Supplemental fibrinogen restores thrombus formation in cardiopulmonary bypass-induced platelet dysfunction ex vivo.

BACKGROUND: Major cardiac surgery related blood loss is associated with increased postoperative morbidity and mortality. Platelet dysfunction is believed to contribute to post-cardiopulmonary bypass (CPB)-induced microvascular bleeding. We hypothesised that moderately hypothermic CPB induces platelet dysfunction and that supplemental fibrinogen can restore in vitro thrombus formation. METHODS: Blood from 18 patients, undergoing first-time elective isolated aortic valve surgery was drawn before CPB, 30 min after initiation of CPB, and after CPB and protamine administration, respectively. Platelet aggregation was quantified by optical aggregometry, platelet activation by flow-cytometric detection of platelet surface expression of P-selectin, annexin V, and activated glycoprotein IIb/IIIa, thrombus formation under flow and effect of supplemental fibrinogen (4 mg ml-1) on in vitro thrombogenesis. RESULTS: Post-CPB adenosine-diphosphate and TRAP-6-induced aggregation decreased by 40% and 10% of pre-CPB levels, respectively (P<0.0001). Although CPB did not change glycoprotein IIb/IIIa receptor expression, it increased the percentage of unstimulated P-selectin (1.2% vs 7%, P<0.01) positive cells and annexin V mean fluorescence intensity (15.5 vs 17.2, P<0.05), but decreased percentage of stimulated P-selectin (52% vs 26%, P<0.01) positive cells and annexin V mean fluorescence intensity (508 vs 325, P<0.05). Thrombus area decreased from 6820 before CPB to 5230 after CPB (P<0.05, arbitrary units [a.u.]). Supplemental fibrinogen increased thrombus formation to 20 324 and 11 367 a.u. before CPB and after CPB, respectively (P<0.001), thereby restoring post-CPB thrombus area to levels comparable with or higher than pre-CPB baseline. CONCLUSIONS: Single valve surgery using moderately hypothermic CPB induces partial platelet dysfunction. Thrombus formation was restored in an experimental study design by ex vivo supplementation of fibrinogen.

Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established. METHODS: We aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. In order to identify which pathways and phenotypes are associated with validated miRNAs we performed target prediction on genes expressed with high confidence in platelets. RESULTS: Circulating levels of miR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 were increased after euglycaemic clamp followed by hypoglycaemic clamp, each with its distinctive time trend. On the contrary, miR-129-2-3p, miR-92a-3p and miR-34a-3p remained unchanged. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (p = 0.002, p < 0.001, p = 0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and von Willebrand factor (vWF). Among all studied miRNAs, miR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Bioinformatic analysis of platelet-related targets of analyzed miRNAs showed strong enrichment of IL-2 signaling. We also observed significant enrichment of pathways and diseases related to cancer, CV diseases, hyperglycemia, and neurological diseases. CONCLUSIONS: Hypoglycaemia can significantly influence the expression of platelet-enriched miRNAs, with a time trend paralleling the time course of platelet activation. This suggests miRNAs could be exploited as biomarkers for platelet activation in response to hypoglycaemia, as they are probably released by platelets upon activation by hypoglycaemic episodes. Should they hold their promise in clinical endpoint studies, platelet-derived miRNAs might become helpful markers of CV risk in subjects with diabetes. Trial registration The study was registered at clinical trials.gov; Impact of Hypoglycaemia in Patients With DIAbetes Mellitus Type 2 on PLATElet Activation (Diaplate), trial number: NCT03460899.

Gender-specific differences in haemostatic parameters and their influence on blood loss in bimaxillary surgery.

OBJECTIVE: The objectives of this prospective cohort study were to establish gender-related differences in blood loss and haemostatic profiles associated with bimaxillary surgery. In addition, we aimed to identify if any gender differences could be established which might help predict blood loss volume. MATERIALS AND METHODS: Fifty-four patients (22 males; 32 females) undergoing bimaxillary surgery for skeletal dentofacial deformities were eligible for inclusion. Blood samples were taken 1 day preoperatively and 48 h postoperatively for detailed gender-specific coagulation analysis incorporating global coagulation assays (endogenous thrombin potential) and specific coagulation parameters. Blood loss was measured at two different time points: (1) the end of surgery, visible intraoperative blood loss (IOB) using 'subtraction method'; and (2) 48 h postoperatively perioperative bleeding volume (CBL-48 h) using 'haemoglobin-balance method' and Nadler's formula. Correlation and regression analyses were performed to identify relevant parameters affecting the amount of blood loss. RESULTS: Significant differences in IOB and CBL-48 h were observed (p < 0.001). Men had higher IOB versus women, lacking statistical significance (p = 0.056). In contrast, men had significantly higher CLB-48 h (p = 0.019). Reduced CBL-48 h was shown to be most closely associated with the level of Antithrombin-III being decreased in females. CONCLUSIONS: Male gender is associated with higher IOB and CBL-48 compared with females. Gender does not affect IOB regarding haemostatic profile but does correlate strongly with procedure length. Conversely, CBL-48 is closely associated with gender-specific imbalances in the anticoagulant system. CLINICAL RELEVANCE: Knowledge of gender-related differences will help clinicians establish predictive factors regarding excessive blood loss in orthognathic surgery and identify at-risk patients.

