Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy

Aims: This study aims to assess subclinical changes in functional and morphological myocardial magnetic resonance parameters very early into an anthracycline treatment, which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP). Methods and results: Thirty sarcoma patients with planned anthracycline-based chemotherapy (360-400 mg/m doxorubicin-equivalent) were recruited. Median treatment time was 19.1 ± 2.1 weeks. Enrolled individuals received three cardiovascular magnetic resonance studies (before treatment, 48 h after first anthracycline treatment, and upon completion of treatment). Native T1 mapping (modified Look-Locker inversion recovery 5s(3s)3s), T2 mapping, and extracellular volume maps were acquired in addition to a conventional cardiovascular magnetic resonance with steady-state free precession cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10%. For analysis, 23 complete data sets were available. Nine patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. When assessed 48 h after first dose of antracyclines, patients with subsequent aCMP had significantly lower native myocardial T1 times compared with before therapy (1002.0 ± 37.9 vs. 956.5 ± 29.2 ms, P  0.05). Patients with aCMP had decreased left ventricular mass upon completion of therapy (86.9 ± 24.5 vs. 81.1 ± 22.3 g; P = 0.02), while patients without aCMP did not show a change in left ventricular mass (81.8 ± 21.0 vs. 79.2 ± 18.1 g; P > 0.05). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy. Conclusions: Early decrease of T1 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy

Fast acquisition of left and right ventricular function parameters applying cardiovascular magnetic resonance in clinical routine - validation of a 2-shot compressed sensing cine sequence

OBJECTIVES: To evaluate if cine sequences accelerated by compressed sensing (CS) are feasible in clinical routine and yield equivalent cardiac morphology in less time. DESIGN: We evaluated 155 consecutive patients with various cardiac diseases scanned during our clinical routine. LV and RV short axis (SAX) cine images were acquired by conventional and prototype 2-shot CS sequences on a 1.5 T CMR. The 2-shot prototype captures the entire heart over a period of 3 beats making the acquisition potentially even faster. Both scans were performed with identical slice parameters and positions. We compared LV and RV morphology with Bland-Altmann plots and weighted the results in relation to pre-defined tolerance intervals. Subjective and objective image quality was evaluated using a 4-point score and adapted standardized criteria. Scan times were evaluated for each sequence. RESULTS: In total, no acquisitions were lost due to non-diagnostic image quality in the subjective image score. Objective image quality analysis showed no statistically significant differences. The scan time of the CS cines was significantly shorter (p < .001) with mean scan times of 178 ± 36 s compared to 313 ± 65 s for the conventional cine. All cardiac function parameters showed excellent correlation (r 0.978-0.996). Both sequences were considered equivalent for the assessment of LV and RV morphology. CONCLUSIONS: The 2-shot CS SAX cines can be used in clinical routine to acquire cardiac morphology in less time compared to the conventional method, with no total loss of acquisitions due to nondiagnostic quality. Trial registration: ISRCTN12344380. Registered 20 November 2020, retrospectively registered

Translating principles of quality control to cardiovascular magnetic resonance: assessing quantitative parameters of the left ventricle in a large cohort

Cardiac magnetic resonance (CMR) examinations require standardization to achieve reproducible results. Therefore, quality control as known as in other industries such as in-vitro diagnostics, could be of essential value. One such method is the statistical detection of long-time drifts of clinically relevant measurements. Starting in 2010, reports from all CMR examinations of a high-volume center were stored in a hospital information system. Quantitative parameters of the left ventricle were analyzed over time with moving averages of different window sizes. Influencing factors on the acquisition and on the downstream analysis were captured. 26,902 patient examinations were exported from the clinical information system. The moving median was compared to predefined tolerance ranges, which revealed an overall of 50 potential quality relevant changes ("alerts") in SV, EDV and LVM. Potential causes such as change of staff, scanner relocation and software changes were found not to be causal of the alerts. No other influencing factors were identified retrospectively. Statistical quality assurance systems based on moving average control charts may provide an important step towards reliability of quantitative CMR. A prospective evaluation is needed for the effective root cause analysis of quality relevant alerts

Adaptation of Brucella melitensis Antimicrobial Susceptibility Testing to the ISO 20776 Standard and Validation of the Method

