Revealing the single-channel characteristics of OprD (OccAB1) porins from hospital strains of Acinetobacter baumannii.

Nowadays, reports of antimicrobial resistance (AMR) against many antibiotics are increasing because of their misapplication. With this rise, there is a serious decrease in the discovery and development of new types of antibiotics amid an increase in multi-drug resistance. Unfermented Acinetobacter baumannii from gram-negative bacteria, which is one of the main causes of nosocomial infections and multi-drug resistance, has 4 main kinds of antibiotic resistance mechanism: inactivating antibiotics by enzymes, reduced numbers of porins and changing of their target or cellular functions due to mutations, and efflux pumps. In this study, characterization of the possible mutations in OprD (OccAB1) porins from hospital strains of A. baumannii were investigated using single channel electrophysiology and compared with the standard OprD isolated from wild type ATCC 19,606. For this aim, 5 A. baumannii bacteria samples were obtained from patients infected with A. baumannii, after which OprD porins were isolated from these A. baumannii strains. OprD porins were then inserted in an artificial lipid bilayer and the current-voltage curves were obtained using electrical recordings through a pair of Ag/AgCl electrodes. We observed that each porin has a characteristic conductance and single channel recording, which then leads to differences in channel diameter. Finally, the single channel data have been compared with the gene sequences of each porin. It was interesting to find out that each porin isolated has a unique porin diameter and decreased anion selectivity compared to the wild type.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Neurological Presentations in Patients with COVID-19 in Cytokine Storm.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection causes a wide variety of neurological disorders by affecting both central and peripheral nervous systems. The cytokine storm (CS) has been blamed for the development of severe neurological disorders in COVID-19. However, the relationship between COVID-19 CS and neurological manifestations has not been adequately studied. Thus, we aimed to investigate the neurological presentations in patients with COVID-19 CS. METHODS: The study population consisted of hospitalized moderate-to-severe COVID-19 patients. It was divided into two groups CS (36 patients, 29.3%) and non-CS (87 patients, 70.7%) based on significant clinical symptoms, elevated inflammatory marker levels, radiological findings, and interleukin-6 levels (IL-6). RESULTS: The three most common neurological symptoms in the CS group were altered level of consciousness, headache, and unsteadiness. Altered level of consciousness was higher in the CS group (69.4%) than the non-CS group (25.3%) (p:0.001). The frequency of headache was comparable in both groups (p:0.186). The number of patients requiring intensive care unit and intubation was higher in the CS group (p:0.005 and p:0.001). The mortality rate in the CS group (38.9%) was higher than the non-CS group (8.0%) (p:0.001). IL-6, CRP, ferritin, neutrophil-lymphocyte ratio, procalcitonin, and D-dimer levels were higher in the CS group (for all p:0.001) while lymphocyte count was lower (p:0.003). CONCLUSION: The most common neurological presentation in patients with CS was altered level of consciousness. The presence of CS was an independent risk factor for high mortality.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

Background/aim: The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods: Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results: This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion: The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

A sensitive indicator for the severity of COVID-19: thiol

Background/aim: Thiol status is a good reflector of the cellular redox and have vital roles in various cellular signaling pathways. The purpose of the study was to investigate thiol status in patients with SARS-CoV-2 infection. Materials and methods: A total of 587 subjects (517 patients/70 healthy controls) were enrolled in the study.The patients were categorized into the groups regarding to the severity of disease (mild, moderate, severe, and critical).Thiol status of all groups were compared. Results: The patients had significantly diminished thiol levels compared to controls. Thiol levels were gradually decreased as the severity of the disease increased. Logistic regression analyses identified that thiol concentrations were an independent risk factor for the disease severity in each phase (mild group OR 0.975, 95%CI 0.965-0.986; moderate group, OR 0.964, 95%CI 0.953-0.976; severe group OR 0.953, 95%CI 0.941-0.965; critical group OR 0.947, 95%CI 0.935-0.960).Thiol test exhibited the largest area under the curve at 0.949, with the highest sensitivity (98.6%) and specificity (80.4%). Conclusions: Depleted thiol status was observed in SARS-CoV-2 infection. Decline of the thiol levels by degrees while the severity of infection increased was closely related to the progression of the disease. This outcome highlights that thiols could be an impressible biomarker for predicting of the severity of COVID-19.

