Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

Antimicrobial Use during the SARS-CoV-2 Pandemic in a Greek Tertiary University Hospital.

In cases of SARS-CoV-2 hospitalization, despite low bacterial co-infection rates, antimicrobial use may be disproportionately high. Our aim was to quantify such usage in COVID-19 patients and identify factors linked to increased antibiotic use. We retrospectively studied patients with SARS-CoV-2 infection who were hospitalized at our institution during the pandemic. In the initial two waves of the pandemic, antimicrobial use was notably high (89% in the first wave and 92% in the second), but it decreased in subsequent waves. Elevated procalcitonin (>0.5 µg/mL) and C-reactive protein (>100 mg/L) levels were linked to antibiotic usage, while prior vaccination reduced antibiotic incidence. Antimicrobial use decreased in the pandemic, suggesting enhanced comprehension of SARS-CoV-2's natural course. Additionally, it was correlated with heightened SARS-CoV-2 severity, elevated procalcitonin, and C-reactive protein levels.

HEPARIN-BINDING PROTEIN LEVELS PREDICT UNFAVORABLE OUTCOME IN COVID-19 PNEUMONIA: A POST HOC ANALYSIS OF THE SAVE TRIAL.

ABSTRACT: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.

Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E/e' was strongly correlated with serum LBP (r = 0.731; P < 0.001), PRA (r = 0.714; P < 0.001) and GFR (r = -0.609; P < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P = 0.01 and 53.3 vs. 28.2%; P = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.

Quality Indicators and Clinical Outcomes of Acute Stroke: Results from a Prospective Multicenter Registry in Greece (SUN4P).

AIM: The Stroke Units Necessity for Patients (SUN4P) project aims to provide essential data on stroke healthcare in Greece. Herein, we present results on established quality indicators and outcomes after first-ever stroke occurrences. METHODS: This prospective multicenter study included consecutive patients admitted to nine hospitals across Greece in 2019-2021. Descriptive statistics were used to present patients' characteristics, key performance measures and stroke outcomes. RESULTS: Among 892 patients, 755 had ischemic stroke (IS) (mean age 75.6 ± 13.6, 48.7% males) and 137 had hemorrhagic stroke (HS) (mean age 75.8 ± 13.2, 57.7% males). Of those, 15.4% of IS and 8% of HS patients were treated in the acute stroke unit (ASU) and 20.7% and 33.8% were admitted to the intensive care unit (ICU) or high-dependency unit (HDU), respectively. A total of 35 (4.6%) out of 125 eligible patients received intravenous alteplase with a door-to needle time of 60 min (21-90). The time to first scan for IS patients was 60 min (31-105) with 53.2% undergoing a CT scan within 60 min post presentation. Furthermore, 94.4% were discharged on antiplatelets, 69.8% on lipid-lowering therapy and 61.6% on antihypertensives. Oral anticoagulants (OAC) were initiated in 73.2% of the 153 IS patients with atrial fibrillation (AF). Among the 687 IS patients who survived, 85.4% were discharged home, 12% were transferred to rehabilitation centers, 1.2% to nursing homes and 1.3% to another hospital. CONCLUSIONS: The SUN4P Registry is the first study to provide data from a prospectively collected cohort of consecutive patients from nine representative national hospitals. It represents an important step in the evaluation and improvement of the quality of acute stroke care in Greece.

Association of Alkaline Phosphatase with Cardiovascular Disease in Patients with Dyslipidemia: A 6-Year Retrospective Study.

BACKGROUND AND AIM: Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. METHODS: We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L. RESULTS: Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03, p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p = 0.008). CONCLUSIONS: The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.

Acute ischaemic stroke in active cancer versus non-cancer patients: stroke characteristics, mechanisms and clinical outcomes.

