Increased Serum Levels of soluble ST2 as a Predictor of Disease Progression in Systemic Sclerosis.

OBJECTIVE: Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. METHOD: Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. RESULTS: Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017-1.126, p < 0.009). CONCLUSION: In the present study, sST2 serum levels were predictive of disease progression in patients with SSc.

Increased extracellular water measured by bioimpedance analysis and increased serum levels of atrial natriuretic peptide in polymyalgia rheumatica patients : Signs of volume overload.

BACKGROUND: Water retention is a typical feature of acute inflammatory episodes, chiefly implemented by the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism counteracting expected water loss, e.g., due to sweating. Both the SNS and HPA axis are activated in polymyalgia rheumatica (PMR). As retention mechanisms may similarly apply in this disease, we hypothesized increased water retention in PMR. METHODS: Using bioimpedance analysis body composition was investigated in 64 healthy controls and 32 treatment-naive PMR patients. All PMR patients satisfied the 2012 EULAR/ACR classification criteria for PMR. 32 PMR patients were tested before and after 7 days of glucocorticoid-based therapy. Serum levels of pro-atrial natriuretic peptide (proANP) were investigated in all PMR patients and 15 healthy controls. RESULTS: Extracellular water (ECW) was markedly higher in PMR patients than in controls (mean ± SD: 49.1 ± 6.0% versus 36.3 ± 2.5% of total body water, p < 0.001). Patients with PMR demonstrated significantly higher serum levels of proANP compared to controls. Even before glucocorticoid treatment was initiated, systolic and diastolic blood pressure were higher in PMR patients compared to controls. Extracellular water levels did not change in PMR patients upon 7 days of intensified treatment. CONCLUSION: This study demonstrated increased extracellular water and elevated serum levels of proANP as signs of fluid overload in patients with PMR. Volume changes are imprinted as long-lasting mechanisms as water distribution is not affected by short-term anti-inflammatory therapy.

[The outbreak of COVID-19 in China]. / Der Ausbruch von COVID-19 in China.

The transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan and Hubei Province differ considerably from those in the rest of China. In Hubei province SARS-CoV­2 led to a dramatic outbreak. Intensive control measures (travel restrictions, isolation of cases, quarantine of contacts and others) led to the control of the outbreak. Despite travel restrictions SARS-CoV­2 was detected in other provinces in the following weeks. Consistent and intensive identification and isolation of infected persons ("containment") was able to prevent an outbreak outside Hubei province, providing an example for the control of SARS-CoV­2.

[Epidemiology of SARS-CoV-2 infection and COVID-19]. / Epidemiologie von SARS-CoV-2-Infektion und COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new ß­Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV­2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2-14) days. Although most infections are uncomplicated, 5-10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV­2, leading to rapid reductions in R. Which of the measures have been effective is still unknown.

[Interpretation of tuberculosis and hepatitis screening before immunosuppressive treatment]. / Interpretation des Tuberkulose- und Hepatitisscreenings vor immunsuppressiver Therapie.

An unrecognized latent tuberculosis infection (LTBI) may be reactivated under immunosuppressive therapy and become life threatening. Diagnosing LTBI requires the combination of targeted patient history and physical examination with the results of an interferon-gamma release assay (IGRA) and in addition, a chest X­ray is needed to rule out active tuberculosis. Established therapies for LTBI reduce the reactivation risk by approximately 80%. For the initial screening of an HBV infection HBsAg and anti-HBc are determined. Hereby, HBsAg carriers (high HBV reactivation risk, indications for antiviral prophylaxis) and serologically resolved HBV infections (low HBV reactivation risk, use of prophylaxis only in high-risk immunosuppression) can be reliably detected. A previously unrecognized HCV infection, with an increased risk of developing liver cirrhosis during immunosuppression, can be detected in screening by anti-HCV antibodies and be successfully treated with antivirals without interferon.

PCR analysis is superior to histology for diagnosis of Whipple's disease mimicking seronegative rheumatic diseases.

OBJECTIVES: The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases. METHOD: Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures. RESULTS: Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms. CONCLUSIONS: A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD.

[Differential diagnosis of granulomatous diseases]. / Differenzialdiagnose granulomatöser Erkrankungen.

Despite advances in the understanding of the pathophysiology, granulomatous diseases remain a diagnostic challenge for the clinician as well as for the pathologist. However, establishing the correct diagnosis of these diseases is a crucial prerequisite of targeted therapy. It is particularly essential to distinguish between an infectious and a non-infectious cause, since anti-infectious and anti-inflammatory or immunosuppressive approaches are opposing. Failure to establish the correct diagnosis can lead to adverse consequences for the patient. An interdisciplinary approach and a critical assessment of clinical, laboratory-chemical, microbiological, imaging, and anatomical-pathological findings are crucial for the evaluation of granulomatous disorders. This overview summarizes important landmarks and their value in the interplay of arriving at the correct diagnosis.

