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.

Detection of Sarcopenia in Patients with Liver Cirrhosis Using the Bioelectrical Impedance Analysis.

Bioelectrical impedance analysis (BIA) is a body composition assessment method. We aimed to determine its accuracy in the detection of sarcopenia in patients with liver cirrhosis (LC), using skeletal muscle index (SMI) at the level of third lumbar vertebra (L3-SMI) obtained using multislice computed tomography as the reference method. Patients with LC were enrolled in the period October 2019-March 2022 and follow-ups were conducted until January 2023. Their BIA parameters were compared against L3-SMI, and BIA cut-off values were proposed using AUROC analysis. Patients underwent outcome analysis based on obtained clinical characteristics. A total of 106 patients were included. We found a fair correlation between BIA parameters with the L3-SMI. We determined cut-off values of ≤11.1 kg/m2 for BIA-SMI (Se 73%, Sp 66%, AUROC 0.737, p < 0.001) and ≤5.05° for phase angle (PA) (Se 79%, Sp 60%, AUROC 0.762, p < 0.001) in the detection of sarcopenia. The relative risk of death was 2.2 times higher in patients with skeletal muscle mass (SMM) ≤ 36.5 kg. SMM was significantly associated with outcome in Kaplan-Meier analysis. This non-invasive and simple method that showed fair performances and a very good outcome prediction could provide for the unmet need for fast and affordable detection of sarcopenia in patients with LC and should be further evaluated.

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.

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.

The Spectrum of Parenchymal Changes in Kidneys Affected by Intrarenal Reflux, Diagnosed by Contrast-Enhanced Voiding Urosonography and DMSA Scan.

Purpose: To describe the parenchymal defects in kidneys with intrarenal reflux (IRR) diagnosed using contrast-enhanced voiding urosonography (ceVUS) and 99mTc-DMSA scintigraphy (DMSA scan). Materials and Methods: A group of 186 uretero-renal units (URUs) was analyzed using ceVUS and DMSA scans: 47 without vesicoureteral reflux (VUR) (group A) and 139 with VURs, comprising 73 VURs without (group B), and 66 with IRR (group C). VURs included non-dilating (grades I-II), mildly non-dilating (grade III), and non-dilating (grades IV-V) grades. The parenchymal changes were analyzed using a DMSA scan. Results: The median age for VUR diagnosis was 16.5 months in girls, and 8.5 months in boys (Z = 3.9; p = 0.001). IRR occurred in 51.4% of boys and in 25.9% of girls (χ2 = 12.4; p < 0.001). The non-dilating VUR occurred in 44% of boys and 24.1% of girls (χ2 = 7.7; p = 0.005). IRRs characterized upper and lower renal segments (81.8 and 63.6%) and middle segments (33.3%). Both incidence and increase in IRR correlated with the grade of VUR (p < 0.001). The incidence of reduced DMSA signal was statistically different among groups A + B and C, but not between groups A and B (χ2 = 32.2; p < 0.001). No statistically significant relationship existed between the reduced DMSA signal and the grade of VUR in group C. The reduced DMSA signal appeared in 9.9% positions in kidneys from group A, 14% from group B, and 32% from group C. Out of all 118 IRRs, 38.1% had reduced and 61.9% had normal DMSA signal. Among 11 parenchymal scars found in all three groups, 2 belonged to group B, 9 to group C, while group A had no scars. Conclusion: The parenchymal changes are the most prominent in the group with IRR, but they do not significantly differ among kidneys with different grades of VUR. VURs of higher grades are associated with a higher incidence of IRR and early clinical presentation. Scars can also appear in lower-grade VURs accompanied by IRR. Boys with VUR have earlier clinical presentation than girls, as they have significantly higher grades of VUR with a higher proportion of IRRs. Therefore, we suggest a subdivision of VURs into those with IRR and abundant parenchymal damage, and those without IRR and less parenchymal damage.

Prognostic Significance of Lymphocyte Infiltrate Localization in Triple-Negative Breast Cancer.

