Can Fractional Exhaled Nitric Oxide (FeNO) Serve as a Clinical Indicator for Patients Hospitalized with Crimean-Congo Hemorrhagic Fever?

Crimean-Congo hemorrhagic fever (CCHF), a zoonotic disease spread by infected viruses, can be a significant cause of morbidity and mortality in endemic areas. This prospective study aimed to establish the relationship between fractional exhaled nitric oxide (FeNO) levels and clinical prognosis of CCHF. The study included 85 participants: 55 patients followed up for CCHF from May to August 2022, and 30 healthy controls. FeNO levels were measured upon hospital admission and were 7.6 ± 3.3 parts per billion (ppb) in patients with mild/moderate CCHF, 2.5 ± 2.1 ppb in patients with severe CCHF, and 6.7 ± 1.7 ppb in the healthy control group. There was no statistically significant difference in FeNO levels between the control group and patients with mild/moderate CCHF (P = 0.09), whereas patients with severe CCHF had lower FeNO levels than those in the control group and patients with mild/moderate CCHF (P < 0.001 for both). FeNO measurement may offer a noninvasive and easily applied approach for predicting the clinical course and prognosis of CCHF in the early stages of the disease.

Evaluation of the role of serum DcR3 levels in the early clinical prognosis of patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease that is transmitted by Hyalomma ticks and is endemic in many parts of the world. This study aimed to determine the relationship between early serum Decoy receptor-3 (DcR3) level and clinical severity in patients with CCHF. METHODS: The study included 88 patients hospitalized for CCHF between April and August 2022 and a control group of 40 healthy individuals. The patients were divided according to clinical course as those with mild/moderate (group 1, n = 55) and severe (group 2, n = 33) CCHF. DcR3 levels were measured by enzyme-linked immunosorbent assay of serum obtained at the time of diagnosis. RESULTS: Fever, hemorrhage, nausea, headache, diarrhea, and hypoxia were significantly more common among patients with severe CCHF than patients with mild/moderate CCHF (p < 0.001, <0.001, 0.02, 0.01, <0.001, and < 0.001, respectively). Group 2 had higher serum DcR3 levels than both group 1 and the control group (p < 0.001 for both). Serum DcR3 levels were also significantly higher in group 1 than in the control group (p < 0.001). Using 98.4 ng/mL as the cut-off value, serum DcR3 had 99% sensitivity and 88% specificity in differentiating patients with severe CCHF from those with mild/moderate CCHF. CONCLUSION: During the high season in our endemic region, CCHF can present with a severe clinical course independent of age and comorbidities, unlike other infectious diseases. Elevated DcR3 observed early in the disease may allow additional immunomodulatory therapies to be tried in addition to antiviral therapy in CCHF, for which treatment options are limited.

Evaluation of IGFBP5 expression and plasma osteopontin level in COVID-19 patients.

PURPOSE: The aim of this study is to investigate insulin-like growth factor binding protein 5 (IGFBP5) expression in coronavirus disease 2019 (COVID-19) patients and its relationships with COVID-19 laboratory findings and plasma osteopontin (OPN) levels. MATERIALS AND METHODS: We enrolled 60 patients with COVID-19 and 30 healthy individuals in this study. mRNA expression of IGFBP5 was measured by RT-PCR. Plasma OPN levels were measured via the ELISA method. RESULTS: Plasma OPN levels were higher and IGFBP5 expression levels were lower in COVID-19 patients than in the healthy individuals (p â€‹= â€‹0.0057 and p â€‹= â€‹0.0142, respectively). Critically ill patients had higher OPN and lower IGFBP5 than non-critically ill patients. Patients with affected lungs demonstrated increased OPN and decreased IGFBP5 (p â€‹= â€‹0.00032 and p â€‹= â€‹0.044, respectively). Receiver operating characteristic (ROC) analysis indicated that IGFBP5 expression and OPN levels can be used discriminate non-critically from critically ill patients (p â€‹= â€‹0.049; p â€‹= â€‹0.0016, respectively). CONCLUSION: This study demonstrated that patients with a poor prognosis had increased OPN and decreased IGFBP5. High values of OPN and low values of IGFBP5 may be considered as signs of disease severity. Tissue-specific IGFBP5 expression may contribute to understanding the role of IGFBP5 in the lungs in COVID-19 cases.

Preliminary investigation of gene expression levels of PAPP-A, STC-2, and HIF-1α in SARS-Cov-2 infected patients.

