Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.

Fibrinolytic potential as a risk factor for postpartum hemorrhage.

Background: Postpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH. Methods: Blood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30-60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop > 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion. Results: Blood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30-60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well. Conclusion: We were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.

Plasma Transfusion in Septic Shock-A Secondary Analysis of a Retrospective Single-Center Cohort.

In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.

Mild Acquired Factor XIII Deficiency and Clinical Relevance at the ICU-A Retrospective Analysis.

Acquired FXIII deficiency is a relevant complication in the perioperative setting; however, we still have little evidence about the incidence and management of this rarely isolated coagulopathy. This study aims to help find the right value for the substitution of patients with an acquired mild FXIII deficiency. In this retrospective single-center cohort study, we enrolled critically ill patients with mild acquired FXIII deficiency (>5% and ≤70%) and compared clinical and laboratory parameters, as well as pro-coagulatory treatments. The results of the present analysis of 104 patients support the clinical relevance of FXIII activity out of the normal range. Patients with lower FXIII levels, beginning at <60%, had lower minimum and maximum hemoglobin values, corresponding to the finding that patients with a minimum FXIII activity of <50% needed significantly more packed red blood cells. FXIII activity correlated significantly with general coagulation markers such as prothrombin time, activated partial thromboplastin time, and fibrinogen. Nevertheless, comparing the groups with a cut-off of 50%, the amount of fresh frozen plasma, thrombocytes, PPSB, AT-III, and fibrinogen given did not differ. These results indicate that a mild FXIII deficiency occurring at any point of intensive care unit stay is also probably relevant for the total need of packed red blood cells, independent of pro-coagulatory management. In alignment with the ESAIC guidelines, the measurement of FXIII in critically ill patients with the risk of bleeding and early management, with the substitution of FXIII at levels <50%-60%, could be suggested.

Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study.

BACKGROUND: Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined. METHODS: In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled. Blood samples were collected at sepsis onset or prior and immediately after the surgical procedure as well as 3 h, 6 h, 12 h, 24 h, 48 h and 7 d later, whereas blood samples from healthy volunteers were collected once. Besides viscoelastic and aggregometric point-of-care testing (POCT), enzyme-linked immunosorbent and thrombin generation assays and liquid chromatography-mass spectrometry-based measurements were performed. RESULTS: As assessed by viscoelastic POCT, fibrinolysis shutdown occurred early in sepsis. Significant increases in tissue plasminogen activator had no effect on thromboelastometrical lysis indices (LIs). Contrariwise, plasminogen activator inhibitor-1 was already significantly increased at sepsis onset, which was paralleled by significantly increased LIs in patients suffering from septic shock in comparison with both control groups. This effect persisted throughout the 7-day observation period and was most pronounced in severely ill as well as non-surviving septic patients. Thromboelastometrical LI, therefore, proved to be suitable for early diagnosis [e.g. LI 45 min: area under the curve (AUC) up to 0.933] as well as prognosis (e.g. LI 60 min: AUC up to 1.000) of septic shock. CONCLUSIONS: Early inhibition of plasminogen activation leads to acute fibrinolysis shutdown with improved clot stability and is associated with increased morbidity and mortality in septic patients. Trial registration This study was approved by the local ethics committee (Ethics Committee of the Medical Faculty of Heidelberg; Trial-Code No. S247-2014/German Clinical Trials Register (DRKS)-ID: DRKS00008090; retrospectively registered: 07.05.2015). All study patients or their legal representatives signed written informed consent.

Following in the footsteps of Hippocrates-interrelation between the incidence of odontogenic abscess and meteorological parameters.

OBJECTIVES: Although many physicians in daily practice assume a connection between odontogenic infections and meteorological parameters, this has not yet been scientifically proven. Therefore, the aim of the present study was to evaluate the incidence of odontogenic abscess (OA) in relation to outdoor temperature and atmospheric pressure. PATIENTS AND METHODS: An analysis of patients with an odontogenic abscess who presented at the emergency department within a period of 24 months was performed. Only patients who had not received surgical or antibiotic treatment prior to presentation and who lived in Berlin/Brandenburg were included. The OA incidence was correlated with the mean/maximum outdoor temperature and atmospheric pressure starting from 14 days before presentation. The statistical analysis was carried out using Poisson regression models with OA incidence as dependent and meteorological parameters as independent variables. RESULTS: A total of 535 patients (mean age 39.4 years; range 1 to 95 years) with 538 cases were included. Of these, 227 were hospitalized. The most frequent diagnosis was a canine fossa abscess. A significant association between mean (p = 0.0153) and maximum temperature (p = 0.008) on the day of the presentation and abscess incidence was observed. Furthermore, a significant correlation between OA incidence and maximum temperature 2 days before presentation was found (p = 0.034). The deviation of the mean temperature on the day of the presentation from the monthly mean temperature had a significant influence (p = 0.021) on the incidence of OA. In contrast to temperature, atmospheric pressure had no significant influence on the incidence of OA. CONCLUSION: This study supports a relationship between the incidence of odontogenic abscess and outdoor temperature, but not atmospheric pressure. A significantly higher frequency of patients with an OA presented at our emergency department on days with (comparably) low and high outdoor temperatures. Furthermore, a significant correlation between incidence and maximum temperature 2 days before presentation was found. CLINICAL RELEVANCE: The treatment of odontogenic infections has become a significant economic burden to public health care facilities. The results of this study may help to adapt the numbers of doctors/dentists on duty in relation to different weather conditions. In any case, it is an impetus to think outside the box.

Odontogenic Abscess-Related Emergency Hospital Admissions: A Retrospective Data Analysis of 120 Children and Young People Requiring Surgical Drainage.

INTRODUCTION: Even today, despite medical progress and intensive health education, odontogenic infections leading to surgical intervention and hospitalization are common in children and young people. The aim of this study was to give a detailed overview of clinical and economic data on children and young people treated and hospitalized due to an odontogenic abscess at a tertiary university hospital. METHODS: A single-center retrospective analysis of patients under the age of 18 years who were hospitalized and surgically treated under local or general anesthesia for an odontogenic abscess during a period of 24 months was performed. RESULTS: A total of 120 patients (77 males; 43 females) within the observation period of 2 years were included. The mean age was 6.3 years (ranging from 1 to 17 years). The most frequent diagnosis was a canine fossa abscess (n = 52; 43.3%) and the left primary maxillary first molar could be identified as the most frequent source of infection. The average length of hospital stay was 1.82 days (ranging from 0 to 8 days). The duration was significantly correlated with the kind of abscess diagnosed (p < 0.001) and the duration of the surgical intervention in patients who were treated under general anesthesia (rho = 0.259, p = 0.005). A statistically significant relationship was observed between the kind of abscess and cost (p < 0.001). CONCLUSION: The length of hospital stay was significantly correlated with the kind of abscess diagnosed. The left primary maxillary first molar could be identified as the most frequent source of infection. A statistically significant relationship was observed between the kind of abscess and cost.