Intensive Care Unit Mortality Trends during the First Two Years of the COVID-19 Pandemic in Greece: A Multi-Center Retrospective Study.

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.

Optimized Treatment of Nosocomial Peritonitis.

This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores the epidemiology, diagnosis, and management of NP, a significant contributor to the mortality of surgical patients worldwide. NP is, per definition, a hospital-acquired condition and a consequence of gastrointestinal surgery or a complication of other diseases. NP, one of the most prevalent causes of sepsis in surgical Intensive Care Units (ICUs), is often associated with multi-drug resistant (MDR) bacteria and high mortality rates. Early clinical suspicion and the utilization of various diagnostic tools like biomarkers and imaging are of great importance. Microbiology is often complex, with antimicrobial resistance escalating in many parts of the world. Fungal peritonitis and its risk factors, diagnostic hurdles, and effective management approaches are particularly relevant in patients with NP. Contemporary antimicrobial strategies for treating NP are discussed, including drug resistance challenges and empirical antibiotic regimens. The importance of source control in intra-abdominal infection management, including surgical and non-surgical interventions, is also emphasized. A deeper exploration into the role of open abdomen treatment as a potential option for selected patients is proposed, indicating an area for further investigation. This review underscores the need for more research to advance the best treatment strategies for NP.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Convolutional Neural Networks for Optical Discrimination Between Histological Types of Colorectal Polyps Based on White Light Endoscopic Images.

The objective of this study was to compare different convolutional neural networks (CNNs), as employed in a Python-produced deep learning process, used on white light images of colorectal polyps acquired during the process of a colonoscopy, in order to estimate the accuracy of the optical recognition of particular histologic types of polyps. The TensorFlow framework was used for Inception V3, ResNet50, DenseNet121, and NasNetLarge, which were trained with 924 images, drawn from 86 patients.

Factors Associated with Interruptions of Enteral Nutrition and the Impact on Macro- and Micronutrient Deficits in ICU Patients.

BACKGROUND AND AIM: Feeding interruptions in critical care patients are often unjustified. We aimed to determine the causes, duration, and frequency of enteral nutrition interruptions (ENIs) and to assess macronutrients and antioxidant deficits according to European Society of Parenteral Enteral Nutrition (ESPEN) guidelines. METHODS: We prospectively enrolled Intensive Care Unit (ICU) patients admitted for more than 48 h with an inability to orally eat from April to December 2019. The type of enteral nutrition, the number of calories administered, the time of feeding initiation, the reasons for delaying feeding, and the causes for ENI were recorded. RESULTS: 81 patients were enrolled, with a median duration of ENIs of 5.2 (3.4-7.4) hours/day. Gastric residual volume (GRV) monitoring-a highly controversial practice-was the most common cause of ENI (median duration 3 (2.3-3) hours/day). The mean energy intake was 1037 ± 281 kcal/day, while 60.5% of patients covered less than 65% of the total energy needs (1751 ± 295 kcal/day, according to mean Body Mass Index (BMI)). The median daily protein intake did not exceed 0.43 ± 0.3 gr/kg/day of the actual body weight (BW), whereas ESPEN recommends 1.3 gr/kg/day for adjusted BW (p < 0.001). The average administration of micronutrients and antioxidants (arginine, selenium, zinc, vitamins) was significantly less than the dietary reference intake (p < 0.01). CONCLUSION: ENIs lead to substantial caloric, protein, and antioxidant deficits.

Occupational Stress and Quality of Life among Health Professionals During the COVID-19 Pandemic.