BACKGROUND: Coronavirus-19 is still considered a pandemic that influences the world. Other molecular alterations should be clearer besides the increasing cytokine storm and pro-inflammatory molecules. Hypoxic conditions that induce HIF-1α lead to stimulate gene expression of STC-2 that targets PAPP-A expression. This study aimed to determine gene expression levels of PAPP-A, STC-2, and HIF-1α in COVID-19 infection. We also aimed to reveal the relationship of these genes with laboratory and clinical data of COVID-19 patients. MATERIALS AND RESULTS: We extracted RNA from peripheral blood samples of COVID-19(+) and COVID-19(-) individuals. The real-time PCR method was used to measure mRNA expression of PAPP-A, STC-2, and HIF-1α. Gene expression analysis was evaluated by the 2-ΔΔCt method. PAPP-A, STC-2, and HIF-1α mRNA expressions of severe patients were higher than healthy individuals (p = 0.0451, p = 0.4466, p < 0.0001, respectively). Correlation analysis of gene expression patterns of severe patients demonstrated a positive correlation between PAPP-A and STC-2 (p < 0.0001, r = 0.8638). CONCLUSION: This is the first study that investigates the relation of PAPP-A, STC-2, and HIF-1α gene expression in patients with COVID-19 infection. Besides the routine laboratory findings, PAPP-A, STC-2, and HIF-1α mRNA expressions may be considered to patients' prognosis as a sign of increased cytokines and pro-inflammatory molecules.

High-Frequency Chest Wall Oscillation in Patients with COVID-19: A Pilot Feasibility Study.

OBJECTIVE: Coronavirus 2019 disease presents in a spectrum that can range from mild viral infection to pneu- monia. Common symptoms of coronavirus disease 2019 pneumonia include cough, sputum, and shortness of breath. High-frequency chest wall oscillation is a pulmonary rehabilitation method used for the recovery of pulmonary functions and removal of secretions in the lungs. The aim of the study was to evaluate the efficacy of high-frequency chest wall oscillation on patients with coronavirus disease 2019 pneumonia. MATERIALS AND METHODS: In this study, 100 patients, between 18 and 70 years old, with a positive polymerase chain reaction result for coronavirus disease 2019, were included. Standard medical treatment was applied to all patients. In group rehabilitation, high-frequency chest wall oscillation treatment was applied twice a day for 20 minutes for 5 days. No additional intervention was made to the control group. Pulmonary function tests and oxygenation were evaluated on the first and fifth days. Patients' high-flow oxygen, non-invasive mechani- cal ventilation, and invasive mechanical ventilation needs were evaluated and recorded. RESULTS: Compared with the control group, the forced expiratory volume in 1 second, forced vital capacity, and peak expiratory flow rates were statistically higher in the rehabilitation group on the fifth day (P < .05). On evaluating the oxygenation of patients, the fifth day to first-day oxygen saturation difference was signifi- cantly higher in rehabilitation group than in control group (P < .05). Furthermore, the number of patients who needed non-invasive mechanical ventilation was lower in the rehabilitation group (P < .05). CONCLUSION: This study demonstrated that pulmonary rehabilitation applied with the high-frequency chest wall oscillation device in patients with coronavirus disease 2019 in the early period contributed to the improvement of oxygenation by providing significant improvement as observed in the pulmonary function tests of the patients.

COVID-19: vaccination vs. hospitalization.

OBJECTIVE: Vaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols. SETTING: Inoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose. METHODS: We collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status. RESULTS: We identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac. CONCLUSION: Effective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination.

Evaluation of 3-month follow-up of patients with postacute COVID-19 syndrome.

In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various postacute signs and symptoms. This study aimed to evaluate patients with postacute COVID-19 over 12 weeks of follow-up. The study included 151 patients who were diagnosed with COVID-19 by real-time polymerase chain reaction of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: nonsevere pneumonia (Group 1), severe pneumonia (Group 2), and severe pneumonia requiring intensive care (Group 3). Evaluation of laboratory parameters at 4 and 12 weeks showed that Group 3 had a higher lactose dehydrogenase (LDH) level and a lower mean platelet volume than the other groups at both time points (p = 0.001 for all). Group 3 also had lower percent predicted forced vital capacity (FVC%), percent predicted forced expiration volume in 1 s (FEV1%), and percent predicted diffusion capacity of the lungs for carbon monoxide divided by alveolar volume (DLCO/VA%) compared to Groups 1 and 2 at Week 4 (p = 0.001, 0.004, 0.001, respectively) and compared to Group 1 at 12 weeks (p = 0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p = 0.001 for all). Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up.

Effect of montelukast therapy on clinical course, pulmonary function, and mortality in patients with COVID-19.

