Blood Transfusions in Major Pancreatic Surgery: A 10-Year Cohort Study Including 1404 Patients Undergoing Pancreatic Resections in Finland.

BACKGROUND: Despite guidelines on blood transfusion (TF) thresholds, there seems to be great variation in transfusion policies between hospitals and surgeons. In order to improve and unify blood transfusion policies, the Finnish Red Cross Blood Service carried out a project concerning the optimal use of blood products (Verivalmisteiden optimaalinen käyttö) between 2002 and 2011. In this study, we determined the blood transfusion trends in major pancreatic surgery in Finland. METHODS: Initially, 1337 patients who underwent major pancreatic resections between 2002 and 2011 were classified into the TF+ or TF- groups. Centers were divided into high-, medium-, and low-volume centers. The blood transfusion trends and the trigger points for blood transfusions in these patients were determined. RESULTS: There were no differences between high-, medium- and low-volume centers in blood usage, trigger points or the use of reserved blood units after pancreatoduodenectomy or total pancreatectomy. However, the trigger points were lowered significantly during the study period at high-volume centers (p = 0.003), and a better use of reserved blood units was found in high- (p < 0.001) and medium-volume (p = 0.043) centers. In addition, a better use of reserved blood units was found in high-volume centers after distal pancreatectomy (p = 0.020). CONCLUSION: Although only minor changes in blood transfusion trends after pancreatoduodenectomy or total pancreatectomy were found generally, the lowering of the transfusion trigger point and the best use of reserved blood units during the study period occurred in high-volume centers.

Platelet donor selection for HLA-immunised patients; the impact of donor-specific HLA antibody levels.

BACKGROUND: Approximately 20% of patients with a recurrently poor platelet transfusion increment show human leukocyte antigen (HLA) alloantibodies. The aim of this study was to analyse the impact of mean fluorescence intensity (MFI) levels of donor-specific HLA antibodies and the feasibility of the HLAMatchmaker algorithm in donor selection. STUDY DESIGN AND METHODS: A total of 270 HLA-typed platelet transfusion responses of 40 patients were included in the study. The patients' immunisation status was determined with Luminex-based methods, and HLA alloantibody strengths were defined as the MFI. For the Matchmaker eplet matching, the HLA-ABC Eplet Matching Version 2.1 was used. RESULTS: In 62% of the 270 transfusions, HLA antibodies against the transfused platelets were present, with a median cumulative MFI level of 2026 (range: 299-29 203). In multivariate analysis, a cumulative MFI level higher than 1000 emerged as an independent risk factor for a poor platelet transfusion increment, along with infection and the age of the product. CONCLUSION: The HLAMatchmaker algorithm alone is not a sufficient tool for donor selection. Donor selection based primarily on the levels of donor-specific HLA antibodies is a preferable practice.

The Use of Blood Products in Adult Patients with Burns.

INTRODUCTION: Burn anemia represents a common complication following a burn injury. Burn anemia etiology carries distinct features occurring at each stage of the post-injury and treatment periods resulting from different causes. We aimed to analyze the use of blood components in Finnish burn victims and to identify patient- and injury-related factors influencing their use. METHODS: To study the use of blood products in burn patients, we used data collected from the Optimal Use of Blood registry, developed through co-operation between 10 major hospital districts and the Finnish Red Cross Blood Service. Burn patients ⩾18 years treated at the Helsinki University Hospital between 2005 and 2011 with an in-hospital stay ⩾1 day who received at least one transfusion during their hospital stay were included in this study. RESULTS: Among all 558 burn patients, 192 (34%) received blood products during their hospital stay. The transfused cohort comprised 192 burn patients. The study cohort received a total of 6087 units of blood components, 2422 units of leukoreduced red blood cells, 1728 units of leukoreduced platelets, and 420 units of single-donor fresh frozen plasma or, after 2007, 1517 units of Octaplas(®) frozen plasma. All three types of blood components were administered to 29% of patients, whereas 45% received only red blood cells and 6% received only Octaplas. Transfused patients were significantly older (p < 0.001), experienced fire-/flame-related accidents and burns to multiple locations (p < 0.001), and their in-hospital mortality exceeded that for non-transfused burn patients fivefold (p < 0.05). DISCUSSION: We show that Finnish adult burn patients received ample transfusions. The number of blood components transfused varied according to the anatomical location of the injury and patient survival. Whether the additional mortality is related directly to transfusions or is merely a manifestation of the more severe burn injury remains unknown.

