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Objectives: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes., Design: Retrospective analysis of data from prospective clinical studies., Setting: Greek ICUs and Internal Medicine departments., Patients and Interventions: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality., Measurements and Main Results: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, β was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern., Conclusions: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: While arterial stiffening is a known risk factor for cardiovascular diseases, it remains unclear whether there is an early vascular aging (EVA) in patients who have experienced acute ischemic stroke (AIS). This systematic review and meta-analysis aims to investigate whether patients with AIS exhibit EVA through pulse wave velocity (PWV) measurements shortly after the stroke onset, shedding light on the relationship between arterial stiffness, hypertension, and stroke., Methods: Thirteen case-control studies were included, comparing PWV measurements between AIS patients and non-AIS individuals. A meta-analysis was performed to compare PWV levels, age, blood pressure, and the prevalence of different cardiovascular risk factors among 1711 AIS patients and 1551 controls., Results: Despite AIS patients showing higher PWV compared to controls (mean difference: 1.72 m/s, 95 % CI: 1.05-2.38, p < 0.001; I 2 = 88.3 %), their age did not significantly differ (95 % CI: -0.47-0.94, p = 0.519; I 2 = 0 %), suggesting EVA in AIS patients. Moreover, AIS patients exhibited elevated systolic and diastolic blood pressure and had higher odds of smoking, hypertension, diabetes, and male gender compared to controls., Conclusions: This study's findings underscore the presence of EVA in AIS patients, evident through increased PWV measurements shortly after stroke onset. Notably, smoking, hypertension, and diabetes mellitus emerge as substantial factors contributing to accelerated arterial stiffness within this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hairy cell leukaemia (HCL) is an uncommon, indolent, B-cell, lymphoproliferative disorder typically involving peripheral blood, spleen and bone marrow. It is commonly presenting with pancytopenia, monocytopenia and massive splenomegaly, while accounting for 2% of lymphoid leukaemias. Cases of extranodal lesions caused by HCL are rare, although these have been reported. Here, we report a case of HCL presenting as a paravertebral mass without systemic involvement., Case Description: A 58-year-old man was admitted to our hospital due to progressive difficulty walking for a month, without any other symptoms. Blood examination noted mild anaemia with Hb=12.6 g/dl and mild thrombocytopenia of 140,000/μl. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging demonstrated a T6 posterior paravertebral mass lesion, extending into the spinal canal with metastatic bone lesions along the thoracic and lumbar spine. Further imaging study with CT indicated mild splenomegaly (13.4 cm) and an enlarged abdominal lymph node (3.5 cm) near celiac trifurcation., Conclusion: A core-needle biopsy from the paravertebral mass was performed. Results showed small-sized cells with round or oval nuclei, and pale cytoplasm with immunophenotype: B-cell origination with CD20+, Cyclin D1+, DBA.44+, Annexin+ and BRAF+, indicative of HCL., Learning Points: Hairy cell leukaemia (HCL) is relatively uncommon, accounting for 2% of all leukaemia cases.Extramedullary and skeletal involvement in HCL is rare and shares morphological characteristics with other peripheral small B-cell lymphoma neoplasms.Spine biopsy is essential for diagnosis in these cases, since it is always helpful to narrow the differential diagnosis.Correct diagnosis is essential for treatment of HCL and leads most patients to clinical remission and sometimes long-term cures., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Objectives: The management of blood pressure (BP) and the role of antihypertensive medications (AHT) in acute ischemic stroke (AIS) remain uncertain. This study aimed to investigate the impact of pre- and intra-stroke AHT use on systolic (SBP), diastolic (DBP), and blood pressure variability (BPV)., Materials and Methods: A post-hoc analysis was conducted on 228 AIS patients from the PREVISE study. All patients underwent 24-hour ambulatory blood pressure monitoring within 48 h of symptom onset. Clinical and laboratory data, as well as AHT details, were recorded. Mean BP parameters and BPV for SBP and DBP were computed. The study endpoint was 3-month mortality., Results: The majority of stroke patients (84.2%) were already taking AHTs. Beta blockers and ACE inhibitors use before and after stroke were linked to higher DBP variability. Prior angiotensin receptor blockers (ARBs) and vasodilators use correlated with increased SBP variability and lower daytime SBP/DBP levels, respectively. The continuation, discontinuation, or change of AHTs after stroke onset did not significantly affect outcomes. Patients under AHTs during AIS exhibited reduced mortality, with those previously using calcium channel blockers experiencing less severe strokes, and those previously using ARBs showing better outcomes at three months., Conclusions: These findings advocate for personalized BP management in AIS, based on a patient's antihypertensive history. These insights could enhance treatment efficacy, guide research, and improve care for acute ischemic stroke patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The COVID-19 pandemic had an adverse impact on several cardiovascular risk factors. This study investigated the prevalence, awareness and treatment of hypertension in Greece before and after the pandemic. Data were collected in the context of the May Measurement Month (MMM) global survey initiated by the International Society of Hypertension., Methods: Adult volunteers (age ≥ 18 years) were recruited through opportunistic screening in public areas across cities in Greece in 2019 and 2022. Medical history and triplicate sitting blood pressure (BP) measurements were taken using validated automated upper-arm cuff devices. The data were uploaded to the international MMM cloud platform. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic ≥90 mm Hg and/or self-reported use of drugs for hypertension. The same threshold was used to define uncontrolled BP in treated individuals., Results: Data from 12,080 adults were collected (5,727/6,353 in MMM 2019/2022; men 46/49%, p < 0.01; mean age 52.7 ± 16.6/54.8 ± 16.2, p < 0.001; smokers, 24.7/30.5, p < 0.001; diabetics 12/11.5%, p = NS; cardiovascular disease 5/5.8%, p = NS). The prevalence of hypertension was 41.6/42.6% (MMM 2019/2022, p = NS), with 21.3/27.5% of individuals with hypertension being unaware of their condition (p < 0.001), 5.6/2.4% aware untreated (p < 0.001), 24.8/22.1% treated uncontrolled (p < 0.05), and 48.3/47.8% treated controlled (p = NS)., Conclusion: In Greece, the COVID-19 pandemic did not appear to affect the prevalence and control of hypertension; however, the rate of undiagnosed hypertension was higher after the pandemic. National strategies need to be implemented for the early detection and optimal management of hypertension in the general population in Greece., Competing Interests: Conflict of interest M.S.K. has received lecture and consulting fees from Elpen, Menarini, Guidotti, and Servier. Α.Κ. has received lecture and consulting fees from Elpen, Menarini, and Servier. D.K. has received lecture and consulting fees from Servier, Elpen, and Menarini. V.K. has received lecture and consulting fees from Elpen, Menarini, Servier, Vianex, Viatris, and Novartis. A.Ma. has received lecture and consulting fees from Menarini and Berlin Chemie Ferrer. G.S.S. has received lecture and consulting fees from Omron Healthcare Japan & Europe, Elpen, Menarini, and Servier., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background: In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary prevention efforts. Despite glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrating improved outcomes for those with diabetes mellitus or obesity, their underutilization persists among eligible individuals. This systematic review and meta-analysis investigated the impact of GLP-1 RAs on stroke risk. The findings aim to optimize the implementation of this therapeutic strategy in patients surviving stroke with diabetes mellitus or obesity., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed MEDLINE and Scopus until 15 November 2023. Eligible studies included randomized cardiovascular outcome trials (CVOTs) with individuals, with or without type 2 diabetes, randomized to either GLP-1 RA or placebo. The outcomes were total strokes, non-fatal strokes, and fatal strokes. Analyses were conducted using RevMan 5.4.1., Results: Among 1369 screened studies, 11 were eligible, encompassing 82,140 participants (34.6% women) with a cumulative follow-up of 247,596 person-years. In the GLP-1 RAs group, the stroke rate was significantly lower compared to placebo (RR: 0.85, 95% CI: 0.77-0.93; NNT: 200), showing no heterogeneity or interaction with administration frequency (daily vs weekly). In addition, the GLP-1 RAs group exhibited a significantly lower rate of non-fatal strokes compared to placebo (RR: 0.87, 95% CI: 0.79-0.95; NNT: 250), with no heterogeneity or interaction based on administration frequency, route (oral vs subcutaneous), or diabetes presence., Conclusion: In this meta-analysis of 11 CVOTs with 82,140 participants, GLP-1 RAs demonstrated a 16% relative reduction in stroke risk compared to placebo. This finding may increase implementation of GLP-1 RAs by stroke specialists in individuals with stroke and comorbid diabetes mellitus or obesity., Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.B. reports participation in trials funded by Amgen, Lilly, Novartis, and Novo Nordisk, and honoraria from Novartis, Novo Nordisk, Sanofi, and Viatris; H.M. reports participation in educational, research, and consulting activities supported by healthcare companies, including AstraZeneca, Gilead, Novartis, Pfizer, Recordati, Sanofi, and Viatris; G.N. reports Advisory Boards/Research support/ Speaker fees from Abbott; Amgen; AstraZeneca; Bayer; BMS; Boehringer Ingelheim; Javelin; Novartis; Pfizer; and Sanofi.