BACKGROUND AND PURPOSE: Demographics, clinical characteristics, stroke mechanisms and long-term outcomes were compared between acute ischaemic stroke (AIS) patients with active cancer (AC) versus non-cancer patients. METHODS: Using data from 2003 to 2021 in the Acute STroke Registry and Analysis of Lausanne, a retrospective cohort study was performed comparing patients with AC, including previously known and newly diagnosed cancers, with non-cancer patients. Patients with inactive cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months, death and cerebrovascular recurrences at 12 months before and after propensity score matching. RESULTS: Amongst 6686 patients with AIS, 1065 (15.9%) had a history of cancer. After excluding 700 (10.4%) patients with inactive cancer, there were 365 (5.5%) patients with AC and 5621 (84%) non-cancer AIS patients. Amongst AC patients, 154 (42.2%) strokes were classified as cancer related. In multivariable analysis, patients with AC were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.03), had fewer vascular risk factors and were 48% less likely to receive reperfusion therapies (aOR 0.52, 95% CI 0.35-0.76). Three-month mRS scores were not different in AC patients (aOR 2.18, 95% CI 0.96-5.00). At 12 months, death (adjusted hazard ratio 1.91, 95% CI 1.50-2.43) and risk of cerebrovascular recurrence (sub-distribution hazard ratio 1.68, 95% CI 1.22-2.31) before and after propensity score matching were higher in AC patients. CONCLUSIONS: In a large institutional registry spanning nearly two decades, AIS patients with AC had less past cerebrovascular disease but a higher 1-year risk of subsequent death and cerebrovascular recurrence compared to non-cancer patients. Antithrombotic medications at discharge may reduce this risk in AC patients.

Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Addition of macrolide antibiotics to ß-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a ß-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. METHODS: The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of ß-lactam plus ß-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). FINDINGS: Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. INTERPRETATION: Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to ß-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. FUNDING: Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Beyond antithrombotics: recent advances in pharmacological risk factor management for secondary stroke prevention.

Patients with ischaemic stroke represent a diverse group with several cardiovascular risk factors and comorbidities, which classify them as patients at very high risk of stroke recurrence, cardiovascular adverse events or death. In addition to antithrombotic therapy, which is important for secondary stroke prevention in most patients with stroke, cardiovascular risk factor assessment and treatment also contribute significantly to the reduction of mortality and morbidity. Dyslipidaemia, diabetes mellitus and hypertension represent common and important modifiable cardiovascular risk factors among patients with stroke, while early recognition and treatment may have a significant impact on patients' future risk of major cardiovascular events. In recent years, there have been numerous advancements in pharmacological agents aimed at secondary cardiovascular prevention. These innovations, combined with enhanced awareness and interventions targeting adherence and persistence to treatment, as well as lifestyle modifications, have the potential to substantially alleviate the burden of cardiovascular disease, particularly in patients who have experienced ischaemic strokes. This review summarises the evidence on the contemporary advances on pharmacological treatment and future perspectives of secondary stroke prevention beyond antithrombotic treatment.

Developing a Tool for Differentiation Between Bacterial and Viral Respiratory Infections Using Myxovirus Resistance Protein A and C-Reactive Protein.

INTRODUCTION: The aim was to assess the performance of a blood assay combining measurements of MxA (myxovirus resistance protein A) and CRP (C-reactive protein) to differentiate viral from bacterial respiratory infections. METHODS: In a prospective study, MxA and CRP were measured in the blood by the AFIAS panel in adults admitted with respiratory infection. Patients were split into discovery and validation cohorts. Final diagnosis was adjudicated by a panel of experts. Microbiology-confirmed cases comprised the discovery cohort, and infections adjudicated as highly probable viral or bacterial comprised the validation cohort. RESULTS: A total of 537 patients were analyzed: 136 patients were adjudicated with definitive viral infections and 131 patients with definitive bacterial infections. Using logistic regression analysis, an equation was developed to calculate the probability for bacterial infection using the absolute value of MxA and CRP. Calculated probability ≥ 0.5 and/or MxA to CRP ratio less than 2 applied as the diagnostic rule for bacterial infections. This rule provided 91.6% sensitivity and 90.4% negative predictive value for the diagnosis of bacterial infections. This diagnostic sensitivity was confirmed in the validation cohort. A MxA/CRP ratio less than 0.15 was associated with unfavorable outcome. CONCLUSION: The calculation of the probability for bacterial infection using MxA and CRP may efficiently discriminate between viral and bacterial respiratory infections.

