MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

Measurement of normal spleen volume and dimensions in all child age groups by abdominal computed tomography.

OBJECTIVE: This study aimed to calculate the spleen size and volume, portal vein diameter, splenic vein diameter, and accessory spleen presence in children aged 0-18 years in the Turkish population by computed tomography, according to age and gender. MATERIALS AND METHODS: Abdominal computed tomography images of 406 children without systemic or organospecific disease were retrospectively analyzed in the study. Maximum interpolar length in axial and coronal sections in addition to maximum width at hilus level in axial sections of the spleen were measured in abdominal computed tomography. Luminal diameter measurements were obtained from axial sections at the level of the liver hilum of the portal vein and the hilus of the spleen of the splenic vein. RESULTS: As age increases, the axial longest dimension (ALD), axial longest thickness (ALT) and coronal longest dimension (CLD) dimensions also increase, and this increase is statistically significant (p<0.001). The lowest splenic volume was measured in the 0-2 age group as 25.3 cm3, and the highest splenic volume was 506.2 cm3 in the 17-18 age group. Splenic vein diameter is between 1.9 mm and 11.0 mm, and the mean splenic vein diameter increases with increasing age. Portal vein diameter is between 4.1 mm and 14.9 mm, and the average portal vein diameter increases with age. The accessory spleen was seen in 22 (5.4%) children. Accessory spleen size ranged from 5 mm to 17 mm. There was a strong positive correlation between spleen volume and splenic vein diameter (r=0.696 p<0.001). Similarly, there was a strong positive correlation between spleen volume and portal vein diameter (r=0.704 p<0.001). CONCLUSIONS: It may be helpful to know the normal spleen volume in healthy children according to age groups in making the correct diagnosis of splenomegaly. We assume that it will play an important role in the accurate diagnosis of portal hypertension to know the upper and lower limits of the portal vein and splenic vein diameters.

Can evaluating adrenal glands in computed tomography contribute to predicting the prognosis of hospitalized COVID-19 patients?

OBJECTIVE: The novel coronavirus disease 2019 (COVID-19) may affect the adrenal glands. Therefore, it is important to evaluate the morphologic appearance of the adrenal glands by thorax computed tomography (CT). On CT scans, stranding in peripheral fatty tissue with enlarged adrenal glands may indicate signs of adrenal infarction (SAI). The present study aimed to evaluate the incidence of SAI and determine whether this finding may contribute to predictions of the prognosis of COVID-19. PATIENTS AND METHODS: A total of 343 patients who had been hospitalized at Malatya Training and Research Hospital between September 1 and 30, 2020, with a diagnosis of COVID-19 were enrolled in this study. All patients underwent thorax CT scans that included their adrenal glands. RESULTS: Of the enrolled patients, 16.0% had SAI. Moreover, 41.8% of patients with SAI and 15.3% of patients without SAI were treated in the Intensive Care Unit (ICU). Patients with SAI had a significantly higher rate of ICU admission (p < 0.001). Mortality rates were also significantly higher among patients with SAI than those without p < 0.001). CONCLUSIONS: In this study, it was found that COVID-19 patients with SAI may have a poorer prognosis. More comprehensive studies are needed on this subject, but the present study may provide helpful preliminary information in terms of prognosis.

The evaluation of the trachea as a new parameter in determining the prognosis of COVID-19: first pilot study.