Introduction: Healthcare professionals, due to the nature of their work, have always experienced occupational stress, depression and low quality of life, which have been aggravated during the COVID-19 pandemic. Aim: A large-scale cross-sectional descriptive correlational study aimed to investigate the impact of the COVID-19 pandemic on Greek healthcare professionals' psychological status and quality of life. Material and Methods: The study was conducted at "Attikon" General University Hospital and the 2nd Health Region in Athens, Greece. An assessment of anxiety and depression was carried out using the Zung's Self-Rating Anxiety and Depression Scale (SAS/SDS). To assess the participants' Quality of Life (QoL) the Short Form Survey-36 (SF-36) was used. Results: 147 healthcare professionals were enrolled in the study. 70.7% experienced normal stress levels, 23.8% mild, 4.8% moderate and 0.7% severe. Mild depression was experienced by 34.7%, moderate by 10.2% and severe by 1.4%, with a 53.7% showing no depressive symptoms. Women experienced higher levels of anxiety and depression (p=0.001 & 0.001 respectively), and were 5.4 times more at risk to develop anxiety [Odds Ratio (OR) 5.357, 95% Confidence Interval (CI), 1.95-14.72: p=0.001] and 3.4 depression (OR, 3.365, 95% CI, 1.59- 7.12: p=0.002). Nurses and other professionals experienced higher stress and depression levels (p=0.004 & 0.040 respectively) than doctors. Participants reporting more exhaustion exhibited higher anxiety and depression levels (p=0.001). Compared to the pre-COVID-19 era, women (p=0.001), other health professionals (p=0.001) and those experiencing more physical burnout during COVID-19 (p=0.005) reported worse physical health. Anxiety and depression were negatively correlated with most sub scales of SF-36 except social functioning and bodily pain (p=0.001). Conclusions: Healthcare professionals' QoL has been affected by the COVID-19 pandemic and they experience higher levels of anxiety and depression. There is a need to develop strategies to address the negative psychological impact of this pandemic on healthcare professionals.

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations.

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (p < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p < 0.001). The AUCTOS/TAC (0.96 (95% CI = 0.93-0.99)) was higher than AUCTAC (z = 20, p < 0.001) or AUCTOS (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.

Post-Traumatic Stress Disorder and Burnout in Healthcare Professionals During the SARS-CoV-2 Pandemic: a Cross-Sectional Study.

INTRODUCTION: Healthcare professionals who are directly involved in the diagnosis, treatment, and general care of patients with SARS-CoV-2 are at risk of developing adverse psychological reactions. A cross-sectional study of healthcare professionals aimed to determine the impact of the SARS-CoV-2 pandemic on the mental health of healthcare professionals in two of the largest referral hospitals in Athens, Greece. METHODS: The study was conducted in the two largest SARS-CoV-2 referral hospitals in Athens, Greece. An assessment and the interrelationship of post-traumatic stress disorder, using the Impact of Event Scale-Revised [IES-R]) and burnout, using the Maslach Burnout Inventory [MBI]) was carried out. RESULTS: A total of 162 subjects were enrolled in the study. Fifty-six (35%) had an IES-R score > 33, suggesting post-traumatic stress disorder. Forty-nine (30%) had an MBI score > 27. Seventy-five (46%) had a personal accomplishment score of < 33 and 46 (28%) had a depersonalization score >10. Stepwise backward logistic regression revealed that the only independent variable that was retained regarding the presence of post-traumatic stress disorder was the emotional exhaustion score of the MBI (at a cut-off of 24 in this scale, the 95% CI of the odds ratio for the presence of post-traumatic stress disorder was 1.077-1.173). CONCLUSIONS: In this sample of first-line Greek healthcare professionals against SARS-CoV-2, most of them were proven to be quite resilient to this challenge. One-third of them had post-traumatic stress disorder, which depended on their degree of emotional exhaustion. Healthcare professionals, as represented by this study, performed their duties without feeling helpless and developing adverse psychological reactions.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

A Severe COVID-19 Case Complicated by Right Atrium Thrombus.

BACKGROUND Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis. Effective anticoagulation therapy may play a dominant role in the management of severe COVID-19 cases. CASE REPORT A 73-year-old man with a 6-day history of fever up to 38.5°C, dyspnea, cough, and fatigue was diagnosed with COVID-19. He had a past medical history significant for hypertension and coronary artery bypass grafting. Two days after hospital admission, the patient developed acute respiratory failure, requiring intubation, mechanical ventilation, and transfer to the intensive care unit (ICU). He received treatment including antibiotics, hydroxychloroquine, tocilizumab, vasopressors, prone positioning, and anticoagulation with enoxaparin at a prophylactic dose. After a 15-day ICU stay, the patient was hemodynamically stable but still hypoxemic; a transthoracic echocardiogram at that time, followed by a transesophageal echocardiogram for better evaluation, revealed the presence of a right atrium thrombus without signs of acute right ventricular dilatation and impaired systolic function. Since the patient was hemodynamically stable, we decided to treat him with conventional anticoagulation under close monitoring for signs of hemodynamic deterioration; thus, the prophylactic dose of enoxaparin was replaced by therapeutic dosing, which was a key component of the patient's successful outcome. Over the next few days he showed significant clinical improvement. The follow-up transesophageal echocardiogram 3 weeks after effective therapeutic anticoagulation revealed no signs of right heart thrombus. CONCLUSIONS The presented COVID-19 case, one of the first reported cases with evidence of right heart thrombus by transesophageal echocardiography, highlights the central role of diagnostic imaging strategies and the importance of adequate anticoagulation therapy in the management of severe COVID-19 cases in the ICU.

Life-threatening antineutrophil cytoplasmic antibody-associated vasculitis after influenza A H1N1 infection requiring veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Antineutrophil cytoplasmic autoantibody-associated vasculitis is an immune-mediated necrotizing vasculitis, affecting small- and medium-sized vessels. CASE REPORT: A 22-year-old female patient with free medical history presented with life-threatening pulmonary hemorrhage due to antineutrophil cytoplasmic autoantibody-associated vasculitis, temporarily associated with influenza A H1N1 infection. Due to rapidly worsening respiratory failure, despite conventional management, veno-venous peripheral extracorporeal membrane oxygenation was initiated and continued for 26 days, with subsequent renal replacement therapy. DISCUSSION: We present a case of severe antineutrophil cytoplasmic autoantibody-associated pulmonary vasculitis, managed with veno-venous extracorporeal membrane oxygenation at the initial phase. Despite the significant challenges raised with the use of extracorporeal membrane oxygenation in pulmonary hemorrhage cases, extracorporeal membrane oxygenation may have a significant impact on outcome in this setting, by providing adequate time for a successful immunosuppressive treatment.

Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept.

Microdialysis-Assessed Adipose Tissue Metabolism, Circulating Cytokines and Outcome in Critical Illness.

Microdialysis (MD) can provide continuous information about tissue composition. To assess in critically ill patients adipose tissue metabolic patterns, the relationships between metabolic patterns and blood cytokine concentration associations of adipose tissue energy metabolism and clinical outcome we studied 203 mechanically ventilated general intensive care unit (ICU) patients. Upon ICU admission an MD catheter was inserted into the subcutaneous adipose tissue of the upper thigh to measure lactate (L), glucose, pyruvate (P), and glycerol. Serum concentrations of IL-10, IL-6, IL-8, and TNF-α were determined within 48 h from ICU admission. Mitochondrial dysfunction was defined as L/P ratio >30 and pyruvate ≥70 µmol/L, ischemia as L/P ratio >30 and pyruvate <70 µmol/L and no ischemia/no mitochondrial dysfunction (i.e. aerobic metabolism) was as L/P ratio ≤30. Metabolism was aerobic in 74% of patients. In 13% of patients there was biochemical evidence of ischemia and in 13% of patients of mitochondrial dysfunction. Mitochondrial dysfunction was associated with poor outcome. In conclusion, MD showed that about two thirds of critically ill patients have normal aerobic adipose tissue metabolism. Mitochondrial dysfunction was not common but was associated with poor outcome. Identifying subgroups of critically ill patients is crucial as different treatment strategies may improve survival.

Adipose Tissue Lactate Clearance but Not Blood Lactate Clearance Is Associated with Clinical Outcome in Sepsis or Septic Shock during the Post-Resuscitation Period.

