Association between hyponatremia, inflammation, and mortality in patients undergoing peritoneal dialysis: A nationwide observations.

INTRODUCTION: Hyponatremia is the most common electrolyte disorder often present in peritoneal dialysis (PD) patients. The aim of this retrospective study was to investigate the effect of hyponatremia on mortality in patients undergoing PD. METHODS: The health records of adult individuals with an inserted PD catheter identified via the centralized national e-health database were used. RESULTS: The mean age of the 846 patients included in the study was 52.48 years (±14.6). The mean sodium level was 136.51 mEq/L. Sodium levels <137 mEq/L were associated with higher death risk independent of comorbidities. There was a 0.821 times less reduction in mortality for each mEq /L increase in serum sodium. CONCLUSION: Our study provides evidence that monitoring and adjusting serum sodium levels is crucial in managing PD patients with hyponatremia, as low serum sodium level was found to be a significant and independent predictor of mortality.

Cost analysis of 25-hydroxy vitamin D tests in Turkiye with big data: A cross-sectional study.

OBJECTIVE: The high prevalence of vitamin D deficiency in the population causes physicians to request more vitamin D tests and increases laboratory costs. It is aimed at investigating the demanded numbers and cost analyzes of 25-hydroxyvitamin D (25(OH)D) tests with the big data obtained from the national information health system of the Turkish Ministry of Health. METHODS: Between 2017 and 2018, all inpatient and outpatient tests and 25(OH)D tests in all medical biochemistry laboratories in Turkiye were determined based on department and institution type. The cost amount, distribution among health institutions, and test request rates were calculated. In both years, the top ten most expensive tests, according to health institutions, were evaluated. RESULTS: The total number of medical biochemistry tests performed in 2017 and 2018 was 1.424.948.155 and 1.713.134.326, respectively. The number of 25 (OH)D tests analyzed in the same years was 8.698.393 and 13.919.127, respectively. When the data of the 2 years are compared, the consumption of 25 (OH)D tests increased by 37% in General hospital laboratories, whereas it increased by 115.09% in primary health laboratories. When all health institutions were evaluated, the increase rate in 25 (OH)D test demand was 60%, while the cost increase rate was 23%. CONCLUSION: This report showed that the demands for 25(OH)D testing are increasing steeply, especially in primary health-care facilities. In this direction, laboratory information system test demand restrictions in accordance with national and international guidelines are important issues for policymakers.

Hypertriglyceridemia and its impact on hematological indicators: A study based on Turkish national health database.

OBJECTIVE: The hematocrit (Hct) to hemoglobin (Hb) ratio, generally at 3.0 in healthy individuals, can vary in certain disease states. An emerging area of interest is the potential influence of triglyceride concentrations on this ratio and hemoglobin A1C (HbA1c) levels. This study aimed to identify the changes in HbA1c and the Hct/Hb ratio as triglyceride concentration increases. METHODS: This research involved an extensive analysis of 35,656,613 laboratory samples taken between January 2015 and December 2022 in Türkiye, including the respective triglyceride, Hb, Hct, and HbA1c results. The laboratory test results were obtained from the national health database of the Turkish Ministry of Health. The triglyceride levels were divided into 24 groups, each incremented by 100 mg/dL from a range of 0-3099 mg/dL. Mean and standard deviation values of Hb and Hct were calculated for each group, and the Hct/Hb ratio was graphically represented. RESULTS: The average HbA1c values ranged between 4.37±0.85 and 7.76±3.19 across the groups, Hb averages ranged from 9.75±1.7 to 14.03±2.21, Hct averages from 27.35±4.97 to 38.86±5.66, and Hct/Hb ratios varied between 2.77 and 3.03. The overall average for all samples was identified as 5.15±0.13 for HbA1c, 38.48±5.13 for Hct, 12.73±1.65 for Hb, and 3.02 for the Hct/Hb ratio. CONCLUSION: It was observed that the Hct/Hb ratio gradually decreased as triglyceride levels increased. Evaluating anemia based on Hb concentration in individuals with hypertriglyceridemia might be misleading. It is recommended to use a correction factor based on triglyceride level.

Investigation of the effect of vitamin K1 prophylaxis on newborn screenings tests in newborns.

Background: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements. Methods: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. Results: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Conclusions: Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. METHODS: We performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. RESULTS: Probable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18-29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. CONCLUSIONS: This nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

False negative effect of high triglycerides concentration on vitamin D levels: A big data study.

