Cytokine generation in stored platelet concentrates

BACKGROUND: Cytokines, because of the nature of their immunoinflammatory actions, are potential mediators of the symptom complex of nonhemolytic transfusion reactions. One possible source of cytokines in the transfusion setting is the stored blood component itself. STUDY DESIGN AND METHODS: To test this possibility, the plasma portion of stored platelet concentrates (PCs) was assayed for the presence of interleukins 1 beta (IL-1 beta), 6 (IL-6), and 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha). Samples were taken from PCs obtained from the inventory of a regional blood center (n = 120; 30 each of 2-, 3-, 4-, and 5-day-old units). RESULTS: Detectable levels of IL-8 were measured in 59 percent of the PCs sampled, ranging from 30 percent of the 2-day-old units to 83 percent of the 5-day-old units. The median IL-8 concentration ranged from undetectable levels in 2-day- old units up to 1100 pg per mL in 5-day-old units. The mean IL-8 concentration in 5-day-old units, 11,600 pg per mL, was 100 times the mean for 2-day-old units, which was 116 pg per mL (p < 0.0001). The highest levels of IL-8, 50,000 to 200,000 pg per mL, in general were found in units with the longest storage times and highest white cell counts. Sequential sampling of 17 individual PCs over 7 days of storage confirmed that IL-8 increases progressively with increasing storage time. Parallel, but smaller, increases in IL-1 beta were observed in those units with high IL-8 concentrations. TNF-alpha was detected in 3 (10%) of 30 five-day-old PCs, but never exceeded 55 pg per mL in any unit tested. IL-6 at levels of 740 and 508 pg per mL was detected in two 5-day-old units with high white cell counts of 9500 and 14,800 per microL, respectively, but not in 21 additional units tested with white cells < or = 9200 per microL or storage time of < or = 2 days. White cell reduction by third-generation filters on Day 1 of platelet storage prevented the generation of IL-8 and IL-1 beta to Day 5 of storage. CONCLUSION: Although IL-8 achieved levels in some units of PCs that appear capable of causing physiologic changes, the potential adverse effect on transfusion recipients of the infusion of cytokines in PCs remains to be investigated.     

Homocysteine and markers of inflammation in acute coronary syndrome

BACKGROUND:

An elevated level of homocysteine (Hcy) has been shown to be a cardiovascular risk factor in the majority of research studies. Recently, it was found to be associated with new risk factors such as inflammatory markers.

OBJECTIVES:

To investigate the distribution of plasma total Hcy (tHcy) and the levels of inflammatory markers in patients with acute coronary syndrome (ACS), and to evaluate the association between these parameters and the severity of the disease.

METHODS:

A total of 122 patients with ACS and 80 control subjects were recruited from the cardiac intensive care unit of the Military Hospital of Tunis, Tunisia. Lipid profile and the levels of tHcy, high-sensitivity C-reactive protein (HsCRP), interleukin (IL)-6, IL-8, IL-1β and tumour necrosis factor-alpha (TNFα) were determined for all participants. The distribution of these parameters were compared between groups and according to the number of diseased vessels in patients with ACS.

RESULTS:

ACS patients had significantly elevated levels of tHcy (P<0.01), HsCRP (P<0.001), IL-6 (P<0.001), TNFα (P<0.001), folates (P<0.05) and vitamin B₁₂ (P<0.001), but lower high-density lipoprotein cholesterol (P<0.05) levels. The analysis of the association between these parameters and the number of diseased vessels showed significant differences in tHcy, HsCRP, IL-6 and TNFα, with positive correlations. Significantly negative correlations were found between the number of diseased vessels and folate (r=−0.34; P<0.01), and vitamin B₁₂ (r=−0.22; P<0.01).

CONCLUSION:

Elevated levels of tHcy, IL-6, TNFα and HsCRP appear to be associated with a greater number of diseased arteries and, consequently, the severity of coronary artery disease.     

