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.

The effect of herbicides on morphological features of pollen grains in Prunus serotina Ehrh. in the context of elimination of this invasive species from European forests.

Prunus serotina Ehrh. is an alien invasive neophyte widespread in European forests. So far, no effective methods of its elimination have been developed. For this reason, the aim of our study was to determine how herbicides affect the morphological characteristics of pollen grains. This knowledge may be crucial to control this invasive species. The current study was carried out in a research area of 2.7 ha located in the Zielonka Forest near Poznan, Poland (N 52°31'58.016″, E 17°05'55.588″). We tested morphological differences among ten features of P. serotina pollen, based on the samples collected from 15 control trees compared to the 50 trees treated with five different herbicides. In total 1950 pollen grains were measured. We confirmed the adopted hypotheses of long-term herbicide influence on P. serotina pollen. Pollen grains from the control trees had a longer equatorial axis, were more elongated in shape and had the largest range of exine thickness compared to the pollen from the herbicide-treated samples. Exine thickness in the control sample was on average 0.74 µm, ranging from 0.42 to 1.19 µm. The average values and the ranges of this trait in the samples treated with herbicides were larger (e.g. average exine thickness was from 0.90 to 0.95 µm). There were differences in the P/E ranges of variability between the control and herbicide-treated samples. In the control sample the P/E ratio was 1.32-2.04 and elongated forms of pollen shapes prevailed, while in the herbicide-treated samples it ranged from 1.03 to 1.47. The share of deformed pollen grains in the herbicide-treated samples was lower than expected, ranging from 8.7 to 25.3%, while in the control samples it was 6%. Logo and Mustang turned out to be the most effective among the herbicides used in the described research. The two used application methods were found to have an effect on pollen quality.

Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection.

Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells' methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target.

Pollen morphology and variability of native and alien, including invasive, species of the genus Spiraea L. (Rosaceae) in Poland.

The pollen morphology was studied in 25 taxa of the genus Spiraea L. The aims of this study were to describe the pollen morphology and variability and to determine whether the pollen features of alien, expansive or invasive Spiraea species differ from those of other taxa. The species of Spiraea were analysed for nine quantitative pollen traits as well as the following qualitative traits: the outline, shape and exine ornamentation. In total, 750 pollen grains were measured. Based on the pollen key exine ornamentation features, then individual Spiraea species were distinguished, while the other species formed groups of usually 2-3, up to 8 species. The most important pollen features included length, width and course of grooves and striae, presence or absence of perforations, as well as their number and diameter. The most variable taxa for all the nine biometric traits jointly were S. ×billardii, S. veitchii, S. nipponica and S. cana. The pollen of the invasive S. tomentosa differed from the other taxa studied, unlike the other invasive species (S. douglasii and S. japonica).

Mineralocorticoid Receptor Antagonist (Potassium Canrenoate) Does Not Influence Outcome in the Treatment of COVID-19-Associated Pneumonia and Fibrosis-A Randomized Placebo Controlled Clinical Trial.

In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.

Kidney damage from nonsteroidal anti-inflammatory drugs-Myth or truth? Review of selected literature.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available drugs with anti-inflammatory and analgesic properties. Their mechanism of action is associated with the enzymes of the arachidonic acid cycle (cyclooxygenases: COX-1 and COX-2). The cyclooxygenase pathway results in the formation of prostanoids (prostaglandins [PGs], prostacyclins, and thromboxanes). It affects various structures of the human body, including the kidneys. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), as well as nephrotic syndrome and chronic kidney disease (CKD). AKI associated with the chronic consumption of NSAIDs is mainly attributed to pharmacological polytherapy and the presence of cardiovascular or hepatic comorbidities. The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2. It is suggested that both COX isoforms play opposing roles in renal function, with natriuresis increased by COX-1 inhibition followed by a drop in a blood pressure, whereas COX-2 inhibition increases blood pressure and promotes sodium retention. TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density. Therefore, nephrotic proteinuria and impairment of renal function may occur. The following article analyzes the association of NSAIDs with kidney disease based on available medical literature.

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.

COVID-19-The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection.

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

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.

Correction: Pollen morphology of Polish species from the genus Rubus L. (Rosaceae) and its systematic importance.

[This corrects the article DOI: 10.1371/journal.pone.0221607.].

COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients.

