Patient blood management in Europe

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed 'patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.     

The locking attachment plate for proximal fixation of periprosthetic femur fractures-a biomechanical comparison of two techniques

Purpose

Mechanical properties of a locking attachment plate construct (LAP-LCP), allowing bicortical screw placement laterally to the prosthesis stem, are compared to a cerclage-LCP construct.

Methods

Eight right synthetic femora with implanted uncemented hip endoprosthesis were cut distally and fixed with LCP, monocortical locking screws and either LAP (n = 4) or cerclage (n = 4). Cyclic testing was performed with monotonically increasing sinusoidal load until failure. Relative movements at the plate–femur interface were registered by motion tracking. Statistical differences were detected by unpaired t-test and general linear model repeated measures.

Results

Stiffness of the LAP-LCP was significantly higher at the beginning (875.4 N/mm ± 29.8) and after 5000 cycles (1213.0 N/mm ± 101.1) compared to the cerclage-LCP (644.96 N/mm ± 50.1 and 851.9 N/mm ± 81.9), with p = 0.013. Relative movements for AP-bending (B) and axial translation (T) of the LAP-LCP at the beginning (0.07° ± 0.02, 0.20 mm ± 0.08), after 500 cycles (0.16° ± 0.10, 0.26 mm ± 0.07) and after 5000 cycles (0.26° ± 0.11, 0.31 mm ± 0.07) differed significantly from the cerclage-LCP (beg.: 0.26° ± 0.04, 0.28 mm ± 0.05; 500 cyc: 0.47° ± 0.03, 0.53 mm ± 0.07; 5000 cyc.: 0.63° ± 0.18, 0.79 mm ± 0.13), with B: p = 0.02, T: p = 0.04. Relative movements for medial bending were not significantly different between the two constructs. Cycles to failure (criterion 1 mm axial translation) differed significantly between LAP-LCP (19,519 ± 1,758) and cerclage-LCP (11,265 ± 2,472), with p = 0.035.

Conclusions

Biomechanically, the LAP-LCP construct improves proximal fixation of periprosthetic fractures compared to the cerclage-LCP construct.     

Labile disulfide bonds in human placental insulin receptor.

The disulfide crosslinking pattern of human placental insulin receptor was investigated using selective reduction with tributylphosphine followed by alkylation with N-[3H]ethylmaleimide. Insulin receptor contains a single sulfhydryl group in each beta subunit whose alkylation with N-[3H]ethylmaleimide inhibits receptor autophosphorylation. Alkylation is partially inhibited by ATP or the nonhydrolyzable substrate analog adenosine 5'-[beta,gamma-imido]triphosphate when the nucleotides are added as Mn2+ complexes. Neither insulin nor 6 M guanidinium chloride renders additional sulfhydryl groups accessible to alkylation. When the receptor is reduced under drastic conditions with tributylphosphine in guanidinium chloride, 32 of the 37 sulfhydryl groups in the receptor's alpha subunit can be alkylated with N-[3H]ethylmaleimide. Surprisingly only three of the 10 cysteines in the beta subunit become titratable under identical conditions. By using highly selective reducing conditions, we were able to determine quantitatively the maximum number of disulfide bridges that link the two alpha beta halves to form the tetrameric structure and those that couple the alpha to the beta subunits. Liberation of two sulfhydryl groups in the alpha and one in the beta subunit resulted in formation of alpha beta dimers. Free beta subunit was formed when an additional disulfide bond was reduced. It is remarkable that the tetrameric structure of this highly complex receptor molecule, which contains a large number of cysteine residues, is maintained by such a small number of disulfide bonds. Three models of the arrangement of the labile disulfide bonds, consistent with these findings, are proposed.     

