Over-production of exopolysaccharide by Lacticaseibacillus rhamnosus CNCM I-3690 strain cutbacks its beneficial effect on the host.

Most lactobacilli produce extracellular polysaccharides that are considered to contribute to the probiotic effect of many strains. Lacticaseibacillus rhamnosus CNCM I-3690 is an anti-inflammatory strain able to counterbalance gut barrier dysfunction. In this study ten spontaneous variants of CNCM I-3690 with different EPS-production were generated and characterized by their ropy phenotype, the quantification of the secreted EPS and genetic analysis. Amongst them, two were further analysed in vitro and in vivo: an EPS over-producer (7292) and a low-producer derivative of 7292 (7358, with similar EPS levels than the wild type (WT) strain). Our results showed that 7292 does not have anti-inflammatory profile in vitro, and lost the capacity to adhere to the colonic epithelial cells as well as the protective effect on the permeability. Finally, 7292 lost the protective effects of the WT strain in a murine model of gut dysfunction. Notably, strain 7292 was unable to stimulate goblet cell mucus production and colonic IL-10 production, all key features for the beneficial effect of the WT strain. Furthermore, transcriptome analysis of colonic samples from 7292-treated mice showed a down-regulation of anti-inflammatory genes. Altogether, our results point out that the increase of EPS production in CNCM I-3690 impairs its protective effects and highlight the importance of the correct EPS synthesis for the beneficial effects of this strain.

Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients - an economic evaluation.

BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25-0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.

Anti-Blood Group Antibodies in Intravenous Immunoglobulin May Complicate Interpretation of Antibody Titers in ABO-Incompatible Transplantation.

Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.

Phenotypically matched vs. traditional screen method for preparing red blood cell units in patients with abnormal placentation: a decision analysis approach.

BACKGROUND: Patients with abnormal placentation are hospitalized approximately 21 days prior to scheduled delivery due to risk of peri-partum bleeding. It is required to have at least one red blood cell (RBC) unit ready throughout hospitalization. This can be accomplished by performing a type and cross (T&C) every 72 h (traditional method) or providing phenotypically matched RBC units (alternative method). METHODS: A Markov-based model was created to compare the cost-benefits between these two methods. A patient either undergoes the traditional or alternative method. If the patient already made an antibody and/or has rare phenotypes requiring frozen RBC unit at admission, then she can only enter the traditional method. All patients receive a T&C at the end of the 21st day in order to prepare RBC units for scheduled delivery. Model parameters are derived from literature and institutional experiences. RESULTS: Simulation was run for modelling of the 21-day hospitalization of each patient. The expected cost per RBC unit of the traditional method is significantly higher than the alternative method (876·59 vs. 608·32 USD, P-value <0·01). For each RBC unit, 4·85 h of technician working time is saved by the alternative method. However, to be cost-beneficial, the alternative method should be used only if the total cost of a RBC unit is <857·67 USD. CONCLUSION: Our model demonstrated that preparing phenotypically matched RBC units at admission is more cost-beneficial comparing to the traditional method of T&C every 72 h if the cost for the matched unit is <857·67 USD.

Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience.

BACKGROUND AND OBJECTIVES: Recombinant activated factor VII (rFVIIa) is often used in off-label indications, including many situations in which the patients are at risk of thrombosis. In this study, we retrospectively reviewed the use of rFVIIa in patients with acute liver failure - UNOS Status 1A (ALF-1A) to determine its efficacy and safety profile. MATERIALS AND METHODS: Using the transplantation records, all adult patients with ALF-1A were identified from 6/2001 to 3/2009. From patients' medical charts, rFVIIa dose, blood component usage, short-term outcomes [length of intensive care unit (ICU) and hospital stay, ability to undergo orthotopic liver transplant (OLT) and in-hospital survival rate] and adverse events were examined. RESULTS: Forty-two patients with ALF-1A were identified. Fifteen patients received rFVIIa with doses ranging between 24·4 µg/kg and 126·8 µg/kg. Three patients received two doses of rFVIIa. The age, baseline activated partial thromboplastin time (aPTT) and platelet (PLT) count were not statistically different between the group receiving rFVIIa versus the group that did not. However, the prothrombin time (PT) was significantly higher in the rFVIIa group. Although the rFVIIa group stayed in the ICU longer and required significant more blood products during admission, there was no statistical difference between the two groups in terms of length of hospital stay, ability to undergo OLT and survival rate. There was no increase in complications, including thrombosis, after receiving rFVIIa. CONCLUSION: Recombinant activated factor VII (rFVIIa) appears to be safe in patients with ALF-1A, but to elucidate its full role, a randomized controlled trial would be ideal.

Update on massive transfusion.

Massive haemorrhage requires massive transfusion (MT) to maintain adequate circulation and haemostasis. For optimal management of massively bleeding patients, regardless of aetiology (trauma, obstetrical, surgical), effective preparation and communication between transfusion and other laboratory services and clinical teams are essential. A well-defined MT protocol is a valuable tool to delineate how blood products are ordered, prepared, and delivered; determine laboratory algorithms to use as transfusion guidelines; and outline duties and facilitate communication between involved personnel. In MT patients, it is crucial to practice damage control resuscitation and to administer blood products early in the resuscitation. Trauma patients are often admitted with early trauma-induced coagulopathy (ETIC), which is associated with mortality; the aetiology of ETIC is likely multifactorial. Current data support that trauma patients treated with higher ratios of plasma and platelet to red blood cell transfusions have improved outcomes, but further clinical investigation is needed. Additionally, tranexamic acid has been shown to decrease the mortality in trauma patients requiring MT. Greater use of cryoprecipitate or fibrinogen concentrate might be beneficial in MT patients from obstetrical causes. The risks and benefits for other therapies (prothrombin complex concentrate, recombinant activated factor VII, or whole blood) are not clearly defined in MT patients. Throughout the resuscitation, the patient should be closely monitored and both metabolic and coagulation abnormalities corrected. Further studies are needed to clarify the optimal ratios of blood products, treatment based on underlying clinical disorder, use of alternative therapies, and integration of laboratory testing results in the management of massively bleeding patients.

Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks.

The hallmark of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce haemolysis in G6PD-deficient RBCs. Although it is not routine practice to screen healthy blood donors for G6PD deficiency, case reports identified transfusion of G6PD-deficient RBCs as causing haemolysis and other adverse events. In addition, some patient populations may be more at risk for complications associated with transfusions of G6PD-deficient RBCs because they receive RBCs from donors who are more likely to have G6PD deficiency. This review discusses G6PD deficiency, its importance in transfusion medicine, changes in the RBC antioxidant system (of which G6PD is essential) during refrigerated storage and mechanisms of haemolysis. In addition, as yet unanswered questions that could be addressed by translational and clinical studies are identified and discussed.

Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients.

BACKGROUND: Hepatitis C virus infection (HCV) is associated with a variety of extrahepatic disorders such as membranoproliferative glomerulonephritis (MPGN), which is generally due to cryoglobulinemia. After liver transplantation for HCV cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver graft is poorly effective and may induce intractable graft rejection. METHODS: We describe the cases of four liver transplant recipients treated with ribavirin for HCV-related glomerulopathy and nephrotic syndrome. RESULTS: The nephrotic syndrome was attenuated or disappeared during ribavirin therapy, and patients showed a marked decrease in proteinuria and an increase in albuminemia. The syndrome relapsed in two patients when ribavirin therapy was stopped, and a favorable response was again obtained in both cases when the treatment was resumed. The main adverse effect of ribavirin was anemia in two patients with renal impairment. No graft rejection occurred. CONCLUSIONS: These findings suggest that continuous therapy with low doses of oral ribavirin may improve the proteinuria of hepatitis C-related glomerulonephritis, at least in liver transplant recipients.

Chlorinated and brominated dioxins and dibenzofurans in human tissue following exposure.

With substantial improvements in analytic techniques over the past decade, it has become possible to measure polychlorinated dioxins (PCDDs) and dibenzofurans (PCDFs) in human tissue in a congener-specific fashion down to the low parts per trillion level. This paper reviews findings using these new techniques from a number of recent medical and environmental case studies. These studies include those of workers exposed to a polychlorinated biphenyl (PCB) transformer fire in the United States, German chemical workers exposed to 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD) while cleaning up after an explosion, workers at a municipal incinerator in New York City, a chemist exposed to brominated and chlorinated dioxins, U.S. veterans and also Vietnamese civilians exposed to Agent Orange contaminated with TCDD in Vietnam, and victims of the polychlorinated dibenzofuran and PCB contaminated rice oil (Yusho) incident in Japan.