[Rapid diagnosis of acquired hemophilia A with ClotPro viscoelastometry analyser]. / A szerzett haemophilia A gyors diagnosztikája ClotPro viszkoelasztometriás készülékkel.

Acquired hemophilia A is a rare condition with the capability of bringing about life-threatening bleeding in the perioperative period, posing a significant challenge for the caregiver anesthetist to identify the underlying cause. However, a quick diagnosis might be supported by viscoelastometry by raising the suspicion of severe and isolated deficiency of the intrinsic coagulation pathway, requiring a prompt consultation with a hematology center. Special laboratory tests of hemostasis are helpful in the differential diagnosis of the detected coagulation disorder. Nevertheless, bypassing agents have gained a crucial role in the treatment of major perioperative blood losses by bypassing Factor VIII inactivated by autoantibodies and thus, initiating coagulation. Early goal-directed supplementation of depleted coagulation factors must also be kept in the focus of the therapy. Orv Hetil. 2023; 164(40): 1600-1604.

New under the sun: ClotPro's ECA-test detects hyperfibrinolysis in a higher number of patients, more frequently and 9 min earlier.

Liver diseases result in a re-balanced state of the haemostatic system with decreased haemostatic reserves. Increased fibrinolytic activity is commonly seen during liver transplants. The aim of this study was to assess whether ClotPro's ECA-test is able to detect hyperfibrinolysis earlier and with higher frequency than ClotPro's conventional viscoelastic assays for the intrinsic and the extrinsic coagulation pathway. From 25 liver transplant recipients, systemic blood samples were collected during surgery. Viscoelastic haemostatic assays with ClotPro's IN-test, EX-test and ECA-test were performed simultaneously from each blood sample. Hyperfibrinolysis was defined on the basis of the manufacturer's prespecified threshold value (maximal lysis >15%). The incidence of hyperfibrinolysis detected with each test was compared with the McNemar test. For each assay, lysis detection time (LDT) was calculated and analysed with the nonparametric Kruskal-Wallis test. A total of 125 tests were performed simultaneously. Compared with the IN-test and the EX-test, the ECA-test detected hyperfibrinolysis in significantly ( P  < 0.001) higher number of patients (9; 11; 14, respectively) and in more measurement points (14; 18; 28, respectively). The analysis of LDT values revealed significant superiority of the ECA-test to the IN-test ( P  = 0.046) and to the EX-test ( P  = 0.035), indicating the profibrinolytic state of the haemostasis 8.9 ±â€Š0.65 and 8.7 ±â€Š0.17 min earlier, respectively. These are preliminary results of the study NCT0424637. ClotPro's ECA-test appeared to detect fibrinolysis in a higher number of patients, more frequently, and the mean time of detection was 9 min earlier than that of the IN-test and the EX-test.

Evolution of liver transplant waiting list in Hungary between 1995 and 2019. / Májvárólista 1995-2019: a hazai adatok nemzetközi összehasonlítása.

