Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Applications of deep learning to the assessment of red blood cell deformability.

BACKGROUND: Measurement of abnormal Red Blood Cell (RBC) deformability is a main indicator of Sickle Cell Anemia (SCA) and requires standardized quantification methods. Ektacytometry is commonly used to estimate the fraction of Sickled Cells (SCs) by measuring the deformability of RBCs from laser diffraction patterns under varying shear stress. In addition to estimations from model comparisons, use of maximum Elongation Index differences (ΔEImax) at different laser intensity levels was recently proposed for the estimation of SC fractions. OBJECTIVE: Implement a convolutional neural network to accurately estimate rigid-cell fraction and RBC concentration from laser diffraction patterns without using a theoretical model and eliminating the ektacytometer dependency for deformability measurements. METHODS: RBCs were collected from control patients. Rigid-cell fraction experiments were performed using varying concentrations of glutaraldehyde. Serial dilutions were used for varying the concentration of RBC. A convolutional neural network was constructed using Python and TensorFlow. RESULTS AND CONCLUSIONS: Measurements and model predictions show that a linear relationship between ΔEImax and rigid-cell fraction exists only for rigid-cell fractions less than 0.2. The proposed neural network architecture can be used successfully for both RBC concentration and rigid-cell fraction estimations without a need for a theoretical model.

Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex.

Coordinated assembly and disassembly of integrin-mediated focal adhesions (FAs) is essential for cell migration. Many studies have shown that FA disassembly requires Ca2+ influx, however our understanding of this process remains incomplete. Here, we show that Ca2+ influx via STIM1/Orai1 calcium channels, which cluster near FAs, leads to activation of the GTPase Arf5 via the Ca2+-activated GEF IQSec1, and that both IQSec1 and Arf5 activation are essential for adhesion disassembly. We further show that IQSec1 forms a complex with the lipid transfer protein ORP3, and that Ca2+ influx triggers PKC-dependent translocation of this complex to ER/plasma membrane (PM) contact sites adjacent to FAs. In addition to allosterically activating IQSec1, ORP3 also extracts PI4P from the PM, in exchange for phosphatidylcholine. ORP3-mediated lipid exchange is also important for FA turnover. Together, these findings identify a new pathway that links calcium influx to FA turnover during cell migration.

Individualized screening for chaperone activity in Gaucher disease using multiple patient derived primary cell lines.

The knowledge of individual response to a therapy, which can be assesed by in vitro screening, is essential for the development of therapeutics. Chaperone therapy is based on the ability of small molecules to fold the mutant protein to recover its function. As a novel approach for the treatment of Gaucher disease (GD), ambroxol was recently identified as a chaperone for GD, caused by the pathogenic variants in GBA gene, resulting in lysosomal enzyme glucocerebrosidase (GCase) deficiency. Since ambroxol activity is mutation-dependent, the assessment of the chaperone action requires adaptation of a cell model with genetic format identical to the patient. We compared the chaperone activity of ambroxol using different primary cells derived from GD patients with different GBA genotypes. Ambroxol enhanced GCase activity in cells with wild type GBA and in those, compound heterozygous for N370S, but was ineffective in cell lines with complex GBA alleles. In cells from patients with neuropathic GD and L444P/L444P genotype, the response to ambroxol was varied. We conclude that chaperone activity depends on diverse factors in addition to a particular GBA genotype. We showed that PBMCs and macrophages are the most relevant cell-based methods to screen the efficacy of ambroxol therapy. For pediatric patients, a non-invasive source of primary cells, urine derived kidney epithelial cells, have a vast potential for drug screening in GD. These findings demonstrate the importance of personalized screening to evaluate efficacy of chaperone therapy, especially in patients with neuronopathic GD.

The acute effects of preoperative ozone theraphy on surgical wound healing.

PURPOSE: To investigate the effects of preoperative rectal ozone insufflation on surgical wound healing over the proinflammatory cytokines and histopathological changes. METHODS: Twenty one rabbits were divided into 3 groups. Sham, surgical wound, and ozone applied (6 sessions, every other day 70 µg/mL in 12 mL O2-O3 mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels from all rabbits were studied at the basal, 24th hour, and 72nd hour. The histopathological examination was done by removing the surgical scar tissue at the end of 72nd hour. RESULTS: TNF-alfa and IL-6 levels were significantly lower compared to the control group, in the rabbits treated with ozone. The increase in angiogenesis, the decrease in the number of inflammatory cells, epidermal and dermal regeneration, better collagen deposition, and increased keratinisation in stratum corneum were observed in the histopathological examination. It was determined that the wound healing noticeably accelerated in the ozone group. CONCLUSION: Preoperative rectal ozone insufflation had a positive effect on surgical wound healing in acute period.

