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Antibiotic resistance in Enterobacter cloacae strains with derepressed/partly derepressed/inducible AmpC and extended spectrum beta-lactamases in Zenica-Doboj Canton, Bosnia and Herzegovina
AIM: To investigate the prevalence of derepressed/partly derepressed/inducible and ESBL/AmpC-producing Enterobacter cloacae isolates and treatment options for infections associated with those isolates. ----- METHODS: Antibiotic susceptibility was determined by disc diffusion and broth microdilution according to CLSI guidelines. Doubledisk synergy test (DDST) was performed in order to screen for ESBLs and combined disk test with phenylboronic acid to detect AmpC β -lactamases. PCR was used to detect blaESBL/blacarb genes. Genetic relatedness of the strains was determined by pulsed-fieldgel-electrophoresis (PFGE). ----- RESULTS: Among 14 isolates with the ESBL positive E. cloaceae producing isolates, four (28.6%), nine (64.3%) and one (7.1%) isolates were derepressed/partly derepressed and inducible AmpC producers. Eleven (out of 14) isolates were resistant to cefotaxime, ceftazidime, ceftriaxone, aminoglycosides and fluoroquinolones. All isolates were susceptible to imipenem and meropenem, 79% to cefepime. Five (out of 14; 35.7%) isolates (four derepressed and one inducible AmpC carrying E. cloaceae) were negative in phenotypic test for ESBLs, but positive for broad spectrum TEM-1 β-lactamase. One (out of four derepressed) also produced CMY-2 β-lactamase. Four (out of nine) partly derepressed isolates were positive with the DDST, but did not yield PCR products with primers targeting TEM, SHV and CTX-M beta-lactamases. Four positive partly derepressed isolates carried a blaCTX-M-1 gene, two blaOXA-1 one blaCTX-M-15, OXA-1 and one blaCTX-M-28, OXA-1 (n=1). ----- CONCLUSION: Microbiology laboratories must be able to detect and recognize AmpC-carrying isolates in a timely manner, especially those that are falsely susceptible in vitro to drugs that may be consideredfor therapy of infected patients
Increased mean platelet volume (MPV) is an independent predictor of inferior survival in patients with primary and secondary myelofibrosis
Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters. MPV was elevated in both PMF and SMF patients in comparison to controls, whereas there was no statistically significant difference between PMF and SMF. Elevated MPV was associated with lower platelets (P = 0.016), higher white blood cells (P = 0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic International Prognostic score category (P = 0.027), while there was no statistically significant association with driver mutations or degree of bone marrow fibrosis. Higher MPV was univariately associated with inferior overall survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007) and SMF patients (HR = 7.22, P = 0.034). These associations remained significant in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more aggressive disease features and exhibits powerful independent prognostic properties in both PMF and SMF settings
Stroke promotes survival of nearby transplanted neural stem cells by decreasing their activation of caspase 3 while not affecting their differentiation
Although transplantation of stem cells improves recovery of the nervous tissue, little is known about the influence of different brain regions on transplanted cells. After we confirmed that cells with uniform differentiation potential can be generated in independent experiments, one million of neural stem cells isolated from B6.Cg-Tg(Thy1-YFP)16Jrs/J mouse embryos were transplanted into the brain 24 h after induction of stroke. The lateral ventricles, the corpus callosum and the striatum were tested. Two and four weeks after the transplantation, the cells transplanted in all three regions have been attracted to the ischemic core. The largest number of attracted cells has been observed after transplantation into the striatum. Their differentiation pattern and expression of neuroligin 1, SynCAM 1, postsynaptic density protein 95 and synapsin 1 followed the same pattern observed during in vitro cultivation and it did not differ among the tested regions. Differentiation pattern of the cells transplanted in the stroke-affected and healthy animals was the same. On the other hand, neural stem cells transplanted in the striatum of the animals affected by stroke exhibited significantly increased survival rates reaching 260 ± 19%, when compared to cells transplanted in their wild type controls. Surprisingly, improved survival two and four weeks after transplantation was not due to increased proliferation of the grafted cells and it was accompanied by decreased levels of activity of Casp3 (19.56 ± 3.1% in the stroke-affected vs. 30.14 ± 2.4% in healthy animals after four weeks). We assume that the decreased levels of Casp3 in cells transplanted near the ischemic region was linked to increased vasculogenesis, synaptogenesis, astrocytosis and axonogenesis detected in the host tissue affected by ischemia
