Vertebral osteomyelitis is characterised by increased RANK/OPG and RANKL/OPG expression ratios in vertebral bodies and intervertebral discs.

Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients. 14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism. Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs. In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO.

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry.

INTRODUCTION: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. RESULTS: In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. CONCLUSION: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

[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.

[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.

[Current treatment of endocarditis : Innovations and controversies]. / Aktuelle Therapie der Endokarditis : Neuerungen und Kontroversen.

Despite many novel diagnostic strategies and advances in treatment, infective endocarditis (IE) remains a severe disease. The epidemiology of IE has shifted and staphylococci have replaced streptococci as the most common cause and nosocomially acquired infections, invasive procedures, indwelling cardiac devices and acquired infections due to intravenous drug abuse are more frequent. The incidence of IE has steadily increased in recent years and the patients affected are older and have more comorbidities. The modern treatment of IE is interdisciplinary. The pharmacotherapy of IE depends on the pathogen and its sensitivity. The presence of a bioprosthetic valve and implantable cardiac devices plays a significant role in selection of antibiotics and duration of treatment. This article provides an update and overview of the current clinical practice in diagnostics and pharmacotherapy of IE in adults with a special focus on partial oral therapy and the role of aminoglycosides.

Outcome-related co-factors in 105 cases of vertebral osteomyelitis in a tertiary care hospital.

PURPOSE: Vertebral osteomyelitis (VO) is an infection of the vertebral body and the adjacent disc space. The aim of our study was to identify outcome-related co-factors of patients with VO treated in the last decade. METHODS AND RESULTS: We retrospectively identified 105 patients with VO (mean age 66.1 years) who had been treated at our institution from 2004 to 2011. The median time of hospitalization at our institution was 31.5 days, and 44 patients required intensive medical care. Back pain and fever were documented in 66.7 and 33.3 % of cases, respectively. The radiologic diagnosis of VO was made in 94.8 % of all obtained magnetic resonance imaging scans and in 66.2 % of all computed tomography (CT) scans. Biopsies were taken in 71 patients, and the causative organisms were identified in 56.2 % of patients, with Staphylococcus aureus being the predominant pathogen. Fifty-six patients underwent surgical treatment. During hospitalization, infectious complications were observed in 63 patients (60.0 %). The most common complications were psoas, paravertebral and epidural abscesses. Patients with S. aureus infections had a significantly higher rate of infectious complications than those without (76.5 vs. 40.3 %, respectively), and were more frequently treated in intensive care units (58.8 vs. 34.7 %, respectively). Overall in-hospital mortality rate was 12.4 %. Elevated C-reactive protein levels at admission, advanced age and a Charlson Comorbidity Index of ≥2 were associated with higher mortality. CONCLUSIONS: Magnetic resonance imaging currently is the imaging procedure of choice for the radiologic diagnosis of VO. Mortality is attributable in part to co-morbidities. However, infections with S. aureus are frequent in this patient population and are associated with a higher rate of complications and a trend towards higher mortality.

[Severe infections : causes and management of sepsis]. / Schwere Infektionen : Ursachen und Management von Sepsis.

The sepsis syndrome has only recently been defined as a clinical syndrome but despite its unspecific definition it has evolved rapidly into an important concept. Although specific therapeutic interventions targeting the inflammatory pathway have not yet been effective in treating sepsis, a better understanding of mechanisms leading to organ dysfunction has led to better management of patients with sepsis. Clinical signs of systemic inflammatory response syndrome (SIRS) or sepsis are hallmarks for the definition of severe infections. Current guidelines are presented for the management of a number of severe infectious syndromes.

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.

The novel adipokine C1q/TNF-related protein-3 is expressed in human adipocytes and regulated by metabolic and infection-related parameters.

BACKGROUND: The growing family of C1Q/TNF-related proteins is characterized by structural homologies to the anti-inflammatory adipokine adiponectin. CTRP-3 was recently reported to function as an anti-inflammatory LPS-antagonist in vitro. MATERIAL AND METHODS: Human subcutaneous and visceral adipocytes and murine 3T3-L1 adipocytes were used for analysis of CTRP-3 expression and function. Western blot analysis of CTRP-3, siRNA mediated knockdown of CTRP-3, Oil red O staining, assessment of basal and epinephrine-induced lipolysis, ELISA-based measurements of supernatant chemokines, recombinant CTRP-3 protein expression, and Staphylococcus aureus (S. aureus) infection assays were used. RESULTS: CTRP-3 is expressed in subcutaneous and visceral adipocytes. CTRP-3 is positively regulated by insulin, whereas chronic LPS-exposure inhibits terminal adipocyte differentiation and CTRP-3 expression. Intracellular infection of adipocytes by S. aureus also decreases CTRP-3 expression. As demonstrated by siRNA-mediated cellular knockdown of CTRP-3 in adipocytes, CTRP-3 regulates resistin secretion and lipolysis. CONCLUSION: CTRP-3 is expressed in human adipocytes and plays an important role in adipocyte physiology such as lipolysis and adipokine secretion. Both, metabolic factors and infection/inflammation-related factors regulate CTRP-3 expression.

