Publications by authors named "Eckstein F"

901 Publications

Automated MRI assessment confirms cartilage thickness modification in patients with knee osteoarthritis: post-hoc analysis from a phase II sprifermin study.

Osteoarthritis Cartilage 2020 11 26;28(11):1432-1436. Epub 2020 Aug 26.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy & Cell Biology, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany. Electronic address:

Background: Sprifermin is under investigation as a potential disease-modifying osteoarthritis drug. Previously, 2-year results from the FORWARD study showed significant dose-dependent modification of cartilage thickness in the total femorotibial joint (TFTJ), medial and lateral femorotibial compartments (MFTC, LFTC), and central medial and lateral TFTJ subregions, by quantitative magnetic resonance imaging (qMRI) using manual segmentation.

Objective: To determine whether qMRI findings from FORWARD could be reproduced by an independent method of automated segmentation using an identical dataset and similar anatomical regions in a post-hoc analysis.

Method: Cartilage thickness was assessed at baseline and 6, 12, 18 and 24 months, using automated cartilage segmentation with active appearance models, a supervised machine learning method. Images were blinded for treatment and timepoint. Treatment effect was assessed by observed and adjusted changes using a linear mixed model for repeated measures.

Results: Based on automated segmentation, statistically significant, dose-dependent structural modification of cartilage thickness was observed over 2 years with sprifermin vs placebo for TFTJ (overall treatment effect and dose response, both P < 0.001), MFTC (P = 0.004 and P = 0.044), and LFTC (both P < 0.001) regions. For highest dose, in the central medial tibial (P = 0.008), central lateral tibial (P < 0.001) and central lateral femoral (P < 0.001) regions.

Conclusions: Cartilage thickness assessed by automated segmentation provided a consistent dose response in structural modification compared with manual segmentation. This is the first time that two independent quantification methods of image analysis have reached the same conclusions in an interventional trial, strengthening the conclusions that sprifermin modifies structural progression in knee osteoarthritis.
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http://dx.doi.org/10.1016/j.joca.2020.08.005DOI Listing
November 2020

Modified frozen elephant trunk procedure as standard approach in acute type A aortic dissection: A propensity-weighted analysis.

J Thorac Cardiovasc Surg 2020 Jul 17. Epub 2020 Jul 17.

Department of Cardiac Surgery, University Hospital, Basel, Switzerland.

Objectives: To evaluate whether the modified frozen elephant trunk (mFET) procedure provides comparable outcome compared with the standard approach for DeBakey type I aortic dissection.

Methods: From November 2008 to December 2018, 262 (mean age 62.7 ± 12.4 years) patients with acute DeBakey type I aortic dissection were included. mFET was performed in 100 (38.2%) patients and isolated ascending aorta and hemiarch replacement (iAoA) were performed in 162 (61.8%). Outcome analyses included in-hospital mortality, stroke rate, incidence of composite cardiovascular events, survival, freedom from aorta-related intervention, as well as freedom from neurologic event. Inverse probability of treatment weighting was applied.

Results: After inverse probability of treatment weighting, in-hospital mortality was greater in the iAoA group. The incidence of cardiac cause of death, new postoperative renal failure, as well as stroke rate were similar in both groups. The survival at 1 year, 3 years, and 4 years was 84%, 81%, and 77%, respectively, in the iAoA group and 91%, 86%, and 86%, P = .025, respectively, in the mFET group. Cause-specific HR for aortic reoperation 1.03 (confidence interval [CI], 0.43-2.48, P = .95) and neurovascular event 2.72 (CI, 0.62-11.93, P = .19) was similar in 2 groups. Subhazard ratio (sHR) for mortality as competing outcome for aorta-related reintervention sHR of 0.52 (CI, 0.32-0.86, P = .011) and neurologic event sHR of 0.45 (95% CI, 0.26-0.76, P = .003) was significantly lower in mFET.

Conclusions: The mFET procedure as surgical treatment modality for DeBakey type I acute aortic dissection may be considered as viable alternative with beneficial mid-term outcome.
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http://dx.doi.org/10.1016/j.jtcvs.2020.05.120DOI Listing
July 2020

Are three antiseptic paints needed for safe preparation of the surgical field? A prospective cohort study with 239 patients.

Antimicrob Resist Infect Control 2020 07 31;9(1):120. Epub 2020 Jul 31.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: Preoperative skin antisepsis is an essential component of safe surgery. However, it is unclear how many antiseptic paints are needed to eliminate bacteria prior to incision. This study compared microbial skin counts after two and three antiseptic paints.

Methods: We conducted a prospective cohort study in non-emergency patients receiving a cardiac/abdominal surgery with standardized, preoperative skin antisepsis consisting of an alcoholic compound and either povidone iodine (PI) or chlorhexidine (CHX). We obtained three skin swabs from the participant's thorax/abdomen using a sterile template with a 25 cm window: After collection of the first swab prior to skin antisepsis, and once the second and third application of PI/CHX had dried out, we obtained a second and third swab, respectively. Our primary outcome was the reduction in microbial skin counts after two and three paints of PI/CHX.

Results: Among the 239 enrolled patients, there was no significant difference in the reduction of mean square root-transformed microbial skin counts with three versus two paints (P = 0.2). But distributions of colony forming units (CFUs) decreased from paint 2 to 3 in a predefined analysis (P = 0.002). There was strong evidence of an increased proportion of patients with zero CFU after paint 3 versus paint 2 (P = 0.003). We did not identify risk factors for insufficient reduction of microbial skin counts after two paints, defined as the detection of > 5 CFUs and/or ≥ 1 pathogens.

Conclusions: In non-emergency surgical patients, three antiseptic paints may be superior to two paints in reducing microbial skin colonization prior to surgery.
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http://dx.doi.org/10.1186/s13756-020-00780-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393917PMC
July 2020

Association of infra-patellar fat pad size with age and body weight in children and adolescents.

Ann Anat 2020 Nov 2;232:151533. Epub 2020 Jul 2.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria; Department of Orthopedic Surgery & Traumatology, Landesklinik Tamsweg, Paracelsus Medical University, Tamsweg, Austria.

