Boris Ehrenstein

Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis

BackgroundTimely identification of pathogens is crucial to minimize mortality in patients with severe infections. Detection of bacterial and fungal pathogens in blood by nucleic acid amplification promises to yield results faster than blood cultures (BC). We analyzed the clinical impact of a commercially available multiplex PCR system in patients with suspected sepsis.MethodsBlood samples from patients with presumed sepsis were cultured with the Bactec 9240™ system (Becton Dickinson, Heidelberg, Germany) and aliquots subjected to analysis with the LightCycler® SeptiFast® (SF) Test (Roche Diagnostics, Mannheim, Germany) at a tertiary care centre. For samples with PCR-detected pathogens, the actual impact on clinical management was determined by chart review. Furthermore a comparison between the time to a positive blood culture result and the SF result, based on a fictive assumption that it was done either on a once or twice daily basis, was made.ResultsOf 101 blood samples from 77 patients, 63 (62%) yielded concordant negative results, 14 (13%) concordant positive and 9 (9%) were BC positive only. In 14 (13%) samples pathogens were detected by SF only, resulting in adjustment of antibiotic therapy in 5 patients (7,7% of patients). In 3 samples a treatment adjustment would have been made earlier resulting in a total of 8 adjustments in all 101 samples (8%).ConclusionThe addition of multiplex PCR to conventional blood cultures had a relevant impact on clinical management for a subset of patients with presumed sepsis.

Influenza pandemic and professional duty: family or patients first? A survey of hospital employees

BackgroundConflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP).MethodsWe surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic.ResultsOf 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients.ConclusionOur results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza.

18F-FDG PET as a diagnostic procedure in large vessel vasculitis—a controlled, blinded re-examination of routine PET scans

Large vessel vasculitis can be visualized by 18F-FDG positron emission tomography (PET). However, the diagnostic value of 18F-FDG PET is yet to be determined. We therefore performed a study to evaluate this technique for the diagnosis of giant cell arteritis (GCA) and Takayasu arteritis (TA). Patients with GCA or TA, who fulfilled the American College of Rheumatology (ACR) criteria and also had a pathologic PET scan in clinical routine, were selected. These PET scans, as well as PET scans obtained from age- and sex-matched control patients, were independently re-evaluated by two experienced nuclear medicine experts. PET scans of 20 patients (17 GCA, 3 TA) and 20 controls were evaluated. In 85% of the examinations, both observers agreed on the diagnosis or exclusion of vasculitis. Specificity was calculated with 80% and sensitivity with 65%, yielding an overall diagnostic accuracy of 72%. The mean maximum standardized uptake values (SUVmax) of the subclavian region was significantly higher in vasculitis than in control patients (2.77 ± 1.02 vs 2.09 ± 0.64; difference 0.69; CI95%: 0.14–1.24, p = 0.0161). SUVmax of the iliacal regions did not differ significantly. Receiver- operating characteristics (ROC) analysis revealed the highest sensitivity of 90% (CI95%: 68–99%) and specificity of 45% (CI95%: 23–69%) for a SUVmax cut-off point of 1.78 (AUC 0.72, (CI95%: 0.56–0.86). PET findings are reproducible and independent of the observer. The low sensitivity and specificity indicate that enhanced vascular uptake might be overrated if clinical details are suggestive for vasculitis. Therefore, the diagnosis of large vessel vasculitis should not be based on PET findings only.

Development and evaluation of a novel ultrasound score for large joints in rheumatoid arthritis: One year of experience in daily clinical practice

To introduce and evaluate a new standardized ultrasound (US) score developed for large joints in patients with rheumatoid arthritis (RA).

Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report

BackgroundCryptococcus neoformans is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, C. neoformans causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis.Case PresentationAn 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with Cryptococcus neoformans, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed.ConclusionsOpportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.

A patient with Pfeifer-Weber-Christian Disease - Successful Therapy with Cyclosporin A: case report

BackgroundPfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article.Case presentationWe here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patients symptoms resolved.ConclusionOur observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.

Quantitative assessment of synovitis in patients with rheumatoid arthritis using fluorescence optical imaging

IntroductionTo prospectively evaluate quantitative assessment of fluorescence optical imaging (FOI) for differentiation of synovitic from non-synovitic joints in patients suffering from rheumatoid arthritis (RA).MethodsFOI of the hands was performed in patients with active RA, and a stratified quantitative fluorescence readout (FLRO) of 3 phases (1-120 s; 121-240 s; 241-360 s) was generated for 5 individual joints of the clinical predominant hand (carpal joint, metacarpophalangeal and proximal interphalangeal joints of digits II & III). To dissect the effect of the overall perfusion of the hand from the perfusion due to synovitis, a fluorescence ratio (FLRA) was additionally calculated, dividing each FLRO by the readout of the eponychium of digit II. The mean FLRO and FLRA were compared between joints with absent vs. present synovitis determined by clinical examination, grayscale, color Doppler ultrasonography, or magnetic resonance imaging (MRI).ResultsThe analysis for 90 individual joints from 18 patients yielded FLRO ranging from 4.4 to 49.0 × 103, and FLRAs ranging from 0.37 to 2.27. Overall, the analyses based on the FLRA revealed a higher discrimination than the analyses related to the FLRO, demonstrating most significant differences in phases 2 and 3. A sensitivity of 26/39 (67%) and a specificity of 31/40 (77%) were calculated for FLRA of phase 3 using a cut-off value of more than 1.2 to detect MRI-confirmed synovitis with FOI.ConclusionsFOI has a potential for visualizing synovitis in subjects with RA. For adequate FOI interpretation, quantitative analysis should be based on the novel FLRA calculated for phases 2 and 3.

