Pan-drug-resistant Acinetobacter baumannii (PDR-AB) causes severe infections and constitutes a threat in several geographic regions. Little is known about the differential effectiveness of last-resort regimens, frequently used in this setting. We compared the effectiveness of two literature-proposed regimens against PDR-AB infections consisting of colistin, ampicillin-sulbactam, and either meropenem (regimen A) or tigecycline (regimen B). This is a retrospective analysis of prospectively collected data from 12 centers on adult patients with hospital-acquired pneumonia (HAP) or bloodstream infection (BSI), who had received definitive treatment with either regimen A or regimen B. The primary outcome was clinical failure, defined as any of the following occurring by day 14 from infection onset: death, initiation of salvage treatment, treatment withdrawal due to toxicity, persistent bacteremia for BSI patients and failure to improve oxygenation for HAP patients before and after propensity matching. Eighty-three patients were included in the primary analysis; 60 had received regimen A and 23 regimen B. Regimen B was significantly associated with clinical failure before and after propensity matching (odds ratios [OR]: 3.11; 95% confidence interval [CI]: 1.10-8.84 vs OR: 3.83; 95% CI: 1.26-11.63), respectively. Salvage therapy and treatment discontinuation due to toxicity were more frequent in patients treated with regimen B. In multivariable analysis, regimen B was independently associated with 28-day mortality before (hazard ratio [HR]: 2.53; 95% CI: 1.08-5.94) but not after propensity matching (HR: 2.64; 95% CI: [0.99-7.02]). Treatment with colistin, ampicillin-sulbactam, and meropenem against severe PDR-AB infections was associated with favorable outcomes compared to colistin, ampicillin-sulbactam, and tigecycline.

Sepsis is heterogeneous, and the optimal strategy for tailoring immunotherapy is uncertain. To investigate whether precision immunotherapy guided by the presence of macrophage activation–like syndrome or sepsis-induced immunoparalysis improves organ dysfunction by day 9. A randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted in 6 countries. Patients with sepsis, defined by Sepsis-3, were included if they had community-acquired or hospital-acquired pneumonia or ventilator-associated pneumonia or bacteremia and sepsis and had displayed either macrophage activation–like syndrome (blood ferritin >4420 ng/mL) or sepsis-induced immunoparalysis (blood ferritin ≤4420 ng/mL and <5000 human leukocyte antigen DR receptors on CD45/CD14 monocytes). The first patient was enrolled August 5, 2021, and the last follow-up, April 29, 2024. Eligible patients were randomized to receive standard care and precision immunotherapy or standard care and placebo. Those in the precision immunotherapy group with macrophage activation–like syndrome received anakinra intravenously (IV) and placebo subcutaneously, and those with sepsis-induced immunoparalysis received subcutaneous recombinant human interferon gamma and IV placebo. Those in the placebo group received both IV and subcutaneous placebo. Treatment was administered for up to 15 days. The primary end point was a decrease of at least 1.4 points in the mean Sequential Organ Failure Assessment (SOFA) score from baseline by day 9. The SOFA score evaluates 6 organ systems, ranging from 0, no dysfunction, to 4, failure, and the total score ranges from 0, normal, to 24, most severe form of multiorgan failure. Key secondary outcomes included 28-day mortality. Of 672 patients assessed for eligibility, 281 were randomized and 276 were included in the primary analysis population (mean [SD] age, 70 [13] years; 93 females [33.7%]; median baseline SOFA score, 9 [IQR, 7-11]). The SOFA decrease end point was attained by 46 of 131 patients (35.1%) in the precision immunotherapy group and by 26 of 145 patients (17.9%) in the placebo group (difference, 17.2% [95% CI, 6.8% to 27.2%]; P = .002). Mortality at 28 days was not statistically significantly different between groups. A total of 1069 serious treatment-emergent adverse events (88.8%) were reported; increased incidence of anemia was noted in the anakinra group; and hemorrhage in the recombinant human interferon gamma group. Among patients with sepsis, precision immunotherapy targeting macrophage activation–like syndrome and sepsis-induced immunoparalysis improved organ dysfunction by day 9 compared with placebo. ClinicalTrials.gov Identifier: NCT04990232

