Patient-reported outcomes after free muscle flap coverage for therapy-resistant neuropathic pain from the ulnar nerve.

Extensive microsurgical neurolysis followed by free gracilis muscle flap coverage can be performed as a last resort for patients with persistent neuropathic pain of the ulnar nerve. All patients who had this surgery between 2015 and 2021 were identified. Data were collected from the medical records of 21 patients and patient-reported outcomes were collected from 18 patients, with a minimum follow-up of 12 months. The median visual analogue pain score decreased significantly 8 months postoperatively from 8.0 to 6.0 and stabilized to 5.4 at the 3-year follow-up. Health-related quality-of-life scores remained diminished compared to normative data. In the treatment of therapy-resistant neuropathic pain of the ulnar nerve, extensive neurolysis with a subsequent free gracilis muscle flap coverage shows a promising reduction of pain that persists at long-term follow-up.Level of evidence: IV.

Sonographic normal values for the cross-sectional area of the ulnar nerve: a systematic review and meta-analysis.

PURPOSE: Nerve size is a commonly used sonographic parameter when assessing suspected entrapment of the ulnar nerve. We aimed to create a robust set of normal values, based on a critical review of published normal values. METHODS: We performed a systematic evaluation of studies on normal ulnar nerve sizes, identified in PubMed, Embase, and Cochrane databases. Using meta-analyses, we determined pooled mean cross-sectional area (CSA) values for different anatomical locations of the ulnar nerve throughout the arm. Subgroup analyses were performed for gender, probe frequency, in- or exclusion of diabetic patients, position of the elbow and Asian versus other populations. RESULTS: We identified 90 studies of which 77 studies were included for further analyses after quality review, resulting in data from 5772 arms of 3472 participants. Subgroup analyses show lower CSA values at at the wrist crease and proximal to the wrist crease when using low frequency probes (< 15 MHz) and at the wrist crease, proximal to the wrist crease, proximal forearm and the distal upper arm in Asians. CSA values were lower when in flexed position compared to extended position for the cubital tunnel inlet only. No difference was found for gender. CONCLUSIONS: Our systematic review provides a comprehensive set of normal values at sites along the entire length of the ulnar nerve. This provides a foundation for clinical practise and upon which future studies could be more systematically compared.

The diagnostic role of ultrasound in cubital tunnel syndrome for patients with a previous cubital tunnel surgery.

BACKGROUND: Ultrasound is widely used in the diagnosis of peripheral nerve compressions. Nevertheless, the role of ultrasound, and in particular the cross-sectional area (CSA) measurements, in the diagnosis of cubital tunnel syndrome (CuTS) is debatable, especially in patients who have had previous surgeries. We evaluated the diagnostic value of ultrasound and CSA measurements in a heterogenous group of CuTS patients suffering from persisting or recurrent CuTS after a previous surgical intervention. METHODS: All patients with persisting or recurrent CuTS after previous surgery, who received a nerve ultrasound with or without CSA measurements in a tertiary referral center between 2015 and 2022, were included. Median CSA was calculated at five locations from the upper arm to the wrist. The sensitivity of ultrasound and electrodiagnostic studies and the correlation between both diagnostic tools were calculated. RESULTS: Thirty-seven nerves from 35 patients who received nerve ultrasound, of which 21 nerves from 19 patients who received additional CSA measurements, were included. Ultrasound indicated signs of persisting or recurrent compression in 73.0% of patients, and ulnar swelling based on CSA measurements was found in 71.4% of patients. Electrodiagnostic testing was positive in 40.7% of patients. CuTS diagnosis was supported by both electrodiagnostic studies and CSA in only 34.6% of patients. CONCLUSIONS: CSA and electrodiagnostic testing in patients with persistent or recurrent symptoms after previous surgery did not correlate well, and the sensitivity of both tests was lower than in diagnostic accuracy studies. Ultrasound was found to be useful in evaluating ulnar nerves after previous surgery.

Submuscular transposition of the ulnar nerve for persistent or recurrent cubital tunnel syndrome: Results of a prospective case series.