Background: Inaccurate test results may be a reason why vitamin D deficiency is seen as a common problem worldwide. Interferences from the sample matrix during testing are the most important factors in measurement errors. In this study, the relationship between triglycerides and total cholesterol levels and vitamin D levels in Turkey was investigated. Methods: The 25-hydroxyvitamin D test results and lipid test results studied in Turkey in 2021 were compared. Data were obtained from the Ministry of Health National Health Database. Simultaneously, 25-hydroxyvitamin D, triglyceride, and total cholesterol levels were studied, and 1,135,644 test results were taken as the basis. Results: In the group of patients with total cholesterol levels between 0-10.33 mmol/L, the proportion of patients below 20 mg/L ranged from 56.8% to 61.8%. In the patient group with cholesterol between 10.36-259 mmol/L, the rate of patients with less than 20 mg/L was between 70.8-100%, while the rate of patients with cholesterol above 100 mg/L was 0%. The mean 25-hydroxyvitamin D level was 20.1 mg/L in the patient group with a total cholesterol level between 0-10.33 mmol/L, and 16 mg/L in the patient group with a cholesterol level above 10.36 mmol/L. The mean 25-hydroxyvitamin D level was 20.11 mg/L in the patient group with triglycerides 0-10.16 mmol/L, and the 25-hydroxyvitamin D level was 12.28 mg/L in the patient group with triglycerides 10.17-113 mmol/L. The proportion of patients with vitamin D levels above 100 mg/L was found to be 0% in the group of patients with triglycerides above 10.17-113 mmol/L. Conclusions: According to this study, there is a risk of toxicity when administering vitamin D therapy in patients with high cholesterol and triglycerides levels. This study is the first of this size in the literature. High triglycerides and cholesterol levels can cause inaccurate measurement of vitamin D levels, so care should be taken when evaluating these tests.

The effect of vitamin D status on non-alcoholic fatty liver disease: a population-based observational study.

INTRODUCTION: The effect of vitamin D status on steatosis has not been fully elucidated. In this study, we planned to investigate this interaction using a large-scale population-based cohort. MATERIAL AND METHODS: Patients diagnosed with simple steatosis (K76.0) and non-alcoholic steatohepatitis (NASH) (K75.8) by using the International Classification of Diseases 10th Revision (ICD-10) coding system, and who had 25-hydroxyvitamin D (25OHD) measurements at the diagnosis, were included in the study. Control group comprised subjects without liver diseases. Age, gender, alanine aminotransferase (ALT) and 25OHD levels, and the date of the measurements were recorded. RESULTS: We compared ALT and 25OHD measurements between the patient and control groups, and between the simple steatosis and NASH subgroups. 25OHD levels were lower and ALT levels were higher in the patient group (p < 0.001, effect size = 0.028, and p < 0.001, effect size = 0.442, respectively). Logistic regression analysis showed that when 25OHD levels decrease by 1 ng/dL, it increases the risk of being in the patient group by 3.7%. CONCLUSION: Our results suggest that vitamin D status may be related to the development of non-alcoholic fatty liver disease (NAFLD). Although this relationship is weak, it may be important in the pathogenesis of steatosis.

The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.

25-hydroxyvitamin D (25-OHD) levels in Turkish geriatric population: A nationwide study.

Background: Across the world, 25-hydroxyvitamin D (25-OHD) deficiency is a major health problem associated with many chronic diseases in the geriatric population. Prior to this study, there were no data regarding 25-OHD levels among individuals over the age of 65 in Turkey. The aim of this study was to assess 25-OHD levels and seasonal variations in these values among people over the age of 65 in Turkey. Methods: This study included vitamin D measurements taken in 2016, 2017, and 2018 from the Turkish population over the age of 65. The age, gender, and seasonal average data of the study population were defined. The study data were obtained from the database of the Ministry of Health, and a Kolmogorov-Smirnov test was used to assess the distribution of the data. Medians and interquartile ranges (IQRs) were calculated for all categories, as the data were nonparametric. Results: The number of vitamin D measurements taken from the geriatric individuals included in this study was 305,329 for 2016, 576,452 for 2017, and 752,837 for 2018. The medians and IQRs of the 25-OHD levels in this population were 16 µg/L (IQR 7.45-24.55 µg/L) for 2016, 16.1 µg/L (IQR 7.8-24.4 µg/L) for 2017, and 16.4 µg/L (IQR 8.95-23.85 µg/L) for 2018. Conclusions: While the 25-OHD levels of older men tended to increase during the period of seasonal sunlight in Turkey, this variability was observed in elderly women. This suggests that older women tend to live more sedentary lives and have insufficient sun exposure. Overall, the median 25-OHD levels of individuals over the age of 65 tended to decrease each year.

The effect of hypertension and antihypertensive therapies on the course of COVID-19 infection: Turkish national health system data.

