Jasna Jevdjic

Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma

Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients.

Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

Immune Response in Severe Infection: Could Life-Saving Drugs Be Potentially Harmful?

Critically ill patients suffer a high rate of nosocomial infection with secondary sepsis being a common cause of death. Usage of antibiotics and catecholamines is often necessary, but it can compromise complex immune response to infection. This review explores influence of these life-saving drugs on host immune response to severe infection.

New aspects of sepsis pathophysiology in critically ill

Jos od doba Hipokrata koji je 400. godine pne prvi opisao sepsu, imunopatofiziologija ovog kompleksnog oboljenja ostaje kontroverzna tema koja je predmet mnogih istraživanja. I autori ovog opsteg pregleda posvetili su se u poslednjoj dekadi ovoj intrigantnoj oblasti i to sa razlictitih aspekata. Naime, proucavali smo disfunkciju razlicitih organa u sepsi (miokarda i pluca), kao i sindrom multiple organske disfunkcije (MODS), zatim imunsku kaskadu sepse i ulogu proi antiinflamatornih citokina, odnos infekcije i inflamacije, acidobazni status bolesnika sa sepsom i genski polimorfizam kod razlicitih medijatora i receptora od znacaja za težinu i ishod sepse . Svojim istraživanjima u protekllih 10 godina obuhvatili smo veoma veliki broj bolesnika sa traumom i ratnom povredom koje su se veoma cesto komplikovale sekundarnom sepsom, kao i sepsom druge etiologije a, takođe, ispitivali smo i skorove sepse kod razlicitih bolesnika.

Prognostic Value And Daily Trend Of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein And Lipopolysaccharide-Binding Protein In Critically Ill Patients: Reliable Predictors Of Outcome Or Not?

Summary Background: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6), neutrophil CD64 expression, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality. Methods: One hundred and two critically ill patients admitted to the intensive care unit of a tertiary university hospital were enrolled in this prospective study. Blood samples were collected on admission (day 1), days 2 and 3. Results: CD64 index was 1.6-fold higher on day 1 and 1.78-fold higher on day 2 in non-survivors (p<0.05). The area under the curve (AUC) for the CD64 index on day 1 for outcome was 0.727. At a cut-off level of 2.80 sensitivity was 75% and specificity was 65%. Patients with CD64 index level on day 1 higher than 2.80 had 2.4-fold higher probability of dying. Odds ratio is 2.40; 95% CI 0.60–9.67. Conclusions: CD64 index on day 1 is a fairly good predictor of outcome. AUCs for IL-6, CRP and LBP were < 0.55, suggesting these biomarkers failed to predict outcome.

Addition of glucagon to adrenaline improves hemodynamics in a porcine model of prolonged ventricular fibrillation.

OBJECTIVE Cardiac arrest is a daunting medical emergency. The aim of the present study was to assess whether the combination of adrenaline and glucagon would improve initial resuscitation success, 48-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. METHODS Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets, which were subsequently left untreated for 8 minutes. The animals were randomized to receive adrenaline alone (n = 10, group C) and adrenaline plus glucagon (n = 10, group G). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Hemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first 60 minutes after return of spontaneous circulation. Survival and a neurologic alertness score were measured at 48 hours after return of spontaneous circulation. RESULTS Return of spontaneous circulation was achieved in 8 animals (80%) from group C and 10 animals (100%) from group G (P = .198). A significant gradual increase in coronary perfusion pressure and diastolic aortic pressure over time, which started 1 minute after the onset of cardiopulmonary resuscitation, was observed. Three animals (30%) from group C and 9 animals (90%) from group G survived after 48 hours (P = .006), whereas neurologic examination was significantly better in the animals of group G (P < .001). CONCLUSIONS In this porcine model of prolonged ventricular fibrillation, the addition of glucagon to adrenaline improves hemodynamics during resuscitation and early postresuscitation period and may increase survival.