Follicular fluid vascular endothelial growth factor is associated with type of infertility and interferon alpha correlates with endometrial thickness in natural cycle in vitro fertilization
The aim of this study was to analyse the presence of vascular endothelial growth factor (VEGF) and interferon alpha (IFN-α) in the follicular fluid (FF) and their possible influence, as pro-angiogenic or anti-angiogenic factors, on in vitro fertilization outcome. The concentrations of VEGF and IFN-α were correlated with oocyte and embryo quality, concentrations of hormones in the serum, perifollicular blood flow and endometrial thickness. VEGF was detected in all FF samples (median 706.6 pg/ml, range 182.9-6638 pg/ml). IFN-α was detected in 60% of the samples (median 6.5 pg/ml, range 0-79.4 pg/ml), while in 40% of the samples its levels were below the test detection limit. VEGF and IFN-α concentrations did not correlate with the cause of infertility, concentrations of FSH, LH, E2 and prolactin, oocyte or embryo quality. Significantly higher concentrations of VEGF have been found in women with primary compared with secondary infertility (p = 0.011, Mann Whitney test). The concentrations of VEGF and IFN-α did not correlate with the resistance index (RI) on days of hCG administration, follicular aspiration and embryo transfer. However, the concentrations of IFN-α correlated with endometrial thickness on the day of embryo transfer (Spearman correlation coefficient ρ = 0.4107; P < 0.05) but not on days of hCG administration and follicular aspiration. The mechanism of VEGF association with the previous ability of having a child needs to be clarified in future studies. The results of this study indicate a possible role of IFN-α in pathways of endometrial remodelling
Toxic liver injury after high-dose methylprednisolone in people with multiple sclerosis
The standard therapy of multiple sclerosis (MS) relapse is high-dose pulse corticosteroid therapy. Although commonly applied and usually well tolerated it may as well carry certain risks for people with MS, the more severe of them being hepatotoxicity. This report describes three cases of acute liver injury following pulse corticosteroid therapy with reference to other possible causative factors. Caution should be exercised when applying high-dose methylprednisolone given the potential liver related adverse events it may cause
Workforce requirements in rheumatology: a systematic literature review informing the development of a workforce prediction risk of bias tool and the EULAR points to consider
Objective: To summarise the available information on physician workforce modelling, to develop a rheumatology workforce prediction risk of bias tool and to apply it to existing studies in rheumatology.
----- Methods: A systematic literature review (SLR) was performed in key electronic databases (1946-2017) comprising an update of an SLR in rheumatology and a hierarchical SLR in other medical fields. Data on the type of workforce prediction models and the factors considered in the models were extracted. Key general as well as specific need/demand and supply factors for workforce calculation in rheumatology were identified. The workforce prediction risk of bias tool was developed and applied to existing workforce studies in rheumatology.
----- Results: In total, 14 studies in rheumatology and 10 studies in other medical fields were included. Studies used a variety of prediction models based on a heterogeneous set of need/demand and/or supply factors. Only two studies attempted empirical validation of the prediction quality of the model. Based on evidence and consensus, the newly developed risk of bias tool includes 21 factors (general, need/demand and supply). The majority of studies revealed high or moderate risk of bias for most of the factors.
----- Conclusions: The existing evidence on workforce prediction in rheumatology is scarce, heterogeneous and at moderate or high risk of bias. The new risk of bias tool should enable future evaluation of workforce prediction studies. This review informs the European League Against Rheumatism points to consider for the conduction of workforce requirement studies in rheumatology
Poremećaj deformacije miokarda procijenjen dvodimenzijskom studijom deformacije u hipertoničara s hipertrofijom interventrikulskoga septuma u izgonskom traktu lijeve klijetke [Myocardial deformation abnormalities assessed by two-dimensional deformation study in hypertensive patients with basal interventricular septal hypertrophy]
Background. A wide range of subclinical changes in left ventricular (LV) geometry and function may be observed, even in the early course of arterial hypertension (AH).
Aims. To investigate if the appearance of isolated basal septal hypertrophy (BSH) could be a marker of incipient intrinsc LV dysfunction.
