Publications by authors named "Cornelis P J Visser"

18 Publications

  • Page 1 of 1

Is the Anterior Injection Approach Without Ultrasound Guidance Superior to the Posterior Approach for Adhesive Capsulitis of the Shoulder? A Sequential, Prospective Trial.

Clin Orthop Relat Res 2021 May 5. Epub 2021 May 5.

Z. Rijs, Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, the Netherlands.

Background: Shoulder injections for conditions such as adhesive capsulitis are commonly performed and can be administered through image-based or landmark-based injection approaches. Ultrasound-guided injections are widely used and accurate because ultrasound allows real-time visualization of the needle and injected contrast. Landmark-based injections would be advantageous, if they were accurate, because they would save the time and expense associated with ultrasound. However, few prospective studies have compared well-described landmark-based shoulder injection techniques without ultrasound.

Question/purpose: Using anatomic landmarks, and without using ultrasound, is the accuracy of glenohumeral injection for adhesive capsulitis greater via the posterior approach or via a new anterior approach?

Methods: Between 2018 and 2020, we treated 108 patients potentially eligible for adhesive capsulitis treatment. These patients had clinical symptoms of aggravating shoulder pain with a duration of less than 4 months and passively impaired, painful glenohumeral ROM. Due to the exclusion of patients with other shoulder conditions (full-thickness rotator cuff ruptures and posttraumatic stiffness), 95 patients received an injection in this sequential, prospective, comparative study. Between 2018 and 2019, 41 patients (17 males and 24 females; mean age 52 ± 5 years; mean BMI 24 ± 3 kg/m2) were injected through the posterior approach, with the acromion as the anatomical landmark, during the first part of the study period. After that, between 2019 and 2020, 54 patients (20 males and 34 females; mean age 54 ± 4 years; mean BMI 23 ± 3 kg/m2) received an injection through a new anterior approach, with the acromioclavicular joint as the anatomic landmark, during the second part of the study period. Injections via both approaches were administered by two experienced shoulder specialists (both with more than 10 years of experience). Both specialists had experience with the posterior approach before this study, and neither had previous training with the new anterior approach. Injections contained a corticosteroid, local anaesthetic, and contrast medium. Radiographs were taken within 20 minutes after the injection, and a radiologist blinded to the technique determined accuracy. Accurate injections were defined as having contrast fluid limited to the glenohumeral joint, while inaccurate injections displayed leakage of contrast fluid into the soft tissue or subacromial space. All of the enrolled patients were analyzed.

Results: In the group with the posterior approach, the accuracy was 78% (32 of 41) in contrast to 94% (51 of 54, odds ratio 0.21 [95% CI 0.05 to 0.83]; p = 0.03) in patients with the new anterior approach.

Conclusion: The new anterior approach without the use of ultrasound was more accurate than the posterior approach. In fact, it was nearly as accurate as previously published ultrasound-guided approaches. We recommend using the new anterior approach for intraarticular glenohumeral injections instead of ultrasound-guided injections because it will save time and costs associated with ultrasound. Still, the clinical effects (anxiety, pain, functional outcome, and adverse events) of the new anterior approach should be compared with ultrasound-guided injections in a randomized study.

Level Of Evidence: Level II, therapeutic study.
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May 2021

Arthroscopic bursectomy less effective in the degenerative shoulder with chronic subacromial pain.

JSES Int 2021 Mar 17;5(2):220-227. Epub 2020 Dec 17.

Department of Orthopedics, Alrijne Hospital, Leiden, the Netherlands.

Background: Varying results after surgery in patients with subacromial pain syndrome (SAPS) have raised the question on whether there is a subgroup of patients that can benefit from surgery. Therefore, we aimed to identify preoperative and peroperative factors associated with a favorable patient-reported outcome after arthroscopic bursectomy in patients with SAPS.

Methods: Patients with chronic SAPS who underwent arthroscopic bursectomy after failed conservative management were included (n = 94). Patients were evaluated at the baseline, and 2 weeks, 8 weeks, 6 months, and 1 year after surgery. The primary outcome was the Western Ontario Rotator Cuff index (WORC) score one year after surgery. The secondary outcome measure was a visual analog scale for pain. Mixed model analyses were used to identify prognostic factors.

