COMORBIDITIES AND SYNDEMICS IN THE COVID-19 AGE: CHALLENGES AND OPPORTUNITIES FOR BRINGING SEPARATED BRANCHES OF MEDICINE CLOSER TO EACH OTHER

The Corona Virus Disease 2019 (COVID-19) as a unique disaster has stressed the extreme importance of the three issues for medicine, society and humanity in general: comorbidity, pandemic and syndemic. There are many reasons why the study of comorbidities and syndemics of COVID-19 is of great importance for researchers, clinicians and health policy makers who are responsible for health care organization and funding in a bid to develop more effective and efficient prevention and treatmen t. Thinking about COVID-19 through a syndemics concept and taking biological, psychological, social and spiritual dimensions into account, physicians could be more effective in clinical practice and community-based interventions. The outcome of SARSCoV- 2 infection is determined by the virus-host interaction, with pathogenicity of SARS-CoV-2 being related to the presence of comorbid diseases. The risk for severe COVID-19 clinical manifestations and death increases with age of patients and comorbidity. General mechanisms of multi-system dysfunction and multi-organ damage reported in COVID-19 are probably related to ubiquitous expression of ACE2 in many tissues and its important role in the renin-angiotensin-aldosterone system (RAAS) functioning. Physicians all over the world should be aware of COVID-19 related comorbidities, multisystem disorders and syndemics, as well as treatment and preventive strategies. COVID-19 age is a right time to reconsider the state of science and practice in comorbidity medicine field from the both epistemological and treatment perspective. Comorbidities and multimorbidities are indifferent to medical specializations, so the integrative and complementary medicine is an imperative in the both education and practice. Shifting the paradigm from vertical and mono-morbid interventions to comorbidity, multimorbidity and multi-system disease approaches enhances effectiveness and efficiency of human resources utilization. The aim of this review is to summarize the theoretical concepts and clinical experience and research regarding comorbidity in general, and specifically related to the COVID-19 pandemic, syndemics and infodemic

Abnormal Systolic Blood Pressure during Treadmill Test and Brachial Artery Flow – Mediated Vasodilatation Impairment

The aim of the study was to assess the relationship between systolic blood pressure during maximal treadmill test (SBPmtt) and flow-mediated vasodilation (FMD). Abnormal rise of SBPmtt is the phenomenon more frequent in hypertensive persons but it could be found in normotensive subjects too. 199 subjects referred to treadmill test were enrolled in the study. Four groups were formed: hypertensives with abnormal SBPmtt (group A), hypertensives with normal SBPmtt (group B), normotensives with abnormal SBPmtt (group C) and normotensives with normal SBPmtt (group D). Rise of SBPmtt above 200 mmHg was considered abnormal reaction. Simple linear regression analysis showed significant inverse relationship between SBPmtt and FMD (F=20.2036, p<0.001, R2=0.0956). Mean FMD index was worst in hypertensive subjects with abnormal SBPmtt (group A), followed by normotensives with abnormal SBPmtt (group C), hypertensives with normal SBPmtt (group B) and the best was in normotensives with normal SBPmtt (3.56±5.17, 4.19±5.14, 6.81±8.43 and 10.92±7.48%, respectively). In multivariate regression analysis FMD showed significant association with abnormal SBPmtt (p<0.001) along with brachial artery diameter (p<0.001), male gender (p<0.001), but not with hypertension (p=0.073), BMI (p=0.137) and total cholesterol (p=0.23) (coefficients: –0.26, –0.40, –0.27, –0.13, –0.11 and –0.07, respectively). There was a significant inverse relationship between SBPmtt and FMD. An impairment of FMD exists in normotensive subjects with abnormal SBPmtt. In hypertensives with abnormal SBPmtt an additional impairment of FMD exists when compared to hypertensives with normal SBPmtt. Abnormal SBPmtt should be taken into account in global cardiovascular risk assessment

Variants of ESR1, APOE, LPL and IL-6 loci in young healthy subjects: association with lipid status and obesity