High infiltration by tumor-infiltrating lymphocytes (TILs) is associated with favorable prognosis in different tumor types, but the clinical significance of their spatial localization within the tumor microenvironment is debated. To address this issue, we evaluated the accumulation of intratumoral TILs (itTILs) and stromal TILs (sTILs) in samples from 97 patients with early triple-negative breast cancer (TNBC) in the center (sTIL central) and periphery (sTIL peripheral) of tumor tissues. Moreover, the presence of primary and secondary lymphoid aggregates (LAs) and the expression levels of the cancer testis antigen (CTA), NY-ESO-1, and PD-L1 were explored. High infiltration by itTILs was observed in 12/97 samples (12.3%), unrelated to age, Ki67 expression, tumor size, histologic type and grade, and LA presence. NY-ESO-1 was expressed in tumor cells in 37 samples (38%), with a trend suggesting a correlation with itTIL infiltration (p = 0.0531). PD-L1 expression was detected in immune cells in 47 samples (49%) and was correlated with histologic grade, sTILs, and LA formation. The presence of primary LAs was significantly correlated with better disease-free survival (DFS) (p = 0.027). Moreover, no tumor progression was observed during >40 months of clinical follow up in the 12 patients with high itTILs or in the 14 patients with secondary LAs. Thus, careful evaluation of lymphoid infiltrate intratumoral localization might provide important prognostic information.

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.

Expression of PD-L1 Is Associated with Inflammatory Microenvironment in Surgical Specimens of Non-Small Cell Lung Cancer.

The aim of this study was to analyse the expression of PD-L1 in non-small cell lung cancer (NSCLC) and its correlation with immune microenvironment response (IMR), clinic-pathological parameters, and outcome. The sample included 76 male and 32 female patients who underwent surgical resection. The mean age of the males was 66 years, and that of the females was 64 years. Adenocarcinoma (ADC) was diagnosed in 68 (63%) cases, squamous cell carcinoma in 35 (32%) cases, and NSCLC (not otherwise specified) in 5 (5%) cases. Metastatic lymph nodes were found in 38 (36%) patients, 18 with N1 nodes and 20 with N2 nodes. PD-L1 expression was valuated as the percentage of positive cancer cells among all cancer cells. Gender, age, and histologic type were not associated with PD-L1 expression (all p > 0.05). The subtypes of ADC were associated with PD-L1 expression (p = 0.050). The papillary subtype was 4.3 times more common among PD-L1 negative than PD-L1 positive ADC; the solid subtype was 1.9 times more common among PD-L1 positive than PD-L1 negative ADC. IMR was predominantly strong in 19 cases, weak in 36, and absent in 53 cases. The median value of PD-L1 expression in cancer cells was positively correlated with IMR (p = 0.039). PD-L1 expression was not correlated with overall survival (p = 0.643). The patients with strong, inflammatory-like IMR had an average survival time that was 12 months longer than patients with absent/low IMR (LR = 2.8; p = 0.132). In conclusion, the papillary subtype was more commonly PD-L1 negative in comparison with other subtypes of ADC. Positive PD-L1 expression in tumour cells was connected with strong, inflammatory-like IMR. Patients with strong IMR tended to experience better outcomes. Further investigations are needed on larger-scale cohorts to elucidate the insights of this descriptive study.

Personalized Approach to Patient with MRI Brain Changes after SARS-CoV-2 Infection.

From the beginning of SARS-CoV-2 virus pandemic, it was clear that respiratory symptoms are often accompanied with neurological symptoms. Neurological manifestations can occur even after mild forms of respiratory disease, and neurological symptoms are very often associated with worsening of the patient's condition. The aim of this study was to show abnormal brain neuroimaging findings evaluated by MRI in patients after SARS-CoV-2 infection and neurological symptoms. Methods: Sixteen patients after mild forms of SARS-CoV-2 infection, twenty-three patients after moderate forms of SARS-CoV-2 infection as well as sixteen healthy participants in the control group underwent MRI 3T brain scan. All subjects in the SARS-CoV-2 group had small, punctuate, strategically located and newly formed hyperintense lesions on T2 and FLAIR sequences. New lesions were formed more often in the bilateral frontal subcortical and bilateral periventricular, correlated with the severity of the clinical picture. These changes indicate an example of silent cerebrovascular disease related to SARS-CoV-2 and once again emphasize the neurotropism of the virus.