Background: Small intestinal bacterial overgrowth (SIBO) occurs frequently in patients with cirrhosis, particularly in those with ascites, and promotes the translocation of gut-derived bacterial products into the portal and systemic circulation. We investigated the effects of SIBO on systemic inflammatory activity, circulatory and renal function, and the degree of liver fibrosis in patients with cirrhosis and ascites., Methods: Eighty patients with cirrhosis and ascites were prospectively enrolled. SIBO was determined by lactulose breath test. Serum levels of lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, and interleukin-6, mean arterial pressure (MAP), cardiac output (CO) by echocardiography, systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, radioisotope-assessed glomerular filtration rate (GFR), and liver stiffness by shear wave elastography were evaluated., Results: SIBO was detected in 58 patients (72.5%). Compared to patients without SIBO, those diagnosed with SIBO had significantly higher LBP levels (P<0.001), significantly lower MAP (P<0.001) and SVR (P<0.001), and significantly higher CO (P=0.002) and PRA (P<0.001). Patients with SIBO had significantly lower GFR (P=0.02) and higher liver stiffness (P=0.04) compared to those without SIBO. The presence of SIBO was independently associated with LBP (P=0.007) and PRA (P=0.01). Among patients with SIBO, peak breath hydrogen concentration was significantly correlated with serum LBP (P<0.001), MAP (P<0.001), CO (P=0.008), SVR (P=0.001), PRA (P=0.005), plasma aldosterone (P<0.001), GFR (P<0.001), and liver stiffness (P=0.004)., Conclusion: SIBO in patients with cirrhosis and ascites may predispose to greater systemic inflammation, circulatory and renal dysfunction, and more advanced liver fibrosis., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Addition of macrolide antibiotics to β-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 β-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 β-lactam plus β-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 β-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., Competing Interests: Declaration of interests EJG-B has received honoraria from Abbott Products Operations, bioMérieux, Brahms, GSK, InflaRx, Swedish Orphan Biovitrum, and Xbiotech; independent educational grants from Abbott Products Operations, bioMérieux, InflaRx, Johnson & Johnson, MSD, UCB, and Swedish Orphan Biovitrum; and funding from the Horizon 2020 European Grants ImmunoSep and RISCinCOVID and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). GP has received honoraria or consulting fees from AstraZeneca, Gilead, GSK, Menarini, MSD, Norma, Pfizer, and Sobi, and research grants from the University of Minnesota/University College London, the Hellenic Institute for the Study of Sepsis, Bausch, Roche, Xenothera, FabNTech, and Pfizer. ICP has received honoraria or served as principal investigator for studies from Boehringer Ingelheim, GlaxoSmithKline, and AstraZeneca. HM reports receiving honoraria, consulting fees, and non-financial support from health-care companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. GND is an advisor or lecturer for Pfizer, Roche, Sanofi, and Sobi; has received research grants from Gilead; and has served as principal investigator in studies for Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics, Sobi, and Intercept Pharmaceuticals. KAk reports receiving honoraria and consulting fees from health-care companies, including Angelini, MSD, Pfizer, Swedish Orphan Biovitrum, 3M hellas, GSK/ViiV, and Gilead. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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.

