Raoul Bergner | Universität Heidelberg (original) (raw)
Papers by Raoul Bergner
International Journal of Molecular Sciences
The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observa... more The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, a...
Background: The estimated cost of Rheumatoid arthritis (RA) in Germany exceeded 6 million € in 20... more Background: The estimated cost of Rheumatoid arthritis (RA) in Germany exceeded 6 million € in 2008, and represents a significant burden to the healthcare system. Drug management of patients with RA aims to relieve pain and modify the disease evolution, and includes non-steroidal anti-inflammatory[for full text, please go to the a.m. URL]
Ultraschall in der Medizin - European Journal of Ultrasound, 2012
Revue du Rhumatisme, 2017
Objectifs : L'atteinte de la hanche est courante dans les affections rhumatologiques mais son dia... more Objectifs : L'atteinte de la hanche est courante dans les affections rhumatologiques mais son diagnostic peut s'avérer difficile en particulier en l'absence d'examen IRM. L'échographie en mode B permet de détecter une dilatation capsulaire mais la différenciation entre un épanchement articulaire et une prolifération synoviale reste difficile puisque ces deux entités apparaissent hypoéchogènes. L'échographie en mode Doppler puissance (DP) ne parvient pas toujours à détecter la vascularisation de la hanche. Nous avons donc évalué l'intérêt de l'échographie de contraste (EC) dans l'exploration de la hanche. Méthodes : 36 hanches de patients atteints d'une maladie rhumatismale connue et présentant des douleurs de la hanche ainsi que 5 hanches de témoins sains ont été analysées au moyen de l'échographie en mode B, du DP et de l'EC. Nous avons procédé à une étude semi-quantitative du rehaussement à l'échographie de contraste pour détecter le degré d'hypervascularisation par comparaison au tissu périarticulaire. En mode B, nous avons mesuré la distance séparant le col fémoral de la capsule articulaire (DNC) puis comparé les résultats avec la marge avasculaire intra-articulaire (AIM) visible à l'EC à l'aide de tests t et de tableaux croisés. Résultats : Les signaux Doppler ont été reçus dans seulement 2/36 cas (5,6 %). L'échographie en mode B permettait d'établir le diagnostic de coxite dans 64 % des hanches symptomatiques. Dans 4 cas (11 %) le diagnostic a été corrigé après le recours à l'EC. Parmi les patients atteints d'une coxite définie, 14 hanches (73,7 %) ont montré une hypervascularisation °2 à l'EC, cinq °1 (26,3 %) et aucune °0 (χ 2 = 3,277, p < 0,001). La différence DNC/AIM était très significative chez les patients souffrant de douleurs de la hanche (p < 0,001, IC 95 % 2,054-4,684) et ceux atteints d'une coxite définie (p < 0,001, IC 95 % 3,268-7,258).
Joint Bone Spine, 2016
Hip involvement is common in rheumatological diseases but can be difficult to diagnose, especiall... more Hip involvement is common in rheumatological diseases but can be difficult to diagnose, especially in absence of MRI. B-mode ultrasound (US) detects joint capsule distention while distinguishing effusion from proliferative synovial tissue is strenuous since both appear hypoechoic. Power Doppler ultrasound (PDUS) often fails to detect vascularisation in the hip. We therefore evaluated contrast-enhanced ultrasound (CEUS) in the hip joint. We investigated 36 hip joints of patients with known rheumatological joint diseases presenting with hip pain and 5 hips of healthy controls using B-mode US, PDUS and CEUS. We assessed CEUS hypervascularisation semiquantitatively comparing to the periarticular tissue. In B-mode, we measured the distance between femoral neck and joint capsule (DNC) and compared the results to the avascular intraarticular margin (AIM) in CEUS using t-tests and crosstables. PDUS signals were received in only 2/36 cases (5.6%). B-mode US established the diagnosis of coxitis in 64% of all symptomatic hip joints. In 4 cases (11%), the diagnosis was revised after the use of CEUS. In patients with definite coxitis, 14 hips (73.7%) showed CEUS hypervascularisation°2, five°1 (26.3%) and none°0 (χ(2)=3.277, P&amp;lt;0.001). The difference DNC/AIM was highly significant in patients with hip pain (P&amp;lt;0.001, 95% CI: 2.054-4.684) and those with definite coxitis (P&amp;lt;0.001, 95% CI: 3.268-7.258). In most cases, clinical parameters together with B-mode US findings are sufficient to diagnose coxitis. However, CEUS is capable of visualizing and quantifying the degree of hypervascularisation and enables the discrimination between effusion and proliferative synovial tissue.