Results: The mean WORC (mean difference 39%, 95% confidence interval (CI) 32.8-45.3, < .001) and visual analog scale pain scores (mean difference 41 mm points, 95% CI 3.37-4.88, < .001) significantly improved one year after surgery. Nineteen patients (20%) developed a postoperative frozen shoulder. A longer duration of preoperative complaints and the peroperative identification of degenerative glenoid cartilage were associated with significantly worse WORC scores, with -0.086% per month (95% CI -0.156 to -0.016,  = .016) and -20% (95% CI -39.4 to -1.26,  = .037), respectively.

Conclusion: We identified demographic and clinical factors that predict the course after arthroscopic subacromial bursectomy. We found that arthroscopic bursectomy is less effective in patients with SAPS with a degenerative shoulder. This finding suggests that an improved treatment effect of arthroscopic subacromial bursectomy can be expected in patients with chronic SAPS if intra-articular pathologies such as glenohumeral osteoarthritis are sufficiently excluded.
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March 2021

Reduced psychosocial functioning in subacromial pain syndrome is associated with persistence of complaints after 4 years.

J Shoulder Elbow Surg 2021 Feb 16;30(2):223-228. Epub 2020 Sep 16.

Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands; Laboratory for Kinematics and Neuromechanics, Department of Orthopaedics and Rehabilitation, Leiden University Medical Center, Leiden, The Netherlands.

Background: Patients with subacromial pain syndrome (SAPS) frequently present with coexisting psychosocial problems; however, whether this also associates with long-term outcome is currently unknown. We assessed whether psychosocial functioning in patients with SAPS is associated with persistence of complaints after 4 years of routine care.

Methods: In a longitudinal study, 34 patients with SAPS were selected after clinical and radiologic evaluation and assessed at baseline and after 4 years. For the assessment of psychosocial functioning, the RAND-36 questionnaire domains of social functioning, role limitations due to emotional problems, mental health, vitality, and general health were evaluated. Complaint persistence at follow-up was assessed by (1) an anchor question (reduced, persistent, or increased symptoms), (2) change in pain (change in visual analog scale score), and (3) change in quality of life (change in Western Ontario Rotator Cuff index score).

Results: Lower baseline mental health (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85-0.98; P = .013), vitality (OR, 0.90; 95% CI, 0.83-0.98; P = .011), and general health (OR, 0.93; 95% CI, 0.88-0.98; P = .009) were associated with persistent complaints as reported by the anchor question, change in visual analog scale score, and change in Western Ontario Rotator Cuff index score.

Conclusions: Evaluating psychosocial functioning parallel to physical complaints is currently not standard procedure in the treatment of SAPS. In this study, we showed that factors related to psychosocial functioning are associated with long-term persistence of complaints in SAPS. Future studies may investigate whether a multimodal treatment with assessment of psychosocial functioning may facilitate pain relief and recovery in SAPS.
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February 2021

Overstuffing in resurfacing hemiarthroplasty is a potential risk for failure.

J Orthop Surg Res 2019 Dec 30;14(1):474. Epub 2019 Dec 30.

Spaarne Hospital, Spaarnepoort 1, 2134, TM, Hoofddorp, the Netherlands.

Purpose: Literature describes the concern of an overstuffed shoulder joint after a resurfacing humeral head implant (RHHI). The purpose of this study was to evaluate inter-observer variability of (1) the critical shoulder angle (CSA), (2) the length of the gleno-humeral offset (LGHO), and (3) the anatomic center of rotation (COR) in a patient population operated with a Global Conservative Anatomic Prosthesis (CAP) RHHI. The measurements were compared between the revision and non-revision groups to find predictive indicators for failure.

