Safety and efficacy of nivolumab as a second line therapy in metastatic renal cell carcinoma: a retrospective chart review

Aim To assess diseases outcomes and tolerability of real-life second-line nivolumab in a series of metastatic renal cell carcinoma (mRCC) patients. ----- Methods This retrospective chart review involved prospectively monitored patients (named patient program) treated with second-line nivolumab for mRCC at the University Hospital Centre Zagreb from February 2016 to March 2018. ----- Results The study enrolled 30 patients, 5 of whom (16.7%) had a complete response. The mean ± standard deviation therapeutic response time to nivolumab treatment was 14.07 ± 8.92 months, with a minimum treatment duration of 2 months and a maximum of 24 months. The median duration of therapy was 17 months (mean: 15.8 months; range: 3-24 months), and 50% (n = 15/30) of patients remained alive at the end of follow up. The most common adverse events associated with nivolumab were fatigue (26.67%; n = 8/30), anemia (10.0%; n = 3/30), adrenal insufficiency (6.67%; n = 2/30: G1 = 1, G2 = 1), grade 2 pneumonitis (6.67%; n = 2/30), grade 2 neuropathy (6.67%; n = 2/30), rash (6.67%; n = 2/30: G1 = 1, G2 = 1), and hepatitis (3.33%; n = 1/30). ----- Conclusion The present study indicates acceptable patient responses and tolerability of nivolumab in mRCC

Povezanost debljine lamele s vidnom oštrinom nakon stražnje slojevite transplantacije rožnice [Correlation of lamella thickness on visual acuity after Descemet's stripping automated endothelial keratoplasty]

Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) is corneal transplantation procedure where the patient's inner dysfunctional layer is replaced. There are contradictory data in the literature about the correlation between lamellar thickness and the visual acuity. Study included 55 eyes after conventional DSAEK and no other comorbidities that could affect visual acuity. Data about lamellar thickness and visual acuity were measured before and 6 months after surgery. The results show that visual acuity before surgery was 0,15 on average and after surgery 0,57. Average postoperative lamella thickness was 142,16 μm. Better visual acuity of 0,63 was achieved with lamellas thinner than 124 μm, while statistically significantly lower visual acuity was 0,51 for lamellas thicker than 124 μm. Postoperative deturgescence of lamellas 6 months after surgery was 12% from initail thickness. The goal after conventional DSAEK is to have postoperative lamellas thinner than 124 μm in the eye, as this will result in better postoperative visual acuity. In order to achieve this requirement, the request for the eye bank should be lamellas thinner than 142 μm before the surgery. This will minimize tissue loss for eye banks and the surgeons will have fewer problems during surgery, while obtaining good final visual acuity

Role of platelet gene polymorphisms in ischemic pediatric stroke subtypes: a case-control study

Aim: To assess the role of human platelet antigens (HPA), P-selectin gene (SELP) polymorphisms, and HPA and SELP haplotypes with factor V (FV) R506Q in ischemic pediatric stroke (IPS) subtypes: cerebral sinovenous thrombosis (CSVT), perinatal (PAIS), and childhood (CAIS) arterial ischemic stroke. ----- Methods: This case-control study enrolled 150 children with confirmed IPS and 150 age- and sex-matched controls. FV R506Q and HPA-1 were genotyped with CVD StripAssay®, HPA-2 and HPA-3 with real-time polymerase chain reaction, SELP S290N, V599L, and T715P with high resolution melting analysis, and SELP N562D with sequence-specific polymerase chain reaction. ----- Results: HPA-1b allele (odds ratio [OR] 2.75, 95% confidence interval [CI] 1.02-7.42, P=0.048) and HPA-1a2a3b (OR 5.46, 95% CI 1.51-19.76, P=0.011), HPA-1b2a3a (OR 7.00, 95% CI 1.25-39.13, P=0.028), and HPA-1b2b3a (OR 11.39, 95% CI 1.39-92.95, P=0.024) haplotypes increased the risk for CSVT. HPA-3b allele was significantly associated with 2-fold lower risk for PAIS (OR 0.49, 95% CI 0.26-0.89, P=0.020) and CAIS (OR 0.47, 95% CI 0.26-0.86, P=0.014) and non-significantly associated with increased risk for CSVT (OR 6.43, 95% CI 0.83-50.00, P=0.022). HPA-1a2b3a haplotype was significantly associated with CAIS (OR 6.76, 95% CI 2.13-21.44, P=0.001). The inclusion of FV R506Q in SELP haplotype analysis increased the risk for PAIS 4-fold in QNDVT carriers (OR 8.14, 95% CI 0.93-71.33, P=0.060) compared with NDVT haplotype (OR 2.45, 95% CI 0.98-6.18, P=0.058), but the result was not significant. ----- Conclusion: Individual HPAs, and particularly HPA haplotypes, are involved in IPS subtypes pathogenesis. A possible risk-inducing synergistic effect of SELP haplotypes with FV R506Q is restricted to PAIS only