The inflammatory/anti-inflammatory balance has an important role in the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease [COVID-19]) infection, which has affected over 200 million people since it first appeared in China in December 2019. This study aimed to determine the effectiveness of montelukast, which has known anti-inflammatory and bronchodilatory effects, in these patients. The prospective randomized controlled study included 180 patients who were hospitalized in the infectious diseases department of our hospital between May and July 2021 and were diagnosed with the delta variant of SARS-CoV-2 by real-time polymerase chain reaction of nasopharyngeal swabs. The patients were divided into three groups and received only standard treatment according to national guidelines (Group 1) or standard treatment plus 10 mg/day montelukast (Group 2) or 20 mg/day montelukast (Group 3). Laboratory parameters and pulmonary function tests (PFTs) at admission and on Day 5 of treatment were compared. Comparison of laboratory parameters on Day 5 showed that Groups 2 and 3 had significantly lower levels of lactate dehydrogenase, fibrinogen, D-dimer, C-reactive protein, and procalcitonin compared with Group 1 (p = 0.04, 0.002, 0.05, 0.03, and 0.04, respectively). In the comparison between Groups 2 and 3, only fibrinogen was significantly lower in Group 3 (p = 0.02). PFT results did not differ between the groups at admission, while on Day 5, only Group 3 showed significant improvements in forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow 25-75 compared with admission (p = 0.001 for all). Montelukast may be beneficial in COVID-19 patients to maintain the inflammatory/anti-inflammatory balance, prevent respiratory failure through its bronchodilator activity, and reduce mortality.

The Epidemiology, Clinical Manifestations, Radiology, Microbiology, Treatment, and Prognosis of Echinococcosis: Results of NENEHATUN Study.

Aim: Echinococcosis, caused by Echinococcus species, is an important zoonotic disease causing major health problems in humans and animals. Herein, we aimed to evaluate the epidemiology, clinical and laboratory parameters, radiological, serological, pathological, and treatment protocols of followed-up cases of hydatidosis. Methods: A total of 550 patients diagnosed with hydatid cyst disease were included in this study. Patients who were positive for one or more of the enzyme-linked immunosorbent assay or indirect hemagglutination test, pathological results, or radiological findings were examined. The data analyzed were collected from nine centers between 2008 and 2020. Records were examined retrospectively. Results: Among the patients, 292 (53.1%) were women and 258 (46.9%) were men. The patients' mean age was 44.4 ± 17.4 years. A history of living in rural areas was recorded in 57.4% of the patients. A total of 435 (79.1%) patients were symptomatic. The most common symptoms were abdominal pain in 277 (50.4%), listlessness in 244 (44.4%), and cough in 140 (25.5%) patients. Hepatomegaly was found in 147 (26.7%), and decreased breath sounds were observed in 124 (22.5%) patients. Radiological examination was performed in all cases and serological methods were also applied to 428 (77.8%) patients. The most frequently applied serological test was IHA (37.8%). A single cyst has been found in 66% patients. Hepatic involvement occurred in 327 (59.4%), pulmonary involvement was found in 128 (23.3%), whereas both of them were recorded in 43 (7.8%) patients. Splenic involvement was only detected in nine (1.6%) patients. Echinococcus granulosus (72.5%) was most frequently detected. Cyst diameters of 56.9% of the patients were in the range of 5-10 cm. A total of 414 (75.2%) patients received albendazole as an antiparasitic. Mortality was noted in nine (1.6%) patients. Conclusion: Echinococcosis is an important public health problem in Turkey. It can affect the social, economic, and political structures of the community. Public education and awareness are extremely important.

The relationship between NLRP3 rs10159239 and Vaspin rs2236242 gene variants and obstructive sleep apnea.

BACKGROUND: In obstructive sleep apnea (OSA), recurrent upper airway obstruction and apnea/hypopnea episodes result in endothelial dysfunction, which leads to the release of many proinflammatory cytokines and reactive oxygen species (ROS). ROS induces NLRP3, a protein involved in the synthesis of interleukin (IL)-1 and IL-18; vaspin is a serine protease inhibitor that has an important role in suppressing the activation of NLRP3 inflammasome. In this study, we aimed to investigate the effect of NLRP3 rs10159239 (rs9239) and vaspin rs2236242 (rs6242) single nucleotide polymorphisms (SNPs) on OSA development. METHODS: This study included 220 individuals who underwent polysomnography (118 patients with OSA and 102 healthy controls). NLRP3 rs9239 and vaspin rs6242 mutation frequencies were analyzed. RESULTS: The NLRP3 rs9239 SNP genotype analysis revealed no statistically significant differences between the OSA and control groups. In the vaspin gene analysis, the rs6242 AA genotype was significantly more frequent in the OSA group compared with the control group, while the AT genotype was more frequent in controls (P = 0.004, P = 0.02). Comparison of rs6242 allele levels showed that the A allele was significantly more frequent in OSA patients than in controls (P = 0.03). The AA genotype was significantly more frequent in patients with severe OSA than in patients with mild or moderate OSA and the control group (P = 0.001 for all). Serum vaspin levels were significantly lower in carriers of the AA genotype than those with AT and TT genotypes (P = 0.001). CONCLUSION: The vaspin rs6242 SNP AA genotype increased susceptibility to OSA, while the AT genotype appeared to be protective. The lower plasma vaspin levels in OSA compared with the control group and in patients with the AA genotype suggest that vaspin may be a protective biomarker for OSA.

