Motility, viability and fertility of goldfish Carassius auratus (Pisces: Cyprinidae) post short-term cryopreservation.

BACKGRUND: Goldfish Carassius auratus is a popular ornamental fish extensively cultured worldwide. Sperm cryopreservation is a common fish breeding method that ensures sperm availability around the year. Studies on cryopreservation of goldfish sperm, especially on the suitability of cryoprotectant types and pre-freezing time, are scarcely available. OBJECTIVE: To determine the most suitable type of cryoprotectant and pre-freezing for the successful cryopreservation of goldfish sperm. MATERIALS AND METHODS: A completely randomized design with two factors was utilized in this study. The first factor is the type of cryoprotectants, which included methanol, ethanol, ethylene glycol, glycerol, and DMSO. The second is pre-freezing times of 10, 20, 30, and 40 min at each of the pre-freezing temperatures of 4 degree C, -10 degree C, and -79 degree C, meaning that the total times for the ramping down of temperature were 30, 60, 90 and 120 min, respectively. The Ringer solution and 10% egg yolk were used as extender and extracellular cryoprotectant. The sperm was stored at -179 degree C for 7 days. RESULTS: The ANOVA test showed that cryoprotectants and pre-freezing significantly affected the motility, viability, and fertility of goldfish sperm after freezing in liquid nitrogen for 7 days (P<0.05). Furthermore, 10% DMSO combined with 15% egg yolk with an pre-freezing time of 20 min can maintain sperm motility, viability, and fertility higher than other treatments, by 79%, 80%, and 33%, respectively. The agarose gel electrophoresis showed no DNA fragmentation in all samples, including fresh sperm. CONCLUSION: We conclude that 10% DMSO combined with 15% egg yolk and 20 min pre-freezing is the best treatment for goldfish sperm cryopreservation. DOI: 10.54680/fr23310110412.

Glacier retreat reorganizes river habitats leaving refugia for Alpine invertebrate biodiversity poorly protected.

Alpine river biodiversity around the world is under threat from glacier retreat driven by rapid warming, yet our ability to predict the future distributions of specialist cold-water species is currently limited. Here we link future glacier projections, hydrological routing methods and species distribution models to quantify the changing influence of glaciers on population distributions of 15 alpine river invertebrate species across the entire European Alps, from 2020 to 2100. Glacial influence on rivers is projected to decrease steadily, with river networks expanding into higher elevations at a rate of 1% per decade. Species are projected to undergo upstream distribution shifts where glaciers persist but become functionally extinct where glaciers disappear completely. Several alpine catchments are predicted to offer climate refugia for cold-water specialists. However, present-day protected area networks provide relatively poor coverage of these future refugia, suggesting that alpine conservation strategies must change to accommodate the future effects of global warming.

Future trends in measuring physiology in free-living animals.

Thus far, ecophysiology research has predominantly been conducted within controlled laboratory-based environments, owing to a mismatch between the recording technologies available for physiological monitoring in wild animals and the suite of behaviours and environments they need to withstand, without unduly affecting subjects. While it is possible to record some physiological variables for free-living animals using animal-attached logging devices, including inertial-measurement, heart-rate and temperature loggers, the field is still in its infancy. In this opinion piece, we review the most important future research directions for advancing the field of 'physiologging' in wild animals, including the technological development that we anticipate will be required, and the fiscal and ethical challenges that must be overcome. Non-invasive, multi-sensor miniature devices are ubiquitous in the world of human health and fitness monitoring, creating invaluable opportunities for animal and human physiologging to drive synergistic advances. We argue that by capitalizing on the research efforts and advancements made in the development of human wearables, it will be possible to design the non-invasive loggers needed by ecophysiologists to collect accurate physiological data from free-ranging animals ethically and with an absolute minimum of impact. In turn, findings have the capacity to foster transformative advances in human health monitoring. Thus, we invite biomedical engineers and researchers to collaborate with the animal-tagging community to drive forward the advancements necessary to realize the full potential of both fields. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.

Relationship of BMI z score to fat percent and fat mass in multiethnic prepubertal children.

