The Predictors of Early Treatment Effectiveness of Intravitreal Bevacizumab Application in Patients with Diabetic Macular Edema.

The aim of this study was to establish whether multiple blood parameters might predict an early treatment response to intravitreal bevacizumab injections in patients with diabetic macular edema (DME). Seventy-eight patients with non-proliferative diabetic retinopathy (NPDR) and DME were included. The treatment response was evaluated with central macular thickness decrease and best corrected visual acuity increase one month after the last bevacizumab injection. Parameters of interest were the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), vitamin D, and apolipoprotein B to A-I ratio (ApoB/ApoA-I). The NLR (2.03 ± 0.70 vs. 2.80 ± 1.08; p < 0.001), MLR (0.23 ± 0.06 vs. 0.28 ± 0.10; p = 0.011), PLR (107.4 ± 37.3 vs. 135.8 ± 58.0; p = 0.013), and SII (445.3 ± 166.3 vs. 675.3 ± 334.0; p < 0.001) were significantly different between responder and non-responder groups. Receiver operator characteristics analysis showed the NLR (AUC 0.778; 95% CI 0.669-0.864), PLR (AUC 0.628; 95% CI 0.511-0.735), MLR (AUC 0.653; 95% CI 0.536-0.757), and SII (AUC 0.709; 95% CI 0.595-0.806) could be predictors of response to bevacizumab in patients with DME and NPDR. Patients with severe NPDR had a significantly higher ApoB/ApoA-I ratio (0.70 (0.57-0.87) vs. 0.61 (0.49-0.72), p = 0.049) and lower vitamin D (52.45 (43.10-70.60) ng/mL vs. 40.05 (25.95-55.30) ng/mL, p = 0.025). Alterations in the NLR, PLR, MLR, and SII seem to provide prognostic information regarding the response to bevacizumab in patients with DME, whilst vitamin D deficiency and the ApoB/ApoA-I ratio could contribute to better staging.

Serum Levels of S100A8/A9 as a Biomarker of Disease Activity in Patients with IgA Vasculitis.

S100A8/A9 protein is a well-known marker of disease activity or severity in many autoimmune and autoinflammatory diseases, but there have not been many studies about the role of S100A8/A9 in IgA vasculitis (IgAV). The aim of our study was to evaluate S100A8/A9 as a possible biomarker of activity in IgAV. We measured the serum levels of S100A8/A9 in pediatric patients with IgA vasculitis at the onset of the disease, after three months, and after six months. We compared these levels between patients with active disease, remission, and a control group, and assessed their correlation with disease activity and other markers of inflammation. Patients with active disease had significantly higher levels of serum S100A8/A9 (median ± SD) than those in the control group at the beginning of the disease (5740 ± 3157 ng/mL vs. 1447 ± 858.3 ng/mL; p < 0.0001), but also three months and six months after disease onset (p < 0.001). There was a positive correlation between S100A8/A9 serum levels and disease activity (p = 0.0003). Patients with active disease had significantly higher levels of S100A8/A9 than those in remission three months after disease onset (p = 0.0260). There was a correlation between S100A8/A9 and C-reactive protein, the C3 component of complement, ferritin, and fibrinogen. Serum levels of S100A8/A9 were also higher in patients with greater skin areas covered with rash. We demonstrated that serum levels of S100A8/A9 correlated well with disease activity and other biomarkers of inflammation in children with IgAV. According to our results, serum S100A8/A9 may be a good indicator of active disease in IgAV.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

