Reduced turnaround time for blood culture: : Experiences from an improvement process

Background Customer satisfaction is important for clinical microbiology laboratories and the most important service aspect is the reliability of responses. One important indicator of the quality of care is turnaround time for a sample referred to a laboratory. Aim This study describes and evaluates an improvement of the blood culture process and evaluates the staff’s experiences of the changes brought by the improvement project. Methods The blood culture process during evenings and nights was re-designed in a cooperation project between the laboratories of clinical microbiology and clinical chemistry in a mid-size Swedish county council. Typing with matrix-assisted laser desorption/ionization time of flight (MALDI ToF) and rapid antibiotic susceptibility testing were also introduced. To describe staff experi-ences semi-structured interviews were performed with twelve of the staff involved. Results The time from sampling to susceptibility testing and typing, for patients with cefotaxime resistant enterobacteriaceae, was before the improvement project on average 55 hours compared to 43 hours after closure of the project. In the qualitative content analysis four categories were found which represented the experience of the staff: patient focus, changed knowledge, cooperation and driving forces. Discussion The study of the implementation of the improvement showed that laboratory staff could handle the change well. The change from traditional biochemical typing, used for over 50 years, to MALDI ToF is indeed a paradigm shift. Nevertheless, nobody was disappointed over the fact that some of the fundamental previous microbiological laboratory work routines were laid to rest

Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis

Purpose The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis. Methods As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays. Results Associations with appendicitis were found for SNPs IL-13 rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17 rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22 rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13 rs1800925 and CTLA4 rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17 rs2275913 and CD44 rs187115. Conclusions The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis

Protein expression and gene polymorphism of CXCL10 in patients with colorectal cancer

Chemokines (chemotactic cytokines) promote leukocyte attraction to sites of inflammation and cancer. Certain chemokines promote and regulate neoplastic progression, including metastasis and angiogenesis. One such chemokine, CXCL10, was found to be expressed in colorectal cancer (CRC) tissue. To gain insight into the prognostic significance of CXCL10, we investigated whether the levels of this chemokine were altered in the colorectal tissue or plasma of CRC patients. Using Luminex technology for protein analyses, we observed a significantly higher CXCL10 protein level in cancer tissue compared to that in paired normal tissue. Moreover, significantly higher plasma levels of CXCL10 were detected in patients compared to those in control subjects and the plasma levels of CXCL10 in disseminated disease were found to be significantly higher compared to those in localized disease. The single‑nucleotide polymorphism rs8878, which has been described in exon 4 in the 3'‑untranslated region of the CXCL10 gene, was investigated using a TaqMan system. There were significant differences in genotype distribution and allelic frequencies between CRC patients and control subjects. In conclusion, altered CXCL10 protein concentrations in CRC tissues or plasma and the rs8878 genotype variant of CXCL10 may contribute to the prediction of clinical outcome

Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis

CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrow-band ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.Funding Agencies|Swedish Psoriasis Foundation; Futurum; Academy of Healthcare; County Council of Jonkoping, Sweden</p

Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin

WNT/beta-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohns disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.Funding Agencies|Swedish Psoriasis Foundation; Futurum-Academy for Health and Care, Region Jonkoping County, Sweden</p

Study of explosive dispersal of solid particles and detonability of two-phase oxygen-aluminium particles mixtures

