Individualized High Dose Intravenous Anakinra Treatment in Cancer Patients with COVID-19 Associated Cytokine Storm: A Retrospective Controlled Study.

Objective: Patients with COVID-19 accompanying cancer have been reported to have higher morbidity and mortality. In this study, we aimed to evaluate the high-dose high intravenous anakinra treatment response and outcome in patients with COVID-19-associated cytokine storm accompanying cancer. Materials and Methods: This retrospective observational study was carried out at a tertiary referral center between September 01, 2021, and February 01, 2022, in Turkey. The study population consisted of two groups: patients receiving high-dose intravenous anakinra and patients treated with standard care. Results: Data from 146 patients in the anakinra group and 114 patients in the control group were analyzed. Malignancy frequency was 11% (n=16) in the anakinra group and 7% (n=8) in the control group. In survival analysis, a significantly lower survival rate was observed in patients with malignancy than those without in the control group (log-rank: p=0.002) and patients with malignancy in the control group compared to the anakinra group (log-rank: p=0.013). However, it did not differ between patients with and without malignancy in the anakinra group (log-rank: p=0.9). Conclusion: In the control group, mortality was higher in patients with malignancy compared to those without malignancy, but not in the anakinra group. Also, mortality was higher in patients receiving SoC compared to anakinra. Intravenous high-dose anakinra treatment is safe and effective in patients with COVID-19 accompanying cancer.

Genetic Investigation of the Trail Mechanism in Diabetic and Non-diabetic Obese Patients.

Obesity is an important healthcare issue caused by abnormally increased adipose tissue because of energy-intake overcoming energy expenditure. Disturbances in the physiological function of adipose tissue mediate the development of diabetes. It is a metabolic disease that results from decreased insulin-levels and/or changes in the insulin action mechanism. Tumor Necrosis Factor-Associated Apoptosis-Inducing Ligand(TRAIL), which is a member of the Tumor Necrosis Factor(TNF)-family with an important role in adipose tissue biology, is included in many studies with its ability to induce apoptosis in cancer cells, but the number of human-studies conducted on the gene related to its protective-role against diabetes and obesity at this level is insufficient. Our study was carried out as a case and control and included three groups (80 diabetic obese, 80 non-diabetic obese, and 80 healthy individuals as the control group). The Real-Time-PZR(RT-qPZR), and DNA Sanger-Sequencing Methods were used for gene expression and gene squences. As a result of the analyses, TRAIL gene expression level was found to be higher in the controls than in the diabetic-obese and non-diabetic-obese group. This change in TRAIL gene expression suggests that TRAIL maybe a protective factor against diabetes. The presence of rs781673405, rs143353036, rs1244378045, rs767450259, rs759369504, rs750556128, and rs369143448 mutations, which was determined with the Sequencing-Method, was shown for the first time in the present study. In addition, it is the first study in which human TRAIL gene-expression and sequencing were performed together. We believe that these data will make an important contribution to the literature.

Functional and Extracellular Production and Antitumor Activity of Mouse Alpha Klotho in Model Microalga Chlamydomonas reinhardtii.

Klotho is a human protein with versatile functions associated with longevity and well-being. α-Klotho (α-KL) deficiency in the circulatory system is associated with reduced life expectancy with numerous disorders such as chronic kidney disease, atherosclerosis, infertility, skin atrophy, emphysema, and osteoporosis. The antagonistic effects of Klotho protein against intractable cancers have also been well documented over the past two decades. In addition, recent findings have also illuminated the importance of soluble Klotho during cognitive development, oxidative stress, cellular apoptosis, and neurodegenerative disorders. The low-cost and sustainable production of alpha Klotho protein is extremely important for its widespread use against different diseases. Here, we report heterologous, functional, and extracellular production of mouse α-KL (mα-KL) protein in model microalga Chlamydomonas reinhardtii. The secretion of mα-KL into the extracellular environment facilitated downstream processes and warranted low-cost purification in high-titer. Furthermore, the anticarcinogenic efficiency of recombinant mα-KL was examined and validated on Rattus norvegicus AR42J pancreas tumors. Microalgae-based photosynthetic, low-cost, and scalable production of mα-KL could be used to develop a variety of cosmetics, pharmaceuticals, and wellness products, all aimed at serving health and well-being.