OBJECTIVE: Coronavirus disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) follows a biphasic disease model consisting of an early viral response phase and an inflammation phase. SARS-CoV-2 has a high affinity for the upper respiratory tract and conjunctiva; hence, it can infect the upper respiratory tract and facilitate airway inflammation. COVID-19 also affects the tracheal epithelial cells. We hypothesized that the size of the trachea increases depending on the severity of the disease, and this increase is an indicator of poor prognosis. There are no studies on this subject in literature, to the best of our knowledge. For this purpose, in this study, the tracheas of 326 patients who reported to the radiology clinic were examined by evaluating the thoracic computed tomography (CT) images. PATIENTS AND METHODS: The patients who were admitted to the Malatya Training and Research Hospital between September and December 2020, had a positive SARS-CoV-2 nasopharyngeal reverse transcription-polymerase chain reaction result, and had undergone thoracic CT, were included in the study. The thoracic CT scans without respiratory artifacts were evaluated, and anteroposterior (AP) and transverse diameters of the trachea were measured at the thyroid and bifurcation levels. RESULTS: We believe that a tracheal AP diameter of >20 mm at the thyroid level and a tracheal AP diameter of 18 mm at the thyroid bifurcation level (according to Group 3 and Group 4) may be indicators of poor prognosis. In terms of survival, a tracheal AP diameter of >18 mm at the bifurcation level can be considered as a poor prognostic factor. CONCLUSIONS: The tracheal diameter may increase in proportion to the severity of inflammation, indicating or accompanying a poor prognosis. Patients with extensive involvement should be monitored closely for the development of tracheal stenosis.

Long-term vitamin-K antagonist use and coronary artery calcification.

BACKGROUND: The aim of this study was to investigate the impact of vitamin K antagonist (VKA) therapy on coronary artery calcification (CAC) by comparing long-term VKA users with metallic prosthetic valves (MPVs) and VKA-free patients undergoing coronary calcium scoring for cardiovascular (CV) risk stratification. METHODS: A total of 108 patients (43 VKA users with MPV and 65 gender-, age-, and risk-factor-matched VKA-free patients) were included in the study. CAC was determined via computed tomography (CT) and quantified on the basis of the Agatston score. The VKA group comprised patients who had an MPV for longer than 5 years, which entailed long-term VKA use. RESULTS: Long-term VKA users had more calcified coronary arteries compared with the control group (178.1 ± 278 vs. 61.1 ± 130.6, p = 0.01). There was no difference between groups in terms of traditional CV risk factors. The mean duration of VKA use was 15 ± 7 years for the patients with MPV. There was no correlation between the duration of VKA use and mean Agatston score (r = 0.2, p = 0.215). CONCLUSION: With its unique selection of patient groups, our study extends the findings of previous research that long-term VKA use is related to CAC as detected via CT scanning. The longer and more potent VKA regimen required for MPV patients is the primary cause of CAC in this group.

Clinical characteristics and prognosis of cardiac tamponade patients: 5­year experience at a tertiary center.

BACKGROUND: Cardiac tamponade (CT) is characterized by compression of the cardiac chambers due to pericardial fluid accumulation. The etiology and prognosis may vary in different regions, and thus patient series from various regions can be useful for exploring the etiological and prognostic disparities. The aim of this study was to determine the clinical characteristics of patients with imminent CT, to evaluate the diagnostic performance of biochemical, microbiologic, and pathologic laboratory analysis, and to ascertain the prognosis of CT patients. METHODS: We enrolled all patients with imminent CT who underwent percutaneous pericardiocentesis between July 2012 and December 2017 in this retrospective study. The patients were classified into three etiology groups: (a) malignancy (MRCT); (b) iatrogenic/mechanical complication of myocardial infarction (IMCT); and (c) other causes (OCT). Clinical information, laboratory findings, and survival data were recorded. RESULTS: In total, 186 pericardiocentesis procedures were performed on 153 consecutive patients with CT. The median follow-up was 137 days (range: 1-1937). The MRCT group had the highest mortality rate (79%) in 12 months, while the OCT group had the lowest rate (27%). We determined that increased age, higher serum urea levels, and malignancy-related CT were independent predictors of mortality. The mortality rates of the MRCT and IMCT groups were similar, with both of them being significantly higher than the rate of the OCT group. In all, 15 patients were diagnosed with a new malignancy via pericardial fluid cytology. CONCLUSION: Patients in the MRCT and IMCT groups had a poor prognosis. The presence of malignancy was found to be the most powerful predictor of mortality in CT patients.