Is There Any Correlation between Baseline Serum Cortisol Levels and Disease Severity in PCR-Positive COVID-19 Patients with and without Diabetes Mellitus?

Background: COVID-19 has caused a pandemic and is associated with significant mortality. The pathophysiology of COVID-19, affecting many organs and systems, is still being investigated. The hypothalamus, pituitary gland, and possibly adrenal glands are the targets of SARS-CoV-2 because of its angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors expression. Hypocortisolemia can be seen in the postinfection period. COVID-19 infection tends to be severe in diabetic patients due to immune dysfunction. In this study, our aim was to investigate the relationship between basal cortisol levels and the course of COVID-19 infection in diabetic and non-diabetic patients. Methods: Our retrospective study included 311 PCR-positive COVID-19 patients over the age of 18 who were hospitalized in Ankara City Hospital Infectious Diseases Department or Intensive Care Unit (ICU) between 15 March 2020 and 15 May 2020. Serum basal cortisol, fasting plasma glucose (FPG), HbA1c values, and diabetes history were recorded within the first 24 h of hospitalization. The presence of pulmonary involvement was noted from the patients' imaging records. Pregnant and breastfeeding women, patients with chronic liver disease or chronic kidney disease, and patients who were already using steroids or had started COVID-19 infection treatment within the 72 h before blood collection were excluded from the study. Results: Of the 311 patients, 100 had Type 2 Diabetes Mellitus (T2D), while 211 did not. The age, serum basal cortisol, and glucose levels of the patients with T2D (64.51 ± 12.29, 19.5 ± 13.12, and 143.5 (77−345)) were higher than those of the patients without T2D (46.67 ± 16.38, 15.26 ± 8.75, and 96 (65−202)), and the differences were statistically significant (p = 0.004, p = 0.004, and p < 0.001, respectively). The basal cortisol values of the ICU patients (27.89 (13.91−75)) were significantly higher than those of the ward patients (13.68 (1.48−51.93)) and patients who were transferred to the ICU from the ward due to worsening conditions (19.28 (7.74−55.21)) (p < 0.001 and p = 0.007, respectively). The factors affecting ICU admission were determined to be age, T2D history, basal cortisol, and elevation in FPG using univariate logistic regression analysis. In the multiple logistic regression analysis, age, basal cortisol level, and infiltrative involvement in thorax CT were determined to be the risk factors affecting intensive care admission. Conclusion: High basal cortisol levels in patients with T2D may predict the severity of COVID-19 infection or mortality. Although high basal cortisol levels are among the risk factors affecting ICU admission, patients with COVID-19 should also be evaluated in terms of clinical and laboratory findings and relative adrenal insufficiency.

The predictive value of epicardial fat volume for clinical severity of COVID-19.

Introduction: Epicardial adipose tissue serves as a source of inflammatory cytokines and mediators. Cytokine storm is an important cause of morbidity and mortality in coronavirus disease 2019 (COVID-19). Objectives: To investigate the association between epicardial fat volume (EFV), inflammatory biomarkers and clinical severity of COVID-19. Methods: This retrospective study included 101 patients who were infected with COVID-19. Serum inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and ferritin levels were measured. Computed tomography images were analyzed and semi-automated measurements for EFV were obtained. The primary composite endpoint was admission to the intensive care unit (ICU) or death. Results: The primary composite endpoint occurred in 25.1% (n=26) of patients (mean age 64.8±14.8 years, 14 male). A total of 10 patients died. EFV, CRP, PCT, ferritin and IL-6 levels were significantly higher in ICU patients. Moreover, a positive correlation was determined between EFV and CRP (r: 0.494, p<0.001), PCT (r: 0.287, p=0.005), ferritin (r: 0.265, p=0.01) and IL-6 (r: 0.311, p=0.005). On receiver operating characteristic analysis, patients with EFV >102 cm3 were more likely to have severe complications. In multivariate logistic regression analysis, EFV independently predicted admission to the ICU at a significant level (OR: 1.02, 95% CI: 1.01-1.03, p=0.025). Conclusion: EFV and serum CRP, IL-6, PCT and ferritin levels can effectively assess disease severity and predict the outcome in patients with COVID-19. EFV is an independent predictor of admission to the ICU in hospitalized COVID-19 patients.

