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Izražaj cirkulirajućih mikronaRNA (miR-125a, miR-125b, miR-126, miR-99b, miR-let7a) u bolesnika s mijelodisplastičnim sindromom [Expression of circulating microRNA (miR-125a, miR-125b, miR-126, miR-99b, miR-let7a) in myelodysplastic syndrome patients]
Get PDFMyelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematologic
disorders of hematopoietic stem cells, followed by ineffective hematopoiesis of
one or more cell lines with the onset of consequent cytopenia with an increased risk
of progression to acute myeloid leukemia. According to the World Health Organization
classification, the diagnosis of MDS is based on morphological, clinical, cytogenetic,
immunophenotypic and biological criteria.
In everyday clinical practice, the diagnosis of MDS is based on invasive cytomorphological
analysis of peripheral blood and bone marrow cells, determination of
blast percent, type and degree of dysplasia, presence of ring sideroblasts, and cytogenetic
analysis of bone marrow cells.
Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding molecules
of 18 to 25 nucleotides in length that play an important role in regulating cell
development and metabolism, their differentiation and proliferation, regulation of the
cell cycle and cell death. Tumor cells release miRNAs into the circulation (plasma,
serum) where they remain relatively stable. Although their discovery allowed linking
of disease and miRNA gene expression, a precondition for their clinical application
was the determination of gene expression by real-time quantitative polymerase chain
reaction with satisfactory efficacy and specificity. In the literature, gene expression of
miRNAs has been linked to the diagnosis, classification and progression of various
diseases.
Many studies have been conducted so far about the molecular mechanisms
and epigenetic pathways in MDS and their prognostic and therapeutic significance,
but few studies have analyzed the importance of miRNAs in MDS.
The aim of this study was to examine the level of change of gene expression
of specific mRNAs (miR-125a, miR-99b, miR-126, miR-125b, miR-let-7a) in plasma of
healthy volunteers and subjects diagnosed with MDS.
Gene expression of these specific mRNAs was determined in plasma samples
from healthy volunteers (18) and subjects with MDS (41). This paper describes for the
first time the expression of a selected miRNA cluster (125a, 125b, 99b, let-7a) in the
plasma of untreated MDS patients.
A significant difference was found between the study group and healthy control
in miR-99b level, where at normalized values relative to miR-126, an increased level
in subjects compared to control was observed 4,521 times (P = 0.004).
Diagnostic and prognostic significance of miR-125a was observed and correlated
negatively with erythrocyte count and hemoglobin level in the diagnosis of
MDS.The results of the study suggest that gene expression of miRNA (125a, 125b,
99b, let7a) could be regulated by the same mechanism and may be clinically relevant
in subjects with MDS
Osjećaj koherentnosti, zdravlje i kvaliteta života adolescenata tijekom srednjoškolskoga obrazovanja [Sense of Coherence, Health and Quality of Life in Adolescents During Secondary Education]
Get PDFAdolescence is marked by constant adaptation to stressful situations. One of those is
the beginning of secondary education and living in dormitories. The aim of the study
was to analyze the relationship between sense of coherence, health and subjective
well-being among adolescents living with parents and those living in dormitories during
their secondary education. The study was conducted on a sample of 441 adolescents.
The results did not support the hypothesis that adolescents living in dormitories have
a lower sense of coherence, poorer health and a lower quality of life compared to those
living with parents as well as that a sense of coherences changes during their
secondary education. The hypothesis that a sense of coherence is associated with
health and adolescents' quality of life during their secondary education was accepted.
Furthermore, subjective quality of life, male gender and mental health singled out as
the key adolescents’ sense of coherence predictor during their secondary education.
Regardless of their accommodation, it is important to implement health-promoting
factors into different areas of adolescent context, especially sense of coherence, so
that a better quality of life and adolescents' health are promoted with salutogenic
activities
Povezanost debljine lamele s vidnom oštrinom nakon stražnje slojevite transplantacije rožnice [Correlation of lamella thickness on visual acuity after Descemet's stripping automated endothelial keratoplasty]
Get PDFDescemet's Stripping Automated Endothelial Keratoplasty (DSAEK) is corneal
transplantation procedure where the patient's inner dysfunctional layer is replaced.