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., (© 2024. The Author(s).)

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., (Copyright © 2024 by the Shock Society.)

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

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.

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., Competing Interests: Competing interests: GN reports speaker fees/advisory boards/research support from Abbott, Amgen, Bayer, BMS/Pfizer, Boehringer Ingelheim, Elpen and Galenica. All fees are paid directly to his institution (University of Thessaly). HM reports speaker fees/advisory boards/research support from Alexion, Amgen, AstraZeneca, Bayer, Elpen, Genesis Pharma, MSD, Pfizer, Sanofi, Servier, Viatris and Winmedica., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023. The Author(s).)

Objective: Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9), a modulator of low-density lipoprotein (LDL) cholesterol metabolism, has been reported to be a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. In the current study, we sought to investigate potential differences in serum PCSK9 levels between infants with deviant birth weight and controls., Methods: We enrolled 82 infants, classified into 33 small (SGA), 32 appropriate (AGA), and 17 large for gestation (LGA) infants. Serum PCSK9 was measured on routine blood analysis within the first postnatal 48 h., Results: PCSK9 was significantly higher in SGA as compared to AGA and LGA infants [322 (236-431) as compared to 263 (217-302) and 218 (194-291) ng/ml respectively, p  = .011]. In comparison to term AGA infants, PCSK9 was significantly elevated in preterm AGA and SGA infants. We also found a significantly higher level of PCSK9 in term female SGA infants as compared to term male SGA infants [325 (293-377) as compared to 174 (163-216) ng/ml, p  = .011]. PCSK9 was significantly correlated with gestational age ( R  = -0.404, p  < .001), birth weight ( R  = -0.419, p  < .001), total cholesterol ( R  = 0.248, p  = .028) and LDL cholesterol ( R  = 0.370, p  = .001). SGA status (OR 2.56, p  = .004, 95% CI 1.83-4.28) and prematurity (OR 3.10, p  = .001, 95% CI 1.39-4.82) were strongly related to serum PCSK9 levels., Conclusion: PCSK9 levels were significantly associated with total and LDL cholesterol. Moreover, PCSK9 levels were higher in preterm and SGA infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.Highlights What's already known? Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9) is a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. Infants that were born with a deviant birth weight have a unique lipoprotein metabolism profile. What this study adds? Serum PCSK9 levels were significantly associated with total and LDL cholesterol. PCSK9 levels were higher in preterm and small for gestation infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.

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., Competing Interests: LJW, BZ, IA, LC, IKJ, JeD, GN, HM, SR, SC, PC, SFTMdB, RP, KK, BC: none related. JCdJ, WMS, HR, JaD and MM report grants from the European Union, all paid to their institution. PMB reports having received grants from the UK National Institute of Health Research, and fees as consultant from CoMind, DiaMedica, Phagenesis and Roche. DvdB reports having received research grants from the European Union, The Netherlands for Health Research and Development, ItsMe Foundation, AMC Foundation and Roche; none related. AHA reports research grants from Boehringer Ingelheim, lectures fee from Abbvie, BMS/Pfizer, Novartis, Roche and Teva and participation in Advisory Board for Lundbeck, Abbvie and MSD; none related. AC reports grants from the European Union and Lombardy Region, for research paid to his institution, and fees as consultant or lecturer from Alexion Pharma, Daiichi Sanky, and Italfarmaco. JK reports lecturer fees from Boehringer Ingelheim, Pfizer and Servier, and travel grants from Boehringer Ingelheim and Servier, none related. SP received research support from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside the submitted work). GT reports grants from the European Union, German Research Foundation, German Federal Ministry of Education and Research, German Innovation Fund for research paid to his institution, and fees as consultant or lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Daiichi Sanky, BristolMyersSqibb/Pfizer, and Stryker. HBvdW reports having received grants from the European Union, the Dutch Heart Foundation, and Stryker for research, and funding for consultancy from Bayer and TargED, all paid to his institution., (© 2023 The Author(s).)