The Importance of Increased Serum GFAP and UCH-L1 Levels in Distinguishing Large Vessel from Small Vessel Occlusion in Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is one of the leading causes of morbidity worldwide, thus, early recognition is essential to accelerate treatment. The only definite way to diagnose AIS is radiological imaging, which is limited to hospitals. However, two serum neuromarkers, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), have been proven as indicators of brain trauma and AIS. We aimed to investigate the potential utility of these markers in distinguishing between large vessel occlusion (LVO) and small vessel occlusion (SVO), considering differences in treatment. Sixty-nine AIS patients were included in our study and divided into LVO and SVO groups based on radiological imaging. Control group consisted of 22 participants without history of neurological disorders. Results showed differences in serum levels of both GFAP and UHC-L1 between all groups; control vs. SVO vs. LVO (GFAP: 30.19 pg/mL vs. 58.6 pg/mL vs. 321.3 pg/mL; UCH-L1: 117.7 pg/mL vs. 251.8 pg/mL vs. 573.1 pg/mL; p < 0.0001), with LVO having the highest values. Other prognostic factors of stroke severity were analyzed and did not correlate with serum biomarkers. In conclusion, a combination of GFAP and UCH-L1 could potentially be a valuable diagnostic tool for differentiating LVO and SVO in AIS patients.

Serum Adropin Levels and Body Mass Composition in Kidney Transplant Recipients-Are There Sex Differences?

Adropin is a secretory peptide that regulates glucose, lipid, and protein metabolism, which is closely related to obesity, insulin resistance, dyslipidemia, and atherogenesis. The serum adropin level is related to sex and depends upon nutritional preferences. This study aims to determine the association between serum adropin levels and body composition parameters in kidney transplant recipients (KTRs), especially emphasizing sex differences. Our case-control study involved 59 KTRs (28 postmenopausal women and 31 men) who were divided into two groups according to sex, and each group of those KTRs was further divided into higher or lower adropin values than the mean value in each sex group. Univariate regression showed a negative association of adropin levels with most anthropometric and body composition parameters in men's KTRs. Contrary to this, the serum adropin level was negatively associated only with phase angle in postmenopausal female KTRs. Multivariate regression showed that skeletal muscle mass and phase angle were the only negative predictors in women's KTRs, whereas in men, negative predictors were BMI and body water. These findings imply that adropin could have a different impact on metabolic homeostasis in KTRs regarding sex and could be considered a negative predictor of body composition in KTRs.

Association between Salivary Cortisol and α-Amylase with the Psychological Profile of Patients with Oral Lichen Planus and Burning Mouth Syndrome: A Case-Control Study.

The aim of our study was to assess the relationship between the concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and the psychological profile of patients with oral lichen planus (OLP) and primary burning mouth syndrome (BMS). A total of 160 subjects participated in this case-control study: 60 patients with OLP; 60 patients with primary BMS; and 40 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 a.m. Salivary biomarkers were analyzed by enzyme-linked immunosorbent assays (ELISAs). Psychological assessment was evaluated with the Depression, Anxiety, and Stress Scale (DASS-21). The patients with primary BMS had higher salivary cortisol concentrations and α-amylase activity (0.52 vs. 0.44 µg/dL; 160,531 vs. 145,804 U/L; one-way analysis of variance (ANOVA) with post hoc Scheffe test) compared with patients with OLP. The patients with primary BMS had statistically significant higher scores for depression, anxiety, and stress compared with patients with OLP and control subjects (p < 0.001, Kruskal-Wallis test). There was a strong positive correlation between anxiety and depression, stress and depression, and stress and anxiety in patients with OLP and BMS (p < 0.001 and p < 0.001, respectively; Spearman's correlation). There was a good positive correlation between symptom intensity (pain/burning) and psychological profile (depression, anxiety, stress) in patients with primary BMS (r = 0.373, p = 0.003; r = 0.515, p < 0.001; r = 0.365, p = 0.004, respectively; Spearman's correlation). This case-control study is the first to compare the psychoendocrinological profile of patients with two different oral diseases. The patients with BMS showed a higher concentration/activity of salivary stress biomarkers (cortisol, α-amylase) and a stronger association with mental disorders compared with patients with OLP. However, an interdisciplinary psychoneuroimmunological approach is equally important in both patient groups (OLP and BMS), regardless of whether mental disorders are the cause or the consequence.

Larger splenic emptying correlate with slower EPOC kinetics in healthy men and women during supine cycling.