Cerebral Vasoreactivity Evaluated by Transcranial Color Doppler and Breath-Holding Test in Patients after SARS-CoV-2 Infection.

From the beginning of the SARS-CoV-2 virus pandemic, it was clear that the virus is highly neurotrophic. Neurological manifestations can range from nonspecific symptoms such as dizziness, headaches and olfactory disturbances to severe forms of neurological dysfunction. Some neurological complication can occur even after mild forms of respiratory disease. This study's aims were to assess cerebrovascular reactivity in patients with nonspecific neurological symptoms after SARS-CoV-2 infection. A total of 25 patients, aged 33-62 years, who had nonspecific neurological symptoms after SARS-CoV-2 infection, as well as 25 healthy participants in the control group, were assessed for cerebrovascular reactivity according to transcranial color Doppler (TCCD) which we combined with a breath-holding test (BHT). In subjects after SARS-CoV-2 infection, there were statistically significantly lower flow velocities through the middle cerebral artery at rest period, lower maximum velocities at the end of the breath-holding period and lower breath holding index (BHI) in relation to the control group. Changes in cerebral artery flow rate velocities indicate poor cerebral vasoreactivity in the group after SARS-CoV-2 infection in regard to the control group and suggest vascular endothelial damage by the SARS-CoV-2 virus.

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.

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.

Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure.

There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.

Prognostic value of connective tissue growth factor and c-Myb expression in IgA nephropathy and Henoch-Schönlein purpura-A pilot immunohistochemical study.

AIM: Adverse and advanced prognostic signs in IgA nephropathy (IgAN) are interstitial fibrosis and tubular atrophy, but early predictors of bad outcome are still lacking. We investigated expression of connective tissue growth factor (CTGF) and c-Myb in renal biopsies of IgAN and Henoch-Schönlein purpura (HSP), because these gene products are indirectly included in fibrosis and epithelial-mesenchymal transition (EMT). METHODS: The sample included 23 patients and 8 controls who underwent nephrectomy due to renal cancer. The slides cut from the paraffin blocks were prepared for standard indirect immunoflourescence, using antibodies to CTGF and c-Myb. Ten high-power non-overlapping fields were photographed on Olympus IX51 microscope. Average percent of positive tubular cells, as well as number of positive cells per glomerulus were calculated. RESULTS: The cytoplasmic tubular CTGF expression was higher in IgAN/HSP than in controls (P < 0.001), whereas no difference was found in glomeruli (P = 0.437). The nuclear c-Myb expresssion in glomeruli and tubules was higher in IgAN/HSP than in controls (P < 0.05). In the follow-up, decline in renal function correlated with glomerular and tubular c-Myb, as well as tubular CTGF expression (all P < 0.05). CONCLUSION: Our results proposed c-Myb and CTGF as novel, early and sensitive markers of chronic kidney disease and worse renal outcome, but larger series are needed.

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.

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study.

BACKGROUND: In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up. METHODS: Twenty males and 13 females with median of age 35 years (min-max: 3-76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed. RESULTS: In GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P = 0.004 and P = 0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P = 0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P = 0.038), tubular atrophy (P = 0.011) and globally sclerotic glomeruli (P = 0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P = 0.024 and P = 0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P = 0.010 and P < 0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P = 0.009), being lower in patients with negative than nuclear or dual dendrin expression (P = 0.034 and P = 0.004, respectively). CONCLUSION: In this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

Prediabetes awareness among Southeastern European physicians.

