A Simple Risk Formula for the Prediction of COVID-19 Hospital Mortality.

SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality in hospitalized patients. We aimed to assess the risk factors for hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. A total of 991 patients hospitalized between January 2021 and March 2021 with a PCR-confirmed SARS-CoV-2 acute respiratory infection in two university hospitals and five rural hospitals were included in this analysis. After excluding patients with unknown outcomes, 790 patients entered the final analyses. Out of 790 patients included in the analysis, 282/790 (35.7%) patients died in the hospital; 162/790 (20.5) were male and 120/790 (15.2%) were female. There were 141/790 (18%) patients with mild, 461/790 (58.3%) with moderate, and 187/790 (23.7%) with severe courses of the disease based mainly on the oxygenation status. The best-performing multivariate regression model contains only two predictors-age and the patient's state; both predictors were rendered significant (p < 0.0001). Both age and disease state are very significant predictors of hospital mortality. An increase in age by 10 years raises the risk of hospital mortality by a factor of 2.5, and a unit increase in the oxygenation status raises the risk of hospital mortality by a factor of 20.

Mortality of hospitalized patients with COVID-19: Effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) assessed by propensity score matching, retrospective analysis.

INTRODUCTION: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. METHODS: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching. RESULTS: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality. CONCLUSION: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality.

Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter?

BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.

The frequency of, and predisposing risk factors for, ciprofloxacin-induced neuro-psychiatric adverse drug reactions.

OBJECTIVES: Ciprofloxacin induces rare neuro-psychiatric adverse drug reactions (ADRs) that are, as yet, not possible to predict due to unknown predisposition factors. BACKGROUND: The aim of the analysis was to assess the frequency of neuro-psychiatric ADRs and to identify potential risk factors that predisposed patients to ciprofloxacin neurotoxicity. METHODS: This observational retrospective study involved the evaluation of the medical records of patients in the Nephrology department and 3rd Internal Clinic of the General University Hospital in Prague. RESULTS: The overall incidence of neurological ADRs was 3.6 %. No neurological ADRs developed in patients aged less than 70 years. The covariates that were significantly more prevalent in the patients who developed neuropsychiatric ADRs were as follows: higher age, a history of neuropsychiatric disorders and the use of anticonvulsants. The administration of drugs from other ATC groups, gender, weight, body mass index, body surface area, renal functions, level of C-reactive protein at the beginning of treatment and the total daily dose/kg did not differ significantly between the two groups. CONCLUSION: Ciprofloxacin neuropsychiatric ADRs are more frequent in older patients with a history of neurologic or psychiatric disorders. No other tested covariates were proven to predispose patients to neuropsychiatric ADRs during treatment with ciprofloxacin (Tab. 2, Ref. 20).

Cardiovascular prevention: early and consistent prevention versus late intervention, complex approach to the treatment of modifiable risk factors: hypertension and dyslipidemia.

Cardiovascular diseases (not including COVID-19 infection) are still one of the most common causes of mortality and morbidity in our country and in developed countries. Today no one questions the intervention of all risk factors for atherosclerosis after a cardiovascular event, although unfortunately even in this case the recommended target values are often not achieved. However, the intervention of risk factors in primary prevention is often neglected. Atherosclerosis is a long-term process, developing since the childhood. It is a continuous process and the event itself is only the culmination of this process. Therefore, it is necessary to intervene in key risk factors early in life, and we have ample evidence that even early pharmacological intervention has a clear effect on slowing or stopping the process of atherosclerosis.

Euvascor - early intervention of hypertension and dyslipidaemia (dual combination of atorvastatin and perindopril).