Introdução: O tecido adiposo epicárdico é fonte de citocinas inflamatórias e mediadores. A tempestade de citocinas é uma importante causa de morbilidade e mortalidade na doença coronavírus 2019 (COVID-19). Objetivos: Investigar a associação entre volume adiposo epicárdico (VAE), biomarcadores inflamatórios e gravidade clínica da COVID-19. Métodos: Este estudo retrospetivo incluiu 101 doentes infetados com COVID-19. Foram avaliados biomarcadores inflamatórios séricos, incluindo os níveis de proteína C-reativa (PCR), de interleucina-6 (IL-6), de procalcitonina (PCT) e de ferritina. Foram analisadas imagens de tomografia computorizada (TC) e foram obtidas medições semi-automáticas do VAE. O endpoint primário composto foi a admissão na unidade de cuidados intensivos (UCI) ou morte. Resultados: O endpoint primário ocorreu em 25,1% (n=26) dos doentes (idade média 64,8±14,8 anos, 14 homens). Um total de 10 doentes morreu. Os níveis de VAE, PCR, PCT, ferritina e IL-6 foram significativamente superiores nos doentes internados na UCI. Além disso, verificou-se uma correlação positiva entre o VAE e a PCR (r: 0,494, p<0,001), PCT (r: 0,287, p=0,005), ferritina (r: 0,265, p=0,01) e IL-6 (r: 0,311, p=0,005). Na análise de regressão logistica multivariada, os doentes com VAE>102 cm3 tinham maior probabilidade de ter complicações graves. Conclusão: O VAE e os níveis séricos de PCR, IL-6, PCT e ferritina podem avaliar a gravidade da doença e prever o resultado em doentes com COVID-19. O VAE constitui um fator preditivo na admissão dos doentes hospitalizados com COVID-19 numa UCI.

Sarcopenia and Its Prognostic Role on Hospitalization and In-Hospital Mortality in Coronavirus Disease 2019 Patients with At Least One Cardiovascular Risk Factor.

BACKGROUND: The coronavirus disease 2019 infection is a global pandemic that has affected the whole world population. We aimed to evaluate the prognostic role of cross-sectional area, muscle index, and muscle attenuation values in computed tomography-based skeletal groups [erector spinae muscle, pectoralis muscle, and total skeletal muscle] of patients hospitalized for coronavirus disease 2019 and with at least 1 cardiovascular risk factor. METHODS: A total of 232 patients with coronavirus disease 2019 and at least 1 cardiovascular risk factor were enrolled in the study, retrospectively. The cross-sectional area, muscle index, and attenuation of erector spine muscle, pectoralis muscle, and total skeletal muscle were automatically measured on computed tomography images. The study population was assigned into tertiles on the basis of the total SMcsa index. The relationship between the values obtained and the length of hospital stay, admission to intensive care unit, the need for invasive mechani cal ventilation, and mortality was investigated. RESULTS: Admission to intensive care unit, need for invasive mechanical ventilation, and mor tality were higher at tertile 3 groups than in the other groups (all P values <.001). Statistically, all muscle measurements were significantly lower in tertile 3 (P <.001). Diabetes mellitus, hypertension, and total SMcsa index were predictors of in-hospital mortality in patients with coronavirus disease 2019 on the basis of Cox regression analysis. In the Kaplan-Meier analysis for the proportion of survivors relative to the total SMcsa index, tertile 3 had the highest mortal ity (survival rates 57%, P < .001). CONCLUSIONS: Sarcopenia and attendant cardiovascular comorbidities can effectively assess dis ease severity and predict outcome in patients with coronavirus disease 2019.

Neurological manifestations of COVID-19 in confirmed and probable cases: A descriptive study from a large tertiary care center.

