Rapid triage and transfer system for patients with proven Covid-19 at emergency department.

BACKGROUND: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. METHODS: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. RESULTS: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. CONCLUSION: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.

Dynamics of the vitamin D C3-epimer levels in preterm infants.

OBJECTIVES: The primary objective was to determine levels of C3-epi-25(OH)D in very low birth weight infants. The secondary objective was to evaluate the possible influence of preterm birth, intrauterine growth restriction (IUGR), and season of birth on the production of C3-epimers. METHODS: A total of 127 infants with birth weight less than 1,500 g met the inclusion criteria of the study. We examined 25-hydroxyvitamin-D [25(OH)D] levels and C3-epi-25(OH)D in maternal serum before labor, and in cord blood and infants' serum on days 14 and 28, and at discharge. RESULTS: The mean levels (±SD) of C3-epi-25(OH)D of the cord, on day 14, on day 28, and at discharge were 2.2 (2.9), 7.7 (5.5), 11.7 (7.6) and 14.9 (11.7) nmol/L respectively. The proportion of total 25(OH)D as the C3-epimer was 6.9% (cord), 16.3% (day 14), 22.4% (day 28) and 23.3% (discharge). A statistically significant correlation between 25(OH)D and C3-epi-25(OH)D can be demonstrated from birth. The severity of immaturity and IUGR did not affect the production of C3-epimers. In summer/autumn vs. winter/spring, the mean (SD) percentage of total 25(OH)D as the C3-epimer significantly differs only in maternal serum samples and umbilical cord samples (p value <0.001). CONCLUSIONS: The production of C3-epi-25(OH)D is functional even in the most immature newborns, has fetal origins, and is largely dependent on circulating 25(OH)D. At the end of the first month of life, C3-epimers make up more than 20% of 25(OH)D.

The Effect of Zonisamide on Rat Bone Mass, Structure, and Metabolism.

INTRODUCTION: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. METHODS: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The femurs were used for biomechanical testing. RESULTS: We found a statistically significant reduction in BMD and biomechanical strength 12 weeks after orchidectomy of the rats (ORX). After ZNS administration to orchidectomized rats (ORX+ZNS) and the sham-operated control rats (SHAM+ZNS), there were no statistically significant changes in BMD, bone turnover markers, or biomechanical properties as compared with the ORX group and SHAM group. CONCLUSIONS: The results suggest that administration of ZNS to rats exerts no negative effect on BMD, bone metabolism markers, or biomechanical properties.

Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up.

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline (ANT)-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent ANT-induced cardiac damage and provide long-lasting cardioprotection. The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II ß (TOP2B)-dependent DNA damage responses in the heart.

The relationship of uremic toxin indoxyl sulfate and intestinal elimination mechanisms in hemodialysis patients.

INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA), that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 µmol/L) in comparison with a wild type genotype (360.5 µmol/L). Discussion/ Conclusion: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.

Quality benchmarking of smartphone laboratory medicine applications: comparison of laboratory medicine specialists' and non-laboratory medicine professionals' evaluation.

OBJECTIVES: There are many mobile health applications (apps) now available and some that use in some way laboratory medicine data. Among them, patient-oriented are of the lowest content quality. The aim of this study was to compare the opinions of non-laboratory medicine professionals (NLMP) with those of laboratory medicine specialists (LMS) and define the benchmarks for quality assessment of laboratory medicine apps. METHODS: Twenty-five volunteers from six European countries evaluated 16 selected patient-oriented apps. Participants were 20-60 years old, 44% were females, with different educational degrees, and no professional involvement in laboratory medicine. Each participant completed a questionnaire based on the Mobile Application Rating Scale (MARS) and the System Usability Scale, as previously used for rating the app quality by LMS. The responses from the two groups were compared using the Mann-Whitney U test and Spearman correlation. RESULTS: The median total score of NLMP app evaluation was 2.73 out of 5 (IQR 0.95) compared to 3.78 (IQR 1.05) by the LMS. All scores were statistically significantly lower in the NLMP group (p<0.05), except for the item Information quality (p=0.1631). The suggested benchmarks for a useful appear: increasing awareness of the importance and delivering an understanding of persons' own laboratory test results; understandable terminology; easy to use; appropriate graphic design, and trustworthy information. CONCLUSIONS: NLMP' evaluation confirmed the low utility of currently available laboratory medicine apps. A reliable app should contain trustworthy and understandable information. The appearance of an app should be fit for purpose and easy to use.

