Monitoring recurrent angioedema: Findings from the Turkish angioedema control test validation study.

BACKGROUND: Determination of control level in recurrent angioedema (RAE) is necessary to guide management. Here, we validated a Turkish version of the angioedema control test (AECT) for 4-week (AECT-4wk) and for 3-month (AECT-3mth) and assessed their utility in monitoring RAE. METHOD: The recommended structured translation process for patient-reported outcome measures was completed. The final versions were administered to 51 patients with mast cell-mediated angioedema (MMAE) and 38 patients with hereditary angioedema, and the minimal clinically important difference (MCID) was determined. Additionally, anchor surveys comprising angioedema activity score for 28 days (AAS-28 day), visual analog score for angioedema control, Likert scale for the control level from the patient's perspective (LS-AEC), angioedema quality of life, short form-12 (SF-12) and patients' assessment of treatment sufficiency were applied. RESULTS: The Turkish AECT versions showed good convergent validity with a substantial correlation with anchor tools and known-group validity. Excellent internal consistency and reproducibility were observed. Equal or more than 10 of 16 points scored with the AECT-4wk and AECT-3mth identified patients with well-controlled disease. The disease activity, control and burden parameters were consistent with the disease control level defined depending on the cut-off point 10 of AECT. Three-point changes in AECT-4wk and -3 mt could detect MCID in disease control in all patients. CONCLUSIONS: Turkish AECT versions are valid and reliable tools for assessing and monitoring disease control in patients with RAE. The use of the Turkish versions of the AECT in routine patient care, clinical trials and angioedema research is recommended.

Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

Introduction: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. Methods: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients' demographic and clinical characteristics were further analyzed depending on the severity of the reaction. Results: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25-75] age: 42 [33-52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1-7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1-6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5-17.0); p = 0.011, OR (CI) = 10.3 (1.6-63.3)]. Conclusion: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.

Positive perception of COVID-19 vaccination in HAE: No significant impact of vaccination on disease course.

Background: There are some adverse effects with coronavirus disease 2019 (COVID-19) vaccines, but the impact of COVID-19 vaccination on attacks in hereditary angioedema (HAE) is not well defined. Objective: We aimed to investigate the influence of COVID-19 vaccination on the course of HAE. Method: The COVID-19 vaccination status was determined in 140 adult patients with HAE. The number and severity of attacks recorded from patients' diaries were evaluated at four different periods, comprising 1 month before the first dose, the period between the first and the second doses of COVID-19 vaccine in all the patients, the period between the second dose and the third doses in those who received three doses, and 1 month after the last vaccination dose. The disease and attack severities were assessed with the disease severity score (DSS) and 10-point visual analog scale, respectively. The patients were divided into two main groups as group 1 (those who had at least two doses of COVID-19 vaccines [n = 114]) and group 2 (those who had no vaccination [n = 26]). Only Sinovac and Biontech, which were only approved in Turkey. Results: The mean ± standard deviation DSS was significantly higher in the patients who experienced an attack after vaccination within 48 hours (6.61 ± 1.88 versus 4.14 ± 1.69; p < 0.001). Long-term prophylaxis was less common in the patients with an increased number of attacks (n = 5 (27.8%) versus n = 54 (56.3%); p = 0.027). The number of patients with less than a high school education was higher in group 2 (n = 23 [88.5%]) than in group 1 (n = 26 [3.1%]) (p < 0.001). The number of patients who had concerns about the triggering of a vaccine-induced HAE attack or about the possible vaccine adverse effects was higher in group 2 (n = 26 [100%]) than in group 1 (n = 74 [64.9%]). Conclusion: It seems that COVID-19 vaccination does not increase HAE attacks regardless of the type of the vaccines. We recommend that HAE activity should be under control before COVID-19 vaccination, and the patients should be well informed about the safety of the vaccines.

Comparison of demographic and clinical characteristics of hospitalized COVID-19 patients with severe/critical illness in the first wave versus the second wave.

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.