The acute effects of preoperative ozone theraphy on surgical wound healing

ABSTRACT PURPOSE: To investigate the effects of preoperative rectal ozone insufflation on surgical wound healing over the proinflammatory cytokines and histopathological changes. METHODS: Twenty one rabbits were divided into 3 groups. Sham, surgical wound, and ozone applied (6 sessions, every other day 70 µg/mL in 12 mL O2-O3 mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels from all rabbits were studied at the basal, 24th hour, and 72nd hour. The histopathological examination was done by removing the surgical scar tissue at the end of 72nd hour. RESULTS: TNF-alfa and IL-6 levels were significantly lower compared to the control group, in the rabbits treated with ozone. The increase in angiogenesis, the decrease in the number of inflammatory cells, epidermal and dermal regeneration, better collagen deposition, and increased keratinisation in stratum corneum were observed in the histopathological examination. It was determined that the wound healing noticeably accelerated in the ozone group. CONCLUSION: Preoperative rectal ozone insufflation had a positive effect on surgical wound healing in acute period.

Is hyperbaric oxygen or ozone effective in experimental endocarditis?

BACKGROUND: Infective endocarditis, a disease with high mortality and morbidity, is most commonly caused by Staphylococcus aureus; mortality and morbidity further increase in the presence of methicillin-resistant strains of S. aureus. Linezolid is the first of the oxazolidinones, a new antibiotic group that has been approved for the treatment of infections caused by gram-positive cocci. Linezolid reduces the quantity of microorganisms in vegetation to some extent; in addition, the use of hyperbaric oxygen (HBO) and ozone (O3) therapies is likely to improve targeted antibacterial effect. MATERIALS AND METHODS: Fifty-six adult male Wistar rats weighing 300-350 g were used. The subjects were divided into groups as follows: Group 1 (n = 8): control group that was not inoculated with microorganisms and was untreated; Group 2 (n = 8): control group that was inoculated with microorganisms but was untreated; Group 3 (n = 8): linezolid treatment group; Group 4 (n = 8): O3 therapy group; Group 5 (n = 8): HBO therapy group; Group 6 (n = 8): linezolid + O3 therapy group; Group 7 (n = 8): linezolid + HBO therapy group. RESULTS: In terms of reducing the number of colonies in the aortic valve, linezolid + HBO therapy was found to be the most effective treatment. Then, respectively linezolid + O3, linezolid, HBO, and O3 were found to be effective. CONCLUSIONS: We found that linezolid significantly reduced the number of bacteria in the vegetation in the experimental endocarditis model, and HBO therapy increases the effectiveness of linezolid and makes this better than O3.

Comparison of the GRACE risk score and the TIMI risk index in predicting the extent and severity of coronary artery disease in patients with acute coronary syndrome.

OBJECTIVE: The prognostic value of the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) and the Thrombolysis In Myocardial Infarction (TIMI) risk index (TRI) has been reported in coronary artery disease (CAD) patients. We aimed to evaluate the relationship between the GRS, TRI, and severity of CAD evaluated by SYNTAX score (SS) in patients with acute coronary syndrome (ACS). METHODS: Patients with ACS who were admitted to the coronary care unit of our institution were retrospectively evaluated in this study. A total of 287 patients with ACS [154 non-ST elevated ACS (NSTE-ACS), 133 ST elevated myocardial infarction (STEMI)] were included in the study. The GRS and TRI were calculated on admission using specified variables. The severity of CAD was evaluated using the SS. The patients were divided into low (GRS<109)-, intermediate (GRS 109-140)-, and high (GRS>140)-risk groups and group 1 (TRI<17), group 2 (TRI 17-26), and group 3 (TRI>26) according to GRS and TRI scores. A Pearson correlation analysis was used for the relation between GRS, TRI, and SS. RESULTS: Patients with a history of coronary artery bypass surgery, those who had missing data for calculating the GRS and TRI, and those whose systolic blood pressure (SBP) was more than 180 mm Hg or whose diastolic blood pressure (DBP) was more than 110 mm Hg were excluded from the study. Were excluded from the study. There were significant differences in mean age (p<0.001), heart rate (p<0.001), SS (p<0.001), TRI (p<0.001), rate of NSTE-ACS (p<0.001), and STEMI (p<0.001) in all patients between the risk groups. There was a positive significant correlation between the GRS and the SS (r=0.427, p<0.001), but there were no significant correlation between the TRI and SS (r=0.121, p=0.135). The area under the ROC curve value for GRS was 0.65 (95% CI: 0.56-0.74, p=0.001) in the prediction of severity of CAD. CONCLUSION: The GRS is more associated with SS than TRI in predicting the severity of CAD in patients with ACS.

Increased Platelet Distribution Width Is Associated With Severity of Coronary Artery Disease in Patients With Acute Coronary Syndrome.