Aging in psoriasis vulgaris: female patients are epigenetically older than healthy controls.

BACKGROUND: Psoriasis vulgaris is a skin autoimmune disease. Psoriatic patients have significantly lowered life expectancy and suffer from various comorbidities. The main goal of the study was to determine whether psoriatic patients experience accelerated aging. As accelerated aging might be the reason for the higher prevalence of comorbidities at lower chronological ages, we also wanted to investigate the relationship between aging and selected parameters of frequent psoriatic comorbidities - endocan, vascular endothelial growth factor and interleukin-17. Samples were obtained from 28 patients and 42 healthy controls. Epigenetic age measurement was based on the Horvath clock. The levels of endocan, vascular endothelial growth factor and interleukin-17 were analyzed using standardized ELISA methods. RESULTS: The difference between the epigenetic age and the chronological age of each individual subject did not increase with the increasing chronological age of patients. We cannot conclude that psoriasis causes accelerated aging. However, the epigenetic and chronological age difference was significantly higher in female patients than in female controls, and the difference was correlated with endocan (r = 0.867, p = 0.0012) and vascular endothelial growth factor (r = 0.633, p = 0.0365) only in female patients. CONCLUSIONS: The findings suggest a possible presence of pathophysiological processes that occur only in female psoriatic patients. These processes make psoriatic females biologically older and might lead to an increased risk of comorbidity occurrence. This study also supports the idea that autoimmune diseases cause accelerated aging, which should be further explored in the future.

Bone disesase in end-stage kidney disease - renal and non-renal components.

Metabolic bone disease in chronic kidney disease and end-stage renal failure represents one of the most severe clinical complication in kidney patients, namely those on maintenance dialysis. Traditionally, bone changes are induced by secondary hyperparathyroidism. The CKD-MBD concept reflects the link between bone and cardiovascular disease in these patients. Studies documented also other bone pathological pathways in renal patients, such as osteoporosis, as in kidney and dialysis patients its risk factors are present as well as in general population. Resulting bone disease in renal disease and failure is far more complex than previously seen. However, the secondary hyperparathyroidism still represents the main pathological pathway.

Antibiotic administration reduces the rate of intraamniotic inflammation in preterm prelabor rupture of the membranes.

BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

Identification of a four-gene methylation biomarker panel in high-grade serous ovarian carcinoma.

Background The lack of effective biomarkers for the screening and early detection of ovarian cancer (OC) is one of the most pressing problems in oncogynecology. Because epigenetic alterations occur early in the cancer development, they provide great potential to serve as such biomarkers. In our study, we investigated a potential of a four-gene methylation panel (including CDH13, HNF1B, PCDH17 and GATA4 genes) for the early detection of high-grade serous ovarian carcinoma (HGSOC). Methods For methylation detection we used methylation sensitive high-resolution melting analysis and real-time methylation specific analysis. We also investigated the relation between gene hypermethylation and gene relative expression using the 2-ΔΔCt method. Results The sensitivity of the examined panel reached 88.5%. We were able to detect methylation in 85.7% (12/14) of early stage tumors and in 89.4% (42/47) of late stage tumors. The total efficiency of the panel was 94.4% and negative predictive value reached 90.0%. The specificity and positive predictive value achieved 100% rates. Our results showed lower gene expression in the tumor samples in comparison to control samples. The more pronounced downregulation was measured in the group of samples with detected methylation. Conclusions In our study we designed the four-gene panel for HGSOC detection in ovarian tissue with 100% specificity and sensitivity of 88.5%. The next challenge is translation of the findings to the less invasive source for biomarker examination, such as plasma. Our results indicate that combination of examined genes deserve consideration for further testing in clinical molecular diagnosis of HGSOC.

Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris.