Methods: Pre- and postoperative radiographs were retrieved from 48 patients who underwent RHHI from 2007 to 2009 using a Global CAP hemiarthroplasty for end-stage osteoarthritis. This cohort consisted of 36 females (12 men) with a mean age of 77 years (SD 7.5). Two musculoskeletal radiologist and two specialized shoulder orthopedic surgeons measured the CSA, LGHO, and COR of all patients.

Results: The inter-observer reliability showed excellent reliability for the CSA, LGHO, and the COR, varying between 0.91 and 0.98. The mean COR of the non-revision group was 4.9 mm (SD 2.5) compared to mean COR of the revision group, 8 mm (SD 2.2) (p < 0.01). The COR is the predictor of failure (OR 1.90 (95%Cl 1.19-3.02)) with a cut of point of 5.8 mm. The mean CSA was 29.8° (SD 3.9) There was no significant difference between the revision and non-revision groups (p = 0.34). The mean LGHO was 2.6 mm (SD 3.3) post-surgery. The mean LGHO of the revision group was 3.9 (SD 1.7) (p = 0.04) post-surgery. Despite the difference in mean LGHO, this is not a predictor for failure.

Conclusion: The CSA, LGHO, and COR can be used on radiographs and have a high inter-observer agreement. In contrast with the CSA and LGHO, we found a correlation between clinical failure and revision surgery in case of a deviation of the COR greater than 5 mm.

Trial Registration: Institutional review board, number: ACLU 2016.0054, Ethical Committee number: CBP M1330348. Registered 7 November 2006.
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December 2019

Altered Cocontraction Patterns of Humeral Head Depressors in Patients with Subacromial Pain Syndrome: A Cross-sectional Electromyography Analysis.

Clin Orthop Relat Res 2019 Aug;477(8):1862-1868

C.L. Overbeek, A. Kolk, J. H. de Groot, A. Jens, J. Nagels, R.G.H.H. Nelissen, Department of Orthopaedics, Leiden University Medical Center, Leiden, the Netherlands C.L. Overbeek, A. Kolk, J. H. de Groot, Laboratory for Kinematics and Neuromechanics, Department of Orthopaedics and Rehabilitation, Leiden University Medical Center, Leiden, the Netherlands C.P.J. Visser, Department of Orthopaedics, Haaglanden Medical Center, The Netherlands P. v.d. Zwaal, Department of Orthopaedics, Alrijne Hospital, The Netherlands.

Background: In approximately 29% to 34% of all patients with subacromial pain syndrome (SAPS) there is no anatomic explanation for symptoms, and behavioral aspects and/or central pain mechanisms may play a more important role than previously assumed. A possible behavioral explanation for pain in patients with SAPS is insufficient active depression of the humerus during abduction by the adductor muscles. Although the adductor muscles, specifically the teres major, have the most important contribution to depression of the humerus during abduction, these muscles have not been well studied in patients with SAPS.

Questions/purposes: Do patients with SAPS have altered contraction patterns of the arm adductors during abduction compared with asymptomatic people?

Methods: SAPS was defined as nonspecific shoulder pain lasting for longer than 3 months that could not be explained by specific conditions such as calcific tendinitis, full-thickness rotator cuff tears, or symptomatic acromioclavicular arthritis, as assessed with clinical examination, radiographs, and magnetic resonance arthrography. Of 85 patients with SAPS who met the prespecified inclusion criteria, 40 were eligible and agreed to participate in this study. Thirty asymptomatic spouses of patients with musculoskeletal complaints, aged 35 to 60 years, were included; the SAPS and control groups were not different with respect to age, sex, and hand dominance. With electromyography, we assessed the contraction patterns of selected muscles that directly act on the position of the humerus relative to the scapula (the latissimus dorsi, teres major, pectoralis major, and deltoid muscles). Cocontraction was quantified through the activation ratio ([AR]; range, -1 to 1). The AR indicates the task-related degree of antagonist activation relative to the same muscle's degree of agonist activation, equaling 1 in case of sole agonist muscle activation and equaling -1 in case of sole antagonistic activation (cocontraction). We compared the AR between patients with SAPS and asymptomatic controls using linear mixed-model analyses. An effect size of 0.10 < AR < 0.20 was subjectively considered to be a modest effect size.

