Osteoproductivity of Injectable Bone Grafts with and without Ostrich Eggshell Membrane Protein in Rabbit Femur.

BACKGROUND: The aim of this study was to evaluate the biocompatibility and effectiveness in terms of osseointegration of dental implants composed of novel injectable bone grafts with and without ostrich eggshell particles and membrane protein in rabbit femur. METHODS: Sixteen adult male New Zealand rabbits were used in this study. A bone defect was created in each animal's right and left femur, and a dental implant was placed adjacent to the defect. Two graft materials were prepared, one containing the membrane protein and the other not. In two groups, the defects were filled with these materials. In the negative control group (NC, (n:8)), the defects were left empty. A commercial product of biphasic calcium sulfate was used as a positive control material (PC, n = 8). The graft groups were defined as the group with the membrane protein (MP+, (n:8)), and without the membrane protein (MP-, n:8). The animals were euthanized at the 12th week after surgery. The samples were investigated using histology, histomorphometry, and micro-computed tomography. Data were statistically analyzed using one-way ANOVA and Tukey's tests (p = 0.05). RESULTS: Both the PC and MP+ groups had similar newly formed bone areas, and the mean values of these groups were significantly (p < 0.05) higher than those of the MP- and NC groups. The PC group had the highest amount of unresorbed material, while the MP- group had the lowest amount of unresorbed material. The bone-implant contact (BIC) scores of the PC and MP+ groups were significantly higher (p < 0.05) than that of the NC group. The connective tissue area of the PC group was the lowest, which was significantly lower than the other groups (p < 0.05). CONCLUSIONS: The grafts produced are highly biocompatible and also showed osteoproductivity. Their cost-effectiveness and osteoproductive activity require further investigation.

The impact of previous SARS-CoV-2 infection on post-vaccine adverse events in individuals vaccinated with TURKOVAC or CoronaVac -inactivated COVID-19 vaccines.

This study- a secondary analysis of data from a randomized, observer-blinded, non-inferiority study among volunteers between 18-55 y old in Türkiye- evaluated the impact of previous SARS-CoV-2 infection before the first dose of inactive TURKOVAC on post-vaccine local and systemic adverse events (AEs) comparing with CoronaVac. Of 1266 participants analyzed, 27.7% had a previous COVID-19 history. Local and systemic AEs were observed in 37.3% and 39% of the participants. The frequency of AEs was slightly higher in the first 30 minutes and 24 hours among participants with a COVID-19 history; none were severe. 1203 participants had a second dose vaccination, and 27.3% had a history of COVID-19. The frequencies of local and systemic AEs after the second dose were similar between those with and without a COVID-19 history. The TURKOVAC and CoronaVac showed similar frequencies of local and systemic AEs in the first 30 minutes after vaccination.

N-(2-Aminobenzoyl)benzotriazole Mediated Synthesis of 3-Acyl-2-alkyl(aryl)-4-hydroxyquinolines and 3-Acylamino-4(3H) quinazolinones.

New methods have been developed for the synthesis of the substituted quinolines and quinazolinones derivatives by utilizing N-(2-aminobenzoyl)benzotriazoles under mild reaction conditions. 3-Acyl-2-alkyl(aryl)-4-hydroxyquinolines were obtained in modarete yields by the reaction of N-(2-aminobenzoyl)benzotriazoles and diketones in the presence of tert-BuOK. 3-Acylamino-4(3H) quinazolinones were obtained in good yields via N-(2-aminobenzoyl)benzotriazoles, orthoester and hyrazides in one-pot.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.

Immunologic burden links periodontitis to acute coronary syndrome: levels of CD4 + and CD8 + T cells in gingival granulation tissue.