Recurrent supraventricular tachycardias prevalence and pathophysiology after RF ablation: A 5-year registry

Background

The introduction of technique of radiofrequency (RF) catheter ablation in 1990, has revolutionized management of different types of paroxysmal supraventricular tachycardia (PSVT). In spite of higher success rate, there were reported recurrences among different types of SVT. The aim of this study was to report the efficacy of RF ablation, its complications, recurrence rate and its predictors.

Methods

The material of this study (our 3rd registry) included patients who underwent electrophysiological study (EPS) and radiofrequency ablation of their supraventricular tachycardia in the past 5 years, starting from January 2002 to January 2007 at The Critical Care Medicine Department, Cairo University.

Results

Out of 400 pts studied, 381 (95%) had been subjected to radiofrequency ablation (RF) ablation while the remaining 19 pts (4.7%) refused ablation for fear of possible complications. Out of the 381 pts, 366 (96%) had their target tachycardia successfully terminated, from them 26 pts (7%) experienced recurrence after having successful RF ablation. Nine pts (34.6%) of total recurrence was reported in pts with AVNRT, 7 pts (26.9%) of total recurrence was reported in pts with AVRT utilizing septal accessory pathway (Rt AS and /or Rt PS AP), 4 pts (15.4%) was reported in pts with double AP, 2 pts (7.7%) of total recurrence was reported in pts with AFl, one pt (3.8%) of total recurrence was reported in cases of AT. Redo ablation have been carried out successfully in 25 pts (96.2%), and one pt (3.8%) refused ablation for fear of possible complications.

Conclusions

Although electrophysiological study and RF ablation eliminated different types of SVT. However, there may be increased incidence of recurrence among pts with AVNRT and AVRT utilizing concealed septal AP and multiple APs secondary to the complexity of AVN physiology, the critical location of septal AP, the clinical expertise, and poor electrophysiological criteria for good procedural success.     

The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport

Fast axonal transport is characterized by the bidirectional, microtubule-based movement of membranous organelles. Cytoplasmic dynein is necessary but not sufficient for retrograde transport directed from the synapse to the cell body. Dynactin is a heteromultimeric protein complex, enriched in neurons, that binds to both microtubules and cytoplasmic dynein. To determine whether dynactin is required for retrograde axonal transport, we examined the effects of anti-dynactin antibodies on organelle transport in extruded axoplasm. Treatment of axoplasm with antibodies to the p150^Glued subunit of dynactin resulted in a significant decrease in the velocity of microtubule-based organelle transport, with many organelles bound along microtubules. We examined the molecular mechanism of the observed inhibition of motility, and we demonstrated that antibodies to p150^Glued disrupted the binding of cytoplasmic dynein to dynactin and also inhibited the association of cytoplasmic dynein with organelles. In contrast, the anti-p150^Glued antibodies had no effect on the binding of dynactin to microtubules nor on cytoplasmic dynein-driven microtubule gliding. These results indicate that the interaction between cytoplasmic dynein and the dynactin complex is required for the axonal transport of membrane-bound vesicles and support the hypothesis that dynactin may function as a link between the organelle, the microtubule, and cytoplasmic dynein during vesicle transport.     

Sexualized drug use (‘chemsex’) and high‐risk sexual behaviours in HIV‐positive men who have sex with men

Objectives

The incidence of sexually transmitted infections (STIs) and HIV infection remains high in gay, bisexual, and other men who have sex with men (MSM) in the UK, and sexualized drug use (“chemsex”) and injecting drug use (“slamsex”) may play a part in this. We aimed to characterize HIV‐positive MSM engaging in chemsex/slamsex and to assess the associations with self‐reported STI diagnoses and sexual behaviours.