Over the last 30 years, the number of cardiovascular causes of death has decreased, but Cardi-ovascular Disease has been the leading cause of mortality and morbidity in the Czech Republic. In spite of a clear decline, this still persisting primacy is due to the failure to achieve the target recommended values and the late initiation of pharmacotherapy. We know that lifetime LDL cholesterol exposure reduced by 1 mmol/l is associated with a 54% reduction in the incidence of coronary events. A lifetime lower systolic BP of 10 mmHg is associated with a 45% reduction in the incidence of coronary events. Lifetime exposure to a combination of LDL cholesterol lower by 1 mmol/l and systolic BP lower by 10 mm Hg was associated with a 78% reduction in the lifetime risk of coronary events and a 68% reduction in the lifetime risk of a cardiovascular death. The benefits of this intervention increase over time - long-term exposure to even a small difference in LDL cholesterol and systolic pressure can significantly reduce the lifetime risk of cardiovascular disease, if it persists over the time. In this respect, the recently presented new common ESC/ EAS recommendations from 2019, that is to focus treatment on dyslipidemia on a lifelong approach of reducing CV risk and therapeutic lifelong intervention with aim to achieve lower LDL cholesterol levels at all risk levels. Perindorpil antihypertezive and atorvasatin hypolipidemic drugs, ideally in a fixed combination, are able to reduce the patient's CV risk early. The ideal motivation for adherence of patients is the introduced concept of the vascular age, respectively the aging.

Baseline Leptin/Adiponectin Ratio is a Significant Predictor of BMI Changes in Children/Adolescents after Intensive Lifestyle Intervention.

INTRODUCTION: Abdominal obesity is a strong cardiometabolic risk factor that often occurs as early as in childhood. The negative effect of abdominal obesity on the metabolism is partially mediated by changes to the production of the major adipocyte hormones leptin and adiponectin. Leptin/adiponectin imbalance is associated with increased risk of developing obesity and type 2 diabetes mellitus. AIM: To determine whether leptin, adiponectin and the leptin/adiponectin ratio are significant predictors of body weight loss in intensively treated children/adolescents. METHODS: 183 paediatric overweight or obese patients (71 boys and 112 girls), aged 7-16 years, were enrolled in a one-month intensive lifestyle intervention programme. Participants reduced their energy intake and engaged in a supervised exercise programme consisting of 5 physical activity units per day. The subjects were examined both before and after the intervention. RESULTS: The mean BMI decrease achieved was-2.38±0.07 kg/m² (P<0.01). The decrease in plasma leptin concentration was-16.59±0.84 ng/mL (P<0.001) and CRP-0.38±0.04 mg/L (P<0.001). Changes in adiponectin concentrations were not statistically significant. The baseline leptin/adiponectin ratio was a significant predictor of decreases in body weight (P<0.005), BMI (P<0.0001) and waist circumference (P<0.05). CONCLUSION: The leptin/adiponectin ratio at baseline may be a useful predictor of results from interventions focused on decreasing BMIs in children/adolescents.

Body Adiposity Changes After Lifestyle Interventions in Children/Adolescents and the NYD-SP18 and TMEM18 Variants.

BACKGROUND This study was carried out to determine the relationship between the common TMEM-18 (rs4854344, G>T) and NYD-SP18 (rs6971091, G>A) gene variants and weight loss after lifestyle interventions (increased physical activity in conjunction with optimal dietary intake) in overweight/obese children/adolescents. MATERIAL AND METHODS We genotyped 684 unrelated, white, non-diabetic children (age 12.7±2.1 years, average BMI at baseline 30.66±4.80 kg/m²). Anthropometric and biochemical examinations were performed before and after 4 weeks of an intensive lifestyle intervention. RESULTS The mean weight loss achieved was 5.20±2.02 kg (P<0.001). NYDSP-18 AA homozygotes had significantly higher abdominal skinfold value before and after the intervention (both, P=0.001). No significant associations between BMI decrease and the NYD-SP18 and TMEM18 variants were found. Associations between all anthropometrical and biochemical changes and genes remained non-significant after data were adjusted for sex, age, and baseline values. CONCLUSIONS Decreased body weight in overweight/obese children is not significantly influenced by the NYD-SP18 rs6971091 or TMEM18 rs4854344 polymorphisms.