Results: Patients with SAPS had a 0.11 higher AR of the teres major (95% CI, 0.01-0.21; p = 0.038), a 0.11 lower AR of the pectoralis major (95% CI, -0.18 to -0.04; p = 0.003), and a 0.12 lower AR of the deltoid muscle (95% CI, -0.17 to -0.06; p < 0.001) than control participants did. These differences were considered to be modest. With the numbers available, we found no difference in the AR of the latissimus dorsi between patients with SAPS and controls (difference = 0.05; 95% CI, -0.01 to 0.12; p = 0.120).

Conclusions: Patients with SAPS showed an altered adductor cocontraction pattern with reduced teres major activation during abduction. The consequent reduction of caudally directed forces on the humerus may lead to repetitive overloading of the subacromial tissues and perpetuate symptoms in patients with SAPS. Physical therapy programs are frequently effective in patients with SAPS, but targeted approaches are lacking. Clinicians and scientists may use the findings of this study to assess if actively training adductor cocontraction in patients with SAPS to unload the subacromial tissues is clinically effective. The efficacy of training protocols may be enhanced by using electromyography monitoring.

Level Of Evidence: Level II, prognostic study.
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August 2019

Response to Beaudreuil and Orcel regarding: "Increased co-contraction of arm adductors is associated with a favorable course in subacromial pain syndrome".

J Shoulder Elbow Surg 2019 06 12;28(6):e195-e196. Epub 2019 Apr 12.

Laboratory for Kinematics and Neuromechanics, Department of Orthopaedics and Rehabilitation, Leiden University Medical Center, Leiden, The Netherlands.

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June 2019

Revision of Failed Resurfacing Hemiarthroplasty: Midterm Results, Survival, and Group Comparison.

Orthopedics 2019 Jan 13;42(1):e111-e117. Epub 2018 Dec 13.

Shoulder arthroplasty is a valuable option for treating glenohumeral osteoarthritis. Revision surgery for a failed shoulder arthroplasty is associated with difficult procedures, complications, and worse outcomes. Compared with a total joint arthroplasty, a resurfacing prosthesis has the supposed advantages of limited perioperative complications and little bone loss during revision. The aim of this study was to describe patient-reported outcome measures of revision surgery from failed uncemented Global CAP (DePuy, Warsaw, Indiana) resurfacing hemiarthroplasty to total shoulder or reverse shoulder arthroplasty. Eleven patients from 2 collaborating institutes had a failed resurfacing prosthesis. Revision surgery was performed to total shoulder prosthesis in 7 patients and to reverse shoulder prosthesis in 3 patients. Data were missing for 1 patient. Outcomes were monitored using the Constant-Murley score, Dutch Simple Shoulder Test, Short Form-12, visual analog scale for pain, and physical examination. Mean time to revision was 54 months (SD, 15.6 months). No perioperative complications occurred. At 42 months of follow-up (SD, 15.9 months), clinical and patient-reported outcomes were excellent. The Constant-Murley score improved a significant 29 points (P<.01). The visual analog scale pain score decreased from 55 to 5 points (P<.01), and the Dutch Simple Shoulder Test and Short Form-12 scores improved significantly (P≤.02). Five-year survival was 82.6% (95% confidence interval, 71.6%-93.6%). At 3.5-year follow-up, clinical and patient-reported outcome measures had satisfying results. [Orthopedics. 2019; 42(1):e111-e117.].
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January 2019

Increased co-contraction of arm adductors is associated with a favorable course in subacromial pain syndrome.

J Shoulder Elbow Surg 2018 Nov 19;27(11):1925-1931. Epub 2018 Sep 19.

Laboratory for Kinematics and Neuromechanics, Department of Orthopaedics and Rehabilitation, Leiden University Medical Center, Leiden, The Netherlands.

Background: Enhancement of arm adductor activity during abduction (ie, adductor co-contraction), may be effective in the treatment of subacromial pain syndrome (SAPS). We assessed whether an increase of adductor co-contraction is associated with a favorable course of SAPS.