[PCR-based detection of pathogens in clinical rheumatology]. / Polymerasekettenreaktion-gestützte Erregerdiagnostik in der Rheumatologie.

In the differential diagnostics of autoimmune-mediated rheumatic diseases, rheumatologists often have to consider infections (e. g. Lyme arthritis) or reactive diseases (e. g. reactive arthritis after urogenital bacterial infections). Furthermore, infections with an atypical presentation or caused by atypical pathogens (opportunistic infections) can complicate the immunosuppressive therapy of autoimmune diseases. For this purpose not only conventional microbiological culture methods but also PCR-based methods are increasingly being applied for the direct detection of pathogens in clinical specimens. The aim of this overview is to present commonly used PCR methods in the clinical practice of rheumatology and to describe their benefits and limitations compared to culture-based detection methods.

[Certified clinical excellence : Suitable tool for patient recruitment?]. / Zertifizierte Behandlungsqualität : Geeignetes Instrument für die Patientenakquise?

BACKGROUND: Medical institutions often spend a lot of time and money to obtain external certification of clinical excellence and the quality of clinical care, with the purported aim of attracting patients. There is, however, little evidence about the role of certification in patients' choice of institution to receive elective inpatient treatment. OBJECTIVE: On admission 413 consecutive patients were anonymously surveyed about the reasons for choosing this institution, a tertiary care rheumatology department, which is currently certified by the cooperation for transparency and quality in healthcare (KTQ) and by the German Association of Rheumatological Acute Care Hospitals (VRA). In a self-administered questionnaire, patients reported reasons for their choice of institution, allowing for more than one reason. RESULTS: Patients reported recommendation by the primary care physician (48 %), recommendation by the attending rheumatologist (39 %), own (30 %) or family/friends (18 %) positive experience as the main reasons for choosing this institution. Certificates of clinical excellence were given as a reason by only 3 % of patients. Similar results were obtained from 42 referring physicians, of which 5 % regarded the KTQ certification and 2 % the VRA certification as one of the decisive factors. CONCLUSION: The results suggest that certification does not meaningfully influence patient choice of clinic for elective inpatient treatment and therefore does not contribute to patient acquisition.

Are histopathological findings of diagnostic value in native valve endocarditis?

BACKGROUND: Optimal management of infective endocarditis (IE) depends on the early detection of IE-causing pathogens and on appropriate antimicrobial and surgical therapy. The current guidelines of the European Society of Cardiology (ESC) recommend histopathological examination as the gold standard for diagnosing IE Habib et al. (Eur Heart J 30:2369-2413, 2005). We hypothesize that histopathological findings do not provide additional information relevant to clinical decision-making. METHODS: We retrospectively reviewed a cohort of patients who had undergone surgery for native valve endocarditis (NVE) at the University Hospital Regensburg between September 1994 and February 2005. All episodes of intraoperatively confirmed endocarditis during this period were included in the study. Data were retrieved from surgical records, microbiological and histopathological reports, and medical files of the treating as well as admitting hospital. Pathogens were correlated with the site of manifestation of the affected heart valve and with clinical and histopathological findings. RESULTS: A total of 163 episodes of NVE were recorded and entered into our study for analysis. The valves affected were the aortic valve (45 %), the mitral valve (28 %), the aortic and mitral valve (22 %), and other valves (5 %). IE-causing pathogens were Staphylococcus aureus (22 %), viridans streptococci (18 %), enterococci (10 %), streptococci other than Streptococcus viridans (9 %), coagulase-negative staphylococci (5 %), miscellaneous pathogens (4 %), and culture-negative endocarditis (33 %). Infection with S. aureus was associated with high rates of sepsis, septic foci, and embolic events, while patients with enterococcal IE showed the highest rate of abscesses. Mortality rate in all subgroups was low without significant differences. However, histopathological findings correlated poorly with the pathogen involved and showed only few significant associations that were without clinical relevance. CONCLUSIONS: The clinical presentation of IE depends on the pathogen involved. Among the episodes of NVE examined, the histopathological examination of resected heart valves did not show any pathogen-specific morphological patterns and therefore did not provide any additional information of clinical value. Based on our findings, we recommend complementary cultures of the resected materials (valve tissue, thrombotic material, pacer wire) and implementation of molecular diagnostic methods (e.g., broad-range PCR amplification techniques) instead of histopathological analyses of resected valve tissue.

