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The role of the University of Zagreb School of Medicine in the development of education, health care, and science in Croatia
Get PDFImmunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)
Get PDFExtensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma
(PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor
cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological
parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein
expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-
Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained
in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in
21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive
correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a
negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed
(p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin
and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the
role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic
cancer
Staged management of a giant cardiac hydatid cyst: a case report
Get PDFBACKGROUND:
We report on a 21-year-old patient with a giant symptomatic hydatid cyst of the interventricular septum, to whom a staged management approach was employed. Induction medical therapy led to a reduction in the size of the cyst, which was then completely removed via surgical excision. -----
CASE PRESENTATION:
A 21-year-old male Caucasian, with main complaints of fatigue and palpitations, was referred to our Centre due to a cystic formation in his left ventricle. The workup consisted of transthoracic echocardiography and cardiac magnetic resonance, which revealed a huge hydatid cyst in an active stage of disease, occupying the basal and mid part of the interventricular septum. Due to the size of the lesion and lack of viable myocardium in the affected area, the patient was declared inoperable and medical therapy was initiated. Serial echocardiography revealed a significant reduction in the size of the lesion and degradation to transitional and inactive stage, after which successful surgical excision of the cyst was performed. In the course of the medical treatment, the patient experienced sustained ventricular tachycardia causing loss of consciousness, which did not reoccur after surgical excision. -----
CONCLUSION:
Medical therapy can result in the degradation of a giant heart hydatid cyst, enabling surgical excision. Heart hydatid cyst can lead to potentially lethal arrhythmia irrespective of its size and stage, which does not reoccur after successful surgical excision
Social egg freezing under public health perspective: just a medical reality or a women’s right? An ethical case analysis
Get PDFIn recent years, a social trend toward delaying childbearing has been observed in women of reproductive age. A novel technomedical innovation was commercialized for non-medical reasons to healthy, ostensibly fertile women, who wished to postpone motherhood for various reasons such as educational or career demands, or because they had not yet found a partner. As a consequence, these women may be affected by age-related infertility when they decide to conceive, and fertility preservation techniques can be obtained through the so-called social egg freezing. This paper examines, from an ethical point of view, the impact of social egg freezing under some aspects that can involve policy making and resources allocation in public health. Due to the increasing demand for this procedure, some debated issues regard if it is reasonable to include social egg freezing in Public Healthcare System and consequently how to manage the storage of cryopreserved oocytes also from individual donors, how to support these egg banks and how to face, in the future, with the possibility that egg freezing will play a role in enabling childbearing for gays, lesbians, and unmarried persons. Social freezing may be advertised to harmonise gender differences, but we wonder if it is the proper solution to the problem or if it could also create further challenges. An ethical argumentation on these topics should address some questions that will be discussed
Effect of clonidine on the cutaneous silent period during spinal anesthesia
Get PDFAim: To investigate the effect of clonidine on the cutaneous silent period (CSP) during spinal anesthesia.
----- Methods: A total of 67 adult patients were included in this randomized, prospective, single-center, double-blind trial. They did not have neurological disorders and were scheduled for inguinal hernia repair surgery. This trial was registered on ClinicalTrials.gov (NTC03121261). The patients were randomized into two groups with regards to the intrathecally administered solution: (1) 15 mg of 0.5% levobupivacaine with 50 µg of 0.015% clonidine, or (2) 15 mg of 0.5% levobupivacaine alone. There were 34 patients in the levobupivacaine-clonidine (LC) group and 33 patients in the levobupivacaine (L) group. CSP and its latency were measured four times: prior to the subarachnoid block (SAB), after motor block regression to the 0 level of the Bromage scale, with ongoing sensory blockade, and both 6 and 24 h after SAB.
----- Results: Only data from 30 patients in each group were analyzed. There were no significant differences between the groups investigated preoperatively and after 24 h. The CSP of the L group at the time point when the Bromage scale was 0 was 44.8 ± 8.1 ms, while in the LC group it measured 40.2 ± 3.8 ms (P = 0.007). The latency in the L group at the time point when the Bromage scale was 0 was 130.3 ± 10.2 ms, and in the LC group it was 144.7 ± 8.3 ms (P < 0.001). The CSP of the L group after 6 h was 59.6 ± 9.8 ms, while in the LC group it was 44.5 ± 5.0 ms (P < 0.001). The latency in the L group after 6 h was 110.4 ± 10.6 ms, while in LC group it was 132.3 ± 9.7 ms (P < 0.001).
----- Conclusion: Intrathecal addition of clonidine to levobupivacaine for SAB in comparison with levobupivacaine alone results in a diminished inhibitory tonus and shortened CSP
Femoral head wear and metallosis caused by damaged titanium porous coating after primary metal-on-polyethylene total hip arthroplasty: a case report
Get PDFExcessive metal femoral head wear has been described only as revision surgery complication after primary ceramic-on-ceramic total hip arthroplasty (THA). Here, we present the first case of metal femoral head wear after primary metal-on-polyethylene THA. A 56-year-old woman was referred to our outpatient clinic 17 years after primary right-sided THA, experiencing pain and decreased right hip range of motion. Radiographic examination revealed acetabular cup dislocation, eccentric femoral head wear, damaged titanium porous coating of femoral stem, metallosis, and pseudotumor formation. Endoprosthetic components were extracted, but further reconstruction was impossible due to presence of large acetabular bone defect. Macro- and micro-structure of extracted components were analyzed. Acetabular liner surface was damaged, with scratches, indentations, and embedded metal debris particles present on the entire inner surface. Analysis of metal debris by energy-dispersive spectroscopy showed that it consisted of titanium and stainless-steel particles. Femoral head was gravely worn and elliptically shaped, with abrasive wear visible under scanning electron microscope. No signs of trunnionosis at head/neck junction were observed. Microstructure of femoral head material was homogeneous austenitic, with microhardness of 145 HV 0.2, which is lower than previously described titanium hardness. In conclusion, detached titanium porous coating of femoral stem can cause stainless-steel femoral head wear in primary metal-on-polyethylene THA. As soon as such detachment becomes evident, revision surgery should be considered to prevent devastating complications
Učinak perinatalne hipoksijsko – ishemijske encefalopatije na projekcijske puteve moždanoga debla u nedonoščeta [Impact of hypoxic-ischemic encephalopathy on projection pathways of the premature infant brainstem]
Get PDFIntroduction: Improved perinatal care has led to increased survival of premature infants. These children often have different motoric, cognitive and psychological disorders. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of white matter injury and long-term neurological deficits in children. The aim of this study is to analyze cerebral volumes and DTI parameters as major site of white matter injury and compare them with recipient areas in pons and cerebellum in order to find possible selective vulnerability for corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles.
Material and methods: In our research we had three groups of participants. The first group consisted of 5 normal term infants (control), the second group included 16 normotypic premature infants without perinatal HIE lesions (normotypic), and the third group included 22 premature infants with perinatal HIE (HIE). Diagnosis of perinatal HIE was based on both MRI and clinical exams. Parental consent for MRI scanning was obtained and all examinations were controlled and approved by the Institutional Review Board of the University of Zagreb School of Medicine. MRI images were obtained using 3T MRI scanner (Magnetom TrioTim, Siemens, Germany), with high resolution T1 MPRAGE sequence in sagittal plane (voxel size = 1x1x1 mm) and dwi sequences (voxel size 1.6x1.6x3 mm). All groups were scanned at two different time points, first at the term or corrected term age and second at the age of two years. Cerebral and cerebellar volumes were measured using semi-automated software (MNI toolbox, Montreal, Canada), and brainstem (mesencephalon, pons, medulla oblongata) was measured using manual segmentation methods (Analyze 8.1, Mayo Clinic, USA). Axonal pathways (corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles) were reconstructed and all parameters (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) have been measured using Diffusion Toolkit and TrackVis software. Statistical analysis was done using MedCalc v12.
Results: Normotypic group showed decreased volumes at corrected term age, but their volumes compensate during growth and at the age of 2 years correspond to control group. Unlike normotypic, group with HIE lesions shows statistically significant reduction of measured volumes during corrected term age comparing with normal group, and also at the age of 2 years comparing with both normal and normotypic group. Volumetric analysis of brainstem parts (mesencephalon, pons, medulla oblongata) and its layers (base, tegmentum, tectum) follows that pattern as well as volumetric analysis of brainstem in general, cerebellum and total brain volume. Parameters measured during DTI analysis (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) for named axonal pathways showed similar pattern in observed groups.
Conclusion: Origin, trajectory and termination areas of measured axonal pathways are reduced after perinatal HIE. We have found that all measured pathways are regularly damaged in perinatal HIE, as a part of general white matter pathology. Our finding is in the agreement that pathways which are part of the periventricular fiber system and periventricular crossroads are vulnerable in HIE. Also, due to the topographical relationship, damaged periventricular fibers will contribute to reduction of brainstem, expecially pons, as well as cerebellum
Uloga pentadekapeptida BPC 157 i sustava NO u prevenciji incizijskih ventralnih hernija i njihov utjecaj na vlačnu čvrstoću rane [The Role of Pentadecapeptide BPC 157 and NO-system on Incisional Ventral Hernia Prevention and Wound Tensile Strength Impact]
Get PDFPositive BPC 157 effect on skin wounds and muscle-tendon is known. Effect on
incisional hernia (IH) prevention has not been studied.
BPC 157, L-NAME and L-arginineffect on IH development and IH size (IHS),
cutaneous wound appearance (CWA), abdominal adhesions (AA) and tensile
strength (TS) was monitored for 7, 14, 21, and 28 days on Wistar rats. Ratswere
continuously treated with BPC 157 (0,16 μg/mL or 0,16 ng/mL, per os), L-NAME (5
mg/kg ip), L-arginin (100 mg/kg ip) and combinations.
BPC 157 reduced the incidence of IH (p(μg) < 0,0001, p(ng) < 0,0001) as well as
IHS. Animals treated with L-NAME and L-arginine had larger IHS than control group
animals. Animals treated with BPC 157 differed in CWA- predominantly regular
healing, as well as less AA, while animals treated with L-NAME, L-arginine and
combination had more AA. Animals treated with BPC 157 for 28 days had greater TS
(p(μg) = 0,0498, p(ng) = 0,0419).
BPC 157 presented preventive effect on IH development, IHS, and long-term positive
TS effect. This implies potential usage in IH prevention
Progesteronska potpora žutom tijelu u stimuliranim ciklusima izvantjelesne oplodnje
Get PDFObjectives: To compare efficacy (on-going pregnancy rate and early abortion rate),
satisfaction and tolerability of different route of progesterone supplementation i.e. oral
dydrogesterone, vaginal progesterone gel, micronized vaginal capsules and combined therapy
of oral micronized progesterone capsules plus vaginal progesterone gel used in luteal support
of stimulated cycles.
Study design: Meta-analysis of three own prospective clinical studies. Study
population consisted of a total of 1508 infertile women undergoing IVF/ICSI treatment in
University Hospital Center ‘‘Sisters of Mercy’’ and IVF Polyclinic, Zagreb, Croatia. Luteal
support was provided as: a) Crinone 8% vaginal progesterone gel (1x90 mg) administered
daily, or Utrogestan vaginal capsules (2x100 mg) administered three times daily; b)
Comibined therapy of Crinone 8% vaginal gel, 1x90 mg daily dose and Utrogestan oral
capsules 3x100 mg, or Crinone 8% vaginal gel, 1x90 mg daily; c) Crinone 8% vaginal
progesterone gel (1x90 mg) administered daily, or oral dydrogesterone Duphaston (2x10 mg)
administered two times daily.
Progesterone was administered from the day of oocyte retrieval (day 0) to menses or, in a case
of pregnancy, until week 10.
Results: The primary outcome aims were on-going pregnancy rate and early abortion
rate. The on-going pregnancy rates were comparable between different routes of progesterone
supplementation in luteal support i.e. in the case of combined oral-vaginal route 39.5% vrs.
Crinone 8% vaginal gel 33.5%; Crinone 8% vaginal gel vrs. Utrogestan vaginal capsules
30.9%; oral progesterone tablets (Duphaston) 30.5% vrs Crinone vaginal progesterone gel
32.9% per ET (RR 0.93-1.18; p= 0.78).