Methods: At baseline and after nearly 4 years of follow-up, electromyography of the latissimus dorsi (LD), teres major (TM), pectoralis major, and deltoid muscle was obtained during isometric abduction and adduction tasks in 26 patients with SAPS. Changes in co-contraction were assessed with change in the activation ratio (ΔAR). The AR ranges between -1 and 1, where lower values indicate more co-contraction. Clinical course was determined from an anchor question (reduced, persistent, or increased complaints), the visual analog scale for pain (VAS), and the Western Ontario Rotator Cuff score (WORC).

Results: In patients indicating persistent complaints (31%), the VAS and WORC remained stable. In patients who indicated reduced complaints (69%), the VAS reduced (z score, -3.4; P = .001) and WORC increased (z score, 3.6; P < .001). Unchanged ARs associated with complaints persistence, whereas decreased AR of the LD (ΔAR, -0.21; 95% confidence interval [CI], -0.36 to -0.06) and TM (ΔAR, -0.17; 95% CI, -0.34 to -0.00) coincided with reduced complaints. There was a significant between-group difference in ΔAR (-0.35; 95% CI, -0.60 to 0.10) and ΔAR (-0.36; 95% CI, -0.66 to -0.05).

Conclusions: Increased co-contraction of the LD and TM is associated with a favorable course of SAPS. This may be explained by widening of the subacromial space accomplished by adductor co-contraction.
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November 2018

The effect of a rotator cuff tear and its size on three-dimensional shoulder motion.

Clin Biomech (Bristol, Avon) 2017 Jun 11;45:43-51. Epub 2017 Apr 11.

Laboratory for Kinematics and Neuromechanics, Department of Orthopaedics and Rehabilitation, Leiden University Medical Center, Postzone J-11-R, PO Box 9600, 2300RC Leiden, the Netherlands. Electronic address:

Background: Rotator cuff-disease is associated with changes in kinematics, but the effect of a rotator cuff-tear and its size on shoulder kinematics is still unknown in-vivo.

Methods: In this cross-sectional study, glenohumeral and scapulothoracic kinematics of the affected shoulder were evaluated using electromagnetic motion analysis in 109 patients with 1) subacromial pain syndrome (n=34), 2) an isolated supraspinatus tear (n=21), and 3) a massive rotator cuff tear involving the supraspinatus and infraspinatus (n=54). Mixed models were applied for the comparisons of shoulder kinematics between the three groups during abduction and forward flexion.

Findings: In the massive rotator cuff-tear group, we found reduced glenohumeral elevation compared to the subacromial pain syndrome (16°, 95% CI [10.5, 21.2], p<0.001) and the isolated supraspinatus tear group (10°, 95% CI [4.0, 16.7], p=0.002) at 110° abduction. Reduced glenohumeral elevation in massive rotator cuff tears coincides with an increase in scapulothoracic lateral rotation compared to subacromial pain syndrome (11°, 95% CI [6.5, 15.2], p<0.001) and supraspinatus tears (7°, 95% CI [1.8, 12.1], p=0.012). Comparable differences were observed for forward flexion. No differences in glenohumeral elevation were found between the subacromial pain syndrome and isolated supraspinatus tear group during arm elevation.

Interpretation: The massive posterosuperior rotator cuff-tear group had substantially less glenohumeral elevation and more scapulothoracic lateral rotation compared to the other groups. These observations suggest that the infraspinatus is essential to preserve glenohumeral elevation in the presence of a supraspinatus tear. Shoulder kinematics are associated with rotator cuff-tear size and may have diagnostic potential.
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June 2017

Subacromial anaesthetics increase asymmetry of scapular kinematics in patients with subacromial pain syndrome.

Man Ther 2016 Dec 17;26:31-37. Epub 2016 Jul 17.

Laboratory for Kinematics and Neuromechanics, Leiden University Medical Center, Postzone J11R, PO Box 9600, 2300RC Leiden, the Netherlands.

