Mdm2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics

The search for inherited cancer susceptibility factors is a major focus of epidemiologic cancer studies. Analyses of single-nucleotide polymorphisms (SNP) in a variety of genes revealed a correlation between a specific allele variant and cancer predisposition. Human mouse double-minute 2 protein (Mdm2) is a cellular E3 ligase capable of ubiquitination and degradation of p53. Therefore, Mdm2 is a crucial factor of cell cycle control and cell survival. The Mdm2 promoter SNP309 was shown to increase Mdm2 expression and can, thereby, inhibit the p53 pathway. This SNP was found to be associated with increased risk and early onset of various malignancies. For prostate cancer no studies are reported to date. In a case–control study we determined the distribution of the Mdm2 SNP309 in 145 male subjects with prostate cancer and in 124 male controls without any malignancy using RFLP analysis. Cases and controls showed a similar distribution of the SNP (P=0.299). Genotype distribution showed neither an association with histopathological characteristics of the tumours nor with prognosis. Age at disease onset was also not modified by the SNP. This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk

Pneumocystis-jirovecii-Pneumonie – eine opportunistische Infektion im Wandel

Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized

Empirische Antibiotikatherapie in der Notaufnahme

Due to the frequency of infectious diseases, antibiotic drugs are important and frequently life-saving medications in the emergency department (ED). On the other hand, rapid treatment decisions have to be made and a significant proportion of inadequate antibiotic prescriptions are observed in clinical practice although decisions in the ED set the course for adequate antibiotic treatment. In order to choose an appropriate treatment strategy, acute life-threatening infections (diagnostics and immediate empirical therapy) have to be differentiated in the ED from less complicated infections (mainly empirical therapy) and complicated infections of a frequently chronic nature (adequate diagnostics, no or delayed therapy). Additionally, this article gives a review of important general aspects of antibiotic therapy in the ED as well as the specific therapy of the most important infectious diseases

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-CoV-2 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-CoV-2 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-CoV-2

Aktuelle Therapie der Endokarditis

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

Epidemiologie von SARS-CoV-2-Infektion und COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta-Coronavirus 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-CoV-2 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-CoV-2, leading to rapid reductions in R. Which of the measures have been effective is still unknown

Mdm2 SNP309 G-Variant Is Associated with Invasive Growth of Human Urinary Bladder Cancer

Objective: Human mouse double minute 2 (Mdm2) is essential in degrading p53 by acting as an ubiquitin ligase and therefore plays a vital role in cell cycle and survival. The G-variant of the Mdm2 SNP309, which is located within the promoter of the Mdm2 gene, increases expression of Mdm2 and thereby inhibits the p53 pathway. Several studies have investigated the influence of this SNP on disease risk and onset of various malignancies. The impact of Mdm2 SNP309 on bladder cancer is still to be established due to inconsistent data. Methods: In a case-control study we determined the distribution of Mdm2 SNP309 genotypes in 111 patients with an early-onset bladder cancer (diagnosis <45 years of age), in 113 consecutive bladder cancer patients and in a control group consisting of 140 patients without any malignancy. Results: There was no significant association between the allelic distribution of the Mdm2 SNP309 and tumor risk, early onset, gender or grade of the tumor. According to tumor stage we found a significant difference in the distribution of the Mdm2 SNP309 between patients with noninvasive and invasive (≥pT1) tumor growth (p = 0.016). In patients with invasive tumors a significant increase of the G allele was found (T/T vs. T/G + G/G; p = 0.023; OR 2.203, 95% CI 1.111-4.369). Conclusion: These data indicate that the G-variant of the Mdm2 SNP309 might influence the development of a more aggressive tumor phenotype in patients with bladder cancer without affecting the overall tumor risk