Increased Kynurenine Indicates a Fatal Course of COVID-19.

(1) Background: An inefficient immune response accompanied by an overwhelming inflammatory reaction is involved in severe courses of COVID-19. Kynurenine (KYN) has important immune-modulatory functions and may contribute to a failure in controlling SARS-CoV-2. The present study aims to explore biomarkers that hint at a fatal outcome of COVID-19 early on. (2) Methods: We established a cohort of 148 hospitalized COVID-19 patients for this study. Thirty-one patients died due to a severe COVID-19 course, and 117 recovered within 90 days. We built a biobank by collecting left-over material from these patients whenever blood arrived at the central laboratory of our University hospital for analysis of routine markers. The scientific laboratory analysis comprised KYN, Tryptophan (TRP), KYN/TRP ratio, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), creatinine, N-terminal pro-natriuretic peptide (NTproBNP), troponin T (TnT), fibrinogen, D-Dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT), protein C, protein S, factor XIII, lupus aPTT, angiotensin-2, vitamin D metabolites, and telomeres in all COVID-19 patients. Basic clinical characteristics and anteceding diseases including cardiovascular, oncologic, renal, hypertension, pulmonary, metabolic (diabetes, obesity) were recorded in a database together with the laboratory data. (3) Results: At the time of diagnosis of SARS-CoV-2 infection those patients who deceased within 90 days afterwards due to COVID-19, had a significantly higher age, higher KYN, KYN/TRP ratio, ferritin, creatinine, and NTproBNP values than SARS-CoV-2 patients who survived COVID-19 along the same time span. In a Kaplan-Meier analysis the variables age, KYN, ferritin, D-Dimer, TnT, NTproBNP, and creatinine showed a significant influence on survival time. Gender, however, showed no influence. In a combined Cox regression analysis KYN had the highest hazard ratio (1.188, 95% CI: 1.071-1.319) followed by age (1.041, 95% CI: 1.011-1.073). In a ROC analysis, KYN values above the cut off limit of 4.82 nmol/l (as specified by Youden index) had a sensitivity of 82% (95% CI: 66-95%) and a specificity of 72% (95% CI: 65-82%) to predict COVID-19 related death within 90 days observation time. (4) Conclusions: Kynurenine is a promising blood biomarker to predict an increased risk of mortality in SARS-CoV-2 infected people already at the time of the first positive SARS-CoV-2 verification detected in these persons.

Advanced isolated light chain amyloid cardiomyopathy with negative immunofixation and normal free light chain ratio.

Amyloid light chain (AL) cardiomyopathy is the most malignant specific cardiomyopathy. According to international recommendations, it should be ruled out non-invasively using the serum free light chain (FLC) ratio and immunofixation electrophoresis in both serum and urine. Here, we report on a 69-year-old female patient with new-onset heart failure with mid-range ejection fraction. Cardiac imaging was highly suggestive of cardiac amyloidosis. Amyloid scintigraphy showed faint myocardial tracer uptake according to Perugini Score 1, but immunofixation was negative and the FLC ratio was normal, despite a slight increase in lambda FLCs. Endomyocardial biopsy revealed advanced myocardial lambda immunoglobulin light chain deposition. Clinically relevant extracardiac amyloid organ infiltration could not be detected. Conclusively, non-invasive testing can in rare cases fail to exclude isolated AL amyloid cardiomyopathy. We suggest that even slight increases in serum lambda or kappa FLCs should be considered abnormal in suspected cardiac amyloidosis if non-invasive testing delivers discrepant results.

Supplemental Fibrinogen Restores Platelet Inhibitor-Induced Reduction in Thrombus Formation without Altering Platelet Function: An In Vitro Study.

