The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis-A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial.

In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon's test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.

Cardiac Delirium Index for Predicting the Occurrence of Postoperative Delirium in Adult Patients After Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative delirium (POD) is a serious complication of cardiac surgery. It is an acute neuropsychiatric syndrome. The aim of this study was to analyze the CARDEL Index, composed of advancing age, preoperative glycated hemoglobin and the platelet-to-WBC ratio (PWR) previously described and calculated, using a different patient database, to assess its usefulness as a marker for predicting postoperative delirium after coronary artery by-pass grafting (CABG). METHODS: A retrospective analysis of 1098 patients who underwent, isolated CABG procedures between 2017 and 2019 was performed. RESULTS: Within the study group, 164/1098 (14.93%) patients were diagnosed with delirium. Preoperative inflammatory parameters were elevated in patients with delirium: White Blood Cell count (p=0.003), Neutrophil count (p=0.016) and C-reactive protein (p<0.001). A decrease in preoperative PWR was shown in patients with delirium (p=0.008). Delirious patients spent more time mechanically ventilated (p<0.001) and had longer hospitalization times (p=0.002). Mortality at 1 year was significantly higher in patients with POD (p<0.001). The CARDEL Index in this study group for POD detection has the largest area under the curve (AUC) of 0.664 (p<0.001) and a cut-off value of 8.08. CONCLUSION: CARDEL Index may be treated as a potentially valuable tool for delirium prediction in patients after CABG.

An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.

The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.

Postoperative Delirium in Patients with Chronic Obstructive Pulmonary Disease after Coronary Artery Bypass Grafting.

BACKGROUND AND OBJECTIVES: The incidence of postoperative delirium (POD) in patients with chronic obstructive pulmonary disease (COPD) is unclear. It seems that postoperative respiratory problems that may occur in COPD patients, including prolonged mechanical ventilation or respiratory-tract infections, may contribute to the development of delirium. The aim of the study was to identify a relationship between COPD and the occurrence of delirium after cardiac surgery and the impact of these combined disorders on postoperative mortality. MATERIALS AND METHODS: We performed an analysis of data collected from 4151 patients undergoing isolated coronary artery bypass grafting (CABG) in a tertiary cardiac-surgery center between 2012 and 2018. We included patients with a clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The primary endpoint was postoperative delirium; Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) was used for delirium assessment. RESULTS: Final analysis included 283 patients with COPD, out of which 65 (22.97%) were diagnosed with POD. Delirious COPD patients had longer intubation time (p = 0.007), more often required reintubation (p = 0.019), had significantly higher levels of C-reactive protein (CRP) three days after surgery (p = 0.009) and were more often diagnosed with pneumonia (p < 0.001). The CRP rise on day three correlated positively with the occurrence of postoperative pneumonia (r = 0.335, p = 0.005). The probability of survival after CABG was significantly lower in COPD patients with delirium (p < 0.001). CONCLUSIONS: The results of this study confirmed the relationship between chronic obstructive pulmonary disease and the incidence of delirium after cardiac surgery. The probability of survival in COPD patients undergoing CABG who developed postoperative delirium was significantly decreased.

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.

Balancing intubation time with postoperative risk in cardiac surgery patients - a retrospective cohort analysis.

INTRODUCTION: Intubation time in patients undergoing cardiac surgery may be associated with increased mortality and morbidity. Premature extubation can have serious adverse physiological consequences. The aim of this study was to determine the influence of intubation time on morbidity and mortality in patients undergoing cardiac surgery. METHODS: We performed a retrospective analysis of data on 1,904 patients undergoing isolated coronary artery bypass grafting (CABG) and stratified them by duration of intubation time after surgery - 0-6, 6-9, 9-12, 12-24 and over 24 hours. Postoperative complications risk analysis was performed using multivariate logistic regression analysis for patients extubated ≤12 and >12 hours. RESULTS: Intubation percentages in each time cohort were as follows: 0-6 hours - 7.8%, 6-9 hours - 17.3%, 9-12 hours - 26.8%, 12-24 hours - 44.4% and >24 hours - 3.7%. Patients extubated ≤12 hours after CABG were younger, mostly males, more often smokers, with lower preoperative risk. They had lower 30-day mortality (2.02% vs 4.59%, P=0.002), shorter hospital stay (7.68±4.49 vs 9.65±12.63 days, P<0.001) and shorter intensive care unit stay (2.39 vs 3.30 days, P<0.001). Multivariate analysis showed that intubation exceeding 12 hours after CABG increases the risk of postoperative delirium (OR 1.548, 95% CI 1.161-2.064, P=0.003) and risk of postoperative hemofiltration (OR 1.302, 95% CI 1.023-1.657, P=0.032). CONCLUSION: Results indicate that risk of postoperative complications does not increase until intubation time exceeds 12 hours. Shorter intubation time is seen in younger, men and smokers. Intubation time >12 hours is a risk factor for postoperative delirium and hemofiltration after cardiac surgery.