Comparison of sonoelastographic values of breast tissue with mammographically and ultrasonically assessed density: a cross-sectional study

Aim: To determine the relationship between breast stiffness assessed with sonoelastography (elasticity) and breast tissue density assessed with mammography (MG) and ultrasound (US). ----- Methods: This cross-sectional study involved 100 women who underwent MG, gray-scale US, and shear-wave sonoelastography during 2013. Mammographic density was categorized into four groups and sonographic density into three groups according to Breast Imaging-Reporting and Data System criteria. The stiffness of breast parenchymal and adipose tissue in all breast quadrants was quantified by shear-wave sonoelastography. Mean elastographic estimates were compared with MG- and US-derived density estimates. ----- Results: Parenchymal and adipose tissue elasticity positively correlated with MG- and US-derived breast density (for parenchyma: for MG Kendall's tau b 0.522; Jonckheere-Terpstra test P<0.001 and for US Kendall's tau b 0.533; Jonckheere-Terpstra test P<0.001); the higher was the breast density on MG and US, the higher was the elastographic stiffness. ----- Conclusion: Sonoelastographic breast stiffness strongly positively correlated with breast density. Thus, sonoelastography may have a potential for estimating the breast cancer risk, which allows a novel application of this technique in routine clinical practice

Prognostički čimbenici vaskulitisa povezanih s antineutrofilnim citoplazmatskim protutijelima koji zahvaća bubreg [Prognostic factors in antineutrophyllic cytoplasmatic antibodies associated vasculitis with kidney involvement]

Introduction: ANCA associated vasculitis with renal involvement are heterogeneous diseases. Some clinical, laboratory and pathohistological parameters determine severity as well as prognosis and outcomes of the disease. ----- Patients and methods: This study included 108 patients diagnosed with pauciimmune glomerulonephritis between 2003 and 2016. All the patients met the Chapell Hill consensus conference criteria for ANCA associated vasculitis. Patient follow up was minimum one year, until death or loss in follow up or until December 2018. Patients were categorized in clinical, serological and histopathological phenotypes based on gathered clinical, laboratory and pathohistological data. We determined predictors for combined ESRD and mortality outcome (ESRDD) as well as individual, mortality, ESRD and relapse rates. ----- Results: Using Cox regression analysis we found lower hemoglobin levels, leukocyte number, C3 staining in blood vessels and IFTA >50% to be independent negative predictors for ESRDD. We found age, hemoglobin levels and BVAS score to be significant negative predictors for death. Significant negative predictors for ESRD in multivariate analysis were a need for renal replacement therapy and IFTA >50%. Negative predictors of relapse were age, serum creatinine levels, diastolic blood pressure and a need for renal replacement therapy. Interestingly ATO was shown to be or had a strong tendency to be a significant negative predictor in univariate analysis for all the outcome except for relapse. ----- Conclusion: The results of this research proved our hypothesis and showed the importance of detailed multidisciplinary approach to AAV patients, detailed laboratory work-up and correlations of laboratory and clinical findings with pathohistological findings. This study was among few or even the first to show hemoglobin concentrations to be not only clinical aspect of AAV but also the independent predictor of outcomes. Results of our study also pointed out to the need to modify current histopathological classification of AAV associated renal damage to include IFTA since we have shown IFTA >50% to be an independent negative predictor for ESRDD, ESRD. We have also shown that the acute tubular damage is significant negative predictor for all the outcomes except for the relapse, in univariate analysis