Evaluation of the relationship between TREM-1/TREM-2 ratio and clinical course in COVID-19 pneumonia.

OBJECTIVE: The inflammatory/anti-inflammatory balance has an important role in the clinical course of SARS-CoV-2 infection (COVID-19), which has affected over 100 million people since it first appeared in China in December 2019. The aim of this study was to investigate the relationship between triggering receptor expressed on myeloid cells (TREM)-1/TREM-2 ratio and COVID-19 severity. METHODS: A total of 171 individuals were included in the study: 121 patients who were admitted to the chest diseases department and intensive care unit of our hospital and diagnosed with COVID-19 by real-time PCR of nasopharyngeal swab samples from December 2020 to March 2021 and a control group consisting of 50 asymptomatic health workers in our hospital who had negative real-time PCR results during routine COVID-19 screening. RESULTS: TREM-1 level was significantly higher in patients with severe disease compared with the moderate and control groups (P = .003, P = .001). TREM-2 levels did not differ significantly in moderate and severe patients (P = .36) but were significantly higher in both patient groups compared with the control group (P = .001 for both). TREM-1/TREM-2 ratio was significantly higher in the severe patient group than in the moderate and control groups (P = .001 for both). In receiver operating characteristic curve analysis of TREM-1/TREM-2 ratio in patients with moderate and severe COVID-19, the area under the curve was 0.723. Using a cut-off value of 0.125 for TREM-1/TREM-2 ratio in the Youden index calculation, the sensitivity was 60% and specificity was 71%. CONCLUSION: Experience with the positive effects of medical treatments to restore inflammatory balance in the course of COVID-19 is steadily increasing. TREM-1 and TREM-2 have an important role in inflammation and may serve as biomarkers and therapeutic targets in the early treatment and follow-up of COVID-19.

Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID-19 pneumonia.

The COVID-19 pandemic, which has ravaged our world for more than a year, still shapes our agenda with a scale of intensity that fluctuates over time. In our study, we aimed to determine the correlation between serum migration inhibitory factor (MIF) level and disease severity in COVID-19 with different prognoses. Between 15 October 2020 and 20 January 2021, 110 patients over the age of 18 who were diagnosed with COVID-19 and 40 volunteer healthcare personnel were included in our study. MIF levels were measured by enzyme-linked immunosorbent assay. In the comparison of serum MIF values in the patient and control group, it was observed that the MIF level was significantly higher in patients with both moderate and severe COVID-19 levels compared to the control group (p = 0.001, 0.001). In the comparison of serum MIF values of moderate to severe COVID-19 patients, it was observed that MIF level was higher in severe patients (p = 0.001). In the receiver operating characteristic curve analysis performed to differentiate between severe and moderate COVID-19 patients with MIF levels, the area under the curve was observed as 0.78. When the cutoff value of the MIF level was taken as 4.455 ng/ml, the sensitivity was 83% and the specificity was 62%. Failure to adequately balance the pro-inflammatory cytokines synthesized in COVID-19 with anti-inflammatory effect is the most important reason for the aggravation of the disease course. Playing a role in pro-inflammatory cytokine synthesis, MIF can provide important information about the disease prognosis in the early period.

Could VEGF-D level have a role in clinical risk scoring, estimation of thrombus burden, and treatment in acute pulmonary thromboembolism?

