Urea to Albumin Ratio Is an Excellent Predictor of Death in Patients With Complicated Intra-Abdominal Infections.

Background: The urea to albumin ratio (UAR) has shown a prognostic value in various clinical settings, however, no study has yet investigated its ability to predict outcome in complicated intra-abdominal infections (cIAIs). Therefore, our aim was to evaluate the association between UAR and mortality in such patients. Patients and Methods: A single-center prospective study including 62 patients with cIAIs was performed at a University Hospital Stara Zagora for the period November 2018 to August 2021. Various routine laboratory and clinical parameters were recorded before surgery and on post-operative day 3. We used serum levels of urea and albumin to calculate the UAR. Results: The observed in-hospital mortality was 14.5%. Non-survivors had higher pre- and post-operative median of UAR than survivors (88.39 vs. 30.99, p < 0.0001 and 106.18 vs. 26.58, p < 0.0001, respectively). Lethal outcome was predicted successfully both by UAR before surgery (area under receiver operating characteristics [AUROC] curves = 0.889; p < 0.0001) at a threshold of 61.42 and on third post-operative day (AUROC = 0.943; p < 0.0001) at a threshold = 55.89. Conclusions: Peri-operative UAR showed an excellent ability for prognostication of fatal outcome in patients with cIAIs.

Better chance of survival is associated with higher neutrophil CD16 expression in patients with complicated intra-abdominal infections.

Aim: The ability of neutrophil CD16 (nCD16) expression to predict outcome in complicated intra-abdominal infections (cIAIs) has not yet been studied; therefore we aimed to evaluate its potential prognostic value in such patients. Methods: Between November 2018 and August 2021 a single-center prospective study was performed in the Department of Surgical Diseases at a University Hospital Stara Zagora. A flow cytometry was used to measure the levels of nCD16 before surgery and on the 3rd postoperative day (POD) in 62 patients with cIAIs. Results: We observed a mortality rate of 14.5% during hospitalization. Survivors had significantly higher perioperative expression of nCD16 than non-survivors (P = 0.02 preoperatively and P = 0.006 postoperatively). As predictor of favorable outcome we found a good predictive performance of preoperative nCD16 (AUROC = 0.745) and a very good predictive performance of postoperative levels (AUROC = 0.846). An optimal preoperative threshold nCD16 = 34.75 MFI permitted prediction of survival with sensitivity and specificity of 66.7% and 77.8%, respectively. A better sensitivity of 72.5% and specificity of 85.7% were observed for threshold = 54.8 MFI on the 3rd POD. Conclusion: Perioperative neutrophil CD16 expression shows a great potential as a predictor of favorable outcome in patients with cIAIs.

Prediction of outcome using CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocyte subpopulations in patients with complicated intra-abdominal infections.

There is still no study investigating the prognostic performance of CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocyte subpopulations in complicated intra-abdominal infections (cIAIs); therefore, we aimed to evaluate the association between monocyte subtypes and outcome in such patients. A single-center prospective study was conducted at a University Hospital Stara Zagora between November 2018 and August 2021. Preoperatively and on the 3rd postoperative day (POD), we measured the levels of CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes in peripheral blood using flow cytometry in 62 patients with cIAIs and 31 healthy controls. Nine of the 62 patients died during hospitalization. Survivors had higher pre-surgery percentages of CD14++CD16- classical monocytes and higher percentage of these cells predicted favorable outcome in ROC analysis (AUROC = 0.781, p = 0.008). The CD14++CD16+ intermediate monocyte percentages were higher in non-survivors both pre- and postoperatively but only the higher preoperative values predicted a lethal outcome (AUROC = 0.722, p = 0.035). For CD14+CD16++ non-classical monocytes, non-survivors had lower percentages on day 3 post-surgery and low percentage was predictive of lethal outcome (AUROC = 0.752, p = 0.046). Perioperative levels of monocyte subpopulations in peripheral blood show a great potential for prognostication of outcome in patients with cIAIs.

Prognostic performance of neutrophil CD64 expression in patients with complicated intra-abdominal infections - a prospective study.