Relationships among oncostatin M, insulin resistance, and chronic inflammation: a pilot study

ABSTRACT Objective Activated macrophages (M1-type macrophages) in adipose tissue secrete many proinflammatory cytokines that induce insulin resistance (IR). Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of Gp130 cytokines, plays an important role in a variety of biological functions, including the regulation of inflammatory responses. Proinflammatory cytokines released in patients with IR trigger a chronic, low-grade inflammatory reaction in blood vessel walls. This inflammator response leads to endothelial damage, which is the main mechanism for atherosclerosis and many cardiovascular diseases. Animal studies have reported a relationship between OSM and IR. To the best of our knowledge, however, few clinical studies have examined this topic. Therefore, we studied the relationship between serum levels of OSM and IR. Subjects and methods This prospective cross-sectional case-control study enrolled 50 people with IR (according to the HOMA-IR and QUICKI indices) and 34 healthy controls. The fasting blood concentrations of insulin, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, C-reactive protein (CRP), and OSM were determined. Results There were no significant differences between the two groups in age, sex, and HbA1c levels. Univariate analyses showed that waist circumference (WC) and levels of fasting glucose, insulin, CRP, HDL-C, OSM, HOMA-IR, and QUICKI differed between the two study groups. In multivariate analyses, both IR indices (QUICKI and HOMA) and OSM differed between the two groups. Conclusion OSM was correlated with the IR indices (QUICKI and HOMA). For simplicity, it might replace the other IR indices in the future. Further detailed studies are needed to confirm this.

Relationships among oncostatin M, insulin resistance, and chronic inflammation: a pilot study.

Objective Activated macrophages (M1-type macrophages) in adipose tissue secrete many proinflammatory cytokines that induce insulin resistance (IR). Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of Gp130 cytokines, plays an important role in a variety of biological functions, including the regulation of inflammatory responses. Proinflammatory cytokines released in patients with IR trigger a chronic, low-grade inflammatory reaction in blood vessel walls. This inflammator response leads to endothelial damage, which is the main mechanism for atherosclerosis and many cardiovascular diseases. Animal studies have reported a relationship between OSM and IR. To the best of our knowledge, however, few clinical studies have examined this topic. Therefore, we studied the relationship between serum levels of OSM and IR. Subjects and methods This prospective cross-sectional case-control study enrolled 50 people with IR (according to the HOMA-IR and QUICKI indices) and 34 healthy controls. The fasting blood concentrations of insulin, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, C-reactive protein (CRP), and OSM were determined. Results There were no significant differences between the two groups in age, sex, and HbA1c levels. Univariate analyses showed that waist circumference (WC) and levels of fasting glucose, insulin, CRP, HDL-C, OSM, HOMA-IR, and QUICKI differed between the two study groups. In multivariate analyses, both IR indices (QUICKI and HOMA) and OSM differed between the two groups. Conclusion OSM was correlated with the IR indices (QUICKI and HOMA). For simplicity, it might replace the other IR indices in the future. Further detailed studies are needed to confirm this.

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.

Serum endotrophin levels in patients with heart failure with reduced and mid-range ejection fraction.

BACKGROUND: Endotrophin, a type VI collagen cleavage product, has fibrosis, and insulin resistance effects. Type VI collagen also plays a role in cardiac fibrosis. In this study, we aimed to investigate the role of endotrophin in the pathogenesis of cardiac fibrosis by determining its levels in patients with heart failure with reduced and mid-range ejection fraction (EF). We also aimed to determine the possible association between endotrophin and treatment that prevents ventricular fibrosis. METHODS: Sixty patients with heart failure with reduced and mid-range EF and 27 volunteers with no cardiac failure were included in this study. In both groups, biochemical tests, EF, and endotrophin levels were measured. ELISA was performed for the determination of endotrophin levels. RESULTS: When compared with the control group, there was no significant difference for endotrophin levels in the patient group (p = .35). Participants in the study were divided into two groups according to their EFs, 40% and less, and 40-49%. They were classified according to their use of renin-angiotensin-aldosterone system (RAAS) blocking drugs. Endotrophin levels were significantly lower in patients with mid-range EFs between 40 and 49% (p = .03) using RAAS blockers. CONCLUSION: This study is the first to evaluate the relationship between endotrophin and heart failure. Endotrophin levels were found to be low in patients with heart failure with mid-range EF who were using RAAS blockers. This suggests that RAAS blockers may influence endotrophin levels and thus could have a role in the prevention of remodelling.