Background: Subacromial pain syndrome (SAPS) and scapular dyskinesis are closely associated, but the role of pain is unknown. We hypothesized that pain results in asymmetrical scapular kinematics, and we expected more symmetrical kinematics after infiltration of subacromial anaesthetics.

Objective: To investigate the effect of subacromial anaesthetics on scapular kinematics in patients with SAPS.

Design: Observational cohort study.

Methods: We evaluated shoulder kinematics in 34 patients clinically and radiologically (magnetic resonance arthrography) identified with unilateral SAPS using three-dimensional electromagnetic motion analysis (Flock of Birds). Scapular internal rotation, upward rotation and posterior tilt of the affected shoulder were compared with the kinematics of the unaffected shoulder and following subacromial anaesthetics. Additionally, the association of pain (Visual Analogue Scale, VAS) and scapular rotation was analysed.

Results: Compared with the contralateral healthy shoulder, 5° more (95% CI 0.4-9.7, p = 0.034) scapular internal rotation was observed in the affected shoulder at 110-120° of abduction. Following subacromial anaesthetics in the affected shoulder, internal rotation increased (2°, 95% CI 0.5-3.9, p = 0.045) and posterior tilt decreased (3°, 95% CI 1.5-5.0, p = 0.001) at 110-120° of abduction. Less scapular upward rotation was significantly associated with higher pain scores before infiltration (R = 0.45, p = 0.013).

Conclusions: More scapular internal rotation was observed in affected shoulders of patients with SAPS compared with unaffected shoulders. Subacromial infiltration did not restore kinematics toward symmetrical scapular motion. These findings suggest that subacromial anaesthesia is not an effective means to instantly restore symmetry of shoulder motion.
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December 2016

Calcific tendinitis of the rotator cuff: a randomized controlled trial of ultrasound-guided needling and lavage versus subacromial corticosteroids.

Am J Sports Med 2013 Jul 21;41(7):1665-73. Epub 2013 May 21.

Department of Orthopaedics, Leiden University Medical Center, Postzone J11R, Postbus 9600, 2300 RC Leiden, the Netherlands.

Background: Calcific tendinitis of the rotator cuff (RCCT) is frequently diagnosed in patients with shoulder pain, but there is no consensus on its treatment.

Purpose: To compare 2 regularly applied RCCT treatments: ultrasound (US)-guided needling and lavage (barbotage) combined with a US-guided corticosteroid injection in the subacromial bursa (subacromial bursa injection [SAI]) (group 1) versus an isolated SAI (group 2).

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: Patients were randomly assigned to the 2 groups. Shoulder function was assessed before treatment and at regular follow-up intervals (6 weeks and 3, 6, and 12 months) using the Constant shoulder score (CS, primary outcome), the Western Ontario Rotator Cuff Index (WORC), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Additionally, calcification location, size, and Gärtner classification were assessed on radiographs. Results were analyzed using the t test, linear regression, and a mixed model for repeated measures.

Results: This study included 48 patients (25 female, 52.1%; mean age, 52.0 ± 7.3 years; 23 patients in group 1) with a mean baseline CS of 68.7 ± 11.9. No patients were lost to follow-up. Four patients in group 1 and 11 in group 2 (P = .06) had an additional barbotage procedure or surgery during the follow-up period because of persisting symptoms and no resorption. At 1-year follow-up, the mean CS in group 1 was 86.0 (95% CI, 80.3-91.6) versus 73.9 (95% CI, 67.7-80.1) in group 2 (P = .005). The mean calcification size decreased by 11.6 ± 6.4 mm in group 1 and 5.1 ± 5.7 mm in group 2 (P = .001). There was total resorption in 13 patients in group 1 and 6 patients in group 2 (P = .07). With regression analyses, correcting for baseline CS and Gärtner type, the mean treatment effect was 20.5 points (P = .05) in favor of barbotage. Follow-up scores were significantly influenced by baseline scores. Results for the DASH and WORC were similar.

Conclusion: On average, there was improvement at 1-year follow-up in both treatment groups, but clinical and radiographic results were significantly better in the barbotage group.
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July 2013

[A woman with a painful swelling of the upper arm].