PURPOSE: The present study investigated whether larger splenic emptying augments faster excess post-exercise O2 consumption (EPOC) following aerobic exercise cessation. METHODS: Fifteen healthy participants (age 24 ± 4, 47% women) completed 3 laboratory visits at least 48-h apart. After obtaining medical clearance and familiarizing themselves with the test, they performed a ramp-incremental test in the supine position until task failure. At their final visit, they completed three step-transition tests from 20 W to a moderate-intensity power output (PO), equivalent to [Formula: see text]O2 at 90% gas exchange threshold, where data on metabolic, cardiovascular, and splenic responses were recorded simultaneously. After step-transition test cessation, EPOCfast was recorded, and the first 10 min of the recovery period was used for further analysis. Blood samples were collected before and immediately after the end of exercise. RESULTS: In response to moderate-intensity supine cycling ([Formula: see text]O2 = ~ 2.1 L·min-1), a decrease in spleen volume of ~ 35% (p = 0.001) was observed, resulting in a transient increase in red cell count of ~ 3-4% (p = 0.001) in mixed venous blood. In parallel, mean blood pressure, heart rate, and stroke volume increased by 30-100%, respectively. During recovery, mean τ[Formula: see text]O2 was 45 ± 18 s, the amplitude was 2.4 ± 0.5 L·min-1, and EPOCfast was 1.69 L·O2. Significant correlations were observed between the percent change in spleen volume and (i) EPOCfast (r = - 0.657, p = 0.008) and (ii) τ[Formula: see text]O2 (r = - 0.619, p = 0.008), but not between the change in spleen volume and (iii) [Formula: see text]O2 peak (r = 0.435, p = 0.105). CONCLUSION: Apparently, during supine cycling, individuals with larger spleen emptying tend to have slower [Formula: see text] O2 recovery kinetics and a greater EPOCfast.

Effects of CBD supplementation on ambulatory blood pressure and serum urotensin-II concentrations in Caucasian patients with essential hypertension: A sub-analysis of the HYPER-H21-4 trial.

HYPER-H21-4 was a randomized crossover trial that aimed to determine if cannabidiol (CBD), a non-intoxicating constituent of cannabis, has relevant effects on blood pressure and vascular health in patients with essential hypertension. In the present sub-analysis, we aimed to elucidate whether serum urotensin-II concentrations may reflect hemodynamic changes caused by oral supplementation with CBD. The sub-analysis of this randomized crossover study included 51 patients with mild to moderate hypertension that received CBD for five weeks, and placebo for five weeks. After five weeks of oral CBD supplementation, but not placebo, serum urotensin concentrations reduced significantly in comparison to baseline (3.31 ± 1.46 ng/mL vs. 2.08 ± 0.91 ng/mL, P < 0.001). Following the five weeks of CBD supplementation, the magnitude of reduction in 24 h mean arterial pressure (MAP) positively correlated with the extent of change in serum urotensin levels (r = 0.412, P = 0.003); this association was independent of age, sex, BMI and previous antihypertensive treatment (ß ± standard error, 0.023 ± 0.009, P = 0.009). No correlation was present in the placebo condition (r = -0.132, P = 0.357). In summary, potent vasoconstrictor urotensin seems to be implicated in CBD-mediated reduction in blood pressure, although further research is needed to confirm these notions.

Diagnostic Utility of Serum Leucine-Rich α-2-Glycoprotein 1 for Acute Appendicitis in Children.