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 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 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.

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.

Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and ClinicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N = 4731 in the SGLT2i arms; N = 4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44-0.86; P = 0.005] and AF/AFL (RR 0.64, 95% CI 0.47-0.87; P = 0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34-0.89; P = 0.01) and AF/AFL (RR 0.50, 95% CI 0.32-0.77; P = 0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43-1.11; P = 0.12) or AF/AFL (RR 0.82, 95% CI 0.53-1.27; P = 0.38). Additionally, a "shorter" duration (< 1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (< 1.5 years; RR 0.58, 95% CI 0.36-0.91; P = 0.02) and AF/AFL (< 1.5 years; RR 0.52, 95% CI 0.34-0.80; P = 0.003). In conclusion, SGLT2i therapy was associated with a significant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting., (© 2022. The Author(s).)

Background: The association between blood pressure (BP) levels and BP variability (BPV) following acute ischaemic stroke (AIS) and outcome remains controversial., Aims: To investigate the predictive value of systolic BP (SBP) and diastolic BP (DBP) and BPV measured using 24-h ambulatory blood pressure monitoring (ABPM) methods during AIS regarding outcome., Methods: A total of 228 AIS patients (175 without prior disability) underwent ABPM every 20 min within 48 h from onset using an automated oscillometric device (TM 2430, A&D Company Ltd) during day time (7:00-22:59) and night time (23:00-6:59). Risk factors, stroke subtypes, clinical and laboratory findings were recorded. Mean BP parameters and several BPV indices were calculated. End-points were death and unfavourable functional outcome (disability/death) at 3 months., Results: A total of 61 (26.7%) patients eventually died. Multivariate logistic regression analysis revealed that only mean night-time DBP (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.00-1.07) was an independent prognostic factor of death. Of the 175 patients without prior disability, 79 (45.1%) finally met the end-point of unfavourable functional outcome. Mean 24-h SBP (HR: 1.03; 95% CI: 1.00-1.05), day-time SBP (HR: 1.02; 95% CI: 1.00-1.05) and night-time SBP (HR: 1.03; 95% CI: 1.01-1.05), SBP nocturnal decline (HR: 0.93; 95% CI: 0.88-0.99), mean 24-h DBP (HR: 1.08; 95% CI: 1.03-1.13), day-time DBP (HR: 1.07; 95% CI: 1.03-1.12) and night-time DBP (HR: 1.06; 95% CI: 1.02-1.10) were independent prognostic factors of an unfavourable functional outcome., Conclusions: In contrast with BPV indices, ABPM-derived BP levels and lower or absence of BP nocturnal decline in the acute phase are prognostic factors of outcome in AIS patients., (© 2022 Royal Australasian College of Physicians.)

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.

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.

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., (© 2023 American Academy of Neurology.)