OBJECTIVE: To investigate the proportional variation of macrophage and T-lymphocytes subpopulations in acute coronary syndrome (ACS) patients, its association with periodontitis (P), and to compare with control individuals. SUBJECTS AND METHODS: Three groups of subjects participated: one group consisted of 17 ACS patients with P (ACS + P), another group consisted of 22 no ACS + P patients, and a control group consisted of 23 participants with gingivitis (no ACS + G). Macrophage, CD4 + , and CD8 + T-lymphocytes and CD4 + /CD8 + ratio values in gingival tissue were determined histometrically. RESULTS: Significant differences were found among three groups regarding the mean number of macrophage (no ACS + P > ACS + P > no ACS + G; p < 0.05) and CD8 + T-lymphocytes (no ACS + P > ACS + P > no ACS + G; p < 0.05). Significant variations were observed between the groups both CD4 + T-lymphocytes densities (ACS + P > no ACS + P and ACS + P > no ACS + G; p < 0.05) and CD4 + / CD8 + ratio (no ACS + P < no ACS + G and ACS + P < no ACS + G; p < 0.05). CONCLUSIONS: The increased number of CD8 + T-lymphocytes in both group ACS + P and group no ACS + P resulted in a reduction of the CD4 + /CD8 + ratio in gingival tissue when compared with no ACS + G group. CLINICAL RELEVANCE: The decrease of CD4 + /CD8 + ratio in gingival tissue reflects periodontitis and may be associated with severe adverse outcomes in people with ACS.

An outbreak analysis of wound infection due to Acinetobacter baumannii in earthquake-trauma patients.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii is still a major contributor to outbreaks and infections health care-associated infections. This study aimed to investigate an outbreak of wound infection due to A baumannii in trauma patients injured in the Kahramanmaras earthquake. METHODS: This retrospective case-control study was conducted on an outbreak of wound infection caused by A. baumannii in trauma patients affected by the February 6 Turkey earthquake. Among the patients who underwent at least one extremity surgery due to earthquake-related crush-trauma injury, patients with wound infection due to A baumannii were included in the case group and without infection were included in the control group. Multivariate analysis and logistic regression were performed to identify risk factors. Environmental cultures were taken to identify the source of the outbreak. Molecular typing by pulsed-field gel electrophoresis was used to confirm the relationships of the wound infection agent A. baumannii strains. RESULTS: A total of 44 patients were included in the case group and 62 patients in the control group. Time under the debris; 22.0 versus 35.7 (odds ratio [OR]:1.02, 95% confidence interval [CI]: 1.00-1.04) and hemodialysis (OR: 6.09, 95% CI: 1.64-22.66) were identified as risk factors for in the multivariate analysis. Performing the first intervention in a fully equipped tertiary hospital was seen as an infection-reducing factor compared to performing it in a field hospital (OR: 0.21, 95% CI: 0.06-0.68). Dressing trolleys and scissors were identified as the source of the outbreak. CONCLUSIONS: After devastating earthquakes, a large number of patients are admitted and require emergency interventions due to life-threatening conditions. Organ failure often develops and requires the use of invasive catheters and procedures. Compliance with infection control measures and clean surgical interventions reduce wound site infections and allow extremities to heal, while problems in adhering to infection control measures can lead to many problems such as outbreaks of gram-negative bacteria. This highlights the importance of infection control measures.

Osteoproductivity in Experimentally Induced Cranial Bone Defects in Rabbits.

Background: Autogenous bone grafts are the gold standard for being used as graft materials in maxillofacial surgery. However, a limited amount of these materials is available from the donor site, and there is also more need for a larger operating area and a second surgery, which frequently leads to unreliable graft incorporation, tooth ankylosis, and root resorption. Therefore, newer bone graft substitutes have been developed as alternatives, among which eggshell powder has been introduced as a bone substitute. This study aimed to evaluate the biocompatibility, resorption kinetics, and osteoproductivity of the unprocessed, CMC-coated, and gelatin-coated ostrich eggshell particles. Methods: Four half-thickness calvarial defects were created in each animal. At the end of the 1st and 3rd months, the defected sites were investigated by clinical, histological, radiological and histomorphometrical methods. Results: Coating the eggshell particles with CMC and gelatin facilitated their surgical application and contributed to new bone formation. However, their newly formed bone rate at the 3rd month was lower than those of the unprocessed eggshell particles. The CMC coating was more effective than gelatin coating in the bone modeling process. Conclusion: Ostrich eggshell particles either in native form or coated with CMC could be used as a bone filler for supporting new bone formation and healing in treatment of osseous defects.

