Pet-related bacterial zoonotic infections: Three cases of severe infections in the immunocompromised host.

Pets can have many positive effects on their owners. However, close contact with pets offers optimal conditions for transmission of micro-organisms. Especially immunocompromised patients are at risk for zoonotic infections. Here we describe the diagnosis, microbiology and treatment of three patients with severe zoonotic infections with Helicobacter canis, Pasteurella multocida and Capnocytophaga canimorsus. With this case report we would like to emphasize the importance of awareness for pet-related zoonotic infections in immunocompromised patients.

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis.

OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.

Assessing recovery after cold challenge and thumb involvement can help to rule out systemic sclerosis in patients presenting with Raynaud's phenomenon.

Objective: Our aim was to study whether recovery from a Raynaud's attack and involvement of the thumb are differentiators for systemic sclerosis (SSc) in patients with Raynaud's phenomenon (RP).Method: A stepwise cooling and recovery procedure was performed, provoking an RP attack, in patients with primary Raynaud's phenomenon (PRP, n = 68) and SSc (n = 18). During the procedure, the perfusion of all five fingers during cooling and recovery was assessed by photoelectric plethysmography.Results: In SSc patients, perfusion after 10 min in one or more fingers was more frequently not restored than in PRP patients (p = 0.001), with a negative predictive value of 98%. The thumb was more frequently involved in SSc patients (p = 0.036), with a negative predictive value of 95%. Positive predictive values were low.Conclusions: In patients with RP, when there is restoration of perfusion in all fingers after 10 min or when the thumb is spared, the presence of an underlying SSc is very unlikely. Although these results need to be validated in a clinical setting in a larger prospective study, these signs can help physicians to select additional testing for SSc in RP patients.

Pulmonary involvement in primary Sjögren's syndrome, as measured by the ESSDAI.

Objective: Systemic features influence disease prognosis and choice of treatment in primary Sjögren's syndrome (pSS). Our aim was to investigate the prevalence of pulmonary involvement in pSS patients and to classify patients according to the pulmonary domain of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).Methods: This retrospective cohort study included consecutive pSS patients, fulfilling American-European Consensus Group/American College of Rheumatology classification criteria, who visited the Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, in 2015. Data on pulmonary complaints and pulmonary tests were obtained from electronic patient records. Pulmonary involvement was recorded if therapy was needed or follow-up was recommended, and when it was possibly or assumed to be related to pSS instead of coincidental factors.Results: Of the 262 included pSS patients, 88 (34%) had pulmonary complaints, mostly cough or dyspnoea on exertion. Pulmonary diagnostics were performed in 225 patients (86%). Pulmonary involvement was present and assumed to be related to pSS in 25 patients (10%) and possibly related to pSS in 14 (5%). Interstitial lung disease (ILD, n = 15), especially non-specific interstitial pneumonia (n = 7), was present most commonly. In total, 16 patients (6%) were scored as low (n = 4), moderate (n = 11), or high activity (n = 1) on the ESSDAI pulmonary domain.Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was present in 10-15% of pSS patients, of which ILD was most common. Of all pSS patients, 6% were scored as active on the pulmonary domain of the ESSDAI.

Diagnostic properties of ultrasound of major salivary glands in Sjögren's syndrome: a meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis on studies examining the properties of ultrasonography of major salivary glands for diagnosing Sjögren's syndrome. MATERIALS AND METHODS: We searched for the literature on eight databases. The quality of included articles was assessed with the QUADAS-2 tool. Publication bias, pooled sensitivity, specificity, diagnostic odds ratio, and 95% confidence intervals (95%CI) were calculated. Meta-regression analysis was performed. RESULTS: We identified 37 studies and 33 ultrasonographic scoring systems. High risk of bias was observed in 'patient selection', 'conduct and interpretation of ultrasound', and 'flow of patients and timing of tests' in 78%, 70%, and 51% of the studies. We included 29 studies in the meta-analysis. Publication bias was highly probable. Pooled sensitivity was 0.69 (95%CI: 0.67-0.71), specificity 0.92 (95%CI: 0.91-0.93), and diagnostic odds ratio 33.89 (95%CI: 20.75-55.35). Significant heterogeneity was detected between studies. Meta-regression analysis showed that studies with high risk of bias in 'conduct and interpretation of ultrasound' and studies evaluating only parenchymal homogeneity had higher log diagnostic odds ratio (1.09 and 2.49, respectively, p < 0.05). CONCLUSIONS: The quality of current studies is low, thus not allowing to judge the likelihood of salivary gland ultrasonography as a reliable and practical tool in diagnosing Sjögren's syndrome.

Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells.

This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3varepsilon-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid-hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab')2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases.