Dexmedetomidine may reduce the risk of acute kidney injury development in critically ill patients during colistin therapy.

INTRODUCTION: Colistin is considered as a last resort therapy for multidrug-resistant gram-negative organisms. It is widely used despite the significant risk of nephrotoxicity. Experimental studies showed the nephroprotective effect of dexmedetomidine, a sedative agent, against colistin toxicity. This study was performed to show the possible nephroprotective effect of dexmedetomidine among critically ill patients who received colistin. METHODS: Adult (>17 years) patients who were admitted to our surgical and medical intensive care unit (ICU) from March 2018 through March 2021, and who received colistin were included. Patients who receive Colistin therapy or intensive care unit follow-up of <72 h (discharge or death) and Acute kidney injury (AKI) or need hemodialysis prior to colistin therapy at the same hospitalization were excluded. AKI risk factors were examined by grouping patients with and without AKI. Patients, receiving colistin concomitantly with dexmedetomidine were also evaluated. RESULTS: Of the 139 patients included, 27 (17.8%) patients received dexmedetomidine. Sixty-five patients (47%) had AKI, at a median 5 (4-7) days after the initiation of colistin. Older age, lower baseline estimated glomerular filtration rate, and vasopressor use were associated with a higher risk of AKI, while dexmedetomidine use was associated with a lower risk. In the multivariate regression model, dexmedetomidine use was independently associated with a lower risk of AKI development (OR 0.20 95% CI 0.07-0.59, p = 0.003). CONCLUSION: In respect to these findings, dexmedetomidine may provide protection against AKI during colistin therapy in critically ill patients.

The effect of frailty on the development of acute kidney injury in critically-ill geriatric patients with COVID-19.

BACKGROUND: Acute kidney injury is strongly associated with mortality in critically ill patients with coronavirus disease 2019 (COVID-19); however, age-related risk factors for acute kidney injury are not clear yet. In this study, it was aimed to evaluate the effects of clinical factors on acute kidney injury development in an elderly COVID-19 patients. METHODS: Critically ill patients (≥65years) with COVID-19 admitted to the intensive care unit were included in the study. Primary outcome of the study was the rate of acute kidney injury, and secondary outcome was to define the effect of frailty and other risk factors on acute kidney injury development and mortality. RESULTS: A total of 132 patients (median age 76 years, 68.2% male) were assessed. Patients were divided into two groups as follows: acute kidney injury (n = 84) and nonacute kidney injury (n = 48). Frailty incidence (48.8% vs. 8.3%, p < 0.01) was higher in the acute kidney injury group. In multivariate analysis, frailty (OR, 3.32, 95% CI, 1.67-6.56), the use of vasopressors (OR, 3.06 95% CI, 1.16-8.08), and the increase in respiratory support therapy (OR, 2.60, 95% CI, 1.01-6.6) were determined to be independent risk factors for acute kidney injury development. The mortality rate was found to be 97.6% in patients with acute kidney injury. DISCUSSION: Frailty is a risk factor for acute kidney injury in geriatric patients with severe COVID-19. The evaluation of geriatric patients based on a frailty scale before intensive care unit admission may improve outcomes.

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

Background: To date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality. Materials and methods: In this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study. Results: A total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66­81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96­58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55­14.46, p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84­51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality. Conclusion: Early detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.

A new colorimetric DPPH• scavenging activity method with no need for a spectrophotometer applied on synthetic and natural antioxidants and medicinal herbs.

2,2-Diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging, the most commonly used antioxidant method with more than seventeen thousand articles cited, is very practical; however, as with most assays, it has the major disadvantage of dependence on a spectrophotometer. To overcome this drawback, the colorimetric determination of the antioxidant activity using a scanner and freely available Image J software was developed. In this new method, the mixtures of solutions of DPPH• and standard antioxidants or extracts of common medicinal herbs were dropped onto TLC plates, after an incubation period. The spot images were evaluated with Image J software to determine CSC50 values, the sample concentrations providing 50% colour reduction, which were very similar with the SC50 values obtained with spectrophotometric method. The advantages of the new method are the use of lower amounts of reagents and solvents, no need for costly spectrophotometers, and thus significantly lowered costs, and convenient implementation in any environment and situation.

Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities.

Compound 2 was synthesized by reacting CS2/KOH with compound 1. The treatment of compound 2 with hydrazine hydrate produced compound 3. Then, compound 3 was converted to Schiff bases (4a-d) by the handling with several aromatic aldehydes. The treatment of triazole compounds 4a-d containing Schiff base with morpholine gave compounds 5a-d. All compounds were tested for their antioxidant and antimicrobial activities. The antioxidant test results of DPPH• radical scavenging and ferric reducing/antioxidant power methods showed good antioxidant activity. The triazole-thiol (3) was the most active, and the effect of the substituent type of the thiophene ring on the activity was same for both Schiff bases (4a-d) and Mannich bases (5a-d). Among the newly synthesized triazole derivatives, the Schiff base 4d and the Mannich base 5d carrying nitro substituent on the thiophene ring showed promising antibacterial and antifungal activity, with lower MIC values than the standard antibacterial ampicillin.

Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin.

Taxifolin, also known as dihydroquercetin, is a flavonoid commonly found in plants. Carbonic anhydrase (CA, EC 4.2.1.1) plays an important role in many critical physiological events including carbon dioxide (CO2)/bicarbonate (HCO3(-)) respiration and pH regulation. There are 16 known CA isoforms in humans, of which human hCA isoenzymes I and II (hCA I and II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of taxifolin against the slow cytosolic isoenzyme hCA I, and the ubiquitous and dominant rapid cytosolic isoenzyme hCA II were studied. Taxifolin, as a naturally bioactive flavonoid, has a K(i) of 29.2 nM against hCA I, and 24.2 nM against hCA II. For acetylcholinesterase enzyme (AChE) inhibition, K(i) parameter of taxifolin was determined to be 16.7 nM. These results clearly show that taxifolin inhibited both CA isoenzymes and AChE at the nM levels.

Antioxidant, antiradical, and anticholinergic properties of cynarin purified from the Illyrian thistle (Onopordum illyricum L.).

Cynarin is a derivative of hydroxycinnamic acid and it has biologically active functional groups constituent of some plants and food. We elucidated the antioxidant activity of cynarin by using different in vitro condition bioanalytical antioxidant assays like DMPD(•+), ABTS(•+), O2(•-), DPPH(•) and H2O2 scavenging effects, the total antioxidant influence, reducing capabilities, Fe(2+) chelating and anticholinergic activities. Cynarin demonstrated 87.72% inhibition of linoleic acid lipid peroxidation at 30 µg/mL concentration. Conversely, some standard antioxidants like trolox, α-tocopherol, butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) exhibited inhibitions of 90.32, 75.26, 97.61, 87.30%, and opponent peroxidation of linoleic acid emulsion at the identical concentration, seriatim. Also, cynarin exhibited effective DMPD(•+), ABTS(•+), O2(•-), DPPH(•), and H2O2 scavenging effects, reducing capabilities and Fe(2+) chelating effects. On the contrary, IC50 and K(i) parameters of cynarin for acetylcholinesterase enzyme inhibition were determined as 243.67 nM (r(2): 0.9444) and 39.34 ± 13.88 nM, respectively. This study clearly showed that cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities.

Oxidative modification of carbonic anhydrase by peroxynitrite trigger immune response in mice and rheumatic disease patients.

BACKGROUND: Carbonic anhydrases (CA) are metalloenzymes with wide tissue distribution, involved in many important physiological processes, and in some rheumatic diseases, autoantibodies are formed against these enzymes. Recent studies have suggested that oxidative stress triggers anti-CA antibody formation. In this study, we aimed to investigate the effects of modification with oxidative/nitrosative stress end products on CA antigenicity in mice and the relationship between the modified CA autoantibodies and oxidant-antioxidant status in patients with rheumatoid arthritis (RA) and Sjögren's syndrome (SjS). METHODS: CA I and CA II isoenzymes were isolated from human erythrocytes and modified with 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and peroxynitrite (PN). Balb-c mice were immunized with these agents to determine the effects of modification on CA antigenicity. The autoantibody titers of modified CA isoenzymes were detected in patients. In addition MDA, 4-HNE, 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured to assess the oxidant-antioxidant status in patients. RESULTS: Modifications of carbonic anhydrase with oxidative stress end products, HNE, MDA and PN, lead to alterations in the immune response to these enzymes in mice. It was found that HNE and MDA decreased the antigenicity while PN increased. In addition, PN-modified CA autoantibody levels were found to be significantly different in both RA and SjS patients compared to their controls (p<0.05). CONCLUSIONS: PN modifications can also trigger an immune response against CA isoenzymes in mice, and PN-modified CA I and CA II autoantibody titers were found at a significantly high level in both RA and SjS patients.

Clinical Significance of Pleural Lactate Measurement in Critically Ill Patients with Parapneumonic Pleural Effusion.

OBJECTIVE: Pleural fluid pH measurement is recommended for tube thoracostomy decisions in complicated parapneumonic pleural effusions. However, pleural fluid pH may be affected by blood pH in critically ill patients with common systemic acid-base disorders. We aimed to investigate the use of pleural fluid lactate to distinguish culture-positive parapneumonic effusions from other pleural effusions. MATERIAL AND METHODS: This prospective observational study included 121 eligible patients (51 female and 70 male). All patients with pleural effusion who underwent thoracentesis were assessed. Pleural fluid lactate was measured by a blood gas analyzer. RESULTS: Of the 121 patients, 30 (24.8%) were transudate and 91 (75.2%) were exudate. Of the 91 patients with exudative pleural effusion, 61 were diagnosed as culture-negative parapneumonic, 13 as culture-positive parapneumonic, 9 as malignant, and 8 as other exudative effusion. There was a strong positive linear association between serum pH and pleural fluid pH (R = 0.77, P < .001). The post hoc tests for pleural fluid lactate revealed there was a significant difference between culture-positive parapneumonic versus culture-negative parapneumonic groups (P = .004), culture-positive parapneumonic versus transudative effusion groups (P < .001), culture-negative parapneumonic versus transudative effusion groups (P = .008) and lastly; malignant effusion versus transudative effusion groups (P = .001). Receiver operating characteristics curve analysis for culture-positive parapneumonic indicated a cutoff of 4.55 mmol/L for pleural fluid lactate to have a sensitivity of 76.9% and a specificity of 84.3% (positive predictive value: 37%, negative predictive value: 96.8%). CONCLUSION: A cutoff of 4.55 mmol/L of pleural fluid lactate can be used as a useful tool to distinguish culture-positive parapneumonic effusions from other effusions in critically ill patients.

Combined Effects of Prone Positioning and Airway Pressure Release Ventilation on Oxygenation in Patients with COVID-19 ARDS.

Objective: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). Invasive mechanical ventilation (IMV) support and prone positioning are essential treatments for severe COVID-19 ARDS. We aimed to determine the combined effect of prone position and airway pressure release ventilation (APRV) modes on oxygen improvement in mechanically-ventilated patients with COVID-19. Methods: This prospective observational study included 40 eligible patients (13 female, 27 male). Of 40 patients, 23 (57.5%) were ventilated with APRV and 17 (42.5%) were ventilated with controlled modes. A prone position was applied when the PaO2/FiO2 ratio <150 mmHg despite IMV in COVID-19 ARDS. The numbers of patients who completed the first, second, and third prone were 40, 25, and 15, respectively. Incident barotrauma events were diagnosed by both clinical findings and radiological images. Results: After the second prone, the PaO2/FiO2 ratio of the APRV group was higher compared to the PaO2/FiO2 ratio of the control group [189 (150-237)] vs. 127 (100-146) mmHg, respectively, (P=0.025). Similarly, after the third prone, the PaO2/FiO2 ratio of the APRV group was higher compared to the PaO2/FiO2 ratio of the control group [194 (132-263)] vs. 83 (71-136) mmHg, respectively, (P=0.021). Barotrauma events were detected in 13.0% of the patients in the APRV group and 11.8% of the patients in the control group (P=1000). The 28-day mortality was not different in the APRV group than in the control group (73.9% vs. 70.6%, respectively, P=1000). Conclusion: Using the APRV mode during prone positioning improves oxygenation, especially in the second and third prone positions, without increasing the risk of barotrauma. However, no benefit on mortality was detected.

Amikacin-induced acute kidney injury in mechanically ventilated critically ill patients with sepsis.

In this retrospective cohort study, we aimed to evaluate the incidence, risk factors and outcomes of amikacin-induced acute kidney injury (AKI) in critically ill patients with sepsis. A total of 311 patients were included in the study. Of them, 83 (26.7%) had amikacin-induced AKI. In model 1, the multivariable analysis demonstrated concurrent use of colistin (OR 25.51, 95%CI 6.99-93.05, p< 0.001), presence of septic shock during amikacin treatment (OR 4.22, 95%CI 1.76-10.11, p=0.001), and Charlson Comorbidity Index (OR 1.14, 95%CI 1.02-1.28, p=0.025) as factors independently associated with an increased risk of amikacin-induced AKI. In model 2, the multivariable analysis demonstrated concurrent use of at least one nephrotoxic agent (OR 1.95, 95%CI 1.10-3.45; p=0.022), presence of septic shock during amikacin treatment (OR 3.48, 95%CI 1.61-7.53; p=0.002), and Charlson Comorbidity Index (OR 1.12, 95%CI 1.01-1.26; p=0.037) as factors independently associated with an increased risk of amikacin-induced AKI. In conclusion, before amikacin administration, the risk of AKI should be considered, especially in patients with multiple complicated comorbid diseases, septic shock, and those receiving colistin therapy.

The Impact of Mechanical Ventilation Modes on Complications of Fiberoptic Bronchoscopy in Critically Ill Patients.

OBJECTIVE: The effects of fiberoptic bronchoscopy are not elucidated in different mechanical ventilation modes. The present study aimed to evaluate the effects of fiberoptic bronchoscopy on lung mechanics, ventilation parameters, and gas exchange in 2 often-used modes, volume control and pressure control, in invasively ventilated patients followed up in the intensive care unit. MATERIAL AND METHODS: Eligible patients were screened and included in the study after intensive care unit-fiberoptic bronchoscopy database search. Patients who underwent fiberoptic bronchoscopy under volume control and pressure control mechanical ventilation modes were compared. The primary outcome was the occurrence of any complication within the first 24 hours after the procedure, and secondary outcomes were changes in lung mechanics (dynamic lung compliance and airway resistance) and gas exchange (arterial partial pressures of oxygen and carbon dioxide). RESULTS: A total of 61 patients (median age: 69 years, 60.7% male) were included. Twenty-nine (47.5%) patients were ventilated in volume control mode and 32 (52.5%) in pressure control mode during the fiberoptic bronchoscopy procedure, and the median (interquartile range) duration of the procedure was 9 [8-11] minutes. Baseline dynamic lung compliance, airway resistance, arterial partial pressures of oxygen and carbon dioxide, and the fraction of inspired O2 were similar in both groups. After fiberoptic bronchoscopy, dynamic lung compliance decreased in both groups, and airway resistance and peak airway pressures increased but reached pre-fiberoptic bronchoscopy values at the 1st hour after the procedure. No significant differences were detected in both groups in terms of blood gas values and lung mechanics in the 1st and 24th hours after the procedure. In both groups, the 24th hour fraction of inspired O2 was the same as the pre-fiberoptic bronchoscopy values, but the ratio of arterial partial pressure of oxygen and the fraction of inspired O2 improved. No complications developed in patients within 24 hours after the procedure. CONCLUSION: No differences were detected in terms of gas exchange and pulmonary mechanics, and complications in volume control and pressure control modes in critically ill intubated patients.

The Safety of Fiberoptic Bronchoscopy in Airway Pressure Release Ventilation Mode in Critically Ill Patients with Severe Acute Respiratory Distress Syndrome: A Preliminary Study.

OBJECTIVE: The most appropriate ventilatory mode during fiberoptic bronchoscopy is still not yet known clearly for patients with acute respiratory distress syndrome. Airway pressure release ventilation is used as a recovery treatment for patients with severe acute respiratory distress syndrome. In this study, the aim was to evaluate the safety of the fiberoptic bronchoscopy process in patients with severe acute respiratory distress syndrome ventilated with airway pressure release ventilation mode and its effect on gas exchange and respiratory mechanics. MATERIAL AND METHODS: Single-center retrospective observational study was performed in the intensive care unit of a tertiary referral center from September 2018 to November 2019. Patients with severe ARDS ventilated with APRV mode and undergoing FB were included. Fiberoptic bronchoscopy was performed by an expert intensivist-pulmonologist. All ventilator parameters set by the clinician were kept stable, and no change was made other than O2 concentration. The mechanical ventilation parameters and arterial blood gas values before and after the procedure and fiberoptic bronchoscopy-related complications were recorded for the first 24 hours. RESULTS: A total of 14 acute respiratory distress syndrome patients who were ventilated with airway pressure release ventilation were enrolled. No significant deteriorations were detected in gas exchange, pulmonary compliance, and airway resistance values in our case series. It was observed that a small reduction in PaO2 and an increase in PaCO2 were present after the 1st hour; however, both were returned to baseline values in the 24th hour. Only 1 patient developed fiberoptic bronchoscopy-induced hypoxemia (7.1%). Complications, such as fiberoptic bronchoscopy-induced barotrauma, pneumothorax, hemodynamic deterioration, and bleeding, were not detected. CONCLUSION: According to our preliminary findings, performing fiberoptic bronchoscopy under airway pressure release ventilation mode by an experienced bronchoscopist does not bring additional complication risks in patients with severe acute respiratory distress syndrome.

Incidence of and risk factors for postintubation hypotension in critically ill patients with COVID-19. / Incidência e fatores de risco para hipotensão pós-intubação em pacientes críticos com COVID-19.

OBJECTIVE: To evaluate the incidence of risk factors for postintubation hypotension in critically ill patients with COVID-19. METHODS: We conducted a retrospective study of 141 patients with COVID-19 who were intubated in the intensive care unit. Postintubation hypotension was defined as the need for any vasopressor dose at any time within the 60 minutes following intubation. Patients with intubation-related cardiac arrest and hypotension before intubation were excluded from the study. RESULTS: Of the 141 included patients, 53 patients (37.5%) had postintubation hypotension, and 43.6% of the patients (n = 17) were female. The median age of the postintubation hypotension group was 75.0 (interquartile range: 67.0 - 84.0). In the multivariate analysis, shock index ≥ 0.90 (OR = 7.76; 95%CI 3.14 - 19.21; p < 0.001), albumin levels < 2.92g/dL (OR = 3.65; 95%CI 1.49 - 8.96; p = 0.005), and procalcitonin levels (OR = 1.07, 95%CI 1.01 - 1.15; p = 0.045) were independent risk factors for postintubation hypotension. Hospital mortality was similar in patients with postintubation hypotension and patients without postintubation hypotension (92.5% versus 85.2%; p = 0.29). CONCLUSION: The incidence of postintubation hypotension was 37.5% in critically ill COVID-19 patients. A shock index ≥ 0.90 and albumin levels < 2.92g/dL were independently associated with postintubation hypotension. Furthermore, a shock index ≥ 0.90 may be a practical tool to predict the increased risk of postintubation hypotension in bedside scenarios before endotracheal intubation. In this study, postintubation hypotension was not associated with increased hospital mortality in COVID-19 patients.

OBJETIVO: Avaliar a incidência de fatores de risco para hipotensão pósintubação em pacientes críticos com COVID-19. METÓDOS: Foi realizado um estudo retrospectivo com 141 pacientes com COVID-19 que foram intubados na unidade de terapia intensiva. Hipotensão pós-intubação foi definida como a necessidade de qualquer dose de vasopressor a qualquer momento em até 60 minutos após a intubação. Pacientes com parada cardiorrespiratória relacionada à intubação e hipotensão antes da intubação foram excluídos do estudo. RESULTADOS: Dos 141 pacientes incluídos, 53 pacientes (37,5%) e 43,6% dos pacientes (n = 17) eram do sexo feminino. A idade mediana do grupo com hipotensão pós-intubação foi de 75 anos (amplitude interquartil: 67,0 - 84,0). Na análise multivariada, índice de choque ≥ 0,90 (RC = 7,76; IC95% 3,14 - 19,21; p < 0,001), níveis de albumina < 2,92g/dL (RC = 3,65; IC95% 1,49 - 8,96; p = 0,005) e níveis de procalcitonina (RC = 1,07, IC95% 1,01 - 1,15; p = 0,045) foram fatores de risco independentes para hipotensão pós-intubação. A mortalidade hospitalar foi semelhante em pacientes com hipotensão pós-intubação e pacientes sem hipotensão pós-intubação (92,5% versus 85,2%; p = 0,29). CONCLUSÃO: A incidência de hipotensão pós-intubação foi de 37,5% em pacientes críticos com COVID-19. Um índice de choque ≥ 0,90 e níveis de albumina < 2,92g/ dL foram independentemente associados à hipotensão pós-intubação. Além disso, índice de choque ≥ 0,90 pode ser uma ferramenta do leito antes da intubação endotraqueal. Neste estudo, a hipotensão pós-intubação não esteve associada ao aumento da mortalidade hospitalar em pacientes com COVID-19.

COVID-19 Pneumonia After SARS-CoV-2 Vaccination with CoronaVac: A Case Series from Turkey.

Coronavirus disease 2019 is a novel viral infection that has caused a pandemic globally. Many kinds of vaccine development studies were conducted to prevent the spread and deaths. The CoronaVac is the most commonly used vaccine in Turkey. Phase 3 trials from various countries revealed that CoronaVac efficacy ranged from 50.7% to 91.25% but increased in moderate or severe cases to 100%. Additionally, it was remarkable owing to high seroconversion rates achieving up to 100%. After the vaccine campaign began in Turkey, critically ill patients continued to admit to our center's intensive care unit though they had been vaccinated with 2 doses of CoronaVac. The clinical course of these patients revealed that they are still at high risk of severe disease and death. Therefore, we aimed to share these patients' clinical characteristics and disease course, laboratory, and radiologic data.

Is serum magnesium level associated with atrial fibrillation in the mixed medical/surgical intensive care unit setting?

Background: Although low serum magnesium level is a a relatively common problem in mixed medical/surgical intensive care units (ICUs), its association with new-onset atrial fibrillation (NOAF) has been studied to a lesser extent. We aimed to investigate the effect of magnesium levels on the development of NOAF in critically ill patients admitted to the mixed medical/surgical ICU. Methods: A total of 110 eligible patients (45 female, 65 male) were included in this case-control study. The age and sex-matched control group (n = 110) included patients with no atrial fibrillation from admission to discharge or death. Results: The incidence of NOAF was 2.4% (n = 110) between January 2013 and June 2020. At NOAF onset or the matched time point, median serum magnesium levels were lower in the NOAF group than in the control group (0.84 [0.73-0.93] vs. 0.86 [0.79-0.97] mmol/L; p = 0.025). At NOAF onset or the matched time point, 24.5% (n = 27) in the NOAF group and 12.7% (n = 14) in the control group had hypomagnesemia (p = 0.037). Based on Model 1, multivariable analysis demonstrated magnesium level at NOAF onset or the matched time point (OR: 0.07; 95%CI: 0.01-0.44; p = 0.004), acute kidney injury (OR: 1.88; 95%CI: 1.03-3.40; p = 0.039), and APACHE II (OR: 1.04; 95% CI: 1.01-1.09; p = 0.046) as factors independently associated with an increased risk of NOAF. Based on Model 2, multivariable analysis demonstrated hypomagnesemia at NOAF onset or the matched time point (OR: 2.52; 95% CI: 1.19-5.36; p = 0.016) and APACHE II (OR: 1.04; 95%CI: 1.01-1.09; p = 0.043) as factors independently associated with an increased risk of NOAF. In multivariate analysis for hospital mortality, NOAF was an independent risk factor for hospital mortality (OR: 3.22; 95% CI: 1.69-6.13, p<0.001). Conclusion: The development of NOAF in critically ill patients increases mortality. Critically ill patients with hypermagnesemia should be carefully evaluated for risk of NOAF.

The Predictive Values of Respiratory Rate Oxygenation Index and Chest Computed Tomography Severity Score for High-Flow Nasal Oxygen Failure in Critically Ill Patients with Coronavirus Disease-2019.

Background: The prediction of high-flow nasal oxygen (HFNO) failure in patients with coronavirus disease-2019 (COVID-19) having acute respiratory failure (ARF) may prevent delayed intubation and decrease mortality. Aims: To define the related risk factors to HFNO failure and hospital mortality. Study Design: Retrospective cohort study. Methods: To this study, 85 critically ill patients (≥18 years) with COVID-19 related acute kidney injury who were treated with HFNO were enrolled. Treatment success was defined as the de-escalation of the oxygenation support to the conventional oxygen therapies. HFNO therapy failure was determined as the need for invasive mechanical ventilation or death. The patients were divided into HFNO-failure (HFNO-F) and HFNO-success (HFNO-S) groups. Electronic medical records and laboratory data were screened for all patients. Respiratory rate oxygenation (ROX) index on the first hour and chest computed tomography (CT) severity score were calculated. Factors related to HFNO therapy failure and mortality were defined. Results: This study assessed 85 patients (median age 67 years, 69.4% male) who were divided into two groups as HFNO success (n = 33) and HFNO failure (n = 52). The respiratory rate oxygenation (ROX) was measured at 1 hour and the computed tomography (CT) score indicated HFNO failure and intubation, with an area under the receiver operating characteristic of 0.695 for the ROX index and 0.628 for the CT score. A ROX index of <3.81 and a CT score of >15 in the first hour of therapy were the predictors of HFNO failure and intubation. Age, Acute Physiology and Chronic Health Evaluation II score, arterial blood gas findings "(i.e., partial pressure of oxygen [PaO2], PaO2 [fraction of inspired oxygen]/SO2 [oxygen saturation] ratio)", and D-dimer levels were also associated with HFNO failure; however, based on logistic regression analysis, a calculated ROX on the first hour of therapy of <3.81 (odds ratio [OR] = 4.78, 95% confidence interval [CI] = 1.75-13.02, P = 0.001) and a chest CT score of >15 (OR = 2.83, 95% CI = 1.01-7.88, P = <0.001) were the only independent risk factors. In logistic regression analysis, a ROX calculated on the first hour of therapy of <3.81 (OR = 4.78, [95% CI = 1.75-13.02], P = 0.001) and a chest CT score of >15 (OR 2.83, 95% CI = 1.01-7.88, P = <0.001) were the independent risk factors for the HFNO failure. The intensive care unit and hospital mortality rates were 80.2% and 82.7%, respectively, in the HFNO failure group. Conclusion: The early prediction of HFNO therapy failure is essential considering the high mortality rate in patients with HFNO therapy failure. Using the ROX index and the chest CT severity score combined with the other clinical parameters may reduce mortality. Additionally, multi-centre observational studies are needed to define the predictive value of ROX and chest CT score not only for COVID-19 but also other causes of ARF.

New-onset atrial fibrillation in critically ill patients with coronavirus disease 2019 (COVID-19).

Background: Mortality in critically ill patients with coronavirus disease 2019 (COVID-19) is high, therefore, it is essential to evaluate the independent effect of new-onset atrial fibrillation (NOAF) on mortality in patients with COVID-19. We aimed to determine the incidence, risk factors, and outcomes of NOAF in a cohort of critically ill patients with COVID-19. Methods: We conducted a retrospective study on patients admitted to the intensive care unit (ICU) with a diagnosis of COVID-19. NOAF was defined as atrial fibrillation that was detected after diagnosis of COVID-19 without a prior history. The primary outcome of the study was the effect of NOAF on mortality in critically ill COVID-19 patients. Results: NOAF incidence was 14.9% (n = 37), and 78% of patients (n = 29) were men in NOAF positive group. Median age of the NOAF group was 79.0 (interquartile range, 71.5-84.0). Hospital mortality was higher in the NOAF group (87% vs 67%, respectively, P = .019). However, in multivariate analysis, NOAF was not an independent risk factor for hospital mortality (OR 1.42, 95% CI 0.40-5.09, P = .582). Conclusions: The incidence of NOAF was 14.9% in critically ill COVID-19 patients. Hospital mortality was higher in the NOAF group. However, NOAF was not an independent risk factor for hospital mortality in patients with COVID-19.

In vitro effects of peroxynitrite treatment on fish liver catalase activity.

The effect of peroxynitrite (PN), a highly toxic agent, on catalase (CAT) activity in fish liver microsomal homogenates was determined. PN was synthesized by mixing acidic hydrogen peroxide solution with sodium nitrite solution and then adding sodium hydroxide solution into the mixture in order to stabilize the highly labile compound peroxynitrous acid (ONOOH) in peroxynitrite anion form (ONOO(- )). The effect of PN and decomposed peroxynitrite (DPN), prepared by preincubation with HCl, was monitored by using a constant amount of homogenate containing the CAT enzyme. Significant losses were observed in the CAT activity of fish liver enzyme after treatment with PN and also with DPN products, the inhibitory effect of PN being slightly more pronounced than that of DPN. IC(50) values were 5.5 and 8.5 microM for PN and DPN, respectively. The PN inhibition of CAT activity is due to both the effects of the secondary and decomposition products of PN and its nitration and oxidation effects on the amino acid residues of the enzyme.

Microwave-assisted synthesis of 4'-azaflavones and their N-alkyl derivatives with biological activities.

4'-Azaflavone (=2-(pyridin-4-yl)-4H-1-benzopyran-4-one; 4) and 3-[(pyridin-4-yl)methyl]-4'-azaflavone (5) were synthesized by a simple environmentally friendly microwave-assisted one-pot method through the cyclization of 3-hydroxy-1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propan-1-one (1), (E)-2'-hydroxy-4-azachalcone (2; chalcone=1,3-diphenylprop-2-en-1-one), and 2'-hydroxy-2-[(hydroxy)(pyridin-4-yl)methyl]-4''-azachalcone (3) under solventless conditions using silica-supported NaHSO(4), followed by treatment with base. In addition, N-alkyl-substituted 4'-azaflavonium bromides 6 and 7 were prepared from compounds 4 and 5, respectively. The antimicrobial and antioxidant activities of compounds 1-7 were tested. The N-alkyl-substituted 4'-azaflavonium bromides 6 and 7 showed high antimicrobial activity against the Gram-positive bacteria and the fungus tested, with MIC values close to those of reference antimicrobials ampicilline and fluconazole. The alkylated compounds 6 and 7 also showed a good antioxidant character in the two antioxidant methods, DPPH (=1,1-diphenyl-2-picrylhydrazyl) radical-scavenging and ferric reducing/antioxidant power (FRAP) tests.