Cytotoxicity, acute and sub-chronic toxicities of the leaves of Bauhinia thonningii (Schumach.) Milne-Redh. (Caesalpiniaceae).

BACKGROUND: Bauhinia thonningii is a plant traditionally used against many human diseases such as gastric ulcers, fever, inflammations, coughs, dysentery, diarrhea, and malaria. In the present investigation, the cytotoxicity of methanol extract of Bauhinia thonningii leaves (BTL), fractions and the isolated phytoconstituents was determined in a panel of 9 human cancer cell lines including drug sensitive and multidrug-resistant (MDR) phenotypes. The acute and sub-chronic oral toxicity of BTL was investigated as well. METHODS: Compounds were isolated using chromatographic techniques while their chemical structures were determined using spectroscopic methods. The resazurin reduction assay (RRA) was used to evaluate the cytotoxicity of samples, propidium iodide (PI) for apoptosis, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining for mitochondrial membrane potential (MMP) analysis, 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining for the quantification of reactive oxygen species (ROS), whereas Caspase Glo assays were combined by means of flow cytometry. Furthermore, the toxicological investigations were performed as recommended by the Organization for Economic Cooperation and Development (OECD). RESULTS: The botanicals as well as 6-C-methylquercetin-3,7-dimethyl ether (2), quercetin-3-O-L-rhamnopyranoside (5), quercetin-3-O-ß-glucopyranoside (6), 6,8-C-dimethylkaempferol 3,7-dimethyl ether (7), and 6,8-C-dimethylkaempferol-3-methyl ether (8) had promising cytotoxic effects in the 9 tested cancer cell lines. The IC50 values below 20 µg/mL (botanicals) or 10 µM (compounds) on at least 1/9 tested cancer cell lines were considered. The best cytotoxic effects with IC50 values below 5 µM were achieved with compounds 7 against CEM/ADR5000 leukemia cells (2.86 µM) and MDA-MB-231-pcDNA breast adenocarcinoma cells (1.93 µM) as well as 8 against CCRF-CEM leukemia cells (3.03 µM), CEM/ADR5000 cells (2.42 µM), MDA-MB-231-pcDNA (2.34 µM), and HCT116 p53-/- cells (3.41 µM). BTL and compound 8 induced apoptotic cell death in CCRF-CEM cells through caspase activation, alteration of MMP, and increased ROS production. BTL did not cause any adverse effects in rats after a single administration at 5000 mg/kg or a repeated dose of 250 mg/kg body weight (b. w.). CONCLUSION: Bauhinia thonningii and its constituents are sources of cytotoxic drugs that deserve more in-depth studies to develop novel antiproliferative phytomedicine to fight cancer including resistant phenotypes.

Late-term cardiac magnetic resonance imaging in multisystem inflammatory syndrome in children.

BACKGROUND: Cardiac involvement in multisystem inflammatory syndrome in children may have a spectrum ranging from mild disease to severe heart failure due to fulminant myocarditis. Cardiac involvement usually resolves after clinical recovery. However, the adverse effects of myocarditis on cardiac function after recovery are not fully known. This study aims to investigate cardiac involvement by performing cardiac magnetic resonance imaging (MRI) after the acute and recovery periods. METHODS: 21 patients with clinical and laboratory signs of myocarditis, including left ventricular systolic dysfunction, mitral regurgitation, elevated troponin T, elevated N-terminal pro-B-type natriuretic peptide and electrocardiographic changes, who had given consent for cardiac MRI, underwent cardiac MRI after completion of the acute and recovery phases. RESULTS: When compared to 16 patients with normal cardiac MRI, five patients with cardiac fibrosis on MRI were older, had greater body mass indexes, lower leucocyte counts, lower neutrophil counts, higher blood urea nitrogen levels and higher creatinine levels. Cardiac fibrosis on MRI was located in the posterior right ventricle insertion point and in mid ventricular septum. CONCLUSIONS: Adolescence and obesity appear as risk factors for the development of fibrosis as a late-term sequela of myocarditis. Furthermore, future studies reporting the follow-up data of patients with fibrosis are necessary to predict and manage adverse outcomes.