This article belongs to the Special Issue Emerging Themes in Brucella and Brucellosis.Brucellosis, mainly caused by Brucella (B.) melitensis, is associated with a risk of chronification and relapses. Antimicrobial susceptibility testing (AST) standards for B. melitensis are not available, and the agent is not yet listed in the EUCAST breakpoint tables. CLSI recommendations for B. melitensis exist, but they do not fulfill the requirements of the ISO 20776 standard regarding the culture medium and the incubation conditions. Under the third EU Health Programme, laboratories specializing in the diagnostics of highly pathogenic bacteria in their respective countries formed a working group within a Joint Action aiming to develop a suitable method for the AST of B. melitensis. Under the supervision of EUCAST representatives, this working group adapted the CLSI M45 document to the ISO 20776 standard after testing and validation. These adaptations included the comparison of various culture media, culture conditions and AST methods. A Standard Operation Procedure was derived and an interlaboratory validation was performed in order to evaluate the method. The results showed pros and cons for both of the two methods but also indicate that it is not necessary to abandon Mueller–Hinton without additives for the AST of B. melitensis.This research was funded by the EU Health Programme 2014–2020, through the Consumers, Health, Agriculture and Food Executive Agency (CHAFEA, European Commission), the Joint Action EMERGE (CHAFEA n° 677 066) and the Joint Action SHARP (848096-SHARP JA).info:eu-repo/semantics/publishedVersio

The effects of reconditioning exercises following prolonged bed rest on lumbopelvic muscle volume and accumulation of paraspinal muscle fat

Reduced muscle size and accumulation of paraspinal muscle fat content (PFC) have been reported in lumbopelvic muscles after spaceflights and head-down tilt (HDT) bed rest. While some information is available regarding reconditioning programs on muscle atrophy recovery, the effects on the accumulation of PFC are unknown. Recently, a device (the Functional Re-adaptive Exercise Device-FRED) has been developed which aims to specifically recruit lumbopelvic muscles. This study aimed to investigate the effects of a standard reconditioning (SR) program and SR program supplemented by FRED (SR+FRED) on the recovery of the lumbopelvic muscles following 60-day HDT bed rest. Twenty-four healthy participants arrived at the facility for baseline data collection (BDC) before the bed rest period. They remained in the facility for 13-days post-HDT bed rest and were randomly allocated to one of two reconditioning programs: SR or SR+FRED. Muscle volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles were measured from axial T1-weighted magnetic resonance images (MRI) at all lumbar intervertebral disc levels. PFC was determined using a chemical shift-based lipid/water Dixon sequence. Each lumbopelvic muscle was segmented into four equal quartiles (from medial to lateral). MRI of the lumbopelvic region was conducted at BDC, Day-59 of bed rest (HDT59), and Day-13 after reconditioning (R13). Comparing R13 with BDC, the volumes of the LM muscle at L4/L5 and L5/S1, LES at L1/L2, and QL at L3/L4 had not recovered (all - P<0.05), and the PM muscle remained larger at L1/L2 (P=0.001). Accumulation of PFC in the LM muscle at the L4/L5 and L5/S1 levels remained higher in the centro-medial regions at R13 than BDC (all - P<0.05). There was no difference between the two reconditioning programs. A 2-week reconditioning program was insufficient to fully restore all volumes of lumbopelvic muscles and reverse the accumulation of PFC in the muscles measured to BDC values, particularly in the LM muscle at the lower lumbar levels. These findings suggest that more extended reconditioning programs or alternative exercises may be necessary to fully restore the size and properties of the lumbopelvic muscles after prolonged bed rest

Intramuscular lipid concentration increased in localized regions of the lumbar muscles following 60-day bedrest