Povezanost grelina i grelinskoga receptora sa stupnjem displazije u adenomima debeloga crijeva [Correlation of ghrelin and ghrelin receptor with the grade of dysplasia in colonic adenomas]

Aim of this study was to investigate the correlation of serum ghrelin and immunohistochemical expression of ghrelin and ghrelin receptor with the grade of dysplasia in colonic adenomas, and compare them with the presence of insulin resistance and metabolic syndrome. The study included 92 participants with colonic adenomas, of whom 43 had high grade dysplasia. In high grade adenomas high expression of ghrelin was 7 times more common than in low grade adenomas (13,95% to 2,04%) and it was absent in normal mucosa. High expression of ghrelin receptor was present in 12,24% low grade, 25,58% high grade adenomas and 2,17% of normal mucosa. Expression of ghrelin positively correlated with expression of ghrelin receptor in high grade dysplasia. Serum deacylated ghrelin negatively correlated with body mass, BMI, waist circumference, insulin, fasting plasma glucose levels and HOMA-IR. High expression of grelin in high grade adenomas is probably due to increased local production of ghrelin, and could in that way have a role in proliferation and tumorigenesis. Serum deacylated ghrelin is negatively correlated with insulin resistance and metabolic syndrome criteria, and could have a protective role in these two conditions

How to face the aging world – lessons from dementia research

A continuous rise in life expectancy has led to an increase in the number of senior citizens, now amounting to a fifth of the global population, and to a dramatic increase in the prevalence of diseases of the elderly. This review discusses the threat of dementia, a disease that imposes enormous financial burden on health systems and warrants efficient therapeutic solutions. What we learned from numerous failed clinical trials is that we have to immediately take into account two major elements: early detection of dementia, much before the onset of symptoms, and personalized (precision) medicine treatment approach. We also discuss some of the most promising therapeutic directions, including stem cells, exosomes, electromagnetic fields, and ozone

Povezanost polimorfizama gena za serotoninski transportni sustav s fenotipom Crohnove bolesti

In this retrospective case-control study we analyzed the potential association of the promoter (5-HTTLPR and rs25531) and intronic Stin2 VNTR polymorphic regions of the SLC6A4 gene with the incidence of Crohn's disease (CD). The study included 192 CD patients and 157 healthy control subjects (age and gender matched with patients group). Genotyping was performed by polymerase chain reaction and correlation of polymorphic SLC6A4 gene variants with CD and its clinical subtypes was analyzed by chi-square and Fisher's exact test, binary logistic regression and haplotype analysis. The results confirmed similar gender (CD: 88 (45.8%) female, 104 (54.2%) male; HC: 84 (53.5%) female, 73 (46.5%) male; χ2 = 2.03, df =1, P = 0.154) and age (CD: 41.34±12.789; HC: 41.68±8.789; P = 0.091) distribution among CD and HC groups involved in the study. Significant difference was observed in STin2 genotype (CD: χ2=15.86, df = 4, P = 0,003; females: χ2 = 15.33, df = 4, P = 0.004) and allele (CD: χ2 = 12.03; df = 2, P = 0.002; females: χ2 = 9.85, df = 2; P = 0.007) distribution between CD and HC and between corresponding female subgroups, with significant negative association (CD: P = 0.013, OR adjusted by age and gender = 0.5, 95% CI=0.29-0.86; females: P = 0.006, OR adjusted by age = 0.32, 95% CI=0.14-0.72) of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD, and significantly higher S-STin2.12 ( 5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution (P = 0.004, OR=1.62, 95 % CI=1.16-2.26) in CD. There was no significant association between 5-HTTLPR and rs25531 genotype or allele frequencies and CD or between any SLC6A4 polymorphic loci among different clinical subtypes of Crohns disease classified according to Montreal consensus. In conclusion, STin2 VNTR polymorphism of SLC6A4 gene may contribute to the pathogenesis of CD