Background: The infra-patellar fat pad (IPFP) represents a potential mediator between obesity, low grade inflammation, and knee osteoarthritis via endocrine pathways. Yet, not only in adults, but also in childhood obesity negatively impacts knee structures.

Objective: The current study therefore investigated the sex-specific growth of the IPFP with age and body weight in healthy children and adolescents.

Materials And Methods: Thirty young healthy subjects (60% girls; age 4-17 years, body weight 14-90 kg in girls and 29-105 kg in boys; BMI 12.2-32.4 kg/m) without magnetic resonance imaging (MRI) knee pathology were studied. The IPFP volume was determined from sagittal T-1 weighted and proton-density spectral attenuated inversion recovery MRIs. The primary analysis focused on the sex-specific IPFP volume/body weight ratio as dependent, and age as independent variable, using linear regression models. A secondary analytic focus was the slope of the age-dependence of IPFP volume, without normalization to body weight.

Results: There was no statistically significant association of the IPFP volume/body weight ratio with age in girls (p = 0.57) or boys (p = 0.31), the R of ranging from -0.32 to 0.14. The ratio was greater in boys (0.54 ± 0.10 cm/kg) than in girls (0.45 ± 0.07 cm/kg) (p < 0.01). The IPFP volume increased by approx. 2 cm per annum in both girls and boys, without any indication of a non-linear relationship.

Conclusion: Our findings reveal that the ratio of the IPFP volume and body weight remains constant between age 4 and 17 in both normal weight girls and boys, and that the IPFP volume increases linearly with age throughout this period.
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http://dx.doi.org/10.1016/j.aanat.2020.151533DOI Listing
November 2020

Is Laminar Cartilage Composition as Determined by T2 Relaxometry Associated with Incident and Worsening of Cartilage or Bone Marrow Abnormalities?

Cartilage 2020 Jun 12:1947603520932197. Epub 2020 Jun 12.

Chondrometrics GmbH, Ainring, Germany.

Objective: To test the hypothesis that superficial cartilage composition (T2) is associated with subsequent incidence or worsening of cartilage damage, and deep T2 with that of bone marrow lesions (BMLs) in knees without radiographic osteoarthritis (ROA).

Design: A total of 201 knees from the Osteoarthritis Initiative without ROA were included: 78 from the healthy reference cohort, 60 without ROA but with risk factors, and 63 without ROA but with contralateral ROA. Year 1 (Y1) superficial and deep cartilage T2 were derived in the medial and lateral (weightbearing) femur (MF/LF) and tibia (MT/LT), using sagittal multiecho spin echo magnetic resonance images. Cartilage and BMLs were assessed in the medial (MFTJ) and lateral femorotibial joint (LFTJ) at Y1 and 3 years later. Binary logistic regression statistics were applied.

Results: Incidence or worsening of cartilage damage was more frequent (MFTJ 15%, LFTJ 13%) than incidence or worsening of BMLs (6.0%, 4.5%). In knees with incident or worsening cartilage lesions in the MF and LT, deep layer T2 in the same plate was elevated (MF, 43.6 ± 4.0 vs. 41.3 ± 3.8 ms, = 0.047; LT, 33.8 ± 2.3 vs. 32.0 ± 2.2 ms, = 0.008) compared to those without. In knees with incident or worsening of BMLs in the LFTC and LT, superficial layer T2 was elevated (LFTJ, 49.6 ± 4.8 vs. 46.7 ± 3.1 ms; LT, 47.4 ± 4.9 vs. 44.0 ± 3.3 ms, both s = 0.04).

Conclusions: Contrary to our hypothesis, increased deep layer cartilage T2 was associated with subsequent worsening of cartilage damage, whereas superficial layer T2 was related to subsequent BML worsening. Yet, this relationship was observed in some, but not in all cartilage plates.
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http://dx.doi.org/10.1177/1947603520932197DOI Listing
June 2020

"Noninfective Endocarditis": A Case Report of Hereditary Coagulation Disorders in a 28-Year-Old Male.

Diagnostics (Basel) 2020 Jun 8;10(6). Epub 2020 Jun 8.

Department of Cardiac Surgery, University Hospital Basel, 4031 Basel, Switzerland.

We report a case of a young male who presented with acute limb ischemia after sport. With no prior history of disease, a non-infective endocarditis of the native aortic valve was diagnosed. After surgical valve replacement, the patient suffered from acute myocardial ischemia under phenprocoumon therapy. Anti-coagulant monitoring was subsequently changed to Factor II analysis after a rare Factor VII deficiency and prothrombin mutation (G20210A) was diagnosed.
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http://dx.doi.org/10.3390/diagnostics10060384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345217PMC
June 2020

The pitfall of gastric perforation by temporary pacemaker wires.

Asian Cardiovasc Thorac Ann 2020 06 3;28(5):290. Epub 2020 Jun 3.

Department of Cardiac Surgery, University Hospital Basel, Switzerland.

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http://dx.doi.org/10.1177/0218492320933771DOI Listing
June 2020

Layer-specific analysis of femorotibial cartilage t2 relaxation time based on registration of segmented double echo steady state (dess) to multi-echo-spin-echo (mese) images.

MAGMA 2020 Dec 26;33(6):819-828. Epub 2020 May 26.

Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, Salzburg, Austria.

Objective: To develop and validate a 3D registration approach by which double echo steady state (DESS) MR images with cartilage thickness segmentations are used to extract the cartilage transverse relaxation time (T2) from multi-echo-spin-echo (MESE) MR images, without direct segmentations for MESE.

Materials And Methods: Manual DESS segmentations of 89 healthy reference knees (healthy) and 60 knees with early radiographic osteoarthritis (early ROA) from the Osteoarthritis Initiative were registered to corresponding MESE images that had independent direct T2 segmentations. For validation purposes, (a) regression analysis of deep and superficial cartilage T2 was performed and (b) between-group differences between healthy vs. early ROA knees were compared for registered vs. direct MESE analysis.

