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Objective.The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT).Methods.HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions.Results.ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819–0.883, and 0.771–0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P= 0.0001 for erosion numbers, width, and depth in axial plane;P= 0.001 for depth in perpendicular plane).Conclusion.This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

Background: Lymphaticovenous anastomosis, a supermicrosurgical technique, creates bypasses between the lymphatic and venous systems. The quality of lymphaticovenous anastomosis depends on the surgeon's dexterity and precision, and is subject to imperfections caused by the physiologic tremor of the human hand. A dedicated robot for microsurgery has been created to overcome these limitations (MUSA, MicroSure, Eindhoven, The Netherlands). This study describes 1-year clinical outcomes of the first-in-human trial of robot-assisted and manual lymphaticovenous anastomosis in patients with breast cancer-related lymphedema.Methods: In this prospective pilot study, women with breast cancer-related lymphedema were randomized into the robot-assisted or manual lymphaticovenous anastomosis group. Outcomes were quality of life, arm circumference, conservative treatment frequency, arm dermal backflow stage, and anastomosis patency.Results: Twenty women were included, of whom eight underwent robot-assisted lymphaticovenous anastomosis surgery and 12 underwent manual surgery. In both groups, quality of life significantly improved at 12 months (robot-assisted surgery, p = 0.045; manual surgery, p = 0.001). Arm circumference did not decrease (robot-assisted surgery, p = 0.094; manual surgery, p = 0.240). Daily use of compression garments decreased by 61.9 percent (robot-assisted surgery) and 70.2 percent (manual surgery). The frequency of manual lymphatic drainage remained similar compared with baseline. Arm dermal backflow stage was reduced in one patient in the robot-assisted group and in five cases in the manual group. Overall, 76.5 percent of the anastomoses were patent (robot-assisted surgery, 66.6 percent; manual surgery, 81.8 percent).Conclusions: After evaluating 1-year follow-up data, this study confirms the feasibility of robot-assisted lymphaticovenous anastomosis surgery. Clinical outcomes were comparable between robot-assisted and manual lymphaticovenous anastomosis. This encourages further research using the new microsurgical robot MUSA for lymphaticovenous anastomosis and other (super)microsurgical procedures.

Contains fulltext : 200372.pdf (Publisher’s version ) (Open Access) Advanced microsurgical procedures are currently limited by human precision and manual dexterity. The potential of robotics in microsurgery is highlighted, including a general overview of applications of robotic assistance in microsurgery and its introduction in different surgical specialties. A new robotic platform especially designed for (super) microsurgery is presented. Results of an in vivo animal study underline its feasibility and encourage further development toward clinical studies. Future directions of robotic microsurgery are proposed.

Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm2 , and 0.48 mm3 versus 1.0, 0.69 mm2 , and 0.23 mm3 , respectively; all p

Advancements in reconstructive microsurgery have evolved into supermicrosurgery; connecting vessels with diameter between 0.3 and 0.8 mm for reconstruction of lymphatic flow and vascularized tissue transplantation. Supermicrosurgery is limited by the precision and dexterity of the surgeon’s hands. Robot assistance can help overcome these human limitations, thereby enabling a breakthrough in supermicrosurgery. We report the first-in-human study of robot-assisted supermicrosurgery using a dedicated microsurgical robotic platform. A prospective randomized pilot study is conducted comparing robot-assisted and manual supermicrosurgical lymphatico-venous anastomosis (LVA) in treating breast cancer-related lymphedema. We evaluate patient outcome at 1 and 3 months post surgery, duration of the surgery, and quality of the anastomosis. At 3 months, patient outcome improves. Furthermore, a steep decline in duration of time required to complete the anastomosis is observed in the robot-assisted group (33–16 min). Here, we report the feasibility of robot-assisted supermicrosurgical anastomosis in LVA, indicating promising results for the future of reconstructive supermicrosurgery., Reconstructive microsurgery is limited by the precision that human hands can achieve. Here, the authors demonstrate in a randomized clinical pilot trial the feasibility of robot-assisted supermicrosurgery using a dedicated microsurgical robot for the completion of lymphatico-venous anastomosis in the treatment of breast cancer-related lymphedema

Incorporation of new technologies advances surgery in general. One example is robot assistance which can potentially overcome limitations in accessibility, dexterity, and ergonomics, thereby improving outcome of surgical procedures. To date, robot assistance has been used successfully in various fields of surgery. Also, in microsurgery robot assistance could offer great advantages as it requires great precision and meticulous technique. Currently available surgical robotic platforms are primarily designed for endoscopic procedures and lack the specific requirements for true microsurgery. Therefore, plastic surgeons of the Maastricht University Medical Center (Maastricht, the Netherlands) teamed up with engineers from the Eindhoven University of Technology (Eindhoven, the Netherlands) and developed the first dedicated robotic platform for (super)microsurgery, the MicroSure Robot (MSR). Level of evidence: Level V, therapeutic study.