BACKGROUND: Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. OBJECTIVE: The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomarkers of severity of psoriasis and to explore possible relationships between these proteins for the purpose of better understanding their roles in the immunopathology of psoriasis. METHODS: The serum levels of selected alarmins were measured in 63 psoriatic patients and 95 control individuals. The levels were assessed by the ELISA technique using commercial kits. The data were statistically processed with MedCalc version 19.0.5. RESULTS: In psoriatic patients, we found significantly increased levels of HMGB1 (p < 0.05), IL-33 (p < 0.01), S100A7 (p < 0.0001), and S100A12 (p < 0.0001). In addition, we found a significant relationship between HMGB1 and S100A7 (Spearman's rho = 0.276, p < 0.05) in the patients and significant relationship between HMGB1 and IL-33 in the controls (Spearman's rho = 0.416, p < 0.05). We did not find any relationship between observed alarmins and the disease severity. CONCLUSIONS: The alarmins HMGB1, IL-33, S100A7, and S100A12 were significantly elevated in the serum of patients, which states the hypothesis that they play specific roles in the immunopathology of psoriasis. However, we have not yet found a relationship between observed alarmins and the disease severity. The discovery of the relationship between HMGB1 and S100A7 is a novelty that should be studied in the future to further clarify its role and importance.

Metabolic Syndrome, Clusterin and Elafin in Patients with Psoriasis Vulgaris.

BACKGROUND: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases. MATERIAL AND METHODS: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. RESULTS: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. CONCLUSION: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.

Novel CYP24A1 Mutation in a Young Male Patient with Nephrolithiasis: Case Report.

BACKGROUND/AIMS: The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, which hydroxylates active forms of vitamin D into inactive forms. Biallelic mutations in the CYP24A1 gene can lead to elevated levels of active vitamin D metabolites and, consequently, to hypercalcemia, hypercalciuria, nephrocalcinosis, and nephrolithiasis; however, monoallelic mutations have been associated only with milder phenotypes. In the present manuscript, we report the case of a young male patient who presented hypercalcemia and nephrolithiasis, suppressed parathormone, and elevated 1,25 dihydroxy vitamin D levels. METHODS: Biochemical analyses were performed on Cobas 8000, F. Hoffmann-La Roche AG, Basel, Switzerland. The proband was initially evaluated for occult malignancies by body imaging, serum electrophoresis, and tumor markers, which did not reveal any pathology. DNA samples of the proband and his sibling were then examined using Sanger sequencing. RESULTS: Genetic analysis revealed 2 compound heterozygous CYP24A1 mutations (p.L148P and p.R223*). The novel nonsense CYP24A1 mutation, p.R223*, was also found heterozygously in other family members with a medical history of nephrolithiasis. CONCLUSIONS: The identification of this gene mutation causing hypercalcemia, hypercalciuria, and renal stones allows the specific management of endogenous vitamin D production.

Goeckerman Therapy of Psoriasis: Genotoxicity, Dietary Micronutrients, Homocysteine, and MTHFR Gene Polymorphisms.

Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats.

Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing. Long-term AML administration does not have a negative impact on bone metabolism and density in male SHR.

Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol.

INTRODUCTION: The aim of study was to evaluate impact of long-term dietary cholesterol overload on the cholesterol homeostasis and liver regeneration. MATERIAL AND METHODS: Serum lipid parameters, 14C-cholesterol incorporation, liver DNA synthesis and protein expression was determined in partially hepatectomized (PH) rats fed with a standard (SLD) or hypercholesterolemic (CHOL) diet. RESULTS: 29-day intake of CHOL diet before PH produced increase in serum total cholesterol, LDL lipoprotein, and triglyceride concentration. PH provoked decrease in serum total cholesterol and triglyceride concentration in both groups. PH was associated with increase in serum ALT activity more pronounced in CHOL animals. Hepatic DNA synthesis was increased after PH in both groups, but lower in CHOL. Hypercholesterolemic diet reduced the absorption of radiolabelled cholesterol in intestine and then activity in blood and liver. The 14C-cholesterol hepatic activities tend to increase after PH in both groups. CHOL diet produced up-regulation of Acyl-CoA:cholesterol acyltransferase-2 protein expression. PH was associated with increase of LDL receptor and Acyl-CoA:cholesterol acyltransferase-2 protein expression in both dietary groups. DISCUSSION: Liver regeneration after PH is negatively influenced by CHOL diet. The increased uptake of cholesterol in the liver after PH associated with up-regulation of LDL receptor protein expression suggests preferential use of extrahepatic cholesterol by the liver.

