A prospective study on endocrine function in patients with long-COVID symptoms.

OBJECTIVE: To investigate hormonal status in patients with long-COVID and explore the interrelationship between hormone levels and long-COVID symptoms. DESIGN: Prospective observational study. PARTICIPANTS: Patients who visited our long-COVID outpatients' clinic due to long-COVID symptoms from February 2021 to December 2022. MEASUREMENTS: Total triiodothyronine, free thyroxine, thyrotropin, thyroglobulin, anti-thyroperoxidase, and antithyroglobulin autoantibodies were measured for thyroid assessment. Other hormones measured were growth hormone, insulin-like growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), total testosterone, plasma insulin, and C-peptide. Blood glucose and glycosylated hemoglobin were also measured. To assess adrenal reserve, an ACTH stimulation test was performed. The fatigue assessment scale (FAS) was used to evaluate fatigue severity. RESULTS: Eighty-four adult patients were included. Overall, 40.5% of the patients had at least one endocrine disorder. These included prediabetes (21.4%), low DHEA-S (21.4%), subclinical hypothyroidism (3.6%), non-specific thyroid function abnormality (7.1%), thyroid autoimmunity (7.1%), low testosterone in males (6.6%), and low IGF-1 (3.6%). All patients had normal adrenal reserve. Long-COVID-19 symptoms were present in all patients and the most commonly reported symptom was fatigue (89.3%). The FAS score was higher than normal (≥ 22) in 42.8% of patients. There were no associations between patients' symptoms and hormone levels. Diabetic patients reported confusion (p = 0.020) and hair loss (p = 0.040) more often than non-diabetics. CONCLUSIONS: The evaluation of endocrine function 3 months after a positive SARS-CoV2 test revealed only subclinical syndromes. The vast majority of patients reported mainly fatigue, among other symptoms, which were unrelated, however, to endocrine function.

The Effects of a Cardiac Rehabilitation Program on Endothelial Progenitor Cells and Inflammatory Profile in Patients with Chronic Heart Failure of Different Severity.

Endothelial dysfunction and inflammation are common pathophysiological characteristics of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are recognized as useful markers of vascular damage and endothelial repair. The aim of this study was to investigate the effects of a cardiac rehabilitation program on EPCs and inflammatory profile in CHF patients of different severity. Forty-four patients with stable CHF underwent a 36-session cardiac rehabilitation program. They were separated into two different subgroups each time, according to the median peak VO2, predicted peak VO2, VE/VCO2 slope, and ejection fraction. EPCs, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 10 (IL-10), and vascular endothelial growth factor (VEGF) were measured. Flow cytometry was used for the quantification of EPCs. Mobilization of EPCs increased and the inflammatory profile improved within each severity group (p < 0.05) after the cardiac rehabilitation program, but there were no statistically significant differences between groups (p > 0.05). A 36-session cardiac rehabilitation program has similar beneficial effects on the mobilization of EPCs and on the inflammatory profile in patients with CHF of different severity.

Persistent Endothelial Lung Damage and Impaired Diffusion Capacity in Long COVID.

Since the beginning of the pandemic, both COVID-19-associated coagulopathy biomarkers and a plethora of endothelial biomarkers have been proposed and tested as prognostic tools of severity and mortality prediction. As the pandemic is gradually being controlled, attention is now focusing on the long-term sequelae of COVID-19. In the present study, we investigated the role of endothelial activation/dysfunction in long COVID syndrome. This observational study included 68 consecutive long COVID patients and a healthy age and sex-matched control group. In both groups, we measured 13 endothelial biomarkers. Moreover, in the long COVID patients, we evaluated fatigue and dyspnea severity, lung diffusion capacity (DLCO), and the 6-min walk (6MWT) test as measures of functional capacity. Our results showed that markers of endothelial activation/dysfunction were higher in long COVID patients, and that soluble intracellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) negatively correlated with lung diffusion and functional capacity (sICAM-1 vs. DLCO, r = -0.306, p = 0.018; vs. 6MWT, r = -0.263, p = 0.044; and sVCAM-1 vs. DLCO, r= -0.346, p = 0.008; vs. 6MWT, r = -0.504, p < 0.0001). In conclusion, evaluating endothelial biomarkers alongside clinical tests might yield more specific insights into the pathophysiological mechanisms of long COVID manifestations.