A rare cause of dilated cardiomyopathy: hypocalcemia

SUMMARY Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.

Malnutrition treatment and follow-up in clinical nutrition outpatient clinics associated with increased muscle mass.

OBJECTIVE: Clinical nutrition outpatient clinics (CNOCs) are the mainstay of the nutrition bundle in hospitals. They are important for the diagnosis, treatment, and follow-up of outpatients with malnutrition (MN) and sarcopenia. The aim of this study was to evaluate changes in muscle mass during the treatment of MN in patients admitted to CNOCs. METHODS: A total number of 1118 patients were included in this retrospective cohort descriptive study. Data including medical history, weight loss, anthropometric measurements, MN diagnosis (according to ESPEN definition), nutrition treatment, bioelectrical impedance analysis and laboratory examinations were noted for the first admission and the follow-up. RESULTS: This retrospective, cohort descriptive study included 1118 patients. The mean age of the participants was 54 ± 22 y (18-101 y) and half of the patients were men. Of the 1118 patients, 37,7% were ≥65 y of age. Cancer (32.2%) was the most frequent diagnosis followed by diabetes (16.7%) and dementia (11.3%). MN prevalence was 51.6%. Protein- and energy-enriched diet, oral enteral nutrition supplementation, tube enteral feeding, and parenteral nutrition were used in 42.7%, 69.6%, 11%, and 2.7% of the patients with MN, respectively. Skeletal muscle mass was significantly increased in MN, cancer, neuromuscular diseases (NMD) and patients ≥65 y of age in the first 6 mo, and could be maintained during the next 6 mo of follow-up. Patients with cancer, chronic kidney disease, and NMD and those ≥65 y of age were able to increase their body mass index. CONCLUSIONS: MN treatment and follow-up can restore muscle mass especially in patients ≥65 y of age and in those with chronic diseases. CNOCs are beneficial in the treatment and follow-up of MN.

A rare cause of dilated cardiomyopathy: hypocalcemia.

Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.

Comparison of amylase and lipase levels of patients with Type 2 diabetes under different treatment modalities.

Aim: Study aims to assess amylase, lipase of patients with Type 2 diabetes under different types of treatments. Materials & methods: Patients' treatment modalities including insulin, metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors, insulin secretagogues, dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists were compared. Results: There was no difference in amylase and lipase levels between dipeptidyl peptidase-4 inhibitor users and non-users (p = 0.2, p = 0.3, respectively) and glucagon like peptide-1 analog users and non-users (p = 0.1, p = 0.7, respectively). Patients who use insulin secretagogues had significantly higher amylase, lipase (77.2 ± 39.8 vs 69.5 ± 33.0, p = 0.038 and 47.2 ± 33.2 vs 39.6 ± 26.8, p = 0.01, respectively) and patients on basal insulin had lower amylase levels (69.9 ± 37.7 vs 77.2 ± 33.7, p = 0.014). Conclusion: Incretin-based therapies showed no difference in amylase and lipase levels whereas there was increase with secretagogues and decrease with basal insulin.

The role of kidney injury molecule-1 in predicting cardiorenal syndrome type 1 after diuretic treatment.

INTRODUCTION: Cardiorenal syndrome (CRS) is defined as acute or chronic dysfunction in the heart and kidney due to important interactions between the heart and kidney disease. The aim of this study was to evaluate prediction of CRS type 1 by measuring kidney injury molecule-1 (KIM-1) and to establish early diagnosis of acute kidney injury (AKI). MATERIAL AND METHODS: During 2015-2016, 146 patients who were admitted to the emergency service with acute decompensated HF were included in the study. We investigated urinary KIM-1 levels in 146 consecutive patients with decompensated heart failure before and after diuretic treatment. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS - version 21.0)/Windows Statistical Software. P-values less than < 0.05 were considered significant. RESULTS: There was a moderate negative correlation between the percentage change of creatinine values and the percentage change of KIM-1 values (r = -0.357, p = 0.016). There was no statistically significant relationship between KIM-1 and the development of CRS type 1 (p = 0.011). CONCLUSIONS: No statistically significant relationship was observed between KIM-1 levels and the development of CRS type 1. In addition, there was no correlation between mortality in patients and KIM-1 values. It is thought that KIM-1 is not a potential prognostic indicator because renal tubular damage is only one of many factors in the pathophysiology of CRS type 1 and heart failure.