No study has directly measured tissue lactate clearance in patients with sepsis during the post-resuscitation period. In this study we aimed to assess in ICU patients with sepsis (n = 32) or septic shock (n = 79)—during the post-resuscitation phase—the relative kinetics of blood/tissue lactate clearances and to examine whether these are associated with outcome. We measured serially—over a 48-h period—blood and adipose tissue interstitial fluid lactate levels (with microdialysis) and we calculated lactate clearance. Statistics included mixed model analysis, Friedman’s analysis of variance, Wilcoxon’s test, Mann-Whitney’s test, receiver operating characteristics curves and logistic regression. Forty patients died (28-day mortality rate = 28%). Tissue lactate clearance was higher compared to blood lactate clearance at 0⁻8, 0⁻12, 0⁻16, 0⁻20 and 0⁻24 h (all p < 0.05). Tissue lactate clearance was higher in survivors compared to non-survivors at 0⁻12, 0⁻20 and 0⁻24 h (all p = 0.02). APACHE II along with tissue lactate clearance <30% at 0⁻12, 0⁻20 and 0⁻24 h were independent outcome predictors. We did not find blood lactate clearance to be related to survival. Thus, in critically ill septic patients, elevated tissue (but not blood) lactate clearance, was associated with a favorable clinical outcome.

Dermatofibrosarcoma protuberans coexisting in a patient with a vascular malformation-a rare coincidence.

Dermatofibrosarcoma protuberans with fibrosarcomatous differentiation (DFSP-FS) is a rare soft tissue tumor with more aggressive behavior and it is not clear what causes this type of skin cancer. We describe the case of a 48-year-old woman who was born with a vascular malformation in the sternal region and presented suddenly with a soft tissue sarcoma (DFSP-FS) in the same territory. She was initially treated by embolization as the sarcoma was misdiagnosed but the tumor within 6 months seemed to be growing rapidly and reached a giant dimension with ulceration and required surgical intervention. The patient underwent a surgical removal of the mass but as the pathology report included a DFSP-FS with close margins,a second operation was required. A wide local excision was performed and reconstruction of defect by using bilateral pectoralis major muscle flaps and a full thickness skin graft from the abdominal wall. Post operatively the patient was treated with radiotherapy.

Microdialysis-Assessed Adipose Tissue Metabolism in Critically Ill Patients.

BACKGROUND: Microdialysis is a minimally invasive technique that allows direct in situ and in vivo sampling, studies and manipulations of the interstitial/extracellular fluid/space. It has been shown to be of use mainly in acute brain injury/neurocritical care. METHODS: Microdialysis has been used to study obesity, diabetes mellitus, inflammation and pharmacokinetics at the adipose tissue level. In critically ill patients (and particularly in those with sepsis or septic shock), within days to weeks, adipose tissue shows profound alterations; under such conditions, the implementation of microdialysis can provide researchers with interesting findings. RESULTS: The well-known association between lipolysis and cortisol has been verified at the tissue level with microdialysis. Specific metabolic aberrations in critically ill patients with septic shock have been noted in adipose tissue - assessed with microdialysis before becoming evident in the systemic circulation. Measurement of the lactate to pyruvate ratio in adipose tissue - also assessed with microdialysis - in patients with septic shock has prognostic value equal to that of universally accepted clinical severity scores. CONCLUSION: Microneedle arrays have been already used to assess interstitial fluid glucose. Possibly, the implementation of microneedle and lab-on-a-chip technology, might complement the current use of microdialysis in the study of the interstitial space/adipose tissue metabolism in health and disease.

Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.

INTRODUCTION: This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. METHODS: Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome. RESULTS: Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, p<0.001). Mean fluorescent intensity (MFI) levels of HSP70 and HSP90 on monocytes and polymorphonuclear cells were significantly higher in SIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (p<0.05 for all comparisons). There was no statistically significant difference between subgroups for levels of T-regulatory cells or relative copies of Suppressor of Cytokine Signalling 3 (SOCS3) proteins. In univariate models percent of CD14/HLA-DR was associated with mortality (OR: 1.8 95%CI 1.02-3.2, p=0.05), while in multivariate models after adjusting for CD14/HLA-DR only younger age and lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with increased chances of survival (beta -0.05, OR 0.9, 95% CI 0.9-0.99, p=0.038 for age and beta -0.11, OR 0.89, 95% CI 0.8-0.99, p=0.037 for APACHE II score). CONCLUSIONS: Significant associations with SIRS and sepsis were found for CD14/HLA-DR expression and monocyte and polymorphonuclear cell levels of HSP70 and 90. The role of these biomarkers in assessing the prognosis of sepsis needs to be further explored and validated in prospective studies.