COMPARATIVE EVALUATION AND PROGNOSTIC UTILITY OF NEURONAL INJURY BIOMARKERS IN COVID-19 PATIENTS: A PROSPECTIVE STUDY.

ABSTRACT: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus.

Testosterone, free, bioavailable and total, in patients with COVID-19.

BACKGROUND: Low testosterone (mainly total testosterone [TTe]) has been noted in patients with COVID-19. Calculated free testosterone (FTe) and bioavailable testosterone (BavTe) may reflect more accurately this hormone's levels. In this study, we sought to assess TTe, FTe as well as BavTe in male patients with COVID-19. METHODS: Sera were collected upon admission from 65 men (10 in the intensive care units [ICU] and 55 in the wards) with polymerase chain reaction - proven COVID-19. A group of age-matched COVID-19-negative men (N.=29) hospitalized in general medical wards served as controls. Age, Body Mass Index (BMI) and 28-day mortality were noted. Measurements included TTe, sex-hormone binding globulin, albumin (the latter two for calculating FTe and BavTe) and laboratory markers of inflammation (white blood cell count [WBC], D-Dimers [D-D], lactate dehydrogenase [LDH], ferritin [Fer] and C-reactive protein [CRP]). RESULTS: Profoundly low TTe, FTe and BavTe were noted in most patients, and were associated with disease severity/outcome (being the lowest in COVID-19 patients in the ICU and overall being lower in non-survivors; analysis of covariance P<0.05). Pearson's correlations for logTe, logFTe or logBavTe versus WBC, D-D, LDH, Ferr or CRP were negative, ranging from -0.403 to -0.293 (P=0.009 to 0.014). CONCLUSIONS: TTe, FTe and BavTe are prone to be low in patients with COVID-19, are negatively associated with disease severity and may be considered to have prognostic value.

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Could Provide Better Accuracy Than Creatinine in Predicting Acute Kidney Injury Development in Critically Ill Patients.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002-1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Soluble Angiotensin Converting Enzyme 2 (ACE2) Is Upregulated and Soluble Endothelial Nitric Oxide Synthase (eNOS) Is Downregulated in COVID-19-induced Acute Respiratory Distress Syndrome (ARDS).

A damaged endothelium is an underlying condition of the many complications of COVID-19 patients. The increased mortality risk associated with diseases that have underlying endothelial dysfunction, such as acute respiratory distress syndrome (ARDS), suggests that endothelial (e) nitric oxide synthase (NOS)-derived nitric oxide could be an important defense mechanism. Additionally, intravenous recombinant angiotensin converting enzyme 2 (ACE2) was recently reported as an effective therapy in severe COVID-19, by blocking viral entry, and thus reducing lung injury. Very few studies exist on the prognostic value of endothelium-related protective molecules in severe COVID-19 disease. To this end, serum levels of eNOS, inducible (i) NOS, adrenomedullin (ADM), soluble (s) ACE2 levels, and serum (s) ACE activity were measured on hospital admission in 89 COVID-19 patients, hospitalized either in a ward or ICU, of whom 68 had ARDS, while 21 did not. In our cohort, the COVID-19-ARDS patients had considerably lower eNOS levels compared to the COVID-19 non-ARDS patients. On the other hand, sACE2 was significantly higher in the ARDS patients. iNOS, ADM and sACE activity did not differ. Our results might support the notion of two distinct defense mechanisms in COVID-19-derived ARDS; eNOS-derived nitric oxide could be one of them, while the dramatic rise in sACE2 may also represent an endogenous mechanism involved in severe COVID-19 complications, such as ARDS. These results could provide insight to therapeutical applications in COVID-19.

Antibody Response Following a Two-Dose mRNA Vaccination Regimen, in Health Care Workers of a Tertiary Hospital in Athens, Greece.