PURPOSE: The aim of this study is to assess the diagnostic utility of serum leucine-rich α-2-glycoprotein 1 (LRG1) in pediatric patients with acute abdominal pain, admitted to the emergency surgical unit, in order to make a prompt and accurate diagnosis of acute appendicitis. PATIENTS AND METHODS: Pediatric patients older than 5 years of age who presented to the emergency department from 15 October 2021 to 30 June 2022 with acute abdominal pain and suspected acute appendicitis were prospectively recruited in the study. Demographic and clinical data, as well as operative and postoperative data, were recorded. A total of 92 patients were equally distributed into two groups: children with acute appendicitis who underwent laparoscopic appendectomy and non-appendicitis patients, presenting with non-specific abdominal pain. LRG1 levels were determined using a commercially available LRG1 enzyme-linked immunosorbent assay (ELISA) kit. Serum LRG1 levels, as well as other inflammatory markers (white blood cell count (WBC), C-reactive protein (CRP) and absolute neutrophil count) were compared between groups. RESULTS: The median level of LRG1 in serum was significantly higher in the group of children with pathohistologically confirmed acute appendicitis than in the control group, at 350.3 µg/mL (interquartile range (IQR) 165.2-560.3) and 25.7 µg/mL (IQR 14.7-36.8) (p < 0.001), respectively. Receiver operating characteristic area under the curve for LRG1 from serum was 1.0 (95% CI 0.96-1.00; p < 0.001) and the value of >69.1 µg/mL was found to perfectly separate acute appendicitis cases from controls. Additionally, as expected, each of the examined laboratory inflammatory markers provided a significantly higher values in the acute appendicitis group compared to the control group: WBC 14.6 × 109/L (IQR 12.7, 18.7) vs. 7.0 × 109/L (IQR 5.4, 9.0) (p < 0.001), CRP 16.3 mg/dL (IQR 6.9, 50.4) vs. 2.2 mg/dL (IQR 2, 2) (p < 0.001) and absolute neutrophil count 84.6% (IQR 79.5, 89.0) vs. 59.5% (IQR 51.5, 68.6) (p < 0.001). CONCLUSIONS: LRG1 in the serum was found to be a promising novel biomarker, with excellent differentiation of acute appendicitis from non-appendicitis cases in children presenting with non-specific abdominal pain.

Diagnostic Accuracy of Leucine-Rich α-2-Glycoprotein 1 as a Non-Invasive Salivary Biomarker in Pediatric Appendicitis.

The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who presented with acute abdomen and suspected acute appendicitis were enrolled in this prospective study. The parameters documented included demographic and clinical information, as well as operative and postoperative data. Patients were divided into two groups: those with acute appendicitis who underwent laparoscopic appendectomy (n = 46) and those without appendicitis (n = 46). The total white blood cell (WBC) count, percent of neutrophils, C-reactive protein (CRP) level, and salivary LRG1 were compared between groups. A commercially available enzyme-linked immunosorbent assay (ELISA) LRG kit was used to measure the LRG levels. The median salivary LRG1 level was significantly higher in the group of children with pathohistologically confirmed acute appendicitis compared to the control group: 233.45 ng/mL (IQR 114.9, 531.2) vs. 55.95 ng/mL (IQR 51.5, 117.9), p < 0.001. LRG1 had an overall good receiver-operator characteristic area under the curve of 0.85 (95% CI 0.76-0.92; p < 0.001). The optimal LRG1 cutoff with best separation between acute appendicitis and the controls was >352.6 ng/mL (95% CI from >270.7 to >352.6). Although the specificity was 100% at this cutoff, the sensitivity for identifying appendicitis was 36%. In addition, a significant difference was found between groups in the laboratory values of all inflammatory markers tested: WBC, absolute neutrophil count, and CRP (p < 0.001 for all). Although LRG1 in saliva showed a good AUC parameter and significantly higher values in patients with acute appendicitis compared to the controls, its usefulness in the patient population who present at emergency departments with abdominal pain is debatable. Future studies should focus on investigating its diagnostic potential.

CBD supplementation reduces arterial blood pressure via modulation of the sympatho-chromaffin system: A substudy from the HYPER-H21-4 trial.