ObjectivesThe purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS).MethodsThirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated.ResultsAt baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (-4.4 versus -1.1 mgHA/cm(3), respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively).ConclusionsHR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs. The study is supported by unrestricted grants from the Weijerhorst foundation (WH-2) and Pfizer (WS2056904).

Objective.High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size.Methods.HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated.Results.Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16–8.90) and mean depth was 1.86 mm (range 0.30–8.00).Conclusion.We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean +/- sd 0.33 +/- 0.63 vs 0.38 +/- 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH >= 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (beta 0.47, 95% CI 0.4-0.6, p < 0.01 and beta 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated. This study was funded by an unrestricted grant from Pfizer and the Weijerhorst Foundation.

Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42mm(2), and 0.48mm(3) versus 1.0, 0.69mm(2), and 0.23mm(3), respectively; all p

Background Preservation, repair and progression of cortical interruptions in finger joints has been observed in RA using conventional radiography, MRI, ultrasound and high-resolution peripheral quantitative computed tomography (HR-pQCT). Accurate and quantitative information about such changes over time, however, is still lacking. Objectives To evaluate changes over one year in cortical interruptions (number, surface area and volume), bone density (vBMD) and micro-structural parameters from HR-pQCT scans of finger joints in RA and healthy subjects (HS) using a recently developed semi-automatic algorithm for cortical interruptions detection.1 Methods Baseline and 1 year follow up HR-pQCT scans of finger joints of 32 patients with RA (221 joints, 53% on biologic DMARDSs (bDMARDs)) and 32 HS (117 joints) were analysed for changes in cortical interruption, density and morphological parameters. Mean changes (at the group level) and proportions of joints (at the joint level) with changes beyond least significant changes were calculated after correction for baseline damage. Results At baseline, 530 interruptions (3.25/joint) were identified in RA, and 136 (1.45/joint) in HS. The mean of the interruption parameters did not change in either group, except for a significant increase in number of interruptions in PIP joints in RA. However, the proportion of joints showing repair in interruption volume was higher in RA than in HS (6.6% versus 1.7%, p=0.041). Changes in cortical interruption parameters were negatively correlated with changes in cortical BMD and thickness (p Conclusions Using HR-pQCT based semi-automatic cortical interruption analysis a large number of interruptions was identified in RA and HS. Cortical interruptions, vBMD and micro-structural parameters were more impaired in RA, of which vBMD and micro-structural parameters further deteriorated. Patients on sDMARDs had more joints with progression in number of interruptions and more loss of vBMD compared to bDMARDs. Reference [1] Peters M, Scharmga A, de Jong J, van Tubergen A, Geusens P, Arts JJ, Loeffen D, Weijers R, van Rietbergen B, van den Bergh J. An automated algorithm for the detection of cortical interruptions on high resolution peripheral quantitative computed tomography images of finger joints. PLoS One2017Apr 20;12(4):e0175829. Disclosure of Interest None declared

Background: We developed a semi-automated algorithm that detects cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), and extended it with trabecular void volume measurement In this study we tested the reproducibility of the algorithm using scan/re-scan data. Methods: Second and third metacarpophalangeal joints of 21 subjects (mean age 49 (SD 11) years, 17 early rheumatoid arthritis and 4 undifferentiated arthritis, all diagnosed < 1 year ago) were imaged twice by HR-pQCT on the same day with repositioning between scans. The images were analyzed twice by one operator (OP1) and once by an additional operator (OP2), who independently corrected the bone contours when necessary. The number, surface and volume of interruptions per joint were obtained. Intra- and inter-operator reliability and intra-operator reproducibility were determined by intra-class correlation coefficients (ICC). Intra-operator reproducibility errors were determined as the least significant change (LSCSD). Results: Per joint, the mean number of interruptions was 3.1 (SD 3.6), mean interruption surface 4.2 (SD 7.2) mm(2), and mean interruption volume 3.5 (SD 10.6) mm(3) for OP1. Intra- and inter-operator reliability was excellent for the cortical interruption parameters (ICC >= 0.91), except good for the inter-operator reliability of the interruption surface (ICC >= 0.70). The LSCSD per joint was 4.2 for the number of interruptions, 5.8 mm(2) for interruption surface, and 3. 2 mm(3) for interruption volume. Conclusions: The algorithm was highly reproducible in the detection of cortical interruptions and their volume. Based on the LSC findings, the potential value of this algorithm for monitoring structural damage in the joints in early arthritis patients needs to be tested in clinical studies. The study is supported by unrestricted grants from the Weijerhorst foundation (WH-2) and Pfizer (WS2056904). The funders had no role in the design of the study, the collection, analysis and interpretation of the data, and in writing the manuscript.

