Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

Introduction

Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O₂) delivery but rarely improves tissue O₂ uptake in patients with sepsis. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis.

Methods

In a prospective randomized trial, 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O₂ saturation (StO₂) and tissue hemoglobin index (THI) were determined with near-infrared spectroscopy, and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage, and glycocalyx compounds (syndecan-1, hyaluronan, and heparan sulfate) were measured in the serum.

Results

No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When within-group changes were examined, microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01), and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO₂ upslope increased in both groups. StO₂ and StO₂ downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03).

Conclusions

This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis, although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings.

Trial registration

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01584999","term_id":"NCT01584999"}}NCT01584999     

Intrahepatic hepatitis C virus RNA quantification in microdissected hepatocytes

BACKGROUND/AIMS: Debate continues on whether serum and intrahepatic HCV viral loads are correlated and if HCV viral load correlates with the severity of liver disease. These difficulties may at least in part be linked to liver cell heterogeneity, when total liver extracts from HCV-infected individuals are tested for HCV RNA quantification. We have therefore investigated the feasibility of quantifying HCV replication using a laser-based microdissection technique. METHODS: We compared the results with those obtained for serum HCV RNA quantification and immunochemistry in the case of HCV antigen detection in the liver. Twenty-one HCV-positive patients with chronic active hepatitis (n=10) or cirrhosis (n=11) were analyzed. RESULTS: A positive correlation (P=0.0019) was observed between HCV RNA quantifications in sera and microdissected cells. Immunohistochemistry demonstrated that HCV antigen hepatocytes were randomly distributed within liver lobules. Their percentage varied in different patients (0-40%), but did not correlate with the HCV viral load. CONCLUSIONS: We have designed a sensitive methodology to evaluate the intrahepatic HCV viral load by combining a standardized RNA quantification method with microdissected hepatocytes from frozen liver needle biopsies. Our results directly demonstrate a positive correlation between serum and intrahepatic viral loads, which therefore provides a reliable reflection of intrahepatic HCV replication.     

Continuous care in the treatment of obesity: an observational multicentre study

OBJECTIVES: To investigate weight loss and reasons for attrition in obese patients on long-term continuous care. DESIGN: Observational study with 36 months of follow-up. Setting. Fifteen Italian obesity centres applying a continuous care model of medical treatment. SUBJECTS: One thousand treatment-seeking obese subjects (785 females, median age 45.1 years, median BMI 37.4 kg m(-2)). Weight loss expectations were systematically recorded at baseline. INTERVENTIONS: An initial intensive treatment period (3-6 months) was followed by a less intensive continuous care (a follow-up control every 2-4 months). Main outcome measures. Attrition, reasons for treatment interruption and BMI change. Data were recorded by telephone interview in dropouts. RESULTS: Only 157 patients (15.7%) were in continuous treatment at 36 months. The main reasons of attrition were logistics, unsatisfactory results and lack of motivation. The only basal predictor for continuous care was lower Expected One-Year BMI Loss (P = 0.016). The probability of dropout increased systematically for any 5% expected BMI loss (Hazard ratio, 1.05; 96% confidence interval, 1.01-1.09). The mean percentage weight loss was greater in continuers (5.2% vs. 3.0% in dropouts; P = 0.016). However, the dropouts satisfied with the results or confident to lose additional weight without professional help reported a mean weight loss of 9.6% and 6.5% respectively. DISCUSSION: Continuous care produces long-term weight loss only in a subgroup of obese patients seeking treatment in medical centres. The finding that subgroups of dropouts report long-term weight loss has implication for the treatment of obesity.     

Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic

Purpose  This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. Methods  Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. Results  Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. Conclusion  The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals. This work was supported by ZonMw, the Netherlands Organization for Health Research and Development.     

Radioimmunoassay typing gives a more precise definition of the HLA association of Type I (insulin-dependent) diabetes

Summary The problem of the HLA association of Type 1 (insulin-dependent) diabetes was re-examined by testing Class II antigenic specificities detectable by radioimmunoassay. Established (DRw53, DQwl, DQw2, DQw3) as well as newly described (DC5, DCalpha3) specificities were typed. The data obtained suggest that the association with DR3 and DR4 is secondary to that with DQ specificities in linkage disequilibrium with DR3 and DR4.     

Bilateral total extraperitoneal inguinal hernia repair (TEP) has outcomes similar to those for unilateral TEP: population-based analysis of prospective data of 6,505 patients

Background  

Whether bilateral total extraperitoneal (TEP) inguinal hernia repair is associated with worse outcomes than unilateral TEP continues to be a matter of debate. This study aimed to compare different outcomes of large cohorts of patients undergoing bilateral versus unilateral TEP.     

Cellular expression and genetic control of ABH antigens in primary sensory neurons of marmoset, baboon and man

ABH antigens have been demonstrated in the posterior root ganglia (PRG) of 3 primate species (marmoset, baboon and man). Their expression corresponded to the ABO phenotype of the individual and was independent of the secretor gene. In marmosets more cells were positive for H (33 +/- 9%) than for A (19 +/- 6%). In baboons A or B antigens were more easily detected (66 +/- 9%) than the H antigens (48 +/- 5%). In humans more than two-thirds of PRG cells were positive for H but only a small proportion of these were positive for A or B. The ABH antigens were found mainly in the small and intermediate-size neurons whose central processes project to lamina II of the spinal cord posterior horn. Unipolar neurons of the Gasserian ganglion, neurons of the mesencephalic nucleus of the trigeminal nerve and of some visceral ganglia have also been shown to express these antigens which are also present in the fibre layer and glomeruli of the olfactory bulbs.     

The effect of positive semen bacterial and Ureaplasma cultures on in-vitro fertilization success

A total of 342 couples planning to undergo in-vitro fertilization(IVF) were examined for the presence of bacteria in semen priorto and during the procedure. Pregnancy rates were analysed retrospectivelyto ascertain any adverse affects if >10 000 colony formingunits (CFU)/ml bacteria were detected in the semen sample. Themost common bacteria isolated from semen were Enterococcus spp.(73%). The presence of these bacteria did not affect the pregnancyrate of the patients with positive cultures prior to (32%) orduring (37%) the IVF procedure compared with those patientsin whom no bacteria were detected (32%). Those patients withsemen cultures positive for Escherichia coli prior to the IVFprocedure, but which cleared after treatment had a higher pregnancyrate (60%) compared with those patients who were positive forE.coli at the time of the attempt The group of patients withStaphylococcus aureus in the semen at the time of IVF also demonstrateda low pregnancy rate (17%). Of the patients, 36 (11%) had positiveUreaplasma cultures from the screening test carried out on thesemen and 22% became pregnant after successful treatment Noneof the three patients with persistently positive cultures becamepregnant in conclusion, the presence of Enterococcus in semendoes not affect pregnancy rates following IVF. E.coli, S.aureusand Ureaplasma urea-lyticum may have a negative effect and shouldbe treated.