The prognostic value of tumor budding in patients who had surgery for rectal cancer with and without neoadjuvant therapy.

BACKGROUND: The aim of this study was to investigate the prognostic value of tumor budding (TB) in rectal cancer patients. TB in the specimens of patients who received neoadjuvant chemoradiotherapy was specifically analyzed. METHODS: This study was conducted on rectal cancer patients treated at Dokuz Eylul University Hospital, Turkey, between January 2000 and June 2010. Prospectively recorded clinicopathological data and the oncological outcomes of patients who received neoadjuvant chemoradiotherapy (CRT) (n = 117) and also patients who did not receive it (n = 113) were analyzed. TB was defined as an isolated single cancer cell or a cluster of cells composed of less than 5 cells of a "budding focus". Budding intensity was scored as follows: none (0), mild (1-5 buds), moderate (6-10 buds), and severe (> 10 buds). Two tumor budding intesity groups were created, TB-1 (none, few) and TB-2 (moderate, severe) for statistical analysis. RESULTS: The median follow-up time was 40.12 ± 27.5 months. The 5-year overall and disease-free survival (DFS) rates were 66% and 62%, respectively. Multivariate analysis of overall survival in all patients showed that TB intensity (HR 2.64; 95% CI 1.46-4.77) and radial margin status (HR 2.16; 95% CI 1.18-3.96) were independent predictors of decreased overall survival. In patients who received CRT, TB (HR 4.87; 95% CI 2.10-11.28) and distant metastasis (HR 4.31; 95% CI 1.81-10.22) were predictive of survival while in patients who did not receive CRT, TB (HR 4.28; 95% CI 1.60-11.49), distant metastasis (HR 2.33; 95% CI 1.19-4.60), radial margin status (HR 2.53; 95% CI 1.09-5.91), and venous invasion (HR 4.48; 95% CI 2.14-9.39) were significantly independent predictors of survival. In multivariate analysis of all patients decreased DFS was correlated with lymph node involvement (HR 2.78; 95% CI 1.60-4.87), venous invasion (HR 1.76; 95% CI 1.00-3.09), and with radial margin status (HR 2.31; 95% CI 1.27-4.22). In multivariate analysis in the CRT group, decreased DFS was significantly associated with lymph node involvement (HR 4.39; 95% CI 1.70-11.33) and radial margin status (HR 2.56; 95% CI 1.12-5.90) while only lymph node involvement (HR 2.33; 95% CI 1.16-4.66) was a significant predictor of decreased DFS in patients who did not receive CRT. CONCLUSIONS: TB has prognostic value as important as lymph node involvement and radial margin status and it may be a helpful prognostic indicator even after CRT. TB should be included in the TNM classification and may be used in planning adjuvant therapy.

CSF flow patterns in the brain in patients with neuro-Behçet disease and Behçet disease.

OBJECTIVE: In the etiopathogenesis of Behcet disease (BD) and Neuro-Behcet disease (NBD), vascular eclipse occurs in both the arteries and veins. The disease affects all vascular structures. The present study evaluates the use of Phase Contrast (PC) Cerebral Spinal Fluid (CSF) Flow Magnetic Resonance Imaging (MRI), a non-invasive technique for measuring CSF dynamics, for determining the level of aqueducts that are influenced in BD and NBD. PATIENTS AND METHODS: The quantitative evaluation of CSF flow in BD and NBD was performed using images obtained at the level of the cerebral aqueduct on the semi-axial plane. The PC-MRI angiography technique was used. RESULTS: There is no distinctive difference between BD and NBD that can be distinguished by the aqueduct diameters of both conditions. A clear increase in aqueduct diameter occurred BD and NBD group when compared to the control group. While there were no differences found between the BD group and the control group regarding peak velocity, average velocity, forward flow, reverse flow, net forward flow, and flow, there were distinctive increases in these various factors in the NBD group. CONCLUSIONS: Using the non-invasive PC-MRI technique, this study found that in BD and NBD patients, changes occurred in CSF flow figures. Increases in CSF parameters were also observed in NBD patients, a finding which may be helpful for future distinction between BD and NBD during diagnosis.