Evidence of Subcutaneous Tissue Lipolysis Enhancement by Endogenous Cortisol in Critically Ill Patients Without Shock.

BACKGROUND/AIM: Cortisol is involved in in many aspects of adipose tissue metabolism. A positive association between plasma cortisol and lipolysis has been observed. Critically ill patients exhibit 'lipemia of sepsis'. The aim of the present study was to study, in septic ICU patients, adipose tissue lipolysis in relation to tissue cortisol using microdialysis (MD). PATIENTS AND METHODS: We studied 17 mechanically-ventilated patients (9 men; mean±SD age=63±19 years) with a diagnosis of severe sepsis. Upon ICU admission, an MD catheter was inserted under sterile conditions into the subcutaneous adipose tissue of the upper thigh. On days 2, 3 and 4, MD samples were collected six times per day for glycerol (used as an index of lipolysis) and tissue cortisol determinations. The mean of these six collections was used for analysis (normal values for adipose tissue glycerol <200 µmol/l). Statistics were carried-out with analysis of covariance (ANCOVA) and linear regression. RESULTS: More than half of the samplings (19/31) indicated accentuated lipolysis with above-normal MD glycerol levels. By ANCOVA, MD glycerol (log values) was associated with MD cortisol (log values) (p=0.012) and was not associated with age or day of sampling. Furthermore, MD glycerol (log values) was positively correlated to MD cortisol (log values) (r=0.490, p=0.012). DISCUSSION: Changes in interstitial/tissue cortisol may not be reflected in (total) plasma cortisol concentration. Thus, it is interesting that we observed, albeit weak, an association between tissue lipolysis (via MD glycerol levels) and MD cortisol, verifying (although modestly so) the well-known association between lipolysis and cortisol.

Esmolol: immunomodulator in pyelonephritis by Pseudomonas aeruginosa.

BACKGROUND: Based on previous animal studies showing promising immunomodulatory efficacy esmolol, a selective ß1-blocker, it was assumed that administration of esmolol in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa would prolong survival and modulate immune response. METHODS: Acute pyelonephritis was induced in 80 rabbits and assigned to eight groups receiving normal saline (controls), esmolol, amikacin, or both agents as pretreatment and as treatment. Blood was sampled for measurement of malondialdehyde and tumor necrosis factor alpha. Animals were followed up for survival, and after death quantitative tissue cultures were performed. The in vitro effect of esmolol on bacterial growth and on the oxidative burst of neutrophils of healthy controls and of sepsis patients was studied. RESULTS: Survival of pretreatment groups administered single esmolol or esmolol and amikacin was prolonged compared with that of controls (P = 0.018 and P = 0.014, respectively); likewise, survival of treatment groups administered single esmolol or both agents was prolonged compared with that of controls (P = 0.007 and P = 0.014, respectively). Circulating malondialdehyde was significantly lower in pretreated animals administered esmolol or esmolol and amikacin compared with that in controls and in treated animals administered both agents compared with in controls (P = 0.020). In these groups, the bacterial load of the lung was significantly lower compared with controls. Serum tumor necrosis factor alpha did not change. Amikacin was increased in serum of esmolol-treated animals at levels which inhibited the in vitro growth of the studied isolate. Esmolol did not modify the in vitro growth of P aeruginosa and the oxidative burst of neutrophils. CONCLUSIONS: It is concluded that esmolol prolonged survival after experimental infection by multidrug-resistant P aeruginosa. Survival benefit may be related with pleiotropic actions connected with modulation of pharmacokinetics and attenuation of inflammation.