OBJECTIVE: The objective of the study is to examine the validity of body mass index z score (zBMI) as a measure of percent body fat in prepubertal children. METHODS: One hundred eleven multiethnic, healthy, Tanner 1 children aged 6-12 years had fat percent and fat mass measured by the four-compartment method as part of the Paediatric Rosetta Body Composition Cohort. Multiple regression models were developed with fat percent as the dependent variable and zBMI, age, sex and ethnicity as independent variables. RESULTS: Body mass index z score predicted fat percent, adjusted for age in both girls (P < 0.001, RMSE 5.67 and R2 0.54) and boys (P < 0.001, RMSE 4.71, R2 0.69). The average model percent error was 20.3% in girls and 21.6% in boys. zBMI2 predicted fat mass when adjusted for age and zBMI in both girls (P < 0.001, RMSE 2.27 and R2 0.82) and boys (P < 0.001, RMSE 2.08 and R2 0.81). The average percent error was 7.2% in girls and 8.7% in boys. Age was associated with percentage body fat (P < 0.01), while ethnicity was not (P > 0.05). CONCLUSIONS: Given the relatively large error in the models, zBMI are not a useful indicator of fat mass in healthy, Tanner 1 children. zBMI2 scores are associated with significantly lower absolute percent errors in girls and boys.

Placental restriction in multi-fetal pregnancies increases spontaneous ambulatory activity during daylight hours in young adult female sheep.

Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n=5 males, 9 females) and PR pregnancies (n=9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P<0.001). In adults, daytime SAA was greater in PR than CON females (P=0.020), with a similar trend in males (P=0.053) and was greater in females than males (P=0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.

In multiple situational light settings, visual observation for skin colour assessment is comparable with colorimeter measurement.

BACKGROUND: Finding inexpensive and reliable techniques for assessing skin colour is important, given that it is related to several adverse human health outcomes. Visual observation is considered a subjective approach assessment and, even when made by trained assessor, concern has been raised about the need for controlled lighting in the study venue. The aim of this study is to determine whether visual skin colour assessments correlate with objective skin colour measurements in study venues with different lighting types and configurations. METHODS: Two trained investigators, with confirmed visual acuity, visually classified the inner, upper arm skin colour of 556 adults using Munsell(®) colour classifications converted to Individual Typology Angle (°ITA) values based on published data. Skin colour at the same anatomic site was also measured using a colorimeter. Each participant was assessed in one of 10 different buildings, each with a different study day. Munsell(®) -derived °ITA values were compared to colorimeter °ITA values for the full sample and by building/day. RESULTS: We found a strong positive, monotonic correlation between Munsell(®) derived °ITA values and colorimeter °ITA values for all participants (Spearman ρ = 0.8585, P < 0.001). Similar relationships were found when Munsell(®) and colorimeter °ITA values were compared for participants assessed in the same building for all 10 buildings (Spearman ρ values ranged from 0.797 to 0.934, all correlations were statistically significant at P < 0.001). CONCLUSION: It is possible to visually assess individual skin colour in multiple situational lighting settings and retrieve results that are comparable with objective measurements of skin colour. This was true for individuals of varying population groups and skin pigmentation.

Difficult airway communication between anaesthetists and general practitioners.

BACKGROUND AND AIMS: Advance warning of patients who are difficult to intubate may prevent an airway catastrophe but relies on effective communication between specialties. Anaesthetists aim to inform general practitioners whenever a difficult airway is encountered and expect general practitioners to include this information in subsequent referrals. We investigated how anaesthetists communicated with general practitioners, their knowledge of the Read Code (used by general practitioner computer systems) for difficult tracheal intubation, and how likely general practitioners were to pass the information on. METHODS AND RESULTS: We surveyed 631 consultant anaesthetists and 217 general practitioners. We found only 125 (20%) anaesthetists consistently wrote difficult airway letters to general practitioners. Only 20 (3%) knew the Read Code for difficult intubation (SP2y3), although 454 (72%) thought it to be useful. Most general practitioners (212, 98%) thought airway information to be important, but only half receiving a difficult airway communication forwarded it on. General practitioners recommended including the Read Code SP2y3 and labelling it 'high priority', ensuring that 'Difficult Tracheal Intubation' would be listed in the Emergency Care Summary generated for hospital referrals. CONCLUSION: Communication between anaesthetists and general practitioners is currently poor, but could be improved by simplifying difficult airway letters and including the SP2y3 code and a statement of priority.

