Search

Objectives: Our aim was to assess blood utilization after implementation of a patient blood management (PBM) program in a Greek tertiary hospital. Methods: An electronic transfusion request form and a prospective audit of transfusion practice were implemented. After the one-year implementation period, a retrospective review was performed to assess transfusion practice in medical patients. Results: Pre-PBM, a total of 9478 RBC units were transfused (mean: 1.75 units per patient) compared with 9289 transfused units (mean: 1.57 units per patient) post-PBM. Regarding the post-PBM period, the mean hemoglobin (Hb) level of the 3099 medical patients without comorbidities transfused was 7.19 ± 0.79 gr/dL. Among them, 2065 (66.6%) had Hb levels &gt, 7.0 gr/dL, while 167 (5.3%) had Hb levels &gt, 8.0 gr/dL. In addition, 331 (25.3%) of the transfused patients with comorbidities had Hb &gt, 8.0 gr/dL. The Hb transfusion thresholds significantly differed across the clinics (p &lt, 0.001), while 21.8% of all medical non-bleeding patients received more than one RBC unit transfusion. Conclusion: A poor adherence with the restrictive transfusion threshold of 7.0 gr/dL was observed. The adoption of a less strict threshold might be a temporary step to allow physicians to become familiar with the program and be informed on the safety and advantages of the restrictive transfusion strategy.

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.

There is a complex and not fully elucidated association between pulmonary arterial hypertension (PAH) and coagulation disorders. The goal of this study was to evaluate platelet function, coagulation and fibrinolysis in PAH patients at diagnosis, before PAH-specific treatment initiation. We enrolled 20 healthy controls and 30 PAH patients (20 with connective tissue disease (CTD-PAH) and 10 idiopathic (iPAH)). None of the participants was on any antiplatelet or anticoagulation therapy. Blood samples from PAH patients were collected during the initial right heart catheterization. All subjects were assessed with platelet function analyzer-100 (PFA-100), epinephrine (Epi) and ADP-induced light transmission aggregometry (LTA), thromboelastometry (ROTEM) and endogenous thrombin potential (ETP). Our results showed that Epi and ADP-LTA values were significantly lower in newly diagnosed PAH patients compared to controls. Disaggregation was present in 73% of patients, a characteristic not seen in healthy individuals. In ROTEM assay, CT and CFT measurements were significantly higher and a angle lower compared to controls. ETP testing revealed significantly reduced outcomes in AUC, Cmax and Tmax. When CTD-PAH and iPAH patient groups were compared, iPAH ADP-LTA values were significantly decreased compared to CTD-PAH. In conclusion, newly diagnosed PAH patients presented with decreased platelet aggregation, clot propagation and thrombin generation, along with delayed initiation of the coagulation process. These hemostatic deficits could indicate an "exhaustion" of the coagulation process that could be caused by endothelial dysfunction and chronic activation of the procoagulant pathways. Further studies are warranted to confirm these laboratory findings and assess their potential clinical significance.

Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

Purpose Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. Methods Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS. Results H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8 % of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0 % of H1 carriers, 64.3 % of H3 carriers, and 65.2 % of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95 % confidence interval (CI) 0.16–0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95 % CI 0.37–1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39–1.70, p = 0.590) for H3 carriers. Conclusions Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.

The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 +/- 18 years; EF, 63% +/- 7%). The systolic (S) and early diastolic (E') velocity of the mitral annulus by TDI and the E/E' as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (P(O2)/Fi(O2)), sepsis, and ICU mortality were assessed. Systolic, E', and E/E' correlated with age, P(O2)/Fi(O2), lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E' (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-alpha, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P0.001), on day 1 (2,197 vs. 221 pg/mL; P0.001), and on day 2 (2,726 vs. 139 pg/mL; P0.001). Median values for TNF-alpha, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.