AIM: The effect of hypertension (HT) and antihypertensive therapies such as renin-angiotensin-aldosterone system (RAAS) blockers on the disease course in COVID-19 patients is controversial. The purpose of this study was to evaluate the effect of HT and antihypertensive therapies on the course of COVID-19 disease. METHOD: The age, sex, comorbid diseases, and antihypertensive therapies of 132,790 patients with positive COVID-19 real-time transcriptase polymerase chain reaction (RT-PCR) tests in the Turkish Health Ministry National COVID-19 database between 11 March and 31 May 2020, were examined and analyzed. RESULTS: Forty-one percent of the 132,790 patients in this study (median age: 40, 47.3% female) were hospitalized for treatment, and 4.5% were followed-up in the intensive care unit (ICU). The most frequent comorbid disease, at 19.5%, was HT (n = 25,863). Mortality was determined in 4.9% of HT patients and 1.9% of non-HT patients (p < .001). HT, age, and male gender emerged as independent predictors of hospitalization and admission to the ICU, while HT was not a predictor of mortality. In addition, no adverse effect of any antihypertensive treatment, including RAAS inhibitors, on mortality was detected. CONCLUSION: Based on Turkish national data, HT is common in COVID-19 patients, but does not appear to be an independent predictor of mortality, and no adverse effect of RAAS inhibitors on COVID-19-related mortality was observed.

Evaluation of the relationship between progression and SARS-CoV-2 viral load in COVID-19 cases in Ankara, Turkey.

INTRODUCTION: Patients infected with SARS-CoV-2 may present with varying clinical pictures. This study aimed to examine the relationship between viral load cycle threshold value, clinical prognosis and other laboratory parameters in initial swab samples on the day of hospitalization. METHODOLOGY: This retrospective and cross-sectional study included 112 patients, who were diagnosed with SARS-CoV-2 via the Bio-Rad CFX96 TouchTM system. Cycle threshold values for the RdRp gene obtained from reverse transcriptase polymerase chain reaction positive patients were recorded. RESULTS: The mean age of the 112 patients was 47.57 ± 17 years. No relationship was found in symptoms, pneumonia, oxygen need, follow-up in intensive care unit, and mortality between patient groups with cycle threshold values of < 30 and ≥ 30. Frequencies of thrombocytopenia (50%) and elevated LDH levels were higher in patients with cycle threshold values of ≥ 30 (p = 0.02 and p = 0.04, respectively). There was a weak but significant correlation between cycle threshold values and CRP levels (Pearson's r = 0.207, p = 0.029). CONCLUSIONS: Symptoms or clinical prognosis were not significantly related to the SARS-CoV-2 viral load levels tested at admission or for the first time within the scope of this study. Thrombocytopenia and elevated LDH rates were higher in patients with cycle threshold values of ≥ 30. A weak but significant correlation was found between the viral load and CRP levels. Large-scale studies are needed to further elucidate this subject matter.

Higher rate of COVID-19 mortality in patients with type 1 than type 2 diabetes: a nationwide study.

INTRODUCTION: COVID-19 disease has a worse prognosis in patients with diabetes, but comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM. MATERIAL AND METHODS: A nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n = 149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n = 163), T2DM (n = 33,478) and those without diabetes (n = 115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation, and mortality. RESULTS: The patients with T1DM had higher mortality than the age- and gender-matched patients with T2DM (n = 489) and those without diabetes (n = 489) (p < 0.001). After further adjustment for the HbA1c, and microvascular and macrovascular complications, the odds of mortality (OR: 3.35, 95% CI: 1.41-7.96, p = 0.006) and ICU admission and/or mechanical ventilation (OR: 2.95, 95% CI: 1.28-6.77, p = 0.011) were significantly higher in patients with T1DM compared to those with T2DM. Older age (OR: 1.06, 95% CI: 1.01-1.12, p = 0.028) and lymphopaenia (OR: 5.13, 95% CI: 1.04-25.5, p = 0.045) were independently associated with mortality in patients with T1DM. CONCLUSIONS: Patients with T1DM had worse prognosis of COVID-19 compared to T2DM patients or those without diabetes. These cases should be cared for diligently until more data become available about the causes of increased COVID-19 mortality in T1DM.

Clinical Characteristics and Outcomes of COVID-19 Patients with Overweight and Obesity: Turkish Nationwide Cohort Study (TurCObesity).

PURPOSE: While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. METHODS: A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. RESULTS: A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04-3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02-1.05; p<0.001) were associated with a higher intubation/mechanical ventilation rate but only obesity was associated with increased mortality (OR, 95% CI: 2.56, 1.40-4.67; p=0.002). Old age, male gender, chronic kidney disease, and high C reactive protein levels were independently associated with COVID-19 mortality in overweight or obese patients. CONCLUSIONS: COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing Enterocolitis.

