Is Routine Ultrasound Examination of the Gallbladder Justified in Critical Care Patients?

Objective. We evaluated whether routine ultrasound examination may illustrate gallbladder abnormalities, including acute acalculous cholecystitis (AAC) in the intensive care unit (ICU). Patients and Methods. Ultrasound monitoring of the GB was performed by two blinded radiologists in mechanically ventilated patients irrespective of clinical and laboratory findings. We evaluated major (gallbladder wall thickening and edema, sonographic Murphy's sign, pericholecystic fluid) and minor (gallbladder distention and sludge) ultrasound criteria. Measurements and Results. We included 53 patients (42 males; mean age 57.6 ± 2.8 years; APACHE II score 21.3 ± 0.9; mean ICU stay 35.9 ± 4.8 days). Twenty-five patients (47.2%) exhibited at least one abnormal imaging finding, while only six out of them had hepatic dysfunction. No correlation existed between liver biochemistry and ultrasound results in the total population. Three male patients (5.7%), on the grounds of unexplained sepsis, were diagnosed with AAC as incited by ultrasound, and surgical intervention was lifesaving. Patients who exhibited ≥2 ultrasound findings (30.2%) were managed successfully under the guidance of evolving ultrasound, clinical, and laboratory findings. Conclusions. Ultrasound gallbladder monitoring guided lifesaving surgical treatment in 3 cases of AAC; however, its routine application is questionable and still entails high levels of clinical suspicion