BACKGROUND: For patients treated with dual antiplatelet therapy, standardized drug-specific 3-to-7 day cessation is recommended prior to major surgery to reach sufficient platelet function recovery. Here we investigated the hypothesis that supplemental fibrinogen might mitigate the inhibitory effects of antiplatelet therapy. METHODS AND RESULTS: To this end blood from healthy donors was treated in vitro with platelet inhibitors, and in vitro thrombus formation and platelet activation were assessed. Ticagrelor, acetylsalicylic acid, the combination of both, and tirofiban all markedly attenuated the formation of adherent thrombi, when whole blood was perfused through collagen-coated microchannels at physiological shear rates. Addition of fibrinogen restored in vitro thrombus formation in the presence of antiplatelet drugs and heparin. However, platelet activation, as investigated in assays of P-selectin expression and calcium flux, was not altered by fibrinogen supplementation. Most importantly, fibrinogen was able to restore in vitro thrombogenesis in patients on maintenance dual antiplatelet therapy after percutaneous coronary intervention. CONCLUSION: Thus, our in vitro data support the notion that supplementation of fibrinogen influences the perioperative hemostasis in patients undergoing surgery during antiplatelet therapy by promoting thrombogenesis without significantly interfering with platelet activation.

Ticagrelor and prasugrel are independent predictors of improved long-term survival in ACS patients.

AIM: To investigate the long-term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS). METHODS: In this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long-term mortality (median: 5.6 years; interquartile range [IQR] 4.9-6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)- and arachidonic acid (AA)-induced platelet aggregation. RESULTS: Type of P2Y12 inhibitor emerged as an independent predictor of long-term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long-term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22-0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20-0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non-ST elevation myocardial infarction (non-STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP- and AA-induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively). CONCLUSION: In the setting of ACS, treatment with ticagrelor or prasugrel reduced long-term mortality and 1-year MACE as compared to clopidogrel.

Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Atherosclerotic Plaque.

Atherosclerosis (AS) leading to myocardial infarction and stroke remains worldwide the main cause for mortality. Vulnerable atherosclerotic plaques are responsible for these life-threatening clinical endpoints. Atherosclerosis is a chronic, complex, inflammatory disease with interactions between metabolic dysfunction, dyslipidemia, disturbed microbiome, infectious triggers, vascular, and immune cells. Undoubtedly, the immune response is a most important piece of the pathological puzzle in AS. Although macrophages and T cells have been the focus of research in recent years, B cells producing antibodies and regulating T and natural killer (NKT) cell activation are more important than formerly thought. New results show that the B cells exert a prominent role with atherogenic and protective facets mediated by distinct B cell subsets and different immunoglobulin effects. These new insights come, amongst others, from observations of the effects of innovative B cell targeted therapies in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These diseases associate with AS, and the beneficial side effects of B cell subset depleting (modifying) therapies on atherosclerotic concomitant disease, have been observed. Moreover, the CANTOS study (NCT01327846) showed impressive results of immune-mediated inflammation as a new promising target of action for the fight against atherosclerotic endpoints. This review will reflect the putative role of B cells in AS in an attempt to connect observations from animal models with the small spectrum of the thus far available human data. We will also discuss the clinical therapeutic potency of B cell modulations on the process of AS.

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and ß-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

Incidence, predictors, and prognosis of premature discontinuation or switch of prasugrel or ticagrelor: the ATLANTIS - SWITCH study.

Aim of the present study was to investigate the frequency and predictors of premature discontinuation or switch of ADP receptor blockers and its association with serious adverse events. For this purpose 571 consecutive ACS patients receiving ticagrelor (n = 258, 45%) or prasugrel (n = 313, 55%) undergoing PCI were enrolled in this prospective, observational, multicenter ATLANTIS-SWITCH substudy. Predictors of premature discontinuation or switch of antiplatelet therapy and their association with major adverse cardiovascular events and TIMI bleeding events were evaluated. Premature stop/switch was found in 72 (12.6%) patients: 34 (5.9%) stopped and 38 (6.7%) switched the ADP blocker. Ticagrelor treated patients were significantly more likely to stop/switch therapy as compared to prasugrel (15.9% vs. 9.2%, p = 0.016). We identified 4 independent predictors for stop/switch of ADP blocker: major surgery, need for oral anticoagulation (OAC), TIMI major bleeding and drug intolerance. TIMI major bleeding was a driver of stop/switch actions and occurred in 4.3% vs 0.2% in patients with vs without stop/switch (p = 0.001). The majority of stop/switch actions (75%) were physicians driven decisions. Importantly, stop/switch of therapy was not associated with increased risk of MACE (p = 0.936). In conclusion premature switch/stop of ADP blockers appears to be safe when mainly driven by physician's decision and clinical indication.