[Fever of unknown origin. Infectious causes]. / Fieber ungeklärter Genese. Infektiöse Ursachen.

Infectious diseases remain one of the most important causes of fever of unexplained origin (FUO). We review the spectrum of infectious diseases in the different clinical situations of patients with FUO, namely in classical FUO, in patients with HIV infection, in health care-associated or nosocomial FUO, and in immunocompromised patients with FUO. The most important question is which clinical features make a specific disease a candidate to cause FUO.

[Suspected borreliosis - what's behind it?]. / Verdacht auf Borreliose - Was hat der Patient?

BACKGROUND AND OBJECTIVE: Borreliosis may be associated with unspecific symptoms and thus not only cause difficulties in diagnosis but also lead to overdiagnosis. PATIENTS AND METHODS: Data on 134 patients (mean age 47 [12 - 78] years, 51.5 % male) with suspected borreliosis presenting at the university hospital Regensburg were analyzed retrospectively. RESULTS: The majority of patients had been adequately treated for borreliosis previously. 34 patients (25.4 %) had proven or possible borreliosis, 20 patients (14.9 %) presented for consultation only. Regarding the remaining 80 patients (59.7 %), in 36 (45 %) a rheumatologic, orthopedic or neurologic disease was found as causal for the presenting symptoms, in 44 (55 %) no somatic disease could be diagnosed. CONCLUSION: A careful differential diagnosis seems mandatory in patients with suspected borreliosis and persistent complaints.

Lack of evidence for persistent nasal colonization with community-acquired methicillin-resistant Staphylococcus aureus in a central European cohort.

One hundred and three patients who had previously tested positive for community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue infection, and the remainder were mostly asymptomatic carriers. Of 103 patients, only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs available, 30.9% were positive for S. aureus but only four yielded Panton-Valentine leukocidin-positive methicillin-resistant S. aureus. In summary, we were unable to find persistent health issues or nasal colonization with cMRSA in a cohort of previously cMRSA-infected/colonized patients.

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.

Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.

Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. PATIENTS AND METHODS: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. RESULTS: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. CONCLUSION: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

Healthcare-associated outbreaks and community-acquired infections due to MRSA carrying the Panton-Valentine leucocidin gene in southeastern Germany.

In response to several isolations of methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leucocidin gene (PVL-MRSA), the present study was conducted to document the spread of infection in a small region of southeastern Germany. During a 9-month period, two healthcare-associated outbreaks with PVL-MRSA occurred, affecting 83 patients, personnel and contacts of personnel, and 34 additional cases were detected in the community. The clinical spectrum ranged from colonization to skin infection and necrotizing pneumonia. The findings represent the largest number of PVL-MRSA cases detected in Germany so far, and demonstrate the potential of this emerging pathogen to spread within the community and in healthcare institutions.

[33-year old patient with thoraco-abdominal pain and differences of blood pressure]. / 33-jährige Patientin mit thorako-abdominellen Schmerzen und Blutdruckdifferenz.

We report on a 33-year-old women with ulcerative colitis, who presented with inspiratory thoracic pain due to perimyocarditis. Furthermore, postprandial abdominal pain associated with diarrhea and different blood pressure values on both arms were recorded. Computed tomography revealed embolism of the pulmonal arteries and angiography demonstrated stenoses of the subclavian and renal arteries and the celiac trunc suggesting the diagnosis of Takayasu's arteritis. A coronary or infectious etiology could be excluded. Since a coincidence of Takayasu's arteritis and ulcerative colitis has been reported in the literature, abdominal pain and diarrhea can either be explained by the inflammatory bowel disease or by chronic ischemia due to intestinal vasculitis. Differential diagnosis will be facilitated by the future course of the disease.

Genetic variability of measles viruses circulating in the Benelux.

In Europe measles incidence remains high and in some parts the disease is likely to be still endemic due to insufficient vaccination. Luxembourg experienced an outbreak with at least 110 cases in 1996, and cases continued to be reported throughout 1997. We used molecular epidemiology to investigate this apparent endemicity. On the basis of their N gene sequences, the isolates were assigned to the typical European C2 and D6 genotypes. Sequence diversity within the outbreak was 0.2%. The nucleotide distance between the C2-viruses of the outbreak and the other C2 isolates was at least three or four times higher, suggesting an independent origin of the latter viruses. Similarly, the four D6 viruses found in Luxembourg were thought to be of at least two or three origins. Thus, we propose here to use intra-outbreak sequence diversity to differentiate between sporadic endemic cases and a "pseudo-outbreak" of multiple unrelated imported cases.