Respiratory quotient estimations as additional prognostic tools in early septic shock

Central venous-to-arterial carbon dioxide difference (P_cvaCO₂), and its correction by the arterial-to-venous oxygen content difference (P_cvaCO₂/C_avO₂) have been proposed as additional tools to evaluate tissue hypoxia. Since the relationship between pressure and content of CO₂ (CCO₂) might be affected by several factors, some authors advocate for the use of C_cvaCO₂/C_avO₂. The aim of the present study was to explore the factors that might intervene in the difference between P_cvaCO₂/C_avO₂ and C_cvaCO₂/C_avO₂, and to analyze their association with mortality. Observational study in a 30-bed mixed ICU. Fifty-two septic shock patients within the first 24 h of ICU admission were studied. After restoration of mean arterial pressure, hemodynamic and metabolic parameters were evaluated. A total of 110 sets of measurements were performed. Simultaneous P_cvaCO₂/C_avO₂ and C_cvaCO₂/C_avO₂ values were correlated, but agreement analysis showed a significant proportional bias. The difference between P_cvaCO₂/C_avO₂ and C_cvaCO₂/C_avO₂ was independently associated with pH, S_cvO₂, baseline C_cvaCO₂/C_avO₂ and hemoglobin. A stepwise regression analysis showed that pH was the single best predictor for the magnitude of such difference, with very limited effect of other variables. At inclusion, variables associated with ICU-mortality were lactate, pH, P_cvaCO₂/C_avO₂, and the difference between P_cvaCO₂/C_avO₂ and C_cvaCO₂/C_avO₂. Initial S_cvO₂, P_cvaCO₂, C_cvaCO₂/C_avO₂, and cardiac index were not different in survivors and non-survivors. In a population of early septic shock patients, simultaneous values of P_cvaCO₂/C_avO₂ and C_cvaCO₂/C_avO₂ were not equivalent, and the main determinant of the magnitude of the difference between these two parameters was pH. The P_cvaCO₂/C_avO₂ ratio was associated with ICU mortality, whereas C_cvaCO₂/C_avO₂ was not.     

A randomized comparison of once versus twice daily recombinant human granulocyte colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation

To evaluate the schedule dependency of granulocyte colony-stimulating factor (G-CSF) (filgrastim) for stem cell mobilization, we conducted a randomized comparison in 50 healthy donors, with one subcutaneous daily injection of 10 microg/kg G-CSF (n = 25) compared with twice injections daily of 5 microg/kg G-CSF (n = 25). The two groups were well balanced for age, body weight and sex. G-CSF application was performed on an out-patient basis and leukapheresis was started in all donors on day 5. The most frequent side-effects of G-CSF were mild to moderate bone pain (88%), mild headache (72%), mild fatigue (48-60%) and nausea (8%) without differences between the two groups. The CD34(+) cell count in the first apheresis was 5.4 x 10(6)/kg donor weight (range 2.8-13.3) in the 2 x 5 microg/kg group compared with 4.0 x 10(6)/kg (range 0.4-8.8) in the 1 x 10 microg/kg group (P = 0.007). The target of collecting > 3.0 x 10(6) CD34(+) cells/kg donor weight with one apheresis procedure was achieved in 24/25 (96%) donors in the 2 x 5 microg/kg group and in 17/25 (68%) donors in the 1 x 10 microg/kg group. The target of collecting > 5.0 x 10(6) CD34(+) cells/kg in the first apheresis was achieved in 64% in the 2 x 5 microg/kg group, but in only 36% in the 1 x 10 microg/kg group. The progenitor cell assay for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) was higher in the 2 x 5 microg/kg group than in the 1 x 10 microg/kg group (7.0 vs. 3.5 x 10(5)/kg, P = 0.01; 6.6 vs. 5.0 x 10(5)/kg; P = 0.1). Administering G-CSF (filgrastim) at a dosage of 5 microg/kg twice daily rather than 10 microg/kg once daily is recommended; this leads to a higher CD34(+) cell yield and requires fewer apheresis procedures without increasing toxicity or cost.     

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p?=?0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p?=?0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32–6.35; HR 2.90; p?=?0.008), but not event-free survival (EFS; 95% CI 0.62–2.67; HR 1.28; p?=?0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01–1.09; HR 1.05; p?=?0.009), while both ANC (95% CI 1.00–1.07; HR 1.04; p?=?0.04) and peripheral blood blast percentage (95% CI 1.02–1.32; HR 1.16; p?=?0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.     

Value of automated segmental motion analysis in the assessment of aortic stenosis severity

BACKGROUND AND AIMS OF THE STUDY: Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity. METHODS: Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated. RESULTS: A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p <0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve area < or =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index >0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively. CONCLUSION: The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.     

Molecular Identity of Hematopoietic Precursor Cells Emerging in the Human Embryo

It is now accepted from studies in animal models that hematopoieticstem cells emerge in the para-aortic mesoderm-derived aorta-gonad-mesonephros region of the vertebrate embryo. We have previously identified the equivalent primitive hematogenous territory in the 4- to 6-week human embryo, under the form ofCD34⁺CD45⁺Lin highproliferative potential hematopoietic cells clustered on the ventralendothelium of the aorta. To characterize molecules involved in initialstem cell emergence, we first investigated the expression in thatterritory of known early hematopoietic regulators. We herein show thataorta-associated CD34⁺ cells coexpress the tal-1/SCL,c-myb, GATA-2, GATA-3, c-kit, and flk-1/KDR genes, as do embryonic andfetal hematopoietic progenitors later present in the liver and bonemarrow. Next, CD34⁺CD45⁺ aorta-associatedcells were sorted by flow cytometry from a 5-week embryo and a cDNAlibrary was constructed therefrom. Differential screening of thatlibrary with total cDNA probes obtained from CD34⁺embryonic liver cells allowed the isolation of a kinase-related sequence previously identified in KG-1 cells. In addition to emerging blood stem cells, KG-1 kinase is also strikingly expressed in alldeveloping endothelial cells in the yolk sac and embryo, which suggestsits involvement in the genesis of both hematopoietic and vascular celllineages in humans.     

Myocardial perfusion in real-time using power modulation. In vivo evidence for microcirculatory damage after acute myocardial infarction

BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received beta-radiation therapy as well as conventional therapy has also not been studied. METHODS: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. RESULTS: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/- 3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0 mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Delta EEM area between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/- 0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.