OBJECTIVE: This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups. STUDY DESIGN: Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC + placebo (saline), and NEC + ASX. Pups in the NEC + ASX group were given 100 mg/kg/day oral ASX from day 1 to day 4 of the study. Saline of 2 mL/kg was given to the NEC + placebo group. Histopathological, immunohistochemical (caspase-3), and biochemical evaluations including the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and nuclear factor erythroid 2-related factor 2 (Nfr-2) activities were all performed. RESULTS: A better survival rate and weight gain were demonstrated in the NEC + ASX group (p < 0.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC + ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p = 0.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS/TAS), IL-1ß, LPO, 8-OHdG, AOPP, caspase-3 (p < 0.001 for all), and TNF-α and MPO (p = 0.001 for both parameters) levels were lower in the NEC + ASX group than in the NEC + placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC + ASX group than in the NEC + placebo group (p = 0.001, 0.001, <0.001, and 0.01, respectively). CONCLUSION: ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties. KEY POINTS: · NEC causes extremely high morbidity and mortality, as well as many complications.. · We investigated the effectiveness of ASX in the experimental NEC model created in rat pups.. · First study examining the effect of ASX on the experimental NEC rat model..

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

Investigation of Viral Load Cycle Threshold Values in Patients with SARS-CoV-2 Associated Pneumonia with Real-Time PCR Method.

INTRODUCTION: In this study, we aimed investigate the relationship of SARS-CoV-2 viral load cycle threshold (Ct) values with pneumonia. METHODOLOGY: A total of 158 patients in whom SARS-CoV-2 was confirmed in upper respiratory tract (URT) samples with molecular method and who had computed tomography (CT) of the chest, between April 2020 and June 2020 were included in this retrospective cross-sectional study. RESULTS: Mean age of 158 PCR positive patients was 45.22 ± 17.89 and 60.8% of them were male. Pneumonia was detected in 40.5% of the patients on their chest CT. A weak but significant correlation was found between SARS-CoV-2 Ct value detected with PCR in analysis of oropharyngeal/ nasopharyngeal (OP/NP) samples and chest CT score (Pearson's r: 0.197, p = 0.01). No correlation was found between the first detected viral load Ct value and age, gender and mortality. There was no significant correlation between chest CT score and mortality. While the areas remaining under ROC curve for Ct value in analysis of OP/NP samples in prediction of chest CT score ≥ 1, ≥ 5 and ≥ 10 were 0.564, 0.640 and 0.703 respectively. CONCLUSIONS: We found that the amount of SARS-CoV-2 viral load (inverse relationship with Ct) detected in OP/NP samples of patients with COVID-19 pneumonia did not reflect the increasing severity of pulmonary lesions on chest CT. Although primary target of SARS-CoV-2 is all epithelial cells of the respiratory tract we believe studies comparing viral loads in lower respiratory tract samples are needed to determine the severity of pulmonary disease.

The therapeutic effect of Apocynin against hyperoxy and Inflammation-Induced lung injury.

Lung damage due to hyperoxia and inflammation are important causes of bronchopulmonary dysplasia (BPD). We aimed to investigate the beneficial effects of Apocynin (Apo) on rat pups exposed to hyperoxia and inflammation. Forty-eight rat pups were randomly divided into 3 groups as hyperoxia (95% O2) + lipopolysaccharide (LPS), hyperoxia + LPS + Apo treated and control (21% O2). Rat pups in the Apo group received Apo at a daily dose of 40 mg/kg. Histopathological (Hematoxylin-Eosin, Masson trichrome), immunochemical (surfactant B and C protein staining) evaluations and biochemical studies incluiding, total antioxidant status (TAS), total oxidant status (TOS), OSI (oxidant stress index), AOPP (advanced protein degradation product), Lipid hydroperoxide (LPO), 8-OHdG, NADPH oxidase activity (NOX), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF- α), interleukin-1 beta (IL-1ß), IL-18, IL-6, caspase-1 and 3, nuclear factor erythroid 2-related factor 2 (NFR2), Nod-like receptor pyrin domain-containing 3 (NLRP3) activities were studied. After Apo treatment, AOPP, LPO, 8-OHdG, NOX, TOS, OSI levels decreased; SOD, CAT, GSH and TAS levels increased (P < 0.05). Apo reduced inflammatory cell infiltration and proinflammatory cytokines with reduction in NLRP3 inflammasome in addition to increased Nrf2 levels. Moreover, caspase-1 and 3 levels decreased with Apo (P < 0.05). Apo was found to provide preventive and therapeutic effects by reducing oxidant stress, blocking inflammation and increasing antioxidant status. Beyond anti-oxidative effects, Apo also have anti-inflammatory effects by suppressing NLRP3 inflammasome activation and inducing Nrf2 as well. Therefore, Apo might be a potential option in the treatment of BPD.

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study.

INTRODUCTION: To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population. RESULTS: A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39-1.08; p = 0.099). CONCLUSIONS: The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.