Összefoglaló. Bevezetés: A májtranszplantációs program részeként 1995 óta létezik folyamatosan vezetett várólista Magyarországon. Célkituzés: A legfontosabb várólista-paraméterek megállapítása és nemzetközi összehasonlítása. Módszer: A szerzok az 1995. január 1. és 2019. december 31. között elso májátültetés céljából várólistára helyezett betegek adatait elemezték. Eredmények: Összesen 1722 beteget helyeztek várólistára, 1608 felnottet, 114 gyermeket. A férfiak aránya 51,2%, az átlagéletkor 45,6 év. Az évente regisztrált új jelöltek száma 25 év során közel az ötszörösére emelkedett. A listára helyezés leggyakoribb indikációja a víruseredetu cirrhosis volt (n = 451). Ezt követte a cholestaticus (n = 314) és az alkoholos májbetegség (n = 264). Rosszindulatú daganat, 82%-ban hepatocellularis carcinoma miatt 215 beteget regisztráltak. Krónikus betegségekben az átlagos Model for End-Stage Liver Disease pontszám a regisztráláskor 13,5 volt. A 2018. december 31-ig listára helyezettek (n = 1618) 61%-a részesült májátültetésben, 24%-a várakozás közben meghalt, 7%-a a mutétre alkalmatlanná vált. A mutét elotti medián várakozási ido 248 nap volt a krónikus és 2 nap az akut betegek listáján. A transzplantált tumoros betegek (n = 132) szignifikánsan rövidebb ideig vártak mutétre (medián 115,5 nap), mint a többi krónikus beteg (n = 803, medián 282 nap). Az Eurotransplanthoz való csatlakozás utáni idoszakban (2013. július 1. és 2018. december 31. között) a transzplantációs arány növekedett (67%), a várólista-halálozás (meghaltak + mutétre alkalmatlanná váltak) 24%-ra csökkent. Megbeszélés: A várólista folyamatos bovülése hozzájárult a hazai májátültetési program fejlodéséhez. A hazai várólista diagnózis szerinti összetétele a mások által közöltekkel nagyrészt egyezik. A transzplantáltak aránya a nemzetközi átlagnak megfelelo. A várólista-halálozás és a mutét elotti várakozási ido a magyarországinál alacsonyabb donációs aktivitású vagy jelentosen nagyobb várólistával rendelkezo országokéhoz hasonló. Következtetés: Várólista-paramétereink javításához a transzplantációk számának további növelése szükséges. Orv Hetil. 2022; 163(8): 301-311. INTRODUCTION: The Hungarian liver transplant program including waiting list started in 1995. OBJECTIVE: Evaluation of the wait-list parameters and comparing them with those in the literature. METHOD: Data of patients listed for primary liver transplantation between 1995 and 2019 were analyzed. RESULTS: A total of 1722 recipient candidates were registered on the liver transplant waiting list: 1608 adults (51.2% men) with mean age of 45.6 year and 114 patients aged <18 year. Virus-induced cirrhosis was the leading indication of listing (n = 451) and cholestatic liver diseases (n = 314) and alcoholic cirrhosis (n = 264) thereafter. The mean Model for End-Stage Liver Disease score was 13.5 for those with chronic disease. 61% of 1618 patients listed before December 31, 2018 underwent liver transplantation and 31% were removed from the wait-list for death or clinical deterioration. After joining Eurotransplant (period of 01. 07. 2013-31. 12. 2018), the transplant rate was 67%, the waiting list removal due to death/too sick for operation decreased to 24%. The median waiting time till transplantation was 248 days for those on elective and 2 days on acute list. Patients grafted with malignancy (n = 132) waited significantly shorter time than those with chronic non-malignant liver disease (median 115.5 versus 282 days). DISCUSSION: The composition of our waiting list by primary liver disease was similar to that of countries with large burden of hepatitis C. Transplant rate was average, wait-list mortality and waiting time were in line with those observed in low-donation countries or in the case of large volume waiting list. CONCLUSION: Listing of increasing the number of patients contributed to evolution of our liver transplant program. To improve our parameters, increasing transplant activity is warranted. Orv Hetil. 2022; 163(8): 301-311.

Gestational hemostasis: a natural model for hemostasis resuscitation of major periprocedural blood loss : "Look deep into nature, and then you will understand everything better." Albert Einstein.

Early goal-directed treatment is an evidence-based approach to guide hemostatic therapy during major periprocedural bleeding. If viscoelastic coagulation tests are not available, an algorithm, termed the pyramid of hemostatic interventions, can help manage severe bleeding. Pregnant women accumulate huge reserves of prothrombotic and antifibrinolytic hemostatic elements to avoid peripartum blood loss. We provide comparison of therapeutic hemostatic approaches and natural gestational process and identified remarkable analogy between early goal-directed management of bleeding and hemostatic adaptation of pregnant woman. Therefore, gestational hemostasis serves as a natural model for goal-directed hemostasis resuscitation and can foster understanding of hemostatic management of periprocedural bleeding.

Perioperative Patient Blood Management: common risk, common tasks, common responsibility / Perioperatív vérfelhasználás: közös kockázat, közös feladatok, közös felelosség.

