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Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype
Get PDFMonosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard-dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on outcomes in patients with a monosomal karyotype. Among monosomal karyo type patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recovery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128
Prospective comparison of two excimer laser platforms in treatment of high astigmatism with laser in situ keratomileusis [Prospektivna usporedba dvije laserske platforme u tretiranju visokog astigmatizma laser in situ keratomijeluzom]
Get PDFPURPOSE: Comparison of Wavelight Allegretto Eye-Q and Schwind Amaris 750S excimer laser
groups after performed LASIK procedure regarding functional parameters – uncorrected (UDVA)
and corrected distant visual acuity (CDVA), residual refractive error, astigmatism outcomes by
means of vector analysis and high order aberrations in patients with high astigmatism (more
than 2 diopters (D)). -----
METHODS: 135 patients with myopic astigmatism (246 eyes) and 102 patients with mixed
astigmatism (172 eyes) underwent LASIK correction (some of the patients had only one eye
operated – the eye that met the criteria for the study, while the other eye had no diopter at all)
and were divided in 4 groups: 1 – myopic astigmatism corrected with Allegretto, 2 – myopic
astigmatism corrected with Amaris, 3 – mixed astigmatism corrected with Allegretto and 4 –
mixed astigmatism corrected with Amaris. Data were analysed to determine significance of
change in spherical correction, astigmatism, UDVA, CDVA, high order aberrations, and also
vector analysis by Thibos (J0 and J45) and Alpins method was performed. -----
RESULTS: Visual acuity improvement for group 1 was statistically significant (p=0.017); for
group 2, 3 and 4 was not statistically significant (p=0.06, p=0.406, p=0.115). None of the eyes
lost any lines of CDVA. Regarding refractive results, for all groups there was almost complete
elimination of spherical and cylindrical refractive error. High-order aberrations results for groups
1 and 2 showed no significant change between preoperative and postoperative high-order
aberrations, while in groups 3 and 4 spherical aberrations changed. Vector analysis by Thibos
showed statistically significant difference between J0 preop and J0 postop for both platforms
(p<0.001). There was statistically significant difference for J45 postoperatively between the
platforms (p=0.012). Correlation between ΔJ0 and preop J0 values (groups 1 and 2) showed
that the difference between these two correlation coefficients was significant (z=−3.086,
p=0.002). There was statistically significant difference in preoperative mean values for J0
(p<0.001) between the groups 3 and 4. There was a statistically significant difference between
J0 preop and J0 postop for both platforms (p<0.001). Correlation between ΔJ0 and preop J0,
and between ΔJ45 and preop J45 for groups 3 and 4 showed that difference between these two
correlation coefficients was significant (z=−3.533, p=0.0004; z=−2.886, p=0.004). Vector analysis
by Alpins showed that negative SIA power (y1) was significantly correlated with negative TIA
power (x1) and sine of the TIA axis (x2) as follows: [a] i, y1=0.829X1–0.403X2–0.325 (F=87.76, R=0.804, P<0.001, N=127); ii, y1=0.891X1–0.037X2-0.192 (F=240.06, R=0.901, P<0.001, N=119)
and [b] i, y1=1.063X1+0.233X2+0.411 (F=990.99, R=0.881, P<0.001, N=61); ii, y1=1.029X1–
0.115X2+0.322 (F=270.12, R=0.908, P<0.001, N=111). The sine of negative SIA axis (y2) was
significantly correlated with negative TIA power (x1) and TIA axis (x2) as follows: [A] I,
y2=0.951x2–0.007x1+0.008 (F=446.58, r=0.950, p<0.001, n=127); II, y2=0.856x2+0.007x
1+0.105 (F=277.18, r=0.912, p<0.001, n=119) and [B] I, y2=0.953x2 +0.009x1+0.075 (F=362.6,
r=0.963, p<0.001, n=61); II, y2=0.977x2–0.004x1+0.002 (F=2910.9, r=0.990, p<0.001, n=111). -----
CONCLUSIONS: Both lasers showed effective in terms of UDVA, CDVA, spherical correction,
and preservation of high-order aberrations. However, Amaris was more effective in cylinder
correction. There was no genuine difference post-operatively between groups treated on two
different laser platforms according to the vector analyses by Thibos. By using Alpins method,
we revealed that both platforms were similar in tending to undercorrect astigmatism; axis
rotational errors were apparent, although overall the two platforms differed in terms of direction;
and the predicted angle between the SIA and TIA tended to increase when the astigmatic
correction was against-the-rule
Učinak pentadekapeptida BPC 157 na posljedice kauterizacije episkleralnih vena štakora [The effect of pentadecapeptide BPC 157 on consequences of episcleral vein cauterization in rats]
