Non-Helicobacter pylori species (NHPS) are newly emerging bacteria that naturally inhabit birds and mammals apart from humans and rarely cause diseases in humans. In recent years, a rise in the ...number of cases associated with NHPS infections in humans has been observed. Among them, infections with Helicobacter (H.) canis are sporadic and challenging to recognise clinically. To date, ten cases of H. canis infections in mainly immunocompromised humans have been reported in the literature. Transmission pathway is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake. No clear guidelines for successful antibiotic regimen are known. Important additional risk factor for infection might be biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions. Herein we present the first case of H. canis bacteraemia in a RA patient treated with novel JAKi tofacitinib.
A 65-year-old female patient with RA and rituximab-induced hypogammaglobulinemia treated with tofacitinib, methotrexate, and methylprednisolone came to a planned visit in our outpatient rheumatology clinic. She presented with a history of back pain that significantly worsened 2 days before visit. She had numbness and tingling sensation in both legs and muscle weakness. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. She was in close contact with her pet dogs. Laboratory examination showed increased markers of inflammation. She was found to have H. canis bacteraemia with underlying multilevel degenerative lumbar spinal stenosis. Identification of H. canis was performed by MALDI-TOF MS and 16 S rRNA gene sequence analysis of isolate from subcultured positive aerobic blood culture bottles. Antimicrobial susceptibility testing showed low minimum inhibitory concentrations to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin. She was treated with combined antibiotic regimen (ceftriaxone, doxycycline) for 14 days, which resulted in total remission of the infection.
Clinicians should recognise H. canis infection risk in patients with recent pet exposure and predisposing factors such as immunodeficiency disorders or diseases that demand immunosuppressive drug therapy. A minimum of two weeks of antibiotic therapy is suggested.
Imbalanced STAT5 phosphorylation in conventional and regulatory CD4 T cell subsets from SLE patients is related to their Bcl‐2 expression, homeostatic‐proliferation differences, and relapsing ...disease.
Activation of the STAT5 signaling pathway up‐regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (Tcons). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA−FOXP3hi activated regulatory T cells (aTregs) were described. We assessed Tcon/Treg subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty‐one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included. Long‐term monitoring was performed in 39 patients with SLE, which were followed longitudinally for up to 1000 d. Significantly increased Bcl2 protein content in T cells from patients with SLE was associated with IL‐7–dependent STAT5 activation, expressed as increased basal levels and nuclear localization of pSTAT5. pSTAT5 levels were significantly increased in the FOXP3 low‐expressing CD4+ T cell subsets but not in the aTreg subset, which was significantly decreased in patients with SLE. In contrast to aTreg, SLE Tcon displayed significantly increased pSTAT5 and Bcl2 levels. Moreover, the percentage of Tcon‐expressing proliferation marker Ki‐67 was significantly increased in patients with SLE and was positively correlated with CD4 T cell pSTAT5 levels. Finally, a subgroup of patients characterized by an increased Tcon–pSTAT5/aTreg–pSTAT5 ratio experienced a more aggressive‐relapsing disease course and displayed higher time‐adjusted cumulative CD4 T cell pSTAT5 levels during follow‐up, which were positively correlated with time‐adjusted cumulative disease activity. Our results indicate that imbalanced STAT5 phosphorylation, which is related to Bcl2 and Ki‐67 expression, may confer survival and proliferative advantage to Tcon over aTreg and could represent a possible marker of SLE disease severity.
Idiopathic inflammatory myopathies (IIMs) are rare systemic diseases associated with significant morbidity and mortality. The aim of our study was to estimate for the first time the survival of IIM ...patients in Slovenia.
We included IIM patients diagnosed between January 2005 and December 2020 and followed at two secondary/tertiary rheumatology centers in the country. To study survival/mortality the censor date of April 14 2021 was set. Kaplan-Meier analysis and standardized mortality ratio (SMR) were plotted using data of age and sex matched Slovenian population as a reference. Cox proportional hazards regression analysis was used to study prognostic factors for IIM mortality.
During the 16-year observation period, we identified 217 new IIM patients. During follow up 65 (30.0%) patients died. In the first year following IIM diagnosis the SMR was nearly 7-fold higher compared to the matched general population SMR 6.88 (95%CI 4.41-10.24) and remained higher also during the following 4 years. However, when excluding IIM patients with cancer, the survival outcome was, except in the first year after IIM diagnosis SMR 5.55 (95%CI 3.10-9.15), comparable to matched general population. In addition to cancer HR 3.71 (95% CI 2.18-6.04), cardiac involvement HR 2.18 (95% CI 1.07-4.45), fever HR 2.13 (95% CI 1.13-4.03), and older age HR 1.07 (95% CI 1.04-1.09) were extracted as prognostic factors associated with death.
The survival of patients with IIM patients was substantially worse compared to matched general population. Cancer was the leading cause of death in our cohort.
The Central European Congress of Rheumatology (CECR) has been organized by seven Central European countries: Austria, Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. These countries ...have lots of similarities, but also differences, with respect to rheumatology research. In this paper, based on questionnaires, we wish to demonstrate achievements and difficulties in rheumatology research performed in our region.