Introduction: Burden of caregivers is a status that was identified as a consequence of daily care. Anxiety and depression are probably related to complex tasks interwined with the care of a family member suffering from chronic kidney disease (CKD)., Purpose: To examine the experienced burden, anxiety and depression of Greek caregivers of patients with End-Stage CKD on dialysis as well as kidney transplant recipients (TX) in relation to their demographic profile and to compare among the groups., Methods: A total of 396 participants (198 couples of patients and caregivers) were recruited. Structured interviews and self-completed questionnaires were obtained from patients undergoing dialysis modalities as well as TX (28 peritoneal dialysis patients, 137 hemodialysis patients, 33 TX) and their caregivers. Zarit Burden Interview, Beck Depression Inventory and the Generalized Anxiety Disorder-2 scales were used as screening tools., Results: The majority of caregivers were females (67.2%), with a median age of 58 years. Total burden was indicated as mild to moderate (Mdn = 36 (24-51)). Caregivers of haemodialysis (HD) patients showed the highest burden (Mdn = 40 (26-53)) followed by peritoneal dialysis(PD) (Mdn = 29 (25-51)) and TX group (Mdn = 28 (21-43)) (p = 0.022). Caregivers' depression and anxiety were related to the type of patients' treatment, as well. Caregivers of HD and PD patients reported significantly higher depression (Mdn = 11 (5-18)) and anxiety scores (Mdn = 3 (2-5)) in comparison to TX caregivers (Mdn = 6 (2-13) and Mdn = 2 (2-4)) (p = 0.045 and p = 0.04, respectively)., Conclusion: Caregivers of TX patients appeared to have less burden, depression and anxiety levels compared with caregivers of patients on dialysis modalities. Caregivers' burden is significantly associated with anxiety, depressive symptoms, gender, duration of caregiving, educational level, financial status and caregivers' age., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Hyponatraemia is common in patients with stroke and associated with adverse outcomes and increased mortality risk. The present review presents the underlying causes and provides a thorough algorithm for the diagnosis and management of hyponatraemia in stroke patients. Concomitant diseases and therapies, such as diabetes, chronic kidney disease and heart failure, along with diuretics, antidepressants and proton pump inhibitors are the most common causes of hyponatraemia in community. In the setting of acute stroke, the emergence of hyponatraemia might be attributed to the administration of hypotonic solutions and drugs (ie. mannitol and antiepileptics), poor solute intake, infections, as well as stroke-related conditions or complications, such as the syndrome of inappropriate secretion of antidiuretic hormone, cerebral salt wasting syndrome and secondary adrenal insufficiency. Diagnostically, the initial step is to differentiate hypotonic from non-hypotonic hyponatraemia, usually caused by hyperglycaemia or recent mannitol administration in patients with stroke. Determining urine osmolality, urine sodium level and volume status are the following steps in the differentiation of hypotonic hyponatraemia. Of note, specific parameters, such as fractional uric acid and urea excretion, along with plasma copeptin concentration, may further improve the diagnostic yield. Therapeutic options are based on the duration and symptoms of hyponatremia. In the case of acute or symptomatic hyponatraemia, hypertonic saline administration is recommended. Hypovolaemic chronic hyponatremia is treated with isotonic solution administration. Although fluid restriction remains the first-line treatment for the rest forms of chronic hyponatraemia, therapies increasing renal free water excretion may be necessary. Loop diuretics and urea serve this purpose in patients with stroke, whereas sodium-glucose transport protein-2 inhibitors appear to be a promising therapy. Nevertheless, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in such patients. Randomized trials designed to compare therapeutic strategies in managing hyponatraemia in patients with stroke are required., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2023.)

Introduction: Heart failure (HF) is a major public health issue associated with significantly increased risk of stroke. It remains uncertain whether oral anticoagulation (OAC) in patients with heart failure and sinus rhythm (HF-SR) could improve prognosis., Methods: We performed a systematic search of PubMed and Embase databases for randomized controlled clinical trials assessing oral anticoagulants versus antiplatelets or placebo in patients with HF or ventricular dysfunction/cardiomyopathy without clinical HF and SR. The outcomes assessed were stroke/systemic embolism, major bleeding, myocardial infarction, all-cause mortality, and HF hospitalization., Results: Seven trials of 15,794 patients were eligible for our analyses. The overall follow-up duration was 32,367 patient-years corresponding to a mean follow-up of 2.05 years per patient. Four trials included patients treated with warfarin and three included patients treated with rivaroxaban. OAC was associated with reduced rate of stroke or systemic embolism compared to control (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.44, 0.73, number needed to treat (NNT): 71.9) but higher rate of major bleeding (OR: 1.92, 95% CI: 1.47, 2.50, number needed to harm (NNH): 57.1). In the subgroup analysis according to the type of OAC, rivaroxaban was associated with significantly reduced rate of stroke or systemic embolism (1.24 vs 1.97 events per 100 patient-years, respectively, OR: 0.63, 95% CI: 0.45, 0.88, NNT: 82) and higher risk of major bleeding (OR: 1.66, 95% CI: 1.26, 2.20) compared to antiplatelets or placebo. There was no significant differences between groups for the outcomes of myocardial infarction, all-cause mortality, and HF hospitalization., Conclusion: This analysis shows that any benefit of OAC for stroke prevention may be offset by an increased risk of major bleeding in HF-SR patients. A well-designed randomized controlled trial of newer safer OACs is needed in this population.

The consistently high prevalence of cardiovascular disease (CVD) has urged the need for punctual and effective prevention. Extended research on this specific area has demonstrated the influence of fetal and neonatal periods on the risk of developing CVD in adulthood. Thus, the role of traditional and novel biological markers to the effective screening of CVD among the neonatal population is widely investigated. The objective of the present narrative review is to examine those neonatal biomarkers that may play a role in the development of CVD, to exhibit scientific data that appertain to their association with various perinatal conditions leading to CVD predisposition, and their potential role on prediction and prevention strategies. Multiple biomarkers, traditional and novel, have been mined across the studied literature. Adiposity, insulin resistance, altered lipid profile, inflammation, and endothelial dysfunction seem among the headliners of CVD. Even though various novel molecules have been studied, their clinical utility remains controversial. Therefore, it is quite important for the scientific community to find elements with strong predictive value and practical clinical use.