Human red blood cell concentrate and platelet suspension are unstable preparations, therefore, they are not part of the international pharmaceutical market for biological and economic reasons. Consequently, they cannot be replaced by external sources. Human allogeneic erythrocyte and platelet preparations should therefore be considered as part of the common national wealth. The amount of transfused red blood cell concentrate has been declining in countries with advanced health systems in recent years. The changes were initially driven by the spread of the concept and practice of liberal and restrictive transfusion triggers. A complex, thoughtful system of perioperative blood utilization, the Patient Blood Management has later emerged, and a paradigm shift in the delivery of life-threatening perioperative bleeding has developed. At the same time, clinical practitioners are facing a new challenge of reducing willingness to donate blood worldwide. The rationalization of the use of human red blood cell concentrate and platelet suspension is essential in Hungary. As a health care measure, the currently rigidly earmarked financial resources available for allogeneic preparations and stable factor concentrates for the treatment of life-threatening haemorrhages need to be changed to be interoperable. The perioperative blood use could additionally be reduced by the widespread dissemination of the Patient Blood Management requiring complex coordinated educational interdisciplinary and logistical work. Orv Hetil. 2020; 161(37): 1545-1553.

National Blood Donation and Blood Saving Program in Hungary. Further steps are required to improve patient safety. / A Nemzeti Véradó és Vérmento Program helyzete Magyarországon. További lépések szükségesek a betegbiztonság fokozásához.

INTRODUCTION AND AIM: In the last decade, guidelines and trainings promoted haemostasis point-of-care tests, availability and application of factor products, while they led to a decrease in blood product consumption. The aim of this study is to examine protocols, conditions in terms of facilities, equipment, personnel of anaesthesia-intensive care units (A-ICU) to improve healthcare services and patient safety. METHOD: In 2019, self-reported questionnaires were sent in e-mail to A-ICUs. Application of guidelines and local protocols, education, haemostasis diagnostic tools, availability of allogeneic transfusion products, stable factor and drug products for restoring haemostasis were evaluated. RESULTS: 49% of A-ICUs filled out 46 questionnaires. 91.3% applied guidelines, 43.5% had local protocols. The lack of haemostasis and Patient Blood Management (PBM) trainings was indicated by 6 and 17 A-ICUs, respectively. Applying MAITT guidelines decreased red blood cell concentrate (RBC), fresh frozen plasma (FFP) and thrombocyte consumption by 65.1%, 67.4% and 30.2%. The availability of laboratory and viscoelastic tests is limited except for blood count, INR, APTI, fibrinogen. Where viscoelastic tests were available, RBC 2.9, FFP 1.7, thrombocyte 2.5 times more physicians per A-ICU beds participated in haemostasis trainings. 32% of A-ICUs can provide the required amount of factor products in the case of massive bleeding. CONCLUSION: Haemostasis and PBM trainings improve the quality of healthcare services if necessary equipment, factor and haemostasis drug products are provided. In order to promote PBM programmes and to improve patient safety, rearrangement of service and financing structure is needed, which must be accompanied by consulting perioperative professionals, general practitioners, and other related experts. Orv Hetil. 2020; 161(37): 1606-1616.

Guidance on the special care of liver or kidney transplant recipients diagnosed with COVID-19 / Az új koronavírus (SARS-CoV-2) okozta fertozésben szenvedo vese- és májátültetett betegek ellátásának speciális szempontjai. (A COVID-19-pandémia orvosszakmai kérdései)

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

Procoagulation, hypercoagulation and fibrinolytic "shut down" detected with ClotPro® viscoelastic tests in COVID-19 patients. / Procoagulatio, hypercoagulatio és fibrinolysis "shut down" kimutatása ClotPro® viszkoelasztikus tesztek segítségével COVID-19-betegekben.