The Relationship Between Cytokine Concentrations and Severity Scoring Index for Crimean-Congo Hemorrhagic Fever.

Background This study aimed to investigate the effects of serum high mobility group box-1 (HMGB1), interleukin (IL)-6, IL-8, IL-1ß, IL-10, and tumor necrosis factor alpha (TNF-α) levels on disease severity and mortality in Crimean-Congo hemorrhagic fever (CCHF) patients. Materials and methods This study was performed prospectively in the intensive care unit (ICU) and infection ward of a tertiary hospital in the Republic of Türkiye. Patients aged 18 years and older diagnosed with CCHF were included. Results Our study included 30 patients, of whom 83.3% were male, where the mean age was 51.6±14.35 years. The most common clinical findings in patients were malaise (90%) and myalgia (63.3%). In our study, IL-1ß levels were found to be 1173.6 (783.0-1823.0) pg/mL, IL-6 69.9 (56.8-133.1) pg/mL, IL-8 191.2 (152.8-516.9) pg/mL, TNF-α 129.5 (104.9-270.8), HMGB1 37.01 (29.26-75.18), and IL-10 190.1 (IQR: 147.8-387.8) pg/mL. The patients' median Severity Scoring Index (SSI) score was found to be 2.5 (1.8-5.5). There was a moderate correlation between the patients' SSI score and serum IL-6 (r=0.464, p=0.010), TNF-α (r=0.420, p=0.021), and IL-10 levels (r=0.518, p=0.003), and a weak correlation between serum HMGB1 (r=0.392, p=0.032). The correlation between SSI and creatine phosphokinase (CPK) levels (r=0.499, p=0.036) was observed to be moderate. Conclusion It was seen that IL-10, IL-6, TNF-α, HMBG-1, and CPK levels evaluated at the CCHF patients' time of admission to the clinic and SSI clinical score were found to be significantly related. It is clear that more studies with patients and groups of healthy volunteers are needed on this subject.

Comparison of a novel antigen detection test with reverse transcription polymerase chain reaction assay for laboratory diagnosis of SARS-CoV-2 infection.

Molecular diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction (RT-PCR) in respiratory specimens is considered the gold standard method. This method is highly sensitive and specific but it has some limitations such as being expensive and requiring special laboratory equipment and skilled personnel. RapidFor™ Antigen Rapid Test Kit is a commercially available Ag-RDT which is produced in Turkey and designed to detect the nucleocapsid antigen of SARS-CoV-2 in nasopharyngeal swab samples. The aim of this study was to evaluate the performance of this novel SARS-CoV-2 antigen detection considering the RT-PCR method as the gold standard. Four hundred forty-four nasopharyngeal swab samples which were collected from the patients who met clinical criteria of COVID-19 from ten centers in Turkey between September 2020 and February 2021 were included in the study. All the nasopharyngeal swab samples were tested for SARS-CoV-2 RNA using commercial RT-PCR kits (Bioeksen and A1 Lifesciences, Istanbul, Turkey) according to the manufacturer's instructions. Viral loads were assessed according to the cycle threshold (Ct) values. RapidFor™ SARS-CoV-2 antigen test (Vitrosens Biotechnology, Istanbul, Turkey) was used to investigate the presence of SARS-CoV-2 antigen in all samples following the manufacturer's instructions. Out of 444 nasopharyngeal swab samples tested, 346 (77.9%) were positive and 98 (22.1%) were negative for SARS-CoV-2 RNA by RTPCR. Overall sensitivity of the RapidFor™. Antigen Rapid Test Kit was 80.3% whereas specificity was found to be 87.8%. Positivity rate of rapid antigen test in samples with Ct values over 25 and below 30 was 82.7%, while it increased to 95.7% in samples 20 ≤ Ct < 25 and reached 100% in samples with Ct values below 20. RapidFor™ SARS-CoV-2 Ag test might be a good choice in the screening of symptomatic and asymptomatic patients and their contacts for taking isolation measures early, with advantages over RT-PCR as being rapid, easy and being applicable in every laboratory and even at point of care.