Functional reconstitution of vascular smooth muscle cells with cGMP-dependent protein kinase I isoforms

The cGMP-dependent protein kinase type I (cGKI) is a major mediator of NO/cGMP-induced vasorelaxation. Smooth muscle expresses two isoforms of cGKI, cGKIalpha and cGKIbeta, but the specific role of each isoform in vascular smooth muscle cells (VSMCs) is poorly understood. We have used a genetic deletion/rescue strategy to analyze the functional significance of cGKI isoforms in the regulation of the cytosolic Ca(2+) concentration by NO/cGMP in VSMCs. Cultured mouse aortic VSMCs endogenously expressed both cGKIalpha and cGKIbeta. The NO donor diethylamine NONOate (DEA-NO) and the membrane-permeable cGMP analogue 8-bromo-cGMP inhibited noradrenaline-induced Ca(2+) transients in wild-type VSMCs but not in VSMCs genetically deficient for both cGKIalpha and cGKIbeta. The defective Ca(2+) regulation in cGKI-knockout cells could be rescued by transfection of a fusion construct consisting of cGKIalpha and enhanced green fluorescent protein (EGFP) but not by a cGKIbeta-EGFP construct. Fluorescence imaging indicated that the cGKIalpha-EGFP fusion protein was concentrated in the perinuclear/endoplasmic reticulum region of live VSMCs, whereas the cGKIbeta-EGFP protein was more homogeneously distributed in the cytoplasm. These results suggest that one component of NO/cGMP-induced smooth muscle relaxation is the activation of the cGKIalpha isoform, which decreases the noradrenaline-stimulated cytosolic Ca(2+) level.     

Active absorption of conjugated bile acids in vivo. Kinetic parameters and molecular specificity of the ileal transport system in the rat

Active transport of conjugated bile acids by the distal ileum is required for efficient enterohepatic cycling of bile acids. Experiments were performed in the rat to obtain accurate values for Tmax and Michaelis constant (Km) of the absorptive area of the rat ileum and to define the structural specificity of the transport system. The distal fifth (20 cm) of the small intestine from an anesthetized animal with a biliary fistula was perfused using solutions of 10 taurine-conjugated bile acids; a flow rate was used that was sufficiently high such that unstirred water layer effects were negligible and the intraluminal concentration remained unchanged throughout the perfused segment. The absorption rate was equated with the rate of hepatic bile acid secretion. Values of Tmax (mumol/min.kg) were markedly influenced by bile acid structure: cholyltaurine, 12.9; ursocholyltaurine, 9.6; ursodeoxycholyl taurine, 5.0; and lagodeoxycholyl-(3 alpha,12 beta-dihydroxy-cholanoic acid)-taurine, 1.2. Decreasing the length of the side chain of ursodeoxycholate conjugates from 8 to 6 carbon atoms was associated with a modest increase in Tmax values from 5.0 to 9.1 mumols/min.kg. Values of Km correlated with Tmax values and ranged from 0.5 to 5 mmol/L, being highest for those bile acids that were best transported. The Tmax for cholyltaurine transport was not reached when the intraluminal concentration was as high as its critical micellization concentration, precluding the definition of its Tmax; however, for ursocholyltaurine, with a critical micellization concentration of 40 mmol/L, saturation of transport was clearly shown. Kinetic parameters could not be obtained for two common dihydroxy conjugates (chenodeoxycholyltaurine and deoxycholyltaurine) because at a transport rate of 2 mumols/min.kg systemic toxicity and death occurred. These studies define the maximal transport capacity of the rat ileum for taurine-conjugated bile acids; they indicate that the ileal transport system in the rat is of low affinity and high capacity for taurine conjugates of hydrophilic bile acids, and they show that both nuclear substituents and side chain length influence the transport rate of taurine-conjugated bile acids.     

Simultaneous stenting of the carotid artery and other coronary or extracoronary arteries: Does a combined procedure increase the risk of interventional therapy?

Simultaneous interventions in carotid and other extracarotid arteries are not performed on a routine basis up to now. In 67 out of 295 consecutive patients (23%) undergoing elective stenting of the internal carotid artery, additional interventions in the coronary arteries (n = 65), the iliac artery (n = 3), renal artery (n = 1), left subclavian artery (n = 3), vertebral artery (n = 4), or a combination thereof were performed. Primary stenting was done in 51 (74%) out of 69 carotid arteries, in 48 (74%) of 65 coronary arteries, and in 10 (91%) of 11 other targeted vessels. Neurological complications consisted of two (2.9%) transient ischemic attacks and one (1.5%) minor stroke. In addition, one (1.5%) myocardial infarction occurred during coronary artery intervention. In comparison, 16 (6.6%) transient ischemic attacks, 1 minor stroke (0.4%), 5 (2.2%) major strokes, and 3 (1.2%) deaths were observed in 228 patients without combined procedures. Simultaneous percutaneous interventions including carotid arteries and other extracarotid arteries are feasible, relatively safe, and cost-effective.