No study yet analyzed the prognostic abilities of neutrophil CD64 expression (nCD64) in complicated intra-abdominal infections (cIAIs), therefore our aim was to evaluate the possible association between this biomarker and outcome in such patients. This single-center prospective study was conducted in the Department of Surgical Diseases at a University Hospital 'Prof. Dr. Stoyan Kirkovich' Stara Zagora for the period November 2018 - August 2021. We used flow cytometry to measure the percentage of nCD64 preoperatively and on the 3rd postoperative day (POD) in 62 patients with cIAIs and 31 healthy controls. Of the 62 enrolled patients, nine (14.5%) died during hospitalization. The perioperative expression of nCD64 was significantly higher in non-survivors compared to survivors (p = 0.02 before surgery and p = 0.024 after surgery). ROC Curve analysis revealed the good prognostic value of pre- and postoperative nCD64 levels as mortality predictors (AUROC = 0.744 and 0.765, respectively). Preoperatively, the identified sensitivity and specificity for nCD64 cut-off = 94.8% were 66.7% and 84.6%, respectively and on the 3rd POD for nCD64 cut-off = 84.85% we observed a sensitivity of 71.4% and a specificity of 78.8%. Neutrophil CD64 shows good prognostic value in patients with cIAIs both preoperatively and on the 3rd POD.

Can we predict death using scoring systems in patients with local peritonitis ? A retrospective study.

INTRODUCTION: Prognostic scores in patients with local peritonitis (LP) have not yet been studied exhaustively. AIM: We, therefore, aimed in this study to evaluate the ability of several scoring systems to predict death in LP. MATERIALS AND METHODS: A retrospective analysis including 68 patients with LP was conducted at Prof. Dr. Stoyan Kirkovich University Hospital in Stara Zagora from January 2017 to August 2021. Clinical and laboratory data needed for calculating the scoring systems were collected at admission or postoperatively. We compared the prognostic performance of WSES SSS, MPI, SIRS, and qSOFA using area under the receiver operation characteristics (AUROC) curves and bivariate correlation analysis. RESULTS: The observed mortality rate was 8.8%. Among all scores, MPI showed the best prognostic performance (AUROC=0.805, 95% CI 0.660-0.950). A threshold MPI >25 points permitted prediction of adverse outcome with a sensitivity of 66.7% and a specificity of 80.6%. The only significant correlation was found between outcome and MPI (p=0.012, r=0.302). Conclusions: The MPI has the ability to prognosticate mortality in patients with LP unlike WSES SSS, qSOFA and SIRS.

Prognostic value of peripheral blood CD14+HLA-DR+ monocytes in patients with acute pancreatitis.

Acute pancreatitis (AP) is characterized by a potent pro-inflammatory response and concomitant anti-inflammatory response leading to a state of immunosuppression. Decreased HLA (Human Leukocyte Antigen)-DR expression on monocytes is a reliable cellular marker of immune suppression. The main objective of this study was to investigate the clinical value of the percentage of peripheral blood CD14+ HLA-DR+ monocytes (mHLA-DR) for diagnosis and assessment of severity, development of organ failures (OF), local complications (LC), and infected necrosis (IN), and outcome in patients with AP. Flow cytometry was used to measure the percentage of peripheral blood mHLA-DR at different time points in 82 patients with AP enrolled during the period of 2012-2018 admitted to University Hospital Stara Zagora, Bulgaria. The percentages of peripheral blood mHLA-DR in AP patients were significantly associated with severity, development of LC, OF, IN (measured at admission, on the 48th hour and on the 5th day) and with outcome (measured on the 5th day) of AP. The value of peripheral blood mHLA-DR may be used as a biological marker in the diagnosis and assessment of severity, development of OF, LC, IN and to predict outcome in AP.

Poor Outcome Could Be Predicted by Lower Monocyte Human Leukocyte Antigen-DR Expression in Patients with Complicated Intra-Abdominal Infections: A Review.

Complicated intra-abdominal infections (cIAIs) are still associated with high morbidity and mortality levels. Early prognostic evaluation is a great challenge, and a serious amount of resources have been used to find the perfect mortality predictor. Monocyte human leukocyte antigen-DR (mHLA-DR) expression has been studied as a biomarker in patients with sepsis and other infections. Our aim was to evaluate the potential prognostic performance of mHLA-DR in patients with cIAIs. Methods: We performed an electronic search of Google Scholar and PubMed databases for articles published before January 2019. The search terms were "HLA-DR," "monocyte HLA-DR," "intra-abdominal infections," "sepsis," "outcome," and "mortality." Results: A total of 12 studies with 761 patients met our inclusion criteria. In 10 studies, poor outcome was predicted by lower mHLA-DR expression, and two studies showed no prognostic value. Conclusion: This review found association between lower mHLA-DR expression and mortality. We concluded that mHLA-DR could be a reliable and meaningful predictor of poor outcome in patients with cIAIs. Nevertheless, more large prospective studies with surgical patients exclusively are needed before using this biomarker in a clinical setting.

