68Ga-PSMA-11 PET/CT mit low-dose CT : Diagnostischer Zugewinn durch minimale kontrastmittelgestützte Urographie

Ziel: Bei der Diagnostik des Prostatakarzinoms mithilfe der 68Ga-PSMA-11 PET/CT können durch renale Elimination verursachte fokale Traceranreicherungen im Ureter Lymphknotenmetastasen imitieren. Ein möglicher Lösungsansatz ist die Durchführung einer CT-Urographie unter Verwendung eines modifizierten Protokolls mit dem Ziel eine klare Identifikation des Ureters zu erreichen und somit eine falsche Interpretation der PET-Bilddaten zu vermeiden. Methode: In dieser retrospektiven Studie wurden CT-Urographie unterstützte 68Ga-PSMA-11 PET/CT Untersuchungen (low-dose CT mit 30 mAs, 120 kV) analysiert. Zur Durchführung der CT-Urographie erhielten die Patienten 10 Minuten vor der Untersuchung intravenös 30 ml iodiertes Kontrastmittel. Alle potentiell pathologischen Traceranreicherungen wurden entweder zur Gruppe der Traceranreicherungen im Ureter oder zur Gruppe der Lymphknotenmetastasen zugeordnet. Diese wurden dann anhand eines punktebasierten Bewertungssystems hinsichtlich des sich ergebenden Nutzens der CT-Urographie und der Hilfe dieser bei der Interpretation bewertet (0Punkte: CT-Urographie wird nicht benötigt bis 3 Punkte: Zuordnung ohne CT-Urographie nicht möglich). Der Erfolg der Kontrastierung wurde anhand der Messung von Hounsfield-Einheiten im Ureter quantifiziert. Zudem erfolgte eine retrospektive Analyse der therapeutischen Relevanz falsch positiver oder falsch negativer Befunde. Dafür wurde eine differente Bewertung der in der CT-Urographie identifizierten kritischen Stellen angenommen. Ergebnisse: In der Studie wurden 189 relevante potentiell pathologische Traceranreicherungen, verteilt auf 120/247 (48,6 %) Patienten, identifiziert, bei denen die implementierte CT-Urographie die Diagnostik erleichterte. Der Ureter konnte in allen n = 247 Untersuchungen eindeutig aufgefunden werden und war an 141/189 (74,6 %) Stellen als ausreichend kontrastiert bewertet worden. Bei der Betrachtung hinsichtlich einer therapeutischen Relevanz zeigte sich, dass in 60/247 (24,3 %) Untersuchungen die CT-Urographie hierfür hilfreich war. In 30/247 (12,1 %) Fällen hätte aus einer Fehldiagnose möglicherweise eine diskrepante Therapie resultiert. Schlussfolgerung: Die Integration der CT-Urographie in die 68Ga-PSMA-11 PET/CT erhöht die diagnostische Sicherheit insbesondere dann, wenn eine low-dose CT zur anatomischen Korrelation verwendet wird. In einer kleinen Subgruppe (12,1 %) konnte hierdurch eine diskrepante Therapie aufgrund einer möglichen Fehlinterpretation oder diagnostischen Unsicherheit vermieden werden. Die CT-Urographie sollte daher standardmäßig in die 68Ga-PSMA-11 PET/CT Protokolle integriert werden.Aim: In the diagnosis of prostate cancer using 68Ga-PSMA-11 PET/CT, focal tracer accumulations caused by renal elimination can mimic ureteral lymph node metastases. A possible solution is the implementation of a modified CT urography protocol to achieve a clear identification of the ureter, thereby preventing a false interpretation of the PET image data. Methods: In this retrospective study, CT-urography supported 68Ga-PSMA-11 PET/CT examinations (low-dose CT with 30 mAs, 120 kV) were analyzed. To perform the CT urography, patients received 30 ml iodinated contrast medium intravenously 10 minutes prior to the examination. All potentially pathological tracer accumulations were assigned either to the group of tracer accumulations in the ureter or to the group of lymph node metastases. Afterwards, these were evaluated by a score-based evaluation system, measuring the resulting benefit of CT urography and the assistance of the latter in interpretation (0 points: CT urography is not required up to 3 points: no differentiation possible without CT urography). The successful obtaining of a contrasted ureter was quantified by the measurement of Hounsfield units in the ureter. In addition, a retrospective analysis was performed to assess the therapeutic relevance of false positive or false negative findings. Therefore, a differential evaluation of the critical sites identified in CT urography was assumed. Results: In the trial, 189 relevant potentially pathological tracer accumulations were detected in 120/247 (48.6 %) patients, in which the implementation of CT urography assisted the diagnosis. The ureter was well detectable in all n = 247 examinations and was evaluated as being sufficiently contrasted at 141/189 (74.6 %) sites. Regarding the therapeutic relevance, CT urography was helpful in 60/247 (24.3 %) examinations. In 30/247 (12.1 %) cases, a misdiagnosis might have resulted in a discrepancy in therapy. Conclusion: The integration of CT urography into 68Ga-PSMA-11 PET/CT imaging improves the diagnostic confidence, particularly when a low-dose CT is used for anatomical correlation. For a small subgroup (12.1 %), the integration of CT urography prevented a discrepant therapy due to a potential misinterpretation or diagnostic uncertainty. Therefore, CT urography should be integrated into the 68Ga-PSMA-11 PET/CT protocols as a standard procedure