BACKGROUND: Submuscular transposition (SMT) of the ulnar nerve is frequently performed as secondary procedure in patients with persistent or recurrent cubital tunnel syndrome (CuTS) despite previous surgery. Good results have been reported for this surgical strategy, but mainly in small retrospective case series. The goal of the present study is therefore to analyze the results prospectively using a patient-reported outcome measure (PROM): patient-rated ulnar nerve evaluation (PRUNE). METHODS: SMT of the ulnar nerve was performed in 30 consecutive patients who were referred because of persistent or recurrent CuTS despite previous surgery. Objective outcome was measured in the outpatient clinic using the Likert scale. The PRUNE questionnaire was obtained pre-operatively, 6 weeks, 3 months, 6 months, and 12 months after the surgery. Simultaneously, 20 patients with primary surgery for CuTS, that underwent simple decompression, were followed. RESULTS: Good outcome (Likert 1 or 2) was obtained in 67% after SMT for persistent/recurrent CuTS and 85% after decompression as primary surgical treatment. PRUNE scores were significantly decreased in both groups at all follow-up moments after surgery compared with pre-operative for the total questionnaire and subscales "pain," "sensory/motor symptoms," and "specific activities." In both groups, PRUNE score remained stable until 12 months of follow-up. CONCLUSION: This prospective study confirms previous results from retrospective studies showing that SMT is an effective surgical option for persistent or recurrent CuTS. Prospective (randomized controlled) trials are needed to compare the effectiveness of SMT to the surgical alternative of subcutaneous transposition of the ulnar nerve.

Extra-articular findings with FDG-PET/CT in rheumatoid arthritis patients: more harm than benefit.

Objective: Whole-body PET with CT scanning using 18F-fluorodeoxyglucose (18F-FDG) is used occasionally in RA patients to detect arthritis. FDG-PET/CT might also detect malignancies, but the amount of incidental findings and the number of relevant malignant diseases that could be missed are currently unknown. We aimed to study the malignancy screening performance of whole-body FDG-PET/CT in longstanding RA patients with low disease activity. Methods: FDG-PET/CT scanning was done in the intervention arm of the Dose REduction Strategy of Subcutaneous TNF-inhibitors (DRESS) study, a randomized controlled trial on dose-tapering of biological DMARDs. The reference standard was clinical diagnosis of malignancy during the 3-year follow-up period of the study. Prevalence of extra-articular abnormalities, follow-up and treatments were summarized post hoc. Results: One hundred and twenty-one scans were carried out in 79 patients. Extra-articular abnormalities were found in 59 of 121 (49%) scans, resulting in additional diagnostic procedures in 21 of 79 (26.6%) patients. Nine patients (7.4%) were suspected of malignancy; none turned out to be malignant. Six clinical malignancies that developed during follow-up were all negative on baseline FDG-PET/CT. Conclusion: Whole-body FDG-PET/CT scanning used in RA patients for imaging of arthritis results in frequent incidental extra-articular findings, whereas some who apparently had normal scans also developed malignancies. Trial registration: Netherlands Trial Register, www.trialregister.nl, NL6771.

The nerve supply to the pectoralis major: An anatomical study and clinical application of the denervation in subpectoral breast implant surgery.

BACKGROUND: Using the subpectoral approach, animation deformity or breast distortion due to pectoralis muscle contraction is common. Although the anatomy of the pectoral nerves has been extensively studied, only few studies have related the location of these nerves to bony landmarks. OBJECTIVE: Our aim is to clarify the anatomy and possible variations of the innervation of the pectoralis major in relation to bony landmarks useful for surgery and to identify the preferred level for (selective) denervation by 1) transecting the nerves and 2) splitting the muscle in subpectoral breast implant surgery in cadavers. METHODS: Fourteen pectoral regions (both left and right side) were dissected on 7 formaldehyde-fixed cadavers. The origin, locations, and course were mapped and (distances to) landmarks were reported. RESULTS: The lateral pectoral nerve, medial pectoral nerve, and ansa pectoralis were identified in all cadavers. Nerve branches pierce the pectoralis minor or run along its upper or lower border. The piercing nerves vary from one to three branches and were consistently located lateral to the midclavicular line. The horizontal and vertical distances to bony landmarks varied greatly and depended on the size and location of the pectoralis minor, except for the nerve running along the upper border of the PMin, which was located consistently around 30% of the clavicular line from the acromioclavicular joint to the sternoclavicular joint. CONCLUSION: We were unable to define a fixed landmark to mark pre- or peroperatively. However, we could define guidelines that help to identify and excise or preserve nerves of interest.

Polymyalgia rheumatica patients with and without elevated baseline acute phase reactants: distinct subgroups of polymyalgia rheumatica?