Can B-domain deletion alter the immunogenicity of recombinant factor VIII? A meta-analysis of prospective clinical studies.

BACKGROUND: As a result of the infrequency of inhibitors in previously treated patients (PTPs) with hemophilia A and the small size of available clinical studies, the immunogenicity of factor (F)VIII products has been difficult to assess. OBJECTIVES: A meta-analysis of prospective clinical studies was conducted to test the hypothesis that de novo inhibitor incidence differs between PTPs receiving full-length recombinant FVIII (FL-rFVIII) and B-domain deleted recombinant FVIII (BDD-rFVIII). METHODS: Prospective studies with data on inhibitors in PTPs receiving FL-rFVIII or BDD-rFVIII were sought using systematic methods including bibliographic database searches. Data were secured from published study reports and inquiries to investigators. Between-group differences in inhibitor incidence rates were evaluated using mixed effects Cox regression. RESULTS: Twenty-nine studies with 3012 total PTPs were included. Patients were at risk of de novo inhibitor development for a median of 79 exposure days. A total of 35 de novo inhibitors were observed. The cumulative hazard for all de novo inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63-1.88%. The corresponding rate for high-titer de novo inhibitors [> 5 Bethesda units (BU)] was 0.29% (CI, 0.01-0.57%). Exposure to BDD-rFVIII was associated with an increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12-24.9; P = 0.0016) and of high-titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17-53.7; P = 0.0037), compared with FL-rFVIII. CONCLUSIONS: This meta-analysis of prospective clinical studies suggests that recombinant FVIII products may differ in immunogenicity.

Controlled release recombinant human interferon-α2b for treating patients with chronic hepatitis C genotype 1: a phase 2a clinical trial.

Better convenience and tolerability and sustained therapeutic concentrations might improve interferon (IFN) treatment for chronic hepatitis C virus (HCV) infection. In an open-label, randomized study, controlled release free (chemically unmodified) recombinant human IFN-α(2b) in poly(ether-ester) microspheres (CR-rhIFN-α(2b)), was injected at doses of 160, 320, 480 or 640 µg every 2 weeks for 12 weeks with concomitant weight-based oral ribavirin in 32 treatment-naïve patients with chronic HCV genotype 1. Treatment was well tolerated, with 31 patients (97%) successfully completing the study. Full doses of CR-rhIFN-α(2b) were administered on 96% of scheduled occasions. Flu-like symptoms were generally mild and brief. Injection site reactions developed in 13 patients (41%), and neutropenia occurred in six of eight patients receiving 640 µg. In the 320, 480 and 640 µg groups, 62-75% of patients achieved a ≥2 log(10) HCV RNA reduction by 4 weeks and 88-100% by 12 weeks. For those groups, the pooled median time to ≥2 log(10) reduction was 11 days (95% confidence interval, 7-35 days). In those groups, viral reduction below the limit of detection was accomplished in 25% of patients by 4 weeks and in 62% by 12 weeks. The 160-µg dose was less potent. After CR-rhIFN-α(2b) injection, stable plateau levels of serum IFN-α(2b) were generally reached within 72 h. Treatment-emergent neutralizing antibodies to IFN-α(2b) were observed in one patient. No antibodies to host plant proteins were detected. CR-rhIFN-α(2b) with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1.

Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials.