Pandemic and post-pandemic influenza A (H1N1) seasons in a tertiary care university hospital-high rate of complications compared to previous influenza seasons.

INTRODUCTION: The aim was to study the characteristics and case severity of patients hospitalized for influenza with a pandemic strain at a German tertiary care university hospital in 2009/10 and 2010/11 and to compare them to two previous influenza seasons. METHODS: An observational study of all patients hospitalized for laboratory-confirmed influenza during the last four influenza seasons at Regensburg University Hospital was undertaken. RESULTS: During the last four seasons, a rising number of patients were admitted due to influenza (4 in 2007/8, 16 in 2008/9, 27 in 2009/10, and 55 in 2010/11). Patients seen in the last two seasons were younger (median age 63 years in 2007/8, 52 years in 2008/9, 42 years in 2009/10, and 48 years in 2010/11) (p = 0.046) and presented with a lower rate of major comorbidities (75 % in 2007/8, 62.5 % in 2008/9, 37 % in 2009/10, and 47.3 % in 2010/11). The pandemic and post-pandemic seasons were characterized by a high rate of seriously ill patients with longer hospitalizations (11 days in 2007/8, 7 days in 2008/9, 22 days in 2009/10 and 2010/11) (p = 0.004) and higher rates of intensive care unit (ICU) admission (25 % in 2007/8, 18.8 % in 2008/9, 66.7 % in 2009/10, and 52.7 % in 2010/11) (p = 0.003) and mechanical ventilation (25 % in 2007/8, 6.3 % in 2008/9, 63 % in 2009/10, and 49.1 % in 2010/11) (p < 0.001). Extracorporeal membrane oxygenation (ECMO) was necessary in 33.3 % of patients in 2009/10 and 25.5 % in 2010/11. We had six fatalities in both pandemic and post-pandemic seasons. CONCLUSION: Compared to seasonal influenza, we observed even more so in the post-pandemic than the pandemic season a higher number of younger patients, with less serious comorbidities often showing a very severe course.

[Vaccination prior to travelling for patients with rheumatic diseases]. / Impfungen vor Reisen bei Patienten mit rheumatischen Erkrankungen.

Rheumatologists increasingly face patient questions about the need, the safety and the effectiveness of travel-related vaccinations. Currently, there are no guidelines on travel vaccinations for patients with inflammatory rheumatic diseases. The use of live attenuated vaccines remains contraindicated in patients receiving relevant immunosuppressive therapy despite some encouraging results from initial pilot studies. However, many inactivated travel vaccines can safely be used for patients with rheumatic diseases. Furthermore, rheumatologists should be vigilant in identifying and closing gaps in the routine vaccinations for patients.

[Ultrasound-guided joint injections in patients with rheumatic diseases]. / Sonographisch geführte Gelenkpunktionen in der Rheumatologie.

Joint and soft tissue injections are routinely performed in daily rheumatology practice to establish the diagnosis or as part of the treatment in patients suffering from rheumatic diseases. Consequently, joint injections have been included in the rheumatology further training curriculum. Despite numerous studies demonstrating a poor accuracy and outcome of joint injections guided only by clinical examination, most of the injection procedures are still performed in a "blind" fashion based on clinical judgment. Ultrasound has evolved as an established imaging method in rheumatology within the past decade and is considered the preferred imaging modality for joint interventions due to its availability and lack of radiation exposure. In this article the indications and important aspects of the practical management of ultrasound-guided injections performed in daily rheumatology practice are summarized.

Risk factors associated with long-term prognosis of patients with Staphylococcus aureus bacteremia.

OBJECTIVE: To estimate risk factors associated with long-term outcome (i.e., 1-year survival) in patients with Staphylococcus aureus bacteremia (SAB). METHODS AND MATERIALS: This was a retrospective study in which the microbiological laboratory data records of patients admitted to the University Hospital of Regensburg between January 2004 and June 2005 were examined to identify those patients with blood cultures positive for S. aureus. Corresponding clinical records for all patients were reviewed using a standardized questionnaire. Of the 119 patients identified with SAB, 80 were available for the >1-year follow-up. RESULTS: Crude 1-year mortality was 47.5; 30- and 90-day mortality was 28.8 and 37.5%, respectively. In-hospital mortality was 28.8%. There were no significant differences in 1-year survival in terms of age, gender, antibiotic resistance, and mode of acquisition (nosocomial vs. community-acquired). A significantly better survival was observed with an identifiable focus present, if the chosen empiric antibiotic therapy was adequate or if the body mass index of the patient was >24. CONCLUSION: In summary, in this patient cohort, considerable additional mortality due to SAB beyond 30 or 90 days was present. Our results suggest that long-term survival data should be taken into account in outcome studies involving patients with S. aureus bacteremia.