Methods. A total of 138 patients with primary arterial hypertension, aged less than 65 years, with no comorbidities and with perserved LV ejection fraction (EF) were included. Complete transthoracic echocardiography study was preformed according to standardized protocol, as well as deformation study using speckle tracking echocardiography. Global and regional longitudinal strain was measured in apical 4-,2- and 3-chamber views according to 18-segments model. Global and regional circumferential and radial strains were measured in short axis view. Patients were divided into two groups according to BHS presence and values were compared.
Results. Basal septal hypertrophy was found in half of the patients (53.6%). The whole cohort had altogether normal LV geometry and global systolic and diastolic function, as well as global indices of radial (GRS 43.86 ± 10.75%) and longitudinal strain (GLS -19.73 ± 2.19%), while global circumferential strain (GCS) was mildly reduced (GCS -19.5 ± 2.81%). BSH patients had more expressed LV geometry changes (LV mass: 89.19±24.59 g/m² vs 109.15±25.33 g/m², p<001; relative wall thickness: 0.3±0.08 vs 0.38±0.11, p<0.001) and have also revealed a specific pattern of longitudinal deformation impairment in three LV segments (basal and mid interventricular septum, basal anteroseptum). A „strain gradient“ from LV base to apex (basal<mid<apical) was observed in the whole population for longitudinal and circumferential strain, and it was more pronounced in the BSH group. This group had more impaired averaged values of six basal LV segments for longitudinal strain and improved circumferential strain averaged for 6 apical segments. Subendocardial longitudinal strain was also more impaired in BSH group. Appearance of BSH, LV remodeling and regional LS impairement correlate with diastolic dysfunction (i.e. impaired relaxation).
Conclusion. Appearance of BSH is found to be a macroscopic marker of the regional and global LV remodeling, as well as a marker of diastolic and regional systolic dysfunction of the basal and mid LV segments
Imunohistokemijska izraženost estrogenskih receptora beta u papilarnom karcinomu štitnjače [Immunohistochemical expression of estrogen receptor beta in papillary thyroid carcinoma]
Papillary thyroid carcinoma occurs more frequently among women of reproductive age,
who additionally make up the best prognostic group. The obtained data suggest a
relation between estrogen and papillary carcinoma. Direct proliferative effect of
estrogen on papillary carcinoma cells has already been proven in vitro, and seems to be
mediated by estrogen receptors (ER). The biological importance of ER beta (ER β)
remains unclear, but recent research point to its possible prodifferentiative and
antiproliferative role.
This study has examined the immunohistochemical expression of ER beta in papillary
thyroid carcinoma. Specimen from 104 patients with papillary carcinoma has been
obtained. The data on age, sex, tumor size and histological subtype, presence of benign
thyroid disease, lymphocytic infiltrate, lymph node metastases, and intraglandular
dissemination were obtained from patient records and pathology reports. The
aforementioned parameters were compared with immunohistochemical reaction to ER
β.
The expression of ER β was present in both nuclei and cytoplasms of carcinoma cells.
Nuclear positivity was more expressed in women younger than 50 years, and
cytoplasmic positivity was more expressed in patients older than 50, irrespective of sex.
The conclusion is that ER beta expression in papillary carcinoma is related with age
and menopausal status in women, which suggests its possible prognostic relevance.
Consequently, further investigations should be made
Navigating Knowledge Landscapes in the digital society: a look back and visions for the future
Epidemic spread of OXA-48 beta-lactamase in Croatia
PURPOSE:
A dramatic increase in OXA-48 β-lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA-48 carbapenemase in Croatia. ----- METHODS:
Carbapenemase and other β-lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole-genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE.
----- RESULTS:
Forty-eight isolates positive for OXA-48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty-three isolates were ESBL positive and harboured group 1 CTX-M 1 β-lactamases. In addition to the β-lactam resistance genes detected by PCR (blaSHV-1, blaOXA-48 and blaOXA-1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia, fluoroquinolone resistance determinants aac(6)Ib-c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread. ----- CONCLUSIONS:
The OXA-48-positive organisms found in this study showed wide variability in antibiotic susceptibility, β-lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM-1 in 2012-2013 to that of OXA-48 in the 2015 to 2017