A new flavonol derivative and other compounds from the leaves of Bauhinia thonningii Schum with activity against multidrug-resistant bacteria.

Investigation of the leaves of Bauhinia thonningii Schum led to the isolation and identification of a new flavonol derivative, 6-C-methylquercetin-3,4'-dimethyl ether (1) together with eleven known compounds (2-13), with two of them (10 and 11) obtained as a mixture. Their structures were established by extensive spectroscopic analyses. Antibacterial activity of compound 1 as well as the reference antibiotic, ciprofloxacin was tested on Gram-negative multidrug-resistant bacteria overexpressing active efflux pumps, and against methicillin-resistant strains of Staphylococcus aureus (MRSA). Samples were tested alone and in combination with an efflux pump inhibitor (EPI), phenylalanine-arginine-ß-naphthylamide (PAßN). Results show that when compound 1 was tested alone, its inhibitory effects were obtained on 7/10 tested bacteria with the highest MIC value of 128 µg/mL whilst in the presence of EPI, this activity significantly increase in all the 10 bacteria. An interesting antibacterial activity was obtained with compound 1 against Klebsiella pneumoniae ATCC11296 (MIC of 4 µg/mL), KP55 and Staphylococcus aureus MRSA6 in the presence of the PaßN.

CD4+ T-Cell Depression is Linked to the Severity of COVID-19 and Predicts Mortality.

Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte subsets. This study aimed to determine the distribution of lymphocytes in patients with various severity levels of COVID-19 and to describe the relationship between the CD4+ T helper and prognosis. Materials and Methods: Adult (>18 years old) patients with COVID-19 who followed up in a tertiary hospital were included in the study prospectively. Demographic and clinical characteristics of the patients were obtained from the hospital records. Peripheral flow cytometry was studied in patients with different severity of COVID-19 and different prognoses. Next, we analyzed the characteristics and predictive values of lymphocyte subsets in COVID-19 patients. Results: Totally 86 patients were included in the study, of which 21 (24.4%) had asymptomatic, 23 (26.7%) had mild/moderate, and 42 (48.8%) had severe/critical COVID-19. Severe/critical patients had lower lymphocyte levels and older age than asymptomatic patients (p<0.001 and p<0.001, respectively). We determined that decreased CD4+ T cell ratio (p<0.001) and CD4+ /CD8+ ratio (p<0.001) were indicative of the severity of the disease. CD4+ T cell ratio on admission (odds ratio [OR]=0.858; p=0.033), day seven CD4+ T cell ratio (OR=0.840; p=0.029), and C-reactive protein (CRP) levels (OR=1.014; p=0.043) were prognostic factors for mortality. According to receiver operating characteristics (ROC) curve analysis, the area under the curve was greater than 0.9 for decreased CD4 + T cell ratio on admission and the seventh day. Conclusion: A low CD4+ T helper ratio predicts a poor prognosis. In combination with CRP, it can be used in clinical follow-up.

Objective Evaluation of Smell and Taste Senses in COVID-19 Patients.