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently linked to increased risk of cardiovascular disease (CVD). HDL lipoproteins may serve as a possible link in this association through their hepatic synthesis and atheroprotective properties. Serum samples were collected from 51 MASLD patients (diagnosed by abdominal ultrasound), 40 with coronary artery disease, and 50 healthy controls. HDL lipid profiles were investigated by proton nuclear magnetic resonance (1H NMR) spectroscopy. Patients with MASLD exhibit an increased percentage of lysophosphatidylcholine and sphingolipid content, mainly due to increased ceramides, and a reduced percentage of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol compared to controls. The % content of total and individual polyunsaturated fatty acids including linoleic, docosahexaenoic, eicosapentaenoic, and arachidonic acid was found to be reduced in patients with MASLD, while saturated fatty acid content was increased compared to the control group. These alterations in fatty acid composition were observed also in CAD patients compared to controls but were more pronounced in CAD patients. Compared to CAD patients, those with MASLD showed an increased content of sphingolipids, ceramides, and glycerolipids and a reduced content of phosphatidylinositol. Changes observed in the lipid composition of HDL lipoproteins in MASLD patients may impair the protective properties of HDL particles, contributing to increased CVD risk.

Acinetobacter baumannii (A. baumannii) is a difficult-to-treat (DTR) pathogen that causes ventilator-associated pneumonia (VAP) associated with high mortality. To improve the outcome of DTR A. Baumannii VAP, nebulized colistin (NC) was introduced with promising but conflicting results on mortality in earlier studies. Currently, NC is used at a much higher daily dose compared to the past. Nevertheless, there is little evidence on the effect of high-dose NC on the outcomes of A. baumannii VAPs, especially in the current era where the percentage of colistin-resistant A. baumannii strains is rising. We conducted a retrospective study comparing bacteremic A. baumannii VAP patients who were treated with and without NC co-administration and were admitted in the Intensive Care Unit of University Hospital of Ioannina from March 2020 to August 2023. Overall, 59 patients (21 and 38 with and without NC coadministration, respectively) were included. Both 28-day and 7-day mortalities were significantly lower in the patient group treated with NC (52.4% vs. 78.9%, p 0.034 and 9.5% vs. 47.4%, p 0.003, respectively). Patients treated with NC had a higher percentage of sepsis resolution by day 7 (38.1% vs. 13.5%, p 0.023) and were more likely to be off vasopressors by day 7 (28.6% vs. 8.1%, p 0.039). The addition of NC in the treatment regime of A. baumannii VAP decreased mortality.

Data on COVID-19 mortality among patients in intensive care units (ICUs) from Eastern and/or Southern European countries, including Greece, are limited. The purpose of this study was to evaluate the ICU mortality trends among critically ill COVID-19 patients during the first two years of the pandemic in Greece and to further investigate if certain patients’ clinical characteristics contributed to this outcome. We conducted a multi-center retrospective observational study among five large university hospitals in Greece, between February 2020 and January 2022. All adult critically ill patients with confirmed COVID-19 disease who required ICU admission for at least 24 h were eligible. In total, 1462 patients (66.35% males) were included in this study. The mean age of this cohort was 64.9 (±13.27) years old. The 28-day mortality rate was 35.99% (n = 528), while the overall in-hospital mortality was 50.96% (n = 745). Cox regression analysis demonstrated that older age (≥65 years old), a body mass index within the normal range, and a delay in ICU admission from symptom onset, as well as worse baseline clinical severity scores upon ICU admission, were associated with a greater risk of death. Mortality of critically ill COVID-19 patients was high during the first two years of the pandemic in Greece but comparable to other countries. Risk factors for death presented in this study are not different from those that have already been described for COVID-19 in other studies.