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

Background: Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke. Methods: We conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR < 1 suggests benefit and an acOR > 1 harm). This trial is registered (ISRCTN82217627). Findings: From April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81-1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77-1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96-1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events. Interpretation: We observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke. Funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No: 634809.

Impact of continued alcohol use on liver-related outcomes of alcohol-associated cirrhosis: a retrospective study of 440 patients.

BACKGROUND AND AIM: The prevalence of alcohol-associated cirrhosis is increasing. In this respect, we investigated the long-term impact of non-abstinence on the clinical course of alcohol-associated cirrhosis. METHODS: We retrospectively evaluated 440 patients with alcohol-associated cirrhosis (compensated cirrhosis: n  = 190; decompensated cirrhosis: n  = 250) diagnosed between January 2000 and July 2017 who consumed alcohol until diagnosis of cirrhosis. We assessed liver-related outcomes including first and further decompensating events (ascites, variceal bleeding, and hepatic encephalopathy), and death in relation to continued alcohol use. RESULTS: Overall, 53.6% of patients remained abstinent (compensated cirrhosis: 57.9%; decompensated cirrhosis: 50.4%). Non-abstinent versus abstinent patients with compensated cirrhosis and decompensated cirrhosis showed significantly higher 5-year probability of first decompensation (80.2% vs. 36.8%; P  < 0.001) and further decompensation (87.9% vs. 20.6%; P  < 0.001), respectively. Five-year survival was substantially lower among non-abstinent patients with compensated cirrhosis (45.9% vs. 90.7%; P  < 0.001) and decompensated cirrhosis (22.9% vs. 73.8%; P  < 0.001) compared to abstinent. Non-abstinent versus abstinent patients of the total cohort showed an exceedingly lower 5-year survival (32.2% vs. 82.4%; P  < 0.001). Prolonged abstinence (≥2 years) was required to influence outcomes. Non-abstinence independently predicted mortality in the total cohort (hazard ratio [HR] 3.371; confidence interval [CI]: 2.388-4.882; P  < 0.001) along with the Child-Pugh class (HR: 4.453; CI: 2.907-6.823; P  < 0.001) and higher age (HR: 1.023; CI: 1.007-1.039; P  = 0.005). CONCLUSION: Liver-related outcomes are worse among non-abstinent patients with alcohol- associated cirrhosis prompting urgent interventions ensuring abstinence.

Inflammation and Venous Thromboembolism in Hospitalized Patients with COVID-19.

BACKGROUND: A link between inflammation and venous thromboembolism (VTE) in COVID-19 disease has been suggested pathophysiologically and clinically. The aim of this study was to investigate the association between inflammation and disease outcomes in adult hospitalized COVID-19 patients with VTE. METHODS: This was a retrospective observational study, including quantitative and qualitative data collected from COVID-19 patients hospitalized at the Infectious Diseases Unit (IDU) of the University Hospital of Ioannina, from 1 March 2020 to 31 May 2022. Venous thromboembolism was defined as a diagnosis of pulmonary embolism (PE) and/or vascular tree-in-bud in the lungs. The burden of disease, assessed by computed tomography of the lungs (CTBoD), was quantified as the percentage (%) of the affected lung parenchyma. The study outcomes were defined as death, intubation, and length of hospital stay (LoS). A chi-squared test and univariate logistic regression analyses were performed in IBM SPSS 28.0. RESULTS: After propensity score matching, the final study cohort included 532 patients. VTE was found in 11.2% of the total population. In patients with VTE, we found that lymphocytopenia and a high neutrophil/lymphocyte ratio were associated with an increased risk of intubation and death, respectively. Similarly, CTBoD > 50% was associated with a higher risk of intubation and death in this group of patients. The triglyceride-glucose (TyG) index was also linked to worse outcomes. CONCLUSIONS: Inflammatory indices were associated with VTE. Lymphocytopenia and an increased neutrophil-to-lymphocyte ratio negatively impacted the disease's prognosis and outcomes. Whether these indices unfavorably affect outcomes in COVID-19-associated VTE must be further evaluated.