[Rheumatoid arthritis and autoimmune hemolysis: B-cell depletion for remission induction in a patient with rheumatoid arthritis and cold agglutinin disease]. / Rheumatoide Arthritis und Autoimmunhämolyse: Remissionsinduktion durch B-Zell-Depletion bei einer Patientin mit rheumatoider Arthritis und Autoimmunhämolyse durch Kälteagglutinine.

Autoimmune hemolysis is a rare complication of systemic rheumatic diseases. We report on a 68-year-old female patient with established, long-standing rheumatoid arthritis, who complained of progressive weakness and worsening of her arthralgia under therapy with leflunomide. Physical and laboratory examination revealed autoimmune hemolysis due to cold agglutinin disease. As hemolysis and arthritis were refractory to steroid treatment, B-cell depletion with rituximab was performed leading to a marked reduction of hemolytic parameters as well as remission of her rheumatoid arthritis.

[Detection of psoriasis arthritis with the GEPARD patient questionnaire in a dermatologic outpatient setting]. / GEPARD-Patientenfragebogen: Erfassung von Patienten mit Psoriasisarthritis aus einem ambulanten dermatologischen Patientenpool.

BACKGROUND: Diagnosis of psoriasis arthritis (PsA) is often delayed in an outpatient dermatological setting. Therefore, we compiled a patient questionnaire (GEPARD, GErman Psoriasis ARthritis Diagnostic questionnaire) to detect PsA in psoriasis outpatients. PATIENTS AND METHODS: Initially, between 2005 and 2007, we evaluated GEPARD in the outpatient setting of our Department of Dermatology with the Vasey and Espinoza criteria. In May 2008, the questionnaire was distributed to practices in the Regensburg area, Germany. Patients who filled out the GEPARD questionnaire were invited for a rheumatological work-up and, where indicated, arthrosonography, conventional X-ray, MRI, and scintigraphy examinations were performed. PsA was classified on the basis of the CASPAR criteria. RESULTS: We calculated a sum cut-off score of >or= 4 positive answers in the first cohort. Of all 54 patients examined 63% could be diagnosed with PsA according to the CASPAR criteria. After a complete work-up with all diagnostic means 79.6% (43 patients) could be detected with inflammatory joint manifestations. CONCLUSION: It is possible to detect PsA patients in a dermatologic outpatient setting with the GEPARD questionnaire.

[Epidemiology of SARS-CoV-2/COVID-19]. / Epidemiologie von SARS-CoV-2/COVID 19: Aktueller Stand.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus, which first appeared in 2019 and rapidly spread causing a worldwide pandemic. Here we present a nonsystematic review of the current knowledge on its epidemiological features. The SARS-CoV­2 replicates mainly in the upper and lower respiratory tract and is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R0) is between 2 and 3 and the median incubation period is 6 days (range 2-14 days). Similar to the related coronaviruses SARS and Middle East respiratory syndrome (MERS), superspreading events play an important role in spreading the disease. The majority of infections run an uncomplicated course but 5-10% of those infected develop pneumonia or a systemic inflammation leading to hospitalization, respiratory and potentially multiorgan failure. The most important risk factors for a complicated disease course are age, hypertension, diabetes, chronic cardiovascular and pulmonary diseases and immunodeficiency. The current infection fatality rate over all age groups is between 0.5% and 1% and the rate rises after the sixth decade of life. Nosocomial transmission and infections in medical personnel have been reported. A drastic reduction of social contacts has been implemented in many countries with outbreaks of SARS-CoV­2, leading to rapid reductions in R0. Most interventions have used bundles and which of the measures have been more effective is still unknown. Using mathematical models an incidence of 0.4%-1.8% can be estimated for the first wave in Germany.

[Infections as causes of fever of unknown origin]. / Infektionen als Ursache von Fieber unklarer Genese.

Infectious diseases are important causes of fever of unknown origin (FUO). The spectrum of infectious agents is broad and diagnosis depends on careful evaluation of individual risk factors. Infectious diseases presenting as FUO are frequently atypical presentations of well known infections, e.g. tuberculosis or infectious endocarditis. In this review we present an overview of infectious causes of FUO classified into community acquired infections, nosocomial infections, and infections in immunocompromised hosts.