The coronavirus disease (COVID-19) pandemic increased the incidence of severe infections caused by multidrug-resistant (MDR) pathogens among critically ill patients, such as Acinetobacter baumannii (AB), whose bloodstream infections (BSIs) have been associated with significant mortality. Whether there is any difference in outcome between COVID-19 and non-COVID-19 patients with AB BSI still remains unknown. We conducted a retrospective study comparing clinical characteristics and outcomes of COVID-19 versus non-COVID-19 critically ill patients with AB BSI. Overall, 133 patients with AB BSI (102 COVID-19, 31 non-COVID-19) were studied. The 28-day mortality rate was high and did not differ significantly (69.6% COVID-19 vs. 61.3% non-COVID-19, p = 0.275). Patients with septic shock had a higher mortality rate irrespective of their status with the majority of deaths occurring during the first 7 days. COVID-19 patients were more likely to have ventilator-associated pneumonia (VAP) as the source of BSI (55.8% vs. 22.3%, respectively, p = 0.0001) and were more likely to develop acute respiratory distress syndrome (ARDS) (78.4% vs. 48.4%, respectively, p = 0.001), sepsis (86.3% vs. 67.7%, respectively, p = 0.03), and septic shock (88.3% vs. 58.1%, respectively, p = 0.007) compared to the non-COVID-19 patient group. In conclusion, COVID-19 patients with A. baumannii BSI have a high rate of mortality and more often develop septic shock, while VAP is the main origin of their BSI.

Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely understood and a great heterogeneity both in terms of clinical expression, patient response to currently available therapeutic interventions and outcomes. This heterogeneity proves to be a major obstacle in our quest to deliver improved treatment in septic critical care patients; thus, identification of clinical phenotypes is absolutely necessary. Although this might be seen as an extremely difficult task, nowadays, artificial intelligence and machine learning techniques can be recruited to quantify similarities between individuals within sepsis population and differentiate them into distinct phenotypes regarding not only temperature, hemodynamics or type of organ dysfunction, but also fluid status/responsiveness, trajectories in ICU and outcome. Hopefully, we will eventually manage to determine both the subgroup of septic patients that will benefit from a therapeutic intervention and the correct timing of applying the intervention during the disease process.

Introduction The effect of various antihypertensive drugs on the glucose homeostasis has been discussed extensively. Dual combination treatment is advised with current guidelines. We present comparative data of the effect of delapril/manidipine versus valsartan/amlodipine versus telmisartan/amlodipine combination treatments, in fasting glucose, fasting insulin, OGTT and HbA1c levels, before and after the 3-month treatment, in hypertensive prediabetic patients. Methods Data were collected from 154 patients from the outpatient clinic for patients with lipid disorders, hypertension and diabetes of our hospital, during the period 2014–2018. A number of 53 persons was randomized in the delapril/manidipine group 30/10 mg per day while 51 persons had been randomized in the group of telmisartan/amlodipine 80/5mg per day and 54 patients in the valsartan/amlodipine 160/5 mg per day. All patients successfully completed the study. Baseline characteristics are presented in Table 1A. Results The resulting alternations in glucose, insulin, OGTT and HbA1c levels, before and after the 3-month treatment are presented on Table 1B for the 3 groups of treatment. Conclusions In the comparison between the groups, a statistically significant difference was found in the change in INS values from the beginning of treatment until 3 months, for the TEL/AMLO treatment group, where a statistically significant difference from the DEL/MANI treatment group (p-value<0.01) and a strong statistically significant difference from the VAL/AMLO treatment group (p-value<0.001) were noted. The TEL/AMLO group had the only decrease in insulin levels compared to the other treatment groups where an increase was observed, after the treatment. The change in OGTT levels showed a statistically significant difference (p-value<0.05) between the DEL/MANI treatment group (a decrease of 6.63%) compared to the TEL/AMLO treatment group (an increase of 1.53%) after 3 months of treatment. Funding Acknowledgement Type of funding sources: None.