Platelet reactivity patterns in patients treated with dual antiplatelet therapy.

AIM: The aim of the present study was to investigate the patterns of platelet reactivity and discriminators of therapeutic response to dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel in patients with acute coronary syndrome (ACS). DESIGN: In this multicentre prospective observational study, 492 patients with ACS were enrolled. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) or arachidonic acid (AA) as agonists in the maintenance phase of treatment with prasugrel or ticagrelor. RESULTS: Age emerged as the strongest variable influencing aspirin response status: The mean AA-induced platelet aggregation in patients <49 years of age was 49% higher than in those >49 years (13.1 U vs 8.8 U; P = 0.011). The second strongest discriminator of aspirin response was sex: Male patients had a 40% higher AA-induced platelet aggregation values than female patients (9.5 U vs 6.8 U; P = 0.026). Platelet count emerged as the only variable influencing ADP antagonists response status showing that patients with platelet count >320 g/L displayed higher ADP-induced platelet aggregation. About 12% of patients had high on-treatment platelet reactivity (HTPR) to aspirin, 3% and 4% a HTPR to prasugrel and ticagrelor, respectively, and only 2% displayed HTPR to dual antiplatelet therapy. CONCLUSION: When potent platelet inhibitors as prasugrel and ticagrelor are administered with aspirin, HTPR to DAPT plays only a marginal role.

Serum 1,3-Beta-D-Glucan Values During and After Laparoscopic and Open Intestinal Surgery.

BACKGROUND: 1,3-beta-D Glucan (BDG) assay has good accuracy for distinguishing patients with invasive fungal infections from patients without. Some procedures and medications affect BDG levels, resulting in false-positive BDG results. The extent of intestinal surgery on BDG kinetics is unknown. We evaluated the influence of laparoscopic and open intestinal surgery on peri- and postsurgical serum BDG values. METHODS: BDG was determined in 346 samples from 50 patients undergoing laparoscopic (24) or open (26) intestinal surgery at the following time points: after insertion of arterial but before skin incision, after skin incision but before dissection of the intestinal mucosa, after completion of anastomosis, after completion of skin sutures, in the evening after surgery, day 2 after surgery, 4-5 days after surgery. RESULTS: BDG was positive (ie, concentration ≥80 pg/mL) in 54% to 61% of patients during laparoscopic and open surgery (highest rates after completion of skin sutures). BDG was still positive in 12% (open) to 17% (laparoscopic) of patients without any suspected or proven fungal infection or anastomotic leakage 4-5 days after surgery. After completion of gut anastomosis, the BDG increase was higher in open compared with laparoscopic intestinal surgery. CONCLUSIONS: The value of positive BDG tests in the perioperative setting up to 5 days postsurgery seems to be limited due to BDG elevations from intestinal surgical procedures.

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients.

Dual antiplatelet therapy is the standard of care for patients with myocardial infarction (MI), who have been resuscitated and treated with therapeutic hypothermia (TH). We compare the antiplatelet effect and bleeding risk of intravenous cangrelor to oral P2Y12-inhibitors in patients with MI receiving TH in a prospective comparison of two matched patient cohorts. Twenty-five patients within the CANGRELOR cohort were compared to 17 patients receiving oral P2Y12-inhibitors. CANGRELOR group (NCT03445546) and the ORAL P2Y12 Group (NCT02914795) were registered at clinicaltrials.gov. Platelet function testing was performed using light-transmittance aggregometry and monitored for 4 days. P2Y12-inhibition was stronger in CANGRELOR compared to ORAL P2Y12 (adenosine diphosphate (ADP) (area under the curve (AUC)) 26.0 (5.9⁻71.6) vs. 160.9 (47.1⁻193.7)) at day 1. This difference decreased over the following days as more patients were switched from CANGRELOR to oral P2Y12-inhibitor treatment. There was no difference in the effect of aspirin between the two groups. We did not observe significant differences with respect to thrombolysis in myocardial infarction (TIMI) or Bleeding Academic Research Consortium (BARC) classified bleedings, number of blood transfusions or drop in haemoglobin B (Hb) or hematocrit (Hct) over time. Cangrelor treatment is not only feasible and effective in resuscitated patients, but also inhibited platelet function more effectively than orally administered P2Y12-inhibitors without an increased event rate for bleeding.

Is There a Role for Preoperative Platelet Function Testing in Patients Undergoing Cardiac Surgery During Antiplatelet Therapy?

