Effect and safety of treatment with ACE-inhibitor Enalapril and ß-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial.

BACKGROUND: X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the ß-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. METHODS TRIAL DESIGN: Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. INCLUSION CRITERIA: DMD boys aged 10-14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS < 28%. Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events. RESULTS: From 3/2010 to 12/2013, 38 patients from 10 sites were centrally randomized after run-in, with 21 patients continuing enalapril and metoprolol medication and 17 patients receiving placebo. Until end of study 12/2015, LV-FS < 28% was reached in 6/21 versus 7/17 patients. Cox regression adjusted for LV-FS after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio: 0.38; 95% confidence interval: 0.12 to 1.22; p = 0.10). Analysis of secondary outcome measures revealed a time-dependent deterioration of LV-FS with no statistically significant differences between the two study arms. Blood pressure, maximal heart rate and mean-NN values were significantly lower at the end of open run-in treatment compared to baseline. Outcome analysis 19 months after randomization displayed significantly lower maximum heart rate and higher noradrenalin and renin values in the intervention group. No difference between treatments was seen for quality of life. As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed. CONCLUSIONS: Our analysis of enalapril and metoprolol treatment in DMD patients with preserved left ventricular function is suggestive to delay the progression of the intrinsic cardiomyopathy to left ventricular failure, but did not reach statistical significance, probably due to insufficient sample size. CLINICAL TRIAL REGISTRATION: DRKS-number 00000115, EudraCT-number 2009-009871-36.

Transmission Risk on a Neonatal Intensive Care Unit: Escherichia coli versus Klebsiella pneumoniae.

Isolation precautions required for neonatal intensive care units are part of a bundle with the aim to prevent transmission, colonization, and infection with multidrug-resistant gram-negative pathogens as neonates face an increased risk of mortality and morbidity in case of infection. The following short report describes a transmission of 3MDRGN Klebsiella pneumoniae on a neonatal intensive care unit in a university hospital in Germany. This transmission occurred even though intensified infection control measures were in place, which impressively shows the importance of surveillance, outbreak management, and awareness of contributing factors regarding outbreak situations.

Cytotoxicity of carbon nanohorns in different human cells of the respiratory system.

One of the new synthetic carbon-based nanomaterials is carbon nanohorns (CNH). A potential risk for employees of production processes is an unintentional intake of these nanomaterials via inhalation. Once taken up, nanoparticles might interact with cells of different tissues as well as with intercellular substances. These interactions may have far-reaching consequences for human health. Currently, many gaps in available information on the CNH toxicological profile remain. The aim of this study was to determine the cytotoxicity of CNH particles on human epithelial cells of the respiratory system with special consideration given to different particle sizes. In all cell lines, cell viability was reduced after 24 h of exposure up to 60% and metabolic activity as evidenced by mitochondrial activity was lowered to 9% at a concentration of 1 g/L. The three respiratory cell lines differed in their sensitivity. The most robust cells were the bronchial epithelial cells. Further, particle size fractions induced different adverse effect strength, whereby no correlation between particle size fraction and toxicity was found. These findings demonstrate the need for further information regarding the behavior and effect strength of nanomaterial. To avoid the production of new harmful materials, a more comprehensive integration of results from toxicity studies in the development processes of engineered nanomaterials is recommended not only from an occupational viewpoint but also from an environmental perspective.

Acetylcholinesterase and neuropathy target esterase activities in 11 cases of symptomatic flight crew members after fume events.

In modern aviation, so-called fume events such as exposure to an unknown mixture of chemicals introduced into the aircraft cabin with bleed air drawn off at the engines may occur. Human exposure may result in (neuro)toxic symptoms described as so-called "aerotoxic syndrome." Currently, among other agents organophosphates (OP) are regarded as a likely cause of the observed adverse effects. After fume events 11 flight crew members (9 female/2 male; ages 23-58 yr) were admitted for a medical examination within 5 d post exposure. Individual acetylcholinesterase (AChE) and neuropathy target esterase (NTE) activities were determined. Anamnesis and clinical findings confirmed prominent symptoms of an intoxication, including headache, cognitive difficulties, and neurological disorders, among others. Patient AChE activities ranged from 37 to 50 U/g hemoglobin (reference values: 26.7-50.9 U/g hemoglobin). Ten individuals showed NTE activities ranging from 3.14 to 6.3 nmol phenyl valerate/(min × mg protein) (reference values: 3.01-24), with one patient exhibiting low NTE activity of 1.4. Biochemical effect monitoring was applied to encompass a broad range of AChE-inhibiting compounds such as OP, carbamates, and isocyanates, or to detect inhibition of NTE. The measured AChE activities indicated a subordinate contribution of OP or related compounds to the observed symptoms. All noted NTE activities were clustered at low levels. Our data suggest a likely inhibition of NTE activities in patients after fume events, which warrants further investigation. The observed symptoms may be linked to known chemical compounds in fume events, and it is not possible to infer a direct correlation between manifestations and AChE -inhibiting compounds at this time.

Use of recombinant activated factor VII (Novoseven) in trauma and surgery: analysis of outcomes reported to an international registry.

The objective was to evaluate the efficacy and safety of recombinant activated factor VII in patients with massive bleeding. Forty-five patients with severe massive hemorrhage requiring>or= 14 transfusion units of packed red blood cells received recombinant activated factor VII. Postdrug blood loss and transfusion requirements were assessed, and mortality was compared with predicted outcomes. Blood loss was markedly reduced in 40 of 43 (93.0%) patients, and transfusion requirements decreased after recombinant activated factor VII administration. Mortality rate in trauma patients who had massive hemorrhage was significantly reduced compared with predictions using scoring systems. This may be associated with the use of recombinant activated factor VII. This study failed to demonstrate an improvement in surgical patients. The absence of concurrent controls prevents definitive conclusions regarding actual safety or efficacy of recombinant activated factor VII.

Overwhelming septic infection with a multi-resistant Staphylococcus aureus (MRSA) after total knee replacement.

INTRODUCTION: The incidence of early deep infection after arthroplasty of the knee is very low but could represent a serious future problem. MATERIAL AND METHODS: The authors report on a 71-year-old woman with gonarthritis who was supplied with a total knee endoprosthesis and developed a local infection followed by septic shock. RESULTS: The infection was evidently caused by a multiresistant Staphylococcus aureus (Staph. aureus). The primary clinical signs closely resembled a necrotizing fasciitis. Systemic and local application of vancomycin led to an improvement of the symptoms at secondary sites, but only the amputation of the primarily infected leg was lifesaving. CONCLUSION: In order to prevent such events, the authors recommend a number of additional presurgical measures. Firstly, a swab from the nose and throat should be taken prior to an elective surgery in patients with elevated risk of immunodeficiency, for example in patients with diabetes. The diabetes should be adequately treated before an elective operation is undertaken. Secondly, an early punction of the knee joint should be carried out if there is any doubt regarding inflammation. Isolated infectious agents should be grounds for early revision, which should always be completed with a rinsing procedure and with adequate antibiotics. Immunotherapy should be taken into consideration. Antiepidemic measures are recommended in cases with known Staph. aureus.