Pour une meilleure compréhension des mécanismes d’explosions de nuages réactifs hétérogènes, la dispersion de particules solides par choc ainsi que la détonabilité des mélanges diphasiques aluminium-oxygène ont été étudiés expérimentalement et numériquement.La dispersion des particules solides est réalisée par l’explosion en champ libre de charges sphériques composées d’un explosif solide central entouré par une couche de particules solides inertes. Les données expérimentales sont obtenues à l’aide de capteurs de pression, d’un piège à particules et d’une caméra rapide.La compaction puis la décompaction de la couche est suivie de la formation d’agglomérats, tandis que certaines particules sont brisées par le choc. Le choc frontal est retardé et l’effet de souffle nettement réduit. Les particules sont réparties dans le nuage en fonction de leur taille. Les simulations numériques 1D sont en accord raisonnable avec les résultats expérimentaux.La détonabilité de mélanges diphasiques oxygène-particules d’aluminium en suspension a été étudiée en initiant une détonation divergente non confinée, dont on enregistre l’évolution temporelle de la pression et la structure cellulaire. Lors d’un amorçage avec 200-250g d’explosif solide (C4), la détonation se forme à une distance 1,6m. Les caractéristiques maximales sont observées à une distance de 2,3m (limite du nuage expérimental) et sont en accord avec les caractéristiques théoriques CJ. La structure cellulaire a été mise en évidence pour la première fois dans ce type de mélange ; sa taille est 10-15cm. Les simulations numériques 2D cylindriques, effectuées avec le code EFAE, donnent une taille de cellule légèrement supérieure.Explosive dispersal of solid particles and detonability of two-phase oxygen-aluminum particles mixtures have been investigated experimentally and numerically in order to get a better understanding of the mechanisms governing the explosion of reactive heterogeneous mixtures.Solid particles were dispersed by the free-field explosion of spherical charges made of a central booster of solid explosive surrounded by a loose-packed density shell of inert particles. Pressure gauges, a particles trap and a high frame rate camera were used to gather experimental data. Compaction and decompaction of the layer are followed by the formation of particle agglomerates, whereas some other particles are burst by the shock. The leading shock is delayed and the blast effect is strongly damped. Particles are spread into the cloud accordingly to their size. 1D numerical simulations agree in general with the experimental results.The detonability of two-phase oxygen-aluminum particles mixtures was studied by initiating an unconfined diverging detonation, during which the temporal pressure evolution and the cellular structure were recorded. The detonation wave formed at 1,6m. With an ignition charge of 200-250g C4, the maximal values of pressure and velocity recorded at a radial distance of 2,3m (corresponding to the border of the cloud) are consistent with the CJ values. The cellular structure was observed for the first time in this kind of mixture with a cell size of 10-15cm. The cell size calculated with a 2D cylindrical simulation (performed with the EFAE code) is slightly larger

Polymorphism of the p38 beta gene in patients with colorectal cancer

The p38 mitogen‑activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, ‑1628A→G) in the promoter region of the p38β gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the ‑1628A→G polymorphism of the p38β gene is not significantly associated with a susceptibility to CRC in a Swedish population

Common 4977 bp deletion and novel alterations in mitochondrial DNA in Vietnamese patients with breast cancer

Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and ageing. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in breast cancer (BC). The aim of this study was to investigate the frequency of mtDNA 4977 bp deletion in BC tissue and its association with clinical factors. We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 106 Vietnamese patients with BC by sequencing PCR products. The mtDNA 4977 bp deletion was significantly more frequent in normal tissue in comparison with paired cancer tissue. Moreover, the incidence of the 4977 bp deletion in BC tissue was significantly higher in patients with estrogen receptor (ER) positive as compared with ER negative BC tissue. Preliminary results showed, in cancerous tissue, a significantly higher incidence of novel deletions in the group of patients with lymph node metastasis in comparison with the patients with no lymph node metastasis. We have found 4977 bp deletion in mtDNA to be a common event in BC and with special reference to ER positive BC. In addition, the novel deletions were shown to be related to lymph node metastasis. Our finding may provide complementary information in prediction of clinical outcome including metastasis, recurrence and survival of patients with BC

EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures: validation in 55 European laboratories

Objectives: When bloodstream infections are caused by resistant bacteria, rapid antimicrobial susceptibility testing (RAST) is important for adjustment of therapy. The EUCAST RAST method, directly from positive blood cultures, was validated in a multi-laboratory study in Europe. Methods: RAST was performed in 40 laboratories in northern Europe (NE) and 15 in southern Europe (SE) from clinical blood cultures positive for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus or Streptococcus pneumoniae. Categorical results at 4, 6 and 8 h of incubation were compared with results for EUCAST standard 16-20 h disc diffusion. The method, preliminary breakpoints and the performance of the laboratories were evaluated. Results: The total number of isolates was 833/318 in NE/SE. The number of zone diameters that could be read (88%, 96% and 99%) and interpreted (70%, 81% and 85%) increased with incubation time (4, 6 and 8 h). The categorical agreement was acceptable, with total error rates in NE/SE of 2.4%/4.9% at 4 h, 1.1%/3.5% at 6 h and 1.1%/3.3% at 8 h. False susceptibility at 4, 6 and 8 h of incubation was below 0.3% and 1.1% in NE and SE, respectively, and the corresponding percentages for false resistance were below 1.9% and 2.8%. After fine-tuning breakpoints, more zones could be interpreted (73%, 89% and 93%), with only marginally affected error rates. Conclusions: The EUCAST RAST method can be implemented in routine laboratories without major investments. It provides reliable antimicrobial susceptibility testing results for relevant bloodstream infection pathogens after 4-6 h of incubation. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.This work was supported by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) through its regular support of the development of EUCAST methodology and by the Medical Research Council of Southeast Sweden (grant number FORSS-744451).publishedVersio