Clinical Nuclear Medicine, 2009
Transplantation is the treatment of choice for hepatocellular carcinoma (HCC) meeting the Milan c... more Transplantation is the treatment of choice for hepatocellular carcinoma (HCC) meeting the Milan criteria. HCC and chronic liver diseases have distinct natural histories for which an equitable transplant policy must account. We enrolled and prospectively followed at a single center 206 consecutive HCC patients that presented within the Milan criteria. Patients were treated per the Barcelona Clinic Liver Cancer (BCLC) algorithm; 95% received resection, ablation, or transarterial chemoembolization. The median follow-up was 16 months. Progression occurred in 84 patients, and 8 patients died. Risk factors for the time to disease progression (death or progression beyond T2) were analyzed in 170 patients with a complete data set. Risk factors with the strongest relationship to progression included tumor diameter and tumor persistence/recurrence after local therapy (hazard ratios of 1.51 and 2.75, respectively, when transplanted patients were censored at the time of transplantation and hazard ratios of 1.53 and 3.66, respectively, when transplantation was counted as an event; P 0.0001). To evaluate the current Model for End-Stage Liver Disease (MELD) exception, we compared the expected progression rate (PR) with our observed PR in 133 stage T2 patients. The current policy resulted in a large overestimation of the PR for T2 HCC and an unsatisfactory performance [Harrell's concordance index (C index) ¼ 0.60, transplant censored; C index ¼ 0.55, transplant as progression]. Risk factors for progression that were identified by univariate analysis were considered for multivariate analysis. With these risk factors and the patients' natural MELD scores, an adjusted model applicable to organ allocation was generated, and this decreased the discrepancy between the expected and observed PRs (C index ¼ 0.66, transplant censored; C index ¼ 0.69, transplant as progression). In conclusion, the current MELD exception largely overestimates progression in T2 patients treated according to the BCLC guidelines. The tumor response to resective or ablative treatment can predict tumor progression beyond the Milan criteria, and it should be taken into account in models designed to prioritize organ allocation.
Journal of Gastrointestinal and Liver Diseases
Background and Aims: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As ... more Background and Aims: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As many patients experience only minor symptoms, a high number of undiagnosed cases must be assumed. In order to successfully identify patients with hepatic sarcoidosis, a throughout characterization of these patients and their course of disease is necessary. Methods: We collected 40 patients from four German centers to evaluate current treatment standards and course of disease. All of our patients underwent liver biopsy with histologically proven granulomatous hepatitis. Results: Detailed characterization of our patients showed an overall benign course of disease. Treatment was very diverse with glucocorticoids for 1 year in 55% (22/40), 5-10 years in 18% (7/40), and permanently in 18% (7/40). Other treatments included disease-modifying anti-rheumatic drugs (DMARDs), the conventional non-biological type in 53% of all patients (of these 81% received azathioprine, 46% metotrexate, 10% hydrox...
Arthritis und Rheuma
Liebe Kolleginnen und Kollegen, in den vergangenen Jahren sind in der Rheumatologie immer wieder ... more Liebe Kolleginnen und Kollegen, in den vergangenen Jahren sind in der Rheumatologie immer wieder neue Krankheitsentitäten entdeckt und neu definiert worden. Teilweise wurden diese früher unter anderen Diagnosen subsummiert und erst die Entdeckung neuer Autoantikörper oder anderer diagnostischer Marker hat den Blick dafür geschärft, dass hier eigenständige Erkrankungen mit unterschiedlichen Verläufen und Therapieansätzen vorliegen. Auf jeden Fall sind diese "neuen Krankheiten" inzwischen ein Teil der täglichen diagnostischen und therapeutischen Herausforderungen für klinisch tätige Rheumatologen. Die vorliegende Ausgabe von arthritis + rheuma widmet sich einigen dieser neuen Krankheitsentitäten und stellt diese dar.
Journal of Clinical Medicine
Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituxi... more Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19+ peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID50 of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all p < 0.001). Longer ...
Einleitung: Die Kapillarmikroskopie ist in der Diagnostik vor allem der Sklerodermie fest etablie... more Einleitung: Die Kapillarmikroskopie ist in der Diagnostik vor allem der Sklerodermie fest etabliert. In der Diagnostik und Beurteilung von Vasculitiden ist der Wert der Kapillarmikroskopie bisher jedoch unbekannt. Wir untersuchten daher Patienten mit ANCA-Vasculitiden auf Kapillarmikroskopische Veränderungen[zum vollständigen Text gelangen Sie über die oben angegebene URL]
Medicine, 2021
Supplemental Digital Content is available in the text Abstract Treatment of ANCA-associated vascu... more Supplemental Digital Content is available in the text Abstract Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality. In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement. Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m2 vs 35 ± 26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m2 vs +6.0 ± 1.1 mL/min/1.73 m2, P = .33). The 2.5–3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2−6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1–4.5], P = .032). A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.