Platelet activation plays a pivotal role in acute coronary syndrome (ACS). We investigated the relationship between platelet distribution width (PDW) and severity of coronary artery disease (CAD) in patients with ACS. A total of 502 patients with ACS were enrolled. High (n = 151) and low PDW (n = 351) groups were defined as patients having values in the third tertile (>17%) and lower 2 tertiles (≤17%). There were significantly higher Gensini score (44 [10-168] vs. 36 [2-132], P < .001), and neutrophil-lymphocyte ratio (3.1 [0.8-12.4] vs. .2.5 [0.3-13], P = .012) and baseline platelet counts were significantly lower (220 [61-623] vs. 233 [79-644] 10(3)/mm3, P = .022) in the high PDW group. The variables PDW >17%, diabetes mellitus, and myocardial infarction were found to be associated with high Gensini score (odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.27-2.88, P = .002; OR: 2.85, 95% CI: 1.91-4.25, P < .001; OR: 2.67, 95% CI:1.74-4.1, P < .001, respectively). An increased PDW (>17%) is associated with severity of CAD in patients with ACS.

The relationship between fragmented QRS complexes and SYNTAX and Gensini scores in patients with acute coronary syndrome.

BACKGROUND: Fragmented QRS (fQRS) complexes on 12-lead electrocardiography (ECG) have been reported to be predictors of cardiac events and all-cause mortality in coronary artery disease (CAD). AIM: To investigate the relationship between fQRS complexes and SYNTAX and Gensini scores in patients with acute coronary syndrome (ACS). METHODS: A total of 302 patients (223 men and 79 women) with ACS (133 ST elevated myocardial infarction [STEMI], 107 non-STEMI [NSTEMI], and 62 unstable angina pectoris [USAP]) were evaluated retrospectively in this study. An fQRS pattern was found in 70 patients (fQRS group) but was not found in 232 patients (non-fQRS group). SYNTAX score > 22 and Gensini score > 20 were defined as high SYNTAX and Gensini scores. The relationship between the presence of fQRS on 12-lead ECG and SYNTAX and Gensini scores was assessed. RESULTS: SYNTAX score (p < 0.001), Gensini score (p < 0.001), NYHA class (p < 0.001), QRS duration (p < 0.001), number of disease vessels (p = 0.003), and high sensitive troponin T levels (p = 0.026) were significantly higher in the fQRS group. The number of fQRS leads (HR 5.79, 95% CI 2.78-12.06, p < 0.001, HR 3.41, 95% CI 1.32-8.78, p = 0.016, respectively) was found to be an independent predictor of high SYNTAX score and high Gensini score in multivariate analysis. CONCLUSIONS: The number of fQRS leads on 12-lead ECG on admission is associated with the severity and complexity of CAD in patients with ACS.

Effects of tenoxicam in experimental corrosive esophagitis model.

Esophageal stricture, one of the important complications of corrosive esophagus, develops following edema and granulation tissue that forms during and after the inflammatory reactions. Tenoxicam, a non-steroid anti-inflammatory drug with a long half-life, prevents various leukocyte functions including phagocyte and histamine secretion by inhibiting prostaglandin synthesis and removes various oxygen radicals in the region of inflammation. We designed this as a histopathological study using tenoxicam in rats for which we created a corrosive esophagus model. After necessary authorizations were obtained, the study was performed in Çanakkale 18 Mart University experimental animal laboratory. Twenty-four Wistar albino rats, weighing 220-240 g, were used for the experiment. Experimental animals were randomized into three groups: tenoxicam group (group T, n:8), control group (group C, n:8), and sham group (group S, n:8). Tenoxicam 0.5 mg/kg/day was administered to animals in group T, where esophageal burn was developed experimentally, 5 mg/kg 0.9% NaCL was administered i.p. to rats in group C for 15 days, once in 24 hours. No procedure was applied to rats in group S. After 15 days, all animals were sacrificed under general anesthesia and their esophagi were extracted. As a result of histopathological evaluation, inflammation and fibroblast proliferation was not observed in rats in the sham group (group S). Intense inflammation was observed in six rats (6+/2-) in the control group, and fibroblast proliferation was observed as 5+/3-. And in treatment groups, inflammation was evaluated as 3+/5-, and fibroblast proliferation as 3+/5-. In our study, histopathologic damage score was higher in the control group (P < 0.005). We deduce that tenoxicam can be useful in the treatment of caustic esophageal injuries in the acute phase, but think that these drugs require further researches and clinical studies before routine clinical use.

Atrial septal defect repair; our early and mid-phase results.

OBJECTIVE: Atrial septal defect is one of the most commonly encountered congenital heart diseases in adults. The effect of age of the patient to the surgery is disputable. The purpose of this report was to evaluate surgical repair in patients with ASD who are operated in our clinic. METHODS: Total 40 patients were subjected to surgical repair due to ASD in Van Yuksek Ihtisas Education and Research Hospital between February 2006 and April 2009. Twenty seven of the patients were female and 13 were male, their ages differed between 8 and 71 and mean age of the patients was 33.70±14.04. RESULT: Operative mortality did not occur. Two of our patients had coronary arterial disease in addition to ASD. ASD repair was performed together with coronary bypass surgery. Closing of ASD resulted in an increase in left ventricular ejection fraction, and a decrease in pulmonary arterial pressure and cardiothoracic ratio. Recovery in the functional capacity was observed post-surgery according to NYHA. CONCLUSION: In this series, surgical results of the patients of various ages, with ASD closed were positive.