INTRODUCTION: International data indicate that arterial, venous and microvascular thrombosis or disseminated intravascular coagulation occur in more than 30% of hospitalized patients with COVID-19. This condition is characterized by high levels of D-dimer and fibrinogen, prolonged prothrombin time and activated partial thromboplastin time. METHOD: Blood samples from three COVID-19 patients treated in a Hungarian intensive care unit were collected and analyzed with ClotPro® tests. EX-tests, IN-test, FIB-tests, RVV-tests, and TPA-tests were performed. The results were interpreted with respect to the clinical condition of the patients. RESULTS: Procoagulation, hypercoagulation and either fibrinolysis or a "shut down" phenomenon of the fibrinolytic process were found with ClotPro®. The ClotPro® parameters were consistent with the conventional coagulation tests and corresponded with the criteria of non-overt disseminated intravascular coagulation. CONCLUSION: These findings encourage further investigations to elucidate the underlying pathophysiology of thromboembolic events in COVID-19 patients and may support the introduction of full dose anticoagulation with or without antiplatelet therapy. Interventional clinical trials may be helpful in defining the appropriate drug(s), for this purpose, the algorithms of administration, and the optimal duration of therapy. At present, the authorization of a clinical trial that attempts to answer these questions is in progress. Orv Hetil. 2020; 161(22): 899-907.

[Volume-based haemostasis reserves in blood product free liver transplantations]. / Térfogatalapú haemostasistartalékok vérmentes májtranszplantációk során.

Introduction: During liver transplantation, haemostasis is typically assessed by means of standard laboratory tests and viscoelastic tests, while dynamic monitoring of coagulation factor specific blood losses is an unusual, yet established approach. Aim: Our aim was to evaluate the volume-based haemostasis reserves in blood product free liver transplants in the first perioperative 48 hours, in association with the Child-Pugh score. Method: Data of 59 blood product free liver transplanted patients' coagulation factor levels, viscoelastic parameters and coagulation factor specific blood losses according to Gross methodological, baseline and 'coagulopathic' trigger levels were analysed. The haemostasis reserves were estimated according to the Child-Pugh classification. Laboratory tests and the calculation of haemostasis reserves were carried out before liver transplantation (T1), at the end of the surgery (T2) and also 12-24-48 hours postoperatively (T3-T4-T5). The viscoelastic tests were performed before liver transplantation (T1) and at the end of the surgery (T2). Results: Fibrinogen levels decreased by 1.2 g/L. Factor II, V, VII, X levels decreased by 26-40%. From T2 to T4, fibrinogen increased by 0.9 ± 0.6 g/L over 24 h (p<0.001). Factor II, V, VII, X levels increased by 12-30% between T3 to T5 (p<0.001). The viscoelastic parameters remained in the normal range during liver transplantation (T1-T2). Haemostasis reserves decreased by 61% at the end of surgery (p<0.001), but reached 88% of the preoperative value on the second postoperative day. The initial reserves of Child B and C groups were 36-41% lower than Child A, nevertheless, these differences were not significant at 48 hours. Conclusion: The volume-based haemostasis approach supplements the standard laboratory and viscoelastic tests. This unusual approach dynamically indicates the actual reserve of haemostasis and shows the 'weakest link' within the system. Orv Hetil. 2020; 161(7): 252-262.

[Liver transplantation in Wilson's disease patients, 1996-2017]. / Májátültetés Wilson-kóros betegekben, 1996­2017.

Introduction: Wilson's disease is a lethal-without-treatment inherited disorder of copper metabolism. Despite the increased focus on the diagnosis and treatment, liver transplantation is needed in a number of cases even nowadays. Aim: To collect and analyze the data of the Hungarian Wilson's disease patients who underwent liver transplantation. Method: Data of 24 Wilson's disease patients who underwent liver transplantation at the Semmelweis University have been analyzed retrospectively. The diagnosis of Wilson's disease was based on the international score system. The diagnosis of acute liver failure corresponded to the King's College criteria. All liver transplantations had been performed at the Department of Transplantation and Surgery of Semmelweis University, in 1996 for the first time. Results: The mean age was 26 years, F/M = 13/11. Twelve patients needed urgent liver transplantation for acute liver failure, and 12 underwent transplantation for decompensated liver cirrhosis. One patient had been retransplanted because of chronic rejection. Three patients with acute on chronic liver failure were transplanted via the Eurotransplant program. The mean time on the waiting list was 3 vs 320 days in acute liver failure and chronic liver disease groups, respectively. The overall 5-year survival was 66%, but it was 80% after 2002 indicating both the learning curve effect and the improvement of vigilance in Hungary. Despite difficulties of the diagnostic process, Wilson's disease was identified in 21/24 patients prior to the transplantation. Conclusion: Liver transplantation is needed in a number of cases of Wilson's disease. The ideal indication and timing of transplantation may improve the survival of the patients. Orv Hetil. 2019; 160(51): 2021-2025.

