Synovial fluid D-lactate - a pathogen-specific biomarker for septic arthritis: a prospective multicenter study.

OBJECTIVES: The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated. METHODS: Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. RESULTS: In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively. CONCLUSIONS: Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Analysis of patients with rheumatoid arthritis and higher radiographic progression: association of very high radiographic progression but not of intermediately high with worsening of patient-related outcomes.

OBJECTIVES: To analyse rheumatoid arthritis (RA)-patients depending on their individual peak radiographic progression. METHODS: We selected for the individual peak radiographic progression (Δ Ratingen scores/time) in patients of the Swiss registry SCQM. The baseline disease characteristics were compared using standard descriptive statistics. The change of DAS 28 (disease activity sore) and HAQ-DI (Health Assessment Questionnaire Disability Index) before and after peak progression was analysed with Wilcoxon signed rank tests. RESULTS: Of the 4,033 patients in the analysis, 3,049 patients had a peak radiographic progression rate between 0 and ≤10 in the Ratingen score per year, 773 between 10 and ≤20, 150 between 20 and ≤30, and 61 of >30 (defining groups A-D). Rheumatoid factor was more frequent in patient groups with a higher peak radiographic progression (71.1%, 79.2%, 85.3%, 88.5%, groups A-D). Peak radiographic progression at a rate >20/year (groups C-D) was not detected after December 2012. When the rate of radiographic progression before and after peak progression was analysed, it was significantly lower. The DAS 28 was significantly higher in all patient groups before peak progression and lower thereafter (p<0.001). Average HAQ-DI scores increased after peak radiographic progression in group D (p=0.005) whereas it was stable or even decreased among the patients of the other patient groups. CONCLUSIONS: These data show that the highest radiographic progression rates are rare and get less frequent over the last years. Higher disease activity precedes radiographic peak progression. Only the highest individual peak (change of Ratingen score >30/year) radiographic progression was followed by an increase of HAQ-DI scores.

Colorectal cancer surveillance by colonoscopy in a prospective, population-based long-term Swiss screening study - outcomes, adherence, and costs.

BACKGROUND: The success of colorectal cancer (CRC) screening depends mainly on screening quality, patient adherence to surveillance, and costs. Consequently, it is essential to assess the performance over time. METHODS: In 2000, a closed cohort study on CRC screening in individuals aged 50 to 80 was initiated in Uri, Switzerland. Participants who chose to undergo colonoscopy were followed over 18 years. We investigated the adherence to recommended surveillance and collected baseline characteristics and colonoscopy data. Risk factors at screening for the development of advanced adenomas were analyzed. Costs for screening and follow-up were evaluated retrospectively. RESULTS: 1278 subjects with a screening colonoscopy were included, of which 272 (21.3%; 69.5% men) had adenomas, and 83 (6.5%) had advanced adenomas. Only 59.8% participated in a follow-up colonoscopy, half of them within the recommended time interval. Individuals with advanced adenomas at screening had nearly five times the risk of developing advanced adenomas compared to individuals without adenomas (24.3% vs. 5.0%, OR 4.79 CI 2.30-9.95). Individuals without adenomas developed advanced adenomas in 4.9%, including four cases of CRC; three of them without control colonoscopy. The villous component in adenomas smaller than 10 mm was not an independent risk factor. Costs for screening and follow-up added up to CHF 1'934'521 per 1'000 persons screened, almost half of them for follow-up examinations; 60% of these costs accounted for low-risk individuals. CONCLUSION: Our findings suggest that follow-up of screening colonoscopy should be reconsidered in Switzerland; in particular, long-term adherence is critical. Costs for follow-up could be substantially reduced by adopting less expensive long-term screening methods for low-risk individuals.

Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report.

Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like syndromes and severe pyogenic infections. Among these, complete C1s deficiency has been reported in nine cases so far. Here, we describe a 34-year-old male patient who presented with severe, recurrent infections since childhood, including meningitides with pneumococci and meningococci, erysipelas, subcutaneous abscess, and recurrent infections of the upper airways. The patient also exhibited adult-onset SLE, meeting 7/11 of the ACR criteria and 34 of the 2019 EULAR/ACR classification criteria, along with class IV-G (A) proliferative lupus nephritis (LN). A screening of the complement cascade showed immeasurably low CH50, while the alternative pathway (AP) function was normal. Subsequent determination of complement components revealed undetectable C1s with low levels of C1r and C1q, normal C3, and slightly elevated C4 and C2 concentrations. The patient had no anti-C1q antibodies. Renal biopsy showed class IV-G (A) LN with complement C1q positivity along the glomerular basement membranes (GBMs) and weak deposition of IgG, IgM, and complement C3 and C4 in the mesangium and GBM. In an ELISA-based functional assay determining C4d deposition, the patient's absent complement activity was fully restored by adding C1s. The genome of the patient was analyzed by whole genome sequencing showing two truncating variants in the C1S gene. One mutation was located at nucleotide 514 in exon 5, caused by a nucleotide substitution from G to T, resulting in a nonsense mutation from Gly172 (p.Gly172*). The other mutation was located at nucleotide 750 in exon 7, where C was replaced by a G, resulting in a nonsense mutation from Tyr250 (p.Tyr250*). Both mutations create a premature stop codon and have not previously been reported in the literature. These genetic findings, combined with the absence of C1s in the circulation, strongly suggest a compound heterozygote C1s deficiency in our patient, without additional defect within the complement cascade. As in a previous C1s deficiency case, the patient responded well to rituximab. The present case highlights unanswered questions regarding the CP's role in SLE etiopathogenesis.