Marathon performance but not BMI affects post-marathon pro-inflammatory and cartilage biomarkers

We tested the hypothesis that changes in serum cartilage oligomeric matrix protein (COMP), tumour necrosis factor α (TNF-α), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) concentration after regular endurance training and running a marathon race depend on body mass index (BMI) and/or on marathon performance. Blood samples were collected from 45 runners of varying BMI and running experience before and after a 10-week marathon training programme and before, immediately and 24 h after a marathon race. Serum biomarker concentrations, BMI and marathon finishing time were measured. The mean (95% confidence interval (CI)) changes from before to immediately after the marathon were COMP: 4.09 U/L (3.39-4.79 U/L); TNF-α: -1.17 mg/L (-2.58 to 0.25 mg/L); IL-6: 12.0 pg/mL (11.4-12.5 pg/mL); and hsCRP: -0.08 pg/mL (-0.14 to -0.3 pg/mL). The mean (95% CI) changes from immediately after to 24 h after the marathon were COMP: 0.35 U/L (-0.88 to 1.57 U/L); TNF-α: -0.43 mg/L (-0.99 to 0.13 mg/L); IL-6: -9.9 pg/mL (-10.5 to -9.4 pg/mL); and hsCRP: 1.52 pg/mL (1.25-1.79 pg/mL). BMI did not affect changes in biomarker concentrations. Differences in marathon finishing time explained 32% of variability in changes in serum hsCRP and 28% of variability in changes in serum COMP during the 24 h recovery after the marathon race (P < 0.001). Slower marathon finishing time but not a higher BMI modulates increases in pro-inflammatory markers or cartilage markers following a marathon race

Preparation data of the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B and crystallization of BRD4(1)-inhibitor complexes

AbstractThis article presents detailed purification procedures for the bromodomains BRD3(1), BRD3(2), BRD4(1), and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1) and BRD4(1) in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC) and by differential scanning fluorimetry (DSF) as well as structural characterizations of BRD4(1) inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T). These data have been reported previously and are discussed in more detail elsewhere [1,2]

Controversial Aspects of Diagnostics and Therapy of Arthritis of the Temporomandibular Joint in Rheumatoid and Juvenile Idiopathic Arthritis: An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project

Introduction: Due to potentially severe sequelae (impaired growth, condylar resorption, and ankylosis) early diagnosis of chronic rheumatic arthritis of the temporomandibular joint (TMJ) and timely onset of therapy are essential. Aim: Owing to very limited evidence the aim of the study was to identify and discuss controversial topics in the guideline development to promote further focused research. Methods: Through a systematic literature search, 394 out of 3771 publications were included in a German interdisciplinary guideline draft. Two workgroups (1: oral and maxillofacial surgery, 2: interdisciplinary) voted on 77 recommendations/statements, in 2 independent anonymized and blinded consensus phases (Delphi process). Results: The voting results were relatively homogenous, except for a greater proportion of abstentions amongst the interdisciplinary group (p < 0.001). Eighty four percent of recommendations/statements were approved in the first round, 89% with strong consensus. Fourteen recommendations/statements (18.2%) required a prolonged consensus phase and further discussion. Discussion: Contrast-enhanced MRI was confirmed as the method of choice for the diagnosis of TMJ arthritis. Intraarticular corticosteroid injection is to be limited to therapy refractory cases and single injection only. In adults, alloplastic joint replacement is preferable to autologous replacement. In children/adolescents, autologous reconstruction may be performed lacking viable alternatives. Alloplastic options are currently still considered experimental

Scleroderma and related disorders: 223. Long Term Outcome in a Contemporary Systemic Sclerosis Cohort

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years. Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice. Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003). During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively). Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets. Disclosure statement: The authors have declared no conflicts of interes