BACKGROUND CONTEXT Prolonged bedrest induces accumulation of intramuscular lipid concentration (ILC) in the lumbar musculature; however, spatial distribution of ILC has not been determined. Artificial gravity (AG) mitigates some adaptations induced by 60-day bedrest by creating a head-to-feet force while participants are in a supine position. PURPOSE To quantify the spatial distribution of accumulation of ILC in the lumbar musculature after 60-day bedrest, and whether this can be mitigated by AG exposure. STUDY DESIGN Prospective longitudinal study. PATIENT SAMPLE Twenty-four healthy individuals (8 females) participated in the study: Eight received 30 min continuous AG (cAG); Eight received 6 × 5min AG (iAG), interspersed with rests; Eight were not exposed to AG (CRTL). OUTCOME MEASURES From 3T magnetic resonance imaging (MRI), axial images were selected to assess lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 intervertebral disc levels. Chemical shift-based 2‐echo lipid/water Dixon sequence was used to measure tissue composition. Each lumbar muscle was segmented into four equal quartiles (from medial to lateral). METHODS Participants arrived at the facility for the baseline data collection before undergoing a 60-day strict 6° head-down tilt (HDT) bedrest period. MRI of the lumbopelvic region was conducted at baseline and Day-59 of bedrest. Participants performed all activities, including hygiene, in 6° HDT and were discouraged from moving excessively or unnecessarily. RESULTS At the L4/L5 and L5/S1 intervertebral disc levels, 60-day bedrest induced a greater increase in ILC in medial and lateral regions (∼+4%) of the LM than central regions (∼+2%; P<0.05). A smaller increase in ILC was induced in the lateral region of LES (∼+1%) at L1/L2 and L2/L3 than at the centro-medial region (∼+2%; P<0.05). There was no difference between CRTL and intervention groups. CONCLUSIONS Inhomogeneous spatial distribution of accumulation of ILC was found in the lumbar musculature after 60-day bedrest. These findings might reflect pathophysiological mechanisms related to muscle disuse and contribute to localized lumbar spine dysfunction. Altered spatial distribution of ILC may impair lumbar spine function after prolonged body unloading, which could increase injury risk to vulnerable soft tissues, such as the lumbar intervertebral discs. These novel results may represent a new biomarker of lumbar deconditioning for astronauts, bedridden, sedentary individuals, or those with chronic back pain. Changes are potentially modifiable but not by the AG protocols tested here

Burkholderia pseudomallei multi-centre study to establish EUCAST MIC and zone diameter distributions and epidemiological cut-off values.

OBJECTIVES: Melioidosis, caused by Burkholderia pseudomallei, requires intensive antimicrobial treatment. However, standardized antimicrobial susceptibility testing (AST) methodology based on modern principles for determining breakpoints and ascertaining performance of methods are lacking for B. pseudomallei. This study aimed to establish MIC and zone diameter distributions on which to set epidemiological cut-off (ECOFF) values for B. pseudomallei using standard EUCAST methodology for non-fastidious organisms. METHODS: Non-consecutive, non-duplicate clinical B. pseudomallei isolates (9-70 per centre) were tested at eight study centres against eight antimicrobials by broth microdilution (BMD) and the EUCAST disc diffusion method. Isolates without and with suspected resistance mechanisms were deliberately selected. The EUCAST Development Laboratory ensured the quality of study materials, and provided guidance on performance of the tests and interpretation of results. Aggregated results were analysed according to EUCAST recommendations to determine ECOFFs. RESULTS: MIC and zone diameter distributions were generated using BMD and disc diffusion results obtained for 361 B. pseudomallei isolates. MIC and zone diameter ECOFFs (mg/L; mm) were determined for amoxicillin-clavulanic acid (8; 22), ceftazidime (8; 22), imipenem (2; 29), meropenem (2; 26), doxycycline (2; none), tetracycline (8; 23), chloramphenicol (8; 22) and trimethoprim-sulfamethoxazole (4; 28). CONCLUSIONS: We have validated the use of standard BMD and disc diffusion methodology for AST of B. pseudomallei. The MIC and zone diameter distributions generated in this study allowed us to establish MIC and zone diameter ECOFFs for the antimicrobials studied. These ECOFFs served as background data for EUCAST to set clinical MIC and zone diameter breakpoints for B. pseudomallei

Whole genome sequencing of Brucella melitensis isolated from 57 patients in Germany reveals high diversity in strains from Middle East