There is increasing discussion of a potential role for statins in the management of sepsis. A search of PubMed, Embase, Scopus and the Cochrane Library databases was performed by combining the terms ‘statins’, ‘infection’, ‘sepsis’, ‘bacteraemia’, ‘pneumonia’, and ‘ICU infections’. A total of 22 studies were retrieved, which included 177 260 people and compared clinical outcomes between 51 193 statin users and 126 067 non-statin users. Nineteen were cohort studies (seven prospective and 12 retrospective), two were retrospective case–control studies, and one was a randomized controlled study. Nine studies examined the use of statins in sepsis, four in community-acquired pneumonia (CAP), three in bacteraemia, and three in post-operative patients. Mortality data were presented in 15 studies; in ten, mortality was lower among statin users (three of six sepsis studies, five of six CAP studies, and two of three bacteraemia studies). In four studies, there was no difference in mortality (two of six sepsis studies, one of six CAP studies, and one of three bacteraemia studies) and in one study there was increased mortality among septic intensive-care unit patients receiving statins. Five of the nine studies that examined the risk of developing sepsis/infection as a primary outcome (six of nine sepsis studies and all studies in the postoperative setting) found a decreased risk among statin users, whereas the remaining studies found no difference. Irrespective of their design (matched vs. non-matched), the majority of the studies suggested that statins have a beneficial effect on the outcome of infection; however, their observational design does not allow us to draw firm conclusions. The clinical benefit of statin therapy in sepsis remains to be determined by ongoing randomized controlled trials.

BACKGROUND: Mechanical ventilation and administration of a high oxygen concentration are simultaneously used in the management of respiratory failure. We conducted this study to evaluate the effect of a high inspired oxygen concentration on ventilator-induced lung injury. METHODS: Forty sets of isolated/perfused rabbit lungs were randomized for 60 min of pressure-control ventilation at a plateau inspiratory pressure of 25 or 15 cm H(2)O and positive end-expiratory pressure of 3 cm H(2)O while receiving 100% or 21% O(2). The temperature, pH, and partial pressure of CO(2) in the perfusate were maintained the same in all groups (n = 10 for each group). The outcome measures used to assess lung injury included: the change in weight gain and ultrafiltration coefficient, the frequency of vascular failure, the histological lesions and the concentration of tumor necrosis factor-alpha and malondialdehyde in the bronchoalveolar lavage fluid. RESULTS: The two groups ventilated at the higher inspiratory pressure/tidal volume experienced greater weight gain and increases in the ultrafiltration coefficient, more frequently suffered vascular failure, and presented higher composite scores of histological damage than the two groups ventilated at the lower inspiratory pressure/tidal volume. Hyperoxia was not found to further increase any of the monitored markers of lung injury. No difference was noticed among the four experimental groups in the alveolar lavage fluid levels of tumor necrosis factor-alpha or malondialdehyde. CONCLUSIONS: These findings suggest that short-term administration of a high oxygen concentration is not a major determinant of ventilator-induced lung injury in this experimental model.

Purpose Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. Patients and methods Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. Results Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. Conclusions The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.

Objective. This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. Patients. Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. Outcome Measures. Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. Results. All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. Conclusions. Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.

Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda®)-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration. Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment. Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3–10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8–3.3%) (P

Objectives: Infections due to multidrug-resistant (MDR) Gram-negative pathogens in the ICU have prompted the use of colistin, an antibiotic forgotten for decades. The aim of this retrospective observational study was to record and present the emergence of colistin-resistant Klebsiella pneumoniae (CRKB) in a Greek ICU. Methods: In a new university tertiary hospital, the first patients admitted in the ICU were already colonized or infected with MDR pathogens, and this led to frequent colistin use as part of empirical or microbiologically documented therapy. Colistin resistance was defined as MIC >4 mg/L by the Etest method. All CRKB isolated in surveillance cultures or clinical specimens in the ICU during the period 2004-5 were recorded along with patients' characteristics. Results: Eighteen CRKB were isolated from 13 patients over a 16 month period, representing either colonizing or infective isolates. Patients' mean age was 70 years, with a mean APACHE II score at admission of 22. They all had a long hospitalization (median 69 days) and a long administration of colistin (median 27 days). Colistin-resistant isolates were implicated as pathogens in two bacteraemias, a ventilator-associated pneumonia and two soft tissue infections. Repetitive extragenic palindromic PCR identified six distinct clones, and horizontal transmission was also documented. Conclusions: Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.