Results: Moderate to high correlations were observed for the deep (r = 0.80) and the superficial T2 (r = 0.81), with statistically significant between-group differences (ROA vs. healthy) of + 1.4 ms (p = 0.002) vs. + 1.3 ms (p < 0.001) for registered vs. direct T2 segmentation in the deep, and + 1.3 ms (p = 0.002) vs. + 2.3 ms (p < 0.001) in the superficial layer.

Discussion: This registration approach enables extracting cartilage T2 from MESE scans using DESS (cartilage thickness) segmentations, avoiding the need for direct MESE T2 segmentations.
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http://dx.doi.org/10.1007/s10334-020-00852-6DOI Listing
December 2020

Echocardiographic and Clinical Follow-up After Aortic Valve Neocuspidization Using Autologous Pericardium.

World J Surg 2020 09;44(9):3175-3181

Department of Cardiac Surgery, University Hospital Basel, Spitalstrasse 21, CH-4031, Basel, Switzerland.

Introduction: Mid-term data from a single centre showed the safety and durability of aortic valve neocuspidization using autologous pericardium (OZAKI procedure). Since validation data from other centres are missing, aim of this study was to analyze echocardiographic and clinical results of our first patients that were operated with the OZAKI technique.

Methods: Thirty-five patients (24 males, median (IQR) age 72.0 (59.0, 76.0) years) with aortic stenosis (AS; n = 10), aortic insufficiency (AR; n = 13) or a combination of both (AS/AR; n = 12), underwent aortic valve neocuspidization in our institution between September 2015 and May 2017. Echocardiographic follow-up was performed using a standardized examination protocol.

Results: Clinical follow-up was completed in 97% of the patients. Median (IQR) follow-up time was 645 (430, 813) days. Mortality rate was 9% (n = 1: aspiration pneumonia; n = 1: unknown; n = 1: anaphylactic shock), and the reoperation rate was 3% (n = 1: endocarditis). No pacemaker implantation was necessary after isolated OZAKI procedures. Echocardiographic follow-up was performed in 83% of the patients (n = 29; median (IQR) time 664 (497, 815) days). Median (IQR) mean and peak gradients were 6 (5,9) mmHg and 12 (8, 17) mmHg. Moderate aortic regurgitation was seen in 2 patients (7%). No severe aortic regurgitation or moderate or severe aortic stenosis occurred within the follow-up period.

Conclusions: The OZAKI procedure is reliable and reoperation due to structural valve deterioration nil within a median 645 days follow-up period. The low rate of moderate aortic regurgitation will be surveilled very closely. Further studies are required to evaluate the significance of this procedure in aortic valve surgery.

Clinical Registration Number: ClinicalTrials.gov (ID NCT03677804).
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http://dx.doi.org/10.1007/s00268-020-05588-xDOI Listing
September 2020

Two cases of successful treatment of acute right heart failure with Impella RP®.

ESC Heart Fail 2020 08 29;7(4):1982-1986. Epub 2020 Apr 29.

Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.

Post-operative right coronary artery occlusion is a serious complication that demands acute coronary revascularization to prevent myocardial infarction. We present two cases with acute right coronary artery obstruction caused by (1) transfemoral aortic valve implantation and (2) acute type A aortic dissection. Although coronary artery bypass grafting was performed intraoperatively, right heart failure was observed in both cases. The Impella RP® device offers temporary right ventricular mechanical support; wherefore, we decided to deploy it in both patients. The devices were uneventfully and successfully implanted to bridge for recovery of the right heart. We report the perioperative course of the patients as well as their condition at 1 year follow-up.
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http://dx.doi.org/10.1002/ehf2.12698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373920PMC
August 2020

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints.

Osteoarthritis Cartilage 2020 06 2;28(6):782-791. Epub 2020 Apr 2.

University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:

Objective: Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up period.

Method: Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren-Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5 mm; knee pain at worst 4-9 in the past 30 days on an 11-point scale, or 0-3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes.

Results: Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively).

Conclusions: 2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.
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http://dx.doi.org/10.1016/j.joca.2020.03.012DOI Listing
June 2020

Association of baseline and change in tibial and femoral cartilage thickness and development of widespread full-thickness cartilage loss in knee osteoarthritis - data from the Osteoarthritis Initiative.

Osteoarthritis Cartilage 2020 06 30;28(6):811-818. Epub 2020 Mar 30.

Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia. Electronic address:

Objective: To investigate whether baseline cartilage thickness and its longitudinal change are associated with incident widespread full-thickness cartilage loss (wsFTCL) in knee osteoarthritis, and whether there are optimal cut-off values for predicting wsFTCL.

Methods: Central medial tibial (cMT) and femoral (cMF) cartilage were assessed using quantitative magnetic resonance imaging data from the Osteoarthritis Initiative cohort (N = 600 knees). Cartilage thickness was measured at baseline and 12 months. wsFTCL was defined semi-quantitatively (scores 2 and 3 from the MRI Osteoarthritis Knee Score) and its incidence at 24 months recorded. Logistic regression was used to determine the odds of developing wsFTCL for baseline and for each 0.1 mm decrease in cartilage thickness. Cut-off values were investigated using the minimal-p method and area under the Receiver Operating Characteristic curves (AUC).

Results: Incident wsFTCL was observed in 66 (12%) and 73 (14%) knees in cMT and cMF, respectively. Lower baseline cMT and cMF cartilage thickness values were associated with wsFTCL (OR = 1.20; 95% CI: 1.11, 1.28 and OR = 1.15; 95% CI: 1.06 to 1.24, respectively). Optimal cut-off AUCs for the tibia and femur were 0.64 (0.57-0.70) and 0.63 (0.57-0.69), respectively. Longitudinal decrease in femoral, but not tibial, cartilage thickness was associated with incident wsFTCL (OR = 1.77; 95% CI: 1.30 to 2.40); optimal cut-off AUC 0.65 (95% CI: 0.58-0.72).

