Outcome Predictors in a Two-Phase Model and Microbiology Findings

Einleitung: Die Studienlage zur Prognose und zu Prognosefaktoren von Patienten mit schwerer Sepsis und Neutropenie auf Intensivstationen ist begrenzt und häufig wird diesen Patienten ein schlechter Outcome vorausgesagt. Ziel dieser Arbeit war (I) die Bestimmung der Mortalität jener Patienten im klinischen Alltag. Zusätzlich sollten Faktoren gefunden werden, welche Einfluss auf den Krankheitsverlauf nehmen (II) und Hypothesen kreiert werden, um die Prognose der Patienten zu verbessern (III). Methodik: Es wurden retrospektiv auf Grundlage der Patientenakte alle Patienten mit einer Neutropenie untersucht, welche sich von 2006 bis 2011 auf der Intensivstation I43 oder I47 des Virchow Klinikums der Charité Berlin in Behandlung befanden.1 558 Patienten mit Neutropenie konnten identifiziert werden, von denen 102 Patienten die Einschlusskriterien erfüllten. Anhand des Krankheitsverlaufes wurde ein 2 -Phasen-Modell entwickelt. In der ersten Phase wurde unterschieden, ob Patienten die initiale Sepsis überwunden haben oder verstorben sind. In der zweiten Phase bzw. Genesungsphase wurden die Patienten betrachtet, welche die Aufnahmekrise bewältigten und im Verlauf auf der Intensivstation verstorben sind oder ihren Aufenthalt überlebten und auf eine Normalstation verlegt worden sind. Ergebnisse: Die Gesamtmortalität der Patienten mit schwerer Sepsis und Neutropenie auf ITS betrug 54,9%. Signifikante Parameter bezüglich der Überwindung der primären Sepsis waren die Schwere der Sepsis bei Aufnahme sowie die Anzahl bzw. Schwere der Organversagen. Ein anhaltendes Organversagen sowie anhaltend erhöhte CRP-Werte waren in der Genesungsphase mit einem negativen Outcome der Patienten assoziiert. Weitere Faktoren mit einer Verschlechterung des Outcomes waren: Bluttransfusionen, eine nicht adäquate antibiotische Therapie zu Beginn der Behandlung, eine CMV-Infektion oder wenn eine Infektion mit Pilzen bzw. resistenten Erregern vorlag. Eine signifikant erhöhte Sterblichkeitsrate und deutlich erhöhte systemische Entzündungsparameter konnten bei Infektionen mit koagulase-negativen Staphylokokken und bei Infektionen mit Enterokokken gefunden werden. Ob es sich dabei um ein Epiphänomen handelt oder die Nachweise von Kokken tatsächlich ursächlich verantwortlich sind, kann aus den vorliegenden Daten nicht gesagt werden. Schlussfolgerung: Die Schwere der initialen Sepsis (erste Phase) und die anhaltenden Dysfunktionen von Organen (zweite Phase) waren mit einer schlechten Outcome-Prognose assoziiert. In Anbetracht der hohen Rate und der schlechten Prognose von Patienten mit gram-positiven Kokken könnte eine frühzeitige antibiotische Therapie mit Wirksamkeit gegen dieses Erregerspektrum die Prognose von Patienten eventuell verbessern.Introduction: Presently there is only limited data on the prognosis and prognostic factors of patients with neutropenic sepsis treated in the ICU. Generally these patients are considered to have a very poor prognosis with regarding survival. The aims of this work were (I) to determine the mortality of these patients, (II) to identify prognostic factors and arguably most importantly (III) to generate hypotheses how to improve the prognosis of these patients. Methods: All patients with neutropenia admitted between 2006 and 2011 into the ICU I43 or I47 of the “Virchow Klinikum” - one of three clinic locations of the “Charité Berlin” - were analyzed retrospectively. Data were retrieved from the electronic patient records. 558 Patients with neutropenia have been identified and 102 of them fulfilled the inclusion criteria. Based on the course of disease a two-phase model of the ICU stay was developed. The first phase we focused whether the patients survived the initial sepsis. In the second or so called recovery phase we subdivided the patients into the group which after overcoming the initial sepsis survived the stay in the ICU or died in the subsequent course of their stay. Results: The overall ICU mortality of patients with a neutropenic sepsis was 54,9%. Parameters associated with overcoming the primary sepsis were the severity of the initial sepsis and the severity of organ failures. Associated with a poor outcome in the phase of recovery were the persistent of organ failures and persistent higher CRP-levels. Other factors associated with poor outcome were blood transfusions, an inappropriate initial antibiotic therapy, an infection with CMV or a fungal infection or the detection of multiresistant bacteria. A significantly higher mortality and a higher degree of systemic inflammation were observed in infections with coagulase-negative Staphylococci and in infections with Enterococci. Conclusion: Severity of the sepsis (in the first phase) and persistent organ dysfunction (in the second phase) were associated with unfavorably outcome. Considering the high rate and worse prognosis of gram-positive cocci early treatment with antibiotics with respective effectivity may improve the prognosis

