STUDY HYPOTHESIS: AGE, GENDER, PRESENCE OF DIABETES MELLITUS OR HYPERTENSION, AND ANTI-HYPERTENSIVE DRUGS ARE INDEPENDENT RISK FACTORS FOR COVID-19 MORTALITY.

We aimed to investigate the effects of comorbid diseases and antihypertensive drugs on the clinical outcome of hospitalized patients with COVID-19 infection. A total of 1045 patients whose data could be gathered and confirmed from both hospital files and Turkish National Health Network records were retrospectively screened, and 264 of 1045 patients were excluded because of having more than one comorbid disease. The study population consisted of a total of 781 patients, of which 482 had no comorbid disease, while the remaining 299 patients had only one comorbid disease. The mortality risk was 7.532 times higher in those over 65 years of age compared to cases younger than 30 years (OR: 7.532; 95% CI: 1.733-32.730); the risk of mortality in men was 2.131 times higher than in women (OR: 2.131; 95% CI: 1.230-3.693); and presence of diabetes mellitus (DM) increased mortality risk 2.784 times (OR: 2.784; 95% CI: 1.288-6.019). While hypertension was not found to be an independent risk factor for COVID-19 mortality, age, gender, and presence of DM were independent risk factors for COVID-19 mortality. There was no association between antihypertensive drugs and mortality. Accordingly, age (>65 years), gender (male), and presence of DM were independent risk factors for COVID-19 mortality, whereas hypertension and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and their combinations with other antihypertensive drugs were not risk factors for COVID-19 mortality.

EFFECT OF MAMMOGRAPHY IMAGING PROCEDURE ON SERUM INFLAMMATORY AND/OR TUMOR MARKER LEVELS.

Mammography is one of the gold standard screening tests for breast cancer. The effects of mammography procedure on blood parameters are not known. This study aimed to investigate whether the procedure-associated breast compression affects the widely and simultaneously performed blood measurements of C-reactive protein (CRP), carcinoembryonic antigen (CEA), and cancer antigen (CA) 15-3. According to breast ultrasound examination results, participants were divided into 3 groups as follows: group 1 (participants with breast mass size ≥20.0 mm, n=48); group 2 (participants with breast mass size <20.0 mm, n=17); and group 3 (participants with no breast mass, n=23). In groups 1 and 2, on the day of the mammographic imaging study, serum CRP, CEA, and CA 15-3 levels were measured before and after the imaging study. Participants in group 3 had their blood parameters measured without mammography and/or any breast compression. Post-mammography blood measurements displayed a significant increase in serum CRP levels, and a significant decrease in serum CEA and CA 15-3 levels in group 1 (in comparison with the same day pre-mammography blood sampling levels; p<0.05 all). Although pre-mammography serum CEA levels in group 1 participants were significantly higher than those in group 2 and 3 participants, this significant elevation became nonsignificant at post-mammography measurements (p<0.05 and p>0.05, respectively). On the day of the mammographic imaging study, the optimal time of blood sampling for testing CRP, CEA and CA 15-3 levels in persons with a breast mass is before, but not after the mammographic imaging procedure. This issue requires additional detailed studies.

In-vitro cytokine production and nasopharyngeal microbiota composition in the early stage of COVID-19 infection.