There are contradictory data in the literature about the correlation between lamellar
thickness and the visual acuity.
Study included 55 eyes after conventional DSAEK and no other comorbidities
that could affect visual acuity. Data about lamellar thickness and visual acuity were
measured before and 6 months after surgery.
The results show that visual acuity before surgery was 0,15 on average and
after surgery 0,57. Average postoperative lamella thickness was 142,16 μm. Better
visual acuity of 0,63 was achieved with lamellas thinner than 124 μm, while
statistically significantly lower visual acuity was 0,51 for lamellas thicker than 124 μm.
Postoperative deturgescence of lamellas 6 months after surgery was 12% from initail
thickness.
The goal after conventional DSAEK is to have postoperative lamellas thinner
than 124 μm in the eye, as this will result in better postoperative visual acuity. In
order to achieve this requirement, the request for the eye bank should be lamellas
thinner than 142 μm before the surgery. This will minimize tissue loss for eye banks
and the surgeons will have fewer problems during surgery, while obtaining good final
visual acuity
Application of a system dynamics model in forecasting the supply and age distribution of physicians
Get PDFAim: To predict the future supply and age distribution of physicians with a simulation model, which can be used as an advising tool for policymakers who decide on enrollment and specialization training (ST) quotas at the national level. -----
Methods: A simulation model was created using the system dynamics (SD) method. Changes in the number of physicians and their age distribution were projected in the context of the expected future changes of the Croatian population under different scenarios covering the period from 2017 to 2041. -----
Results: The two scenarios showed that Croatia would not face physician shortage in the future. The scenario 1 projected that Croatia would certainly reach the current European Union (EU) average of 360 physicians per 100 000 inhabitants by 2021, and that this figure would increase to 430 per 100 000 inhabitants by 2041. The scenario 2 suggested a similar trend, with Croatia reaching the current EU average by 2021 and the number of physicians increasing to 451 per 100 000 inhabitants by 2041. Both scenarios indicated that the Croatian physicians' age distribution will recover in favor of younger age groups of specialists. -----
Conclusion: There is no need to increase the enrollment into the medical schools to ensure sufficient number of physicians per capita in Croatia, but it is necessary to keep the recently reached level of 550 licenses for ST per year. The developed dynamic model is available online and can be adapted to the analysis of different scenarios in different health care system
A randomized, double-blind, efficacy and safety study of PF-05280586 (a Rituximab biosimilar) compared with Rituximab reference product (MabThera®) in subjects with previously untreated CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL)
Get PDFBackground: Biosimilars are highly similar to the licensed biologic ("reference product"), with no clinically meaningful differences in safety, purity, or potency between the two products. -----
Objective: This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera®; rituximab-EU). -----
Patients and methods: Subjects with CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) and an Eastern Cooperative Oncology Group performance status 0-1 were randomized (1:1) to PF-05280586 or rituximab-EU (375 mg/m2 intravenously [once weekly for 4 weeks at days 1, 8, 15, and 22]), stratified using the Follicular Lymphoma International Prognostic Index 2 classification. The primary endpoint was overall response rate (ORR) at week 26 (percentage of subjects achieving complete response [CR] or partial response [PR]). Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the difference in ORR between groups was within the prespecified margin (± 16%). Secondary endpoints included progression-free survival (PFS), CR rate, safety, immunogenicity, PK, and PD. -----
Results: A total of 394 subjects were randomized: PF-05280586 (n = 196) or rituximab-EU (n = 198). ORR at week 26 was 75.5% (PF-05280586) versus 70.7% (rituximab-EU), for a difference of 4.66%; 95% CI (- 4.16 to 13.47), which was entirely within the prespecified equivalence margin. Rates of CR were 29.3% (PF-05280586) versus 31.0% (rituximab-EU). Estimated 1-year PFS rates were 78.2% (95% CI 70.2-84.2) and 83.0% (95% CI 75.0-88.6) for PF-05280586 and rituximab-EU, respectively. Safety, immunogenicity, and mean serum concentrations were similar between groups. -----
Conclusions: The efficacy, safety, immunogenicity, PK, and PD of PF-05280586 and rituximab-EU were similar up to week 52 in subjects with previously untreated CD20-positive LTB-FL
Targeted prostate biopsy using a cognitive fusion of multiparametric magnetic resonance imaging and transrectal ultrasound in patients with previously negative systematic biopsies and non-suspicious digital rectal exam
Get PDFAim: To compare cognitive fusion targeted and systematic prostate biopsy in patients with repeated negative systematic biopsy but persistent clinical suspicion for prostate cancer.