Up to 11% of patients presenting with acute coronary syndromes undergo coronary artery bypass grafting. Guidelines largely recommend a one-size-fits-all preoperative discontinuation period for P2Y12 receptor blockers to avoid bleeding. These recommendations do not account for highly variable pharmacodynamic responsiveness and for variable recovery of platelet reactivity following discontinuation of P2Y12 receptor blockers. Several observational studies have demonstrated that an objective measurement of platelet function among these patients may reduce the waiting period while mitigating the risk of bleeding. Based on these findings, 2 recent guidelines included a Class IIa and IIb recommendation for platelet function testing in patients undergoing cardiac surgery. The following review article describes the rationale for discontinuation of dual antiplatelet therapy before cardiac surgery and the limitations with this approach, available platelet function assays to assess pharmacodynamic effects, and the association between platelet inhibition and other clinical factors with surgery-related bleeding. The information will assist the reader in determining which patients undergoing cardiac surgery might benefit from preoperative platelet function monitoring.

Diagnosis of invasive aspergillosis in hematological malignancy patients: Performance of cytokines, Asp LFD, and Aspergillus PCR in same day blood and bronchoalveolar lavage samples.

BACKGROUND: Aspergillus spp. induce elevated levels of several cytokines. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/tests for invasive aspergillosis (IA). METHODS: This cohort study included 106 prospectively enrolled (2014-2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both, serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, ß-D-glucan, and cytokines that have shown significant associations with IA before. RESULTS: Among 106 cases, 11 had probable IA, and 32 possible IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed better performance in BALF versus blood, with the exception of serum interleukin (IL)-8 which was the most reliable blood biomarker. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) showed promise for differentiating probable IA from no IA. CONCLUSIONS: High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

Impaired aspirin-mediated platelet function inhibition in resuscitated patients with acute myocardial infarction treated with therapeutic hypothermia: a prospective, observational, non-randomized single-centre study.

The majority of resuscitated patients present with underlying cardiac disease, and out of these myocardial infarction is most common. Immediate interventional treatment is recommended and routinely requires dual antiplatelet therapy including aspirin and a P2Y12-inhibitor. Therapeutic hypothermia or target temperature management is also recommended in these patients. Cardiogenic shock as well as reduced body temperature impacts platelet reactivity and its medical inhibition. The study aims to quantify aspirin- and P2Y12-mediated platelet inhibition in patients presenting with myocardial infarction and cardiopulmonary resuscitation. Twenty-five resuscitated patients were enrolled in this prospective, observational, non-randomized single-centre study. These patients were compared to 77 matched controls from the ATLANTIS-ACS database of non-resuscitated patients with myocardial infarction. Platelet function testing was performed by light transmittance aggregometry. Aspirin reactivity was monitored by inducing platelet aggregation with collagen and arachidonic acid, respectively. P2Y12 inhibition was recorded by stimulation of platelet aggregation with adenosine diphosphate. To quantify the overall platelet response, thrombin receptor-activated peptide was used. Aspirin-mediated platelet reactivity decreased significantly in resuscitated patients during the first days and was significantly weaker on day 3 (collagen AUC 253.8 (122.7-352.2) vs. 109.0 (73.0-182.0); p = 0.022). P2Y12-mediated platelet inhibition was also impaired in resuscitated patients on day 3 (mean ADP AUC (IQR): CPR 172.1 (46.7-346.5) vs. control 43.9 (18.9-115.2); p < 0.05). Aspirin- and P2Y12-mediated platelet inhibition is impaired in resuscitated patients treated with therapeutic hypothermia. On day 3, we recorded lowest inhibitory effects of both drug types and patients might be at particular risk at that time. Potentially, intravenous aspirin and P2Y12 inhibitors might still supply a more predictable and stable platelet inhibition.

Levels of interleukin (IL)-6 and IL-8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis.

Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at -70°C for retrospective determination of cytokines. IL-6 and IL-8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL-10 (P = .059). In multivariate conditional logistic regression analysis, IL-10 remained a significant predictor of IPA in serum and IL-8 among BALF cytokines. In conclusion, levels of IL-6 and IL-8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL-10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy.

INTRODUCTION: The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. MATERIALS AND METHODS: Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. RESULTS: No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 - 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. CONCLUSIONS: Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced.

Chemotherapy-Induced Intestinal Mucosal Barrier Damage: a Cause of Falsely Elevated Serum 1,3-Beta-d-Glucan Levels?

Blood citrulline and intestinal fatty acid binding protein were determined as biomarkers for intestinal mucositis. Biomarker levels were correlated with corresponding serum 1,3-beta-D-glucan levels in 56 samples obtained from 33 cases with underlying hematological malignancies receiving induction chemotherapy. No correlation between biomarkers of intestinal mucositis and BDG levels was observed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.).