Early abortion rate was almost equal between different routes of progesterone
supplementation with the exception of comparison between combined progesterone therapy
6.4% and vaginal progesterone gel 15.6%, which presented lower abortion rate with the use of
combined progesterone therapy (RR 0.41; 95%CI 0.22-0.79; p <0.01). Early abortion rate in
other comparison arms was as following: Crinone 8% vaginal gel 10.8% vrs. Utrogestan
vaginal capsules 14.7%; Crinone 8% vaginal gel 6.8% vrs. Duphaston oral progesterone
tablets 10.1% that give a meta-analysis RR 0.59; 95%CI 0.43-0.82 and p=0.44.
Overall tolerability showed similar rates but vaginal bleeding was significantly more
present with the use of Crinone 8% vaginal gel when compared with the combined therapy
(RR 0.21; 95%CI 0.07-0.61; p<0.01) and oral progesterone tablets. Interference with coitus
and local adverse side effects such as perineal irritation (RR 0.06; 95%CI 0.01-0.47; p<0.01)
and vaginal discharge (RR 0.08; 95%CI 0.02-0.32; p<0.001) occurred significantly more with
the use of vaginal progesterone (capsules and vaginal gel) than with the use of oral
dydrogesterone.
Satisfaction assessment showed significantly more absolutely satisfied patients with
the used of oral progesterone tablets (Duphaston) in comparison with vaginal progesterone
gel. Almost the same result was noticed with the use of vaginal gel vrs vaginal capsules.
Overall the patients were significantly more satisfied with the use of vaginal progesterone gel,
combined oral-vaginal progesterone therapy and oral vaginal tablets then with the use of
vaginal progesterone capsules. Users of oral progesterone tablets showed significantly more
absolute satisfaction and significantly less absolute dissatisfaction when compared with all
other routes of progesterone supplementation.
Conclusions: All routes of progesterone supplementation in luteal phase support of
induced cycles showed almost equall efficacy considering rate of on-going pregnancy and
early abortion rate. Oral tablets of dydrogesterone are effective drug, well tolerated with less
adverse side effects such as perineal irritation and vaginal discharge and more overall
satisfaction among patients when compared with combined therapy and vaginal route of
progesterone use and can be considered for routine luteal support
Fosforilirani receptor HER-2 kao pokazatelj rezistencije karcinoma dojke na terapiju trastuzumabom [Phosphorylated HER-2 receptor as an indicator of breast cancer resistance to trastuzumab]
Get PDFAbout 20-25% of breast cancers have over-expressed HER2 receptor, leading to aggressive
behavior of cancer and poor disease course. Implementing anti-HER2 therapy with
trastuzumab improved disease outcome and survival of patients. Yet, a significant number
of patients do not respond to therapy.
HER1, HER2, HER3 and HER4 receptors belong to the epidermal growth factor receptors
family. Bonding of growth factor to the receptor activates dimerization of HER receptors,
resulting in phosphorylation on cytoplasmic domain and activating the signaling pathway.
Our study was performed on 124 samples of HER2 positive breast cancer with the
assumption that HER2 phosphorylation is a true marker of receptor's activity and that
HER2 dimerization with other HER receptors contributes to the acquisition of trastuzumab
resistance. We performed immunohistochemical staining using specific primary antibodies
against phosphorylated HER2, HER1, HER3 and HER4, and investigated the correlation
between their expression and correlation with the resistance.
Our results found that HER2 receptor is predominantly phosphorylated (66.2% pHER2+)
and positive pHER2 status is a marker of a good response to trastuzumab (P <0.001).
Negative phosphorylated status of HER2 is significant in the HER2 intrinsic group where
33.3% of the patients had a disease recurrence. HER1, HER3 and HER4 receptors were
expressed in 9.7%, 70.2% and 71% of HER2 positive carcinomas, retrospectively. Coexpression
of pHER2 and HER3 showed a statistically significant correlation (P=0.013).
Patients with negative pHER2 and positive HER3 or HER4 had poor survival, and
resistance was recorded in 35.3% of pHER2‒ /HER3+/HER4+.
We can conclude that the positive phosphorylation status of HER2 determines patients who
will benefit from trastuzumab therapy. Negative status of pHER2 refers to patients who
should undergo dual therapy in first line treatment, especially in the HER2 intrinsic breast
cancer group