Murat Kizilgun

Hypoxic-ischemic encephalopathy (HIE) is a type of brain injury caused by a lack of oxygen to the brain during the neonatal period. In this study, the effect of therapeutic hypothermia (TH) on the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome and related molecules in neonates with HIE was investigated. Objective: We aimed to investigate inflammasomes and related molecules in neonates with HIE. Patients and Method: Prospective single-center study of NLRP3 inflammasome and related molecules in term neonates with HIE exposed to therapeutic hypothermia. Peripheral venous blood samples for NLRP3, IL1-β, TAS, TOS, OSI, IL-18, and Caspase-1 measurements were obtained immediately after birth, before, and within 24 hours after TH in infants with HIE treated with therapeutic hypothermia. Results: Results were compared between the healthy newborn and HIE groups. During the study period, 46 neonates in the HIE group and 46 neonates in the healthy newborn group were included in the study. It was observed that NLRP3, Caspase-1, IL1-β, IL-18, TOS, and OSI values increased significantly before TH and decreased significantly after TH (p<0.05). It was found that the TAS value was significantly lower in patients with HIE before TH, but it increased significantly after TH and came closer to the value of the healthy group (p<0.05). Conclusions: NLRP3, IL-1β, IL-18, Caspase-1, TOS, and OSI levels decreased during TH, whereas TAS levels increased. Our findings suggest that TH may be associated with changes in NLRP3 inflammasome-related biomarkers.

Objectives The signaling pathways activated in periodontitis is important to treat or to prevent the disease. Recent data have established the role of inflammasomes in periodontitis. The purpose of this study was to determine the concentrations of NLRP3, IL-1β, IL-18, Caspase-1, and Nrf2 in gingival-crevicular-fluid (GCF) from patients with Stage3 periodontitis following nonsurgical-periodontal-treatment (NSPT), to compare them with clinical periodontal parameters, and to evaluate these parameters as potential biomarkers of response to NSPT. Methods A total of 129 individuals (Healthy, n:64; periodontitis, n:65) involved in the study. GCF was collected from the distal and mesial regions of 5 single-rooted anterior teeth and clinical periodontal parameters [plaque index(PI), bleeding-on-probing(BOP), probing-pocket-depth(PPD) and clinical-attachment-loss(CAL)] were obtained before and 6 month after NSPT. Levels of biochemical parameters (NLRP3, IL-18, IL-1β, Caspase-1 and Nrf2) were evaluated in GCF samples by ELISA. Results All biochemical and clinical periodontal parameters decreased significantly in the periodontitis group after NSPT (P < 0.001). Except for PI, IL-1β and IL-18, all parameters were significantly higher in the Post-Treatment groups compared to the Healthy group (P < 0.001). IL-1β and IL-18 reached healthy levels with 6-month follow-up of NSPT. All biochemical parameters were significantly correlated with full-mouth clinical periodontal parameters in the Pre-Treatment and Post-Treatment groups (P < 0.01). Conclusion The tested biochemical parameters play important roles in the pathogenesis of periodontitis. IL-1β and IL-18 support their potential as clinically important biomarkers for treatment monitoring. Elevated levels of NLRP3, Caspase-1, and Nrf2 may indicate ongoing inflammatory activity rather than complete resolution after treatment. Clinical applicability must be confirmed by larger, longitudinal studies using advanced molecular techniques. Clinical Relevance Monitoring the decrease of IL-1β and IL-18 with NSPT in GCF samples may indicate that these markers are promising treatment follow-up biomarkers.

Purpose: This study investigated the predictive value of thyroid hormones in septic patients. Materials and Methods: Our study was conducted in patients with sepsis in intensive care unit (ICU). Free triiodothyronine (fT3) and free thyroxine (fT4) levels taken at the time of hospitalization and at the 48th hours were measured and the fT3 / fT4 ratio was calculated. Calculated fT3 and fT4 change between first and 48th hours. Results: 192 patients with sepsis were included in the study. In non-survivor patients, first fT3 (1.60±0.57 ng/dL v.s. 2.01±0.41 ng/dL) and fT3 / fT4 ratio (1.34±0.88 v.s. 1.79±0.91) were found to be significantly lower than 48th hours fT3 (0.77±0.39 ng/dL v.s. 1.87±0.49 ng/dL) and fT3 / fT4 ratio (0.60±0.51 v.s. 1.66±1.21) survivors. It was found that the first fT3 levels (-0.83±0.45 v.s. -0.23±0.14) and fT3 / fT4 ratio (-0.73±0.62 v.s. -0.12±0.11) decreased significantly more at 48th hour in non-survivors than survivors. The 48th hours fT3 level and the change in fT3 between the first and 48th hour were found to be the most significant parameters for the mortality indicator. Conclusion: fT3 / fT4 ratio has predictive value for mortality in patients with sepsis in ICU. In addition, fT3 was found to be an indicator for mortality predictivity both at admission and at 48th hours.