Background: The course of serum cytokine levels in patients with postoperative systemic inflammatory response syndrome (SIRS) after major abdominal surgery remains currently unclear. Methods: Blood was sampled pre- and post-operatively and on days 1 and 2 in 40 patients undergoing major abdominal surgery. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL) -6, IL-8, and IL-10 were measured by the LINCOplex assay; those of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay. Results: Compared to their pre-operative values, sTREM-1 was elevated on day 2; TNFα on day 1; IL-6 and IL-10 post-operatively and on days 1 and 2; and IL-8 post-operatively and on day 1. The duration of operation correlated with TNFα and IL-10 at all sampling times, and with IL-6 post-operatively. There were no differences in cytokine concentrations between patients who exhibited post-operative complications and those who did not. IL-10/TNFα below 30 was found in all patients with complications (100%) and in 20 patients without complications (64.5%, p: 0.043). Conclusions: SIRS following major surgery is characterised by complex alterations in cytokine concentrations. The balance between TNFα and IL-10 seems to determine the occurrence of post-operative complications.

MD is a bedside in vivo sampling technique that permits continuous analysis of a patient's interstitial fluid chemistry. As the interstitial fluid bathes the cells, its composition reflects the local metabolic activity of those cells thus reflecting intracellular metabolic changes and disorders. The primary substances that provide information about metabolism are lactate, pyruvate, glycerol and glucose. In addition, blood metabolic alterations have been well characterized in severely ill patients. In vivo MD is performed by implanting a commercially available catheter that mimics a blood capillary at the site of interest.

Background A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis. Methods Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes. Results The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502). Conclusions Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.

The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. We assessed simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of ARDS patients.

Despite a documented decrease in sepsis-associated mortality in the developed world over the past decade, sepsis remains a major public health problem that claims more than 200,000 deaths each year in the United States (US) alone (1,2). The ongoing challenge to understand the complex biological mechanisms underlying susceptibility to infection and organ dysfunction and its associated mortality is complemented by the persistent need for high-quality clinical epidemiology studies that provide investigators and health-policy makers with updated data about disease patterns.

There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular at

Even though red blood cell (RBC) transfusion is a common intervention in the critical care setting, there is a paucity of data regarding its impact on tissue metabolism. The aim of this study was to explore the effect of RBC transfusion on microdialysis-assessed interstitial fluid metabolic parameters in septic patients.

Background Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis. Methods Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients. Results Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis. Conclusions Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes. This study aimed to describe the kinetics of MD-derived metabolites during the course of critical sepsis, to assess whether these metabolites are useful in grading sepsis severity, and to investigate their prognostic use. To this end, 54 mechanically ventilated septic patients were prospectively studied, out of which 39 had shock. Upon sepsis onset, an MD catheter was inserted into the subcutaneous adipose tissue of the upper thigh. Dialysate samples were analyzed for glucose, pyruvate, lactate, and glycerol. Sampling was performed six times per day for a maximum of 6 days. The daily mean values of MD measurements were calculated for each patient. Arterial blood was analyzed for glucose, lactate, and glycerol concomitantly with dialysate sampling. Blood glucose and tissue glucose levels along with lactate levels were high during the entire study period. Tissue pyruvate and glycerol were also raised, whereas the lactate-pyruvate ratio was preserved. At study entry, patients with septic shock had higher tissue lactate (3.3 vs. 1.9 mmol/L, P = 0.01) and glycerol (340 vs. 169 μmol/L, P = 0.04) levels compared with those without shock. Nonsurvivors had higher tissue lactate (P = 0.008), glycerol (P = 0.004), and pyruvate (P = 0.002) levels than survivors during the whole observation period. Logistic regression analysis showed that age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.004-1.150; P = 0.03), Sequential Organ Failure Assessment score on day 1 (OR, 1.550; 95% CI, 1.043-2.312; P = 0.03), and tissue glycerol on day 1 (OR, 1.007; 95% CI, 1.001-1.012; P = 0.01) predicted mortality independently. In conclusion, critical sepsis is characterized by high tissue lactate and pyruvate levels and a preserved lactate-pyruvate ratio, suggesting a nonischemic mechanism for raised blood lactate levels. Septic shock is associated with higher tissue lactate and glycerol levels compared with sepsis without shock. Elevated tissue lactate, pyruvate, and glycerol levels are related to poor clinical outcome, with the latter constituting an independent predictor.

Clostridium difficile infection is an emerging and often difficult-to-treat iatrogenic complication. Recent data suggest that tigecycline, a novel antibiotic with broad-spectrum antibacterial activity, can be used successfully to treat patients with severe Clostridium difficile infection. We report a 70-year-old man who developed severe Clostridium difficile infection, was admitted to the intensive care unit and eventually succumbed to complications of his illness despite receiving tigecycline for approximately three weeks in combination with vancomycin, metronidazole and intravenous immunoglobulin. Additionally, we discuss the unique challenges that emerged during tigecycline treatment, such as the development of Proteus mirabilis bacteraemia and of colonisation with Acinetobacter baumannii resistant to tigecycline. Finally, we review data on other cases reported in the medical literature. Even though tigecycline looks promising for the treatment of Clostridium difficile infection, we urge caution against its indiscriminate use for off label indications.

Background: Tuberculosis (TB) and malignancy represent global threats claiming millions of lives and inflicting formidable suffering worldwide. Surprisingly, the pathophysiological and practical implications of their co-existence have received little attention. Methods: Therefore, we sought to review the available literature on the field and identify data regarding the association between TB and malignancy in order to highlight the neglected aspects of this association and probably derive clinically useful information. We searched PubMed up to June 2008 for case reports, case series, non-comparative and comparative studies that were written in English and reported data on the occurrence of both TB infection and a neoplastic disorder in the same patient(s). The development of mycobacterial infections in patients with immunocompromized conditions is well known and was considered outside the scope of this review. Evidence synthesis: The synthesis of the available evidence enabled us to establish three different types of association between malignancy and TB: (i) the development of cancer on the background of a previous tuberculous infection; (ii) the concurrent existence of TB and malignancy in the same patient(s) or clinical specimen(s); and (iii) the diagnostic challenges arising from the multi-faceted presentations of these two disorders. Conclusions: We conclude that clinicians need to be aware of the protean manifestations of TB and cancer and maintain a high index of suspicion for simultaneous and/or misleading presentations. In addition, further research is required to determine if a tuberculous infection, being similar to other chronic infections and inflammatory conditions, may facilitate carcinogenesis.