----- Methods: The study enrolled 63 patients with at least one previously negative systematic biopsy who underwent targeted prostate biopsy using multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) in addition to standardized systematic biopsy from July 2016 to May 2018. Multiparametric MRI was performed with 3 Tesla device by uro-radiologists experienced in prostate cancer. Lesions with Prostate Imaging Reporting and Data System 3, 4, and 5 were considered suspicious. Targeted biopsies were performed with cognitive fusion of TRUS and mpMRI.
----- Results: Prostate cancer detection, using either targeted or systematic biopsy, was 60.32%. Targeted biopsies were positive in 52.38% and systematic biopsies in 47.62% of patients. The median highest percentage of cancer involvement per biopsy core was significantly higher in targeted cylinders. The biopsies obtained by using the two techniques did not significantly differ in Gleason score.
----- Conclusion: Cognitive targeted prostate biopsy based on mpMRI presents a valuable addition to systematic biopsy in patients with repeated negative systematic biopsies but persistent clinical suspicion of prostate cancer
Aktivnost eritrocitne glutation S-transferaze u djece oboljele od HenochSchönleinove purpure [Erythrocyte glutathione S-transferase activity in children with Henoch-Schönlein purpura]
Get PDFIntroduction: Henoch-Schönlein purpura (HSP) is the most common vasculitis of
the childhood. Among all possible symptoms / complications, nephritis (HSPN) is
the main and almost only cause of morbidity and mortality in HSP. The aim of this
study was to investigate the value of erythrocyte glutathione S-transferase (eGST) activity as an early predictor of nephritis in HSP. -----
Subjects and methods: Ninety-seven children with HSP were enrolled into the
study. The control group consisted of 52 children without clinical and laboratory
signs of inflammation. In all patients e-GST activity was determined
spectrometrically from the whole blood samples, after incubation with a
commercial GST assay at the time of enrolment and twice more in regular
intervals during follow up period of six months. In children from the control group
e-GST activity was determined at the time of enrolment. -----
Results: At the beginning of the disease the e-GST activity values were
significantly higher in the group of patients with HSPN compared to the group of
HSP patients without nephritis: median (interquartile range) 5,70 U/gHb (4,38-7,50
U/gHb) compared to 3,10 U/gHb (2,20-4,20 U/gHb); P˂0,001. Similar results were
obtained after the comparison of the patients with HSPN and control group: 5,70
U/gHb (4,38-7,50 U/gHb) vs. 3,13 U/gHb (1,91-4,20 U/gHb); P˂0,001. There were no
statistically significant differences between the group of HSP patients without
nephritis and a control group (P=0,837). During the follow up period of six months,
a significant decrease of e-GST activity was observed in the HSPN patients, but it was still significantly higher compared to the group of HSP patients without
nephritis (P˂0,001 / P˂0,001).
In the ROC analysis of the e-GST activity determination value in the prediction of
HSP nephritis, at the e-GST values >4,1 U/gHb a significant area under the curve
(AUC) of 91.1% (P < 0.001) and sensitivity of 90.5% and specificity of 72.7% was
found at the beginning of the study. The sensitivity of the nephritis detection tests
decreased, and the specificity increased during the follow up period. No significant
correlation between e-GST activity and severity of skin changes, or used therapy
was found. Among the routine laboratory tests, a consistent, statistically
significant, positive correlation was found only between e-GST activity and the
number of erythrocytes per mm3 in urine samples. -----
Conclusion: e-GST activity is a reliable, independent marker of early nephritis risk
assessment in children with HSP. As a sensitive and specific, feasible and
inexpensive laboratory test, it has potential practical utility in the diagnostic
algorithm and monitoring of the children with HSP