WHAT IS STRESS HYPERGLYCEMIA? A SUGGESTION FOR AN IMPROVEMENT OF ITS DEFINITION.

Context: Stress hyperglycemia has been studied in numerous critical illnesses for several decades. Despite the extensive accumulation of knowledge about this topic, the definition of stress hyperglycemia is not updated since 2007. Subjects and Methods: We performed a narrative review about stress hyperglycemia in acute myocardial infarction (AMI), aiming to improve its current definition and to give evidence supporting this. Results: The definition of stress hyperglycemia in 2021 we recommend is: "SH is a high ABGly in an AMI patient irrespective of DM status. It can be calculated as e.g., "stress hyperglycemia ratio" or "admission glucose delta"/"glycemic gap". This definition may serve to start a consensus document of the experts in the field. The evidence accumulates supporting the possibility to recognize stress hyperglycemia also in AMI patients with diabetes mellitus (DM) by calculating glycemia during the previous 2-3 months using glycated hemoglobin. Moreover, it is now obvious that 2007 definition of stress hyperglycemia did not take into account the necessity to separate cut-offs for the subgroups with vs. without DM. Conclusions: We demonstrated the insufficiency of the current 2007 definition of stress hyperglycemia, provided evidence-based recommendation for the improvement and suggested the need for a consensus of the experts on this topic. In order to optimize the treatment of stress hyperglycemia in numerous critical illnesses, we ought to have its universal definition (as we already have the universal definition of AMI).

CUSHING'S SYNDROME, A RISK FACTOR FOR VENOUS THROMBOEMBOLISM IS A CANDIDATE FOR GUIDELINES.

OBJECTIVES: The present paper aims to review important contemporary information about VTE risk in endogenous and exogenous CS, as a substantial discrepancy exists between the results of a recent meta-analysis confirming the increased risk for VTE and the absence of CS in VTE guidelines. METHODS: An extensive search of relevant databases (e.g. PubMed, Google Scholar, and Scopus) was performed in order to establish the interconnectedness of the following terms: Cushing's syndrome, venous thromboembolism, deep vein thrombosis, pulmonary embolism. RESULTS: The analysis demonstrated that patients with CS have about ten times the risk for VTE, particularly during the first year following the diagnosis of CS. Oral glucocorticoid users (with iatrogenic CS) have a 3-fold increase in risk of VTE in comparison with non-users. The most recent 2019 meta-analysis encompassed 7142 patients with endogenous CS (including Cushing's disease) undergoing transsphenoidal surgery or adrenalectomy, and their risk of unprovoked VTE was almost 18 times higher in comparison with a healthy population. CONCLUSION: Over the past 50 years considerable evidence of increased VTE risk in CS has been accumulated. It pertains to both endogenous and exogenous type of CS and has been confirmed in the vast majority, if not all the available studies, including meta-analyses. Nevertheless, official CS guidelines make no mention of CS as a VTE risk factor, even though it is important that not only physicians who treat CS, but also physicians who manage patients with suspected VTE be aware of increased VTE risk.

High likelihood for atrial fibrillation in Cushing's syndrome.

OBJECTIVE: This review analyzes the prevalence of the most important comorbidities associated with atrial fibrillation (AF) in the growing population of patients with Cushing's syndrome (CS). MATERIALS AND METHODS: The review is arranged in a way to list important risk factors for AF and the references, which suggest the significant prevalence of these particular risk factors in CS. The search is conducted on PubMed, Science Direct, Springer, Wiley, SAGE, Oxford Press, and Google Scholar. PubMed search for "Cushing's syndrome atrial fibrillation" on 8/7/2019 revealed 4 papers only. None of them either analyzed or implicated high risk for AF in CS. RESULTS: Arterial hypertension (AHT) can be found in approximately 80% of adult individuals with endogenous CS and in 20% of patients with exogenous CS. The reported prevalence of diabetes mellitus (DM) is from 13% to 47% in CS patients and the risk for de novo DM is approximately two-fold higher in individuals treated with glucocorticoids. High risk for myocardial infarction (MI) with hazard ratio (HR) 3.7 (95% confidence intervals, CI 2.4-5) in patients with endogenous CS was found. In CS patients the obesity can be detected in up to 41% and overweight in 21-48%. Left ventricular hypertrophy (LVH), pulmonary thromboembolism (PTE), infections, and hypokalemia are also more prevalent in CS as compared to healthy population. All cited comorbidities have been associated with AF. Therefore, clustering of the important factors associated with AF is confirmed repeatedly in CS. CONCLUSIONS: The prevalence of AF in CS should be studied more precisely, both in a scientific way and at the individual patient's level.

Pulse Wave Velocity: Retrospective Analysis in a Balkan Normotensive and Hypertensive Population: A Study of 9923 Patients.