COQ2 polymorphisms are not associated with increased risk of statin-induced myalgia/myopathy in the Czech population.

BACKGROUND: The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS. METHODS: Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci. RESULTS: Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed. CONCLUSIONS: The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.

[A diet suitable for patients with dyslipidemia and metabolic syndrome]. / Dieta pri dyslipidemii a metabolickém syndromu.

Atherosclerosis or cardiovascular disease is the leading cause of mortality and morbidity in developed countries. Intervention of its risk factors is pharmacological but non-pharmacological intervention must be its integral part. Dietary recommendations for dyslipidemia are long known however it is necessary to emphasize the importance of their compliance. Presently, these recommendations for adult population to prevent from atherosclerosis are based on healthy nourishment, especially to have sufficient consumption of fish, fresh vegetable and fruit and to avoid consumption of secondary processed meat especially, i.e. smoked meat. Nowadays, there is a diverting trend from recommendation to strictly avoid cholesterol in the diet.Key works: atherosclerosis - cholesterol - diet intervention - dyslipidemia - fatty acids.

SLCO1B1 polymorphism is not associated with risk of statin-induced myalgia/myopathy in a Czech population.

BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study. MATERIAL/METHODS: SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment. RESULTS: Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis. CONCLUSIONS: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

The Impact of Physical Activity and Dietary Measures on the Biochemical and Anthropometric Parameters in Obese Children. Is There Any Genetic Predisposition?

AIM: The aim of the study was to monitor the importance of laboratory, anthropometric and genetic determination of the presence of risk factors for atherosclerosis, obesity, dyslipidemia and components of the metabolic syndrome in obese children and the response to dietary and regimen interventions in obese children. METHODS: As a part of the study, 353 paediatric patients (46% boys, 54% girls) with obesity and dyslipidemia, aged 8-16 years, participated in a one-month lifestyle intervention programme. The programme involved a reduction of energy intake and supervised exercise programme consisting of 5 exercise units per day, each 50 minutes long. Standard biochemical methods were applied, including Lp-PLA2, as were anthropometric measurements and genetic analyses. RESULTS: During the reduction programme for the children there was a statistically significant decrease in all anthropometric indicators of bodyweight (p<0.001) as well as in lipid parameters and LpLPA2. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight in comparison to non-carriers. CONCLUSION: Child obesity is an important social issue. After regimen interventions, there is weight loss as well as an improvement in biochemical parameters. There are individuals with a genetic predisposition for obesity, as well as individuals with a better response to regimen interventions which could, among other things, be determined by the FTO and MC4R genotypes.

[Non-pharmacological treatment - results from Podebrady]. / Nefarmakologická lécba - výsledky z Podebrad.

OBJECTIVES: The study was aimed to determine risk factors of atherosclerosis after one month lifestyle intervention in overweight/obese children and also FTO and MC4R gene variants associated with obesity. DESIGN AND METHODS: 350 non-diabetic Czech children (age 13.7 ± 2.1 years, 163 ± 10.6 cm hight) was examined. Before and after 4 weeks of lifestyle intervention (comprising a reduction of energy intake), biochemical and anthropometrical measurements were performed. RESULTS: The mean weight loss achieved was 6.2 ± 2.1 kg (P < 0.001). Significant associations between BMI decrease and FTO and MC4R variants were found. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight in comparison to the non-carriers (P < 0.0009 for BMI and P < 0.002 for body weight). The differences remain significant after adjustment for sex age and baseline values (P = 0.004 for BMI and P = 0.01 for body weight). CONCLUSIONS: It is necessary to look for the risk individuals with wrong response to the regime intervention. This individuals is necessary early treat with drugs to prevention clinically complications.Key words: childhood obesity - components of metabolic syndrome - predisposition - response to intervention.

The effect of coenzyme Q10 in statin myopathy.