Background: Family members of Intensive Care Unit (ICU) patients are subject to a higher risk of depression, anxiety, and stress-related disorders. This psychological distress inevitably affects their perception of the quality of care that their relative receives. The aim of this study is to enlighten the effect of psychopathology, resilience, and self-compassion on the satisfaction of family members of ICU patients and examine the role of self-compassion and resilience as explaining variables of the psychopathology and satisfaction relation. Methods: One hundred and seventy-six family members participated in the study. Each participant completed the Symptom Check List 90 (SCL-90-R), the Family Satisfaction in the Intensive Care Unit (FS-ICU) questionnaire, the Connor-Davidson Mental Endurance Scale (CD-RISC), and the Self-Compassion scale (SCS). Analysis of variance and path analysis was applied in order to test the research hypotheses. Results: The patient’s age, patient’s gender, type of relation, and age of the family member did not have a statistically significant direct or interaction effect on the satisfaction of the family members. The psychopathology had a significant negative correlation with the total satisfaction of the family members. The self-compassion was found to have a significant direct effect on psychopathology and a significant indirect effect on satisfaction via resilience, while both resilience and self-compassion had significant direct or indirect effects on satisfaction. Self-compassion was found to eliminate the mediation role of resilience on psychopathology and the resilience and psychopathology effect on satisfaction. Conclusions: Self-compassion emerged as the most important personality characteristic concerning the satisfaction of family members of ICU patients. Our study indicates that interventions aiming to enhance self-compassion will help patients’ relatives cope with the particularly stressful experience of the intensive care unit.

Journal of Medical VirologyVolume 93, Issue 1 p. 120-121 LETTER TO THE EDITOR Tocilizumab's efficacy in patients with Coronavirus Disease 2019 (COVID-19) is determined by the presence of cytokine storm Ioannis Andrianopoulos, Corresponding Author Ioannis Andrianopoulos [email protected] orcid.org/0000-0001-9609-2728 Intensive Care Unit, University Hospital of Ioannina, Ioannina, Greece Correspondence Dr Ioannis Andrianopoulos, Intensive Care Unit, University Hospital of Ioannina, Stavros Niarchos Avenue, 45500 Ioannina, Greece. Email: [email protected]Search for more papers by this authorAthanasios Papathanasiou, Athanasios Papathanasiou Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this authorGeorgios Papathanakos, Georgios Papathanakos orcid.org/0000-0003-2521-5326 Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this authorAristeidis Chaidos, Aristeidis Chaidos Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UKSearch for more papers by this authorVasilios Koulouras, Vasilios Koulouras Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this author Ioannis Andrianopoulos, Corresponding Author Ioannis Andrianopoulos [email protected] orcid.org/0000-0001-9609-2728 Intensive Care Unit, University Hospital of Ioannina, Ioannina, Greece Correspondence Dr Ioannis Andrianopoulos, Intensive Care Unit, University Hospital of Ioannina, Stavros Niarchos Avenue, 45500 Ioannina, Greece. Email: [email protected]Search for more papers by this authorAthanasios Papathanasiou, Athanasios Papathanasiou Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this authorGeorgios Papathanakos, Georgios Papathanakos orcid.org/0000-0003-2521-5326 Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this authorAristeidis Chaidos, Aristeidis Chaidos Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UKSearch for more papers by this authorVasilios Koulouras, Vasilios Koulouras Intensive Care Unit, University Hospital of Ioannina, Ioannina, GreeceSearch for more papers by this author First published: 22 June 2020 https://doi.org/10.1002/jmv.26209Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Borku Uysal B, Ikitimur H, Yavuzer S, et al. ''Tociluzumab challenge: a series of cytokine storm therapy experience in hospitalized COVID-19 pneumonia patients''. J Med Virol. 2020. https://doi.org/10.1002/jmv.26111 10.1002/jmv.26111 Web of Science®Google Scholar 2Capra R, De Rossi N, Mattioli F, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020; 76: 31-35. https://doi.org/10.1016/j.ejim.2020.05.009 10.1016/j.ejim.2020.05.009 CASPubMedWeb of Science®Google Scholar 3Klopfenstein T, Zayet S, Lohse A, et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Med Mal Infect. 2020. https://doi.org/10.1016/j.medmal.2020.05.001 10.1016/j.medmal.2020.05.001 Web of Science®Google Scholar 4Toniati P, Piva S, Cattalini M, et al. 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The prevalence of acinetobacter baumannii (AB) as a cause of hospital infections has been rising. Unfortunately, emerging colistin resistance limits therapeutic options and affects the outcome. The aim of the study was to confirm our clinically-driven hypothesis that intensive care unit (ICU) patients with AB resistant-to-colistin (ABCoR) bloodstream infection (BSI) develop fulminant septic shock and die. We conducted a 28-month retrospective observational study including all patients developing AB infection on ICU admission or during ICU stay. From 622 screened patients, 31 patients with BSI sepsis were identified. Thirteen (41.9%) patients had ABCoR BSI and 18/31 (58.1%) had colistin-susceptible (ABCoS) BSI. All ABCoR BSI patients died; of them, 69% (9/13) presented with fulminant septic shock and died within the first 3 days from its onset. ABCoR BSI patients compared to ABCoS BSI patients had higher mortality (100% vs. 50%, respectively (p = 0.001)), died sooner (p = 0.006), had lower pH (p = 0.004) and higher lactate on ICU admission (p = 0.0001), and had higher APACHE II (p = 0.01) and Charlson Comorbidity Index scores (p = 0.044). In conclusion, we documented that critically ill patients with ABCoR BSI exhibit fulminant septic shock with excessive mortality. Our results highlight the emerging clinical problem of AB colistin resistance among ICU patients.