Monitoring of central venous oxygen saturation (ScvO2) is considered comparable with mixed venous oxygen saturation (SvO2) in the initial resuscitation phase of septic shock. Our aim was to assess their agreement in septic shock in the intensive care unit setting and the effect of a potential difference in a computed parameter, namely, oxygen consumption (VO2). In addition, we sought for a central venous to pulmonary artery (PA) lactate gradient. We enrolled 37 patients with septic shock who were receiving noradrenaline infusions, and their attending physicians had placed a PA catheter for fluid management. Blood samples were drawn in succession from the superior vena cava, right atrium (RA), right ventricle, and PA. Hemodynamic and treatment parameters were monitored, and data were compared by correlation and Bland-Altman analysis. Mixed venous oxygen saturation was lower than ScvO2 (70.2% +/- 11.4% vs. 78.6% +/- 10.2%; P < 0.001), with a bias of -8.45% and 95% limits of agreement ranging from -20.23% to 3.33%. This difference correlated significantly to the noradrenaline infusion rate and the oxygen consumption and extraction ratio. These lower SvO2 values resulted in computed VO2v higher than the VO2cv (P < 0.001), with a bias of 104.97 mL min(-1) and 95% limits of agreement from -4.12 to 214.07 mL min(-1). Finally, lactate concentration was higher in the superior vena cava and RA than in the PA (2.42 +/- 3.15 and 2.35 +/- 3.16 vs. 2.17 +/- 3.19 mM; P < 0.01 for both comparisons). Thus, our data suggest that ScvO2 and SvO2 are not equivalent in intensive care unit patients with septic shock. Additionally, the substitution of ScvO2 for SvO2 in the calculation of VO2 produces unacceptably large errors. Finally, the decrease in lactate between RA and PA may support the hypothesis that the mixing of RA and coronary sinus blood is at least partially responsible for the difference between ScvO2 and SvO2.

Summary: Background: Acute respiratory tract infections (RTIs) are an important cause of morbidity in the military setting. Respiratory viruses are the most frequently implicated pathogens, especially adenovirus and respiratory syncytial virus. We performed this study to investigate the role of factors such as obesity, cigarette smoking, and educational level on the development of respiratory tract infections in a military recruit setting. Methods: A cohort of 472 military recruits was prospectively followed up for the basic training period of 3 weeks. Symptoms of infections were monitored during this period. Results: Eighty-four of 472 recruits (17.8%) were diagnosed with infection; 55 (65.5%) with upper RTI (mainly rhinitis), 23 (27.4%) with flu-like syndrome, and 6 (7.1%) with tonsillitis. There was no association between age, BMI, or smoking status and symptomatic RTI (p > 0.05). Conclusions: Occurrence of respiratory tract infections in military recruits is common, at least in some populations and settings. We did not find an association between risk factors such as BMI and smoking and symptomatic respiratory infection in our population, a result that may be associated with the limited power of this study. Keywords: Age, Army, BMI, Bronchitis, Common cold, Influenza, Obesity, Pharyngitis, Respiratory tract infection, Smoking, Tonsillitis

Purpose. To determine the inter-relationships between cytokine levels and physiological scores in predicting outcome in unselected, critically ill patients. Methods. To this end, 127 patients (96 men), having a mean ± SD age of 45 ± 20 years, with a wide range in admission diagnoses (medical, surgical, and multiple trauma patients) were prospectively investigated. Severity of critical illness and organ dysfunction were graded by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, respectively. Blood samples were drawn on admission in the ICU to determine pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10. The main outcome measure was 28-day mortality. Results. Overall, 88 patients survived and 39 patients died. Univariate logistic regression analysis showed that SOFA, APACHE II, IL-8, IL-6, and IL-10 on admission in the ICU were related to mortality. Multiple logistic regression analysis in the entire cohort of critically ill patients revealed that SOFA (OR = 1.341, p p = 0.01) constituted independent outcome predictors. receiver operator characteristics curve analysis showed that SOFA, APACHE II, and IL-6 had the highest area under the curve values. IL-6 correlated with APACHE II ( r s = 0.44, p r s = 0.40, p Conclusions. In mixed ICU patients cytokine concentrations on admission in the ICU represent independent outcome predictors in the presence of disease severity scores.

An evaluation of a recent study by MacLaren R, Reynolds PM, Allen RR et al: Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014, 174:564-574.