Get PDFIn female Wistar rats, 220 – 250 g, two dorsal and one temporal episcleral vein were isolated and cauterized. Medication was BPC 157 (10 μg/kg or 10 ng/kg) intraperitoneally (5 ml/kg) or locally (2x2 drops per day), either immediately before surgery and then once time daily; or at 24 h after surgery and then once time daily. Controls simultaneously received an equal volume of saline. Intraocular pressure, pupillar function were measured 24 hours, 4 and 6 weeks after procedure. Non-invasive IOP measurements were taken by aplanation tonometer “Tonopen XL”. Pupillar function was photographed by USB “Veho Discovery VMS-004 Deluxe” microcamera. Photographs were taken before and after medication application and analyzed with special camera software for measurement of pupillar diameter (r) in mm, range (C) in mm and surface (S) in mm2. Camera was previously calibrated using graph paper. Vascularization of the eye fundus and presentation of optic disc were analyzed with microcamera and “VOLK Digital Widefield lupe” 90D. Pathohistological analysis was performed after sacrifice. Episcleral vein cauterization caused high intraocular pressure, changes in pupillar function, retinal ischemia and optic nerve disk atrophy. BPC 157 applied locally or intraperitoneally normalized intraocular pressure, pupillar function, antagonized retinal ischemia and optic nerve atrophy
Učinak pentadekapeptida BPC 157 na tubularnu nekrozu u štakora izazvanu gentamicinom
Get PDFIntroduction: we have investigated the effect of pentadecapeptide BPC 157 on aminoglycoside nephrotoxicity (AN) in the rats after application of high dose of gentamicin. We assume that BPC 157 has nephroprotective effect by modulating overstimulative activity of iNOS in AN. Therefore we applied various combinations of L-NAME and L-arginin with BPC 157 and gentamicin. -----
Materials and methods: We have used male Wistar albino rats, body weight 150-200 grams. Rats have been randomized in 17 groups, 10 rats per group. Gentamicin in dose 100 mg/kg of body weight was administered to the rats in all groups. BPC 157 in attributable groups (AG) was administered intraperitoneally and per orally in AG. L-NAME, L-arginin and adequate combination were administered in AG. -----
Results: Clinical appearance was measured and scored, and score is significantly higher in all groups which were not been treated with BPC 157. Daily diuresis has been measured, polyuria is significantly higher and starts earlier in groups which are not treated with BPC 157, and anuric phase is not noted in BPC 157 treated rats. Significantly higher levels of creatinine and magnesium are noted in groups that are not treated with BPC 157. L-arginin raises creatinine values and concomitant L-arginin and L-NAME aggravates it more. Relative mass (RM) of kidney has been measured and results show higher RM in all groups that are not treated with BPC 157 which is probably caused by interstitial oedema. Finally, kidney samples will be patohystologicaly analysed and score is significantly better in BPC 157 treated rats. -----
Conclusion: we have proven that pentadecapeptide BPC 157 has a nephroprotective effect. BPC 157 decreases AN and mortality in AN which is evident in significantly better (p < 0,01) clinical status of the animal, absence of oliguric and anuric phase AN, lower creatinine, urea, calcium and magnesium levels, and PHD kidney findings showing either mild tubular lesions or virtually neat findings. BPC 157 effect is achieved by interference with the NO system, but also by other mechanisms that are not exclusively dependent on the NO system
Utjecaj polimorfizma rs3812718 gena SCN1A na učinkovitost lamotrigina u bolesnika s parcijalnom epilepsijom [Influence of rs3812718 polymorphism in the SCN1A gene on lamotrigine efficacy in patients with partial epilepsy]
Get PDFPolymorphism rs3812718 (IVS 5 - 91G > A) of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate sensitivity and responsiveness to common antiepileptic drugs. The purpose of this study was to investigate the effect of SCN1A rs3812718 (IVS 5 – 91 G > A) polymorphism on the response to lamotrigine. SCN1A rs3812718 (IVS 5 – 91 G > A) polymorphism was genotyped in 100 patients with focal epilepsy. After the introduction of lamotrigine, follow-up visits were performed every 3 months and lamotrigine dose was adjusted, in order to control disease, up to the maximum tolerable dose. Lamotrigine responsiveness was defined as a 75% and more reduction in seizure frequency on a stable dose of lamotrigine during 12 consecutive months. There was no significant difference in genotype and allele distribution between the responder and non-responder groups and no significant differences in the prevalence of responsiveness to lamotrigine between carriers of different genotypes. Average maintenance lamotrigine doses in the responder group differed by genotype in the order AA > GA > GG, but these differences did not reach statistical significance. Our data suggest no association between SCN1A rs3812718 (IVS 5 – 91 G > A) polymorphism and response to lamotrigine
