Croatian Medical Journal最新文献

Soluble fibrin is composed mainly of desA fibrin and fibrinogen oligomers consisting of fewer than 16 monomers partially cross-linked by factor XIIIa. Soluble fibrin cannot stimulate Glu-plasminogen activation by tissue plasminogen activator (t-PA); therefore, it may not be a direct predecessor of D-dimer. However, within the microcirculatory system, soluble fibrin oligomers may form microclots. Fibrin microclots stimulate Glu-plasminogen activation by t-PA, a process resulting in the formation of Glu-plasmin. Glu-plasmin dissolves the microclots, forming D-dimer. In normal and pathological blood plasma samples, soluble fibrin levels are substantially higher than those of D-dimer. Their concentrations in the plasma are also regulated by transendothelial transfer, absorption by blood macrophages, and binding and internalization with low-density lipoprotein receptors of the cells of the reticuloendothelial system. Therefore, the exact mechanisms of fibrin clots formation and elimination in normal and pathological conditions remain unclear. In this study, we reviewed findings on the molecular mechanisms of the formation and dissolution of fibrin clots, fibrin-dependent activation of Glu-plasminogen by t-PA, and blood plasma behavior in the microcirculatory system. Finally, we proposed a model that explains the relations of D-dimer and soluble fibrin underlying the common and separate mechanisms of their formation and elimination.

Aim: To assess the effectiveness of fraction of inspired oxygen (FiO2) titration guided by oxygen reserve index (ORi) in preventing hyperoxia in intensive care unit (ICU) patients receiving mechanical ventilator support.

Methods: Patients aged 18 years and older who were admitted to a tertiary ICU and required mechanical ventilator support were randomly divided into two groups: the control group (n=30) and the oxygen saturation (SpO2) +ORi group (n=30). In the SpO2+ORi group, the goal was to maintain SpO2 between 95% and 98% and ORi at 0.00. In both groups, SpO2, ORi, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide, positive end-expiratory pressure, FiO2, and hemodynamic parameters were recorded every six hours for two consecutive days.

Results: A very strong positive linear correlation was found between PaO2 and ORi (r=0.937; P<0.001). In the ORi+SpO2 group, PaO2 values were significantly lower and decreased with FiO2 titration over time. Severe hyperoxia was observed in 24.8% of the control group and in only 3.3% of the ORi+SpO2 group. When PaO2>120 mm Hg, FiO2>0.40 was found in 83.5% of the control group, and in 40% of the ORi+SpO2 group.

Conclusion: FiO2 titration guided by ORi+SpO2 effectively prevents hyperoxia and reduces the exposure time to hyperoxia in critically ill patients.

Aim: To compare interleukin-2 levels (IL-2) and IL-2 gene site 1 methylation levels between preterm newborns (PN) and full-term newborns (FN) and investigate their association with the environmental exposure of their mothers during pregnancy.

Methods: IL-2 and IL-2 gene site 1 methylation levels were assessed in 50 PN and 56 FN. Newborns' mothers filled in questionnaires about their living and occupational environments, habits, diets, and hobbies.

Results: The mothers of PN were significantly more frequently agrarian/rural residents than the mothers of FN. PN had significantly higher IL-2 levels, and significantly lower methylation of IL-2 gene site 1 levels than FN.

Conclusion: IL-2 levels, hypomethylation of the IL-2 gene site 1, and the mother's rural residence (probably due to pesticide exposure) were predictive biomarkers for preterm birth. For the first time, we present the reference values for the methylation of IL-2 gene site 1 in PN and FN, which can be used in the clinical setting and biomonitoring.

Liver cirrhosis is an increasing public health problem and a major cause of morbidity and mortality. Accordingly, cirrhotic cardiomyopathy, a frequently underdiagnosed condition, is becoming a growing health problem. In the last 20 years, cardioselective biomarkers have been investigated for their diagnostic and prognostic properties for numerous conditions. The aim of this article is to review the literature on the relationship between the most commonly used cardioselective biomarkers (cardiac troponins I and T, N-terminal pro-B-type natriuretic peptide, brain natriuretic peptide, and heart-type fatty-acid binding protein) and the presence, functional stage, and clinical outcomes of liver cirrhosis. Elevated plasma levels of these biomarkers have been reported in patients with liver cirrhosis, and there is mounting evidence on their predictive value for clinical outcomes in this disease. In addition, elevated plasma levels of these biomarkers have been reported in patients before, during, and after liver transplantation, but in fewer studies. Due to their predictive value for clinical outcomes, we advocate the use of these markers in patients with liver cirrhosis and cirrhotic cardiomyopathy, as well as in candidates for liver transplant.

Aim: To evaluate the association between carotid intima-media thickness (CIMT) at hospital admission and unfavorable outcomes in adults without advanced vascular diseases presenting with non-severe COVID-19 pneumonia to assess the feasibility of evaluating CIMT as a risk stratification aid in this setting.

Methods: This proof-of-concept nested case-control study enrolled consecutive non-vaccinated adults free of advanced vascular diseases presenting with verified non-severe COVID-19 pneumonia between December 2020 and June 2021. CIMT was measured at admission, and patients were managed in line with the national Ministry of Health guidelines. Those who died or required mechanical ventilation (MV) during the index hospital stay were considered cases and were matched (entropy balancing, exact matching) on a set of covariates to survivors not requiring MV (controls). Frequentist and Bayesian logistic models were fitted to the case status.

Results: The study enrolled 207 patients: 27 (13%) cases and 180 controls. All were retained in the analysis after entropy balancing, while 27 cases were exactly matched to 99 controls. Higher CIMT at the proximal internal carotid artery (both left and right) was consistently associated with higher odds of being a case: all odds ratio point-estimates were ≥1.50 with lower limits of the 99% confidence intervals/credibility intervals ≥1.00 with two-sided probabilities of OR>1.00 greater than 99.5%. The susceptibility of the estimates to unmeasured confounding was low.

Conclusion: This study supports the feasibility of CIMT as a risk stratification aid in adults free of advanced vascular disease presenting with non-severe COVID-19 pneumonia.

Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

Aim: To evaluate the treatment response to compressed colchicine tablets in familial Mediterranean fever (FMF) patients with resistance or intolerance to coated colchicine. The secondary aim was to determine the demographic and clinical characteristics of responders to compressed colchicine.

Methods: We retrospectively reviewed the medical records of 1574 pediatric patients with FMF treated at Ankara Bilkent City Hospital. Sixty-one patients did not respond to coated colchicine and were switched to compressed colchicine. In these patients, the number of attacks and the International Severity Score for FMF (ISSF) during the 6 months before and 3, 6, 9, 12, and 24 months after switching from coated colchicine to compressed colchicine were recorded.

Results: Twelve of 61 patients (19.7%) who were switched to compressed colchicine due to intolerance responded to treatment. Of the 49/61 patients (80.3%) who were switched due to uncontrolled attacks and persistent subclinical inflammation, 25 responded to treatment. The frequency of attacks and ISSF decreased after switching. At the end of the two-year follow-up, 42 patients responded to compressed colchicine, and 19 patients received compressed colchicine plus interleukin-1-targeting drugs.

Conclusions: Compressed colchicine was shown to be a useful treatment option before initiating biological agents in non-responders to coated colchicine, especially those with side effects.