The Cost and the Value of Stroke Care in Greece: Results from the SUN4P Study.

The aim of this study was to measure the one-year total cost of strokes and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first-ever acute strokes, hemorrhagic strokes, and ischemic strokes, (ICD-10 codes: I61, I63, and I64) admitted within 48 h of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality, and informal care costs were considered. We used an annual time horizon, including all costs for 2021, irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at EUR 343.1 mil. a year in 2021, (EUR 10,722/patient or EUR 23,308 per QALY). Out of EUR 343.1 mil., 53.3% (EUR 182.9 mil.) consisted of direct healthcare costs, representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at EUR 160.2 mil. The mean productivity losses were estimated to be 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality, and 42.4 days lost due to informal caregiving by family members. This study highlights the burden of stroke and underlines the need for stakeholders and policymakers to re-organize stroke care and promote interventions that have been proven cost-effective.

Remdesivir: Effectiveness and Safety in Hospitalized Patients with COVID-19 (ReEs-COVID-19)-Analysis of Data from Daily Practice.

Remdesivir was the first antiviral approved for treating COVID-19. We investigated its patterns of use, effectiveness and safety in clinical practice in Greece. This is a retrospective observational study of hospitalized adults who received remdesivir for COVID-19 in September 2020-February 2021. The main endpoints were the time to recovery (hospital discharge within 30 days from admission) and safety. The "early" (remdesivir initiation within 24 h since hospitalization) and "deferred" (remdesivir initiation later on) groups were compared. One thousand and four patients (60.6% male, mean age 61 years, 74.3% with severe disease, 70.9% with ≥1 comorbidities) were included, and 75.9% of them were on a 5-day regimen, and 86.8% were in the early group. Among those with a baseline mild/moderate disease, the median (95% CI) time to recovery was 8 (7-9) and 12 (11-14) days for the early and deferred groups, respectively (p < 0.001). The corresponding estimates for those with a severe disease were 10 (9-10) and 13 (11-15) days, respectively (p = 0.028). After remdesivir initiation, increased serum transaminases and an acute kidney injury were observed in 6.9% and 2.1%, respectively. Nine (0.9%) patients discontinued the treatment due to adverse events. The effectiveness of remdesivir was increased when it was taken within 24 h since admission regardless of the disease severity. Remdesivir's safety profile is similar to that described in clinical trials and other real-world cohorts.

Midday Dipping and Circadian Blood Pressure Patterns in Acute Ischemic Stroke.

The purpose of this study was to investigate the alterations in blood pressure (BP) during midday and the changes in circadian BP patterns in the acute phase of ischemic stroke (AIS) with the severity of stroke and their predictive role outcomes within 3 months. A total of 228 AIS patients (a prospective multicenter follow-up study) underwent 24 h ambulatory blood pressure monitoring (ABPM). Mean BP parameters during the day (7:00-22:59), the midday (13:00-16:59), and the night (23:00-6:59), and midday and nocturnal dipping were calculated. Midday SBP dippers had less severe stroke, lower incidence of hypertension and SBP/DBP on admission, lower levels of serum glucose and WBCs, and delayed initiation of ABPM compared to risers. There was a reverse relation between midday SBP dipping and both nocturnal dipping and stroke severity. The "double dippers" (midday and nocturnal dipping) had the least severe stroke, the lowest SBP/DBP on admission, the lowest heart rate from ABPM, and a lower risk of an unfavorable outcome, while the "double risers" had the opposite results, by an approximately five-fold risk of death/disability at 3 months. These findings indicate different circadian BP patterns during the acute phase of AIS, which could be considered a marker of stroke severity and prognosis.

Glycemic Dysregulation, Inflammation and Disease Outcomes in Patients Hospitalized with COVID-19: Beyond Diabetes and Obesity.