Since the beginning of 2020, the whole world has been struggling with the pandemic of Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7). Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs. Individualized treatment decisions should be based on the clinical condition and co-morbidities of each patient.

COVID-19: Pain Management in Patients with SARS-CoV-2 Infection-Molecular Mechanisms, Challenges, and Perspectives.

Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache. The exact mechanisms of headache and myalgia during viral infection are still unknown. Moreover, many patients with respiratory failure get admitted to the intensive care unit (ICU) for ventilatory support. Pain in ICU patients can be associated with viral disease itself (myalgia, arthralgia, peripheral neuropathies), may be caused by continuous pain and discomfort associated with ICU treatment, intermittent procedural pain and chronic pain present before admission to the ICU. Undertreatment of pain, especially when sedation and neuromuscular blocking agents are used, prone positioning during mechanical ventilation or extracorporeal membrane oxygenation (ECMO) may trigger delirium and cause peripheral neuropathies. This narrative review summarizes current knowledge regarding challenges associated with pain assessment and management in COVID-19 patients. A structured prospective evaluation should be undertaken to analyze the probability, severity, sources and adequate treatment of pain in patients with COVID-19 infection.

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.

COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection.

In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients' quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.

Pollen morphology of Polish species from the genus Rubus L. (Rosaceae) and its systematic importance.

The genus Rubus L. (Rosaceae) not been investigated satisfactorily in terms of palynology. This genus is taxonomically very difficult due to the large number of species and problems with their delimitation, as well as very different distribution areas of particular species. The aim of this study was to investigate pollen morphology and for the first time the ranges of intrageneric and interspecific variability of Rubus species, as well as verify the taxonomic usefulness of these traits in distinguishing studied taxa from this genus. The selected species of the genus Rubus were analysed for 11 quantitative pollen characteristics and the following qualitative ones: exine ornamentation, pollen outline and shape, as well as bridge structure. Analyses were conducted on a total of 1740 pollen grains, which represent 58 blackberry species belonging to a majority of subgenera and all the sections and series found in Poland. The most important characters included exine ornamentation (exine ornamentation type, width and direction of grooves and striae, number and diameter of perforations) and length of the polar axis (P). The arrangement of the examined species on the dendrogram does not corroborate division of the genus Rubus into subgenera, sections and series currently adopted in taxonomy. This fact is not surprising because the taxonomy of the genus was not based on pollen characters. Pollen features should be treated in taxonomy as auxiliary, because they fail to differentiate several (10) individual species, while the other ones create groups with similar pollen traits.

Acute and Chronic Pain Learning and Teaching in Medical School-An Observational Cross-Sectional Study Regarding Preparation and Self-Confidence of Clinical and Pre-Clinical Medical Students.

Background and objectives: Adequate pain management is a major challenge of public health. The majority of students graduating from medical schools has insufficient education and experience with patients suffering pain. Not enough is being taught regarding pain in non-verbal patients (children, critically ill in the intensive care unit, demented). Chronic pain is the most difficult to optimize and requires appropriate preparation at the level of medical school. Our aim was to evaluate attitudes, expectations and the actual knowledge of medical students at different levels of their career path regarding the assessment and treatment of acute and chronic pain. Materials and Methods: We performed an observational cross-sectional study that was based on a survey distributed among medical students of pre-clinical and post-clinical years at the Pomeranian Medical University in Szczecin, Poland. The survey included: demographic data, number of hours of formal pain teaching, actual knowledge of pain assessment, and pain treatment options in adults and children. Results: We received responses from 77/364 (21.15%) students and 79.2% of them rated the need to obtain knowledge regarding pain as very important (10/10 points). Post-clinical group declared having on average 11.51 h of acute pain teaching as compared to the 7.4 h reported by the pre-clinical group (p = 0.012). Graduating students also reported having significantly more classes regarding the treatment of chronic pain (6.08 h vs. 3.79 h, p = 0.007). The average level of comfort in the post-clinical group regarding treatment of acute pain was higher than in the pre-clinical group (6.05 vs. 4.26, p = 0.006), similarly with chronic pain treatment in adults (4.33 vs. 2.97, p = 0.021) and with pain treatment in children (3.14 vs. 1.97, p = 0.026). Conclusions: This study shows that education about pain management is a priority to medical students. Despite this, there continues to be a discrepancy between students' expectations and the actual teaching and knowledge regarding effective pain management, including the vulnerable groups: chronic pain patients, children, and critically ill people.

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.