Intra- and inter-operator reliability of the cortical interruption parameters. Table with the intra- and inter-operator reliability of the cortical interruption parameters. Values are as value (95% Confidence Interval) ICC, intra-class correlation coefficient; SDRMS, root mean square of the standard deviation; LSCSD, absolute least significant change (DOCX 20Â kb)

Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm

Background Rheumatoid arthritis (RA) is characterized by peri-articular bone loss. In patients with RA, lower bone density and structural integrity, and an increased number of erosions compared to healthy controls (HCs) has been demonstrated using High-Resolution peripheral Quantitative CT (HR-pQCT) (1,2). To further characterize RA-related changes, we recently introduced a method for quantifying small cortical interruptions in finger joints (3). Objectives To investigate the cortical and trabecular bone density, structure, and cortical interruptions in MCP joints in early and late RA patients compared to HCs using HR-pQCT imaging. Methods The 2nd and 3rd MCP joint of 70 subjects (mean age 53.1 (SD 9.2) years) were evaluated by HR-pQCT (82μm isotropic voxel size): 38 HCs, 10 early RA (diagnosis ≤2 years ago) and 22 late RA (diagnosis ≥10 years ago). Images were analyzed for cortical interruptions, and for cortical and trabecular bone density and structure. Descriptives were analyzed per joint by one-way ANOVA with Bonferroni post-hoc testing or Kruskal-Wallis with Mann-Whitney post-hoc testing, as appropriate. Results Significant differences with respect to all parameters were found across the groups (Table 1). In early and late RA, the percentage of joints with at least 1 interruption was higher, and number of trabeculae, cortical thickness, total density and cortical density were lower than in HC. In addition, in late RA, number of interruptions, interruption volume and trabecular separation were higher, and trabecular density was lower than in HC. Bone loss at the cortical and trabecular bone was primarily observed at the rim of the joint (Figure 1, arrows

Objectives To introduce a fully-automated algorithm for the detection of small cortical interruptions (>= 0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully-and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully-and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully-and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully-vs. semi-automated procedure (respectively, 8.6mm(2) vs. 5.8mm(2) and 6.1mm(2), p = 0.01). Reliability was almost perfect between the fully-and semi-automated procedure for both the number and surface of interruptions (ICC >= 0.95) and the proportion of matching interruptions was high (>= 76%). Also the inter-operator reliability was almost perfect (ICC >= 0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. This work was supported by: Weijerhorst Foundation (JvdB), http//www.deweijerhorst.nl/ weijerhorst/home. funding that was used to purchase the HR-pQCT scanner and pay half of the PhD student salaries of MP and AS. It was also supported by Pfizer (PG), grant number: WS2056904, http//www.pfizer.nl/. This funding was used to perform our study (NL42300.068.12 / METC 12-2-037) of HR-pQCT imaging in patients with RA compared to conventional imaging techniques.

Rheumatoid arthritis is a chronic disease characterised by joint inflammation causing damage to the bones, including those of the fingers. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new CT technique only used in research settings that allows detailed imaging of the bones. This dissertation shows that HR-pQCT is a reliable and sensitive technique. In the future, HR-pQCT may be used to monitor and evaluate treatment effects in clinical trials. HR-pQCT may also be used to study bone abnormalities in other rheumatic diseases.

Objective.Conventional radiographs (CR) of the hands are the gold standard for imaging bone erosions. The presence of bone erosions, reflected by the presence of cortical breaks, is a poor prognostic factor in patients with rheumatoid arthritis (RA). The availability of high-resolution peripheral quantitative computed tomography (HR-pQCT) enables detailed investigation of cortical breaks in rheumatic diseases. The aim of this image review is to show HR-pQCT images of the spectrum of cortical breaks with and without underlying trabecular bone changes in metacarpophalangeal (MCP) joints of healthy controls (HC) and patients with RA, with corresponding images on CR and magnetic resonance imaging (MRI).Methods.Second and third MCP joints of 41 patients (of which 10 were early RA with ≤ 2 years and 24 longstanding RA with ≥ 10 years of disease duration) and 38 HC were imaged by CR, MRI, and HR-pQCT (XtremeCT1, Scanco Medical AG). Representative images of the spectrum of cortical breaks were selected.Results.Cortical breaks were found in early and longstanding RA, but also in HC. They were heterogeneous in size, location, and number per joint, with a variety of surrounding cortical and underlying trabecular bone characteristics.Conclusion.Using HR-pQCT images of MCP joints, heterogeneous cortical breaks with and without surrounding trabecular bone changes were found, not only in RA but also in HC. The underlying mechanisms and significance of this spectrum of cortical breaks as found with high 3-D resolution needs further investigation.

2 × 2 contingency tables. 2 × 2 contingency tables for Reader 1 (all joints and MCP and PIP separately) and Reader 2 (all joints and MCP and PIP joints separately). (DOCX 17 kb)

Einleitung: Die HR-pqCT (High-resolution peripheral quantitative computed tomography) ist ein hochsensitives Instrument zur Detektion von Knochenläsionen; dies birgt jedoch das Risiko, erosive Veränderungen in pathologischen und normalen Knochen zu überinterpretieren. Gegenstand unserer[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)