We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals and personnel working in COVID-19 clinics. Notably, individuals with a prior COVID-19 infection mounted a significantly higher antibody titer following the first dose than the rest of the population; the same was true for those working in COVID-19 clinics, even without history of previous infection.

Thyroid hormone alterations in critically and non-critically ill patients with SARS-CoV-2 infection.

OBJECTIVE: Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients. DESIGN: Cohort observational study. METHODS: We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism. RESULTS: A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of negative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare. CONCLUSIONS: NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients.

Glycemia, Beta-Cell Function and Sensitivity to Insulin in Mildly to Critically Ill Covid-19 Patients.

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.

Serum Coenzyme Q10 Levels are Decreased in Critically-Ill Septic Patients: Results From a Preliminary Study.

BACKGROUND: The increased oxidative stress resulting from the inflammatory responses in sepsis initiates changes in mitochondrial function which may result in organ damage, the most common cause of death in the intensive care unit (ICU). Deficiency of coenzyme Q10 (CoQ10), a key cofactor in the mitochondrial respiratory chain, could potentially disturb mitochondrial bioenergetics and oxidative stress, and may serve as a biomarker of mitochondrial dysfunction. Hence, we aimed to investigate in initially non-septic patients whether CoQ10 levels are decreased in sepsis and septic shock compared to ICU admission, and to evaluate its associations with severity scores, inflammatory biomarkers, and ICU outcomes. METHODS: Observational retrospective analysis on 86 mechanically-ventilated, initially non-septic, ICU patients. CoQ10 was sequentially measured on ICU admission, sepsis, septic shock or at ICU discharge. CoQ10 was additionally measured in 25 healthy controls. Inflammatory biomarkers were determined at baseline and sepsis. RESULTS: On admission, ICU patients who developed sepsis had lower CoQ10 levels compared to healthy controls (0.89 vs. 1.04 µg/ml, p < 0.05), while at sepsis and septic shock CoQ10 levels decreased further (0.63 µg/ml; p < 0.001 and 0.42 µg/ml; p < 0.0001, respectively, from admission). In ICU patients who did not develop sepsis, admission CoQ10 levels were also lower than healthy subjects (0.81 µg/ml; p < 0.001) and were maintained at the same levels until discharge. CONCLUSION: CoQ10 levels in critically-ill patients are low on ICU admission compared to healthy controls and exhibit a further decrease in sepsis and septic shock. These results suggest that sepsis severity leads to CoQ10 depletion.

Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort.

We aimed to examine whether low intensive care unit (ICU) admission 25-hydroxyvitamin D (25(OH)D) levels are associated with worse outcomes of COVID-19 pneumonia. This was a prospective observational study of SARS-CoV2 positive critically ill patients treated in a multidisciplinary ICU. Thirty (30) Greek patients were included, in whom 25(OH)D was measured on ICU admission. Eighty (80%) percent of patients had vitamin D deficiency, and the remaining insufficiency. Based on 25(OH)D levels, patients were stratified in two groups: higher and lower than the median value of the cohort (15.2 ng/mL). The two groups did not differ in their demographic or clinical characteristics. All patients who died within 28 days belonged to the low vitamin D group. Survival analysis showed that the low vitamin D group had a higher 28-day survival absence probability (log-rank test, p = 0.01). Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors. When the cohort was divided at the median 25(OH)D value, the low vitamin D group had an increased risk of 28-day mortality. It seems plausible, therefore, that low 25(OH)D levels may predispose COVID-19 patients to an increased 28-day mortality risk.

Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19.