BACKGROUND: To determine and compare nasopharyngeal microbiota (NM) composition, in vitro basal (Nil tube), provoked (Mitogen tube) production of cytokines at the early stage of COVID-19. METHODS: This cross-sectional study included 4 age and sex-matched study groups; group 1 (recovered COVID-19) (n = 26), group 2 (mild COVID-19) (n = 24), group 3 (severe COVID-19) (n = 25), and group 4 (healthy controls) (n = 25). The study parameters obtained from the COVID-19 (group 2, and 3) at the early phase of hospital admission. RESULTS: The results from the reaserch deoicted that the Mean ± SD age was 53.09 ± 14.51 years. Some of the in vitro cytokines production was significantly different between the study groups. Some of the findinggs on cytokines depicted a significant differences between study groups were interleukin (IL)-1ß Nil, IL-1ß Mitogen, and their subtraction (i.e Mitogen-Nil). Regarding IL-10, and IL-17a levels, Mitogen, and Mitogen-Nil tube production levels were significantly different between the groups. Surprisingly, most of these measures were lowest in the severe COVID-19 patients' group. Using discriminant analysis effect size (LEfSe), Taxa of NM with significant abundance was determined. About 20 taxa with an LDA score > 4 were identified as candidate biomarkers. Some of these taxa showed a significant correlation with IL-1ß and IL-10 Mitogen and Mitogen- Nil levels (R > 0.3 or < -0.3, p < 0.05). CONCLUSIONS: The findings of this perticular study regarting the early stage of COVID-19 showed that in vitro cytokines production, studies might be more useful than the ordinary cytokines' blood level measurement. Besides, the study identified some NM species that could be candidate biomarkers in managing this infection. However, further detailed studies are needed in these fields.

SYNTHETIC CANNABINOID BONZAI RELATED CREATINE KINASE ENZYME ELEVATION: A TURKISH CENTER STUDY.

Synthetic cannabinoid (locally named 'Bonzai' in Turkey) use is increasing worldwide (especially among people with low income). One of its harmful adverse effects is an increase in serum levels of muscle enzymes (i.e., creatine kinase [CK]). The aim of this study was to determine the prevalence of Bonzai use in patients admitted with elevated CK levels and to compare the 1-month survival status of Bonzai users with that of non-Bonzai users. This retrospective study was conducted on a total of 468 patients, median (min-max) age 48±22 (18-93) years. It was found that 10.68% (n=50) of the patients presenting with elevated CK levels were using Bonzai (group 1), while the remaining 418 (89.32%) patients were non-Bonzai users (group 2). Median age was higher in group 2 as compared with group 1 (p=0.001). In group 1, the predominance of male (M) over female (F) patients was interestingly high, yielding a F:M ratio of 1/49 (χ2=110.03, p<0.001). The prevalence of Bonzai use among patients admitted to our center with elevated CK levels was 10.68%. The Bonzai group patients were younger and mostly males, and none of them died at 1 month of admission. These findings may help in the management of such clinical conditions and could be a pathfinder for further studies in this field.

Serum C-Reactive Protein and Sex Hormone Levels in the Early Hyperacute Phase of Stroke.

BACKGROUND: To see the relationship of early admission parameters with the type of stroke and/or with the 30-days mortality from this disease. METHODS: Stroke patients at their early hyperacute phase (n = 180) were enrolled in this study (156 ischemic strokes and 24 hemorrhagic strokes). Blood levels of C-reactive protein (CRP), testosterone, and estradiol were determined at admission, before any specific intervention. Patients' clinical data, including the above-mentioned laboratory parameters, were compared between the above two stroke types (in total and between sexes). RESULTS: The mean age of the patients was 69.55 ± 12.03 years old (69.92 ± 11.94 years old in ischemic stroke and 67.12 ± 12.54 years old in hemorrhagic stroke). Serum estradiol levels of both males of ischemic stroke and females of hemorrhagic stroke patients were significantly higher than the females of the ischemic stroke. Serum CRP levels of both females and males of the hemorrhagic group were higher than their peers of the opposite group. Early admission serum CRP level ≥ 0.74 mg/dL in males helped predict hemorrhagic stroke while a serum estradiol level ≥ 14.07 ng/mL helped predict the same type of stroke in females. CONCLUSIONS: Our study results show that simple early laboratory measures (such as CRP and estradiol) may help in the early phase management of stroke. Further studies are needed to confirm our findings.

Annual influenza vaccination effect on the susceptibility to COVID-19 infection.

