE) cohort (back pain ≥ 3 months, ≤ 2 years, onset < 45 years), baseline and follow-up MR scans acquired 9-12 months apart were fused into a single color-encoded image through locally-rigid image registration to evaluate inflammatory changes in 23 vertebral units (VUs). Scoring was performed by two expert readers on a (-2, 2) scale using an interactive scoring tool. For comparison of direction of change (increase/decrease) indicated by an existing reference, Berlin method scores ((-3, 3) scale) of the same MR scans from a different ongoing study were used. The distributions of VU-level differences between CA readers and between the CA and Berlin methods (sign of change scores) across patients were analyzed descriptively. Patient-level agreement between CA readers was assessed by intraclass correlation coefficient (ICC). RESULTS: Five patients were excluded from evaluation due to failed vertebrae segmentation. Patient-level inter-reader agreement ICC was 0.56 (95% CI: 0.22 to 0.78). Mean VU-level inter-reader differences across 25 patients ranged (-0.04, 0.12) with SD range (0, 0.45). Across all VUs, inter-reader differences ranged (-1, 1) in 573/575 VUs (99.7%). Mean VU-level inter-method differences across patients ranged (-0.04, 0.08) with SD range (0, 0.61). Across all VUs, inter-method differences ranged (-1, 1) in 572/575 VUs (99.5%). CONCLUSIONS: Fusion of MR scans of the spine from two time points into a single color-encoded image allows for direct visualization and measurement of inflammatory changes over time in patients with suspected axSpA.

The yield of a positive MRI of the spine as imaging criterion in the ASAS classification criteria for axial spondyloarthritis: results from the SPACE and DESIR cohorts.

OBJECTIVES: To assess the prevalence of spinal inflammation on MRI in patients with chronic back pain (CBP) of maximally 3 years duration and to evaluate the yield of adding a positive MRI-spine as imaging criterion to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). METHODS: Baseline imaging of the sacroiliac joints (X-SI), MRI of the sacroiliac joints (MRI-SI) and MRI-spine were scored by ≥2 experienced central readers per modality in the SPondyloArthritis Caught Early (SPACE) and DEvenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohorts. Inflammation suggestive of axSpA was assessed in the entire spine. A positive MRI-spine was defined by the presence of ≥5 inflammatory lesions. Alternative less strict definitions were also tested. RESULTS: In this study, 541 and 650 patients with CBP from the SPACE and DESIR cohorts were included. Sacroiliitis on X-SI and MRI-SI was found in 40/541 (7%) and 76/541 (14%) patients in SPACE, and in DESIR in 134/650 (21%) and 231/650 (36%) patients, respectively. In SPACE and DESIR, a positive MRI-spine was seen in 4/541 (1%) and 48/650 (7%) patients. Of the patients without sacroiliitis on imaging, 3/447 (1%) (SPACE) and 8/382 (2%) (DESIR) patients had a positive MRI-spine. Adding positive MRI-spine as imaging criterion led to new classification in only one patient in each cohort, as the other patients already fulfilled the clinical arm. Other definitions of a positive MRI-spine yielded similar results. CONCLUSION: In two cohorts of patients with CBP with a maximum symptom duration of 3 years, a positive MRI-spine was rare in patients without sacroiliitis on MRI-SI and X-SI. Addition of MRI-spine as imaging criterion to the ASAS axSpA criteria had a low yield of newly classified patients and is therefore not recommended.

Sacroiliac radiographic progression in recent onset axial spondyloarthritis: the 5-year data of the DESIR cohort.

OBJECTIVE: To estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression. METHODS: X-SIJ and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations. RESULTS: In 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients. CONCLUSIONS: Five-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.