INTRODUCTION: Greece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95% CI 0.06-0.26). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in a nosocomial setting and assess potential risk factors. METHODS: HCWs from two hospitals participated in the study. Hospital-1 was a tertiary university affiliated center, involved in the care of COVID-19 patients while hospital-2 was a tertiary specialized cardiac surgery center not involved in the care of these patients. A validated, CE, rapid, IgM/IgG antibody point-of-care test was used. Comparative performance with a reference globally available assay was assessed. RESULTS: 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.26% (95% CI 0.43, 3.26) overall and 0.53% (95% CI 0.06, 2.78) and 2.70% (95% CI 0.57, 9.19) in hospital-1 and hospital-2, respectively although the study was underpowered to detect statistically significant differences. The overall, hospital-1, and hospital-2 seroprevalence was 10, 4 and 22 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals. CONCLUSIONS: These data have implications for the preparedness of a second wave of COVID-19 epidemic, given the low burden of SARS-CoV-2 infection rate, in concordance with national projections.

Clinical Study of Hyperglycemia and SARS-CoV-2 Infection in Intensive Care Unit Patients.

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.

Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis.

Increasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P = 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P = 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P = 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P = 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. NCT00297674.).

Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response*.

OBJECTIVES: To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release. DESIGN: Prospective study in patients with septic shock treated with low doses of hydrocortisone. SETTING: ICUs and general wards. PATIENTS: Over a 2-year period, 170 patients with septic shock treated with low doses of hydrocortisone were enrolled. Blood was sampled from 34 patients for isolation of peripheral blood mononuclear cells and cytokine stimulation before and 24 hours after the start of hydrocortisone. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After quartile analysis, patients were divided into those with early initiation of hydrocortisone (< 9 hr after vasopressors, n = 46) and those with late initiation of hydrocortisone (> 9 hr after vasopressors, n = 124). After adjusting for disease severity and type of infection, a protective effect of early hydrocortisone administration against unfavorable outcome was found (hazard ratio, 0.20; p = 0.012). Time of discontinuation of vasopressors was earlier among patients with initiation of hydrocortisone within 9 hours. Production of tumor necrosis factor-α was lower among patients who had had hydrocortisone early. CONCLUSIONS: In patients receiving hydrocortisone for septic shock, early initiation of treatment was associated with improved survival. This treatment was also associated with attenuated stimulation of tumor necrosis factor-α.

Risk factors for carbapenem-resistant Gram-negative bacteremia in intensive care unit patients.

PURPOSE: Carbapenem-resistant (CR) Gram-negative pathogens have increased substantially. This study was performed to identify the risk factors for development of CR Gram-negative bacteremia (GNB) in intensive care unit (ICU) patients. METHODS: Prospective study; risk factors for development of CR-GNB were investigated using two groups of case patients: the first group consisted of patients who acquired carbapenem susceptible (CS) GNB and the second group included patients with CR-GNB. Both case groups were compared to a shared control group defined as patients without bacteremia, hospitalized in the ICU during the same period. RESULTS: Eighty-five patients with CR- and 84 patients with CS-GNB were compared to 630 control patients, without bacteremia. Presence of VAP (OR 7.59, 95 % CI 4.54-12.69, p < 0.001) and additional intravascular devices (OR 3.69, 95 % CI 2.20-6.20, p < 0.001) were independently associated with CR-GNB. Presence of VAP (OR 2.93, 95 % CI 1.74-4.93, p < 0.001), presence of additional intravascular devices (OR 2.10, 95 % CI 1.23-3.60, p = 0.007) and SOFA score on ICU admission (OR 1.11, 95 % CI 1.03-1.20, p = 0.006) were independently associated with CS-GNB. The duration of exposure to carbapenems (OR 1.079, 95 % CI 1.022-1.139, p = 0.006) and colistin (OR 1.113, 95 % CI 1.046-1.184, p = 0.001) were independent risk factors for acquisition of CR-GNB. When the source of bacteremia was other than VAP, previous administration of carbapenems was the only factor related with the development of CR-GNB (OR 1.086, 95 % CI 1.003-1.177, p = 0.042). CONCLUSIONS: Among ICU patients, VAP development and the presence of additional intravascular devices were the major risk factors for CR-GNB. In the absence of VAP, prior use of carbapenems was the only factor independently related to carbapenem resistance.

Epidemiology, risk factors for and outcome of candidaemia among non-neutropenic patients in a Greek intensive care unit.

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case-control study was performed in a 25-bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non-albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09-7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48-25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12-1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00-2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59-0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.