Conclusion: Lower baseline cMT and baseline/change (decrease) over 12 months in cMF cartilage thickness were associated with incident, location-specific, wsFTCL at 24 months. Optimal cut-off values were relatively low and of uncertain utility for predicting incident wsFTCL.
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http://dx.doi.org/10.1016/j.joca.2020.03.011DOI Listing
June 2020

Changes in Medial Meniscal Three-Dimensional Position and Morphology As Predictors of Knee Replacement in Rapidly Progressing Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2021 07;73(7):1031-1037

Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria, and Chondrometrics GmbH, Ainring, Germany.

Objective: To assess whether quantitative changes in the meniscus predict progression from early knee osteoarthritis (OA) to knee replacement (KR).

Methods: A nested case-control study was conducted among Osteoarthritis Initiative participants: all 35 case knees with baseline Kellgren/Lawrence (K/L) grade ≤2 that had KR between 36 and 60 months were matched 1:1 by age, sex, and baseline K/L grade to 35 control knees without subsequent KR. Quantitative 3-dimensional medial meniscus position and morphologic measures were determined from magnetic resonance imaging at the visit just before KR and 2 years before. Paired t-tests and case-control odds ratios (ORs, standardized per SD of change in controls) were used to compare changes between groups.

Results: Cases (52% women, age 65 ± 7 years, body mass index [BMI] 30 ± 4 kg/m , K/L grades 0/1/2: 5/8/22 participants, respectively) and controls (52% women, age 64 ± 7 years, BMI 30 ± 5 kg/m , K/L grades 0/1/2: 9/4/22 participants, respectively) were similar. Compared to control knees, KR case knees displayed longitudinal changes, specifically, a decrease in tibial plateau coverage, an increase in meniscal extrusion, and a decrease in meniscal width. The odds for KR increased with greater reduction in the percentage of tibial plateau coverage (OR 2.28 [95% CI confidence interval (95% CI) 1.43, 3.64]), a greater increase in maximal extrusion (OR 1.40 [95% CI 1.12, 1.75]), and a greater reduction of mean meniscal width (OR 2.01 [95% CI 1.23, 3.26]). The odds for KR increased with medial compartment cartilage thickness loss (OR 2.86 [95% CI 1.51, 5.41]) for comparison.

Conclusion: Quantitative measures of meniscal position and morphology are associated with subsequent KR in knees with rapidly progressing knee OA. These findings show that structural changes of the meniscus are related to an important clinical and economic outcome of knee OA.
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http://dx.doi.org/10.1002/acr.24193DOI Listing
July 2021

Analysis of Myocardial Ischemia Parameters after Coronary Artery Bypass Grafting with Minimal Extracorporeal Circulation and a Novel Microplegia versus Off-Pump Coronary Artery Bypass Grafting.

Mediators Inflamm 2020 25;2020:5141503. Epub 2020 Jan 25.

Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.

Background: To compare the performance of our institutionally refined microplegia protocol in conjunction with minimal extracorporeal circulation system (MiECC) with off-pump coronary artery bypass grafting (OPCAB).

Methods: We conducted a single center study including patients undergoing isolated CABG surgery performed either off-pump or on-pump using our refined microplegia protocol in conjunction with MiECC. We used propensity modelling to calculate the inverse probability of treatment weights (IPTW). Primary endpoints were peak values of highsensitivity cardiac troponin T (hs-cTnT) during hospitalization, and respective first values on the first postoperative day. Endpoint analysis was adjusted for intraoperative variables.

Results: After IPTW, we could include 278 patients into our analyses, 153 of which had received OPCAB and 125 of which had received microplegia. Standardized differences indicated that treatment groups were comparable after IPTW. The multivariable quantile regression yielded a nonsignificant median increase of first hs-cTnT by 39 ng/L (95% CI -8 to 87 ng/L, = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84.

Conclusion: The use of our institutionally refined microplegia in conjunction with MiECC was associated with similar results with regard to ischemic injury, expressed in hs-cTnT compared to OPCAB. MACCE was seen equally frequent. ICU discharge was earlier if microplegia was used.
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http://dx.doi.org/10.1155/2020/5141503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056992PMC
December 2020

Impact of Diabetes Mellitus on Knee Osteoarthritis Pain and Physical and Mental Status: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2021 04 17;73(4):540-548. Epub 2021 Mar 17.

Chondrometrics GmbH, Ainring, Germany, and Paracelsus Medical University, Salzburg, Austria.

Objective: Diabetes mellitus (DM) appears to increase osteoarthritic knee pain, which may be related to greater adiposity and more advanced disease status often observed in individuals with osteoarthritis (OA) and DM. We aimed to assess whether OA knee pain and health status are worse in individuals with OA and DM, independent of these potential confounders.

Methods: We included 202 OA participants with DM and 2,279 without DM from the Osteoarthritis Initiative. Knee pain was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a numeric rating scale (NRS). Physical and mental status were assessed by the Medical Outcomes Study Short Form 12 (SF-12) questionnaire, physical component summary (PCS) score and mental component summary (MCS) score, and by the Center for Epidemiologic Studies Depression Scale (CES-D). Linear regression models assessed the influence of DM, adjusted for age, sex, body mass index (BMI), and radiographic severity.

Results: OA participants with DM reported worse knee pain and greater physical and mental issues compared with participants without DM. Individuals with DM had worse KOOS pain (β = -4.72 [95% confidence interval (95% CI) -7.22, -2.23]) and worse NRS pain (β = 0.42 [95% CI 0.04, 0.80]) independent of BMI, OA severity, age, and sex. The negative influence of DM was also apparent for SF-12 PCS (β = -3.49 [95% CI -4.73, -2.25]), SF-12 MCS (β = -1.42 [95% CI -2.57, -0.26]), and CES-D (β = 1.08 [95% CI 0.08, 2.08]).

Conclusion: Individuals with knee OA experience on average higher pain intensity and a worse physical and mental health status if they have DM. Linear regression models show that DM is a risk factor for higher pain, in addition to and independent of greater BMI and radiographic OA severity.
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http://dx.doi.org/10.1002/acr.24173DOI Listing
April 2021

Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial.

Ann Rheum Dis 2020 04 25;79(4):525-528. Epub 2020 Feb 25.

University of Maryland School of Medicine, Baltimore, Maryland, USA.

Objectives: In the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.

Methods: Patients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.

Results: Thinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.