OBJECTIVE: Pulmonary embolism (PE) is usually a complication of deep vein thrombosis and is an important cause of mortality and morbidity. Vascular endothelial growth factor D (VEGF-D) is a secretory protein that plays a role in the remodelling of blood vessels and the lymphatic system. This study aimed to determine the relationship between VEGF-D level and clinical risk scoring in patients with PE. METHODS: The study included 117 patients admitted for PE that were divided into four groups: high-risk patients (n = 35), high-intermediate-risk patients (n = 30), low-intermediate-risk patients (n = 24), and low-risk patients (n = 28). Plasma VEGF-D was measured from peripheral venous blood samples (5 mL) using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Pulmonary Artery Obstruction Index (PAOI) was calculated from CT angiography imaging. RESULTS: There was no significant difference in troponin-I and NT-proBNP levels between the high-intermediate-risk and high-risk PE patients (P = .134, .146). VEGF-D and PAOI levels were found to be statistically significantly higher in high-risk patients compared with high-intermediate-risk patients (P = .016, .001). VEGF-D level was moderately correlated with mean pulmonary artery pressure and PAOI (r = .481, P = .01; r = .404, P = .01). In ROC curve analysis, a cut-off of 370.1 pg/mL for VEGF-D had 91.4% sensitivity and 67% specificity in the differentiation of high-intermediate-risk and high-risk PE patients. CONCLUSION: This study showed that plasma VEGF-D level was more reliable than troponin-I and NT-proBNP in clinical risk scoring and demonstrating thrombus burden. VEGF-D can be used as a biomarker in clinical risk scoring and estimation of thrombus burden in patients with acute PE.

Is endogenous carboxyhaemoglobin level a useful biomarker of clinical course and prognosis in COVID-19 patients?

OBJECTIVE: SARS-CoV-2 has caused nearly 4 million confirmed cases of COVID-19 worldwide in the approximately 4 months since it emerged in Wuhan, China in December 2019. Comorbidities increase morbidity and mortality in COVID-19, and many laboratory parameters have been associated with mortality. The aim of the present study was to identify the relationship between endogenous carboxyhaemoglobin (COHb) level and the clinical course and prognosis of COVID-19. METHODS: The study included 48 non-smokers or ex-smokers aged 18 years or older who presented to the emergency department, were diagnosed with COVID-19 by real-time PCR analysis of nasopharyngeal swab sample and were treated in the pulmonary diseases ward of the Atatürk University hospital after 24 March 2020 and 15 April 2020. The patients' laboratory parameters and demographic data were analysed retrospectively. RESULTS: Prothrombin time and C-reactive protein (CRP), troponin-I, and D-dimer levels decreased in COVID-19 patients during follow-up (P = .024, P = .001, P = .001, P = .001), while PaO2 /FiO2 ratio and COHb increased (P = .002, P = .001). COHb level at admission was significantly lower in patients who developed macrophage activation syndrome (MAS), acute respiratory distress syndrome (ARDS), and those who died compared with the other patients (P = .002, P = .001). COHb level on day 5 of treatment was significantly higher in patients with ARDS and patients who died (P = .001, P = .001). Significant correlations were detected between COHb level and CRP (r=-0.425, P = .001), ferritin (r = -.395, P = .001) and PaO2 /FiO2 ratio (r = .431, P = .001). CONCLUSIONS: COHb level may be an easily accessible biomarker that guides early follow-up and treatment planning to avoid ARDS, MAS and mortality in COVID-19.

Evaluation of the relationship between pentraxin 3 (PTX3) rs2305619 (281A/G) and rs1840680 (1449A/G) polymorphisms and the clinical course of COVID-19.

Macrophage activation syndrome (MAS) is one of the main causes of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the relationship between the pentraxin 3 (PTX3) gene polymorphisms rs2305619 (281A/G) and rs1840680 (1449A/G) and the development of MAS in patients with COVID-19. The study included a total of 94 patients aged 18-45 who were diagnosed as having COVID-19 between June and December 2020. PTX3 281A/G and 1449A/G polymorphism frequencies were evaluated. PTX3 281A/G allele and genotype frequencies did not deviate from Hardy-Weinberg (HW) equilibrium in the MAS or non-MAS group (χ2 : 0.049, df: 2, p = 0.976, χ2 : 0.430, df: 2, p = 0.806). PTX3 1449A/G allele and genotype frequencies deviated significantly from HW equilibrium in the non-MAS group (χ2 : 6.794, df: 2, p = 0.033) but not in the MAS group (χ2 : 2.256, df: 2, p = 0.324). The AG genotype was significantly more frequent in the non-MAS group, while the AA genotype was significantly more frequent in the MAS group (χ2 : 11.099, df: 2, p= 0.004). Analysis of the PTX3 1449A/G polymorphism showed that individuals with the GG genotype had higher serum PTX3 levels than those with the AA and AG genotypes (p = 0.001 for both). Analysis of the PTX3 1449A/G polymorphism in patients with COVID-19 showed that those with the AG genotype were relatively more protected from MAS compared with individuals with the AA genotype. In addition, lower serum PTX3 levels are observed in patients carrying the A allele.