Blood, 2005
Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic b... more Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic bone pain, improving quality of life in patients with malignant bone disease. However, clinical studies have highlighted that some, but not all intravenous (i.v.) bisphosphonates are associated with an increased risk of renal toxicity. The renal safety of bisphosphonates is particularly important in patients with multiple myeloma or in the elderly, who often have some degree of underlying renal damage and are at high risk of renal failure. In phase III trials, the renal safety profile of i.v. ibandronate was comparable to placebo. This agent may therefore be suitable for use in patients with impaired renal health. The current open-label study assessed the renal safety of ibandronate in elderly patients with multiple myeloma and varying stages of pre-existing renal impairment. Patients with multiple myeloma (creatinine clearance 8–139mL/min) received i.v. ibandronate (6mg, infused over 30 ...
Blood, 2010
4935 Background Doxorubicin (Dox) is the back bone of chemotherapy in the therapy of several type... more 4935 Background Doxorubicin (Dox) is the back bone of chemotherapy in the therapy of several types of carcinomas, lymphomas and acute leukemias. Obese patients (Body Mass Index…
Zeitschrift für Rheumatologie, 2018
ObjectiveIn distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonog... more ObjectiveIn distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonography including the detection of the double contour sign (DCS) and hypervascularization using power Doppler ultrasound (PDUS) is an important step in the diagnostic process. But are these sonographic features equally reliable in every accessible joint under real-life conditions?MethodsWe retrospectively analyzed 362 patients with acute arthritis and evaluated the DCS and the degree of PDUS hypervascularization in patients with gout and in those with arthritis other than urate arthritis (non-UA). We classified all joints into the groups small, medium, and large. Sensitivities, specificities, positive and negative predictive values (PPV/NPV), and a binary regression model were calculated. We also evaluated the influence of serum uric acid levels (SUA) on the presence of a DCS in each joint category.ResultsSensitivity of the DCS in gout was 72.5% in the entire cohort, 66.0% in large, 78.8% in medium, and 72.3% in small joints. In wrist joints the DCS sensitivity maxed at 83.3%, with a specificity of 81.8%. The lowest rates of DCS sensitivity were found in gout patients with elbow joint involvement (42.9%). In all joints except metatarsophalangeal joint 1 (MTP-1), the incidence of a DCS increased by the increment of SUA levels above 7.5 mg/dl (p < 0.001). PDUS signals were most commonly found in medium and small joints and were only scarce in large joints, independent of the underlying diagnosis.ConclusionsIn our study we detected different rates of accuracy regarding DCS and PDUS in patients with acute arthritis. The best results were seen in medium-size joints, especially wrists.ZusammenfassungZielBei der Unterscheidung zwischen Gichtarthritis und nichtkristallassoziierten Arthritiden ist die Arthrosonographie zur Detektion des Doppelkonturzeichens (DCS) und der Hypervaskularisation im Power-Doppler-Ultraschall (PDUS) ein wichtiger Schritt im diagnostischen Prozess. Aber sind diese sonographischen Zeichen unter Alltagsbedingungen gleichsam zuverlässig in allen untersuchbaren Gelenken?MethodenRetrospektiv wurden die Daten von 362 Patienten mit akuter Arthritis und das DCS analysiert sowie die Hypervaskularisation im PDUS bei Fällen mit Uratarthritis (UA) vs. Nichturatarthritis (non-UA) ausgewertet. Alle Gelenke wurden der Größe nach in klein, mittel und groß eingeordnet. Es wurden Sensitivitäten, Spezifitäten, positive und negative prädiktive Werte und eine binäre Regression kalkuliert. Außerdem werteten die Autoren den Einfluss der Serumharnsäure auf die Detektierbarkeit eines DCS in jeder Gelenkkategorie aus.ErgebnisseDie Sensitivität des DCS bei Gicht in der gesamten Kohorte lag bei 72,5 %, bei großen Gelenken bei 66,0 %, bei mittleren betrug sie 78,8 % und bei kleinen 72,3 %. Die beste Sensitivität war bei Handgelenken mit 83,3 % bei einer Spezifität von 81,8 % zu verzeichnen. Die niedrigste Sensitivität fanden die Autoren bei Ellbogenmanifestation (42,9 %). Bei allen Gelenken außer dem Metatarsophalangealgelenk 1 (MTP-1) war die Inzidenz eines DCS bei Serumharnsäurewerten >7,5 mg/dl signifikant erhöht (p < 0,001). PDUS-Signale wurden unabhängig von der Diagnose am häufigsten bei mittleren und kleinen, dagegen kaum bei großen Gelenken gefunden.SchlussfolgerungenIn der vorliegenden Studie war die Genauigkeit der Vorhersage einer Gichtarthritis durch das DCS sowie das Auftreten von PDUS-Hypervaskularität je nach Gelenk unterschiedlich. Die besten Ergebnisse wurden in mittelgroßen Gelenken, insbesondere Handgelenken, erzielt.