A combination of C-reactive protein and quick sequential organ failure assessment (qSOFA) score has better prognostic accuracy than qSOFA alone in patients with complicated intra-abdominal infections.

INTRODUCTION: Complicated intra-abdominal infections (cIAIs) remain a serious challenge because of their unacceptably high mortality rates. Among different prognostic scoring systems quick-sequential organ failure assessment (qSOFA) score is the most recent. However, as mortality predictor in surgical patients, qSOFA showed lack of sensitivity. The aim of this study was to find prognostic superiority of our new qSOFA-CRP score in patients with cIAIs. MATERIALS AND METHODS: We retrospectively analyzed 78 patients presented to ED and admitted to Department of Surgical Diseases between January 2017 and October 2018 with diagnosis cIAIs. CRP levels, qSOFA score and systemic inflammatory response syndrome (SIRS) were established at admission. We analyzed area under receiver operating characteristics (AUROC) curves of SIRS, qSOFA and qSOFA-CRP and performed a comparison to explore their prognostic values. RESULTS: The identified in-hospital mortality was 25.6%. qSOFA-CRP score showed the best prognostic performance compared to qSOFA alone (AUROC = 0.818 vs. 0.746, p = .0219) and SIRS (AUROC = 0.818 vs. 0.579, p = .0009). The new qSOFA-CRP score ≥2 points showed excellent specificity (91.4%) and the highest sensitivity in comparison to qSOFA ≥2 and SIRS ≥2 (60% vs. 35% vs. 40%) for mortality prediction. CONCLUSIONS: qSOFA-CRP score showed better prognostic value than quick-SOFA alone in patients with cIAIs.

Neutrophil CD64 - A potential biomarker in patients with complicated intra-abdominal infections? - A literature review.

Complicated intra-abdominal infections (cIaIs) respresent a serious cause of morbidity and mortality. Early diagnosis and well-timed treatment can improve patients' outcome, whereas the delay in management often result in rapid progression to circulatory collapse, multiple organ failure, and death. Neutrophil CD64 antigen expression has been studied for several years as infectious and sepsis biomarker and has several characteristics that make it good for clinical employment. It has been suggested to be predictive of positive bacterial cultures and a useful test for management of sepsis and other significant bacterial infections. Our review concluded that the neutrophil CD64 expression could be a promising and meaningful biomarker in patients with cIaIs. It shows good potential for evaluating the severity of the disease and could give information about the outcome. However, more large studies should be performed before using it in clinical practice.

Increased Circulating CD4+CD25+CD127low/neg Regulatory T-cells as a Prognostic Biomarker in Acute Pancreatitis.

OBJECTIVE: Early detection of severe forms with unfavorable outcome is the cornerstone that could provide reduction of morbidity and mortality in acute pancreatitis (AP). METHODS: The percentage of circulating CD4CD25CD127 regulatory T-cells (Tregs) was determined at admission, on the 48th hour, and on the fifth day in 72 patients with AP. We divided patients in 2 groups-Sev1, which includes 19 patients (26.4%) with moderate AP and 39 patients (54.2%) with mild disease, and Sev2, which includes 14 patients (19.4%) with severe AP. Seven patients (9.7%) developed septic complications. The mortality in our group was 9.7%. RESULTS: The patients in Sev2 had higher percentage of Tregs at admission and on the fifth day compared with patients in Sev1 (P = 0.007 and P = 0.033, respectively). There was no significant difference in percentage of Tregs at admission, on the 48th hour, and on the fifth day in patients who developed and did not develop infected necrosis (P = 0.50, P = 0.72, and P = 0.92, respectively). Patients with poor outcome had elevated percentage of Tregs on the fifth day (P = 0.045). CONCLUSIONS: The percentage of circulating Tregs may be implicated in the development of early immune suppression in AP. Elevated percentage of circulating Tregs at admission in AP is an independent prognostic biomarker for severe disease.

Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis.

Development of acute pancreatitis illustrates the need to understand the basic mechanisms of disease progression to drive the exploration of therapeutic options. Cytokines play a major role in the pathogenesis of acute pancreatitis as underlying systemic inflammatory response, tissue damage, and organ dysfunction. However, little is known about circulating concentrations of these inflammatory markers and their real impact on clinical practice. Experimental studies have suggested that the prognosis for acute pancreatitis depends on the degree of pancreatic necrosis and the intensity of multisystem organ failure generated by the systemic inflammatory response. This suggests an intricate balance between localized tissue damage with proinflammatory cytokine production and a systemic anti-inflammatory response that restricts the inappropriate movement of proinflammatory agents into the circulation. Implication of such mediators suggests that interruption or blunting of an inappropriate immune response has the potential to improve outcome. A detailed understanding of pathophysiological processes and immunological aspects in patients with acute pancreatitis is the basis for the development of therapeutic strategies that will provide significant reductions in morbidity and mortality.

