Prognostic significance of red cell distribution width and its relation to increased pulmonary pressure and inflammation in acute heart failure

Background: Red cell distribution width (RDW) in acute heart failure (AHF) is accepted as a prognostic indicator with unclear pathophysiological ties. The aim of this study was to evaluate the prognostic value of RDW in AHF patients in relation to clinical and echocardiographic data.Methods: 170 patients with AHF were retrospectively studied. All patients had laboratory testing and an echocardiogram performed within 24 h of admission to the Cardiology Department. Results: During the mean 193 ± 111 days of follow-up, 33 patients died. More advanced age, high RDW and low peak early diastolic velocity of the lateral mitral annulus (MVe’) were independent predictors of all-cause mortality with hazard ratios of: 1.05 (95% CI 1.02–1.09), p < 0.005, 1.40 (95% CI 1.22–1.60), p < 0.001, and 0.77 (95% CI 0.63–0.93), p < 0.007, respectively. In a stepwise multiple linear regression model, RDW was correlated with hemoglobin concentration (standardized b = –0.233, p < 0.001), mean corpuscular volum (standardized b = –0.230, p < 0.001), mean corpuscular hemoglobin concentration (standardized b = –0.207, p < 0.007), the natural logarithm of C-reactive protein (CRP) (standardized b = 0.184, p < 0.004) and tricuspid regurgitation peak gradient (TRPG) values (standardized b = 0.179, p < 0.006), whereas MVe’ was correlated with atrial fibrillation (standardized b = 0.269, p < 0.001).Conclusions: The present data demonstrates a novel relation between higher levels of RDW and elevatedTRPG and high sensitivity CRP values in patients with AHF. These findings suggest that RDW, the most important mortality predictor, is independently associated with elevated pulmonary pressure and systemicinflammation in patients with AHF. Moreover, in AHF patients, more advanced age and decreased MVe’ are also independently associated with total mortality risk

Carotid intima–media thickness (IMT) in patients with severe familial and non-familial hypercholesterolemia: The effect of measurement site on the IMT correlation with traditional cardiovascular risk factors and calcium scores

Background: The carotid intima–media thickness (IMT) measurement may be carried out proximally (pIMT) or distally (dIMT) in relation to the bulb of the common carotid artery which has significant implications on the results and correlation with risk factors. The aim of the study was to compare the pIMT and dIMT in patients with familial hypercholesterolemia confirmed by genetic testing (FH group) and patients with severe non-familial hypercholesterolemia, with negative results of genetic testing (NFH group) and to determine the correlation of results with traditional atherosclerotic risk factors and calcium scores.Methods: A total of 86 FH and 50 NFH patients underwent pIMT and dIMT measurements of both carotid arteries as well as computed tomography (CT) with coronary and thoracic aorta calcium scoring.Results: The meanpIMT of both right and left common carotid artery were significantly higher in patients with FH compared to the NFH group (meanpRIMT 0.721 ± 0.152 vs. 0.644 ± 0.156, p < 0.01, meanpLIMT 0.758 ± 0.173 vs. 0.670 ± 0.110, p < 0.01). Patient age, pre-treatment lowdensity lipoprotein (LDL) cholesterol levels (LDLmax) at baseline and systolic blood pressure were independent predictors of pIMT increases in both carotid arteries. Smoking history, age and LDLmax were independent predictors of dIMT increase. There was a significant correlation between the calcium scores of the ascending aorta, coronary artery and aortic valve and all IMT parameters.Conclusions: The IMT measured proximally better between patients with familial and non-familial hypercholesterolemia. The association between IMT and traditional cardiovascular risk factors varies between measurement sites. IMT values correlate CT calcium scores in all patients with hypercholesterolaemia regardless of genetic etiology

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?

CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients’ survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death

Immunohistochemical Expression of CD44, MMP-2, MMP-9, and Ki-67 as the Prognostic Markers in Non-Clear Cell Renal Cell Carcinomas—A Prospective Cohort Study

CD44 is the most frequently reported marker of the cancer stem cells in renal cell carcinoma (RCC). Matrix metalloproteinases MMP-2 and MMP-9 are key regulators of tumor invasion and metastasis. The aim of this study was to investigate the clinicopathologic and prognostic values of the immunohistochemical expression of CD44, MMP2, MMP9, and Ki-67 in papillary and chromophobe RCCs. In the case of papillary RCC, MMP-2 expression was positively correlated with patient age (p p p p p > 0.05), whereas there was a positive correlation between increased MMP-9 expression and shorter overall survival (p < 0.05). Taken together, carcinogenesis in papillary RCC is probably dependent on both cancer stem cells and metalloproteinases activity. Expression of CD44 and MMP-9 can significantly improve the prediction of papillary RCC prognosis in the future