Clinical Lymphoma Myeloma and Leukemia, 2015
was 39.1% in stage I, 41.4% in II, and 18.4% in III. Patients with standard and high cytogenetic ... more was 39.1% in stage I, 41.4% in II, and 18.4% in III. Patients with standard and high cytogenetic risk were 57.5% and 37.9%. More than a half of patients (59.8%) were treated with thalidomide induction. Patients with low and high BM FDG uptake were 69 and 18. High cytogenetic risk (RR 8.20, P1⁄40.018), anemia (RR 5.07, P1⁄40.056), BM plasma cells more than 30% (HR 3.68, P1⁄40.050) and extramedullary disease (EMD; RR 7.72, P1⁄40.017) were associated with high uptake. Three year progression free survival rate was 52.8% in low group and 31.8% in high group (P1⁄40.3916). Overall survival (OS) rate for 5 years in low group was 54.7%, while it was 45.4% (HR 1.976, 95% CI 0.26-0.75, P1⁄40.0538) in high group. To enhance homogeneity of the study population, we run subgroup analyses of patients with thalidomide based induction regimen (n1⁄448). Patients with low and high uptake were 34 and 14, respectively. Five year OS in high group was 48.5% (HR 2.41, 95% CI 0.1762-0.7395, P1⁄40.043), while it was 61.0% in low group. ECOG 2 (HR 2.78, P1⁄40.045), BM plasma cells 30% (HR 3.98, P1⁄40.005), ISS stage III (HR 4.18, P1⁄40.013), elevated LDH (HR 1.33, P1⁄40.004) and 2 microglobulin (HR 4.43, P1⁄40.019). Autologous hematopoietic stem cell transplantation (HR 0.23, P1⁄40.020) and the absence of EMD (HR 0.36, P1⁄40.049) were related with better prognosis. Conclusion: Initial high BM FDG uptake by direct visual assessment in MM showed correlations with poor prognosis and more aggressive disease. This finding could make possible simple and fast prediction of prognosis in MM.
Zeitschrift für Rheumatologie, 2017
Joint Bone Spine, 2016
Please cite this article in press as: Löffler C, et al. In arthritis the Doppler based degree of ... more Please cite this article in press as: Löffler C, et al. In arthritis the Doppler based degree of hypervascularisation shows a positive correlation with synovial leukocyte count and distinguishes joints with leukocytes greater and less than 5/nL. Joint Bone Spine (2016),
Zeitschrift f�r Rheumatologie, 2004
Rheumatologie-Integration in die studentische Ausbildung (RISA) Zur aktuellen Struktur der intern... more Rheumatologie-Integration in die studentische Ausbildung (RISA) Zur aktuellen Struktur der internistischen Rheumatologie an deutschen Hochschulen (RISA III) Zusatzmaterial online Die Fragebögen zur Erhebung der im Beitrag vorgestellten Daten finden Sie als "Supplementary Material" unter
Diagnostics, 2021
Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition ... more Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) remains a hurdle in daily practice without imaging or arthrocentesis. We performed a retrospective analysis of consecutive patients with gout, CPPD, and OA at a tertiary rheumatology center. A total of 277 patients were enrolled, with 164 suffering from gout, 76 from CPPD, and 37 from OA. We used ANOVA and conditional inference tree analysis (Ctrees) to find associations between clinical, laboratory, and imaging data and gout, OA, and CPPD. The sonographic double contour sign was unable to differentiate gout from CPPD. Ctrees were able to exclude OA and CPPD as possible differentials based on elevated uric acid, C-reactive protein (CRP), presence of arterial hypertension, and sex, diagnosing gout with a sensitivity and specificity of 95.1% and 41.6%, respectively. Elevated CRP was observed using simple linear regressions in patients with type II diabetes, higher cumulative...
International Journal of Molecular Sciences
The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observa... more The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, a...