Immune response in healthy volunteers after acute exposure to alcohol

Introduction: Acute Alcohol exposure is related to increased susceptibility to infections.The purpose of the study was to investigate the effect of acute exposure to alcohol on immune response, via the pro- and anti-inflammatory cytokine production, in an ex-vivo model of whole blood stimulation with lipopolysacharide (LPS). Methods: Whole blood was taken from healthy volunteers and was placed in tubes containing EDTA and immediately transferred to the lab. Whole blood samples were divided in 14 groups: the control group (without any intervention), the LPS group (with LPS alone), and 12 alcohol groups with (6 groups) and without LPS stimulation (6 groups) using six different doses of alcohol (final concentrations 5‚ 12.5‚ 25‚ 50‚ 100 and 200mM). Blood samples were diluted 1:10 in RPMI 1640 culture medium (100 μl whole blood added in 900 μl RPMI 1640). LPS (500 pg) was added after pretreatment with alcohol for 10 minutes according to the study protocol. After incubation period of 4 hours at 37°C, samples were centrifuged (3.000 rpm, 5 minutes, r.t.). Culture supernatants were collected and stored at –80°C until measurements. TNFa, ΙL-6, ΙL-10, sTNFR Ι and sTNFR ΙΙ levels (pg/ml) were determined in culture supernatant using the ELISA method.Results: We studied 24 healthy male volunteers aged 36.5 ± 1.4 (X ± SEM). Alcohol had no effect on cytokine production when incubated with whole blood alone. TNF-α, IL-6 and IL-10 were significantly increased after LPS stimulation, compared to controls. Alcohol had no effect on IL-6 production after LPS challenge, but significantly decreased TNF-α and IL-10 production in the presence of LPS challenge at 25mM to 200mM, in a dose dependent manner, compared to the LPS group. Alcohol had no effect on sTNFR I production when incubated with or without LPS. Alcohol significantly increased sTNFR II levels after LPS stimulation, compared to the control group. Alcohol, when incubated with whole blood alone at lower doses (<50mM), decreased sTNFR II levels, but an increase in sTNFR II levels was observed at the higher doses of 100 and 200mM of alcohol, compared to LPS stimulation, which was statistically significant compared to the costimulated samples with both alcohol, at lower doses, and LPS ex vivo.Conclusions: TNF-α and IL-10 were significantly decreased after acute alcohol exposure, in a dose depended manner, in a model of whole blood stimulation with LPS ex-vivo. Our observations indicate a suppressive effect of alcohol on both pro-inflammatory and anti-inflammatory responses. It was also indicated, that alcohol has a differential effect on sTNFR II production of whole blood in either the presence or the absence of LPS challenge ex-vivo, depending on the alcohol concentration.Εισαγωγή: Η οξεία έκθεση στην αλκοόλη σχετίζεται με αύξηση της επίπτωσης των λοιμώξεων. Σκοπός της μελέτης: ήταν η διερεύνηση της ανοσιακής απόκρισης στην οξεία έκθεση στην αλκοόλη, μέσω της παραγωγής προ- και αντι-φλεγμονωδών κυτταροκινών, μετά διέγερση ολικού αίματος με LPS ex-vivo.Μέθοδος: Τα δείγματα ολικού αίματος ελήφθησαν από υγιείς εθελοντές, τοποθετήθηκαν σε σωληνάρια με EDTA και μεταφέρθηκαν άμεσα στο εργαστήριο. Τα δείγματα χωρίστηκαν σε 14 ομάδες: την ομάδα ελέγχου (καμία παρέμβαση), την ομάδα της LPS (προσθήκη μόνον LPS) και 12 ομάδες αλκοόλης με και χωρίς LPS, με προσθήκη έξι διαφορετικών δόσεων αλκοόλης (τελικές συγκεντρώσεις: 5‚ 12.5‚ 25‚ 50‚ 100 και 200mM). Tα ηπαρινισμένα δείγματα του ολικού αίματος αραιώθηκαν 1:10, σε καλλιεργητικό μέσο RPMI 1640 (100μl από το κάθε δείγμα αίματος προστέθηκαν σε 900 μl RPMI 1640). Έγινε προσθήκη LPS (500pg) μετά 10 λεπτά από την προσθήκη της αλκοόλης, σύμφωνα με το πρωτόκολλο της μελέτης. Ακολούθησε επώαση των δειγμάτων για 4 ώρες στους 37° C. Στη συνέχεια έγινε φυγοκέντρηση (3.000rpm για 5min σε Θ.Δ.) και επακολούθησε διαχωρισμός του υπερκείμενου ορού, που διατηρήθηκε στους -80° C μέχρι να γίνουν οι μετρήσεις. Στο υπερκείμενο του αίματος των δειγμάτων προσδιορίστηκαν οι συγκεντρώσεις (pg/ml) των: TNF-a, ΙL-6, ΙL-10, sTNFR Ι και sTNFR ΙΙ, με τη μέθοδο ELISA.Αποτελέσματα: Μελετήθηκαν 24 υγιείς άνδρες εθελοντές ηλικίας 36.5 ± 1.4 (X ± SEM). Η αλκοόλη από μόνη της δεν είχε καμία επίδραση στην παραγωγή κυτταροκινών. Τα επίπεδα του TNF-α, της IL-6 και της IL-10 αυξήθηκαν σημαντικά μετά από διέγερση με LPS, συγκριτικά με την ομάδα ελέγχου. Η προσθήκη αλκοόλης δεν επηρέασε την παραγωγή της IL-6 μετά από διέγερση με LPS. Προκάλεσε όμως δοσοεξαρτώμενη μείωση της παραγωγής του TNF-α και της IL-10 σε συγκεντρώσεις 25mM έως 200mM σε σχέση με τη διέγερση με LPS. Η αλκοόλη δεν είχε επίδραση στην παραγωγή του sTNFR I με ή χωρίς διέγερση με LPS. Η διέγερση με LPS ex-vivo προκάλεσε στατιστικά σημαντική αύξηση των επιπέδων του sTNFR II, συγκριτικά με την ομάδα ελέγχου. Η αλκοόλη σε μικρές συγκεντρώσεις(<50mM) φάνηκε να προκαλεί μείωση των επιπέδων του sTNFR II. Αύξηση των επιπέδων του sTNFR II παρατηρήθηκε σε μεγαλύτερες συγκεντρώσεις αλκοόλης, που ήταν στατιστικά σημαντική σε συγκεντρώσεις αλκοόλης 100mM και 200mM μετά από διέγερση με LPS ex vivo συγκριτικά με τα δείγματα, που έγινε συνδιέγερση με μικρές συγκεντρώσεις αλκοόλης και LPS. Συμπεράσματα: Η οξεία έκθεση στην αλκοόλη προκάλεσε με δοσοεξαρτώμενο τρόπο στατιστικά σημαντική μείωση της παραγωγής TNF-α και IL-10 στο ολικό αίμα μετά διέγερση με LPS ex-vivo. Οι παρατηρήσεις μας δείχνουν ότι η αλκοόλη διαθέτει κατασταλτική δράση τόσο στην προφλεγμονώδη όσο και στην αντιφλεγμονώδη απόκριση. Επίσης, διαπιστώθηκε ότι η αλκοόλη έχει διαφορική δράση στην παραγωγή των sTNFR II στο ολικό αίμα με ή χωρίς διέγερση με LPS ex-vivo, που εξαρτάται από τη συγκέντρωση της αλκοόλης

Evaluation of Bone Metabolism in Critically Ill Patients Using CTx and PINP

Background. Prolonged immobilization, nutritional and vitamin D deficiency, and specific drug administration may lead to significant bone resorption. Methods and Patients. We prospectively evaluated critically ill patients admitted to the ICU for at least 10 days. Demographics, APACHE II, SOFA scores, length of stay (LOS), and drug administration were recorded. Blood collections were performed at baseline and on a weekly basis for five consecutive weeks. Serum levels of PINP, β-CTx, iPTH, and 25(OH)vitamin D were measured at each time-point. Results. We enrolled 28 patients of mean age 67.4 ± 2.3 years, mean APACHE II 22.2 ± 0.9, SOFA 10.1 ± 0.6, and LOS 31.6 ± 5.7 days. Nineteen patients were receiving low molecular weight heparin, 17 nor-epinephrine and low dose hydrocortisone, 18 transfusions, and 3 phenytoin. 25(OH)vitamin D serum levels were very low in all patients at all time-points; iPTH serum levels were increased at baseline tending to normalize on 5th week; β-CTx serum levels were significantly increased compared to baseline on 2nd week (peak values), whereas PINP levels were increased significantly after the 4th week. Conclusions. Our data show that critically ill patients had a pattern of hypovitaminosis D, increased iPTH, hypocalcaemia, and BTMs compatible with altered bone metabolism

Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma

Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT 65MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving \u3b2-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of 65 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infection