Ned Tijdschr Geneeskd 2013 ;157(14):A6045

Rijnland Ziekenhuis, afd. Orthopedie, Leiderdorp, the Netherlands.

A 81-year-old woman presented at the emergency department with a painful right arm due to a comminuted fracture of the humeral head. Operation was postponed because of a wound and vulnerable skin due to a large hematoma. By the time of the operation, the humeral head had migrated subcutaneously which resulted in a solid swelling of the upper arm.
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May 2013

Muscle characteristics in patients with chronic systemic inflammation.

Muscle Nerve 2012 Aug;46(2):204-9

Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

Introduction: Histological characteristics of age-related muscle wasting are type II muscle fiber atrophy, accumulation of oxidative stress-induced lipofuscin granules and decreased satellite cell numbers. There is increasing clinical evidence for a strong correlation between chronic systemic inflammation and age-related muscle wasting. The aim of this study was to determine the impact of chronic systemic inflammation on age-related histological muscle characteristics.

Methods: As a model for chronic systemic inflammation, we included 10 patients suffering from rheumatoid arthritis (RA) and 27 control patients suffering from osteoarthritis (OA). Biopsies were taken from the vastus medialis muscle.

Results: No significant differences were found in type II muscle fiber atrophy, lipofuscin accumulation, or satellite cell number in RA compared with OA patients.

Conclusions: These results suggest there is no association between chronic systemic inflammation in RA and age-related muscle characteristics. Future research should focus on inflammation and satellite cell function.
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August 2012

Regenerative potential of human muscle stem cells in chronic inflammation.

Arthritis Res Ther 2011 15;13(6):R207. Epub 2011 Dec 15.

Department of Orthopaedics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Introduction: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.

Methods: As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.

Results: After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.

Conclusions: In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.
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December 2012

Study protocol subacromial impingement syndrome: the identification of pathophysiologic mechanisms (SISTIM).

BMC Musculoskelet Disord 2011 Dec 14;12:282. Epub 2011 Dec 14.

Department of Orthopaedics, Leiden University Medical Centre, Postzone J11R, Postbus 9600, 2300 RC Leiden, The Netherlands.

Background: The subacromial impingement syndrome (SIS) is the most common diagnosed disorder of the shoulder in primary health care, but its aetiology is unclear. Conservative treatment regimes focus at reduction of subacromial inflammatory reactions or pathologic scapulohumeral motion patterns (intrinsic aetiology). Long-lasting symptoms are often treated with surgery, which is focused at enlarging the subacromial space by resection of the anterior part of the acromion (based on extrinsic aetiology). Despite that acromionplasty is in the top-10 of orthopaedic surgical procedures, there is no consensus on its indications and reported results are variable (successful in 48-90%). We hypothesize that the aetiology of SIS, i.e. an increase in subacromial pressure or decrease of subacromial space, is multi-factorial. SIS can be the consequence of pathologic scapulohumeral motion patterns leading to humerus cranialisation, anatomical variations of the scapula and the humerus (e.g. hooked acromion), a subacromial inflammatory reaction (e.g. due to overuse or micro-trauma), or adjoining pathology (e.g. osteoarthritis in the acromion-clavicular-joint with subacromial osteophytes).We believe patients should be treated according to their predominant etiological mechanism(s). Therefore, the objective of our study is to identify and discriminate etiological mechanisms occurring in SIS patients, in order to develop tailored diagnostic and therapeutic strategies.

Methods: In this cross-sectional descriptive study, applied clinical and experimental methods to identify intrinsic and extrinsic etiologic mechanisms comprise: MRI-arthrography (eligibility criteria, cuff status, 3D-segmented bony contours); 3D-motion tracking (scapulohumeral rhythm, arm range of motion, dynamic subacromial volume assessment by combining the 3D bony contours and 3D-kinematics); EMG (adductor co-activation) and dynamometry instrumented shoulder radiographs during arm tasks (force and muscle activation controlled acromiohumeral translation assessments); Clinical phenotyping (Constant Score, DASH, WORC, and SF-36 scores).