Liver Transplant for Metastatic Neuroendocrine Tumors: A Single-Center Experience in Hungary.

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher. METHODS: We performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months. RESULTS: Ten liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence. CONCLUSION: Patient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.

[Forced steps for making improvements in severe perioperative haemorrhage]. / Lépéskényszerben ­ új feladatok az életveszélyes perioperatív vérzések ellátásában.

Severe perioperative bleeding increases perioperative morbidity and mortality. The management of the consequences imposes high burden on the human and financial resources of healthcare providers. Since 2009, there has been a continued worldwide decline in demand for allogenic blood products. This tendency can mainly be attributed to Perioperative Blood Management Program and to new innovative management applying haemostatic factor concentrates, viscoelastic assays and guidelines for treatment of the severe periprocedural bleeding patients. One of the major challenges of our times is still to match blood supply with demand. The new diagnostic and therapeutic modalities for managing the bleeding patients require new financial resources on the one hand and, on the other hand, call for redistribution of the material means provided by the health care system. Achieving interoperability between financial resources allocated to allogenic blood products and factor concentrates, the current state-of-the-art approach for managing the bleeding patient can be used to save blood and the lives of patients simultaneously. Orv Hetil. 2019; 160(6): 203-213.

[Anesthetics and intensive therapeutic aspects of liver transplantation]. / A májátültetés aneszteziológiai-intenzív terápiás vonatkozásai.

One of the most prominent results of our age is organ transplantation, the single treatment option for patients with end-stage organ failure. The success of transplants depends on the donor care, the patient preoperative preassessment, the perioperative care of organ transplantation and aftercare. Successful transplantation therefore requires a prominent level of continuous collaboration between the surgeon, anaesthesiologist, radiologist, internal medicine and hepatologist, laboratory physician and almost all their associates. The complex interdisciplinary approach based on the research results can be used to improve the patient's condition through pharmacotherapy, physiotherapy and psychotherapy during the time spent on waiting lists. The emergence of more active, targeted therapeutic options in perioperative graft resuscitation may help the currently inferior quality transplantable grafts or resuscitation out (machine perfusion) or in the recipient, thereby increasing the number of liver transplants. Deeper knowledge of hemostatic processes, along with the development of surgical techniques, would increase the number of blood transplant free transplants, thus improving the long-term survival of grafts. The present study aims at presenting the anaesthesia and early intensive therapy aspects of liver transplantation from aptitude assessment, through anaesthesia to early intensive therapeutic treatment. Orv Hetil. 2018; 159(46): 1891-1897.

Delta Procalcitonin Is a Better Indicator of Infection Than Absolute Procalcitonin Values in Critically Ill Patients: A Prospective Observational Study.