UNLABELLED: In a cross-design synthesis, total fractures were similarly reduced by bisphosphonates among postmenopausal women in randomized trials (23.8%) and highly compliant/persistent patients in observational studies of large databases from routine practice (20.3%). Bisphosphonates also reduced nonvertebral, vertebral and hip fractures in randomized trials and observational studies. In the real-word setting, compliant/persistent patients can gain a benefit from bisphosphonates comparable to that of randomized trial participants. INTRODUCTION: The purpose of the study was to determine whether clinical fracture risk reduction by bisphosphonate treatment in women with postmenopausal osteoporosis differs between randomized controlled trials and routine practice. METHODS: Randomized trials comparing bisphosphonate with placebo and observational studies comparing highly compliant/persistent with less compliant/persistent patients were sought by electronic searches and ancillary methods. Clinical fracture data were extracted from the study reports and quantitatively combined by random effects metaanalysis. RESULTS: The odds ratio (OR) for all clinical fractures in randomized trials of 0.762, with a 95% confidence interval (CI) of 0.680-0.855, was closely similar to that in the observational studies (OR, 0.797; CI, 0.748-0.850). Pooled clinical fracture reduction across both study designs was 22%. Nonvertebral, vertebral, and hip fractures were also significantly reduced by bisphosphonate treatment in both randomized trials and observational studies. CONCLUSIONS: Compliant/persistent patients in the "real-world" setting benefit from bisphosphonate treatment to a similar extent as patients in randomized trials.

A non-Smad mechanism of fibroblast activation by transforming growth factor-beta via c-Abl and Egr-1: selective modulation by imatinib mesylate.

The nonreceptor protein tyrosine kinase c-Abl regulates cell proliferation and survival. Recent studies provide evidence that implicate c-Abl as a mediator for fibrotic responses induced by transforming growth factor-beta (TGF-beta), but the precise mechanisms underlying this novel oncogene function are unknown. Here, we report that when expressed in normal fibroblasts, a constitutively active mutant of Abl that causes chronic myelogenous leukemia (CML) stimulated the expression and transcriptional activity of the early growth response factor 1 (Egr-1). Mouse embryonic fibroblasts (MEFs), lacking c-Abl, were resistant to TGF-beta stimulation. Responsiveness of these MEFs to TGF-beta could be rescued by wild-type c-Abl, but not by a kinase-deficient mutant form of c-Abl. Furthermore, Abl kinase activity was necessary for the induction of Egr-1 by TGF-beta in normal fibroblasts, and Egr-1 was required for stimulation of collagen by Bcr-Abl. Lesional skin fibroblasts in mice with bleomycin-induced fibrosis of skin displayed evidence of c-Abl activation in situ, and elevated phospho-c-Abl correlated with increased local expression of Egr-1. Collectively, these results position Egr-1 downstream of c-Abl in the fibrotic response, delineate a novel Egr-1-dependent intracellular signaling mechanism that underlies the involvement of c-Abl in certain TGF-beta responses, and identify Egr-1 as a target of inhibition by imatinib. Furthermore, the findings show in situ activation of c-Abl paralleling the upregulated tissue expression of Egr-1 that accompanies fibrosis. Pharmacological targeting of c-Abl and its downstream effector pathways may, therefore, represent a novel therapeutic approach to blocking TGF-beta-dependent fibrotic processes.

Meta-analytic evidence of increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII.

A recent meta-analysis of 13 observational studies suggested reduced haemostatic efficacy during prophylaxis and shortened half-life of B-domain deleted factor VIII (BDD-rFVIII) as compared with full-length factor VIII (FL-FVIII). The meta-analysis included a multivariate model that took both dose and age into account. In addition, several assumptions and interpretations were required in order to conduct the meta-analysis. It is important to test the impact of such assumptions and interpretations through sensitivity analysis. In the published meta-analysis, results of several sensitivity analyses were described involving the effect of study design; heterogeneity of subjects in some studies; type of assay used for half-life determinations; and year of publication. In two subsequent brief reports, additional sensitivity analyses addressed choice of median-to-mean conversion factor over a wide range of scenarios and use of age at start of prophylaxis vs mean age during prophylaxis in the multivariate model. A recognized inherent difficulty in the meta-analysis of multiple published reports from similar studies is the possibility of some subject or data overlap. Therefore, the present communication details further sensitivity analyses encompassing assumptions regarding the possibility of subject duplication in a subgroup of subjects from one study and possible duplication of pharmacokinetic data from two smaller studies within the reports of two larger studies. All the sensitivity analyses support the main conclusions of the meta-analysis, namely, that BDD-rFVIII substantially increases the risk of breakthrough bleeding during prophylaxis, possibly at least partly because of shorter half-life than that of FL-FVIII.

Increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII--a robust meta-analytic finding.

Meta-analyses of observational studies have become increasingly common to support evidence-based clinical decisions. We analyzed currently available clinical studies of full-length factor VIII (FL-FVIII) vs. B-domain deleted recombinant factor VIII (BDD-rFVIII) using a random effects model to investigate possible differences in clinical efficacy in patients treated during prophylaxis. Some studies reported breakthrough bleeding incidence as mean annual total bleeds, whereas others reported median bleeds. In accord with the consensus recommendations by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group, all available studies where included. For analysis, data were combined by converting median to mean annual total bleeds using a conversion factor of 2.6, based on clinical data previously compiled by the Universal Data Collection Program of the U.S. Centers for Disease Control and Prevention. To evaluate the sensitivity of our model upon the choice of conversion factor, we re-estimated incidence rate ratios for breakthrough bleeding over a wide range of conversion factors from 1.4-2.6. Even at the lowest extreme conversion factor of 1.4, bleeding incidence was statistically higher in patients treated with BDD-rFVIII compared with FL-FVIII. We also examined the impact of reported patient age on our multivariate model. Exposure to BDD-rFVIII remained an independent predictor of bleeding, regardless of patient age at start or mean age during prophylaxis. These analyses further support the robustness of our meta-analysis and its conclusions.

Differential trafficking of transforming growth factor-beta receptors and ligand in polarized epithelial cells.

Epithelial cells in vivo form tight cell-cell associations that spatially separate distinct apical and basolateral domains. These domains provide discrete cellular processes essential for proper tissue and organ development. Using confocal imaging and selective plasma membrane domain activation, the type I and type II transforming growth factor-beta (TGFbeta) receptors were found to be localized specifically at the basolateral surfaces of polarized Madin-Darby canine kidney (MDCK) cells. Receptors concentrated predominantly at the lateral sites of cell-cell contact, adjacent to the gap junctional complex. Cytoplasmic domain truncations for each receptor resulted in the loss of specific lateral domain targeting and dispersion to both the apical and basal domains. Whereas receptors concentrate basolaterally in regions of direct cell-cell contact in nonpolarized MDCK cell monolayers, receptor staining was absent from areas of noncell contact. In contrast to the defined basolateral polarity observed for the TGFbeta receptor complex, TGFbeta ligand secretion was found to be from the apical surfaces. Confocal imaging of MDCK cells with an antibody to TGFbeta1 confirmed a predominant apical localization, with a stark absence at the basal membrane. These findings indicate that cell adhesion regulates the localization of TGFbeta receptors in polarized epithelial cultures and that the response to TGFbeta is dependent upon the spatial distribution and secretion of TGFbeta receptors and ligand, respectively.

Central venous access devices in haemophilia.

Central venous access devices (CVADs) can facilitate repeated and/or urgent administration of coagulation factors in haemophilic patients. We conducted a systematic review and meta-analysis of complication rates and risk factors for poor outcome. Forty-eight studies with a total of 2704 patients and 2973 CVADs were included. The primary indications for CVADs were immune tolerance therapy (34.9% of patients), difficult venous access (31.8%) and prophylaxis (29.1%). Fully implanted CVADs were employed in 77.4% of cases and external CVADs in 22.6%. A total of 1190 infections were reported, and the pooled incidence of infection was 0.66 per 1000 CVAD days [confidence interval (CI), 0.44-0.97 per 1000 CVAD days]. Among patients developing infection, the pooled time to first infection was 295 days (CI, 181-479 days). Presence of inhibitors was an independent risk factor for infection with an incidence rate ratio (IRR) of 1.67 (CI, 1.15-2.43). Infection was less likely in patients >6 years of age (IRR, 0.46; CI, 0.27-0.79) and recipients of fully implanted CVADs (IRR, 0.31; CI, 0.12-0.86). Available information on thrombosis was limited, with only 55 cases being reported. Eventually, 31.3% of CVADs were removed, and infection was the reason for removal in 69.9% of cases and thrombosis in 4.1%. The pooled time period CVADs remained indwelling prior to removal or the expiration of the study observation period was 578 days per CVAD (CI, 456-733 days per CVAD). CVADs can confer major benefits in patients with haemophilia requiring long-term venous access, and serious complications are rare.