Objective: The severe acute respiratory syndrome-coronavirus-2 pandemic is one of the largest of the recent times and can cause many symptoms including smell and taste disorders. In the literature, smell disorders caused by coronavirus disease-2019 (COVID-19) have been reported within a wide range from 3.2% to 98.3%. A small number of these studies demonstrated smell and taste disorders through objective tests. Our aim in this study was to determine the prevalence of smell and taste disorders in hospitalized patients due to COVID-19 infection. Methods: The study was carried out with 100 patients who were positive for real-time polymerase chain reaction and treated at the Kayseri City Hospital, and 100 healthcare worker relatives. We used the Connecticut Chemosensory Clinical Research Center test to evaluate the sense of smell. Sense of taste was evaluated using four different standardized bottles of preparations, and the results were scored according to the patients' statements. Results: Patient (Group 1) and control (Group 2) groups were compared for age, gender, smell and taste disorders. There were 39 women and 61 men in the patient group, and 40 women and 60 men in the control group. Mean age was 50.2±1.37 (range 21-70) years in Group 1 and 47.6±1.25 (range 18-70) years in Group 2, and there was no significant difference between the two groups. While the rate of smell disorder was 80% in Group 1, we found this rate as 35% in Group 2. Taste disturbance was identified in 38 patients, of whom 16 had mild hypogeusia, 17 had moderate hypogeusia, four had severe hypogeusia, and one patient had ageusia. We found that taste disorder was 38% in Group 1 and 3% in Group 2. Conclusion: Smell and taste dysfunctions are very common symptoms in COVID-19 patients. The results obtained using objective test methods are higher than the rates obtained from patient statements.

The course of COVID-19 in patients with hematological malignancies and risk factors affecting mortality: A cross-sectional study.

Objective: This study aimed to determine the clinical outcomes and risk factors affecting mortality in patients with COVID-19 following hematological malignancy (HM). Methods: Patients diagnosed with HM and hospitalized for COVID-19 were included in this retrospective study. The age, demographic and clinical characteristics, prognosis and treatment of surviving and non-surviving patients were compared. Results: A total of 49 patients were included in this study, 17 (34.6%) of whom died within 28 days of being diagnosed with COVID-19. Older age (p = 0.001), diabetes (p = 0.001), chronic obstructive pulmonary disease (p = 0.002), secondary infection (p < 0.001) and secondary bacterial infection (p = 0.005) were statistically significantly higher in non-survivors. The remission status of HM was higher in surviving patients (p < 0.001). In multivariate regression analysis, age (OR: 1.102, p = 0.035) and secondary infection (OR: 16.677, p = 0.024) were risk factors increasing mortality, the remission status of HM (OR: 0.093, p = 0.047) was a protective factor from mortality. Conclusion: The older age, the remission status of HM and secondary infection due to COVID-19 were determined as prognostic factors predicting mortality in HM patients with following COVID-19.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Efficacy, Immunogenicity, and Safety of the Two-Dose Schedules of TURKOVAC versus CoronaVac in Healthy Subjects: A Randomized, Observer-Blinded, Non-Inferiority Phase III Trial.

We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18-55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 µg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86-90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95-60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.

Quick COVID-19 Severity Index, CURB-65 and Quick SOFA Scores Comparison in Predicting Mortality and Risk Factors of COVID-19 Patients.

BACKGROUND: This study aimed to investigate CURB-65, quick COVID-19 Severity Index (qCSI) and quick Sepsis Related Organ Failure Assessment (qSOFA) scores in predicting mortality and risk factors for death in patients with COVID-19. METHODS: We retrospectively analyzed a total of 1919 cases for whom the rRT-PCR assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. For mortality risk factors, univariate and multivariate logistic regression analyses were used. Receiver operator characteristics (ROC) analysis and Kaplan-Meier survival analysis were performed for CURB-65, qCSI and qSOFA scores. RESULTS: The patients' average age was 45.7 (21.6) years. Male patients accounted for 51.7% (n=992). In univariate analysis, some clinical variables including age over 65 years and comorbid diseases such as hypertension, chronic kidney disease, malignancy, lymphopenia, troponin, lactate dehydrogenase (LDH) and fibrinogen elevation were associated with the mortality rate. In multivariate logistic regression analysis: Neutrophil lymphocyte ratio (NLR) 3.3 and above (OR, 9.1; 95% CI, 1.9-42), C-reactive protein (CRP)30 mg/L and above (OR, 4.1; 95% CI, 1.2-13.6), D-dimer 1000 ng/mL and above (OR, 4; 95% CI, 1.5-10.7) and age (OR, 1.11; 95% CI, 1.04-1.18-year increase) were identified as risk factors for mortality among COVID-19 patients. The CURB-65 and qCSI scores exhibited a high degree of discrimination in mortality prediction (AUC values were 0.928 and 0.865, respectively). Also, the qSOFA score had a moderate discriminant power (AUC value was 0.754). CONCLUSION: CURB-65 and qSCI scores had a high discriminatory power to predict mortality. Also, this study identified CURB-65, qCSI and qSOFA scores, NLR, CRP, D-dimer level, and annual age increase as important mortality risk factors.