Discussion: By relating anatomic properties, kinematics and muscle dynamics to subacromial volume, we expect to identify one or more predominant pathophysiological mechanisms in every SIS patient. These differences in underlying mechanisms are a reflection of the variations in symptoms, clinical scores and outcomes reported in literature. More insight in these mechanisms is necessary in order to optimize future diagnostic and treatment strategies for patients with SIS symptoms.

Trial Registration: Dutch Trial Registry (Nederlands Trial Register) NTR2283.
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December 2011

Transition of healthy to diseased synovial tissue in rheumatoid arthritis is associated with gain of mesenchymal/fibrotic characteristics.

Arthritis Res Ther 2006 ;8(6):R165

Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

The healthy synovial lining layer consists of a single cell layer that regulates the transport between the joint cavity and the surrounding tissue. It has been suggested that abnormalities such as somatic mutations in the p53 tumor-suppressor gene contribute to synovial hyperplasia and invasion in rheumatoid arthritis (RA). In this study, expression of epithelial markers on healthy and diseased synovial lining tissue was examined. In addition, we investigated whether a regulated process, resembling epithelial to mesenchymal transition (EMT)/fibrosis, could be responsible for the altered phenotype of the synovial lining layer in RA. Synovial tissue from healthy subjects and RA patients was obtained during arthroscopy. To detect signs of EMT, expression of E-cadherin (epithelial marker), collagen type IV (indicator of the presence of a basement membrane) and alpha-smooth muscle actin (alpha-sma; a myofibroblast marker) was investigated on frozen tissue sections using immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from healthy subjects were isolated and subjected to stimulation with synovial fluid (SF) from two RA patients and to transforming growth factor (TGF)-beta. To detect whether EMT/fibrotic markers were increased, expression of collagen type I, alpha-sma and telopeptide lysylhydroxylase (TLH) was measured by real time PCR. Expression of E-cadherin and collagen type IV was found in healthy and arthritic synovial tissue. Expression of alpha-sma was only found in the synovial lining layer of RA patients. Stimulation of healthy FLSs with SF resulted in an upregulation of alpha-sma and TLH mRNA. Collagen type I and TLH mRNA were upregulated after stimulation with TGF-beta. Addition of bone morphogenetic protein (BMP)-7 to healthy FLS stimulated with SF inhibited the expression of alpha-sma mRNA. The finding that E-cadherin and collagen type IV are expressed in the lining layer of healthy and arthritic synovium indicates that these lining cells display an epithelial-like phenotype. In addition, the presence of alpha-sma in the synovial lining layer of RA patients and induction of fibrotic markers in healthy FLSs by SF from RA patients indicate that a regulated process comparable to EMT might cause the alteration in phenotype of RA FLSs. Therefore, BMP-7 may represent a promising agent to counteract the transition imposed on synoviocytes in the RA joint.
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February 2007

Comparative prospective trial of 3 intramedullary plugs in cemented total hip arthroplasty.

J Arthroplasty 2002 Aug;17(5):576-8

Department of Orthopaedics, Rijnland Hospital, Leiderdorp, The Netherlands.

We assessed the occlusion and stability of 3 intramedullary plugs used to restrict the femoral canal before primary cemented arthroplasty. In a prospective, randomized trial the Biosem (SEM, Montrouge, France), Cemlock (Sulzer Orthopaedic Ltd, Baar, Switzerland), and Thackray (DePuy International Ltd, Leeds, England) plug were compared in 93 hip joints replaced by the Stanmore hip prosthesis. We considered a range of 1 cm on the postoperative radiograph a measuring fault. According to the definition, 43% (40/93) were not stable. The percentages of deficient plugs were: Biosem 78% (25/32), Cemlock 32% (9/28), and Thackray 18% (6/33). The differences found between the Biosem and Cemlock and between the Biosem and Thackray were significant. No significant effect was seen regarding the sizes of the plugs used. Comparison of the smaller sizes of the prosthesis versus the larger sizes showed a significant effect on the stability of the plugs.
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August 2002