In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4
FOXP3
regulatory T cells (Tregs) were described. In the ...present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity. The highest STAT1 MFI was found in CD45RA
FOXP3
-activated Treg (aTreg) subset, which demonstrated the highest STAT1 phosphorylation responses among SLE CD4 T cells and significant decrease in proliferation marker Ki-67 expression after IFN-alpha stimulation. Percentage of Ki-67
aTregs was significantly decreased in SLE patients and was negatively correlated with CD4 T cell STAT1 MFI. A subgroup of SLE patients characterized by lower aTreg counts experienced more severe relapsing disease course during 1,000 days of follow-up. Mean CD4 T cell STAT1 MFI in follow-up samples from SLE patients was negatively correlated with mean of follow-up aTreg counts. Our findings indicate that augmented STAT1 signaling may be involved in perturbed aTreg homeostasis, which could represent a possible marker of SLE disease severity.
To recognise possible retinal changes in patients with SLE treated with chloroquine phosphate, as depending on the duration of treatment.
The study included 41 patients (82 eyes) who received ...treatment for SLE with chloroquine or hydroxychloroquine phosphate and had not previously been diagnosed with retinal pathology. Participants were divided into two groups according to the duration of treatment. The first group included 18 patients (36 eyes) treated for up to five years and the second group consisted of 23 patients (46 eyes) treated from five to twenty years. We performed a thorough eye exam, including best-corrected visual acuity, colour vision, visual field examination, dilated fundus examination, autofluorescence imaging, color fundus photography and spectral domain optical coherence tomography.
Mean duration of treatment in the first group was 2.79 ± 1.37 years, and in the second group 8.67 ± 2.26 years. The difference in central retinal thickness between the two groups was not statistically significant (p > 0.05). Comparison of parafoveal thickness between the two groups was statistically non-significant in all quadrants (p > 0.05). Visual field examination, autofluorescence images and colour fundus photographs were without noteworthy pathology.
Our results indicate that there were no significant changes in retinal structure between groups that depended on the duration of treatment. Hence, we can conclude that a yearly follow-up of these patients is sufficient to discover possible preclinical maculopathy.
Highlights ► Atherosclerosis is accelerated in selected group of female RA patients. ► We were not able to confirm that IgA anti-β2GPI may represent an independent risk factor for atherosclerosis. ► ...Homocysteine and Apo B have an important impact on the development of atherosclerosis in female RA patients.
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and morbidity due to the higher risks for cardiovascular disease. Traditional risk factors are ...insufficient to predict accelerated atherosclerosis in RA patients. The aim of this long-term prospective study was to investigate the relationships of asymptomatic atherosclerosis with traditional risk factors as well as inflammatory markers in patients with RA and matched healthy controls. Laboratory test results, concentrations of inflammatory mediators, matrix metalloproteases (MMP) and inflammation markers in a total of 70 (60 at follow-up) premenopausal healthy women with RA and 40 (34 at follow-up) matched controls were compared. B-mode ultrasound was applied for imaging of the carotid arteries for detection of asymptomatic atherosclerosis. Correlations with different factors were evaluated. The expression levels of intercellular adhesion molecules, vascular cell adhesion molecules (VCAMs), interleukin 6, tumour necrosis factor alpha and MMP-3 were significantly higher in the patient group during the follow-up period. The extent of plaque formation was greater in the patient group as compared to that in the control group (42.4% vs. 12.9%, respectively, p = 0.005), as was the cIMT (p = 0.001). By bivariate regression analysis, only VCAM expression was predictive of plaque formation (r = 0. 341, p = 0.016), but not for cIMT (r = -0.130, p = 0.327) in premenopausal female patients with RA at 15 years. These findings indicate that asymptomatic atherosclerosis is accelerated in premenopausal women with RA. During follow-up, there was an association between inflammation and accelerated atherosclerosis. Furthermore, VCAM was significantly correlated with plaque formation in RA patients. KEYWORDS: Rheumatoid arthritis; atherosclerosis; cardiovascular disease; metalloproteases
Rheumatoid arthritis (RA) is a chronic inflammatory disease, associated with increased mortality and morbidity due to the higher cardiovascular risk in these patients. Traditional risk factors are ...not the only answer for the accelerated atherosclerosis. In long term prospective study, we investigated the relationship between asymptomatic atherosclerosis and traditional risk factors as well as inflammatory markers in patients with RA and matched healthy controls. We studied the laboratory test results, the concentrations of inflammatory mediators, matrix metalloproteases (MMP) and inflammation markers in the total of 70 (60 at follow-up) premenopausal healthy women with RA and 40 (34 at follow-up) matched controls’. We used the B-mode ultrasound imaging of carotid arteries for detection of asymptomatic atherosclerosis. Correlation with different factors was evaluated. Statistically significant higher values of inflammatory markers such as selective adhesion molecules ICAM & VCAM, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and MMP-3 in patients` group were found in the follow-up study. More plaques were found in the patients’ group (42.4% vs. 12.9%; p=0.005), as compared with the controls’ group. The patients had also higher values of cIMT (p=0.001). Using bivariate regression analysis only VCAM was found as a prognostic factor for plaque occurrence (r= 0. 341, p=0.016), but not for cIMT (r= -0.130, p=0.327) in premenopausal female patients with RA after the follow-up. Therefore, the asymptomatic atherosclerosis is accelerated in premenopausal women with RA. The results of our follow-up study showed the association between the inflammation and accelerated atherosclerosis. Furthermore, VCAM was found to have statistically significant correlation with plaque occurrence in these patients.
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