Conclusions: Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.

Trial Registration Number: NCT01919164.
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http://dx.doi.org/10.1136/annrheumdis-2019-216453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147175PMC
April 2020

The effect of weight loss on the progression of meniscal extrusion and size in knee osteoarthritis: a post-hoc analysis of the Intensive Diet and Exercise for Arthritis (IDEA) trial.

Osteoarthritis Cartilage 2020 04 31;28(4):410-417. Epub 2020 Jan 31.

Institute of Anatomy, Department of Imaging and Functional Muskuloskelel Research; Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany. Electronic address:

Objective: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time.

Design: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance.

Results: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (β: -24.59 μm, 95%CI: -41.86, -7.33) and mean (β: -19.08 μm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups.

Conclusions: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit.

Clinical Trial Registration: NCT00381290.
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http://dx.doi.org/10.1016/j.joca.2020.01.006DOI Listing
April 2020

Impact of Modified Frozen Elephant Trunk Procedure on Downstream Aorta Remodeling in Acute Aortic Dissection: CT Scan Follow-Up.

World J Surg 2020 05;44(5):1648-1657

Department of Cardiac Surgery, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.

Objectives: The aim was to evaluate the impact of a modified frozen elephant trunk procedure (mFET) on remodeling of the downstream aorta following acute aortic dissections.

Methods: Over a period of 8 years, 205 patients (mean age 62.6 ± 12.6 years) underwent a mFET (n = 69, 33.7%) or isolated ascending aorta replacement (n = 136, 66.3%) (iAoA). Aortic diameter was assessed at the aortic arch (AoA), at the mid of the thoracic aorta (mThA), at the thoracoabdominal transition (ThAbd) and at the celiac trunk level (AbdA).

Results: Mean follow-up was 3.3 ± 2.6 years. In-hospital mortality was 14% (n = 28), 7% in mFET and 17% in the iAoA group (p = 0.08). At the end of the follow-up, overall survival was 84% (95% CI 70-92%) and 75% (65-82%) and freedom from aorta-related reoperation was 100% and 95% (88-98%) for mFET and iAoA, respectively. At iAoA, the average difference in diameter change per year between mFET and iAoA was for total lumen 0 mm (- 0.95 to 0.94 mm, p = 0.99), and for true lumen, it was 1.23 mm (- 0.09 to 2.55 mm) per year, p = 0.067. False lumen demonstrated a decrease in diameter in mFET as compared to iAoA by - 1.43 mm (- 2.75 to - 0.11 mm), p = 0.034. In mFET, at the aortic arch level the total lumen diameter decreased from 30.7 ± 4.8 mm to 30.1 ± 2.5 mm (Δr  + 2.90 ± 3.64 mm) and in iAoA it increased from 31.8 ± 4.9 to 34.6 ± 5.9 mm (Δr + 2.88 ± 4.18 mm).

Conclusion: The mFET procedure provides satisfactory clinical outcome at short term and mid-term and has a positive impact on aorta remodeling, especially at the level of the aortic arch.
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http://dx.doi.org/10.1007/s00268-020-05374-9DOI Listing
May 2020

Longitudinal changes in location-specific cartilage thickness and T2 relaxation-times after posterior cruciate ligament reconstruction for isolated and multiligament injury.

Clin Biomech (Bristol, Avon) 2020 10 23;79:104935. Epub 2019 Dec 23.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremburg, Salzburg, Austria. Electronic address:

Background: Knee cartilage undergoes pathological changes after anterior cruciate ligament rupture. However, little is known about the development and progression of structural pathology after posterior cruciate ligament (PCL) injury. This study aimed to determine the location-specific longitudinal changes in knee cartilage morphology (thickness) and composition (T2 relaxation-times) after PCL rupture and reconstruction (PCLR) and compare these to uninjured controls.

Methods: Fifteen adults (mean age 39 years (standard deviation 10), 12 men) with PCLR for isolated and multiligment injury had MRIs acquired at a minimum 5 years post-PCLR and 1 year later. Location-specific changes in knee cartilage thickness and T2 relaxation-times were determined quantitatively after segmentation, and compared with annualised cartilage changes in 13 active controls (mean age 45 years (standard deviation 4), 6 men).

Findings: Following PCLR, the annual loss of cartilage thickness was greatest in the medial femoral condyle (mean -4.0%, 95% confidence interval [95% CI] -6.7, -1.4), medial tibia (mean -3.7%, 95% CI -6.1, -1.3), and patella (mean -3.2%, 95% CI -4.7, -1.6). In the medial femoral condyle and trochlea, the PCLR group lost significantly more cartilage thickness than uninjured controls (mean difference -3.7%, 95% CI -0.9, -6.5; and -1.8%, 95% CI -0.1, -3.6, respectively). Deep and superficial zone T2 relaxation-times were relatively constant over time, without longitudinal differences between PCLR and control knees.

Interpretation: PCL reconstructed knees displayed substantially greater rates of cartilage loss in the medial tibiofemoral and patellofemoral compartments compared to uninjured controls, highlighting that the process of degeneration remains active many years after injury.
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http://dx.doi.org/10.1016/j.clinbiomech.2019.12.017DOI Listing
October 2020

Bretschneider (Custodiol®) and St. Thomas 2 Cardioplegia Solution in Mitral Valve Repair via Anterolateral Right Thoracotomy: A Propensity-Modelled Comparison.

Mediators Inflamm 2019 4;2019:5648051. Epub 2019 Dec 4.

Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.

Background: Single-dose cardioplegia is preferred in minimal invasive mitral valve surgery to maintain the adjustment of the operative site without change of preset visualization. The aim of our study was to compare two widely used crystalloid cardioplegias Bretschneider (Custodiol®) versus St. Thomas 2 in patients who underwent mitral valve repair via small anterolateral right thoracotomy.

Material And Methods: From May 2012 until February 2019, 184 isolated mitral valve procedures for mitral valve repair via anterolateral right thoracotomy were performed using Bretschneider (Custodiol®) cardioplegia ( = 123) or St. Thomas ( = 61). Primary efficacy endpoint was peak postoperative high-sensitivity cardiac troponin (hs-cTnT) during hospitalization. Secondary endpoints were peak creatine kinase-muscle brain type (CK-MB) and creatine kinase (CK) as well as safety outcomes. We used inverse probability of treatment weighting (IPTW) in order to adjust for confounding by indication.