During the early phase of the COVID-19 pandemic, it was thought that virus affects only the respiratory system. However, now it is clear that it can affect other systems too, particularly the nervous system. We aimed to identify the most common neurological symptoms and findings of COVID-19 in hospitalized patients and investigate the relationship between these symptoms and clinical, radiological, and laboratory findings. A total of 307 patients, including 125 women and 182 men, were included in the study. They were classified as "confirmed cases" or "probable cases" based on confirmatory tests, including polymerase chain reaction testing of a nasopharyngeal sample or validated antibody test. All medical records, including medical history, clinical course, laboratory data, and radiographic studies, were evaluated by two expert neurologists. Altered mental status (AMS) is the most common neurological finding in both confirmed (68.1%) and probable cases (71.8%). Pre-existing neurological diseases were detected as an independent risk factor for AMS. The mortality rate of patients with AMS was dramatically higher than normal mental status in both confirmed (43.9% vs. 6.2%) and probable cases (47.3% vs. 6.9%) (for both p:0.001). The frequency of seizure attacks was 13.2% in confirmed and 17.5% in probable cases (p:0.321). The mortality rate was higher in patients with a seizure attack in both groups. We conclude that AMS was one of the most common neurological manifestations in this cohort of COVID-19 patients. The development of mental deterioration increases mortality dramatically. Also, the existence of seizure attacks was associated with a high mortality rate.

Intrathecal and Intraventricular Administration of Antibiotics in Gram-Negative Nosocomial Meningitis in a Research Hospital in Turkey.

AIM: To evaluate the gram-negative nosocomial meningitis cases which were treated with intrathecal (IT) / intraventricular (IVT) antibiotics. MATERIAL AND METHODS: Medical records were reviewed for IT/IVT antibiotherapy. Gram-negative nosocomial meningitis cases treated with IT/IVT antibiotherapy additional to systemic antibiotics were included. All patients? sex, age, SOFA scores, surgical history, cerebrospinal fluid (CSF) culture results, CSF cell counts, systemic and IT/IVT antibiotics, their dosages and duration, CSF culture sterility and sterility time, 28-day mortality due to meningitis, and all other causes were recorded and analyzed. RESULTS: Thirteen patients were included between 2014 and 2018. Most common microorganism was Acinetobacter baumannii (A.baumannii) (8/13). IT/IVT antibiotics were chosen according to susceptibility. Colistin was used in eight patients, amikacin was used in four, and one patient used amikacin and colistin consecutively. Culture negativity could not be achieved in two patients. Eight patients clinically improved but five patients had no clinical response. 28-day mortality due to infection occured in 2 of 13 patients (15%). 28-day all-cause mortality occured in 3 of 13 patients (23%). CONCLUSION: In our study, CSF culture negativity rate was high. IT/IVT antibiotic therapy should be considered as an effective and acceptable treatment option, especially in patients who do not respond to standard IV antibiotherapy.

Increasing resistance of nosocomial Acinetobacter baumannii: are we going to be defeated?

AIM: To investigate the change of the antibiotic resistance profiles of the nosocomial Acinetobacter baumannii isolates in intensive care units (ICUs) between the years 2008 and 2011. MATERIALS AND METHODS: A. baumannii isolates that were responsible for ICU-acquired nosocomial infections between 2008 and 2011 were included in the study. The susceptibility rates of the antibiotics that are mainly used in the treatment of Acinetobacter infections were compared by years. Clinical and Laboratory Standards Institute criteria were used to determine antimicrobial susceptibility. RESULTS: There were 252 infection episodes detected in 229 hospitalized patients in the ICU that were caused by A. baumannii. Imipenem resistance was found as 98.9% in 2011 whereas it was 54% in 2008. A significant increase was observed for meropenem resistance from 2008 (73.5%) to 2011 (98.9%). Colistin resistance, confirmed by E-test, was found in 4 strains. The resistance rates of other antimicrobial agents were as follows: ampicillin/sulbactam 95.7% and 93.5%, cefoperazone/sulbactam 45.7% and 90.3%, netilmicin 41.7% and 53%, gentamicin 96% and 87.2%, and trimethoprimsulfamethoxazole 91.7% and 72%, in 2008 and 2011, respectively. The resistance rate to tigecycline increased to 81.3% in 2011 from 12.5% in 2008.