Background The visual analogue scale (VAS) has been used as a diagnostic tool for the evaluation of the severity of olfactory and gustatory dysfunction (OGD) caused by SARS-CoV2 infection. The main objective of the present study was the evaluation of OGD with VAS in COVID-19-positive patients in Northwestern Greece and its possible association with the patients' self-reported symptoms of olfactory and gustatory dysfunction. Methods The presence of olfactory and gustatory symptoms and their severity were assessed by questionnaire along with the use of specific odorants and tastant ingredients, in three time periods: prior to COVID-19, during COVID-19 (initial diagnosis) and post-COVID-19 disease (at four weeks from disease onset). Three hundred COVID-19-positive patients (home-quarantined and hospitalized) tested with RT-PCR test in the University Hospital of Ioannina Greece were included in this study. Statistical analysis was performed on SPSS Statistics 26.0 (IBM Corp., Armonk, NY) Results Out of a total of 300 patients, 146 and 190 patients had mild hyposmia and hypogeusia respectively, followed by patients with severe hyposmia or hypogeusia (118 and 88 respectively), at the time of COVID-19 onset (initial diagnosis). An increase in the number of patients with recovery of symptoms was observed during the follow-up period, during which only eight patients had non-resolving severe symptoms (six patients with hyposmia and two with hypogeusia). On further analysis, a statistically significant association was found between the severity of symptoms (assessed by VAS score) and the self-reported symptoms of sensory dysfunction by the patients. There was a significant association between the groups of patients with mild hyposmia and patients that reported no loss of smell; between the patients with moderate hyposmia and the patients who reported "loss of smell"; and between the patients with severe hyposmia and the group of patients who reported a loss of smell, at the COVID-19 onset period. Similarly, patients with mild hyposmia were associated with those that reported a loss of smell at the same time. The severity of hyposmia was also associated with the reported symptom of "loss of taste" at the time of COVID-19 diagnosis. Similar findings were observed regarding the severity of hypogeusia and the reported symptom of "loss of taste" among the groups of patients. Finally, the severity of hypogeusia was associated with smell loss at the time of initial diagnosis of the infection. Conclusion Similar to the literature data, our findings indicate that hyposmia and hypogeusia are common symptoms of COVID-19 disease with varying severity. In our study, most of the patients exerted a complete recovery of these OGD symptoms. In addition, we found an association between olfactory dysfunction and self-reported sensory of taste as well as gustatory dysfunction and sensory of smell. Finally, we found that the VAS score was a reliable diagnostic tool in the estimation of OGD in this cohort of patients. However, our results need to be confirmed by larger-scale trials., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Zarachi et al.)

Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19., Materials/methods: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA)., Results: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations., Conclusions: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.

Objective: The purpose of this study was to investigate the association of blood pressure (BP) time-in-target range (TTR) derived from 24-h ambulatory BP monitoring (ABPM) during the acute phase of ischemic stroke (AIS), with the severity of stroke and its predictive value for the 3 months outcome., Methods: A total of 228 AIS patients (prospective multicenter follow-up study) underwent ABPM every 20 min within 48 h from stroke onset using an automated oscillometric device. Clinical and laboratory findings were recorded. Mean BP parameters, BP variability and TTR for SBP (90-140 mmHg), DBP (60-90 mmHg), and mean arterial pressure (MAP) were calculated. Endpoints were death and disability/death at 3 months., Results: A total of 14 942 BP measurements were recorded (∼66 per AIS patient) within 72 h of stroke onset. Patient's 24-h TTR was 34.7 ± 29.9, 64.3 ± 24.2, and 55.3 ± 29.4% for SBP, DBP and MAP, respectively. In patients without prior hypertension, TTR was lower as stroke severity increased for both DBP (P = 0.031) and MAP (P = 0.016). In 175 patients without prior disability, increase in TTR of DBP and MAP associated significantly with a decreased risk of disability/death (hazard ratio 0.96, 95% CI 0.95-0.99, P = 0.007 and hazard ratio 0.97, 95% CI 0.96-0.99, P = 0.007). TTR of SBP in 130-180 mmHg and 110-160 mmHg ranges seems to be related with mortality and disability outcomes, respectively., Conclusion: TTR can be included for a more detailed description of BP course, according to stroke severity, and for the evaluation of BP predictive role, in addition to mean BP values, derived from ABPM during the acute phase of AIS., Clinical Trial Registrationurl: http://www.clinicaltrials.gov. Unique identifier: NCT01915862., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes., Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949)., Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI < 2, OR: 0.38, 95% CI 0.21-0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients <65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment., Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90., Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB., Competing Interests: A.An. is partly funded by the Italian Ministry of Health under “Fondi Ricerca Corrente” – L1P1. L.D. has received consultation honoraria from Sobi. M.B. has received funds for research grants and/or advisor/consultant and/or speaker/chairman from Angelini, Astellas, Bayer, Biomerieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi and Nabriva. M.G.N. was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research. P.P. has received honoraria from GILEAD Sciences, Janssen, and MSD. H.M. reports receiving honoraria, consulting fees and non-financial support from healthcare companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. G.N.D. is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, Sobi, received research grants from Abbvie, Gilead and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. E.J.G.-B. has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and Xbiotech Inc; independent educational grants from Abbott CH, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and Xbiotech Inc. and funding from the Horizon 2020 Marie Skłodowska-Curie International Training Network “the European Sepsis Academy” (granted to the National and Kapodistrian University of AthensNational and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). The other authors do not disclose any conflict of interest., (© 2022 The Author(s).)