A survey of patients' views from eight European countries of interpretive support from Specialists in Laboratory Medicine.

BACKGROUND: There is increasing interest in direct patient engagement including receiving their laboratory medicine results. We previously established an appetite for Specialists in Laboratory Medicine to support patients in understanding results. The aim of this study was to establish whether patients agreed with such an approach, determined through surveying views in eight European countries. METHODS: A standardized five-question survey was administered across eight European countries to a total of 1084 individuals attending medical outpatient clinics, with 100 patients each in Poland, Serbia, Netherlands, Turkey and Czech Republic, 101 in Estonia, 116 in Denmark and 367 in Norway. The responses across countries were compared using the chi-square test (p<0.05). RESULTS: Patients wanting their results ranged from 50% to 94% (mean 65%) of those responding positively, a mean of 72% wanted additional information with their results; direct receipt was preferred over referral to a website. Specialists in Laboratory Medicine providing such information were acceptable to a mean of 62% of those respondents wishing their results; in countries where payment was possible, there was little interest in making additional payment for such a service. CONCLUSIONS: A clear proportion of patients are interested in receiving their laboratory medicine results, the majority with explanatory notes; a role for Specialists in Laboratory Medicine is acceptable and raises the potential for direct engagement by such specialists with patients offering a new paradigm for the provision of laboratory medicine activities.

Next-Generation Sequencing Approach in Methylation Analysis of HNF1B and GATA4 Genes: Searching for Biomarkers in Ovarian Cancer.

DNA methylation is well-known to be associated with ovarian cancer (OC) and has great potential to serve as a biomarker in monitoring response to therapy and for disease screening. The purpose of this study was to investigate methylation of HNF1B and GATA4 and correlate detected methylation with clinicopathological characteristic of OC patients. The study group consisted of 64 patients with OC and 35 control patients. To determine the most important sites of HNF1B and GATA4, we used next-generation sequencing. For further confirmation of detected methylation of selected regions, we used high-resolution melting analysis and methylation-specific real-time polymerase chain reaction (PCR). Selected regions of HNF1B and GATA4 were completely methylation free in all control samples, whereas methylation-positive pattern was observed in 32.8% (HNF1B) and 45.3% (GATA4) of OC samples. Evaluating both genes together, we were able to detect methylation in 65.6% of OC patients. We observed a statistically significant difference in HNF1B methylation between samples with different stages of OC. We also detected subtype specific methylation in GATA4 and a decrease of methylation in late stages of OC. The combination of unmethylated HNF1B and methylated GATA4 was associated with longer overall survival. In our study, we employed innovative approach of methylation analysis of HNF1B and GATA4 to search for possible epigenetic biomarkers. We confirmed the significance of the HNF1B and GATA4 hypermethylation with emphasis on the need of selecting the most relevant sites for analysis. We suggest selected CpGs to be further examined as a potential positive prognostic factor.

Systemic Inflammation, Oxidative Damage to Nucleic Acids, and Metabolic Syndrome in the Pathogenesis of Psoriasis.

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls.

Parathyroidectomy in Hyperparathyroidism-Associated Calciphylaxis in End-Stage Renal Disease Should be Prompt and Radical - a Case Report with Two Original Therapeutic Modifications and Successful Outcome.

We present a case of severe calciphylaxis in both thighs and calves in a patient with end-stage renal disease and advanced secondary hyperparathyroidism with successful outcome after modified therapeutic approach. The cause of calciphylaxis is multifactorial. In our case, not only severe hyperparathyroidism and mediocalcinosis, but also medication (warfarin, calcium and active vitamin D) was involved. Because the initial conservative therapy was not successful, we indicated parathyroidectomy. However, we were not able to localize parathyroid glands and we contraindicated bilateral neck exploration due to the patient's critical status. Therefore, we decided for total thyroidectomy with total parathyroidectomy. Surgery was uncomplicated and histology confirmed that all four parathyroid glands were removed. The expected post-operative hypocalcaemia was asymptomatic and we did not use any calcium supplementation or vitamin D. Thyroid hormone replacement was easy. After surgery, the large and multiple subcutaneous defects started to heal. We achieved complete healing within several months of continuing dedicated care. There is no recurrence after three years. Prompt and radical surgical parathyroidectomy was extremely useful in our patient.