OBJECTIVES: We aimed to study the effect of seasonal influenza (flu) vaccination on the susceptibility to coronavirus disease 2019 (COVID-19). METHODS: A total of 203 healthcare workers of a pandemic centre of Istanbul, Turkey, were included in this retrospective study. According to the presence or absence of flu vaccination, participants were divided into group 1 and group 2. A comparison of the rate of COVID-19 was done between these two groups. Also, the mean age and the sex ratio of females/males were evaluated and compared between these two groups. RESULTS: Group 1 participants (n = 65) were older than participants in group 2 (n = 138) (p < 0.05). Despite of this, interestingly, the COVID-19 infection rate was lower in the 1st group (in comparison to the 2nd group) (p < 0.05). CONCLUSION: Our study results showed that, even if low, the flu vaccination may have a protective effect on the susceptibility to COVID-19 infection. Using this beneficial adjuvant effect of the vaccine may help us in this unpredictable battle with the COVID-19 pandemic. Further studies are needed to confirm this assumption.

MATERNAL GUT MICROBIOTA IN PREGNANCIES RESULTING IN DOWN SYNDROME NEWBORNS - A PILOT STUDY.

Down syndrome (DS) is one of the main genetic abnormalities of newborns. Therefore, prenatal diagnosis of this syndrome is of paramount importance to the family and the community. The microbiota system is important in early brain development. We tried to study and compare gut microbiota (GM) composition in pregnancies that resulted in DS neonates with pregnancies that resulted in healthy children. The study population consisted of 21 pregnant women having delivered DS newborns (group 1) and 22 pregnant women who had given birth to healthy newborns (group 2). The GM composition was determined and compared between the two groups. There were no significant age and gestational age differences between the two groups (p>0.005 both). Regarding GM analysis, microorganisms of the families Clostridiaceae and Pasteurellaceae were more abundant in the group of women having delivered DS neonates than the group of women having delivered healthy newborns (p<0.05). The results of our pilot study showed that the GM system might have a role in the pathophysiology of DS. The GM changes may be used in the prenatal diagnosis and prevention of this syndrome. Further studies are needed in this field.

Serum Levels and Urinary Excretion of Tenascin-C and TIMP-1 in Acute Kidney Injury.

BACKGROUND: Both the extracellular matrix molecule tenascin-C (Tn-C) and tissue inhibitors of metalloproteinases (TIMPs) have a role in tissue injury, inflammation, and remodeling. In this pilot study, we tried to evaluate the role of these markers in acute kidney injury (AKI). METHODS: A total of 52 subjects were enrolled in this study. Group 1 consisted of 27 patients with AKI (stage 1, 2, and 3), and Group 2 consisted of 25 age- and gender-matched healthy subjects. Serum and urine samples (to determine Tn-C and TIMP-1) were obtained from the participants at the beginning of the study. Second samples were obtained from Group 1 patients when renal function improved (at discharge). RESULTS: Serum TIMP-1 concentrations (admission and discharge) were higher in Group 1 than Group 2 (p = 0.0001 for both comparisons). Tn-C excretion in spot urine was significantly higher in healthy controls than at the admission levels of the patient group (p = 0.036). However, TIMP-1 excretion in spot urine was lower in healthy controls than in admission and discharge levels of the patient group (p = 0.0001 for both comparisons). CONCLUSIONS: Our results show that these biomarkers (especially TIMP-1) may have a role in the pathophysiology of AKI. Further studies are needed in this field.

Early effect of the fear of terrorism on a hospital's emergency department use and on the incidence of cardiovascular events: A Turkish multicenter study.

BACKGROUND: To our knowledge, the early effect of the fear caused by terrorism on human health, especially its effect on the number of visits to medical emergency departments (EDs), has not yet been studied. OBJECTIVES: To observe the effect of fear from terrorist alerts on the use of EDs and on the rate of cardiovascular (CV) and/or cerebrovascular events. SETTING: In Istanbul, Turkey, there was a terror alert on the weekend of 19 and 20 March 2016. In this multicenter retrospective study, we compared the data of patients from that weekend with those from the preceding and following weekends. PATIENTS: A total of 12 324 adult patients' records were included in this study: 4562 patients in the first weekend, 3627 patients in the second, terror alert weekend, and 4135 patients in the third weekend. MEASUREMENTS: The ED, CV, and cerebrovascular incidence rates of the above three groups were compared. RESULTS: The rate of ED use was the least in the weekend of the terror alert; the highest rate occurred during the weekend prior to it (female applications decreased more [P = 0.03]). The medical center that was the farthest from the crowded central places of the city and from the place where suicide bombing occurred was less affected by the decrease in use. CONCLUSIONS: Fear associated with terrorism may affect human health indirectly by preventing patients from reaching the necessary emergency healthcare facilities. This finding may be a pathfinder to decision-makers in such extraordinary emergency conditions. Further studies are needed in this field.