Neutropenic sepsis in the ICU: Outcome predictors in a two-phase model and microbiology findings

Objective. Patients with neutropenic sepsis have a poor prognosis. We aimed to identify outcome predictors and generate hypotheses how the care for these patients may be improved. Methods. All 12.352 patients admitted between 2006 and 2011 to the medical ICUs of our tertiary university center were screened for neutropenia; out of 558 patients identified, 102 fulfilled the inclusion criteria and were analyzed. Severity markers and outcome predictors were assessed. Results. The overall ICU mortality was 54.9%. The severity of sepsis and the number of organ failures predicted survival of the primary septic episode (APACHE II 22.8 and 29.0; SOFA 7.3 and 10.1, resp.). In the recovery phase, persistent organ damage and higher persistent C-reactive protein levels were associated with a poor outcome. Blood transfusions and CMV infection correlated with an unfavorable prognosis. Ineffective initial antibiotic therapy, fungal infections, and detection of multiresistant bacteria displayed a particularly poor outcome. Infections with coagulase-negative staphylococci and enterococci were associated with a significantly higher mortality and a high degree of systemic inflammation. Conclusion. Patients with persistent organ dysfunction show an increased mortality in the further course of their ICU stay. Early antimicrobial treatment of Gram-positive cocci may improve the outcome of these patients

Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

Abstract Background One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. Method In this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure. Results We identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined to cytokeratin 19 and cytokeratin 14 double positive cells. Conclusion This study illustrates how phage display can be applied towards the discovery of proteins which exhibit changes in their expression patterns. We identified the mitochondrial protein Mrps18a as being upregulated in human breast cancer cells compared to normal breast cells

Deep Infiltrating Colorectal Endometriosis Treated With Robotic-Assisted Rectosigmoidectomy

Background and Objective: Deep infiltrating pelvic endometriosis with bowel involvement is one of the most aggressive forms of endometriosis. Nowadays, robotic technology and telemanipulation systems represent the latest developments in minimally invasive surgery. the aim of this study is to present our preliminary results and evaluate the feasibility of robotic-assisted laparoscopic colorectal resection for severe endometriosis.Methods: Between September 2009 and December 2011, 10 women with colorectal endometriosis underwent surgery with the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA). We evaluated the following parameters: short-term complications, clinical outcomes and long-term follow-up, pain relief recurrence rate, and fertility outcomes.Results: Extensive ureterolysis was required in 8 women (80%). Ovarian cystectomy with removal of the cystic wall was performed in 7 women (70%). Torus resection was performed in all women, with unilateral and bilateral uterosacral ligament resection in 1 woman (10%) and 8 women (80%), respectively. in addition to segmental colorectal resection in all cases, partial vaginal resection was necessary in 2 women (20%). An appendectomy was performed in 2 patients (20%). the mean operative time with the robot was 157 minutes (range, 90-190 minutes). the mean hospital stay was 3 days. Six patients had infertility before surgery, with a mean infertility time of 2 years. After a 12-month follow-up period, 4 women (67%) conceived naturally and 2 (33%) underwent in vitro fertilization.Conclusion: We show that robotic-assisted laparoscopic surgery for the treatment of deep infiltrating bowel endometriosis is feasible, effective, and safe.Univ São Paulo, Hosp Clin, Fac Med, São Paulo, BrazilCtr Endometriose São Paulo, São Paulo, BrazilAlbert Einstein Hosp, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilDigimagem Med Diagnost, Radiol Brazilian Coll, São Paulo, BrazilUniv Cent Florida, Dept Obstet & Gynecol, Orlando, FL 32816 USAFlorida Hosp Celebrat Hlth, Celebration, FL USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc