Prognostic Value of "Basal-like" Morphology, Tumor-Infiltrating Lymphocytes and Multi-MAGE-A Expression in Triple-Negative Breast Cancer.

"Basal-like" (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy.

Opportunistic measures of bone mineral density at multiple skeletal sites during whole-body CT in polytrauma patients.

Whole-body CT in polytrauma patients revealed bone mineral density variations throughout the skeleton. Bone density was the highest in cranial bones and the lowest in proximal extremities and pelvis. Skeletal age-related changes were generally more pronounced than sex-related changes. Cranial bones did not follow the same aging pattern compared to other bones. INTRODUCTION: Whole-body CT (WBCT) in polytrauma patients enables the detection of numerous incidental findings, such as estimates of bone mineral density (BMD) at multiple skeletal sites. This could help in better understanding of age- and sex-related changes in BMD through skeleton. METHODS: Data were retrospectively retrieved from the WBCTs requested during a 2-year period. BMD, expressed in CT Hounsfield units (HU), was measured at frontal and occipital bone, four vertebrae (C4, Th7, L4, and S2), iliac bone, and proximal humerus and femur. Measurements were done on native and postcontrast scans. The population sample was age-, sex-, and visceral fat volume adjusted for analysis. RESULTS: A total of 296 patients were included, with a median age of 51 years. BMD varied from the highest HU in cranial bones (629 HU) to the lowest HU in the pelvic bones (114 HU), P < 0.001. Sex differences were independent predictors of BMD in cranial bones and proximal humerus. The age-related decline in BMD was significant in all other bones, but the association with age differed among the measurement's sites. Visceral fat showed the strongest correlation with the lumbar spine and iliac wing, although multivariate analysis revealed it was not an independent predictor of bone density, such as age and sex. CONCLUSIONS: BMD varies through skeleton, being the highest in the proximal axial skeleton. Age-related changes in BMD are significant and more pronounced than sex-related changes in almost all bones. Cranial bones do not follow the same pattern compared to other bones.

ACEF performed better than other risk scores in non-ST-elevation acute coronary syndrome during long term follow-up.

BACKGROUND: Risk stratification of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) is an important clinical method, but long-term studies on patients subjected to all-treatment strategies are lacking. Therefore, the aim was to compare several established risk scores in the all-treatment NSTE-ACS cohort during long-term follow-up. METHODS: Consecutive patients (n = 276) with NSTE-ACS undergoing coronary angiography were recruited between September 2012 and May 2015. Six risk scores for all patients were calculated, namely GRACE 2.0, ACEF, SYNTAX, Clinical SYNTAX, SYNTAX II PCI and SYNTAX II CABG. The primary end-point was Major Adverse Cardiovascular Events (MACE) which was a composite of cardiac death, nonfatal myocardial infarction, ischemic stroke or urgent coronary revascularization. RESULTS: During a median follow-up of 33 months, 64 MACE outcomes were recorded (23.2%). There was no difference between risk score categories, except in the highest risk group of ACEF and SYNTAX II PCI scores which exhibited significantly more MACE (51.6%, N = 33 and 45.3%, N = 29, P = 0.024, respectively). In the multivariate Cox regression analysis of individual variables, only age and atrial fibrillation were significant predictors for MACE (HR 1.03, 95% CI 1.00-1.05, P = 0.023 and HR 2.02, 95% CI 1.04-3.89, P = 0.037, respectively). Furthermore, multivariate analysis of the risk scores showed significant prediction of MACE only with ACEF score (HR 2.16, 95% CI 1.36-3.44, P = 0.001). The overall performance of GRACE, SYNTAX, Clinical SYNTAX and SYNTAX II CABG was poor with AUC values of 0.596, 0.507, 0.530 and 0.582, respectively, while ACEF and SYNTAX II PCI showed the best absolute AUC values for MACE (0.630 and 0.626, respectively). CONCLUSIONS: ACEF risk score showed better discrimination than other risk scores in NSTE-ACS patients undergoing all-treatment strategies over long-term follow-up and it could represent a fast and user-friendly tool to stratify NSTE-ACS patients.

Types of Parenchymal Changes Diagnosed on DMSA Scans of Kidneys Affected by Different Grades of Vesicoureteral Reflux.

BACKGROUND Renal parenchymal damage and scarring usually is associated with urinary tract infection (UTI), whereas the impact of vesicoureteral reflux (VUR) on the kidneys is unclear. We aimed to compare kidneys with all grades of VUR (grades Io-V) and those without VUR by using direct radionuclide cystography, voiding cystourethrography, and findings from 99mTc-DMSA scintigraphy (DMSA scan). MATERIAL AND METHODS The present analysis included 253 renal ureteral units (RUU) from 129 children with VUR and recurrent UTI and children with a single febrile UTI associated with abnormal ultrasonographic findings. The 6 grades of VUR (Io, I, II, III, IV, and V) and 35 RUUs without VUR were divided into 4 groups: 1. Non-dilated VUR (grades Io-II); 2. Mildly dilated VUR (grade III); 3. Dilated VUR (grades IV-V); and 4. The control group. RESULTS DMSA scanning showed significant differences between the groups with non-dilated VUR, grade III VUR, grades IV-V VUR, and the control group in kidney width (χ²=30.5; P<0.001); position and shape (χ²=30.6; P<0.001); intensity of activity (χ²=38.1; P<0.001); distribution of activity (χ²=34.5; P<0.001); and existence of scars (χ²=16; P<0.001). The probability of abnormalities on DMSA scans increased with the VUR grade. However, inside the groups of dilated and non-dilated VUR we found no significant statistical differences between those characteristics. CONCLUSIONS Our results indicate that kidneys without VUR or with non-dilated lateral VUR and dilated VUR on the contralateral side represent 2 different categories of parenchymal changes.

Right ventricular free wall strain in acutely decompensated heart failure patients with ischemic and non-ischemic cardiomyopathy.

AIMS: Right ventricular (RV) dysfunction is a predictor of adverse outcomes among patients with HF with reduced ejection fraction (HFrEF); however, differences in RV parameters in HFrEF patients with ischemic (ICM) and non-ischemic cardiomyopathies (NICM) are not well understood. We investigated echocardiographic characteristics, including RV strain, in patients with acute decompensated heart failure (ADHF) and compared patients with ICM and NICM etiology. METHODS: Consecutive patients who presented with ADHF and NYHA class III-IV were prospectively enrolled if they had LVEF < 40% and history of ICM or NICM. All patients underwent clinical exam, laboratory evaluation and 2-D echocardiographic assessment of the left ventricular (LV) and RV function, LV and RV global longitudinal strain (LVGLS, RVGLS), and RV free wall strain (RVfwLS). RESULTS: Of 84 patients, 44 had ICM and 40 NICM. The groups had similar blood pressure, NT-proBNP, and echocardiographic parameters of LV function including LVGLS. Absolute RVGLS values were lower than RVfwLS values in both groups. Patients with NICM had significantly lower RVfwLS, but not RVGLS, compared to patients with ICM (-13% to -17%, p = 0.006). Similar differences in RVfwLS were seen in patients in NYHA class III (NICM vs ICM: -13% and -17%, respectively, 95% CI: -8.5 to -.5) and NYHA class IV (NICM vs ICM: -13.8% and -17%, respectively, 95% CI: -6.4 to -.59). CONCLUSION: Among patients hospitalized with ADHF, patients with nonischemic etiology compared with the patients with ICM, have more severe RV dysfunction measured by RVfwLS, despite similar extent of LV impairment and the same functional limitation class.

MAGE-A4 and MAGE-A1 Immunohistochemical Expression in High-grade Endometrial Cancer.

The aim was to investigate MAGE-A4 and MAGE-A1 protein expression in high-grade endometrial cancer and determine its correlation with histologic subtype, FIGO stage, presence of vascular invasion, disease free, and overall survival. Immunohistochemical staining was performed by using 77B (MAGE-A1) and 57B (MAGE-A4) monoclonal antibodies on paraffin-embedded sections from high-grade endometrial cancers diagnosed in University Hospital Split between 1998 and 2011 (n=77). Median follow-up time for survivors was 48 mo. MAGE-A4 was found to be expressed in 33% of endometrioid type endometrial cancers grade 3 and in 27% of serous and clear cell carcinomas. MAGE-A1 was found to be expressed in 93% endometrioid endometrial cancer grade 3 and 86% of serous and clear cell carcinomas. Univariate analysis showed that positive immunohistochemical staining for MAGE-A4 was associated with decreased disease free and overall survival in patients with high-grade endometrial cancer. Multivariate analysis showed an association between MAGE-A4 overexpression and decreased disease free but not overall survival in high-grade endometrial cancer. No correlation was found between MAGE-A1 immunohistochemical expression and patient survival. There was no significant correlation between MAGE-A4 and MAGE-A1 expression and histologic subtype, FIGO stage, lymph node metastasis, muscular infiltration, and lymphovascular invasion. MAGE-A4 immunohistochemical expression is associated with decreased disease free and overall survival in patients with high-grade endometrial cancer. Our findings suggest that MAGE-A1 may be expressed in the epithelial cells of the normal endometrium. MAGE-A1 is highly expressed in high-grade endometrial cancer, with no impact on survival.

The Utility of Thyroid Transcription Factor 1 (TTF-1), Napsin A, Excision Repair Cross-Complementing 1 (ERCC1), Anaplastic Lymphoma Kinase (ALK) and the Epidermal Growth Factor Receptor (EGFR) Expression in Small Biopsy in Prognosis of Patients with Lung Adenocarcinoma - A Retrograde Single-Center Study from Croatia.

BACKGROUND The present study was carried out in order to evaluate our institutional experience with small biopsy in diagnosis and molecular testing of lung adenocarcinoma. Few specific and predictive markers have been evaluated and correlated with clinicopathologic characteristics and survival in patients with lung adenocarcinoma who received platinum-based chemotherapy. There have not been such reports from Croatia. MATERIAL AND METHODS A total of 142 cases of lung adenocarcinoma were retrospectively investigated in small biopsies for the immunohistochemical expression of TTF-1, napsin A, ERCC1, ALK, and the EGFR mutation by real-time polymerase chain reaction (rtPCR). RESULTS TTF-1, napsin A, and ERCC1 expression was found in 81%, 78%, and 69% of patients, respectively, and the expressions were not significantly associated with subtype. Expression of ALK was found in 4% and EGFR mutation in 10% of patients. Exon 19 deletions were the most common. Longer survival was significantly associated with TTF-1 positivity (p=0.007) and napsin A positivity (p=0.026). Higher relative risk of death significantly correlated with positive expression of ERCC1 (p=0.041). CONCLUSIONS Positive TTF-1 and napsin A expressions in lung adenocarcinoma tissues were useful diagnostic and favorable prognostic parameters. Positive ERCC1 expression was identified as a negative prognostic marker in patients treated with platinum-based chemotherapy. The percentages of EGFR and ALK mutations corresponded to those in previously published reports for Caucasians.

Incarcerated Inguinal Hernia Mesh Repair: Effect on Testicular Blood Flow and Sperm Autoimmunity.

BACKGROUND The aim of our study was to determine an influence of incarcerated inguinal hernia mesh repair on testicular circulation and to investigate consequent sperm autoimmunity as a possible reason for infertility. MATERIAL AND METHODS This prospective study was performed over a 3-year period, and 50 male patients were included; 25 of these patients underwent elective open mesh hernia repair (Group I). Group II consisted of 25 patients who had surgery for incarcerated inguinal hernia. Doppler ultrasound evaluation of the testicular blood flow and blood samplings for antisperm antibodies (ASA) was performed in all patients before the surgery, on the second day, and 5 months after. Main outcome ultrasound measures were resistive index (RI) and pulsative index (PI), as their values are inversely proportional to testicular blood flow. RESULTS In Group I, RI, and PI temporarily increased after surgery and then returned to basal values in the late postoperative period. Friedman analysis showed a significant difference in RI and PI for all measurements in Group II (p<0.05), with a significant decrease between the preoperative, early, and late postoperative periods. All final values were within reference range, including ASA, despite significant increase of ASA in the late postoperative period. CONCLUSIONS Although statistically significant differences in values of testicular flow parameters and immunologic sensitization in observed time, final values remained within the reference ranges in all patients. Our results suggest that the polypropylene mesh probably does not cause any clinically significant effect on testicular flow and immunologic response in both groups of patients.

Classical Hodgkin Lymphoma with Positive Epstein-Barr Virus Status is Associated with More FOXP3 Regulatory T Cells.

BACKGROUND Classical Hodgkin lymphoma (cHL) is characterized by sparse malignant Hodgkin and Reed-Sternberg cells dispersed in an inflammatory microenvironment. Immune evasion of malignant cells is partially due to the existence of a subpopulation of immunosuppressive regulatory T cells (Treg). The aim of this study was to analyze T cell composition in cHL with special emphasis on Treg in regard to Epstein-Barr virus (EBV) status, subtype, and patient age. MATERIAL AND METHODS The study included 102 patients with cHL diagnosed during a 12-year period. EBV status of cHL was assessed immunohistochemically using antibodies directed to the EBV- encoded LMP1. To define T lymphocyte populations, slides were double-stained with FOXP3 for Treg, and CD4 or CD8 for T cells. In each case the number of single- and/or double-positive cells was counted on an image analyzer in 10 high-power fields. Statistical analysis was performed and differences were considered significant at P<0.05. RESULTS EBV-positive status of cHL was confirmed in 30 (29%) cases, mainly in patients older than 54 years and in mixed cellularity subtype. In EBV-positive cHL, higher numbers of CD8+ cells were found. In cHL with positive EBV status, more FOXP3+ Treg were found, as well as higher numbers of FOXP3+CD4+ Treg compared with EBV-negative cHL. The number of CD4+ cells decreased with age. The frequency of FOXP3+CD8+ Treg was variable, without a statistically significant association with age or EBV status. CONCLUSIONS EBV status has an impact on composition of T cell populations in the cHL microenvironment.

Lipocalin-2 and matrix metalloproteinase-9 expression in high-grade endometrial cancer and their prognostic value.

AIMS: To demonstrate lipocalin-2 (LCN-2) immunohistochemical expression together with matrix metalloproteinase-9 (MMP-9) protein in high-grade endometrial cancer and determine their correlations with FIGO (International Federation of Gynecology and Obstetrics) stage, histological subtype, presence of vascular invasion, patient age and overall and disease-free survival. METHODS AND RESULTS: Immunohistochemical staining was performed using LCN-2 and MMP-9 antibodies on high-grade endometrial cancer (n = 85) diagnosed at Split University Hospital Centre during 1998-2010. Immunohistochemical expression was determined on archived paraffin-embedded samples and scored semiquantitatively. Survival time was analysed using the Kaplan-Meier method, and the log-rank test was used to assess between-group differences. The Cox proportional hazard regression model was used on multivariate survival analysis. Patients were followed from the time of primary surgery until death or last follow-up until December 2012. LCN-2 and MMP-9 were highly expressed in high-grade endometrial cancer. Univariate analysis showed positive immunohistochemical staining for LCN-2 and MMP-9 to be associated with shorter survival in patients with high-grade endometrial cancer. Multivariate analysis showed LCN-2 overexpression to be associated with shorter overall and disease-free survival in high-grade endometrial cancer. CONCLUSIONS: Our findings suggest that LCN-2 expression may be an important independent indicator of shorter survival in patients with high-grade endometrial cancer.

Depression and Self-Esteem in Early Adolescence.

AIM: Depression prevalence has increased in the last few decades, affecting younger age groups. The aim of this research was to determine the range of depression and low self-esteem in elementary school children in the city of Split. Testing was carried out at school and the sample comprised 1,549 children (714 boys and 832 girls, aged 13). METHODS: Two psychological instruments were used: the Coopersmith Self-Esteem Inventory (SEI) and the Children and Adolescent Depression Scale (SDD). RESULTS: The average value of scores obtained by SEI test was 17.8 for all tested children. No statistically significant difference was found be-tween boys and girls. It was found that 11.9% of children showed signs of clinically significant depression, and 16.2% showed signs of depression. Statistically significant association between low self-esteem and clinically significant depression was found. No statistically significant difference among boys and girls according to dimension of cognitive depression was found, whereas statistically significant level of emotional depression was higher in girls than boys. It was found that both dimensions of depression decreased proportionally with the increase of SEI test score values: cognitive and emotional dimension of depression. CONCLUSION: The results of this study show that it is necessary to provide early detection of emotional difficulties in order to prevent serious mental disorders.

The OSR1 rs12329305 polymorphism contributes to the development of congenital malformations in cases of stillborn/neonatal death.

BACKGROUND: Involvement of development-related gene polymorphisms in multifactorial/polygenic etiology of stillborn/neonatal deaths due to malformations has been insufficiently tested. Since these genes showed evolutional stability and their mutations are very rare, we can assume that their polymorphic variants may be a risk factor associated with the occurrence of developmental disorders of unknown etiology or can enhance the phenotypic variability of known genetic disorders. MATERIAL AND METHODS: To determine the association of 3 polymorphisms involved in the regulation of the early embryonic development of different organs, we conducted an association study of their relation to the particular malformation. We selected 140 samples of archived paraffin tissue samples from deceased patients in which fetal/neonatal autopsy examination had shown congenital abnormalities as the most likely cause of death. The polymorphisms of OSR1 rs12329305, rs9936833 near FOXF1, and HOXA1 rs10951154 were genotyped using the TaqMan allelic discrimination assay. RESULTS: After Bonferroni correction for multiple testing, significant allelic association with stillborn/neonatal deaths was observed for rs12329305 (p=7×10-4). In addition, association analysis for the same polymorphism was shown in the subgroup with isolated anomalies (1.25×10^-5), particularly in the subgroup of cases with kidney and heart anomalies (p=4.18×10^-5, p=5.12×10^-8, respectively). CONCLUSIONS: The findings of the present study showed, for the first time, the role of the OSR1 rs12329305 polymorphism in the development of congenital malformations in cases of stillborn/neonatal death, particularly in those with congenital kidney and heart developmental defects.

Asymmetrical fetal growth is not associated with altered trophoblast apoptotic activity in idiopathic intrauterine growth retardation.

AIM: To investigate whether there is difference in trophoblast apoptosis between infants with asymmetrical idiopathic intrauterine growth retardation (IUGR) and those with symmetrical fetal growth appropriate for gestational age (AGA). METHODS: Data and placentas from 52 singleton term pregnancies with idiopathic IUGR, from which a subgroup of 33 (63.4%) infants with asymmetrical growth and malnutrition was identified using the ponderal index served as a study group. The control group included 60 (86.9%) infants with symmetrical growth, identified by the same criterion among 69 normal singleton pregnancies with AGA. IUGR was defined by birthweight less than the 10th percentile of standard values. Ponderal index value was considered as the measurement of fetal growth proportionality. RESULTS: The proportion of fetal thinness up to ponderal index value was greater in the IUGR group than control (χ(2) = 9.2; P = 0.002). There was no statistically significant difference in the cytotrophoblast proliferation (t = 0.88; P = 0.373), trophoblast expression of the Bcl-2 anti-apoptotic factor (z = 0.66; P = 0.505), total trophoblast apoptotic index (t = 0.45; P = 0.651), as in cytotrophoblast (t = 0.01; P = 0.988) and syncytiotrophoblast apoptotic index (t = 0.34; P = 0.730) between the idiopathic asymmetrical IUGR and control group. CONCLUSION: Asymmetry of fetal growth is a result of rather long-term placental nutritive insufficiency in which trophoblasts have a central role. Although being crucial for its functioning, the proliferative and apoptotic trophoblast activity remains unaltered in the placentas from pregnancies with idiopathic IUGR and asymmetrical fetal growth. The results obtained in this study indicate that placental nutritive insufficiency may develop without any deviation in the physiological trophoblast regeneration via apoptosis.

Comparison of thermal damage of the internal thoracic artery using ultra high radiofrequency and monopolar diathermy.

BACKGROUND: The internal thoracic artery (ITA) has been accepted worldwide as a first choice conduit for myocardial revascularisation. It still remains questionable what is the best method for ITA harvesting in a skeletonized fashion according to structural integrity of artery, as a risk factor of early and late graft failure. The purpose of this study was to determine the impact of the ultra-high radiofrequency energy used for ITA harvesting on arterial structural integrity, in particular on the endothelial layer. METHODS: Seventy-four ITA specimens were divided into two groups depending on device used for harvesting (radiofrequency-knife (RF) or electrocauter (EC)). Thermal damage on arterial structural integrity was measured using light microscope, morphometric imaging analysis and immunohistochemical methods. RESULTS: Thermal damage of endothelium was 2.8 times higher in EC than in RF group (p = 0.041) and 5 times higher in patients older than 66 years of age (p = 0.002). Extent of endothelial damage (graded from 0 to 3) was significantly higher in EC group (p = 0.03). Also, in EC group, in patients older than 66 years of age higher proportion of extent of endothelial damage was found (p = 0.027). CONCLUSIONS: The endothelial damage was more often in EC than in RF group as in the patients older than 66 years of age. Demonstrated results suggest that the radiosurgery in comparison to conventional electrocautery is safe and effective method, and significantly reduces thermal damage to endothelial layer of artery.

Admission Hemoglobin Associated with Increased Mortality in Hip Fracture Surgical Patients: An Observational Study.

In hip fracture patients, who are mostly elderly, preexisting anemia can be worsened when combined with trauma and surgery. To this date, there is no unequivocal approach about transfusion thresholds. We analyzed hemoglobin (Hb) and hematocrit (Hct) levels at three time points in surgical patients with proximal femoral fractures (PFF) to see which levels were triggers for transfusions and whether transfusions were related to mortality after hospital discharge. A total of 956 patients were operated on from 1 January 2021 to 31 December 2022 at the University Hospital of Split and included in the study. There were more women (74%); 47% patients had admission Hb < 120 g/L. Transfusion was given preoperatively to 88, intraoperatively to 74 and postoperatively to 309 patients. Transfusion thresholds were as follows: Hb 84 g/L preoperatively, 99 intraoperatively and 83 postoperatively. After hospital discharge, 10.79% of patients died within the 1st month and 23% within 6 months. In the group of non-survivors, 60% of patients had admission Hb ≤ 117 g/L and the proportion of patients transfused preoperatively was two times higher. Preoperative transfusion thresholds could be set to higher levels for patients with surgically treated PFF. However, that could increase mortality even more. Further investigation is necessary.

Long-term quality of life of patients treated in paediatric intensive care unit.

UNLABELLED: The changes in long-term quality of life (QOL) of children treated in paediatric intensive care unit (PICU) were investigated in relation to their QOL before critical illness together with the influence of underlying chronic health condition and severity of illness estimated by Paediatric Index of Mortality 2 on the long-term outcome. This study included 189 children treated in PICU and 179 children from outpatient clinics as controls. QOL was evaluated according to the Royal Alexandra Hospital for Children Measure of Function (RAHC MOF). The long-term QOL in 70 % of children treated in PICU was good, although there was a significant diminution of QOL in children treated in PICU in comparison with their preadmission scores and with the children from outpatient clinics who served as controls (p < 0.001). Severity of illness had a significant impact on children's QOL (p = 0.016) 6 months after treatment in PICU. Twenty-four months after discharge, the RAHC MOF score was still decreased in 19 % of children treated in PICU, and in significantly more patients with a chronic health condition (CHC) treated in PICU, than in their peers from outpatient clinics (p = 0.029). Reduced QOL was significantly more frequent in children with neurodevelopmental disability than in children without CHC 24 months after discharge from PICU (p = 0.013). CONCLUSION: Acute illness has a significant impact both on children with and without CHC after treatment in PICU 6 months after discharge. Twenty-four months after discharge, comorbidity was identified as the decisive factor for diminished QOL in children after PICU treatment.

Prognostic value of MVD, LVD and vascular invasion in lymph node-negative colon cancer.

BACKGROUND/AIMS: To clarify the influence of microvessel density (MVD), lymphangiogenesis (LVD), and vascular invasion on prognosis in lymph node-negative colon cancer. METHODOLOGY: We performed immunohistochemical analysis from 152 Duke's B colon carcinomas, CD34 and LYVE-1 antibodies. Carcinomas were graded as low or high grade. χ2 test was used to examine their relationships and correlations with clinicopathological parameters. Survival time was analyzed and the differences between groups were assessed. RESULTS: A statistically significantly correlation was found between increasing MVD with age >60 years, tumor size >4cm, and poor tumor differentiation (χ2=40.018, p<0.001). The increase in MVD was associated with shorter DFS (p<0.001) and shorter OS in patients with colon cancer (p<0.001). LVD was statistically significantly associated with increasing the number of newly created blood vessels (χ2=96.6, p<0.001), low degree of tumor differentiation (χ2=96.6, p<0.001), and vascular invasion (χ2=51.8, p<0.001) in colon cancer. Log rank analysis showed that positive staining for MVD and LVD, high histological grade, vascular invasion, male gender, and age >60 years were connected with shorter survival of patients with Dukes B colon cancer 45 vs. 100 months (p=0.016 to <0.001). CONCLUSIONS: Positive expression MVD and LVD was significantly correlation with survival time and with high tumor grade and vascular invasion in patients with Dukes B colon cancer. The correlation of MVD and LVD with vascular invasion in Dukes B colon cancer indicates the need for further confirmation as a possible predictive marker.

Association of cephalometric changes after 5 years of complete dentures wearing and oral health-related quality-of-life.