Objectives: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19., Methods: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death., Results: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations., Conclusions: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment., Clinicaltrials: gov, NCT04680949 and NCT04357366., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [ER, AA are employees at MeMed Diagnostics. GB’s work was partly funded by the Italian Ministry of Health ‘Fondi Ricerca Corrente’ to IRCCS Sacro Cuore Don Calabria Hospital. GND has acted as advisor/lecturer for Ipsen, Pfizer, Genkyotex, Novartis and Sobi; received research grants from Abbvie and Gilead; PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc., Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. MGN was supported by an ERC Advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. EJGB has received honoraria from Abbott CH, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and XBiotech Inc; independent educational grants from Abbott CH, AbbVie, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Novartis, Sobi, UCB and XBiotech Inc.; and funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and from the Horizon Europe project EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). The other authors do not have any competing interest to declare.]., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden. In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition. Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition. Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination. Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.

Aims: It is unclear whether early cardiac rhythm control is beneficial in patients with acute ischemic stroke and paroxysmal atrial fibrillation (PAF). We sought to investigate whether PAF self-termination and in-hospital sinus rhythm (SR) restoration is associated with improved outcome in ischemic stroke patients with PAF, compared to those with sustained atrial fibrillation (AF)., Methods: Consecutive patients with first-ever acute stroke and confirmed PAF during hospitalization were followed for up to 10 years after the index stroke or until death. We investigated the association of in-hospital self-terminated PAF and PAF conversion to SR compared to sustained AF with 10-year all-cause mortality, stroke recurrence, and major adverse cardiovascular events (MACE). Cox regression analysis was performed to identify independent predictors of each outcome., Results: Among 297 ischemic stroke patients with in-hospital PAF detection, PAF was self-terminated in 87 (29.3%) patients, while 143 (48.1%) patients received antiarrhythmic medication in order to achieve PAF conversion to SR. During a median (Interquartile range, IQR) period of 28 (4-68) months, among patients with self-terminated PAF there were 13.5 deaths, 3.6 stroke recurrences, and 5.3 MACE per 100 patient-year while in patients who underwent medical PAF conversion there were 11.7 deaths, 4.6 stroke recurrences, and 5.8 MACE per 100 patient-year. Patients with sustained AF experienced 23.8 deaths, 8.7 stroke recurrences, and 13.9 MACE per 100 patient-years. In multivariable analysis, compared to patients with sustained AF, PAF self-termination was associated with significantly lower 10 years-risk of death (adjusted hazards ratio (adjHR): HR: 0.63, 95% Confidence interval: 0.40-0.96), stroke recurrence (adjHR: HR: 0.41, 95% CI: 0.19-0.91), and MACE (adjHR: 0.43, 95% CI: 0.23-0.81), while PAF medical conversion to SR was associated with lower 10 years-risk of death (adjHR: 0.65, 95% CI: 0.44-0.97) and MACE (adjHR: 0.56, 95% CI: 0.33-0.95)., Discussion: This study showed that in-hospital PAF self-termination was associated with lower risk of 10-year mortality, stroke recurrence, and MACE, potentially attributed to the lower burden of AF, whereas in-hospital PAF conversion to SR was associated with lower risk of 10-year mortality and MACE., Conclusion: Early restoration of sinus rhythm is associated with improved survival and MACE in patients with acute ischemic stroke and PAF., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. D. Sagris reports no disclosures, Dr. E. Korompoki reports no disclosures, Dr. G. Ntaios reports speaker fees/advisory boards/research support from: Abbott; Amgen; Bayer; BMS/Pfizer; Boehringer-Ingelheim; Elpen; Galenica. All fees are paid directly to his institution (University of Thessaly), Dr. S. Tzeis reports no disclosures, Dr. E. Manios reports no disclosures, Dr. J. Kanakakis reports no disclosures, Dr. H. Milionis reports speaker fees/advisory boards/research support from: Alexion, Amgen, AstraZeneca, Bayer, Elpen, Genesis Pharma, MSD, Pfizer, Sanofi, Servier, Viatris, Winmedica, Dr. P. Papanagiotou: reports no disclosures, Dr. G. Andrikopoulos reports speaker fees/advisory boards/research support from: AstraZeneca, Abbot, Bard, Bayer Healthcare, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, ELPEN, Galenica, Lilly, Medtronic, Menarini, MSD, Pfizer, Sanofi, Servier, StJude, Unifarma, and Vianex, Dr. GY Lip: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally, Dr. K. Vemmos: reports speaker fees/advisory boards from: Amgen; Bayer; BMS/Pfizer; Boehringer-Ingelheim; Elpen., (© European Stroke Organisation 2022.)