Cardiovascular disease (CVD) is the major cause of death in patients with type-2 diabetes mellitus (T2DM), although the factors that accelerate atherosclerosis in these patients are poorly understood. The identification of the altered quantity and quality of lipoproteins, closely related to atherogenesis, is limited in routine to a pattern of high triglycerides and low HDL-cholesterol (HDL-C) and in research as dysfunctional HDLs. We used the emerging NMR-based lipidomic technology to investigate compositional features of the HDLs of healthy individuals with normal coronary arteries, drug-naïve; recently diagnosed T2DM patients with normal coronary arteries; and patients with recent acute coronary syndrome. Patients with T2DM and normal serum lipid profiles even at diagnosis presented significant lipid alterations in HDL, characterized by higher triglycerides, lysophosphatidylcholine and saturated fatty acids; and lower cholesterol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, plasmalogens and polyunsaturated fatty acids, an atherogenic pattern that may be involved in the pathogenesis of atherosclerosis. These changes are qualitatively similar to those found, more profoundly, in normolipidemic patients with established Coronary Heart Disease (CHD). We also conclude that NMR-based lipidomics offer a novel holistic exploratory approach for identifying and quantifying lipid species in biological matrixes in physiological processes and disease states or in disease biomarker discovery.

How to cite this article: Papathanakos G, Andrianopoulos I, Papathanasiou A, Lepida D, Koulouras V. Adapting in the COVID-19 Era. Indian J Crit Care Med 2020;24(12):1286–1287.

We read with great interest the research article written by Borku Uysal B et al which is in accordance with the so far accumulating knowledge that tocilizumab is an effective treatment for COVID-19 cytokine storm syndrome (CSS). This article is protected by copyright. All rights reserved.

OBJECTIVESAltered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia.METHODSFifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA.RESULTSA two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patients <65 years old.CONCLUSIONSStandard linezolid dosing is likely to provide insufficient target attainment against MRSA in obese patients. Body weight and especially age are important characteristics to be considered when administering linezolid to treat MRSA infections.

BACKGROUND:Pulmonary hypertension (PH), regardless of its etiology, is associated with an impaired outcome in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to determine the incidence, cause, and effect of PH as detected by echocardiography in COPD patients. METHODS:Patients with confirmed COPD of any stage were evaluated by echocardiography for the likelihood of PH according to the proposed criteria. Patients with possible/likely to have PH underwent right heart catheterization, upon agreement, to confirm the presence, severity, and cause of PH. RESULTS:Of 91 patients, 39 were in stable condition (group A) and 52 with COPD exacerbation (group B). Group B patients presented with PH and left ventricular diastolic dysfunction more often than group A patients. One of two fulfilled the criteria for possible/likely PH. The incidence of likely/possible PH was significantly higher in group B. Nineteen group B patients with likely/possible PH underwent RHC, and PH was confirmed in 15 cases and in 73.3% was associated with left heart disease. The presence of possible/likely PH was associated with a statistically significant increase in mortality compared to those with unlikely PH. CONCLUSIONS:The use of echocardiographic criteria for the presence of PH is adequate for the screening of COPD patients. Patients with acute exacerbation of COPD and possible/likely PH demonstrate worse mortality compared to patients unlikely to have PH.