Brain natriuretic peptide increases in septic patients without severe sepsis or shock

BACKGROUND: B-type natriuretic peptide (BNP) production increases in critically ill septic patients. We assessed the hypothesis that BNP is elevated in patients with community-acquired infections without severe sepsis or septic shock. METHODS: We studied 54 patients [20 males, median age 39 (interquartile range 23, 71)] without heart disease, persistent arrhythmias, or renal failure. BNP was measured in all patients at hospital admission and at pre-discharge and in a control group of 52 individuals. Myoglobin levels were also measured in septic patients. RESULTS: The infection was microbial in 40 patients, viral in 11, and of undefined etiology in 3. A systemic inflammatory response was evident in 38 patients on the initial evaluation. BNP on admission was higher in patients than in controls [25 (10, 82) pg/ml vs. 13 (5, 30) pg/ml, p=0.01] and it decreased to 16 (5, 47) pg/ml pre-discharge (p=0.0002). Multiple logistic regression identified the presence of microbial infection as the only independent predictor of an elevated BNP value on admission [adjusted odds ratio 9.8 (1.02-93.8), p=0.04]. In patients with microbial infection, location of infection in the lower respiratory tract and the presence of diabetes mellitus were independent predictors of the magnitude of BNP increase. Myoglobin was also increased on hospital admission 80 (37, 231) ng/ml and decreased pre-discharge to 59 (38, 94) ng/ml, p=0.004. Myoglobin level changes from admission to discharge were more prominent with increasing age and in females. CONCLUSION: BNP levels are elevated in the acute phase of community-acquired microbial infections without severe sepsis or septic shock.     

Spondylodiscitis due to Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an increasingly recognized cause of severe nosocomial infections, especially in immunocompromised patients. Community-acquired infections have also been reported. Spondylodiscitis due to S. maltophilia has only once before been described in the literature. We present a case of spondylodiscitis due to community-acquired S. maltophilia infection in a renal transplant recipient with liver cirrhosis.     

Differences in the evolution of imipenem susceptibility among Klebsiella pneumoniae and Escherichia coli isolates during a 6-year period in a tertiary care hospital

The evolution of imipenem disk-diffusion susceptibility results of 2652 strains of Klebsiella pneumoniae and 7596 Escherichia coli isolated during the period 2000-2005 were analysed. Screening for production of metallo-beta-lactamases was performed using the EDTA-synergy method. The percentage rate of K. pneumoniae isolates having a zone diameter < or =25 mm increased from 20% in 2000 to 41% in 2005, whereas the respective rate of isolates having a zone diameter > or =30 mm decreased from 48 to 23%. These changes were more evident during 2000-2002, followed in 2003 by the isolation of the first imipenem-resistant strains. Regarding E. coli, a similar decrease was observed (the rates of isolates having a zone diameter < or =25 mm and > or =30 mm changed from 7% and 68% in 2000, to 32% and 36% in 2005, respectively) following the respective changes of K. pneumoniae. A total of 20 K. pneumoniae strains, but no E. coli, were confirmed as metallo-beta-lactamase producers. In conclusion, a decrease of the imipenem susceptibility prior to the isolation of the first resistant strains in a tertiary care hospital was detected, as well as differences in this decrease between the two species. These findings indicate that monitoring of the evolution of imipenem susceptibility in real-time may help in unveiling forthcoming resistance and in implementing the appropriate diagnostic techniques.     

Novel processing of Notch 1 within its intracellular domain by a cysteine protease

In order to study N1 processing, we expressed human N1 (hN1) in HEK293 cells (293-hN1). Following Western blot analysis of 293-hN1 extracts, we detected, in addition to full-length hN1 and the N1 extracellular domain truncated form (N1-TM), a novel extracellular domain truncated form of hN1 with a COOH-terminal deletion, designated hN1-TMdeltaCT. Treatment of cells with the gamma-secretase inhibitor L-685,458 resulted in an accumulation of hN1-TMdeltaCT suggesting that this fragment is a gamma-secretase substrate. To identify the proteolytic activity(ies) that generates hN1-TMdeltaCT, we treated 293-hN1 cells with inhibitors of proteasome, calpains, caspases, serine and cysteine proteases. Despite the presence of a caspase-3 cleavage site within hN1 intracellular domain, none of the caspase inhibitors inhibited hN1-TMdeltaCT production. The proteasomal inhibitors used had also no effect. Incubation of cells with the cysteine protease inhibitor E64d resulted in the accumulation of hN1-TM and the inhibition of hN1-TMdeltaCT production suggesting a precursor-product relationship and that a cysteine protease is involved. Similarly, treatment of cells expressing amyloid precursor protein or E-cadherin with E-64d resulted in the accumulation of COOH-terminal fragments suggesting that these proteins are also processed within their intracellular domain by a cysteine protease. Processing towards hN1-TMdeltaCT requires maturation and transport of hN1 to the cell surface since treatment with brefeldin A inhibited its production and resulted in accumulation of hN1. Processing of hN1 within its intracellular domain could generate fragments that can exert novel functions and/or interfere with the function of hN1 intracellular domain.     

The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.     

External quality assessment of SARS-CoV-2 serology in European expert laboratories,April 2021

BackgroundCountries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration.AimThe aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing.MethodsThe EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries.ResultsThe overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards.ConclusionOur EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.     

Cardiac tamponade complicating ventricular arrhythmia ablation: Real life data on incidence,management, and outcome

Background and Objective

Cardiac tamponade during ablation procedures is a life-threatening complication. While the incidence and management of tamponade in atrial fibrillation ablation have been extensively described, the data on tamponade during ventricular ablations are very limited. The purpose of this study is to shed light on the incidence, typical perforation sites, and optimal management as observed through real-life data in a tertiary referral center for ventricular ablation.

Methods and Results

Consecutive patients with structural heart disease undergoing ventricular tachycardia ablation from 2008–2020 were analyzed. Of the 1078 patients undergoing 1287 ventricular ablation procedures, 20 procedures (1.5%) were complicated by cardiac tamponade. In all but one patient, the tamponade was treated with emergent pericardial drainage, while nine patients eventually underwent surgical repair. The perforation occurred during transseptal or subxiphoid puncture in six patients, during ventricle mapping in two patients, and during ablation in five patients (predominantly basal left ventricle). Steam pop as definite perforation cause could only be established in two patients. Regardless of the management of the complication, all patients survived to discharge.

Conclusion

Cardiac tamponade during ventricular ablation occurred in 1.5% of the procedures. In nine patients cardiac repair was necessary. Perforation was mostly associated with subxiphoid puncture or ablation of the basal left ventricle.