Background
Autologous stem cell transplantation (auto‐SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known.
Study design and ...methods
Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto‐SCT was evaluated.
Results
A higher graft CD34+ cell content predicted faster platelet recovery after auto‐SCT in both the short and long term. In patients with standard‐risk cytogenetics, a higher graft CD34+ count (>2.5 × 106/kg) was linked with shorter progression‐free survival (PFS; 28 vs. 46 months, p = 0.04), but there was no difference in overall survival (OS) (p = 0.53). In a multivariate model, a higher graft CD34+CD133+CD38− (>0.065 × 106/kg, p = 0.009) and NK cell count (>2.5 × 106/kg, p = 0.026), lenalidomide maintenance and standard‐risk cytogenetics predicted better PFS. In contrast, a higher CD34+ count (>2.5 × 106/kg, p = 0.015) predicted worse PFS. A very low CD3+ cell count (≤20 × 106/kg, p = 0.001) in the infused graft and high‐risk cytogenetics remained predictive of worse OS.
Conclusions
Autograft cellular composition may impact outcome in MM patients after auto‐SCT. More studies are needed to define optimal graft composition.
Coagulation factor XII (FXII) is a plasma serine protease that belongs to the contact activation complex responsible for initiating the intrinsic coagulation pathway. FXII deficiency is a rare ...congenital disorder that is not associated with an increased tendency for bleeding. However, as contact activation is impaired in FXII deficiency, both the celite- and kaolin-initiated activated clotting time (ACT) measurements are prolonged markedly, which poses a challenge for anticoagulation monitoring in patients undergoing cardiac surgery. The authors successfully have used the standard Hemochron Jr. ACT+ test, which is activated by silica and phospholipid in addition to kaolin, to monitor anticoagulation for cardiopulmonary bypass in two patients with severe FXII deficiency. The ACT+ test showed low baseline values, increased adequately in response to heparin, and decreased to baseline after protamine. Importantly, there was no abnormal intra- or postoperative bleeding nor any thrombotic complications. Furthermore, in vitro dose-response ACT+ testing of FXII-deficient blood with increasing heparin concentrations supports the use of ACT+ in FXII deficiency.
BACKGROUND
Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non‐Hodgkinʼs lymphoma (NHL).
STUDY DESIGN AND METHODS
In this ...prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome.
RESULTS
Multiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 106/kg vs. 3.9 × 106/kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count <20 × 106/L) was higher in NHL patients (15% vs. 3%, p < 0.001). Plerixafor was added to rescue the mobilization failure in 17 MM patients (12%) and in 35 NHL patients (26%; p = 0.002). The infused grafts contained more natural killer (NK) and CD19+ cells in MM patients. Blood platelet and NK‐cell counts were higher in MM patients posttransplant. Early treatment‐related mortality was low in both groups, but NHL patients had a higher late (>100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003).
CONCLUSIONS
Non‐Hodgkinʼs lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.
We were interested in whether C-reactive protein (CRP) and procalcitonin (PCT) distinguish sepsis from non-septic controls and whether a combination of CRP, PCT, and neutrophil CD64 improves ...identification of sepsis in the intensive care unit (ICU).
We analyzed the CRP and PCT concentrations from 27 patients with sepsis and 15 ICU controls. In addition, CD64 on neutrophils was measured using quantitative flow cytometry. We present a multiple marker analysis for sepsis diagnostics combining neutrophil CD64, CRP, and PCT using post-test analysis.
The CRP and PCT values separated sepsis and non-septic ICU patients. In post-test analysis, CRP provided a positive probability of 0.48 and a negative probability of 0.053 for sepsis in the ICU; while, the corresponding values were 0.35 and 0.0059, respectively, for PCT and 0.62 and 0.0013, respectively, for neutrophil CD64. When neutrophil CD64 was analyzed with PCT and CRP, the probabilities were 0.98 and <0.001, respectively.
Neutrophil CD64 expression was superior to PCT and CRP for the identification of sepsis in ICU. Positive post-test probability for any combinations of simultaneously analyzed CRP, PCT and CD64 showed improved diagnostic accuracy for sepsis. This approach may be useful for guiding antibiotic treatment in ICU.
•Neutrophil CD64 was better than PCT and CRP in the identification of sepsis in ICU.•PCT and CRP distinguished sepsis from non-septic ICU controls.•Simultaneous analysis of CD64, PCT and CRP showed improved diagnostic accuracy.
The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide ...analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (>1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis.
To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls.
Chorionic villus sampling was conducted after cesarean ...section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups.
Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB.
There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.
Postoperative thromboembolism is a significant cause of prolonged recovery in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). ...Thromboelastography (TEG) can detect hypercoagulable states and predict thromboembolic complications after surgery. This study assessed the impact of CRS and HIPEC on TEG values.
TEG parameters reaction time (R), kinetics time (K), angle (α), maximum amplitude (MA), and lysis percent at 60 min (LY60) were determined preoperatively, and at the end of CRS, during HIPEC, and at the end of the operation using blood samples from 15 HIPEC patients. Platelets, P-TT, and aPTT were also determined before and after CRS.
A total of 75 samples were analyzed. During CRS, there was a significant reduction in the mean MA (3.06 mm, p = 0.001). The mean P-TT declined by 32% (p < 0.001) and mean platelets by 55 × 10
9
/L (p < 0.001). During HIPEC, the mean R and K shortened by 1.04 min (p = 0.015) and 0.18 min (p = 0.018), respectively, whereas α increased by 2.48° (p = 0.005).
During CRS, both TEG and conventional laboratory tests indicated hypocoagulation. During HIPEC, however, the initiation of coagulation and the kinetics of thrombin formation were accelerated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Obesity causes a prothrombotic state and is known as a predisposing factor for thromboembolic events. In this pilot study, we assessed the impact of surgery for obesity and the subsequent ...weight loss on blood coagulation using traditional coagulation tests and thromboelastography (TEG).
Material and Methods
We studied blood samples from 18 patients receiving bariatric surgery. Besides traditional blood coagulation tests and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation, the TEG parameters reaction time (
R
), kinetics time (
K
), angle (
α
), maximum amplitude (MA), clot strength (
G
), and lysis percent at 60 min (LY60) were determined preoperatively and on the first postoperative day and 6 months after surgery.
Results
Altogether, 54 samples were analyzed. The median MA (71.3 mm),
G
(12,403.3 d/sc), and hsCRP (3.5 mg/l) were elevated preoperatively. The median hsCRP further increased on the first day postoperatively, but declined to the normal range 6 months after surgery, while MA and G remained elevated. In traditional coagulation tests, there was an increase in median fibrinogen and D-dimer postoperatively. D-dimer normalized (0.4 mg/l) during the study period, while the fibrinogen level (4.1 g/l) remained above the upper limit of normal.
Conclusions
Measured by TEG, patients receiving bariatric surgery have hemostatic abnormalities indicating hypercoagulation at the 6-month follow-up visit, suggesting an elevated risk for thromboembolic events for at least 6 months after surgery.
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