Elevated anticardiolipin antibodies in schizophrenic patients before and during neuroleptic medication.

The objective of this study was to examine the prevalence of IgG and IgM anticardiolipin antibodies (aCL) in schizophrenic patients and to determine the relation of aCL levels with neuroleptic medication and psychotic symptoms. Twenty-three patients with acute episodes of chronic schizophrenia, drug-free for at least 3 months before entering the study, were tested for aCL at admission (T1) and 42 days (T2) after neuroleptic treatment started. Blood samples were taken from 20 healthy volunteers as well. Diagnosis was performed according to DSM-IV. Serum samples were analysed for IgG and IgM autoantibodies against beta2-glycoprotein-1-cardiolipin complex by commercially available ELISA kits (Binding-site, UK). Significantly higher levels of aCL antibodies of both isotypes were found in schizophrenic patients versus controls. In patients IgM-aCL positivity was significantly more frequent than in controls. The elevated IgM-aCL and IgG-aCL values were not associated with neuroleptic treatment and psychotic symptoms, as measured by the Positive and Negative Syndrome Scale and the Pentagonal Structural Model of Schizophrenic Symptoms. The negative correlation of IgM-aCL and IgG-aCL with the positive symptoms scale and the autistic preoccupation scale (Pentagonal Structural Model) may indicate the consumption of these antibodies in the exacerbation of the disease.

Increased apoptosis of peripheral blood mononuclear cells (PBMC) during general and epidural anaesthesia in dogs.

The objective of the study was to investigate the hypothesis that perioperative lymphocytopenia was due to apoptosis of these cells induced by either halothane or epidural anaesthesia in dogs. The relationship between apoptosis induction and plasma concentrations of the stress hormone cortisol and the cytokines TNF-alpha and IL-10 was examined as well. The study was performed on 22 healthy mongrel dogs, equal numbers from both genders, weighing 18.3 +/- 2.9 kg, and aged between 3-5 years. Dogs were divided in three groups. Eight of the animals were anaesthetized with halothane, another eight received epidural anaesthesia using lidocaine, and six served as controls. Venous blood samples were obtained immediately before (0 minute) anaesthesia, during deep anaesthesia (120 minute), and on the next day (24 hour) in order to determine the following parameters: the total lymphocyte counts, the percentage of apoptotic peripheral blood mononuclear cells (PBMC) by flow cytometry, plasma concentrations of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay (ELISA), and plasma cortisol levels by radioimmune assay. Both halothane and epidural anaesthesia in dogs induces apoptosis of PBMC with slight decrease in total lymphocyte counts. These immunomodulatory effects were transient and faded till the 24th hour. Concerning the mechanism of inducing lymphocyte apoptosis by general or epidural anaesthesia, it seemed that neither cortisol, nor the tested cytokines TNF-alpha and IL-10 were implicated in this process. Further investigations are necessary to confirm this assumption.

Expression of ICAM-1, VCAM-1, E-selectin and TNF-alpha on the endothelium of femoral and iliac arteries in thromboangiitis obliterans.

Immunohistochemical light and electron microscopical analysis of surgical biopsies obtained from femoral and iliac arteries of patients with thromboangiitis obliterans (TAO) were performed to investigate the presence of tumour necrosis factor-alpha (TNF-alpha) and expression of the endothelial cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Expression of ICAM-1, VCAM-1 and E-selectin was increased on endothelium and some inflammatory cells in the thickened intima in all TAO patients. Ultrastructural immunohistochemistry revealed contacts between mononuclear blood cells and ICAM-1-, and E-selectin-positive endothelial cells. These endothelial cells showed morphological signs of activation. The present data indicate that endothelial cells are activated in TAO and that vascular lesions are associated with TNF-alpha secretion by tissue-infiltrating inflammatory cells, ICAM-1-, VCAM-1- and E-selectin expression on endothelial cells and leukocyte adhesion via their ligands. The preferential expression of inducible adhesion molecules in microvessels and mononuclear inflammatory cells suggests that angiogenesis contributes to the persistence of the inflammatory process in TAO.