Bleeding complications in cholecystectomy: a register study of over 22,000 cholecystectomies in Finland.

BACKGROUND: Major bleeding is rare but among the most serious complications of laparoscopic surgery. Still very little is known on bleeding complications and related blood component use in laparoscopic cholecystectomy (LC). The aim of this study is to compare bleeding complications, transfusion rates and related costs between LC and open cholecystectomy (OC). METHODS: Data concerning LCs and OCs and related blood component use between 2002 and 2007 were collected from existing computerized medical records (Finnish Red Cross Register) of ten Finnish hospital districts. RESULTS: Register data included 17175 LCs and 4942 OCs. In the LC group, 1.3% of the patients received red blood cell (RBC) transfusion compared to 13% of the patients in the OC group (p < 0.001). Similarly, the proportions of patients with platelet (0.1% vs. 1.2%, p < 0.001) and fresh frozen plasma (FFP) products (0.5% vs. 5.8%) transfusions were respectively higher in the OC group than in the LC group. The mean transfused dose of RBCs, PTLs and FFP product Octaplas or the mean cost of the transfused blood components did not differ significantly between the LC and OC groups. CONCLUSIONS: Laparoscopic cholecystectomy was associated with lower transfusion rates of blood components compared to open surgery. The severity of bleeding complications may not differ substantially between LC and OC.

Human umbilical cord blood-derived mesenchymal stromal cells display a novel interaction between P-selectin and galectin-1.

Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert immunomodulatory properties that have great potential in therapies for various inflammatory and autoimmune disorders. However, intravenous delivery of these cells is followed by massive cell entrapment in the lungs and insufficient homing to target tissues or organs. In targeting to tissues, MSCs and other therapeutic cells employ similar mechanisms as leucocytes, including a cascade of rolling and adhesion steps mediated by selectins, integrins and their ligands. However, the mechanisms of MSCs homing are not well understood. We discovered that P-selectin (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown to be a key mediator of the immunosuppressive effects of human MSCs. We conclude that this novel interaction is likely to play a major role in the immunomodulatory targeting of human UCB-derived MSCs.

Usefulness of maternal anti-HPA-1a antibody quantitation in predicting severity of foetomaternal alloimmune thrombocytopenia.

OBJECTIVE: To study the clinical usefulness of maternal anti-HPA-1a antibody levels in predicting severe foetomaternal alloimmune thrombocytopenia (FMAIT). BACKGROUND: Recent studies using an international anti-HPA-1a standard have shown a correlation between maternal antibody levels and neonatal thrombocytopenia. Cut-off values for identifying high-risk pregnancies have also been suggested. MATERIALS: In 1986-2010, HPA-1a alloimmunisation was confirmed in 84 women with 129 pregnancies. Maternal samples were obtained at delivery and during subsequent pregnancies. Anti-HPA-1a was quantified using a MAIPA assay with a detection limit of 0·8 IU mL(-1) (WHO reference serum 03/152). Antibody levels were compared with the severity of neonatal disease in the index and in the subsequent pregnancies. RESULTS: In the index cases, the correlation between an anti-HPA-1a level and neonatal platelet count did not reach statistical significance (n = 77, P = 0·074). However, the platelet counts and antibody levels in cases with cutaneous (n = 45) or intracranial haemorrhage (n = 7) were significantly different from cases with no evidence of bleeding (n = 20). In the subsequent pregnancies, there was a stronger association between the second trimester anti-HPA-1a level and the foetal platelet count (n = 16, P = 0·046). The positive predictive value of the maternal antibody level for a foetal platelet count <20 × 10(9) L(-1) was 90%, but the negative predictive value only 31%. CONCLUSION: Although a higher anti-HPA-1a level correlated with a more severe neonatal disease, barely detectable antibody levels were also observed in severely affected pregnancies. Cut-off values with sufficient sensitivity and specificity to identify these foetuses could not be found. A previous obstetric history still remains the most useful predictive parameter for severe FMAIT in clinical practice.

A zebrafish model of PINK1 deficiency reveals key pathway dysfunction including HIF signaling.

The PTEN induced putative kinase 1 (PINK1) gene is mutated in patients with hereditary early onset Parkinson's disease (PD). The targets of PINK1 and the mechanisms in PD are still not fully understood. Here, we carried out a high-throughput and unbiased microarray study to identify novel functions and pathways for PINK1. In larval zebrafish, the function of pink1 was inhibited using splice-site morpholino oligonucleotides and the samples were hybridized on a two-color gene expression array. We found 177 significantly altered genes in pink1 morphants compared with the uninjected wildtype controls (log fold change values from -1.6 to +0.9). The five most prominent pathways based on critical biological processes and key toxicological responses were hypoxia-inducible factor (HIF) signaling, TGF-ß signaling, mitochondrial dysfunction, RAR activation, and biogenesis of mitochondria. Furthermore, we verified that potentially important genes such as hif1α, catalase, SOD3, and atp1a2a were downregulated in pink1 morphants, whereas genes such as fech, pax2a, and notch1a were upregulated. Some of these genes have been found to play important roles in HIF signaling pathways. The pink1 morphants were found to have heart dysfunction, increased erythropoiesis, increased expression of vascular endothelial growth factors, and increased ROS. Our findings suggest that a lack of pink1 in zebrafish alters many vital and critical pathways in addition to the HIF signaling pathway.

Toll-like receptor gene polymorphisms confer susceptibility to graft-versus-host disease in allogenic hematopoietic stem cell transplantation.

Graft-versus-host disease (GvHD) is a major complication in hematopoietic stem cell transplantation (HSCT). The immune response against gut microbes is thought to be an important factor in the beginning of GvHD. Toll-like receptors (TLR) recognize molecular structures of microbes and viruses and play central part in the innate immunity. We studied whether genetic variation in the TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 genes confers susceptibility to GvHD in 305 human leucocyte antigen-identical sibling donor HSCT's performed in a single Finnish centre. The results showed that the genetic markers rs4833079 (P = 0.035) in TLR1, rs4837656 (P = 0.032) and rs17582214 (P = 0.029) in TLR4, rs10737416 (P = 0.048) in TLR5, rs6531656 (P = 0.035) in TLR6, and rs337629 (P = 0.005) in TLR10 were associated with the occurrence of acute GvHD. Interestingly, two markers in the TLR5 gene, rs2800230 (P = 0.010) and rs2800237 (P = 0.017), were associated with chronic GvHD. These results indicate that many genes of the TLR system are involved in the overall genetic risk for GvHD and emphasize the role of innate immunity in GvHD.

Mutational analysis of the Pseudomonas syringae pv. tomato hrpA gene encoding Hrp pilus subunit.

Plant pathogenic Pseudomonas syringae strains harbour a type III secretion pathway suggested to be involved in the delivery of effector proteins from the bacteria into plant cells. During plant interaction, the bacteria apparently produce surface appendages, termed Hrp pili, that are indispensable for the secretion process. We have created an insertion mutation library, as well as deletion mutations to hrpA, the structural gene encoding Hrp pilin. Analysis of the mutants revealed gene regions important for hrpA expression, pilus assembly and pilus-dependent autoagglutination of the bacteria. The majority of insertions in the amino-terminal half of the pilin were tolerated without bacterial interaction with plants being affected, while the carboxy-terminus appeared to be needed for pilus assembly. Insertions in the 5' non-translated region and the first codons within the open reading frame affected mRNA production or stability and abolished protein production.