Comparison of serum paraoxonase and arylesterase activities between iron deficiency anemia patients and chronic kidney disease patients with anemia.

OBJECTIVE: Altered paraoxonase (PON) and arylesterase (ARE) activities have been shown in anemic chronic kidney disease (CKD) patients and in iron deficiency anemia (IDA) patients. Whether accompanying anemia alone is responsible for this diminished PON and ARE activities in CKD patients or an additive factor for this is not well studied. Therefore, we tried to clarify this issue here. METHODS: A total of 82 subjects that consisted of 19 patients with IDA (group 1), 23 anemic CKD patients (group 2), and 40 age and sex matched healthy subjects (group 3) were enrolled. Carotid intima media thickness (CIMT), serum total thiol (-SH), PON, and ARE activities of the participants were analyzed. RESULTS: Group 2 patients had significantly lowest serum levels of Total -SH, PON and ARE. Further comparison showed that total -SH, PON and ARE levels were lower in group 1 than group 3 (p = 0.0001 in both). Regarding comparison of group 1 and 2, only serum ARE levels were significantly lower in group 2 (p = 0.001). PON activity was not different between group 1 and group 2 whereas ARE activity was lower in group 2 than groups 1 and 3. In addition, correlation analysis showed that CIMT was negatively correlated with PON and ARE. CONCLUSIONS: This markedly decreased ARE activity in CKD patients, which could not be explained by the anemia alone, may have a role in the pathogenesis of increased atherosclerosis in such patients. Still further studies are needed to certain this.

Heat shock protein 70 is a useful marker for predicting colorectal cancer.

PURPOSE: In colorectal cancer (CRC), as in most of other malignancies, heat shock proteins (HSPs) are overexpressed and are associated with apoptosis, cancer cell proliferation, differentiation, invasion, and metastasis. HSP70 is one of the HSPs and has a promising future in cancer studies for both diagnostic and therapeutic applications. In this study, we tried to evaluate the serum levels of HSP70 in CRC patients, and to evaluate its predictive value of detecting CRC. METHODS: This prospective study was consisted of 33 patients diagnosed with CRC and 31 healthy subjects who were matched for age. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum levels of HSP70 in patients with CRC and in the healthy control group. A cut-off value for HSP70 was also determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Patients with CRC had significantly higher HSP70 concentrations compared with the control group (4.52 ± 1.83 vs 1.22 ± 0.48 ng/ml, p=0.001), the cut-off value was ≥2.25 ng/ml (95% CI 0.993-1.003, p<0.001). The sensitivity and specificity of elevated serum HSP70 in the CRC group were 96.77 and 96.96%, respectively. Also, HSP70 levels were significantly higher with rectal disease localization (p=0.01). CONCLUSION: This study shows that the serum level of HSP70 is elevated in patients with CRC. HSP70 may be utilized as an adjunct to other diagnostic or screening tests.

Association of plasma growth arrest-specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes.