Background: More than 768 million people have been affected by COVID-19. Identifying lymphocyte subsets and cytokine level abnormalities in COVID-19 patients is essential to gain new insights and data on immunity mechanisms against viral infections. Objectives: We used flow cytometry to determine the relationship between disease severity, lymphocyte subsets distribution, and cytokine level alterations in COVID-19 patients. Methods: Totally 94 COVID-19 patients (32 mild, 31 moderate, and 31 severe) and 27 healthy individuals were included in the cross-sectional study. The distribution of peripheral lymphocyte subsets and cytokine levels was assessed by flow cytometry. Results: The percentages of CD56+ natural killer (NK) cells in all patient groups and total T lymphocytes in moderate and severe groups were significantly lower than those in the control group (P < 0.001). Also, IL-2 (P < 0.001), IL-17A (P < 0.001), IL-4 (P < 0.001), IL-6 (P < 0.001), TNF-α (P = 0.004), IP-10 (P < 0.001), IFN-λ1 (IL-29) (P < 0.001), IFN-λ2/3 (IL-28A/B) (P = 0.011), IFN-β (P < 0.001), IL-10 (P < 0.001), and IFN-γ (P < 0.001) levels were statistically higher in patients than in the controls. Conclusions: Our data revealed that increased levels of certain cytokines in peripheral blood contribute to disease severity. Increased CRP (OR: 1.012, %95 CI: 1.002 - 1.023, P = 0.038) and IL-10 (OR: 1.068, %95 CI: 1.000 - 1.141, P = 0.049) levels, decreased CD56+ NK percentage (OR: 0.576, %95 CI: 0.376 - 0.882, P = 0.011) and lymphocyte count (OR: 0.02, %95 CI: 0.001 - 0.368, P = 0.009), and the presence of diabetes mellitus and mechanical ventilation were independent predictors of mortality.

Objective A Disintegrin and Metalloproteinase with Thrombospondin-9 (ADAMTS-9), one of the ADAMTS enzymes, is expressed in all fetal tissues, unlike other ADAMTS enzymes, and is thus thought to play a role in fetal development. In this context, the objective of this study is to investigate the relationship between ADAMTS-9 activity and the development of congenital heart diseases (CHD) with a view to using ADAMTS-9 level as a biomarker for CHDs. Study Design Newborns diagnosed with CHD and healthy newborns were included in the study as the CHD and control groups, respectively. Gestational age, maternal age, and mode of delivery information pertaining to the mothers and Apgar score and birthweight information pertaining to the newborns were recorded. Blood samples were taken from all newborns to determine their ADAMTS-9 levels in the first 24 hours of life. Results Fifty-eight newborns with CHD and 46 healthy newborns were included in the study. Median ADAMTS-9 levels were 46.57 (interquartile range [IQR]: 33.31 [min: 26.92, max: 124.25]) and 23.36 (IQR: 5.48 [min: 11.7, max: 37.71]) ng/mL in the CHD and control groups, respectively. ADAMTS-9 levels in the CHD group were statistically significantly higher than in the control group (p = 0.000). ADAMTS-9 levels of the CHD and control groups were analyzed by the receiver operating characteristics curve. The area under the curve value for ADAMTS-9 levels of >27.86 ng/mL as the cut-off value for predicting the development of CHD in newborns was 0.836 (95% confidence interval [CI]: 0.753–0.900, p = 0.0001). ADAMTS-9 levels of >27.86 ng/mL were determined to predict the development of CHD in newborns with a sensitivity of 77.78% (95% CI: 65.5–87.38) and a specificity of 84.78% (95% CI: 71.1–93.60). Conclusion In conclusion, it was found that the serum ADAMTS-9 levels were significantly higher in newborns with CHD than in healthy newborns. In parallel, ADAMTS-9 levels above a certain cut-off value were associated with CHD. Key Points

Purpose: There are not enough studies evaluating the change in electrolytes and hormones in patients with sepsis. The aim of our study is to evaluate the relationship between the changes in serum calcium (Ca), magnesium (Mg), phosphorus (P), 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) levels and mortality in patients with sepsis. Materials and Methods: Our study was conducted on patients with sepsis who were hospitalized in the intensive care unit (ICU) between October 2017 and January 2019. The levels of Ca, Mg, P, 25(OH)D and PTH, together with demographic and clinical characteristics of non-survivor and survivor patients, were compared. Results: A total of 225 patients were enrolled into the study. Of the 225 patients, 94 patients (41.2%) died and 131 patients (58.8%) were discharged. PTH and P levels were found to be significantly higher, and 25(OH)D, Ca, and Mg levels were significantly lower in non-survivor patients than in survivor patients. Conclusions: During sepsis, the change in Ca metabolism which is in a delicate balance, in the direction of hypocalcemia, hypomagnesemia, hyperphosphatemia, low 25(OH)D and high PTH were found to be associated with mortality.

Objectives The objective of this study is to investigate the cardiovascular risk factors associated with metabolic syndrome (MetS), which is increasingly becoming prevalent in childhood obesity. Methods A total of 113 patients, 76 of whom were between the ages of 10 and 17 (mean age: 14.5 ± 1.8 years) and diagnosed with obesity (30 non-MetS and 46 MetS using IDF) and 37 of whom constituted the control group, participated in the study. Echocardiographic examination and atherogenicity parameters (Atherogenic index of plasma [AIP: logTG/HDL], total cholesterol/HDL, and TG/HDL ratio and non-HDL) were evaluated. Results The most common component accompanying obese MetS was found to be hypertension and low HDL. While obesity duration, body mass index (BMI), blood pressure, fasting insulin, insulin resistance, atherogenicity parameters were determined to be significantly higher in the obese-MetS group. Echocardiography showed that while the thickness, volume, and diameter of LV end-diastolic wall, left ventricular mass (LVM), LVM index (LVMI g/m 2 ) and relative wall thickness (RWT) were significantly high in the MetS group, however, mitral E/A ratio was significantly lower (p<0.05). Change in LV geometry consistent with concentric remodeling (increased RWT, normal LVMI) was visible in obese groups. LVM were positively significantly related to BMI, waist circumference, insulin resistance, blood pressure, LDL level, and negative to mitral E/A ratio. In the obese-MetS group, LVMI was positively correlated to office systolic BP, left atrium end-diastolic volume/index. Conclusions LVMI and atherogenicity parameters that were found to be significantly higher in obese MetS exhibit increased cardiovascular risk in childhood.