Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Cardiovascular-Kidney-Metabolic Syndrome: Association with Adverse Events After Major Noncardiac Surgery.

BACKGROUND: The American Heart Association (AHA) recently defined the cardiovascular-kidney-metabolic syndrome (CKM) as a new entity to address the complex interactions between heart, kidneys, and metabolism. The aim of this study was to assess the outcome impact of CKM syndrome in patients undergoing noncardiac surgery. METHODS: This is a secondary analysis of a prospective international cohort study including patients aged ≥45 years with increased cardiovascular risk undergoing noncardiac surgery. Main exposure was CKM syndrome according to the AHA definition. The primary end point was a composite of major adverse cardiovascular events (MACE) 30 days after surgery. Secondary end points included all-cause mortality and non-MACE complications (Clavien-Dindo class ≥3). RESULTS: This analysis included 14,634 patients (60.8% male, mean age = 72±8 years). MACE occurred in 308 patients (2.1%), and 335 patients (2.3%) died. MACE incidence by CKM stage was as follows: CKM 0: 5/367 = 1.4% (95% confidence interval [CI], 0.4%-3.2%); CKM 1: 3/367 = 0.8% (95% CI, 0.2%-2.4%); CKM 2: 102/7440 = 1.4% (95% CI, 1.1%-1.7%); CKM 3: 27/953 = 2.8% (95% CI, 1.9%-4.1%); CKM 4a: 164/5357 = 3.1% (95% CI, 2.6%-3.6%); CKM 4b: 7/150 = 4.7% (95% CI, 1.9%-9.4%). In multivariate logistic regression, CKM stage ≥3 was independently associated with MACE, mortality, and non-MACE complications, respectively (MACE: OR 2.26 [95% CI, 1.78-2.87]; mortality: OR 1.42 [95% CI: 1.13 -1.78]; non-MACE complications: OR 1.11 [95% CI: 1.03-1.20]). CONCLUSION: The newly defined CKM syndrome is associated with increased morbidity and mortality after non-cardiac surgery. Thus, cardiovascular, renal, and metabolic disorders should be regarded in mutual context in this setting.

Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients.

Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.

Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN).

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

Concentration of Apoptotic Factors in Bronchoalveolar Lavage Fluid, as Potential Brain-Lung Oxygen Relationship, Correspond to the Severity of Brain Injury.

BACKGROUND: The mechanism of acute brain injury initiates a cascade of consequences which can directly cause lung damage, and this can contribute to poor neurological outcomes. The aim of this study was to evaluate concentration of different apoptotic molecules in the bronchoalveolar lavage fluid (BALF) in patients after severe brain injury and to correlate them with selected clinical variables and mortality. METHODS: Patients with brain injury receiving BALF operation were included in the study. BALF samples were collected within the first 6-8 hours after traumatic brain injury (A) and at days 3 (B) and 7 (C) after admission to the intensive care unit (ICU). Changes in the BALF nuclear-encoded protein (Bax), apoptotic regulatory protein (Bcl-2), pro-apoptotic protein (p53) and its upregulated modulator (PUMA), apoptotic protease factor 1 (APAF-1), Bcl-2 associated agonist of cell death (BAD) and caspase-activated DNase (CAD) were analysed. These values were correlated with the selected oxygenation parameters, Rotterdam computed tomography (CT) score, the Glasgow Coma Score and 28-day mortality. RESULTS: We found a significant increase in the concentration of selected apoptotic factors at admission (A), at day 3 (B) and day 7 (C) after severe brain damage contrasted with baseline level A (p < 0.001, separately). That concentration of selected apoptotic factors was significantly correlated with the severity of the injury and mortality. CONCLUSIONS: Activation of different apoptotic pathways seems to be an important process occurring in the lungs of patients in the early phases after severe brain trauma. Levels of apoptotic factors in the BALF correlates with the severity of brain injury.

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.

Microchimerism as Post-Transplant Marker of a Chronic Rejection Process.

The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10-4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection.

The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis.

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

The future of intensive care: delirium should no longer be an issue.

In the ideal intensive care unit (ICU) of the future, all patients are free from delirium, a syndrome of brain dysfunction frequently observed in critical illness and associated with worse ICU-related outcomes and long-term cognitive impairment. Although screening for delirium requires limited time and effort, this devastating disorder remains underestimated during routine ICU care. The COVID-19 pandemic brought a catastrophic reduction in delirium monitoring, prevention, and patient care due to organizational issues, lack of personnel, increased use of benzodiazepines and restricted family visitation. These limitations led to increases in delirium incidence, a situation that should never be repeated. Good sedation practices should be complemented by novel ICU design and connectivity, which will facilitate non-pharmacological sedation, anxiolysis and comfort that can be supplemented by balanced pharmacological interventions when necessary. Improvements in the ICU sound, light control, floor planning, and room arrangement can facilitate a healing environment that minimizes stressors and aids delirium prevention and management. The fundamental prerequisite to realize the delirium-free ICU, is an awake non-sedated, pain-free comfortable patient whose management follows the A to F (A-F) bundle. Moreover, the bundle should be expanded with three additional letters, incorporating humanitarian care: gaining (G) insight into patient needs, delivering holistic care with a 'home-like' (H) environment, and redefining ICU architectural design (I). Above all, the delirium-free world relies upon people, with personal challenges for critical care teams to optimize design, environmental factors, management, time spent with the patient and family and to humanize ICU care.

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.

Melatonin and the Brain-Heart Crosstalk in Neurocritically Ill Patients-From Molecular Action to Clinical Practice.

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain-heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.

CXCL8, CCL2, and CMV Seropositivity as New Prognostic Factors for a Severe COVID-19 Course.

The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts.

BACKGROUND: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. METHODS: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1-15, 2002 (SOAP study, n = 3147), and May 8-18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. RESULTS: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1-7) days after admission in SOAP and 2 (1-6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. CONCLUSION: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.

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.

Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation.

Oxidative stress is an imbalance between pro- and antioxidants that adversely influences the organism in various mechanisms and on many levels. Oxidative damage occurring concomitantly in many cellular structures may cause a deterioration of function, including apoptosis and necrosis. The damage leaves a molecular "footprint", which can be detected by specific methodology, using certain oxidative stress biomarkers. There is an intimate relationship between oxidative stress, inflammation, and functional impairment, resulting in various diseases affecting the entire human body. In the current narrative review, we strengthen the connection between oxidative stress mechanisms and their active compounds, emphasizing kidney damage and renal transplantation. An analysis of reactive oxygen species (ROS), antioxidants, products of peroxidation, and finally signaling pathways gives a lot of promising data that potentially will modify cell responses on many levels, including gene expression. Oxidative damage, stress, and ROS are still intensively exploited research subjects. We discuss compounds mentioned earlier as biomarkers of oxidative stress and present their role documented during the last 20 years of research. The following keywords and MeSH terms were used in the search: oxidative stress, kidney, transplantation, ischemia-reperfusion injury, IRI, biomarkers, peroxidation, and treatment.

COVID-19: ICU delirium management during SARS-CoV-2 pandemic.

The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

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.

Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery-Review.

Postoperative cognitive disorders after cardiac surgery may manifest as postoperative delirium (POD) or later as postoperative cognitive dysfunction (POCD). The incidence of POD after cardiac surgery ranges from 16% to 73%. In contrast to POD, POCD is usually diagnosed after the discharge from hospital, with an incidence of 30 to 70% of cases, very often noticed only by close relative or friends, decreasing after six (20-30%) and twelve (15-25%) months after surgery. Perioperative cognitive disorders are associated with adverse short- and long-term effects, including increased morbidity and mortality. Due to the complexity of delirium pathomechanisms and the difficulties in the diagnosis, researchers have not yet found a clear answer to the question of which patient will be at a higher risk of developing delirium. The risk for POD and POCD in older patients with numerous comorbidities like hypertension, diabetes, and previous ischemic stroke is relatively high, and the predisposing cognitive profile for both conditions is important. The aim of this narrative review was to identify and describe biomarkers used in the diagnosis of delirium after cardiac surgery by presenting a search through studies regarding this subject, which have been published during the last ten years. The authors discussed brain-derived biomarkers, inflammation-related biomarkers, neurotransmitter-based biomarkers, and others. Work based on inflammation-related biomarkers, which are characterized by the low cost of implementation and the effectiveness of delirium diagnosis, seems to be the closest to the goal of discovering an inexpensive and effective marker. Currently, the use of a panel of tests, and not a single biomarker, brings us closer to the discovery of a test, or rather a set of tests ideal for the diagnosis of delirium after cardiac surgery.

The Relationship between Selected Bioelements and Depressiveness Associated with Testosterone Deficiency Syndrome in Aging Men.

Background and Objectives: Abnormal concentrations of bioelements (magnesium, manganese, chromium, copper, zinc) have been associated with physical and emotional dysfunctions, including depression. This association, however, has not been analyzed in testosterone deficiency syndrome (TDS) or patients with depressiveness, i.e., when individual symptoms do not form the picture of a full-syndrome depressive disorder. This study aimed to assess the relationship between concentrations of selected bioelements and the incidence of depressive symptoms in men aged 50 years and older with a concurrent testosterone deficiency syndrome. Material and Methods: Blood samples were taken from 314 men; the mean age of the population was 61.36 ± 6.38 years. Spectrophotometric method for biochemical analysis of magnesium (Mg), manganese (Mn), chromium (Cr), copper (Cu), and zinc (Zn) was used. The diagnosis of testosterone deficiency syndrome (TDS) was based on the total testosterone (TT), free testosterone (FT), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) levels by ELISA. Each participant completed the Androgen Deficiency in Aging Male (ADAM) questionnaire, as well as the Beck Depression Inventory (BDI-Ia) measuring the severity of depressive symptoms. Results: Emotional disturbances manifested as depressive symptoms were diagnosed in 28.7% of all participants and testosterone deficiency syndrome in 49.3%. In the TDS group, the analysis showed a significant correlation between the level of manganese (R = 0.225, p = 0.005) and chromium (R = 0.185, p = 0.021) with the incidence of depression. Conclusions: The results of our study demonstrated a relationship between manganese and chromium concentrations with the incidence of depression in men aged 50 years and older with a concurrent testosterone deficiency syndrome. This may indicate that there is a correlation between these bioelements, as well as emotional disorders manifested as depressive symptoms in aging men with a diagnosed testosterone deficiency.