We aimed to evaluate the impact of biologic treatment on subclinical atherosclerosis and risk factors for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Forty-nine biologic naïve RA patients, treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), who were eligible for treatment with a biologic agent, were included in the study. The serum levels of lipid parameters, as well as disease activity parameters were determined in RA patients before and after 3 and 6 months of therapy. Carotid artery intima-media thickness (cIMT) was measured before and after treatment. A comparison analysis of change of these parameters was also performed between anti-tumor necrosis factor (anti-TNF) and non-anti-TNF users. Furthermore, 31 non-smoking healthy volunteers, matched for age and gender, were used as a control group. At baseline, RA patients had a decrease in serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels compared with controls (209 ± 63 vs 233 ± 44 and 58 ± 15 vs 61 ± 14, p < 0.004), while cIMT was higher versus controls [0.9 (0.8-1) vs 0.6 (0.5-0.7), p < 0.001]. TC, HDL-C and apolipoprotein A1 levels were significantly increased 3 months after treatment (209 ± 63, 58 ± 15, 162 ± 32, vs 227 ± 45, 60 ± 15, 169 ± 29, respectively, p < 0.03) and this observation remained stable at a 6-month follow-up. After 6 months, there was also a statistically significant decrease in the cIMT [0.9 (0.8-1) vs 0.7 (0.6-0.8), p < 0.001]. Anti-TNF and non-anti-TNF users had comparable changes in cardiovascular risk parameters. The atherogenic lipid profile and subclinical atherosclerosis are features of RA, which appeared improved after biologic therapy initiation., (© 2022. Springer Japan KK, part of Springer Nature.)

Greece introduced a 13-valent pneumococcal conjugate vaccine (PCV13) into the infant national immunization program in 2010 (3 + 1 schedule until June 2019). Since 2015, PCV13 has been recommended for adults aged 19-64 years with comorbidities and adults ≥65 years sequentially with 23-valent pneumococcal polysaccharide vaccine (PPSV23). We examined pneumococcal serotype distribution among Greek adults aged ≥19 years hospitalized with community-acquired pneumonia (CAP) during November 2017-April 2019. This was an interim analysis of EGNATIA, a prospective study of adult hospitalized CAP in the cities of Ioannina and Kavala. Pneumococcus was identified using cultures, BinaxNow®, serotype-specific urinary antigen detection assays (UAD-1/2). Our analysis included overall 482 hospitalized CAP patients (mean age: 70.5 years; 56.4% male). 53.53% of patients belonged to the highest pneumonia severity index (PSI) classes (IV-V). Pneumococcus was detected in 65 (13.5%) patients, with more than half (57%) of cases detected only by UAD. Approximately two-thirds of pneumococcal CAP occurred in those aged ≥65 years (n = 40, 8.3% of CAP). More than half of pneumococcal CAP (n = 35, 53.8%) was caused by PCV13 serotypes. Most frequently detected PCV13 serotypes were 3, 19A, 23F, collectively accounting for 83% of PCV13 vaccine-type (VT) CAP and 6% of all-cause CAP. Overall, 82.9% of PCV13 VT CAP occurred among persons with an indication (age/risk-based) for PCV13 vaccination. Even with a mature PCV13 childhood immunization program, a persistent burden of PCV13 VT CAP exists in Greek adults. Strategies to increase PCV13 (and higher-valency PCVs, when licensed) coverage in adults should be implemented to reduce the disease burden.

The purpose of this study was to investigate the reliability of the novel Functional Bedside Aspiration Screen (FBAS) to predict aspiration risk in acute stroke and to guide initial therapy needs. We conducted a prospective validation study of the FBAS 10-point scale in 101 acute ischemic stroke patients. Outcome measures were compared with the Penetration Aspiration Scale (PAS) via the Flexible Endoscopic Swallowing Study. Correlations with the Functional Oral Intake Scale (FOIS) and the Therapy Requirement Scale (TRS) were analyzed. We observed a 65.8% sensitivity and 70.2% specificity ( p = 0.004) for predicting penetration risk (for PAS score ≥ 3) and a 73% sensitivity and 62% specificity for predicting aspiration risk (PAS score ≥ 6). For patients with a modified ranking scale 0-2 ( n = 44) on admission, the predictive measurements of the FBAS yielded sensitivity and specificity values of 66.7% and 88.6% ( p = 0.011). A significant negative correlation was found with PAS measurements, whereas a positive correlation was observed regarding FOIS. Significantly lower FBAS scores were observed in patients with high requirements for therapeutic interventions and dietary modification. FBAS may be regarded as an alternative time-efficient clinical support tool in settings in which instrumentation is not directly accessible. Further studies including a larger cohort of acute stroke patients with more severe neurological deficits are necessary.

Background: COVID-19 has been frequently associated with an increased risk of thrombotic complications. There have also been reports of an increased likelihood of stroke, although its true incidence in patients with COVID-19 is currently unknown., Methods: Electronic databases PubMed and Scopus were searched from inception up to July 30, 2021 to identify randomized controlled studies in patients with confirmed COVID-19 undergoing one or more interventions. Studies were screened for eligibility using a predefined inclusion criterion and selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model meta-analysis was conducted, and heterogeneity was assessed using I-squared test., Results: Out of 3960 potentially eligible articles, 77 randomized studies (38 732 patients) were included. Mean age of the study population was 55±9.3 years. Females constituted 38% of the study population and mean duration of follow-up after study enrollment was 23±12.9 days. Cumulative incidence of stroke in the overall study population was 0.001 (95% CI, 0.001-0.002) with a total of 65 events in 38 732 patients, corresponding to an absolute incidence of 0.168%. Incidence of stroke in the inpatient population was 0.001 (95% CI, 0.001-0.002; 65 events in 37 069 patients), corresponding to an absolute incidence of 0.175%. No strokes were observed in the outpatient setting., Conclusions: The overall incidence of stroke in patients with COVID-19 appears to be lower than that reported in previous observational reports.

Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.