P1294Evaluation of right atrium mechanics and relation with loading conditions by speckle tracking echocardiography.

PURPOSE: The aim of this study is to evaluate the right atrial (RA) mechanics and change in echocardiographic parameters used for assessment of RA by examining the end stage kidney patients before and after the hemodialysis (HD). METHODS: Patients between 18 and 85 years of age, receiving HD for at least 6 months were included. The echocardiographic images were obtained before and after hemodialysis therapy. Two-dimensional speckle tracking strain analysis was performed for right atrium in 62 patients. Reference points for analysis are set on the "P" waves. RA reservoir, conduit and contraction phase longitudinal strain (Figure 1) and strain rates (Figure 2) were calculated. The changes in echocardiographic methods before and after hemodialysis were examined. Correlation between volume depletion and change in echocardiographic parameters were calculated. RESULTS: 62 patients (49.7 ± 16.9 years of age, 22 women) were included in study. The mean volume of ultrafiltration was 2958.12 ± 1050.5 ml . The chamber sizes RA are decreased after hemodialysis (RA major diameter; 4.74 ± 0.62 cm vs. 4.46 ± 0.54 cm p<0.001, RA area; 13.8 ± 3.0 cm2 vs. 10.6 ± 2.8 cm2 p<0.001). Two dimensional speckle tracking analysis showed that; RA reservoir phase strain (% 45.60 ± 10.8 vs. % 38.15 ± 8.11 p<0.001). RA conduit phase strain rate (-1.46 ± 0.82 s-1 vs. -1.2 ± 0.56 s-1 p<0.001) measurements are volume dependent. RA reservoir phase strain rate (2.25 ± 0.65 s- vs. 2.5 ± 0.54 s-1 p:0.091) RA contraction strain (% -16.73 ± 6.8 vs. % -16.35 ± 7.1 p:0.835) and RA contraction strain rate (-2.15 ± 0.95 s-1 vs. -2.21 ± 0.72 s-1 p:0.596) are volume independent parameters. RA reservoir phase strain (r=0.332. p:0.008) showed significant correlation with the ultra filtrated volume. CONCLUSION: Strain rates of RA reservoir phase and RA contraction and RA contraction strain are found to be volume independent measurements obtained by speckle tracking. Explaining RA mechanics with echocardiography is an easy and repeatable assessment which also elucidates more about cardiac pathophysiology and hemodynamics of patients. Moreover defining novel volume independent parameters for evaluation of RA would contribute to clinical perspectives of patients. Abstract P1294 Figure.Abstract P1294 Figure.

Combination Therapy in Pulmonary Arterial Hypertension: Single Centre Long-term Experience.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vascular bed and causes right heart failure and death. Combination therapy which targets three different pathways is necessary due to the progressive nature of the disease. In patients with PAH, there are two approaches in combination therapy: "first-line up-front" and "sequential add-on" treatment. In "firstline up-front" treatment, patients receive double or triple drug therapy from the start. In the "sequential add-on" approach, a single drug is initially started and then according to the patient's requirements, a second or third drug is added. There is insufficient evidence about the efficiency and safety of treatment approaches. In this study, we aimed to evaluate the treatment approach in patients with PAH at a tertiary centre. METHODS: Pulmonary arterial hypertension was diagnosed according to clinical, echocardiographic and right heart catheterization findings. The patients received bosentan, sildenafil and iloprost treatment in accordance with guidelines recommendations. Clinical worsening in patients was defined as death, requirement of hospitalization for PAH, a 15% decline in the six-minute walk test (6MWT) distance, deterioration in functional capacity, and symptoms and findings of right heart failure. RESULTS: At the end of the follow-up period, clinical and echocardiographic findings, brain natriuretic peptide (BNP) levels and oxygen saturation were similar between patients who completed the study with monotherapy and with combination therapy. The follow-up period was significantly longer in patients who required combination treatment. Two patients (6.9%) died and four patients (13.8%) were hospitalized due to recurrent symptoms and findings of right heart failure. At the end of follow-up, 10 patients (34.5%) completed the study with a single drug, 15 patients (51.7%) with two drugs and four patients (13.8%) with three drugs. CONCLUSION: In this study, combination therapy was given to patients as "sequential add-on therapy". At the end of the follow-up period, monotherapy was sufficient in 34.5% of patients of the study group and in eight patients, sildenafil or prostaglandin analogues were added; a total of 15 patients (48.4%) completed the study under dual therapy. Four patients (12.9%) received combination therapy with three drugs.