Background: The estimated cost of Rheumatoid arthritis (RA) in Germany exceeded 6 million € in 20... more Background: The estimated cost of Rheumatoid arthritis (RA) in Germany exceeded 6 million € in 2008, and represents a significant burden to the healthcare system. Drug management of patients with RA aims to relieve pain and modify the disease evolution, and includes non-steroidal anti-inflammatory[for full text, please go to the a.m. URL]
Ultraschall in der Medizin - European Journal of Ultrasound, 2012
Revue du Rhumatisme, 2017
Objectifs : L'atteinte de la hanche est courante dans les affections rhumatologiques mais son dia... more Objectifs : L'atteinte de la hanche est courante dans les affections rhumatologiques mais son diagnostic peut s'avérer difficile en particulier en l'absence d'examen IRM. L'échographie en mode B permet de détecter une dilatation capsulaire mais la différenciation entre un épanchement articulaire et une prolifération synoviale reste difficile puisque ces deux entités apparaissent hypoéchogènes. L'échographie en mode Doppler puissance (DP) ne parvient pas toujours à détecter la vascularisation de la hanche. Nous avons donc évalué l'intérêt de l'échographie de contraste (EC) dans l'exploration de la hanche. Méthodes : 36 hanches de patients atteints d'une maladie rhumatismale connue et présentant des douleurs de la hanche ainsi que 5 hanches de témoins sains ont été analysées au moyen de l'échographie en mode B, du DP et de l'EC. Nous avons procédé à une étude semi-quantitative du rehaussement à l'échographie de contraste pour détecter le degré d'hypervascularisation par comparaison au tissu périarticulaire. En mode B, nous avons mesuré la distance séparant le col fémoral de la capsule articulaire (DNC) puis comparé les résultats avec la marge avasculaire intra-articulaire (AIM) visible à l'EC à l'aide de tests t et de tableaux croisés. Résultats : Les signaux Doppler ont été reçus dans seulement 2/36 cas (5,6 %). L'échographie en mode B permettait d'établir le diagnostic de coxite dans 64 % des hanches symptomatiques. Dans 4 cas (11 %) le diagnostic a été corrigé après le recours à l'EC. Parmi les patients atteints d'une coxite définie, 14 hanches (73,7 %) ont montré une hypervascularisation °2 à l'EC, cinq °1 (26,3 %) et aucune °0 (χ 2 = 3,277, p < 0,001). La différence DNC/AIM était très significative chez les patients souffrant de douleurs de la hanche (p < 0,001, IC 95 % 2,054-4,684) et ceux atteints d'une coxite définie (p < 0,001, IC 95 % 3,268-7,258).
Joint Bone Spine, 2016
Hip involvement is common in rheumatological diseases but can be difficult to diagnose, especiall... more Hip involvement is common in rheumatological diseases but can be difficult to diagnose, especially in absence of MRI. B-mode ultrasound (US) detects joint capsule distention while distinguishing effusion from proliferative synovial tissue is strenuous since both appear hypoechoic. Power Doppler ultrasound (PDUS) often fails to detect vascularisation in the hip. We therefore evaluated contrast-enhanced ultrasound (CEUS) in the hip joint. We investigated 36 hip joints of patients with known rheumatological joint diseases presenting with hip pain and 5 hips of healthy controls using B-mode US, PDUS and CEUS. We assessed CEUS hypervascularisation semiquantitatively comparing to the periarticular tissue. In B-mode, we measured the distance between femoral neck and joint capsule (DNC) and compared the results to the avascular intraarticular margin (AIM) in CEUS using t-tests and crosstables. PDUS signals were received in only 2/36 cases (5.6%). B-mode US established the diagnosis of coxitis in 64% of all symptomatic hip joints. In 4 cases (11%), the diagnosis was revised after the use of CEUS. In patients with definite coxitis, 14 hips (73.7%) showed CEUS hypervascularisation°2, five°1 (26.3%) and none°0 (χ(2)=3.277, P&amp;lt;0.001). The difference DNC/AIM was highly significant in patients with hip pain (P&amp;lt;0.001, 95% CI: 2.054-4.684) and those with definite coxitis (P&amp;lt;0.001, 95% CI: 3.268-7.258). In most cases, clinical parameters together with B-mode US findings are sufficient to diagnose coxitis. However, CEUS is capable of visualizing and quantifying the degree of hypervascularisation and enables the discrimination between effusion and proliferative synovial tissue.