Data concerning the effects of cannabidiol (CBD) on blood pressure (BP) is controversial. HYPER-H21-4 was a randomized, placebo-controlled, crossover trial which sought to elucidate if 5-week administration of CBD will reduce BP in hypertensive patients. In the substudy of this trial, we aimed to establish the mechanistic background of CBD-induced BP reduction. Specifically, we explored the dynamic of catestatin, a sympathoinhibitory peptide implicated in the pathophysiology of hypertension. In the present analysis, 54 patients with Grade 1 hypertension were included. 5-week administration of CBD but not placebo reduced serum catestatin concentration in comparison to baseline (13.50 [10.85-19.05] vs. 9.65 [6.37-12.26] ng/mL, p < 0.001). Serum catestatin levels at the start of the treatment period demonstrated a negative correlation with the extent of reduction in mean arterial pressure (r = -0.474, p < 0.001). Moreover, the extent of change in catestatin serum levels showed a strong correlation with the extent of mean arterial pressure reduction (r = 0.712, p < 0.001). Overall, the results of the present study imply that the antihypertensive effects of CBD may be explained by its interaction with the sympatho-chromaffin system, although further research is warranted.

Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation.

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.

Association between Brain Injury Markers and Testosterone in Critically-Ill COVID-19 Male Patients.

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18−65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4−366.4) vs. 146.4 (92.5−243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2−40.1) vs. 29.8 (21.8−39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = −0.452, p < 0.001; r = −0.430, p < 0.001 and r = −0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients.

Serum Catestatin Levels Correlate with Ambulatory Blood Pressure and Indices of Arterial Stiffness in Patients with Primary Hypertension.

Accumulating data suggests that catestatin, an eclectic neuroendocrine peptide, is involved in the pathophysiology of primary hypertension (PH). Nevertheless, clinical studies concerning its role in PH are still scarce. Therefore, in the present study, we aimed to explore an association between serum catestatin levels, ambulatory blood pressure (BP) and arterial stiffness in patients with PH and healthy controls. In this single-center study, 72 patients aged 40−70 diagnosed with PH, and 72 healthy controls were included. In patients with PH, serum catestatin concentrations were significantly higher in comparison to the healthy controls (29.70 (19.33−49.48) ng/mL vs. 5.83 (4.21−8.29) ng/mL, p < 0.001). Untreated patients had significantly higher serum catestatin than patients treated with antihypertensive drugs (41.61 (22.85−63.83) ng/mL vs. 24.77 (16.41−40.21) ng/mL, p = 0.005). Multiple linear regression analysis showed that serum catestatin levels retained a significant association with mean arterial pressure (ß ± standard error, 0.8123 ± 0.3037, p < 0.009) after model adjustments for age, sex and body mass index. Finally, catestatin levels positively correlated with pulse wave velocity (r = 0.496, p < 0.001) and central augmentation index (r = 0.441, p < 0.001), but not with peripheral resistance. In summary, increased serum catestatin concentration in PH, predominantly in the untreated subgroup, and its association with ambulatory BP and arterial stiffness address the role of this peptide in PH.

Laboratory policies and practices for thyroid function tests in Croatia: survey on behalf of Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: Laboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and postanalytical practices and policies in Croatia. Materials and methods: Working Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions. Results: Fifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer's declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer's reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles). Conclusion: This survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.

Prognostic Value of Catestatin in Severe COVID-19: An ICU-Based Study.

Catestatin is a pleiotropic peptide with a wide range of immunomodulatory effects. Considering that patients with a severe COVID-19 infection have a major immunological dysregulation, the aim of this study was to evaluate catestatin levels in patients with COVID-19 treated in the intensive care unit (ICU) and to compare them between the fatal and non-fatal outcomes. The study included 152 patients with severe COVID-19, out of which 105 had a non-fatal outcome and 47 had a fatal outcome. Serum catestatin levels were estimated by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. The results show that catestatin levels were significantly lower in the fatal group compared to the non-fatal group (16.6 ± 7.8 vs. 23.2 ± 9.2 ng/mL; p < 0.001). Furthermore, there was a significant positive correlation between serum catestatin levels and vitamin D levels (r = 0.338; p < 0.001) while there was also a significant positive correlation between serum catestatin levels and growth differentiation factor-15 (GDF-15) levels (r = −0.345; p < 0.001). Furthermore, multivariate logistic regression showed that catestatin, GDF-15 and leukocyte count were significant predictors for COVID-19 survival. These findings imply that catestatin could be playing a major immunomodulatory role in the complex pathophysiology of the COVID-19 infection and that serum catestatin could also be a predictor of a poor COVID-19 outcome.