Predictive value of global and territorial longitudinal strain imaging in detecting significant coronary artery disease in patients with myocardial infarction without persistent ST-segment elevation.

INTRODUCTION: Two-dimensional (2D) speckle-tracking echocardiographic (STE) imaging is frequently performed in the assessment of cardiovascular diseases. We aim to investigate the role of the global and territorial longitudinal strain (GLS and TLS) values assessed via 2D STE imaging to detect significant coronary artery disease (CAD) in non-ST-segment elevation myocardial infarction (NSTEMI) patients without wall-motion abnormalities. METHODS: This study enrolled 150 patients with the diagnosis of NSTEMI. Patients who had typical chest pain with unstable angina characteristics within the last 24 hours were 18-80 years of age and had a typical rise and/or fall of cardiac biomarkers were included. Myocardial functions were assessed via myocardial deformation analyses of 2D STE images. RESULTS: The mean age of the CAD group was 52.91 ± 9.11, vs 50.31 ± 8.32 in the control group. In the CAD group, 56 patients were male (65%), whereas 21 were male (60%) in control group. GLS and TLS assessments demonstrated a statistically significant difference between CAD and control groups, with GLS values of -16.27 ± 1.91 and -18.74 ± 1.93 (P < 0.001), TLS-LAD values of -15.67 ± 1.83 and -18.54 ± 1.97 (P < 0.001), TLS-RCA values of -17.04 ± 1.81 and -19.20 ± 1.86 (P < 0.001), and TLS-Cx values of -17.40 ± 2.08 and -18.34 ± 2.18 (P = 0.028), respectively. Correlation analyses revealed that as high-sensitivity troponin (hsTnT) values increased, GLS decreased significantly, and further, an increase in severity of CAD resulted in decreased TLS-LAD, -CX and -RCA (TLS-LAD: P < 0.001, r = -0.743; TLS-CX: P < 0.001, r = -0.449; TLS-RCA: P < 0.001, r = -0.737). Multivariate analyses indicated that GLS and GRACE ACS risk scores are independent predictors of CAD in patients with NSTEMI (GLS: OR = 0.514, P < 0.001; GRACE score: OR = 0.938, P = 0.007). CONCLUSIONS: Global longitudinal strain (GLS) assessed with 2D STE is a promising, easy to perform and quick imaging method to predict CAD in patients with NSTEMI.

The Detailed Comparison of Cell Death Detected by Annexin V-PI Counterstain Using Fluorescence Microscope, Flow Cytometry and Automated Cell Counter in Mammalian and Microalgae Cells.