Clinical Nuclear Medicine, 2009
Transplantation is the treatment of choice for hepatocellular carcinoma (HCC) meeting the Milan c... more Transplantation is the treatment of choice for hepatocellular carcinoma (HCC) meeting the Milan criteria. HCC and chronic liver diseases have distinct natural histories for which an equitable transplant policy must account. We enrolled and prospectively followed at a single center 206 consecutive HCC patients that presented within the Milan criteria. Patients were treated per the Barcelona Clinic Liver Cancer (BCLC) algorithm; 95% received resection, ablation, or transarterial chemoembolization. The median follow-up was 16 months. Progression occurred in 84 patients, and 8 patients died. Risk factors for the time to disease progression (death or progression beyond T2) were analyzed in 170 patients with a complete data set. Risk factors with the strongest relationship to progression included tumor diameter and tumor persistence/recurrence after local therapy (hazard ratios of 1.51 and 2.75, respectively, when transplanted patients were censored at the time of transplantation and hazard ratios of 1.53 and 3.66, respectively, when transplantation was counted as an event; P 0.0001). To evaluate the current Model for End-Stage Liver Disease (MELD) exception, we compared the expected progression rate (PR) with our observed PR in 133 stage T2 patients. The current policy resulted in a large overestimation of the PR for T2 HCC and an unsatisfactory performance [Harrell's concordance index (C index) ¼ 0.60, transplant censored; C index ¼ 0.55, transplant as progression]. Risk factors for progression that were identified by univariate analysis were considered for multivariate analysis. With these risk factors and the patients' natural MELD scores, an adjusted model applicable to organ allocation was generated, and this decreased the discrepancy between the expected and observed PRs (C index ¼ 0.66, transplant censored; C index ¼ 0.69, transplant as progression). In conclusion, the current MELD exception largely overestimates progression in T2 patients treated according to the BCLC guidelines. The tumor response to resective or ablative treatment can predict tumor progression beyond the Milan criteria, and it should be taken into account in models designed to prioritize organ allocation.
Journal of Gastrointestinal and Liver Diseases
Background and Aims: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As ... more Background and Aims: Liver involvement in sarcoidosis may occur in up to 60% of all patients. As many patients experience only minor symptoms, a high number of undiagnosed cases must be assumed. In order to successfully identify patients with hepatic sarcoidosis, a throughout characterization of these patients and their course of disease is necessary. Methods: We collected 40 patients from four German centers to evaluate current treatment standards and course of disease. All of our patients underwent liver biopsy with histologically proven granulomatous hepatitis. Results: Detailed characterization of our patients showed an overall benign course of disease. Treatment was very diverse with glucocorticoids for 1 year in 55% (22/40), 5-10 years in 18% (7/40), and permanently in 18% (7/40). Other treatments included disease-modifying anti-rheumatic drugs (DMARDs), the conventional non-biological type in 53% of all patients (of these 81% received azathioprine, 46% metotrexate, 10% hydrox...
Arthritis und Rheuma
Liebe Kolleginnen und Kollegen, in den vergangenen Jahren sind in der Rheumatologie immer wieder ... more Liebe Kolleginnen und Kollegen, in den vergangenen Jahren sind in der Rheumatologie immer wieder neue Krankheitsentitäten entdeckt und neu definiert worden. Teilweise wurden diese früher unter anderen Diagnosen subsummiert und erst die Entdeckung neuer Autoantikörper oder anderer diagnostischer Marker hat den Blick dafür geschärft, dass hier eigenständige Erkrankungen mit unterschiedlichen Verläufen und Therapieansätzen vorliegen. Auf jeden Fall sind diese "neuen Krankheiten" inzwischen ein Teil der täglichen diagnostischen und therapeutischen Herausforderungen für klinisch tätige Rheumatologen. Die vorliegende Ausgabe von arthritis + rheuma widmet sich einigen dieser neuen Krankheitsentitäten und stellt diese dar.
Journal of Clinical Medicine
Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituxi... more Background: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. Methods: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19+ peripheral B-cells were quantified using flow cytometry. Results: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID50 of 0 (0–1:20) compared to 1:320 (1:160–1:320) in healthy controls (for all p < 0.001). Longer ...
Einleitung: Die Kapillarmikroskopie ist in der Diagnostik vor allem der Sklerodermie fest etablie... more Einleitung: Die Kapillarmikroskopie ist in der Diagnostik vor allem der Sklerodermie fest etabliert. In der Diagnostik und Beurteilung von Vasculitiden ist der Wert der Kapillarmikroskopie bisher jedoch unbekannt. Wir untersuchten daher Patienten mit ANCA-Vasculitiden auf Kapillarmikroskopische Veränderungen[zum vollständigen Text gelangen Sie über die oben angegebene URL]
Medicine, 2021
Supplemental Digital Content is available in the text Abstract Treatment of ANCA-associated vascu... more Supplemental Digital Content is available in the text Abstract Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality. In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement. Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m2 vs 35 ± 26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m2 vs +6.0 ± 1.1 mL/min/1.73 m2, P = .33). The 2.5–3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2−6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1–4.5], P = .032). A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.