Purpose. To investigate whether absolute value of procalcitonin (PCT) or the change (delta-PCT) is better indicator of infection in intensive care patients. Materials and Methods. Post hoc analysis of a prospective observational study. Patients with suspected new-onset infection were included in whom PCT, C-reactive protein (CRP), temperature, and leukocyte (WBC) values were measured on inclusion (t 0) and data were also available from the previous day (t -1). Based on clinical and microbiological data, patients were grouped post hoc into infection- (I-) and noninfection- (NI-) groups. Results. Of the 114 patients, 85 (75%) had proven infection. PCT levels were similar at t -1: I-group (median [interquartile range]): 1.04 [0.40-3.57] versus NI-group: 0.53 [0.16-1.68], p = 0.444. By t 0 PCT levels were significantly higher in the I-group: 4.62 [1.91-12.62] versus 1.12 [0.30-1.66], p = 0.018. The area under the curve to predict infection for absolute values of PCT was 0.64 [95% CI = 0.52-0.76], p = 0.022; for percentage change: 0.77 [0.66-0.87], p < 0.001; and for delta-PCT: 0.85 [0.78-0.92], p < 0.001. The optimal cut-off value for delta-PCT to indicate infection was 0.76 ng/mL (sensitivity 80 [70-88]%, specificity 86 [68-96]%). Neither absolute values nor changes in CRP, temperature, or WBC could predict infection. Conclusions. Our results suggest that delta-PCT values are superior to absolute values in indicating infection in intensive care patients. This trial is registered with ClinicalTrials.gov identifier: NCT02311816.

Early procalcitonin kinetics and appropriateness of empirical antimicrobial therapy in critically ill patients: A prospective observational study.

PURPOSE: The purpose was to investigate the value of procalcitonin (PCT) kinetics in predicting the appropriateness of empirical antimicrobial treatment in critically ill patients. MATERIALS AND METHODS: This prospective observational study recruited patients in whom empirical antimicrobial therapy was started for suspected infection. Biochemical and physiological parameters were measured before initiating antimicrobials (t0), 8 hourly (t8, t16, t24), and then daily (day2-6). Patients were grouped post hoc into appropriate (A) and inappropriate (IA) groups. RESULTS: Of 209 patients, infection was confirmed in 67%. Procalcitonin kinetics were different between the IA (n = 33) and A groups (n = 108). In the IA group, PCT levels (median [interquartile range]) increased: t0= 2.8 (1.2-7.4), t16= 8.6 (4.8-22.1), t24= 14.5 (4.9-36.1), P< .05. In the A group, PCT peaked at t16 and started to decrease by t24: t0= 4.2 (1.9-12.8), t16= 6.99 (3.4-29.1), t24= 5.2 (2.0-16.7), P< .05. Receiver operating characteristic analysis revealed that a PCT elevation greater than or equal to 69% from t0 to t16 had an area under the curve for predicting inappropriate antimicrobial treatment of 0.73 (95% confidence interval, 0.63-0.83), P< .001; from t0 to t24, a greater than or equal to 74% increase had an area under the curve of 0.86 (0.77-0.94), P< .001. Hospital mortality was 37% in the A group and 61% in the IA group (P= .017). CONCLUSIONS: Early response of PCT in the first 24 hours of commencing empirical antimicrobials in critically ill patients may help the clinician to evaluate the appropriateness of therapy.

Can procalcitonin levels indicate the need for adjunctive therapies in sepsis?

After decades of extensive experimental and clinical research, septic shock and the related multiple organ dysfunction still remain the leading cause of mortality in intensive care units (ICUs) worldwide. Defining sepsis is a difficult task, but what is even more challenging is differentiating infection-induced from non-infection-induced systemic inflammatory response-related multiple organ dysfunction. As conventional signs of infection are often unreliable in intensive care, biomarkers are used, of which one of the most frequently investigated is procalcitonin. Early stabilisation of vital functions via adequate supportive therapy and antibiotic treatment has resulted in substantial improvements in outcome over the last decades. However, there are certain patients who may need extra help, hence modulation of the immune system and the host's response may also be an important therapeutic approach in these situations. Polyclonal intravenous immunoglobulins have been used in critical care for decades. A relatively new potential approach could be attenuation of the overwhelming cytokine storm by specific cytokine adsorbents. Both interventions have been applied in daily practice on a large scale, with firm pathophysiological rationale but weak evidence supported by clinical trials. The purpose of this review is to give an overview on the pathophysiology of sepsis as well as the role and interpretation of biomarkers and their potential use in assisting adjunctive therapies in sepsis in the future.

[Bacterial infection after orthotopic liver transplantation]. / Bakteriális infekciók májátültetés után.

INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.

Sepsis: From Pathophysiology to Individualized Patient Care.

Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review.