Results: Peak hs-cTnT was higher after use of Bretschneider (Custodiol®) (geometric mean 716 mg/L, 95% confidence interval (CI) 605-847 mg/L) vs. St. Thomas 2 (561 mg/L, CI 467-674 mg/L, = 0.047). Peak CK-MB (geometric mean after Bretschneider (Custodiol®): 40 g/L, CI 35-46, St. Thomas 2: 33 g/L, CI 27-41, = 0.295) and CK (geometric mean after Bretschneider (Custodiol®): 1370 U/L, CI 1222-1536, St. Thomas 2: 1152 U/L, CI 972-1366, = 0.037) showed the same pattern. We did not see any difference with respect to postoperative complications between treatment groups after IPTW.

Conclusion: Use of St. Thomas 2 cardioplegia was associated with lower postoperative peak levels of all cardiac markers that reflect cardiac ischemia such as hs-cTnT, CK, and CK-MB as compared to Bretschneider (Custodiol®) in propensity-weighted treatment groups.
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http://dx.doi.org/10.1155/2019/5648051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914981PMC
June 2020

Clinical evaluation of fully automated thigh muscle and adipose tissue segmentation using a U-Net deep learning architecture in context of osteoarthritic knee pain.

MAGMA 2020 Aug 23;33(4):483-493. Epub 2019 Dec 23.

ETH, Zurich, Switzerland.

Objective: Segmentation of thigh muscle and adipose tissue is important for the understanding of musculoskeletal diseases such as osteoarthritis. Therefore, the purpose of this work is (a) to evaluate whether a fully automated approach provides accurate segmentation of muscles and adipose tissue cross-sectional areas (CSA) compared with manual segmentation and (b) to evaluate the validity of this method based on a previous clinical study.

Materials And Methods: The segmentation method is based on U-Net architecture trained on 250 manually segmented thighs from the Osteoarthritis Initiative (OAI). The clinical evaluation is performed on a hold-out test set bilateral thighs of 48 subjects with unilateral knee pain.

Results: The segmentation time of the method is < 1 s and demonstrated high agreement with the manual method (dice similarity coeffcient: 0.96 ± 0.01). In the clinical study, the automated method shows that similar to manual segmentation (- 5.7 ± 7.9%, p < 0.001, effect size: 0.69), painful knees display significantly lower quadriceps CSAs than contralateral painless knees (- 5.6 ± 7.6%, p < 0.001, effect size: 0.73).

Discussion: Automated segmentation of thigh muscle and adipose tissues has high agreement with manual segmentations and can replicate the effect size seen in a clinical study on osteoarthritic pain.
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http://dx.doi.org/10.1007/s10334-019-00816-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351818PMC
August 2020

The effects of intensive dietary weight loss and exercise on gait in overweight and obese adults with knee osteoarthritis. The Intensive Diet and Exercise for Arthritis (IDEA) trial.

J Biomech 2020 01 31;98:109477. Epub 2019 Oct 31.

Department of Kinesiology, East Carolina University, Greenville, NC, USA. Electronic address:

The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus exercise (D + E) interventions. We previously reported that the clinical benefits of D + E were significantly greater than with either intervention alone (e.g., greater pain reduction, and better function, mobility, and health-related quality of life). We now test the hypothesis that D + E has greater overall benefit on gait mechanics compared to either intervention alone. Knee joint loading was analyzed using inverse dynamics and musculoskeletal modeling. Analysis of covariance determined the interventions' effects on gait. The D + E group walked significantly faster at 18-month follow-up (1.35 m s) than E (1.29 m s, p = 0.0004) and D (1.31 m s, p = 0.0007). Tibiofemoral compressive impulse was significantly lower (p = 0.0007) in D (1069 N s) and D + E (1054 N s) compared to E (1130 N s). D had significantly lower peak hip external rotation moment (p = 0.01), hip abduction moment (p = 0.0003), and peak hip power production (p = 0.016) compared with E. Peak ankle plantar flexion moment was significantly less (p < 0.0001) in the two diet groups compared with E. There also was a significant dose-response to weight loss; participants that lost >10% of baseline body weight had significantly (p = 0.0001) lower resultant knee forces and lower muscle (quadriceps, hamstring, and gastrocnemius) forces than participants that had less weight loss. Compared to E, D produces significant load reductions at the hip, knee, and ankle; combining D with E attenuates these reductions, but most remain significantly better than with E alone.
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http://dx.doi.org/10.1016/j.jbiomech.2019.109477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949016PMC
January 2020

Fatty acid-based monolayer culture to promote in vitro neonatal rat cardiomyocyte maturation.

Biochim Biophys Acta Mol Cell Res 2020 03 23;1867(3):118561. Epub 2019 Oct 23.

Cardiac Surgery and Engineering Group, Departments of Biomedicine and Surgery, University of Basel and University Hospital Basel, 4031 Basel, Switzerland. Electronic address:

The development of functional and reliable in vitro cardiac models composed of fully mature cardiomyocytes is essential for improving drug screening test quality, therefore, the success of clinical trial outcomes. In their lifespan, cardiomyocytes undergo a dynamic maturation process from the fetal to adult stage, radically changing their metabolism, morphology, contractility and electrical properties. Before employing cells of human origin, in vitro models often use neonatal rat cardiomyocytes (NRCM) to obtain key proof-of-principles. Nevertheless, NRCM monolayers are prone to de-differentiate when maintained in culture. Supplementation of free fatty acids (FFA), the main energy source for mature cardiomyocytes, and co-culture with fibroblasts are each by itself known to promote the shift from fetal to adult cardiomyocytes. Using a co-culture system, our study investigates the effects of FFA on the cardiomyocyte phenotype in comparison to glucose as typical fetal energy source, and to 10% serum used as standard control condition. NRCM decreased their differentiation status and fibroblasts increased in number after 7days of culture in the control condition. On the contrary, both glucose- and FFA-supplementation better preserved protein expression of myosin-light-chain-2v, a marker of mature cardiomyocytes, and the fibroblast number at levels similar to those found in freshly isolated NRCM. Nevertheless, compared to glucose, FFA resulted in a significant increase in sarcomere striation and organization. Our findings constitute an important step forward towards the definition of the optimal culture conditions, highlighting the possible benefits of a further supplementation of specific FFA to promote CM maturation in a co-culture system with FB.
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http://dx.doi.org/10.1016/j.bbamcr.2019.118561DOI Listing
March 2020

Association of body composition, physical activity and physical performance with knee cartilage thickness and bone area in young adults.