Blood, 2005
Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic b... more Bisphosphonates effectively reduce the number of skeletal-related events and relieve metastatic bone pain, improving quality of life in patients with malignant bone disease. However, clinical studies have highlighted that some, but not all intravenous (i.v.) bisphosphonates are associated with an increased risk of renal toxicity. The renal safety of bisphosphonates is particularly important in patients with multiple myeloma or in the elderly, who often have some degree of underlying renal damage and are at high risk of renal failure. In phase III trials, the renal safety profile of i.v. ibandronate was comparable to placebo. This agent may therefore be suitable for use in patients with impaired renal health. The current open-label study assessed the renal safety of ibandronate in elderly patients with multiple myeloma and varying stages of pre-existing renal impairment. Patients with multiple myeloma (creatinine clearance 8–139mL/min) received i.v. ibandronate (6mg, infused over 30 ...
Blood, 2010
4935 Background Doxorubicin (Dox) is the back bone of chemotherapy in the therapy of several type... more 4935 Background Doxorubicin (Dox) is the back bone of chemotherapy in the therapy of several types of carcinomas, lymphomas and acute leukemias. Obese patients (Body Mass Index…
Zeitschrift für Rheumatologie, 2018
ObjectiveIn distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonog... more ObjectiveIn distinguishing urate arthritis (UA) from non-crystal-related arthritides, joint sonography including the detection of the double contour sign (DCS) and hypervascularization using power Doppler ultrasound (PDUS) is an important step in the diagnostic process. But are these sonographic features equally reliable in every accessible joint under real-life conditions?MethodsWe retrospectively analyzed 362 patients with acute arthritis and evaluated the DCS and the degree of PDUS hypervascularization in patients with gout and in those with arthritis other than urate arthritis (non-UA). We classified all joints into the groups small, medium, and large. Sensitivities, specificities, positive and negative predictive values (PPV/NPV), and a binary regression model were calculated. We also evaluated the influence of serum uric acid levels (SUA) on the presence of a DCS in each joint category.ResultsSensitivity of the DCS in gout was 72.5% in the entire cohort, 66.0% in large, 78.8% in medium, and 72.3% in small joints. In wrist joints the DCS sensitivity maxed at 83.3%, with a specificity of 81.8%. The lowest rates of DCS sensitivity were found in gout patients with elbow joint involvement (42.9%). In all joints except metatarsophalangeal joint 1 (MTP-1), the incidence of a DCS increased by the increment of SUA levels above 7.5 mg/dl (p < 0.001). PDUS signals were most commonly found in medium and small joints and were only scarce in large joints, independent of the underlying diagnosis.ConclusionsIn our study we detected different rates of accuracy regarding DCS and PDUS in patients with acute arthritis. The best results were seen in medium-size joints, especially wrists.ZusammenfassungZielBei der Unterscheidung zwischen Gichtarthritis und nichtkristallassoziierten Arthritiden ist die Arthrosonographie zur Detektion des Doppelkonturzeichens (DCS) und der Hypervaskularisation im Power-Doppler-Ultraschall (PDUS) ein wichtiger Schritt im diagnostischen Prozess. Aber sind diese sonographischen Zeichen unter Alltagsbedingungen gleichsam zuverlässig in allen untersuchbaren Gelenken?MethodenRetrospektiv wurden die Daten von 362 Patienten mit akuter Arthritis und das DCS analysiert sowie die Hypervaskularisation im PDUS bei Fällen mit Uratarthritis (UA) vs. Nichturatarthritis (non-UA) ausgewertet. Alle Gelenke wurden der Größe nach in klein, mittel und groß eingeordnet. Es wurden Sensitivitäten, Spezifitäten, positive und negative prädiktive Werte und eine binäre Regression kalkuliert. Außerdem werteten die Autoren den Einfluss der Serumharnsäure auf die Detektierbarkeit eines DCS in jeder Gelenkkategorie aus.ErgebnisseDie Sensitivität des DCS bei Gicht in der gesamten Kohorte lag bei 72,5 %, bei großen Gelenken bei 66,0 %, bei mittleren betrug sie 78,8 % und bei kleinen 72,3 %. Die beste Sensitivität war bei Handgelenken mit 83,3 % bei einer Spezifität von 81,8 % zu verzeichnen. Die niedrigste Sensitivität fanden die Autoren bei Ellbogenmanifestation (42,9 %). Bei allen Gelenken außer dem Metatarsophalangealgelenk 1 (MTP-1) war die Inzidenz eines DCS bei Serumharnsäurewerten >7,5 mg/dl signifikant erhöht (p < 0,001). PDUS-Signale wurden unabhängig von der Diagnose am häufigsten bei mittleren und kleinen, dagegen kaum bei großen Gelenken gefunden.SchlussfolgerungenIn der vorliegenden Studie war die Genauigkeit der Vorhersage einer Gichtarthritis durch das DCS sowie das Auftreten von PDUS-Hypervaskularität je nach Gelenk unterschiedlich. Die besten Ergebnisse wurden in mittelgroßen Gelenken, insbesondere Handgelenken, erzielt.