Polish Adaptation of the Social Communication Questionnaire (SCQ) and Female Autism Phenotype: An Investigation of Potentially Sex-Biased Items in the Screening Assessment and Their Impact on Scores

Standardized screening assessments and sex differences in autism spectrum disorder (ASD) are still under-explored in Poland. This study investigated the differences between Polish ASD females and males based on the responses provided by parents/caregivers to a Polish adaptation of the Social Communication Questionnaire, SCQ Lifetime and SCQ Current. The study included 90 ASD participants from Mental Health Services and Autism Clinics in Poland with no intellectual disability and no profound communication difficulties. Parents provided information on the SCQ items which were compared under three domains of the Autism Diagnostic Interview-Revised (ADI-R). Four SCQ items with the examples were investigated. No significant differences were found between the two sexes in the three domains. The repetitive use of objects declined with age in ASD males. Although the findings of the present study did not reveal substantial gender biases in the Polish adaptation of the SCQ, it is necessary to take into account potential gender differences in the clinical presentation of ASD and in the adaptation of screening and diagnostic tools

Periostin in Angiogenesis and Inflammation in CRC&mdash;A Preliminary Observational Study

Background and Objectives: To assess the periostin level and the concentrations of pro-inflammatory cytokines: TNF&alpha;, IFN-&gamma;, IL-1&beta; and IL-17 in tumor and marginal tissues of CRC and to investigate the influence of periostin on angiogenesis by MVD (microvessel density) and concentration of VEGF-A in relation to clinicopathological parameters of patients. Materials and Methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of periostin, VEGF-A, TNF&alpha;, IFN&gamma;, IL-1&beta; and IL-17, we used the commercially available enzyme- linked immunosorbent assay kit. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope Results: We found significantly higher concentrations of periostin, VEGF-A, IFN-&gamma;, IL-1 &beta;, IL-17 and TNF&alpha; in the tumor samples compared with surgical tissue margins. The tumor concentrations of periostin were correlated with tumor levels of VEGF-A, IFN-&gamma;, IL-1&beta; and TNF&alpha;. We observed significant correlation between margin periostin and VEGF-A, IFN-&gamma;, IL-17 and TNF&alpha; in tumor and margin specimens. Additionally, we found a significantly negative correlation between periostin tumor concentration and microvessel density at the invasive front. Tumor periostin levels were also correlated positively with tumor budding. Conclusions: Periostin activity may be associated with pro-inflammatory cytokine levels: TNF&alpha;, IFN-&gamma;, IL-1&beta; and IL-17. Our results also suggest the role of periostin in angiogenesis in CRC and its upregulation in poorly vascularized tumors. Further research on the regulations between periostin and cytokines are necessary to understand the interactions between tumor and immune tumor microenvironment, which could be helpful in the development of new targeted therapy

Assessment of the RANTES Level Correlation and Selected Inflammatory and Pro-Angiogenic Molecules Evaluation of Their Influence on CRC Clinical Features: A Preliminary Observational Study

Background and Objectives: Assessment of RANTES level and concentrations of inflammatory cytokines: programmed death ligand 1 (PD-L1), interferon gamma IFN-&gamma;, tumor necrosis factor alpha (TNF-&alpha;), transforming growht factor &beta; (TGF-&beta;) (and angiogenesis factors: vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor C (VEGF C) in tumor and margin tissues of colorectal cancer (CRC,) and evaluation of RANTES influence on histopathological parameters (microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs)), in relation to patients&rsquo; clinical features. Materials and Methods: The study used 49 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of RANTES, PD-L1, IFN-&gamma;, TNF-&alpha;, TGF-&beta;, VEGF-A, and VEGF-C, we used the commercially available enzyme-linked immunosorbent assay kit. Additionally, RANTES and PD-L1 expression was assessed with the use of IHC staining in both tumor cells and TILS in randomly selected cases. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope. Results: We found significantly higher levels of RANTES, PD-L1, IFN-&gamma;, TNF-&alpha;, TGF-&beta;, VEGF-A, and VEGF-C in the tumor in comparison with the margin. The RANTES tumor levels correlated significantly with those of PD-L1, TNF-&alpha;, TGF-&beta;, VEGF-A, and VEGF-C. The RANTES margin levels were significantly associated with the margin levels of all proteins investigated&mdash;PD-L1, IFN-&gamma;, TNF-&alpha;, TGF-&beta;, VEGF-A, and VEGF-C. Additionally, we observed RANTES- and PD-L1-positive immunostaining in TILs. In a group of 24 specimens, 6 different CRC tumors were positive for RANTES and PD-L1 immunostaining. The IFN-gamma concentration in both tumor and margin and TGF-&beta; in tumor correlated with TILs. TILs were negatively associated with the patients&rsquo; disease stage and N parameter. Conclusions: RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine&ndash;cytokine network involved in the modulation of TME composition in CRC. Further research may verify which processes are responsible for the associations observed in the study