Safety of human albumin--serious adverse events reported worldwide in 1998-2000.

BACKGROUND: Previous pharmacovigilance studies have indicated a low rate of adverse events in patients receiving human albumin. However, the incidence of adverse events is likely to have been underestimated because of under-reporting. A more accurate estimate may be possible during a period such as 1998-2000, when awareness regarding albumin safety was heightened by publication of a meta-analysis. METHODS: All serious adverse event reports received, and total doses of albumin distributed worldwide from the beginning of 1998 to the end of 2000 by 10 major suppliers of therapeutic human albumin were compiled. RESULTS: Distributed albumin doses totalled 1.62 x 10(7). The total numbers of non-fatal and fatal serious adverse events reported were 198 and 13, respectively. The incidence of all reported serious non-fatal and fatal adverse events was 5.28 per 10(6) doses (CI 1.60-17.4 per 10(6) doses). For non-fatal serious adverse events only, the observed incidence was 4.65 per 10(6) doses (CI 1.34-16.2 per 10(6) doses). No patient death was classified as probably related to albumin administration. The observed incidence of fatal serious adverse events possibly related to albumin was 0.185 per 10(6) doses (CI 0.0597-0.574 per 10(6) doses). The observed incidence of all non-fatal and fatal serious adverse events was significantly higher during the 1998-2000 period as compared with 1990-1997 (incidence rate ratio 4.98; CI 3.94-6.29), probably chiefly as a result of reduced under-reporting. CONCLUSIONS: Although the observed incidence of adverse events is likely to be an underestimate, nevertheless both non-fatal and fatal serious adverse events in albumin recipients appear to be rare. These results add further support to the excellent safety record of human albumin.

Albumin administration--what is the evidence of clinical benefit? A systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVE: The advantages of albumin over less costly alternative fluids continue to be debated. Meta-analyses focusing on survival have been inconclusive, and other clinically relevant end-points have not been systematically addressed. We sought to determine whether albumin confers significant clinical benefit in acute illness compared with other fluid regimens. METHODS: Database searches (MEDLINE, EMBASE, Cochrane Library) and other methods were used to identify randomized controlled trials comparing albumin with crystalloid, artificial colloid, no albumin or lower-dose albumin. Major findings for all end-points were extracted and summarized. A quantitative meta-analysis was not attempted. RESULTS: Seventy-nine randomized trials with a total of 4755 patients were included. No significant treatment effects were detectable in 20/79 (25%) trials. In cardiac surgery, albumin administration resulted in lower fluid requirements, higher colloid oncotic pressure, reduced pulmonary oedema with respiratory impairment and greater haemodilution compared with crystalloid and hydroxyethylstarch increased postoperative bleeding. In non-cardiac surgery, fluid requirements, and pulmonary and intestinal oedema were decreased by albumin compared with crystalloid. In hypoalbuminaemia, higher doses of albumin reduced morbidity. In ascites, albumin reduced haemodynamic derangements, morbidity and length of stay and improved survival after spontaneous bacterial peritonitis. In sepsis, albumin decreased pulmonary oedema and respiratory dysfunction compared with crystalloid, while hydroxyethylstarch induced abnormalities of haemostasis. Complications were lowered by albumin compared with crystalloid in burn patients. Albumin-containing therapeutic regimens improved outcomes after brain injury. CONCLUSIONS: Albumin can bestow benefit in diverse clinical settings. Further trials are warranted to delineate optimal fluid regimens, in particular indications.

Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis.

Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.