Detection of psoriasis arthritis with the GEPARD patient questionnaire in a dermatologic outpatient setting

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.ZusammenfassungHintergrundDie Diagnose einer Psoriasisarthritis (PsA) bei Patienten mit Psoriasis in alleiniger dermatologischer Betreuung ist unter Umständen verzögert. Wir entwickelten einen Patientenfragebogen für Patienten mit Psoriasis im ambulanten, dermatologischen Bereich zur Erfassung einer PsA (GEPARD, „GErman Psoriasis ARthritis Diagnostic questionnaire“).ZielKönnen mit dem GEPARD Patienten mit PsA aus dem ambulanten dermatologischen Patientenpool erfasst werden?MethodenWir evaluierten zunächst zwischen 2005 und 2007 den GEPARD an Patienten unserer Klinik für Dermatologie mit den Kriterien nach Vasey und Espinoza und verteilten ab Mai 2008 den Fragebogen in dermatologischen Praxen der Oberpfalz und Niederbayerns. Patienten, die den GEPARD ausfüllten, wurden zu einer rheumatologischen Visite eingeladen und – falls indiziert – auch durch Arthrosonographie, konventionelle Röntgenuntersuchung, MRT oder Skelettszintigraphie untersucht. Der Klassifikation einer PsA wurden in der klinisch-rheumatologischen Visite 2008 die CASPAR-Kriterien zugrunde gelegt.ErgebnisseIm ersten Teil der Studie wurde ein Summengrenzwert für eine PsA berechnet. Im zweiten Teil wurde entsprechend den CASPAR-Kriterien bei 63% von 54 untersuchten Patienten eine PsA diagnostiziert. Nach der zusätzlichen apparativen Diagnostik konnte bei 79,6% (43 Patienten) eine entzündliche Gelenkmanifestation erfasst werden.SchlussfolgerungMit dem GEPARD können Patienten mit PsA aus dem ambulanten dermatologischen Bereich herausgefiltert werden.AbstractBackgroundDiagnosis 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 methodsInitially, 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.ResultsWe calculated a sum cut-off score of ≥ 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.ConclusionIt is possible to detect PsA patients in a dermatologic outpatient setting with the GEPARD questionnaire.

The role of domestic hygiene in inflammatory bowel diseases: hepatitis A and worm infestations.

Background Environmental factors are likely to be involved in the pathogenesis of inflammatory bowel disease (IBD), as the incidence of both Crohns disease (CD) and ulcerative colitis (UC) increased with improved living standards in Europe after World War II. On the basis of earlier reports suggesting that hygienic standards may also play a role in the pathogenesis of IBD, we investigated the influence of hepatitis A seroprevalence as an indicator for poorer hygienic conditions and worm infestations in IBD. Methods Hepatitis A seroprevalence was examined in patients with UC and CD. Patients with minor endocrinological disorders served as controls. All patients were questioned about immunizations, parasitic infections (worms), contact with animals, living on a farm, and ever traveling abroad. Patients were excluded for active hepatitis A immunization or recent passive immunization. Results are presented as Mantel–Haenszel odds ratios with 95% confidence interval, adjusted for age group. Results The sample included 307 patients (73 CD, 48 UC, and 186 controls). Hepatitis A seroprevalence was strongly associated with age older than 50 years. Age adjusted Mantel–Haenszel odds ratios were 0.25 (0.09–0.71) for UC and 0.75 (0.38–1.46) for CD versus controls. For parasitic infections, the odds ratios were 1.15 (0.52–2.53) for UC and 0.34 (0.13–0.89) for CD. Conclusion We were able to demonstrate a negative association of hepatitis A infection with UC only. In contrast, a novel finding was a strong protective effect of worm infestations for the occurrence of CD, but not UC.

Low rate of clinical consequences derived from results of blood cultures obtained in an internal medicine emergency department.

Background:Blood cultures detect bacteremia in individual patients and help define local pathogen and resistance spectra. At the same time, the benefits of blood culture results in the management of individual patients – and therefore their cost–effectiveness – are disputed.Patients and Methods:During 1 calendar year, we conducted a prospective study of emergency department admissions with blood culture draws and at least a 3–day hospitalization afterwards. We prospectively surveyed treating physicians on usefulness of blood culture results for patient management.Results:428 diagnostic episodes (emergency visits) involving 390 patients occurred during the study period from 10/2002 to 10/2003. The analysis included 188/428 (44%) episodes with blood culture draws performed according to the predefined clinical standard where patients were hospitalized with sufficient duration. Absence of therapeutic consequences in response to blood culture results was reported for 138/142 (97%) of episodes with negative blood culture results, for 16/21 (76%) with blood culture results positive only for skin flora, and for 14/25 (56%) of episodes with blood cultures positive for obligate pathogens. Treating physicians regarded the blood culture results necessary for clarifying the etiology in 34/188 (18%) episodes, and rated blood culture results necessary for their therapeutic decisions in 29/188 (15%) episodes.Conclusion:Negative blood culture results rarely changed the management of medical inpatients. Our study suggests that in settings with broad–spectrum empirical antibiotic therapy positive blood culture results for obligate pathogens trigger adjustment of the antibiotic therapy in only about half of instances. Many blood cultures drawn in the emergency department where considered unnecessary by ward physicians. Guidelines for preventing unnecessary blood culture draws are warranted in order to increase the rate of their meaningful clinical consequences for medical inpatients initially treated with broad–spectrum empirical antibiotics.