AIMS: New biomarkers are required to detect diabetic nephropathy earlier in persons with type 2 diabetes mellitus. Recent experimental studies indicate that growth arrest-specific protein 6 (Gas6) may have a role in pathogenesis of complications associated with diabetes. The objective of the current study is to examine whether plasma Gas6 concentrations are associated with albuminuria in persons with type 2 diabetes mellitus. METHODS: About 32 patients with diabetes which have micro or macroalbuminuria, 37 patients with diabetes and normoalbuminuria, and 30 healthy volunteers were recruited. Plasma Gas6 levels were measured by ELISA. Hemoglobin A1c (HbA1c), serum C reactive protein, fibrinogen and 24-h urine samples for microalbuminuria were analyzed by Primus PDQ, Beckman Coulter Immage 800, STA Compact and Roche Cobas Integra 800 analyzer, respectively. Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) for Windows 11.5. RESULTS: There was a noteworthy difference among the three groups for Gas6 according to the Kruskal-Wallis test (p < 0.01). Plasma Gas6 concentrations were higher in patients with micro or macroalbuminuria [20.9 ng/mL (16.7-27.0); median (25-75% percentile)] compared to patients with normoalbuminuria [16.5 ng/mL (13.1-22.9)], and healthy controls [15.3 ng/mL (8.3-33.6)]. CONCLUSIONS: In conclusion, this is the first study indicating that plasma Gas6 levels are associated with albuminuria in patients with type 2 diabetes. This study could be considered a starting point to focus on the association between Gas6 and diabetic nephropathy.

Evaluation of the Prevalence of Barotrauma and Affecting Factors in Patients with COVID-19 during Follow-Up in the Intermediate Care Unit.

It is known that pneumothorax (PX) and pneumomediastinum (PM) develop due to COVID-19 disease. The objective of our study was to determine the prevalence of PX/PM due to COVID-19 in the intermediate intensive care unit (IMCU) and to evaluate the factors causing barotrauma and also the clinical outcomes of these patients. A total of 283 non-intubated patients with COVID-19 pneumonia followed up in the IMCU in a 1-year period were included in the study. The patients were classified as group 1 (having barotrauma) and group 2 (without barotrauma). The rate of barotrauma was 8.1% (n = 23, group 1). PX developed on the right hemithorax in 12 (70.6%) patients. Group 1 had statistically significantly higher 28-day mortality rates compared with group 2 (p = 0.014). The eosinophil and d-dimer levels of the patients in group 1 were higher, while C-reactive protein (CRP), fibrinogen, and albumin levels were lower than Group 2 (p < 0.001, p = 0.017, p = 0.001, p < 0.001), and p < 0.001, respectively). The similar rates of NIMV administration in our study groups support that barotrauma is not the only mechanism in the development of PX/PM. The findings of high blood eosinophil count and low blood levels of CRP, albumin, and fibrinogen in the barotrauma group of our study might be a pathfinder for future studies.

Oxidative stress and autonomic nervous system functions in restless legs syndrome.

BACKGROUND: Oxidative stress has been implicated in over 100 disorders in recent years; however, the situation in restless legs syndrome (RLS) has not been studied yet. METHODS: Fifty patients with RLS not medicated for RLS and 50 sex- and age-matched, healthy controls and controls with no pathology except mild iron deficiency or iron deficiency anaemia were enrolled. Patients with secondary RLS other than iron deficiency were excluded. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), arylesterase (ARE), paraoxonase (PON), stimulated paraoxonase (stim-PON), lipid hydroperoxides (LOOHs), acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE) were measured. Heart rate variability (HRV) analysis was performed. RESULTS: TOS, ARE and AChE were increased (P = 0·018, P < 0·001 and P < 0·001, respectively), whereas LOOHs were decreased (P < 0·001) in RLS group. TAS, OSI, PON and stim-PON were comparable. Erythrocyte sedimentation rate (ESR) and mean platelet volume (MPV) were increased (P = 0·021 and P = 0·037, respectively) in RLS group. HRV triangular index (HRVi) was lower (P = 0·012) in RLS group. Other HRV parameters were similar. CONCLUSIONS: Increased AChE and decreased LOOHs, which were influenced by increased PON1, were considered as indicators of efforts towards the protection of dopaminergic activity in central nervous system in RLS group. Increased ESR, MPV and low HRVi indicate elevated sympathetic activity in RLS group. Elevated sympathetic activity might be beneficial in relieving RLS symptoms, also causing increases in TOS. The evidence we found regarding oxidative stress and autonomic nervous system might be seminal in RLS treatment.

Prevalence of gluten sensitive enteropathy antibodies in restless legs syndrome.