Serum Adropin Levels Are Reduced in Adult Patients with Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Adropin is a novel marker of metabolic syndrome and insulin resistance. The aim of this study was to explore the association of serum adropin levels with hepatosteatosis among adult patients. MATERIALS AND METHODS: Serum biochemical parameters including liver and renal function tests, insulin levels, and serum adropin levels were compared between adult patients with nonalcoholic fatty liver disease (NAFLD) and healthy control cases. RESULTS: A total of 51 patients with a mean age of 37.9 ± 9.96 years diagnosed with grade 2-3 hepatosteatosis and 30 healthy control cases with a mean age of 34.8 ± 9.5 years were included in the study. Serum adropin levels in the NAFLD group were statistically significantly lower than in the control cases (588.4 ± 261.0 vs. 894.2 ± 301.2, respectively; p < 0.001). The study participants were further subdivided into 2 groups as patients with (n = 35) or without (n = 46) insulin resistance using the serum homeostatic model of assessment-insulin resistance (HOMA-IR). Serum adropin levels were statistically significantly lower in patients with insulin resistance (p < 0.01). There was a negative correlation between adropin levels and serum insulin, HOMA-IR, urea, gamma-glutamyl transferase, total cholesterol, and triglyceride levels. CONCLUSION: We observed a decrease in serum adropin levels among adult patients with NAFLD. We also found lower levels of serum adropin in patients with insulin resistance, supporting previous data in the literature. Studies investigating the association of adropin levels with other inflammatory parameters are warranted to define its exact role in the pathogenesis of hepatosteatosis.

Choice of treatment based on Turkish hypertension consensus report: Do we follow the recommendations?

OBJECTIVE: The aim of this study was to determine how often the recommendations of the Turkish Hypertension Consensus Report are followed, and to draw attention to the report. METHODS: The demographic information of 1000 patients diagnosed with hypertension and the details of the antihypertensive medications prescribed at the outpatient service of a tertiary care hospital were recorded, and the data were compared with the recommendations of the report. RESULTS: The mean age of the patients was 62±11 years. In all, 623 (62.3%) of the 1000 patients were women, and 377 (37.7%) were men. A combination of an angiotensin II receptor blocker (ARB) and a diuretic was the most frequently observed prescription. A diuretic was the most used antihypertensive drug (58.7%), followed by an ARB (48.8%). However, as a monotherapy, a calcium channel blocker (CCB) was the most commonly used antihypertensive drug (19.2%). The most frequently used antihypertensive drug group in older patients was diuretics (63.6%), as proposed in the report. Beta blockers (49.1%) were used more often than expected. For the diabetic group also, a diuretic (60.7%) was the most frequently used antihypertensive drug, followed by an ARB (51.1%) and a CCB (45.2%). Angiotensin-converting enzyme (ACE) inhibitors (34.6%) were the fifth most preferred antihypertensive drug class. However, when ACE inhibitors and ARBs were considered as a single group, known as renin-angiotensin system (RAS) blockers, these RAS blockers were the most prescribed antihypertensive drug class, followed by diuretics. In the group of patients with coronary artery disease, treatment was found to be generally consistent with the report, but the use of diuretics was greater than expected. Lastly, 124 of 160 patients who had chronic kidney disease were given RAS blocker therapy, which was in line with the consensus report recommendations. CONCLUSION: Antihypertensive therapies were individualized, as suggested by the consensus report. However, there are proposals still to be considered in special patient groups.

Cisplatin nephrotoxicity is not detected by urinary cell-cycle arrest biomarkers in lung cancer patients.

PURPOSE: Cisplatin is a chemotherapeutic agent with potential nephrotoxicity. Delayed increase in serum creatinine after cisplatin administration shows that serum creatinine may not be a sufficient marker for early detection of nephrotoxicity. Urinary insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) which are cell-cycle arrest biomarkers have been proposed recently for early detection of acute kidney injury (AKI). Herein, we evaluated urinary TIMP-2/IGFBP7 levels before and after cisplatin administration to patients with lung cancer and their role was examined in the early diagnosis of AKI. METHODS: Patients with glomerular filtration rate above 60 mL/min who had cisplatin treatment were enrolled. Urinary TIMP-2/IGFBP7 and serum creatinine levels were measured before and at 24th hour after cisplatin administration. Serum creatinine level was also measured at 48th hour after treatment. RESULTS: Cisplatin-associated AKI was detected in 13 patients (28%) among the 45 patients enrolled. There was no difference between creatinine, IGFBP7 and (IGFBP7 × TIMP-2)/1000 levels before and after treatment; urinary TIMP-2 level at 24th hour was significantly higher than the level before the treatment (p = 0.02). (IGFBP7 × TIMP-2)/1000 values were not different between patients with or without AKI. The area under the curve of (IGFBP7 × TIMP-2)/1000 at 24th hour of the treatment was 0.46 (CI 0.26-0.67). CONCLUSION: Although urinary IGFBP7 and TIMP-2 levels are used as biomarkers for early detection of AKI for patients in intensive care units and after surgery, they seem not to be useful for early detection of AKI due to cisplatin.