Methods

Data from a 2014 survey of people attending HIV clinics in England and Wales were linked to clinical data from national HIV surveillance records and weighted to be nationally representative. Multivariable logistic regression assessed the associations of chemsex and slamsex with self‐reported unprotected anal intercourse (UAI), serodiscordant UAI (sdUAI) (i.e. UAI with an HIV‐negative or unknown HIV status partner), sdUAI with a detectable viral load (>50 HIV‐1 RNA copies/mL), hepatitis C, and bacterial STIs.

Results

In the previous year, 29.5% of 392 sexually active participants engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated with increased odds of UAI [adjusted odds ratio (AOR) 5.73; P < 0.001], sdUAI (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01), hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P < 0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05), hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P < 0.001).

Conclusions

Three in ten sexually active HIV‐positive MSM engaged in chemsex in the past year, which was positively associated with self‐reported depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STIs, and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI epidemics in the UK.     

Effects of methylene blue-treated plasma on red cells and stored platelet concentrates

BACKGROUND: Photochemical methods can effectively inactivate extracellular viruses and bacteria found in blood components. Treatment of plasma with methylene blue (MB), a phenothiazine dye, and visible light inactivates enveloped viruses including HIV-1. The effects of MB- treated plasma on cellular components stored in vitro have not been well characterized. STUDY DESIGN AND METHODS: MB-treated plasma (83 microg MB/250 mL plasma) was added to single-donor platelets, stored AS- 1 red cells (RBCs), irradiated RBCs, and frozen-deglycerolized RBCs. In vitro platelet assays performed after 1 and 5 days of storage in MB- treated plasma included pH, pO2, pCO2, HCO3, platelet number, lactate dehydrogenase, glucose, osmotic recovery, and CD62 expression. RBC components were examined at specific intervals for leakage of potassium, plasma hemoglobin level, and percentage of hemolysis. Direct antiglobulin tests, osmotic fragilities, and RBC antigen stability tests were also performed on RBCs stored in MB-treated plasma. Components stored with autologous plasma or nontreated allogeneic plasma served as controls. RESULTS: Similar storage-induced changes in pH, glucose, and platelet numbers, as well as increases in lactate dehydrogenase, CD62 expression, and lactate were seen in single-donor platelets stored with MB-treated and control plasma. Platelet morphology scores and osmotic recoveries were not altered. Plasma hemoglobin and potassium and percentage of hemolysis increased equally in the various RBC components stored with MB-treated or nontreated plasma. Osmotic fragility and RBC antigen stability were not appreciably altered by MB-treated plasma. CONCLUSION: Plasma treated by MB photoinactivation can be used for in vitro resuspension and storage of platelets or RBCs, because of the lack of influence of MB-treated plasma on a variety of in vitro platelet and RBC assays.     

In vitro characteristics of volume-reduced platelet concentrate stored in syringes

For convenience, small volumes of platelet concentrate (PC) intended for neonatal patients are often dispensed in syringes. The PC, however, may remain in the syringe for up to several hours before the actual transfusion. As there are few data on the effect of such syringe storage on PCs, the in vitro syringe storage properties of small volumes of 1- and 5-day-old units, and volume-reduced units of PC were evaluated. In four separate experiments, PCs were stored in syringes in volumes of 10, 15, or 30 mL for up to 6 hours at 20 to 24 degrees C without agitation. Platelets were evaluated for pH, platelet count, and a variety of biochemical and in vitro functional assays. Results showed that even with the equivalent of a full unit of platelets stored in the syringe for up to 6 hours, the pH did not fall below 6.0. Although there was an increase in lactate production and consumption of glucose, which paralleled the decline in pH, the changes were not greater than those seen in platelets stored up to 5 days in gas-permeable blood bags. Similar results were seen for PCs stored in syringes for 6 hours at 37 degrees C. All of the pH levels recorded at the end of 6 hours of syringe storage were above the minimum required level of pH 6.0. Data from in vitro platelet assays imply that at any time during their shelf life, PCs can be stored in gas-impermeable polypropylene syringes for up to 6 hours and can maintain acceptable storage characteristics; in vivo data are needed to confirm these observations.