Acute Anterior Myocardial Infarction Accompanied by Acute Inferior Myocardial Infarction: A Very Rare Coronary Artery Anomaly.

Coronary artery anomalies are rare and mostly silent in clinical practice. First manifestation of this congenital abnormality can be devastating as syncope, acute coronary syndrome, and sudden cardiac death. Herein we report a case with coronary artery anomaly complicated with ST segment myocardial infarction in both inferior and anterior walls simultaneously diagnosed during primary percutaneous coronary intervention.

Rapidly progressing A/H1N1 (09) pandemic influenza virus infection in pregnancy.

We presented a pandemic H1N1 2009 influenza virus infection in two pregnant women who were referred to the intensive care unit (ICU) with a rapidly progressive disease course. Both women had unremarkable past medical history. The first woman had the symptoms of fever, cough, dyspnea and tachypnea lasting for four days. The second woman refused to take oseltamivir treatment. They were both referred to ICU with the diagnosis of pneumonia and acute respiratory distress syndrome. The second woman was intubated for two days in ICU. Both women showed a gradual improvement in their follow up and were discharged. Early admission, prompt diagnosis and early recourse to antiviral treatment gives better results in H1N1 infected pregnant women (Fig. 2, Ref. 10).

Action of an HMG CoA reductase inhibitor, lovastatin, on apoptosis of untransformed and ts-SV40 transformed human smooth muscle cells derived from saphenous vein.

The effect of lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl coenzyme A (HMG CoA) reductase, was examined on human vascular smooth muscle cells (HVSMC). Untransformed HVSMC were obtained from saphenous vein and in addition an SV-40 transformed immortalized cell line (HVTs-SM1) derived from saphenous vein smooth muscle was also used. HVTs-SM1 cell proliferation and DNA synthesis were measured, and cell cycle analysis was performed by flow cytometry. Apoptosis in both cell types was assessed by a combination of flow cytometry, terminal deoxynucleotidyl transferase (TUNEL) reagent-based immunocytochemistry, DAPI staining, and DNA agarose gel electrophoresis. Lovastatin had no effect on apoptosis of HVSMC over 96 h in serum-free conditions or after stimulation with platelet-derived growth factor (PDGF-BB), although PDGF-BB increased apoptosis in HVSMC, and this was prevented by lovastatin. In HVTs-SM1 cells lovastatin inhibited cell proliferation and DNA synthesis and induced apoptosis in a time- and concentration-dependent manner. The effects of lovastatin on cell proliferation, DNA synthesis, and apoptosis were prevented by coincubation with mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. Lovastatin does not induce apoptosis in saphenous vein HVSMC in culture and inhibits PDGF-BB-induced DNA synthesis and apoptosis. In contrast, in SV40 transformed immortalized HVTs-SM1 cells, lovastatin induces apoptosis and inhibits cell proliferation and DNA synthesis. The pro-apoptotic effects of lovastatin in SV40 transformed HVTs-SM1 cells may be related to the enhanced rate of proliferation or deregulation of the cell cycle in this cell line.