Findings BMI was increased (>25) in 22% of young healthy subjects. Increased cholesterol values (>5.0 mmol/L) were found in 23% of subjects, LDL-C (>3.0 mmol/L) in 23%, triglycerides (>1.7 mmol/L) in 11% of subjects. We found statistically significant differences in subjects' weight (p = 0.015), BMI (p = 0.023), and waist-hip ratio (WHR) (p = 0.015) in regard to their diet type; subjects with Mediterranean diet had the lowest values compared to those on continental and mixed diet. Significant associations were found for: LPL genetic polymorphic variant and abdominal obesity (p = 0.013), APO epsilon4 allele and hypercholesterolemia (p = 0.003), and ESR1-TA long allele and hypercholesterolemia (p = 0.011). ----- Background Human obesity is a multifactorial syndrome influenced also by genetic factors. Among gene variants found to be involved in body weight regulation and development of obesity, particular attention has been paid to polymorphisms in genes associated with obesity-related metabolic disorders. We explored the association of genetic polymorphisms of: estrogen receptor alpha (ESR1-TA repeats); interleukin-6 (IL-6 G-174C); apolipoprotein E (APO epsilon2, epsilon3, epsilon4); lipoprotein lipase Pvu II (LPL P+/-), with clinical variables: gender, age, body mass index (BMI), diet type and biological variables: triglycerides, cholesterol, HDL-C, LDL-C, CRP, homocysteine, urate, and glucose in 105 healthy young subjects (20-35 yrs) of Croatian origin. ----- Methods Genotyping of IL-6, LPL was performed by PCR-RFLP, of APOE by real-time PCR, and of ESR1 by PCR and capillary electrophoresis. Association analyses were performed of alleles and genotypes with biological variables. ----- Conclusion ESR-1, LPL, and APO E genetic polymorphic variants could represent predictive genetic risk markers for obesity-related metabolic disorders in young healthy subjects. Mediterranean type of diet is also an important protective factor against abdominal obesity

The effects of saffron (Crocus sativus L.) on mental health parameters and C-reactive protein: A meta-analysis of randomized clinical trials

Background: The findings of trials investigating the effects of saffron (Crocus sativus L.) supplementation on depression, anxiety, and C-reactive protein (CRP) are inconsistent. The current meta-analysis of randomized controlled trials (RCTs) was carried out to assess the effects of saffron (Crocus sativus L.) administration on mental health parameters and CRP levels. Methods: Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30th July 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Results: Twenty one trials were included in this meta-analysis. Consumption of saffron resulted in a significant reduction in Beck Depression Inventory (BDI) (11 studies with 12 effect size) (WMD: �4.86; 95 CI: �6.58, �3.14), Beck Anxiety Inventory (BAI) (5 studies) (WMD: �5.29; 95 CI: �8.27, �2.31) and Pittsburgh Sleep Quality Index (PSQI) scores (3 studies with 4 effect size) (WMD: �2.22; 95 CI: �2.73, �1.72). Saffron intake did not affect Hamilton Depression Rating Scale (HDRS-D), Hamilton Anxiety Rating Scale (HARS-A) scores and C-reactive protein (CRP) levels. Conclusions: This meta-analysis demonstrated that saffron intake significantly reduced BDI, BAI and PSQI scores, but did not affect HDRS-D, HARS-A scores and CRP levels. © 2019 Elsevier Lt

Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022)