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterised by pain and stiffness of neck, shoulder- and hipgirdle, typically with elevated acute phase reactants (APR). However, patients may present with normal APR. Our aim was to explore whether normal APR were due to 1) 'caught early in the disease', 2) misdiagnosis, or 3) a distinct subset of PMR with different clinical presentation and prognosis. METHODS: This was a retrospective cohort study on patients with clinical PMR diagnosis visiting the rheumatologists of the Sint Maartenskliniek from April 2008 to September 2017. RESULTS: Of 454 patients, 62 patients had normal, and 392 elevated APR. Normal APR patients had longer symptom duration before diagnosis (13 vs. 10 weeks; p=0.02), however, during follow-up 31% developed elevated APR. In elevated APR patients with previous APR data available while already symptomatic, 58% had earlier normal APR. Fewer normal APR patients had peripheral arthritis (2% vs. 9%;p=0.04), and anaemia (17% vs. 43%; p=0.001). More often they had a previous PMR diagnosis (16% vs. 8%; p=0.057) and a shorter median time to glucocorticoid-free remission (552 vs. 693 days; n=36 vs. 160; p=0.02). Route of GC administration differed between groups (p=0.026). Fewer patients received methotrexate; 3 vs. 12%; p=0.046). No difference in alternative diagnosis was observed. CONCLUSIONS: PMR patients with long-term normal APR seem to be a milder subset of PMR in clinical presentation and prognosis. Additionally, our data also suggest there is a subgroup with normal APR who are caught early in the disease. Misdiagnosis does not appear to play a role.

Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial.

BACKGROUND: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. METHODS: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. DISCUSSION: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. TRIAL REGISTRATION: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).

The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis: a systematic literature review.

The effect of TNF-α inhibitors (TNFi), with or without concomitant NSAIDs, on radiographic progression in axial SpA remains unclear. Therefore, we performed a systematic literature review up to January 2019 to determine whether longer use of standard dose TNFi is superior vs lower duration or lower dose TNFi therapy, conventional synthetic DMARDs alone, or no therapy in inhibiting radiographic progression in patients with axial SpA. Our search yielded 373 titles of which 14 full text articles and five abstracts were eligible for quantitative analysis. Studies had an overall moderate to critical risk of bias. Data could not be pooled due to clinical and methodological heterogeneity. Individual studies showed conflicting results with mainly no significant difference in radiographic progression when comparing effect of TNFi therapy to no TNFi therapy or when comparing to less TNFi therapy until 2 years of follow-up. Results that are more significant are shown after 2 years' follow-up, mainly in subgroups with baseline syndesmophytes. Data on the additional or synergistic effect of concomitant NSAID use were inconclusive.

Patient Acceptable Symptom State in Knee Osteoarthritis Patients Succeeds Across Different Patient-reported Outcome Measures Assessing Physical Function, But Fails Across Other Dimensions and Rheumatic Diseases.

OBJECTIVE: The aims of this study are (1) to establish the Patient Acceptable Symptom State (PASS) cutoff values of different patient-reported outcome measures (PROM) assessing physical function in patients with knee osteoarthritis (OA), and (2) to assess the influence of sex, age, duration of symptoms, and presence of depressive feelings on being in PASS. METHODS: Patients fulfilling the clinical American College of Rheumatology knee OA criteria received standardized nonsurgical treatment and completed different questionnaires at baseline and 3 months assessing physical function: Knee Injury and Osteoarthritis Outcome Score, Lequesne Algofunctional Index, Lower Extremity Functional Scale, numerical rating scale, and the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index. PASS values were defined as the 75th percentile of the score of questionnaires for those patients who consider their state acceptable. RESULTS: Of the 161 included patients, 62% were women with a mean age of 59 years (SD 9) and body mass index of 30 kg/m2 (SD 5). Standardized PASS values (95% CI) for different questionnaires for physical function varied between 48 (44-54) and 54 (50-56). Female patients and patients feeling depressed were found to have a lower probability to be in PASS for physical function, with OR (95% CI) varying from 0.45 (0.23-0.91) to 0.50 (0.26-0.97) and from 0.27 (0.14-0.55) to 0.38 (0.19-0.77), respectively. CONCLUSION: PASS cutoff values for physical function are robust across different PROM in patients with knee OA. Our results indicate that PASS values are not consistent across dimensions and rheumatic diseases, and that the use of a generic PASS value for patients with OA or even patients with other rheumatic diseases might not be justifiable.

Ultra-low dose of rituximab in rheumatoid arthritis: study protocol for a randomised controlled trial.

BACKGROUND: A standard low-dosing schedule of rituximab (RTX; 2 × 500 mg or 1 × 1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2 × 1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an 'ultra-low' dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions. METHODS/DESIGN: REDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1 × 500 or 1 × 200 mg) compared to standard low dose (1 × 1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRP < 2.9) after the previous RTX infusion and DAS28CRP < 3.5 at moment of retreatment, are randomised in a ratio of 1:2:2 to 1 × 1000 mg, 1 × 500 mg or 1 × 200 mg. The primary objective is testing non-inferiority of the ultra-low-dose vs. standard low-dose RTX, by comparing mean change in DAS28CRP from baseline to six months to the non-inferiority margin of 0.6. Secondary outcomes over the same period are: function; quality of life; safety; costs; and pharmacokinetics and dynamics as process measures. DISCUSSION: This study protocol shares characteristics of both early dose finding trials as well as late pragmatic clinical studies. Several choices in the design of this trial are described and possible consequences for RA treatment and expected biosimilar introduction are discussed. TRIAL REGISTRATION: Dutch Trial Register, NTR6117 . Registered on 15 November 2016 (CMO NL57520.091.16 , 8 November 2016).

The effects of an educational meeting and subsequent computer reminders on the ordering of laboratory tests by rheumatologists: an interrupted time series analysis.

OBJECTIVES: To examine the effects of an educational meeting and subsequent computer reminders on the number of ordered laboratory tests. METHODS: Using interrupted time series analysis we assessed whether trends in the number of laboratory tests ordered by rheumatologists between September 2012 and September 2015 at the Sint Maartenskliniek (the Netherlands) changed following an educational meeting (September 2013) and the introduction of computer reminders into the Computerised Physician Order Entry System (July 2014). The analyses were done for the set of tests on which both interventions had focussed (intervention tests; complement, cryoglobulins, immunoglobins, myeloma protein) and a set of control tests unrelated to the interventions (alanine transferase, anti-cyclic citrullinated peptide, C-reactive protein, creatine, haemoglobin, leukocytes, mean corpuscular volume, rheumatoid factor and thrombocytes). RESULTS: At the start of the study, 101 intervention tests and 7660 control tests were ordered per month by the rheumatologists. After the educational meeting, both the level and trend of ordered intervention and control tests did not change significantly. After implementation of the reminders, the level of ordered intervention tests decreased by 85.0 tests (95%-CI -133.3 to -36.8, p<0.01), the level of control tests did not change following the introduction of reminders. CONCLUSIONS: In summary, an educational meeting alone was not effective in decreasing the number of ordered intervention tests, but the combination with computer reminders did result in a large decrease of those tests. Therefore, we recommend using computer reminders in addition to education if reduction of inappropriate test use is aimed for.

The value of routine creatine kinase and thyroid stimulating hormone testing in patients with suspected fibromyalgia: a cross-sectional study.

OBJECTIVE: The aim was to examine the prevalence of abnormal creatine kinase (CK) and thyroid stimulating hormone (TSH) values and previously unknown myopathy or thyroid disease in patients with suspected FM syndrome (FMS). METHODS: All adult patients with suspected FMS referred to the study hospital between November 2011 and April 2014 could participate. Patients with a history of myopathy or a previous diagnosis of thyroid disorder were excluded. Outcome measures were the percentages of abnormal CK and TSH values and the final diagnosis in those patients. RESULTS: Three hundred and seventy-three patients were included in this study (94% female, mean age 42 years). Of these patients, 7.5% (95% CI: 5.2, 10.6%) had an abnormal CK according to the local reference values. Applying the European Federation of the Neurological Societies guideline, this changed to 0.5% (95% CI: 0.2, 1.9%). In none of these patients was hyperCKaemia-related myopathy diagnosed, and the final diagnosis was FMS in 89% of the patients. Of the total number of patients, 3.5% (95% CI: 2.1, 5.9%) had an elevated TSH and 1.4% (95 CI: 0.6, 3.1%) a lowered TSH, with one patient having a somewhat lowered free thyroid hormone level. The final diagnosis was FMS in all these patients. CONCLUSION: Abnormal CK and TSH values are rare in patients with suspected FMS and do not result in an alternative diagnosis. Therefore, it seems that routine testing of CK and TSH levels in patients with suspected FMS referred to secondary care does not contribute to the diagnostic process.