Clinical Lymphoma Myeloma and Leukemia, 2015
was 39.1% in stage I, 41.4% in II, and 18.4% in III. Patients with standard and high cytogenetic ... more was 39.1% in stage I, 41.4% in II, and 18.4% in III. Patients with standard and high cytogenetic risk were 57.5% and 37.9%. More than a half of patients (59.8%) were treated with thalidomide induction. Patients with low and high BM FDG uptake were 69 and 18. High cytogenetic risk (RR 8.20, P1⁄40.018), anemia (RR 5.07, P1⁄40.056), BM plasma cells more than 30% (HR 3.68, P1⁄40.050) and extramedullary disease (EMD; RR 7.72, P1⁄40.017) were associated with high uptake. Three year progression free survival rate was 52.8% in low group and 31.8% in high group (P1⁄40.3916). Overall survival (OS) rate for 5 years in low group was 54.7%, while it was 45.4% (HR 1.976, 95% CI 0.26-0.75, P1⁄40.0538) in high group. To enhance homogeneity of the study population, we run subgroup analyses of patients with thalidomide based induction regimen (n1⁄448). Patients with low and high uptake were 34 and 14, respectively. Five year OS in high group was 48.5% (HR 2.41, 95% CI 0.1762-0.7395, P1⁄40.043), while it was 61.0% in low group. ECOG 2 (HR 2.78, P1⁄40.045), BM plasma cells 30% (HR 3.98, P1⁄40.005), ISS stage III (HR 4.18, P1⁄40.013), elevated LDH (HR 1.33, P1⁄40.004) and 2 microglobulin (HR 4.43, P1⁄40.019). Autologous hematopoietic stem cell transplantation (HR 0.23, P1⁄40.020) and the absence of EMD (HR 0.36, P1⁄40.049) were related with better prognosis. Conclusion: Initial high BM FDG uptake by direct visual assessment in MM showed correlations with poor prognosis and more aggressive disease. This finding could make possible simple and fast prediction of prognosis in MM.
Zeitschrift für Rheumatologie, 2017
Joint Bone Spine, 2016
Please cite this article in press as: Löffler C, et al. In arthritis the Doppler based degree of ... more Please cite this article in press as: Löffler C, et al. In arthritis the Doppler based degree of hypervascularisation shows a positive correlation with synovial leukocyte count and distinguishes joints with leukocytes greater and less than 5/nL. Joint Bone Spine (2016),
Zeitschrift f�r Rheumatologie, 2004
Rheumatologie-Integration in die studentische Ausbildung (RISA) Zur aktuellen Struktur der intern... more Rheumatologie-Integration in die studentische Ausbildung (RISA) Zur aktuellen Struktur der internistischen Rheumatologie an deutschen Hochschulen (RISA III) Zusatzmaterial online Die Fragebögen zur Erhebung der im Beitrag vorgestellten Daten finden Sie als "Supplementary Material" unter
Diagnostics, 2021
Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition ... more Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) remains a hurdle in daily practice without imaging or arthrocentesis. We performed a retrospective analysis of consecutive patients with gout, CPPD, and OA at a tertiary rheumatology center. A total of 277 patients were enrolled, with 164 suffering from gout, 76 from CPPD, and 37 from OA. We used ANOVA and conditional inference tree analysis (Ctrees) to find associations between clinical, laboratory, and imaging data and gout, OA, and CPPD. The sonographic double contour sign was unable to differentiate gout from CPPD. Ctrees were able to exclude OA and CPPD as possible differentials based on elevated uric acid, C-reactive protein (CRP), presence of arterial hypertension, and sex, diagnosing gout with a sensitivity and specificity of 95.1% and 41.6%, respectively. Elevated CRP was observed using simple linear regressions in patients with type II diabetes, higher cumulative...