The prevalence of restless legs syndrome (RLS) is increased in gluten sensitive enteropathy (GSE); but prevalence of GSE is not known in RLS. 96 RLS patients and 97 healthy controls, both with or without iron deficiency were enrolled. All secondary RLS patients except iron deficiency were excluded. Subjects underwent a thorough biochemistry and routine blood analyses, and tissue transglutaminase antibodies (TTGA), endomysium antibodies (EMA) and gliadin antibodies (AGA) were also tested. In RLS patients positivity rates of all GSE antibodies were similar to those in controls. The rate of iron deficiency anaemia in RLS patients with at least one positive GSE antibody was significantly higher than that of RLS patients whose GSE antibodies were all negative. The prevalence of GSE antibodies in RLS patients is not increased. GSE might have a role in the aetiology of RLS in association with iron deficiency anaemia. Since the prevalence of GSE antibodies is not increased in RLS, it seems unlikely that GSE is involved in the aetiology of RLS through different mechanisms (e.g. immunological mechanisms) other than iron deficiency as proposed in some published papers.

The Effect of Polypharmacy on the Charlson Comorbidity Index and Katz Index in Aging People with and without Diabetes Mellitus.

OBJECTIVE: The prevalence of diabetes mellitus is growing worldwide, as well as in the aging population, and its comorbidity and mortality rates are higher in aging people than they are in young people. It has been observed that the number of drugs used increases in aging patients, especially in diabetic patients. This study aimed to investigate the relationship between polypharmacy and modified Charlson Comorbidity Index (CCI) and Katz Index of Independence in Activities of Daily Living (Katz ADL) scores in aging diabetic and non-diabetic patients. MATERIALS AND METHODS: This prospective study included 184 diabetic and 62 non-diabetic subjects who were ≥65 years old. Comorbidity was determined with CCI, and dependency on daily basic activities was assessed with Katz ADL. RESULTS: CCI and the number of drugs were significantly higher in diabetic groups (P = .001). In all subjects and in the diabetic group, there was a negative correlation between CCI and Katz ADL (r = -0.343, P = .001; r = -0.383, P = .001, respectively); there was a positive correlation between CCI and number of drugs (r = 0.430, P = .001; r = 0.248, P = .001, respectively). CONCLUSION: We found an increase in the number of drugs taken by the aging patients, positively correlated with the CCI score. The increase in the number of drugs used is closely related to the insufficiency in daily life activity and comorbidity, and this predicts 10-year survival. Patients should be directed to special centers or physicians who will be scheduled for multidisciplinary treatment for the prevention of polypharmacy, especially in the aging.

Splenomegaly in primary antiphospholipid syndrome without accompanying portal hypertension or comorbidity.

OBJECTIVE: To demonstrate the presence of splenomegaly in primary antiphospholipid syndrome (PAPS) patients without accompanying portal hypertension or comorbidity. METHODS: Twelve patients (7 women) aged 23-65 years followed upon the diagnosis of PAPS were enrolled in the study. We documented the identified causes of splenomegaly in patients with PAPS, and searched for the potential causes of splenomegaly in patients with spleen enlargement. PAPS patients with or without splenomegaly were evaluated in terms of demographic and clinical findings. RESULTS: Splenomegaly was present in 6 of the 12 patients. In these patients, there were no infections, hematological disorders, portal hypertension or malignancy that might lead to splenomegaly. The long axis of spleen was found to be in the range of 137-155 mm in patients with splenomegaly. Splenomegaly was more frequently determined in female PAPS patients. The splenomegaly group had a longer duration of disease (median 5.5 vs. 0.75 years) and a higher number of thrombotic events (median 3 vs. 1.5). The splenomegaly group was especially composed of patients who never received any anticoagulant and acetylsalicylic acid, or who used these agents irregularly for very short periods. CONCLUSION: Splenomegaly was observed in association with disease duration, frequency of thrombotic events and irregular antiaggregant or anticoagulant treatment in patients with PAPS, in the absence of comorbidity or portal hypertension.