The evaluation of cell wellness is an important task for molecular biology research. This mainly comprises the assessment for morphology and viability of culturing cells. Annexin V-Propidium iodide counterstaining has been currently one of the common and easy methods to discriminate apoptotic and necrotic cell profiles. The method is operated by fluorescence-based detection of counterstain via laser beam-employed instruments including flow cytometer, fluorescence microscope and automated cell counter. The detection is primarily conducted based on the same principle; however the efficiency of instruments may vary. Here we evaluated the efficiency of those instruments for the clear-cut detection of cell death through various mammalian and microalgae cell lines. To the best of our knowledge, this is the first study revealing comparative analyses of apoptotic and necrotic cells in mammalian and microalgae cells using Annexin V-PI counterstain detected by flow cytometer, fluorescence microscope and automated cell counter. Fluorescence microscope and cell counter instruments were also tested and compared for the traditional trypan blue-based cell viability detection performance. For these, cell death was induced by UV-irradiation and/or bee venom for mammalian (pancreatic cancer, metastatic breast cancer and mouse fibroblasts) and microalgae cells (Chlorella vulgaris), respectfully. Findings postulated that automated cell counter and fluorescence microscopy revealed similar patterns for the detection by both counterstain and trypan blue in mammalian cells. Interestingly, flow cytometry did provide an accurate and significant detection for only one mammalian cell line when UV-treatment was followed by routine Annexin V-Propidium iodide counterstaining. Unlike, only flow cytometry revealed a significant change in the detection of death of microalgae cells by Annexin V-Propidium iodide method, but both Annexin and conventional trypan blue methods were not applicable for the automated cell counter and microscopic detections for microalgae cells. The related outputs propose that the obtaining reliable quantitation strongly depends on cell type and instruments used. These suggest the necessity of optimization and validation endeavors before any cell death detection initiative. The analytical outcomes present insights into detailed assessment of cell death detection of eukaryotic cells and provide a direction to researchers to consider.

Effect of Glycemic Regulation on Endocan Levels in Patients With Diabetes: A Preliminary Study.

Endothelial-specific molecule 1 (endocan) is expressed by endothelial cells and may have a major role in the regulation of cell adhesion and in the pathogenesis of inflammatory disorders. We aimed to assess change in endocan levels after 3 months of lifestyle change recommendations and guideline-based treatment. Diabetic patients (n = 77) who had neither chronic kidney disease nor chronic inflammatory disease were included. After baseline evaluation, the patients were advised lifestyle changes, and their medical treatment was determined individually according to recommendations of the American Diabetes Association (ADA) guidelines. At the end of third month patients were reevaluated. Baseline endocan levels were significantly increased in the study group compared with the control group. The third-month laboratory workup showed significant reductions in hemoglobin A1c, urinary albumin-to-creatinine ratio (UACR), and endocan levels. Only δ-UACR was independently correlated with δ-endocan in multivariate linear regression analysis. Our findings suggest that serum endocan concentrations are elevated in patients with type 2 diabetes and decrease following anti-hyperglycemic treatment. Furthermore, decrease in endocan concentrations might be associated with improved glycemic control and reductions in UACR.

Serum Endocan Level and the Severity of Coronary Artery Disease: A Pilot Study.

Endothelial-specific molecule 1 (endocan) is expressed in endothelial cells. We investigated the relationship between acute coronary syndrome (ACS) and serum endocan levels. We included 30 individuals as a control group and 53 patients diagnosed with ACS. The severity of coronary artery disease was assessed by a modified Gensini stenosis and SYNTAX scoring system. There was a significant difference in serum endocan levels between the control group and the ACS group (0.75 ± 0.13 vs 0.86 ± 0.25 ng/mL, P = .014). There was also a significant difference in serum endocan levels between diabetic patients with ACS and nondiabetic patients with ACS (1.02 ± 0.33 vs 0.81 ± 0.21 ng/mL, P = .016). There was no significant correlation between serum endocan level, Gensini, and SYNTAX score (r = .11, P = .53 and r = .16, P = .37). Endocan, a new biomarker of endothelial pathology, is significantly increased in patients with ACS.

Rosai-Dorfman disease with diffuse gastrointestinal involvement.

Rosai-Dorfman disease, formerly known as 'sinus histiocytosis with massive lymphadenopathy', is a rare self-limiting histiocytic proliferative disorder typically presenting early in life with cervical lymphadenopathy and nonspecific systemic symptoms. Although it is usually a nodal disease, extranodal lesions may be encountered in some cases. The gastrointestinal tract is uncommonly affected in Rosai-Dorfman disease and its diagnosis depends on clinical suspicion and careful histopathological examination of biopsy samples taken from involved gastrointestinal segments. Here, we report a case of atypical Rosai-Dorfman disease with systemic symptoms and diffuse gastrointestinal involvement that led to a diagnostic and therapeutic challenge.