Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis

Background. Secondary hemophagocytic syndrome (SHPS) and sepsis, although very similar in their clinical manifestations and laboratory parameters, essentially differ in terms of methods of their treatment. SHPS therapy is aimed at immunosuppression, whereas in sepsis anti-infectious treatment is required. To choose the correct therapy a rapid differential diagnosis is necessary. Aim. Search and analysis of criteria of differential diagnosis between SHPS and sepsis. Materials & Methods. The data of 102 patients were analyzed: 55 SHPS patients (median age 60 and range 18–81 years) and 47 sepsis patients (median age 60 and range 18–89 years). SHPS was diagnosed on the basis of HLH-2004 and H-Score criteria. Sepsis was confirmed by documented inflammatory lesions and systemic inflammatory reactions. Microbiologically confirmed sepsis was reported in 10 (21 %) patients. In all sepsis patients multiple organ failure was identified. Results. The study of SHPS and sepsis groups revealed significant differences (p < 0.05) in the levels of C-reactive protein, procalcitonin, creatinine, albumin, and sodium. It was also found out that splenomegaly rate and the levels of triglycerides, ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in SHPS were significantly higher than in sepsis, but the levels of glycosylated ferritin (%GF), fibrinogen, leukocytes, neutrophils, and thrombocytes were lower. The following medians (quartiles 1–3) were reported in SHPS and sepsis, respectively: triglycerides (mmol/L) were 3.1 (2.3–3.8) and 1.5 (0.8–2.7), total ferritin (ng/mL) was 7,170 (3,159.2–12,551.0) and 1,274 (559.0–3,041.5), %GF was 26.5 (16.7–37.3) and 54.5 (37.7–71.8), fibrinogen (g/L) was 2.8 (1.4–4.4) and 5.3 (2.8–6.8), ALT (IU/L) was 50 (20–102) and 30 (15.3–55.5), AST (IU/L) was 66 (40.0–105.6) and 36 (24.6–78.0), leukocytes (×109/L) were 3.7 (2.1–5.5) and 8.9 (6.5–14.5), thrombocytes (×109/L) were 56 (25.2–93.5) and 157 (97–308). According to ROC analysis the areas under the curve were as follows: 0.88 for neutrophil level, 0.85 for total ferritin, %GF, leukocytes, and thrombocytes, 0.74 for triglycerides, 0.71 for fibrinogen, 0.65 for sodium, and 0.61 for ALT and AST. Conclusion. In differential diagnosis between SHPS and sepsis most important are the levels of total ferritin, its glycosylated fraction, and triglycerides; less important are fibrinogen, neutrophils, thrombocytes and spleen size. As diagnosis and differential diagnosis between SHPS and sepsis are based on the sum total of clinical and laboratory markers, none of the specified characteristics can serve as a reliable parameter if taken separately

Vasopressin, Central Autonomic Control and Blood Pressure Regulation

Purpose of Review: We present recent advances in understanding of the role of vasopressin as a neurotransmitter in autonomic nervous system control of the circulation, emphasizing hypothalamic mechanisms in the paraventricular nucleus (PVN) involved in controlling sympathetic outflow toward the cardiovascular system. Recent Findings: Suggest that somato-dendritically released vasopressin modulates the activity of magnocellular neurons in the PVN and SON, their discharge pattern and systemic release. Advances have been made in uncovering autocrine and paracrine mechanisms controlling presympathetic neuron activity, involving intranuclear receptors, co-released neuroactive substances and glia. Summary: It is now obvious that intranuclear release of vasopressin and the co-release of neuroactive substances in the PVN, as well as the level of expression of vasopressin receptors, modulate sympathetic outflow to the cardiovascular system and determine vulnerability to stress. Further research involving patho-physiological models is needed to validate these targets and foster the development of more efficient treatment.</p

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)