AIMS/INTRODUCTION: Prediabetes (PD) represents a transitional state where the glucose levels are higher than normal, but not enough for diabetes mellitus diagnosis. As there is a growing number of the population with PD, its early detection and treatment could prevent the development of diabetes mellitus and its complications. We aimed to assess the overall knowledge of PD among medical professionals of different varieties. MATERIALS AND METHODS: A questionnaire-based study addressing PD and type 2 diabetes mellitus knowledge among Southeastern European general practitioners, postgraduates, physicians and superior specialists was carried out. RESULTS: A total of 397 physicians completed the questionnaire. The total rate of correct answers from diabetologists, non-diabetologist internists, residents and general practitioners was 69, 56.1, 54 and 53%, respectively. Questions related to the PD definition achieved a total of 46.6% correct answers. Correct responses considering the numerical definition of impaired fasting glucose and impaired glucose tolerance were 46.3 and 46.8%, respectively. Younger physicians had better knowledge of numerical values regarding PD and type 2 diabetes mellitus criteria (P < 0.001). CONCLUSIONS: The present results show that overall knowledge of PD is poor among Southeastern European physicians, which necessitates adequate educational programs on PD in this region.

Formula for the prediction of apnea / hypopnea index in children with obstructive sleep apnea without polysomnography according to the clinical parameters: Is it reliable?

PURPOSE OF THE STUDY: The aim of the study was to propose "the risk formula" for obstructive sleep apnea in children according to the general and local clinical parameters and findings relevant for obstructive sleep apnea (OSA) severity. The unmet need for this formula arises from the economic burden of polysomnography (device, staff, training, special sleep centers, etc) as the golden standard for the diagnostics. MATERIALS AND METHODS USED: The study was performed from January 2013 until January 2016 in the Sleep Center, Department for Neuroscience, School of Medicine of the University of Split, Department of Pediatrics, University Hospital Split, Croatia and ENT Dept. University Hospital in Split, Croatia. Inclusion criteria were: age > two years, AHI >1 diagnosed by polysomnography. Exclusion criteria were: chronic lung disease, active tonsillitis/pharyngitis at the time of the physical exam and syndromes that affect breathing. All polysomnograms were scored by a qualified sleep technologist and interpreted by two board certified sleep physicians independently. Age, sex, BMI, Mallampati score, tonsillar size and adenoids size were recorded. All statistical calculations were performed using SPSS 20. RESULTS: In total 60 children were included in the study. The median of age was 5 years (range 2-9). There were 19 (32%) girls and 41 (68%) boys. Of all evaluated predictors, there were statistically significant differences in the values of AHI among children with different modified Mallampati score (χ2 = 28.2; p < 0.001), different size of tonsils (χ2 = 25.3; p < 0.001) and different size of adenoids (z = 2.7; p = 0,006) in univariate regression analysis. Strong positive association of AHI with modified Mallampati score (standardized B = 0.51; partial correlation = 0.542, r = 0.631) was found, as well as positive correlation of AHI with tonsillar size (standardized B = 0.246; partial correlation = 0.295,R = 0.489) in the multivariate forward stepwise regression analysis. CONCLUSION: Even though we are aware that PSG is the gold standard for diagnostics of SDB there is a significant financial burden for this diagnostic procedure. That is why there is a necessity for establishing good clinical standards and possible formula for OSA severity evaluation. We propose formula which includes Mallampati score and tonsillar size for OSA -risk calculation in order to perform early therapeutic intervention thereby reducing the risk of long-term negative consequences. We recommend this formula as the screening formula in circumstances where PSG is not available, in cases when the "waiting list" is too long or when a child can not cooperate to perform it. In developing countries like Croatia on time intervention with reduced procedure-associated costs is of the utmost importance.

Perinatal risk factors in newborns with gastrointestinal perforation.

AIM: To investigate correlation of perinatal risk factors in newborns with gastrointestinal perforation (GIP). METHODS: Single-center retrospective cohort study was conducted between January 1990 and December 2012. Medical records on all newborns with GIP were reviewed (n = 35). Surgical records and histopathologic examination of all perforated intestine samples were also reviewed. RESULTS: The most common cause of GIP was necrotizing enterocolitis (51.4%). The most common site of perforation was large intestine. Mortality rate was 31%. Infants with GIP more frequently had very low birth weight (< 1500 g), especially birth weight below 10th percentile according to gestational age. Ponderal index was not differing between infants with GIP and control subjects. In infants with GIP anemia was more frequently found than in control group. CONCLUSION: GIP in newborns is mostly disease of infants with birth weight below 10th percentile according to gestational age. GIP occurs more often in infants with anemia.

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.