OBJECTIVE: The aim was to investigate cephalometric changes after 5 years of wearing complete dentures (CDs) and to asses a possible relationship between changes in cephalometric parameters and patients' oral health-related quality-of-life (OHRQoL). MATERIALS AND METHODS: New complete maxillary and mandibular dentures were fabricated for 30 participants. Two lateral radiographs were obtained from each participant with their CDs in the position of maximal intercuspidation (centric relation): the first radiograph was obtained at the CDs delivery and the second one after 5 years of CDs wearing. A questionnaire (OHIP 14) was given to all participants at the 5-year appointment. RESULTS: Significant differences in most linear and angular cephalometric measurements were found after 5 years of CDs wearing, due to the reduction of the height of the lower third of the face and the forward shifting of the mandible. A significant correlation between the OHIP summary scores and five cephalometric variables was found (ANS-Xi/Xi-Pm angle, FH/N-Pog angle, SN/Go-Gn angle, Go-Gn/ANS-PNS angle and occlusal plane/FH), indicating that more severe cephalometric changes were related with the increase of OHIP scores. CONCLUSION: Changes of cephalometric angles due to lowering of the face and forward shifting of the mandible were related to the decreased OHRQoL (increased OHIP scores).

[Anticoagulant therapy in patients with permanent atrial fibrillation - evidence based medicine and clinical practice]. / Antikoagulantno lijecenje u bolesnika s trajnom fibrilacijom atrija - medicina utemeljena na dokazima i klinicka praksa.

Objective of study was to assess the concordance of the tromboprophylactic treatment in patients with permanent atrial fibrillation (pAF) with guidelines of the European Society of Cardiology. Prospective cross-sectional study consecutivelly included 674 patients (400 S59%C male) discharged from cardiology department with the diagnosis pAF. The thromboembolic risk (TE) has been established according to CHA2DS2-VASc score, whereas the bleeding risk has been assessed according to HAS-BLED score. 578 (86%) belonged to the group of high, 57 (8%) to the group of moderate, and 39 (6%) patients to the group of low TE risk. 601 (89%) patients received thromboprophylaxis: 310 (46%) warfarin, 258 (38%) acetylsalicylic acid, and 33 (5%) patients clopidogrel. Warfarin has been prescribed to 47% of patients with high, 49% of patients with moderate and to 26% of patients with low TE risk (P=0.03). Acetylsalicylic acid (ASA) has equally been prescribed to patients of all TE risk groups: low, moderate and high (39% vs. 39% vs.38%/o; P=0.998). ASA (P<0.001) and warfarin (P=0.007) have been used more frequently in the group of patients with high bleeding risk, in which the same incidence of warfarin and ASA administration has been registered (53% vs. 47%; P=0.416). Age > or =75 has been an independent predictor of non-administration (OR 1.7; 95% CI 1.2-2.4; P=0.003), whereas the history of stroke was for warfarin administration (OR 0.47; 95% CI 0.29-0.76; P-0.002). In prescribing thromboprophylaxis to patients with pAF, cardiologists do not observe the recommended clinical guidelines. Despite nonexistence of contraindications, a significant number of patients with high TE risk has not been administered warfarin. At the same time, warfarin has been administered to the patients with low TE risk, exposing them unnecessarily to the undesired effect of anticoagulant treatment.

Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer.

Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 and IFN-γ in the tumor and regional lymph node (LN) of patients with GC and compared it with clinical and pathological data. Paraffin blocks were collected from 97 patients undergoing gastrectomy/lymphadenectomy for GC. Double immunohistochemistry was performed for CD8 and PD-L1 and double immunofluorescence for CTLA-4 and IFN-γ. Statistical significance was set at p < 0.05. PD-L1 expression in tumor cells was associated with intestinal GC type (p = 0.046), the density of macrophages and CD8 + T cells (p < 0.001, both). The median number of CD8+ T cells was higher in PD-L1-positive than in -negative tumors. A cut-off of 28.5 CD8 + T cells in one high-magnification field predicted PD-L1-positive tumors (AUROC 0.797, sensitivity 74.2%, specificity 77.3%). IFN-γ expression in tumor cells was found in 37 GCs and was positively associated with CTLA4+ lymphocytes in the LN (p = 0.027) and CTLA4+/IFN-γ+ in tumors and the LN (all p < 0.001). The median overall survival (OS) was 17 months. In the group of deceased patients, IFN-γ expression in metastases correlated with lower OS (RHO = -0.314, p = 0.008). PD-L1 expression in tumor cells correlated with CD8 + T cells and macrophages in the TME and IFN-γ expression with suppressive CTLA4+/IFNγ+ immune cells in the TME and LN.