Decreased migration with locally administered bisphosphonate in cemented cup revisions using impaction bone grafting technique

Background and purpose — Impaction bone grafting (IBG) in revision hip surgery is an established method in restoring bone stock deficiencies. We hypothesized that local treatment of the morsellized allograft with a bisphosphonate in cemented revision would, in addition to increased bone density, also reduce the early migration of the cup as measured by radiostereometry (RSA).

Patients and methods — 20 patients with aseptic cup loosening underwent revision using the IBG technique. The patients were randomized to either clodronate (10 patients) or saline (10 patients, control group) as local adjunct to the morsellized bone. The outcome was evaluated by dual-energy X-ray absorptiometry (DXA) during the first year regarding periacetabular bone density and with radiostereometric analysis (RSA) for the first 2 years regarding cup migration.

Results — 2 patients were lost to follow-up: 9 patients remained in the clodronate and 9 in the control group. Less proximal migration was found in the clodronate group compared with the controls, measured both over time (mixed-models analysis, p = 0.02) as well as at the specified time points up to 2 years (0.22?mm and 0.59?mm respectively, p = 0.02). Both groups seemed to have stabilized at 1 year. We found similar bone mineral density measured by DXA, and similar RSA migration in the other directions. No cups were re-revised.

Interpretation — Local treatment of the allograft bone with clodronate reduced early proximal migration of the revised cup but without any measurable difference in periacetabular bone density.     

Veno-arterial CO2 difference and lactate for prediction of early mortality after cardiac arrest

Patients admitted to intensive care after cardiac arrest are at risk of circulatory shock and early mortality due to cardiovascular failure. The aim of this study was to evaluate the ability of the veno-arterial pCO₂ difference (∆pCO₂; central venous CO₂ – arterial CO₂) and lactate to predict early mortality in postcardiac arrest patients. This was a pre-planned prospective observational sub-study of the target temperature management 2 trial. The sub-study patients were included at five Swedish sites. Repeated measurements of ∆pCO₂ and lactate were conducted at 4, 8, 12, 16, 24, 48, and 72 h after randomization. We assessed the association between each marker and 96-h mortality and their prognostic value for 96-h mortality. One hundred sixty-three patients were included in the analysis. Mortality at 96 h was 17%. During the initial 24 h, there was no difference in ∆pCO₂ levels between 96-h survivors and non-survivors. ∆pCO₂ measured at 4 h was associated with an increased risk of death within 96 h (adjusted odds ratio: 1.15; 95% confidence interval [CI]: 1.02–1.29; p = .018). Lactate levels were associated with poor outcome over multiple measurements. The area under the receiving operating curve to predict death within 96 h was 0.59 (95% CI: 0.48–0.74) and 0.82 (95% CI: 0.72–0.92) for ∆pCO₂ and lactate, respectively. Our results do not support the use of ∆pCO₂ to identify patients with early mortality in the postresuscitation phase. In contrast, non-survivors demonstrated higher lactate levels in the initial phase and lactate identified patients with early mortality with moderate accuracy.     

Transendothelial transport: the vesicle controversy

The relative contribution of transcytosis vs. large pore transport to the passage of macromolecules across microvascular endothelia has been a controversial issue for nearly half a century. To separate transcytosis from 'porous' transport, the transcytosis inhibitors N-ethylmaleimide (NEM) and filipin have been tested in in situ or ex vivo perfused organs with highly conflicting results. In continually weighed isolated perfused organs, where measurements of pre- and post-capillary resistances, capillary pressure and capillary filtration coefficients can be repeatedly performed, high doses of NEM and filipin increased the bulk transport of macromolecules from blood to tissue, despite producing vasoconstriction. By contrast, in in situ perfused organs, marked reductions in the tissue uptake of albumin tracer have been observed after NEM and filipin. When tissue cooling has been employed as a means of inhibiting (active) transcytosis, results have invariably shown a low cooling sensitivity of albumin transport, compatible with passive transendothelial passage of albumin. This observation is further strengthened by the commonly observed dependence of albumin transport upon the capillary pressure and the rate of transcapillary convection. For low-density lipoprotein (LDL), a cooling-sensitive, non-selective transport component has been discovered, which may be represented by filtration through paracellular gaps, lateral diffusion through transendothelial channels formed by fused vesicles, or by transcytosis. From a physiological standpoint there is little evidence supporting active transendothelial transport of most plasma macromolecules. This seems to be supported by studies on caveolin-1-deficient mice lacking plasmalemmal vesicles (caveolae), in which there are no obvious abnormalities in the transendothelial transport of albumin, immunoglobulins or lipoproteins. Nevertheless, specific transport in peripheral capillaries of several hormones and other specific substances, similar to that existing across the blood-brain barrier, still remains as a possibility.     

Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia

Recent studies on the immunoglobulin variable heavy chain (IgV(H)) genes have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists of at least 2 clinical entities with either somatically mutated or unmutated V(H) genes. We have analyzed the V(H) gene mutation status and V(H) gene usage in 119 B-CLL cases and correlated them to overall survival. A novel finding was the preferential use of the V(H)3-21 gene in mutated cases, whereas biased V(H)1-69 gene usage was found in unmutated cases as previously reported. Interestingly, the subset of mutated cases using the V(H)3-21 gene displayed distinctive genotypic/phenotypic characteristics with shorter average length of the complementarity determining region 3 and clonal expression of lambda light chains. In addition, this mutated subset showed significantly shorter survival than other mutated cases and a similar clinical course to unmutated cases. We therefore suggest that B-CLL cases with mutated V(H)3-21 genes may constitute an additional entity of B-CLL.