INTRODUCTION: During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients with and without diabetes and obesity. MATERIALS AND METHODS: Epidemiological, clinical, and laboratory data were collected from the University Hospital of Ioannina COVID-19 Registry and included hospitalized patients from March 2020 to December 2022. The study cohort was divided into three subgroups based on the presence of DM, obesity, or the absence of both. RESULTS: In diabetic patients, elevated CRP, IL-6, TRG/HDL-C ratio, and TyG index, severe pneumonia, and hyperglycemia were associated with extended hospitalization. Increased IL-6, NLR, and decreased PFR were associated with a higher risk of death. In the obese subgroup, lower levels of PFR were associated with longer hospitalization and a higher risk of death, while severe lung disease and hyperglycemia were associated with extended hospitalization. In patients without DM or obesity severe pneumonia, NLR, CRP, IL-6, insulin resistance indices, and hyperglycemia during hospitalization were associated with longer hospitalization. CONCLUSION: Inflammatory markers and disease severity indices were strongly associated with disease outcomes and hyperglycemia across all subgroups.

Stroke Patients' Management During COVID-19 Pandemic: Results from the Sun4Patients Web-Based Registry.

Covid-19 pandemic has influenced stroke care in different ways. Recent reports demonstrated a sharp decline in acute stroke admissions worldwide. Even for patients presented to dedicated healthcare services, management at the acute phase may be sub-optimal. On the other hand, Greece has been praised for the early initiation of restriction measures which were associated with a 'milder' surge of SARS-CoV-2 infection. Methods Data derived from a prospective cohort multicenter registry. The study population consisted of first-ever acute stroke patients, hemorrhagic or ischemic, admitted within 48 hours of symptom onset in seven national healthcare system (NHS) and University hospitals in Greece. Two different time periods have been considered, defined as "before Covid-19" (15/12/2019-15/02/2020) and "during Covid-19" (16/02/2020-15/04-2020) era. Statistical comparisons on acute stroke admission characteristics between the two different time periods have been performed. Results This exploratory analysis of 112 consecutive patients showed a reduction of acute stroke admissions by 40during Covid-19 period. No significant differences were observed regarding stroke severity, risk factor profile and baseline characteristics for patients admitted before and during Covid-19 pandemic period. There is a significant delay between symptom onset to CT scan during Covid-19 era compared to the period before pandemic reached Greece (p=0.03). Conclusions The rate of acute stroke admissions has been reduced by 40% during Covid-19 pandemic. Further research is needed to clarify whether the reduction in stroke volume is actual or not and identifying the reasons underlying the paradox.

Clinical and Demographic Characteristics, Mechanisms, and Outcomes in Patients With Acute Ischemic Stroke and Newly Diagnosed or Known Active Cancer.

BACKGROUND AND OBJECTIVES: Patients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS), and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether patients with AIS with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer (NC) and previously known active cancer (KC) and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups. METHODS: Using 2003-2021 data from the Acute STroke Registry and Analysis of Lausanne registry, we compared patients with KC with patients with NC (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables. RESULTS: Among 6,686 patients with AIS, 362 (5.4%) had active cancer (AC), including 102 (1.5%) with NC. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with AC, 152 (42.5%) AISs were classified as cancer related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with NC had less prestroke disability (adjusted odds ratio [aOR] 0.62, 95% CI 0.44-0.86) and fewer prior stroke/transient ischemic attack events (aOR 0.43, 95% CI 0.21-0.88) than patients with KC. Three-month mRS scores were similar between cancer groups (aOR 1.27, 95% CI 0.65-2.49) and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95% CI 1.49-43.17) and metastatic cancer (aOR 2.19, 95% CI 1.22-3.97). At 12 months, mortality risk was higher in patients with NC vs patients with KC (hazard ratio [HR] 2.11, 95% CI 1.38-3.21), while recurrent stroke risk was similar between groups (adjusted HR 1.27, 95% CI 0.67-2.43). DISCUSSION: In a comprehensive institutional registry spanning nearly 2 decades, 5.4% of patients with AIS had AC, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with NC had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with KC.