Brucellosis, a worldwide common bacterial zoonotic disease, has become quite rare in Northern and Western Europe. However, since 2014 a significant increase of imported infections caused by Brucella (B.) melitensis has been noticed in Germany. Patients predominantly originated from Middle East including Turkey and Syria. These circumstances afforded an opportunity to gain insights into the population structure of Brucella strains. Brucella-isolates from 57 patients were recovered between January 2014 and June 2016 with culture confirmed brucellosis by the National Consultant Laboratory for Brucella. Their whole genome sequences were generated using the Illumina MiSeq platform. A whole genome-based SNP typing assay was developed in order to resolve geographically attributed genetic clusters. Results were compared to MLVA typing results, the current gold-standard of Brucella typing. In addition, sequences were examined for possible genetic variation within target regions of molecular diagnostic assays. Phylogenetic analyses revealed spatial clustering and distinguished strains from different patients in either case, whereas multiple isolates from a single patient or technical replicates showed identical SNP and MLVA profiles. By including WGS data from the NCBI database, five major genotypes were identified. Notably, strains originating from Turkey showed a high diversity and grouped into seven subclusters of genotype II. MLVA analysis congruently clustered all isolates and predominantly matched the East Mediterranean genetic clade. This study confirms whole-genome based SNP-analysis as a powerful tool for accurate typing of B. melitensis. Furthermore it allows special allocation and therefore provides useful information on the geographic origin for trace-back analysis. However, the lack of reliable metadata in public databases often prevents a resolution below geographic regions or country levels and corresponding precise trace-back analysis. Once this obstacle is resolved, WGS-derived bacterial typing adds an important method to complement epidemiological surveys during outbreak investigations. This is the first report of a detailed genetic investigation of an extensive collection of B. melitensis strains isolated from human cases in Germany

Beitrag zur Bestimmung von Strontium-090 neben Strontium-089 im Abwasser

Bei der Strahlenschutzüberwachung radioaktiver Abwässer ist häufig die alleinige Bestimmung der Gesamt-$\alpha$-und $\beta$-Aktivität nicht ausreichend, so daß eine weitergehende Analyse notwendig wird. Hierbei kann man sich mit Vorteil der qualitativen und quantitativen $\gamma$-Spektroskopie bedienen, sofern die kontaminierenden Radionuklide nicht reine $\beta$-Strahler sind. Ein Radionuklid, für das diese Einschränkung gilt, ist bekanntlich $^{90}$Sr, das wegen seiner hohen Radiotoxizität und der deshalb niedrigen Abwasserfreigrenze besondere Aufmerksamkeit beansprucht. Es läßt sich nur nach einerhinreichend guten Abtrennung von anderen Radionukliden über seine $\beta$-Emission oder die seiner Tochter $^{90}$Y durch Zählung bestimmen. Eine zusätzliche Erschwerung der $^{90}$Sr-Bestimmung entsteht durch die unbedingt notwendige Diskriminierung gegenüber dem wesentlich weniger gefährlichen, ebenfalls reinen $\beta$-Strahler $^{89}$Sr, dessen Abwasserfreigrenze um zwei Größenordnungen höher liegt. Störungen durch andere Sr-Isotope lassen sich entweder meßtechnisch bequem eliminieren oder sind wegen der Kurzlebigkeit der Isotope in den meisten Fällen unbedenklich. Es existiert eine große Zahl von Bibliographien, Zusammenfassungen und Monographien, die sich mit der Bestimmung von Radiostrontium in den verschiedenstenMaterialien beschäftigen [1 bis 13]. Speziell der $^{90}$Sr-Analyse in wäßrigen Systemen sind viele Arbeiten gewidmet [8, 14 bis 46], wobei Spaltproduktlösungen häufig als Untersuchungsobjekt im Mittelpunkt stehen [14, 15, 16, 21, 30, 31, 32, 34, 36, 37, 42]. Relativ wenig berichtet wurde bisher über die Isolierung und Bestimmung von $^{90}$Sr in chemisch verunreinigten Betriebsabwässerngrößerer kerntechnischer und Kernforschungs-Anlagen [20, 35, 43]. Diese Abwässer stehen mit dem Grad ihrer radioaktivenKontamination zwischen den Spaltproduktlösungen aus der Kernbrennstoffaufbereitung einerseits und Regen-, Zisternen- und Oberflächenwässern andererseits. Dies führt dazu, daß vor der Isolierung eines Radionuklids eine Anreicherung im allgemeinen nicht zu umgehen ist. Ziel unserer Bemühungen war es, ein Verfahren zur Bestimmung von $^{90}$Sr neben $^{89}$Sr auszuarbeiten, das1. in seinem Anreicherungsschritt die chemische Beschaffenheit unseres Abwassers berücksichtigt, 2. eine einfach auszuführende Radiostrontiumisolierung mit nachfolgender $^{90}$Y-Abtrennung gewährleistet und 3. mit hoher Gesamtausbeute arbeitet, so daß eine minimale $^{90}$Y-Nachbildungszeit ausreichend ist