Background The prevalence of hepatitis B virus infection in Greece has been decreasing over the last decades. However, recent epidemiological data are lacking. Methods We studied 1,840 Army recruits from 05/2004 until 10/2005, and performed serological testing for HBsAg, anti-HBsAg, and anti-HBcAg. We also examined their association with several factors, including age, residential area, socioeconomic class, and educational level. Results Mean age (± SD) of the recruits was 20.5 (± 2.1) years. Antibodies to HBV core antigen [anti-HBcAg (+)] were found in 31 (1.68%) of 1,840 participants. Only 6 (0.32%) were HBsAg (+)/anti-HBsAg (-)/anti-HBcAg (+), while 21 (1.14%) were HBsAg (-)/anti-HBsAg (+)/anti-HBcAg (+), and 4 (0.22%) were HBsAg (-)/anti-HBsAg (-)/anti-HBcAg (+). Overall, 1,144 recruits (62.17%) had antibodies against HBsAg [HBsAg (-)/anti-HBsAg (+)/anti-HBcAg (-)]; 665 recruits (36.14%) had undetectable anti-HBsAg levels. Multivariable analysis showed that younger age (OR: 0.87; 95% CI: 0.82–0.92) and advanced educational level (OR: 1.59; 95% CI: 1.32–1.93) were independently associated with serologic evidence suggestive of previous HBV vaccination. Conclusion We document a further decline of the prevalence of chronic HBV infection among Greek military recruits, a fact that may support the effectiveness of the ongoing immunization programme.

We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.

We conducted a case-control study to identify risk factors associated with the isolation of Pseudomonas aeruginosa strains susceptible only to polymyxin from blood by comparing data between 16 patients with blood isolates that were susceptible only to polymyxins and 40 patients with blood isolates that were susceptible to carbapenems. The multivariable analysis showed that exposure to carbapenems was associated with the development of P. aeruginosa bacteremia susceptible only to polymyxin (odds ratio, 9.0; 95% confidence interval, 2.4 to 34.3; P = 0.001).

Background Tuberculosis (TB) remains one of the leading causes of death among infectious diseases worldwide. Despite its low incidence rates in countries of Western Europe and North America, the resurgence of TB in Eastern Europe and the increased immigration from high-incidence countries imply that extreme vigilance is required in order to detect early, treat, and isolate all new cases. In this study, we analyzed the prevalence and predictors of tuberculin skin testing positivity in Hellenic Army recruits. Methods The study population consisted of 953 Greek military recruits enlisted inthe Army during the period from November 2005 toFebruary 2006. Tuberculin skin testing was performed on all study subjects upon enrollment, according to the routine procedures. A tuberculin skin test reaction size >15 mm was considered positive for all study participants. Epidemiological data regarding age, repatriation status, geographic area of residence, smoking habits, and parental occupation were collected by means of personal interviews. In addition, body weight, height, and body mass index were measured. Results The mean age of the studied subjects (± SD) was 23.5 (± 6.4) years. The overall prevalence of tuberculin positivity was 3.9% (37/953), and bivariable analysis showed that it was associated with lower weight (p = 0.047) and repatriation status (p < 0.001). Tuberculin skin testing was positive in 2.6% of natives (24/900) and 24.5% of repatriates (13/53). A backward, stepwise multivariable logistic regression model showed that only repatriation status was independently associated with tuberculin positivity (p < 0.001; odds ratio [OR]: 14.1; 95% confidence interval [CI]: 6.5–30.3). Conclusion While the incidence of tuberculosis in the native Greek population is low, and comparable to other Western European countries, the extremely high tuberculin positivity in repatriated persons underscores the importance of actively screening for TB in order to promptly identify, isolate, and treat cases of active and latent infection.

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a chronic, relapsing, inflammatory condition with skin and osteoarticular manifestations. Its etiology remains unclear, and various treatment regimens with steroids and nonsteroidal antiinflammatory drugs frequently fail to control the disease, while exposing patients to the side effects of these drugs. Because the SAPHO syndrome manifests as a destructive inflammatory bone disease, use of bisphosphonates that possess antiosteoclastic and probably antiinflammatory properties has been suggested to be helpful. To our knowledge, this is the first reported case of successful treatment with zoledronic acid of SAPHO syndrome that was resistant to conventional treatment.