Rheumatology (Oxford) 2020 07;59(7):1607-1616

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

Objective: To describe associations of body composition, physical activity and physical performance with knee cartilage thickness and subchondral bone area in young adults.

Methods: Body composition, physical activity and physical performance were measured 4-5 years prior to knee MRI. Cartilage thickness and bone area were measured quantitatively from MRI. Associations were assessed using linear regression analysis, with mediators being identified using mediation analysis.

Results: Participants (n = 186) were 31-41 years of age when the MRI was acquired and 48% were female. Greater lean mass was positively associated with cartilage thickness [β = 6.52 μm/kg (95% CI 0.86, 12.18)] and bone area [β = 13.37 mm2/kg (95% CI 5.43, 21.31)]. Physical performance measures were positively associated with cartilage thickness [long jump: β = 2.44 μm/cm (95% CI 0.70, 4.18); hand grip strength: 7.74 μm/kg (95% CI 1.50, 13.98); physical work capacity: 1.07 μm/W (95% CI 0.29, 1.85)] and bone area [long jump: β = 3.99 mm2/cm (95% CI 0.64, 7.34); hand grip strength: 19.06 mm2/kg (95% CI 7.21, 30.92); leg strength: 3.18 mm2/kg (95% CI 1.09, 5.28); physical work capacity: 3.15 mm2/W (95% CI 1.70, 4.60)]. Mediation analysis suggested these associations were mediated by lean mass (effect mediated: 27-95%).

Conclusion: Greater lean mass and better physical performance measured 4-5 years prior were associated with greater knee cartilage thickness and subchondral bone area in young adults, and the associations of physical performance were largely mediated by lean mass. These findings suggest lean mass may play an important role in maintaining knee joint health in young adults.
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http://dx.doi.org/10.1093/rheumatology/kez498DOI Listing
July 2020

Assessment of compromised parasternal skin perfusion after left internal mammary artery harvesting with a novel laser Doppler imaging.

J Cardiovasc Surg (Torino) 2019 Dec 4;60(6):742-748. Epub 2019 Oct 4.

Division of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.

Background: Our aim was to investigate the impact of the non-skeletonized (pedicled) versus the skeletonized left internal mammary (LIMA) harvesting technique on the postoperative sternal and parasternal skin perfusion in patients undergoing coronary artery bypass grafting (CABG), as compared to patients undergoing non-CABG heart surgery.

Methods: We included 142 patients who underwent non-bypass (N.=39) or CABG surgery (N.=103). CABG cases were differentiated according to the LIMA harvesting technique: skeletonized (N.=74) or non-skeletonized (N.=29). Parasternal and sternal skin perfusion measurements via a Laser Doppler Imaging tool were performed on the preoperative day and 5-7 days postoperatively, using a grid of 15 spatially segregated measurement points across the chest and normalization to a distinct reference point. Data were analyzed retrospectively.

Results: In the CABG group, the non-skeletonized LIMA harvesting resulted in a near-significant (P=0.057, two-sided Student t-test, 95% CI -[0.111, 0.002]), and the skeletonized LIMA harvesting in a significant (P< 0.001, 95% CI [-0.096, -0.032]) post-surgical decrease of left-sided parasternal skin perfusion in arbitrary perfusion units (APU), as compared to right-sided parasternal skin perfusion. No corresponding differences were found for the non-bypass group (P=0.5, 95% CI [-0.065, 0.033]). The harvesting techniques did not yield significantly different post-surgical parasternal skin perfusion measures in the CABG group (P=0.6).

Conclusions: Measurement of parasternal skin perfusion using Laser Doppler Imaging is feasible. Both harvesting techniques resulted in a reduced parasternal/sternal skin perfusion upon removal of the internal mammary artery.
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http://dx.doi.org/10.23736/S0021-9509.19.10832-4DOI Listing
December 2019

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

JAMA 2019 10;322(14):1360-1370

Institute of Anatomy, Department of Imaging and Functional Musculoskeletal Research, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug.

Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.

Design, Setting, And Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported.

Interventions: Participants were randomized to 1 of 5 groups: intra-articular injections of 100 μg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 μg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks.

Main Outcomes And Measures: The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%).

Results: Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 μg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 μg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 μg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 μg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 μg of sprifermin administered every 6 months or every 12 months, or for 30 μg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 μg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 μg of sprifermin every 12 months: n = 50 [45.0%]; 30 μg of sprifermin every 6 months: n = 40 [36.0%]; and 30 μg of sprifermin every 12 months: n = 48 [44.0%]).

Conclusions And Relevance: Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 μg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain.

Trial Registration: ClinicalTrials.gov Identifier: NCT01919164.
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http://dx.doi.org/10.1001/jama.2019.14735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784851PMC
October 2019

Baseline structural tissue pathology is not strongly associated with longitudinal change in transverse relaxation time (T2) in knees without osteoarthritis.

Eur J Radiol 2019 Sep 20;118:161-168. Epub 2019 Jul 20.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Strubergasse 21, 5020, Salzburg, Austria; Chondrometrics GmbH, 83404, Ainring, Germany.

Purpose: To evaluate whether baseline MRI-defined structural abnormalities are associated with subsequent change in laminar femorotibial cartilage transverse relaxation time (T2) of participants without radiographic signs, symptoms or risk factors for knee osteoarthritis (OA).