We compared pulse wave velocity (PWV) between hypertensive patients and control patients to identify demographics and patient characteristics related to PWV. We retrospectively analyzed 9923 participants (3105 controls and 6818 hypertensive patients) from 5 outpatient hypertensive clinics (in Serbia and Greece). Pulse wave velocity had different distribution between controls and hypertensive patients ( P < .001). The magnitude of PWV increase was related to blood pressure (BP) category (from optimal to stage III hypertension; P < .001). Even in hypertensive patients with systolic BP (SBP) <140 and/or diastolic BP (DBP) <90 mm Hg, PWV was greater than in control patients ( P < .001). Pulse wave velocity was associated with almost all baseline characteristics of hypertensive patients (body mass index [BMI], gender, age, SBP, DBP, smoking status, and heart rate; P < .001). This association remained after adjustment of PWV confounders. There were 2231 (32.7%) hypertensive patients who had reached SBP <140 mm Hg and DBP <90 mm Hg. Pulse wave velocity was increased in hypertensive patients, and the degree of PWV increase was associated with baseline BP as well as with anthropometric parameters (eg, BMI, gender, age, heart rate, and smoking status).

Correlation between ECG changes and early left ventricular remodeling in preadolescent footballers.

The aim of this study was to assess the early electrocardiogram (ECG) changes induced by physical training in preadolescent elite footballers. This study included 94 preadolescent highly trained male footballers (FG) competing in Serbian Football League (minimum of 7 training hours/week) and 47 age-matched healthy male controls (less than 2 training hours/week) (CG). They were screened by ECG and echocardiography at a tertiary referral cardio center. Sokolow-Lyon index was used as a voltage electrocardiographic criterion for left ventricular hypertrophy diagnosis. Characteristic ECG intervals and voltage were compared and reference range was given for preadolescent footballers. Highly significant differences between FG and CG were registered in all ECG parameters: P-wave voltage (p < 0.001), S-wave (V1 or V2 lead) voltage (p < 0.001), R-wave (V5 and V6 lead) voltage (p < 0.001), ECG sum of S V1-2 + R V5-6 (p < 0.001), T-wave voltage (p < 0.001), QRS complex duration (p < 0.001), T-wave duration (p < 0.001), QTc interval duration (p < 0.001), and R/T ratio (p < 0.001). No differences were found in PQ interval duration between these two groups (p > 0.05). During 6-year follow-up period, there was no adverse cardiac event in these footballers. None of them expressed pathological ECG changes. Benign ECG changes are presented in the early stage of athlete's heart remodeling, but they are not related to pathological ECG changes and they should be regarded as ECG pattern of LV remodeling.

Method for the measurement of antioxidant activity in human fluids.

AIM: To develop a new, simple, and cheap method for estimating antioxidant activity in human fluids. METHODS: The assay measured the capacity of the biological fluids to inhibit the production of thiobarbituric acid reactive substances (TBARS) from sodium benzoate under the influence of the free oxygen radicals derived from Fenton's reaction. A solution of 1 mmol/litre uric acid was used as standard. RESULTS: The following mean (SD) antioxidative activities were found (as uric acid) in the various biological fluids: serum, 2.04 (0.20) mmol/litre; urine, 176.5 (25.6) micromol/litre; cerebrospinal fluid, 95.0 (26.9) micromol/litre; aqueous humour oculi, 61.25 (9.9) micromol/litre; saliva, 838.5 (48.2) micromol/litre; tears, 247.0 (17.0) micromol/litre; ascites fluid, 270.0 (63.3) micromol/litre; kidney cyst fluid, 387.1 (28.1) micromol/litre. Small samples of the biological material were needed for the analyses: 10 microl of serum and 50-100 microl of other body fluids. In the sera of 48 healthy individuals there was a significant positive correlation between values obtained with the Randox method (as a reference method) and the new method proposed here (correlation coefficient, 0.8728; mean difference between methods, <0.4%). CONCLUSIONS: This method is easy, rapid, reliable, and practical for the routine measurement of total antioxidant activity in serum and other human body fluids. Small samples of biological material are needed for the analyses and the results are comparable with the reference (Randox) method.

[Immune complexes in diabetes mellitus]. / Imunski kompleksi u dijabetesu melitusu.

Research in recent years has documented more exactly the genetic and immunopathogenetic basis of insulin-dependent diabetes mellitus. Also, in some genetically susceptible subjects, a triggering event activates both cellular and humoral immunity, with diminishing of b cellular mass. Early intervention to prevent diabetes development as well as to prevent microvascular complications is identification of individuals in whom autoimmunity has been activated. One of the non-specific tests is a screening test for the detection of circulating immune complexes /CIC/ by precipitating tests using polyethylene glycol it was performed in series of healthy, insulin-dependent and non-insulin dependent diabetic subjects. Highly increased precitability was seen in a great percentage of pathological sera. In spite of the non-specific method for immune complexes detection, positive results obtained by PEG method generally presumed that diabetes represent immune complex disease.