Risk factors and lethality associated with Candidemia in severe COVID-19 patients.

Background and Purpose: Candidemia remained important in the intensive care units (ICU) during the COVID-19 pandemic. This study aimed to investigate the clinical and laboratory data on candidemia in COVID-19 patients. Materials and Methods: The baseline characteristics, as well as laboratory and clinical findings of candidemia and non-candidemia patients, were compared. Candidemia was defined as the isolation of Candida spp. from blood cultures. The isolates were identified by VITEK® 2 (bioMérieux, France) commercial method. Antifungal susceptibility was assessed using the E-test method. Univariate and multiple binary logistic regression analyses were performed to compare the variables. Results: In total, 126 patients with the COVID-19 disease were included. Candidemia was diagnosed in 44 (35%) of the patients. The number of patients with diabetes mellitus and chronic renal failure was higher in the candidemia group. In the candidemia group, the duration of ICU stay of patients, the 30-day mortality rate, mechanical ventilation therapy, and systemic corticosteroids (Prednisone) usage were significantly higher in candidemia patients. Moreover, the median white blood cell, neutrophils, and lactate dehydrogenase were higher in the candidemia group.Univariate and multiple binary logistic regression analyses were performed to compare the variables. Isolated species were identified as Candida albicans (n=12, 41%), Candida parapsilosis (n=7, 24%), Candida glabrata (n=6, 21%), Candida tropicalis (n=3, 10%), and Candida dublinensis (n=1, 3%). In total, three isolates of six C. glabrata species had dose-dependent sensitivity to fluconazole, and one C. parapsilosis was determined to be resistant. Conclusion: The COVID-19 patients who are admitted to ICU have many risk factors associated with candidemia. The most common risk factors for the development of candidemia were mechanical ventilation, diabetes mellitus, neutrophilia, and low hemoglobin level. The most frequently isolated species was C. albicans. Moreover, caspofungin was found to be the most effective drug in vitro. No significant resistance pattern was detected against the isolated species. It should be noted that risk-stratified antifungal prophylaxis in the ICU is possible.

Lymphocyte Subsets in Mild COVID-19 Pediatric Patients.

OBJECTIVE: The reasons for a high prevalence of asymptomatic or mild coronavirus disease (COVID-19) and rare severe disease in children have been explained by non-immune and immune mechanisms. This study aimed to evaluate the immune system's response to severe acute respiratory syndrome coronavirus 2 by investigating lymphocyte subsets. MATERIALS AND METHODS: This study included 33 coronavirus disease positive children, of whom 12 had mild disease and 21 had an asymptomatic infection as the patient group and 26 ageand gender-matched healthy children as the control group. The demographic information, symptoms, physical examination findings, complete blood count, C-reactive protein (CRP), procalcitonin, and lymphocyte subsets were recorded in all subjects. RESULTS: Leukocyte, lymphocyte, monocyte count, and hemoglobin levels of our pediatric coronavirus disease patients were similar to the control group. Neutrophil was lower in the coronavirus disease cases compared to the control group. CRP and procalcitonin levels of asymptomatic cases were similar to the control group. B cell count, CD8+ T cell count, and CD4/CD8 ratio (dividing the CD4 cell count by the CD8 cell count) ratio were similar in the patient and control groups. Natural killer, T cell, and CD4+ T cell counts were significantly higher in the whole patient group compared to the control group. CONCLUSION: One reason for mild severe acute respiratory syndrome coronavirus 2 infection in children may be an increase in some lymphocyte subsets such as natural killer cells, T cell, and CD4+ T cell. Understanding the answer to the question of why children develop more protective immunity to the virus could be an essential step for developing new treatments.