Characteristics of immune response in urosepsis

Termin sepsa odnosi se na klinicki odgovor organizama na prisustvo infekcije. Posto je ocito da slican, ili cak identican odgovor može nastati i u odsustvu infekcije, uveden je termin sindrom sistemskog inflamatornog odgovora (SIRS), bez obzira na uzrok. Uzroci SIRS-a mogu biti infektivni agensi, kao i neinfektivni koji obuhvataju traumu tkiva, pankreatitis, opekotine, ishemiju, hemoragicki sok, ostecenje tkiva izazvano imunskim mehanizmima, egzogenom primenom medijatora inflamacije (npr. citokina). Najcesca komplikacija SIRS-a je razvoj disfunkcije organskih sistema. Tako mogu nastati: sindrom respiratornog distresa odraslih (ARDS), sok, renalna i hepaticka insuficijencija, kao i sindrom multiple organske disfunkcije (MODS). MODS predstavlja dinamican proces razvoja poremecaja funkcije organa kod kriticno obolelih, koji ima faznu evoluciju. Na Internacionalnoj konferenciji o definicijama sepse koja je održana 2001. godine doslo se do zakljucka da su sadasnji koncepti sepse i njenih komplikacija korisni za klinicare i istraživace, ali ne omogucavaju precizno utvrđivanje prirode odgovora organizma na infekciju. Dijagnosticki kriterijumi SIRS-a su previse senzitivni i nespecificni. Tada je predložen PIRO, koncept ciji se akronim sastoji od sledecih elemenata: P – predispozicija, I – insult (infekcija, trauma), R – response, odgovor organizma (medijatori inflamacije) i O – organ dysfunction, disfunkcija organa koja cini MODS . Uprkos savremenim metodama lecenja kriticno obolelih, incidencija teske sepse u SAD se povecala na 300 /100 000 bolesnika. Mortalitet od teskog oblika sepse se prakticno izjednacio sa mortalitetom od akutnog infarkta miokarda (oko 215 000 smrtnih slucajeva godisnje). Imunoinflamatorni odgovor je od sustinskog znacaja za povoljan ishod insulta, ali se može dogoditi da svojim nekontrolisanim tokom i razvojem prouzrokuje ostecenje organizma. Sinergija i interakcija komponenata imunskog sistema diktiraju imunostimulaciju ili imunosupresiju. Anergija, jedan od fundamentalnih mehanizama endogene imunske supresije, rezultat je dejstva dva entiteta imunskog mehanizma koji su pogubna posledica teske traume: sistemske, nediskriminantne, ekscesivne inflamacije celog organizma sa jedne strane i paralize celularne imunske funkcije sa druge strane. Danas se zna da su određeni delovi imunskog sistema stimulisani, dok su drugi suprimirani u kompleksnom nizu događaja koji jos uvek nije sasvim razjasnjen. Nakon dejstva insulta (infekcije), imunoinflamatorni sistem može postati hiperaktivan. Endotelne i epitelne celije, kao i neutrofili, makrofage i limfociti proizvode snažne proinflamatorne citokine: tumor nekrozis faktor-α (TNF-α), interleukine (IL-1 i 8), interferon-γ (IFN-γ). Istovremeno, veoma je izražena sinteza proteina akutne faze i aktivacija sistema komplementa, sto dovodi do produkcije C5a, koji pojacava produkciju citokina. Aktivisana kaskada koagulacije cesto rezultuje diseminovanom intravaskularnom koagulopatijom. Fagociti reaguju na mnoge od ovih medijatora oslobađanjem granularnih enzima i sintezom reaktivnih kiseonicnih metabolita, koji su kljucni za ubijanje bakterija, ali takođe izazivaju i ostecenje tkiva .

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

Background Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. Methods A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. Results NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. Conclusions NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

Analgesic efficacy and safety of four different anesthesia/postoperative analgesia protocols in patients following total hip arthroplasty

Background/Aim. Hip replacement surgery can initiate significant postoperative pain caused by bone alterations, implant, and soft tissue or nerve injuries. Postoperative analgesia using regional techniques has been shown to have numerous advantages over the intravenous use of morphine. However, numerous side effects and complications of postoperative continuous epidural analgesia have been reported recently. The aim of this prospective, randomized study was to investigate whether continuous lumbar plexus block can be a safe and efficacious alternative for postoperative analgesia in comparison with epidural analgesia and patient-controlled analgesia with morphine (PCA morphine) for hip arthroplasty. Methods. This prospective study included 60 patients, scheduled for total hip arthroplasty. Patients were randomized into 4 groups: the group central nerve block - epidural (CNB), the group peripheral nerve block - lumbar plexus block (PNB), the group spinal anesthesia-PCA morphine (SAM) and the group general anesthesia-PCA morphine (GAM). The quality of analgesia and side effects (hypotension, nausea, vomiting, urinary retention) were recorded in all groups at 4 h, 12 h, and 24 h after surgery. Pain scores were assessed using Visual Analogue Scale (VAS), both at rest and on moving. Results. Our findings demonstrated that the use of a continuous lumbar plexus block provides effective analgesia at rest and on moving, during 24 h after hip arthroplasty. Pain scores varied significantly among the groups 4 h postoperatively (F = 21.827; p < 0.01), 12 h postoperatively (F = 41.925; p < 0.01) and 24 h postoperatively (F = 33.768; p < 0.01) with the highest scores ≥ 3 in the GAM group. Patients from the PNB group had satisfactory analgesia, comparable with patients from the CNB group. The incidence of nausea was significantly lower in the PNB group 12 h after the operation (x2 = 9.712; p < 0.01). The incidence of urine retention was significantly different 12 h after the operation, with a presence only in the CNB group, with the incidence of 33.3% (x2 = 16.365; p < 0.01). In all studied groups, the incidence of hypotension was not significantly different postoperatively. Conclusion. Administration of postoperative analgesia using continuous lumbar plexus block produces satisfactory analgesia with a low incidence of side effects when compared to epidural analgesia or parenteral opioids following hip arthroplasty.

Fatigue in Patients with Autoimmune Thyroid Diseases

Abstract Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, but fatigue in autoimmune thyroid disease (AITD) has not been investigated so far. The aim of this study was to examine fatigue in patients with AITD and to analyse the correlation between fatigue and the serum concentrations of thyroid antibodies, thyroid function and depression. This cross-sectional clinical study included 62 patients with increased concentrations of thyroperoxidase antibodies (TPOAbs) as confirmation of AITD and 52 healthy individuals who were negative for thyroid antibodies; all controls were euthyroid. Thyroid antibodies, free thyroxine and thyroid-stimulating hormone were measured in the sera of all subjects. The Fatigue Severity Scale was used to measure the severity of fatigue; the level of depression was measured by the Beck Depression Inventory. Eight (12.9%) patients had evident fatigue, 7 (11.3%) patients had fatigue limit values, and 47 (75.8%) patients had no fatigue. The frequency of fatigue was highly significant and almost three times higher in the AITD patients compared to the control group, in which only 2 (3.8%) patients had evident fatigue. The majority of patients with fatigue had normal thyroid function, and only one (1.6%) patient had overt hypothyroidism. Seven (11.3%) patients had both fatigue and depression, whereas one (1.6%) patient had fatigue without depression. We did not find significant correlations between fatigue and the concentrations of thyroid antibodies, but we found statistically significant correlations between fatigue and depression in AITD patients.