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group

Učinak deksametazona na aktivnost butirilkolinesteraze i lipide plazme u štakora

The paper describes the effect of glucocorticoide dexamethasone (DM) given intraperitoneally on the catalytic activity of butyrylcholinesterase (BuChE) measured in plasma, liver and white adipose tissue of rats of both sexes. Effects of DM on the concentration of plasma lipids and lipoproteins were also tested. Rats were given multiple (2 and 4) pharmacological doses (0.4 and 3.0 mg kg-1 body mass) of DM. All animals were sacrificed 48 h after the last dose. Administration of DM significantly decreased the catalytic activity of BuChE in plasma and liver of all treated groups regardless of sex. BuChE catalytic activity in white adipose tissue differed depending on the dose and frequency of administration. In contrast to liver where both doses caused significant BuChE inhibition, the lower DM dose did not inhibit BuChE activity in adipose tissue, and the inhibition achieved by the higher dose was not as strong as in liver. This result corroborates an earlier hypothesis that BuChE is also synthesized in the adipose tissue. DM significantly increased plasma concentrations of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol and decreased the low-density lipoprotein (LDL) cholesterol concentration. Neither positive correlation between BuChE and triglycerides nor negative correlation between BuChE and HDL was found. Changes in lipid profile during DM treatment were not sex- and time-dependent.U radu su opisani učinci glukokortikoida deksametazona (DM) na katalitičku aktivnost butirilkolinesteraze (BuChE) u plazmi, jetri i bijelom masnom tkivu štakora oba spola. Ispitan je i učinak DM na koncentracije plazmatskih lipida i lipoproteina. Štakori su tretirani višekratno (2 i 4 puta) farmakološkim dozama (0,4 i 3,0 mg kg–1 tjelesne mase) DM koji je primijenjen intraperitonealno. Životinje su žrtvovane 48 sati nakon što su primile zadnju dozu. Utvrđeno je da DM značajno snižava katalitičku aktivnost BuChE u plazmi i jetri štakora oba spola. Rezultati katalitičkih aktivnosti BuChE u bijelom masnom tkivu bili su različiti ovisno o veličini doze i broju aplikacija. Za razliku od jetre, gdje su obje doze izazvale značajnu inhibiciju BuChE, u masnom tkivu niža doza nije inhibirala aktivnost enzima, a inhibicija s višom dozom nije bila tako snažna kao u jetri. Rezultati govore u prilog hipotezi da se BuChE osim u jetri sintetizira i u masnom tkivu. Također je utvrđeno da DM značajno povećava koncentraciju triglicerida, ukupnog kolesterola i HDL-kolesterola, te smanjuje koncentraciju LDL-kolesterola u plazmi. Međutim, nije utvrđena pozitivna korelacija između BuChE i triglicerida, niti negativna korelacija između BuChE i HDL. Promjene koncentracija lipidnih frakcija tijekom primjene DM nisu ovisile o spolu eksperimentalnih životinja niti o trajanju pokusa

Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology

Cardiovascular events remain one of the most frequent causes of mortality and morbidity worldwide. The majority of cardiac events occur in individuals without known coronary artery disease (CAD) and in low- to intermediate-risk subjects. Thus, the development of improved preventive strategies may substantially benefit from the identification, among apparently intermediate-risk subjects, of those who have a high probability for developing future cardiac events. Cardiac computed tomography and myocardial perfusion scintigraphy (MPS) by single photon emission computed tomography may play a role in this setting. In fact, absence of coronary calcium in cardiac computed tomography and inducible ischaemia in MPS are associated with a very low rate of major cardiac events in the next 3-5 years. Based on current evidence, the evaluation of coronary calcium in primary prevention subjects should be considered in patients classified as intermediate-risk based on traditional risk factors, since high calcium scores identify subjects at high-risk who may benefit from aggressive secondary prevention strategies. In addition, calcium scoring should be considered for asymptomatic type 2 diabetic patients without known CAD to select those in whom further functional testing by MPS or other stress imaging techniques may be considered to identify patients with significant inducible ischaemia. From available data, the use of MPS as first line testing modality for risk stratification is not recommended in any category of primary prevention subjects with the possible exception of first-degree relatives of patients with premature CAD in whom MPS may be considered. However, the Working Group recognizes that neither the use of computed tomography for calcium imaging nor of MPS have been proven to significantly improve clinical outcomes of primary prevention subjects in prospective controlled studies. This information would be crucial to adequately define the role of imaging approaches in cardiovascular preventive strategie