Pojavnost mutacije gena BRAF u displastičnom nevusu i melanomu in situ
Get PDFMutations in the BRAF gene are common in melanomas and represent an early oncogenic event at their occurrence. The idea of this study is that the BRAF mutation analysis in samples of dysplastic nevi and melanoma in situ may help enlighten the unclear role of dysplastic nevi as precursor melanoma lesions.The objectives of the study were to determine and compare the frequency of BRAF gene mutations in dysplastic nevi and melanomas in situ and determine whether there is a correlation between the presence of BRAF gene mutations and various anamnestic, clinical and pathohistological variables. A total of 175 patients, i.e. 106 patients with dysplastic nevi, 41 patients with melanoma in situ and 28 patients with lentigo maligna melanoma, were included in the study. DNA has been extracted from tissue samples of all patients embedded in paraffin and analyzed using the competitive allele-specific TaqMan polymerase chain reaction in real time, all in order to determine the presence of BRAF V600E and V600K mutations.The obtained mutation data were compared with anamnestic, clinical and pathohistological data using appropriate statistical methods. Out of a total of 175 patients, BRAF mutation was found in 87 patients (49.7%): 68 (38.9%) patients with V600E and 20 (11.4%) patients with V600K. There was no statistically significant difference in the presence of BRAF mutation in patients with dysplastic nevi (58.5% of mutated) and those with melanoma in situ (60.9% of mutated) (p=0,371). In patients with dysplastic nevi, V600E mutation was significantly more common (89% of patients with mutation), while the V600K mutation was more common in patients with melanoma in situ (52% of patients with mutation). There was a statistically significant connection between the presence of BRAF mutations, tumor localization and the age of the patient (p=0,0001). Patients with mutation were younger than patients without mutations. No statistically significant connection between the presence of BRAF mutation and sex (p=0,104), tumor size (p=0,404), or previous melanoma diagnosis (p=0,856) has been found. The results of this study imply that BRAF mutations in dysplastic nevi have an important, but in itself insuffitient, role in triggering malignant transformation and onset of melanoma. In this respect, this research is a contribution to a better understanding of the etiopathogenesis of melanoma and the role of dysplastic nevi as precursor lesions
Hepatitis E seroprevalence and associated risk factors in Croatian liver transplant recipients
Get PDFIntroduction: Solid-organ transplant recipients are at risk of hepatitis E virus (HEV) infection. We analyzed the seroprevalence/
risk factors of HEV in Croatian liver transplant recipients. ----- Methods: Two hundred forty-two serum samples were tested for
HEV immunoglobuline IgG/IgM and HEV RNA. Sociodemographic data and risk factors were collected using a questionnaire.
----- Results: HEV IgG seroprevalence rate was 24.4%. Positive/equivocal HEV IgM were found in two patients. HEV RNA was not
detected. Logistic regression showed that older age, female gender, rural area/farm, water well, and septic tank were associated
with HEV seropositivity. ----- Conclusions: This study revealed a high exposure rate to HEV in Croatian liver recipients
Serum concentrations of Citrate, Tyrosine, 2- and 3- Hydroxybutyrate are associated with increased 3-month mortality in acute heart failure patients
Get PDFConsidering the already established relationship between the extent of the metabolic dysfunction and the severity of heart failure (HF), it is conceivable that the metabolomic profile of the serum may have a prognostic capacity for 3-month mortality in acute heart failure (AHF). Out of 152 recruited patients, 130 serum samples were subjected to the metabolomic analyses. The 3-month mortality rate was 24.6% (32 patients). Metabolomic profiling by nuclear magnetic resonance spectroscopy found that the serum levels of 2-hydroxybutyrate (2-HB), 3-hydoxybutyrate (3-HB), lactate, citrate, and tyrosine, were higher in patients who died within 3 months compared to those who were alive 3 months after onset of AHF, which was confirmed by univariable logistic regression analyses (p = 0.009, p = 0.005, p = 0.008, p<0.001, and p<0.001, respectively). These associations still remained significant for all tested metabolites except for lactate after adjusting for established prognostic parameters in HF. In conclusion, serum levels of 2-HB, 3-HB, tyrosine, and citrate measured at admission are associated with an increased 3-month mortality rate in AHF patients and might thus be of prognostic value in AHF