Dynamic of Serum TWEAK Levels in Critically Ill COVID-19 Male Patients.

Although the number of cases and mortality of COVID-19 are seemingly declining, clinicians endeavor to establish indicators and predictors of such responses in order to optimize treatment regimens for future outbreaks of SARS-CoV-2 or similar viruses. Considering the importance of aberrant immune response in severe COVID-19, in the present study, we aimed to explore the dynamic of serum TNF-like weak inducer of apoptosis (TWEAK) levels in critically-ill COVID-19 patients and establish whether these levels may predict in-hospital mortality and if TWEAK is associated with impairment of testosterone levels observed in this population. The present single-center cohort study involved 66 men between the ages of 18 and 65 who were suffering from a severe type of COVID-19. Serum TWEAK was rising during the first week after admission to intensive care unit (ICU), whereas decline to baseline values was observed in the second week post-ICU admission (p = 0.032) but not in patients who died in hospital. Receiver-operator characteristics analysis demonstrated that serum TWEAK at admission to ICU is a significant predictor of in-hospital mortality (AUC = 0.689, p = 0.019). Finally, a negative correlation was found between serum TWEAK at admission and testosterone levels (r = -0.310, p = 0.036). In summary, serum TWEAK predicts in-hospital mortality in severe COVID-19. In addition, inflammatory pathways including TWEAK seem to be implicated in pathophysiology of reproductive hormone axis disturbance in severe form of COVID-19.

Effects of Moderate Consumption of Red Wine on Hepcidin Levels in Patients with Type 2 Diabetes Mellitus.

Iron overload is often associated with type 2 diabetes (T2D), indicating that hepcidin, the master regulator of iron homeostasis, might be involved in diabetes pathogenesis. Alcohol consumption may also result in increased body iron stores. However, the moderate consumption of wine with meals might be beneficial in T2D. This effect has been mainly attributed to both the ethanol and the polyphenolic compounds in wine. Therefore, we examined the effects of red wine on hepcidin in T2D patients and non-diabetic controls. The diabetic patients (n = 18) and age- and BMI-matched apparently healthy controls (n = 13) were men, aged 40−65 years, non-smoking, with BMI < 35 kg/m2. Following a 2-week alcohol-free period, both groups consumed 300 mL of red wine for 3 weeks. The blood samples for the iron status analysis were taken at the end of each period. The red wine intake resulted in a decrease in serum hepcidin in both the diabetic subjects (p = 0.045) and controls (p = 0.001). The levels of serum ferritin also decreased after wine in both groups, reaching statistical significance only in the control subjects (p = 0.017). No significant alterations in serum iron, transferrin saturation, or soluble transferrin receptors were found. The suppression of hepcidin, a crucial iron-regulatory hormone and acute-phase protein, in T2D patients and healthy controls, is a novel biological effect of red wine. This may deepen our understanding of the mechanisms of the cardiometabolic effects of wine in T2D.

Laboratory medicine in pandemic of COVID-19.

After the outbreak in China in the year 2019, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) quickly spread around the world causing a protracted pandemic. Approximately one-third of infections appear to be asymptomatic. Symptomatic disease is characterized primarily by symptoms of respiratory tract infection of varying severity. But Coronavirus Disease 2019 (COVID-19) is much more than an acute respiratory disease because SARS-CoV-2 affects many organs inducing a vast number of symptoms such as cardiovascular, neurological, gastrointestinal, dermatological, with numerous complications. Short and long-term effects of infection, severe ones, and especially mild forms of the disease which affect a huge number of patients need to be further investigated. Laboratory medicine has a crucial role in early diagnosis of the disease, recognition of the patients who need hospital care, and close monitoring of hospitalized patients to timely identify associated clinical complications as well as follow-up of patients with long-term COVID-19.