To the Editor, Nasogastric tube (NGT) insertion is a procedure performed routinely in critical care settings. However, NGT placement often proves to be a daunting task, especially in the setting of anesthetized/uncooperative patients with anatomic distortion (i.e., patients with cervical spine instability and/or restricted neck movement) and an endotracheal tube (ETT) already in situ for airway protection and support of the respiratory system. In fact, serious complications secondary to NGT placement appear often in the literature. Therefore, NGT insertion may be a complex procedure that requires skill, experience, and the ability to improvise if it does not proceed smoothly. A 63-year-old male patient, who was sedated and mechanically ventilated in our intensive care unit, had a hard cervical collar in place after sustaining severe traumatic brain injury, cervical spine fracture, and multiple long bone fractures in a motor vehicle accident. The NGT was unintentionally removed during routine patient care, and despite many gentle and prolonged attempts, the on-call physicians’ efforts to re-insert the NGT were unsuccessful. The presence of the cervical collar created poor laryngoscopic views, even with the left molar approach, and the patient’s cervical spine injury did not allow maneuvres that could facilitate NGT insertion, such as neck flexion, turning the head laterally, lateral neck pressure, and forward displacement of the larynx. To this end, a number of techniques to advance the NGT were attempted without success, including blind insertion plus a combination of direct laryngoscopy and use of Magill forceps, placement of fingers in the posterior pharynx to guide the NGT tip downward, deflation of the ETT cuff, and use of a frozen NGT. Finally, a 9.5-mm internal diameter ETT (‘‘conduit’’ ETT) was placed in the oropharynx and—under direct laryngoscopy—was continually kept in contact with the posterior pharyngeal wall and behind the ETT already in place while simultaneously being advanced gently and as far as possible into the esophagus. A well-lubricated 14-Fr NGT was threaded into the ‘‘conduit’’ ETT and was advanced into the full length of the stomach without difficulty during the first attempt. Afterward, the ‘‘conduit’’ ETT was withdrawn and the NGT was pulled back, positioned at the appropriate length, and fastened in the usual way. It is worth noting that no change of head or neck position, no ETT cuff deflation, and no involvement of an assistant were necessary during this alternative mode of NGT insertion. The only technical requirement was to ensure that the ‘‘conduit’’ ETT diameter could accommodate the NGT, including its funnel-shaped proximal end. We did not determine fibreoptically the point where the NGT met resistance and was successfully bypassed by the ‘‘conduit’’ ETT. However, it has been previously shown that the most common sites of resistance at the laryngeal level are the piriform sinuses and the arytenoid cartilages. In conclusion, the use of an ETT as an introducer can facilitate NGT insertion in difficult settings. This alternative mode of NGT insertion is easy, inexpensive, and widely available in the operating room and the intensive care unit. In our view, it is worth considering this blind approach before the physician resorts to other techniques (i.e., videolaryngoscopy) that are either more expensive or that necessitate the involvement of additional equipment. P. Kopterides, MD (&) C. Papageorgiou, MD G. Dimopoulos, MD A. Armaganidis, MD 2nd Critical Care Department, ‘‘Attiko’’ University Hospital, 1 Rimini Str., Haidari, Athens, Greece e-mail: petkop@ath.forthnet.gr

Introduction Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury. Methods Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF. Results High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation. Conclusions Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.

In the critical care setting, blood lactate (BL) concentration is measured to assess - albeit indirectly - tissue oxygenation. In addition, serial BL measurements are clinically useful since a drop in BL is a good prognostic finding, whereas persistent BL elevation portends poor outcome. Microdialysis (MD) enables direct monitoring of tissue metabolic changes. This study aimed to describe the dynamics of MD-assessed tissue lactate (TL) vis-a-vis BL in septic patients with and without shock.

Altintas and colleagues made a nice contribution on the field of acute lung injury (ALI), showing that pretreatment with simvastatin attenuates lung injury induced by oleic acid and endotoxin in mice.[1][1] Although the authors cited a few papers to state that “the available studies on statins in

Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.