Method: We studied all right knees with longitudinal MRI data of the refined Osteoarthritis Initiative Healthy Reference cohort. Baseline osteophytes, effusion-synovitis, Hoffa-synovitis, bone marrow lesions, cartilage lesions, and meniscus morphology and - extrusion were scored semiquantitatively from MR images by an expert reader. Deep and superficial layer cartilage T2 was computed in the medial and lateral femorotibial compartment (MFTC/LFTC) at baseline and at 1- and 4-year follow-up from multi-echo spin-echo MR images. Statistical analyses were performed using UNIANOVA.

Results: 82 participants (age 54.1 ± 7.2y, BMI 24.2 ± 3.0 kg/m²; 61% women, bilateral Kellgren-Lawrence 0) were studied. Number of baseline MRI pathologies was not significantly associated with longitudinal change in MFTC or LFTC cartilage T2 over 1 or 4 years. Feature-specific analyses suggested that presence of baseline MFTC osteophytes may be associated with prolongation in superficial MFTC cartilage T2 over one (0.8 vs. 0.0 ms, p = 0.02) and four years (2.3 vs. 0.9 ms, p = 0.01), and that MFTC meniscal damage or extrusion may be associated with prolongation in deep layer T2 times over the first year (0.7 vs. 2.1 ms, p = 0.02).

Conclusions: Our study does not provide evidence that, in knees without radiographic OA, baseline structural MRI abnormalities are strongly related to compositional progression during normal aging and/or the potentially earliest phases of the disease as measured by cartilage T2.
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http://dx.doi.org/10.1016/j.ejrad.2019.07.013DOI Listing
September 2019

Aortic root and ascending aorta dimensions in acute aortic dissection.

Perfusion 2020 03 31;35(2):131-137. Epub 2019 Jul 31.

Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.

Objectives: Aim of this study was to evaluate ascending aorta and aortic root dimension at acute type A dissection (acute aortic dissection) and to identify demographics elements being allied to the acute event.

Methods: In a period between 2009 and 2017, 225 (n = 71, 32% female, mean age = 63 ± 12 years) patients eligible for analysis of ascending aorta and 223 (n = 70, 31% female, mean age = 63 ± 13 years) of aortic root were included in this study. Aortic diameter was assessed in preoperative computed tomography scan. The predissection diameters were modeled from the diameters obtained at diagnosis, assuming 30% augmentation of the diameter at acute event.

Results: The mean diameter of the ascending aorta at dissection was 46 ± 8 mm and the modeled diameter was 32.3 ± 5.7 mm. The diameter of the aortic root at dissection was 42 ± 8 mm and modeled diameter was 29.5 ± 5.6 mm. In multivariate analysis, female gender (p = 0.026) and history of cerebrovascular event (p = 0.001) were associated with acute aortic dissection in small aortic root. Patient age (p < 0.001) and history of inguinal hernia (p = 0.001) in ascending aorta <55 mm correlated with acute aortic dissection.

Conclusion: Modeling indicates that more than 90% of patients had aortic root and ascending aorta diameter <45 mm. It seems that the aortic diameter expansion over the 55 mm in development of acute aortic dissection is overestimated. Parameters other than aortic size were identified, which may be considered when patients at high risk for dissection were identified.
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http://dx.doi.org/10.1177/0267659119858848DOI Listing
March 2020

Reduction in Thigh Muscle Strength Occurs Concurrently but Does Not Seem to Precede Incident Knee Pain in Women: Data From the Osteoarthritis Initiative Cohort.

Am J Phys Med Rehabil 2020 01;99(1):33-40

From the Institute of Anatomy, Department of Imaging and Functional Musculoskeletal Research, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria (AR, WW, AGC, FE); Department of Orthopedic Surgery and Traumatology, Landesklinik Tamsweg, Tamsweg, Austria (AR); and La Trobe Sport and Exercise Medicine Research Centre, La Trobe University, School of Allied Health, Bundoora, Melbourne, Victoria, Australia (AGC).

Objective: The aim of the study was to investigate whether muscle strength declines before or concurrent with incident knee pain in subjects with and without radiographic knee osteoarthritis.

Design: Osteoarthritis initiative participants with incident knee pain (occurrence of infrequent/frequent knee pain during the past 12 mos at two consecutive follow-up time points (either years Y3 + Y4 or Y4 + Y5) were compared with controls (no incident knee pain) with 2-yr changes in knee extensor strength during BL➔Y2 (before) and Y2➔Y4 (concurrent).

Results: Two hundred two knees (49% women, 40% radiographic knee osteoarthritis) displayed incident pain, and 439 did not (46% women, 23% radiographic knee osteoarthritis). Women with radiographic knee osteoarthritis displayed a significantly greater (P = 0.04) reduction in knee extensor strength concurrent with incident pain compared with controls (mean = -17.6 N vs. +4.5 N), but men did not. A similar trend was observed in women without radiographic knee osteoarthritis, but this was not statistically significant (P = 0.08). There was no significant relationship with change in extensor strength before incident pain (P ≥ 0.43).

Conclusions: These results suggest that in women, incident knee pain is accompanied by a concurrent reduction in knee extensor strength, whereas loss in strength does not precede incident knee pain. The findings encourage interventional studies that attempt to attenuate a decline in extensor strength once knee symptoms occur.
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http://dx.doi.org/10.1097/PHM.0000000000001271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920538PMC
January 2020

Radiographically normal knees with contralateral joint space narrowing display greater change in cartilage transverse relaxation time than those with normal contralateral knees: a model of early OA? - data from the Osteoarthritis Initiative (OAI).

Osteoarthritis Cartilage 2019 11 10;27(11):1663-1668. Epub 2019 Jul 10.

Institute of Anatomy, Paracelsus Medical University Salzburg & Nuremberg, Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany.

Objective: To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees.

Methods: 120 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus.

Results: Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval [CI] [0.4, 2.0]) than in matched KLG0 reference knees (0.1 ms; 95% CI [-0.5, 0.7]). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment.

Conclusions: Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees. CLINICALTRIALS.

Gov Identification: NCT00080171.
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http://dx.doi.org/10.1016/j.joca.2019.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803071PMC
November 2019
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