OBJECTIVES: Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. DESIGN/SETTING: Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. RESULTS: Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 µg/ml to 2.66 µg/ml; p<0.0001). CONCLUSION: After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

Lifestyle modification induced weight loss and changes of cardiometabolic risk factors including lowering of inflammatory response in obese children.

OBJECTIVES: Obesity is associated with increased inflammation which represents a link to atherosclerosis and cardiovascular disease. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent marker of inflammation and atherosclerosis risk. To assess the impact of weight loss on metabolic markers of atherosclerosis including Lp-PLA2 we examined a group of Czech non-diabetic obese/overweight children exposed to a lifestyle intervention. PATIENTS AND METHODS: Fourty unrelated overweight/obese non-diabetic Czech children (13.7 ± 2.1 years, average BMI at baseline 29.8 ± 2.6 kg/m2) underwent 4 weeks of lifestyle modification (reduction of energy intake to age matched optimum and supervised physical activity). Anthropometrical and biochemical variables were determined at baseline and after the intervention. Lp-PLA2 mass concentration was assessed using the ELISA kit. Wilcocson's rank test and Spearman's correlation were used for statistical analysis. RESULTS: A significant decrease of BMI and waist circumference was associated with significant changes of plasma lipoprotein and glycaemia levels. Mass concentration of Lp-PLA2 at the baseline was 402 ± 94 µg/ml, after the intervention 368 ± 105 µg/ml (p=0.008). Change in Lp-PLA2 was associated with triglyceride level decrease (p=0.009). CONCLUSION: Intensive lifestyle modification leading to body weight decrease results in significant changes of plasma lipoprotein levels and, also, a drop of Lp-PLA2 levels in paediatric obese patients. However, even after the intervention Lp-PLA2 concentrations in this patient group remain elevated suggesting possible increased atherosclerosis risk in later life.

APOE polymorphism as a potential determinant of functional fitness in the elderly regardless of nutritional status.

OBJECTIVES: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. MATERIAL AND METHODS: We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. RESULTS: APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. CONCLUSIONS: APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.

Variability in apo(a) gene regulatory sequences, compound genotypes, and association with Lp(a) plasma levels.

OBJECTIVES: Lipoprotein(a) is an independent risk factor of atherosclerosis. DESIGN AND METHODS: We assigned frequencies of six polymorphic sites from apo(a) gene transcription control regions, linkage disequilibrium, and 5-polymorphic compound genotypes association with Lp(a) levels. RESULTS: Significant linkage disequilibrium between polymorphic sites was detected. Compound genotypes were significantly associated with Lp(a) levels (P<0.0001). Major 5-polymorphic genotypes were distributed in a broad range of concentrations. CONCLUSIONS: Major 5-polymorphic compound genotypes are not associated with restricted range of Lp(a) levels.

Detection of variability in apo(a) gene transcription regulatory sequences using the DGGE method.

BACKGROUND: Increased lipoprotein(a), Lp(a), concentration is an independent risk factor for premature atherosclerosis. Apolipoprotein(a), apo(a), determines properties of the lipoprotein and its production rate is the limiting step in Lp(a) particle formation. METHODS: Subjects covering the whole range of Lp(a) concentration were separated into quintiles. A randomly chosen sample from each quintile was derived, there being a total number of 713 individuals. The DGGE method was used to scan the known transcription regulatory regions of apo(a) gene (promoter; DHII and DHIII enhancers) for variability and its distribution across quintiles. RESULTS: Besides 5 previously reported nucleotide substitutions (+121 G>A; +93 C>T; -1712 G>T; -1617 C>A; -1230 A>G) 16 unreported rare sequence variants were detected. All polymorphic variants were distributed throughout the quintiles with several significant differences. The novel +62 C variant was found only among individuals with Lp(a) levels over 16 mg/dl. CONCLUSION: The apo(a) gene transcription regulatory regions were not revealed to be extremely polymorphic. However, we should consider a combined effect of all polymorphic sites from the whole apo(a) gene locus, including the apo(a) gene length polymorphism, when dealing with high population variability of Lp(a) levels.