Management Strategies in Hemodialysis Vascular Access

Since the introduction of the AV fistula and the use of interposition graft little improvement has been made in the vascular access field. Still, vascular access related complications, are one of the most important reasons for patient hospitalization, morbidity and even mortality (1,2). Interestingly, the costs of vascular access related care was found to be more than fivefold higher for patients with AVG compared with patients with a functioning AVF (3). In an attempt to improve overall patency rates and reduce access related costs, the NFK-DOQI committee currently recommends that in any dialysis center the majority of new dialysis patients should have a primary AVF constructed (4,5). Unfortunately, creation of an AVF is not always possible as a consequence of prior vascular access surgery, insufficient caliber of forearm vessels or sclerosis caused by prior venipunctures. Although less thrombotic and infectious complications occur in AVF, the AVF is not ideal, i.e. 100% successful. Adequate maturation of AVF, i.e. sufficient dilatation and arterialization, fails in up to 30% of all newly created fistulae, resulting in delayed initiation of dialysis treatment or placement of temporary central venous dialysis catheters, and related morbidity (6-10). Optimalization of patient selection could improve AVF patency rates and access related morbidity. Considering the increasing age of hemodialysis patients, prolongation of the dialysis therapy, and the worldwide increase of the number of patients requiring hemodialysis, the number of AV grafts will probably increase rather than decrease. As a consequence, vascular access complications, particularly thrombosis, will continue to challenge vascular access care in the future

Short- and long-term functional effects of percutaneous transluminal angioplasty in hemodialysis vascular access

The efficacy of percutaneous transluminal angioplasty (PTA) is usually expressed as the angiographic result. Access flow (Qa) measurements offer a means to quantify the functional effects. This study was performed to evaluate the short-term functional and angiographic effects of PTA and to determine the longevity of the functional effects during the follow-up period. Patients with an arteriovenous graft (AVG) or an arteriovenous fistula (AVF) who were eligible for PTA (Qa values of <600 ml/min) were included. Ultrasound-dilution Qa measurements were obtained shortly before PTA and periodically after PTA, beginning 1 wk after the procedure. The short-term effects were expressed as the increase in Qa and the reduction of stenosis. The long-term effects were expressed as patency and the decrease in Qa after PTA. Ninety-eight PTA procedures for 60 patients (65 AVG and 33 AVF) were analyzed. Qa improved from 371 +/- 17 to 674 +/- 30 ml/min for AVG and from 304 +/- 24 to 638 +/- 51 ml/min for AVF (both P < 0.0001). In 66% (AVG) and 50% (AVF) of cases, Qa increased to levels of >600 ml/min. The degree of stenosis decreased from 65 +/- 3 to 17 +/- 2% for AVG and from 72 +/- 5 to 23 +/- 7% for AVF (both P < 0.005). The reduction of stenosis was not correlated with DeltaQa (r(2) = 0.066). Six-month unassisted patency rates after PTA were 25% for AVG and 50% for AVF. The decreases in Qa were 3.7 +/- 0.8 ml/min per d for AVG and 1.8 +/- 0.9 ml/min per d for AVF. Qa values before PTA and DeltaQa were correlated with the subsequent decrease in Qa (P < 0.005). In conclusion, Qa increases after PTA but, in a substantial percentage of cases, not to levels of >600 ml/min. Qa values before PTA and the increase in Qa were correlated with long-term outcomes, whereas angiographic results were not. These data, combined with literature data, suggest that there is optimal timing for PTA

Aberrant Receptor-Mediated Endocytosis of Schistosoma mansoni Glycoproteins on Host Lipoproteins

BACKGROUND: Bilharzia is one of the major parasitic infections affecting the public health and socioeconomic circumstances in (sub) tropical areas. Its causative agents are schistosomes. Since these worms remain in their host for decades, they have developed mechanisms to evade or resist the immune system. Like several other parasites, their surface membranes are coated with a protective layer of glycoproteins that are anchored by a lipid modification. METHODS AND FINDINGS: We studied the release of glycosyl-phosphatidylinositol (GPI)-anchored proteins of S. mansoni and found them in the circulation associated with host lipoprotein particles. Host cells endocytosed schistosomal GPI-anchored proteins via their lipoprotein receptor pathway, resulting in disturbed lysosome morphology. In patients suffering from chronic schistosomiasis, antibodies attacked the parasite GPI-anchored glycoproteins that were associated with the patients' own lipoprotein particles. These immunocomplexes were endocytosed by cells carrying an immunoglobulin-Fc receptor, leading to clearance of lipoproteins by the immune system. As a consequence, neutral lipids accumulated in neutrophils of infected hamsters and in human neutrophils incubated with patient serum, and this accumulation was associated with apoptosis and reduced neutrophil viability. Also, Trypanosoma brucei, the parasite that causes sleeping sickness, released its major GPI-anchored glycoprotein VSG221 on lipoprotein particles, demonstrating that this process is generalizable to other pathogens/parasites. CONCLUSIONS: Transfer of parasite antigens to host cells via host lipoproteins disrupts lipid homeostasis in immune cells, promotes neutrophil apoptosis, may result in aberrant antigen presentation in host cells, and thus cause an inefficient immune response against the pathogen

A symptom-based algorithm for calcium management after thyroid surgery: a prospective multicenter study

Objective: Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed symptom-based treatment algorithm including a protocolized attempt to phase out supplementation. Methods: In a prospective multicenter study, patients were treated according to the new algorithm and compared to a historical cohort of patients treated with a biochemically based approach. The primary outcome was the proportion of patients receiving calcium and/or alfacalcidol supplementation. Secondary outcomes were calcium-related complications and predictors for supplementation. Results: One hundred thirty-four patients were included prospectively, and compared to 392 historical patients. The new algorithm significantly reduced the proportion of patients treated with calcium and/or alfacalcidol during the first postoperative year (odds ratio (OR): 0.36 (95% CI: 0.23–0.54), P < 0.001), and persistently at 12 months follow-up (OR: 0.51 (95% CI: 0.28–0.90), P < 0.05). No severe calcium-related complications occurred, even though calcium-related visits to the emergency department and readmissions increased (OR: 11.5 (95% CI: 4.51–29.3), P <0.001) and (OR: 3.46 (95% CI: 1.58–7.57), P < 0.05), respectively. The proportional change in pre- to post operative parathyroid hormone (PTH) was an independent predictor for supplementation (OR: 1.04 (95% CI: 1.02–1.07), P < 0.05). Conclusions: Symptom-based management of postthyroidectomy hypocalcemia and a protocolized attempt to phase out supplementation safely reduce d the proportion of patients receiving supplementation, although the number of calcium-related hospital visits increased. For the future, we envision a more individualized treatment approach for patients at risk for delayed symptomatic hypocalcemia, including the proportional change in pre- to post- operative PTH

Protein 4.1G binds to a unique motif within the Fc-gamma RI cytoplasmic tail

The C-terminal domain of protein 4.1G was identified to interact with the cytosolic tail of the high affinity IgG receptor, Fc gamma RI, in yeast two-hybrid screens. Proteins of the 4.1 family have previously been found to mediate receptor/cytoskeleton interactions. In the study presented here, we show an alternatively spliced 4.1G product to be associated with increased Fc-gamma RI binding in yeast two-hybrid assays, and to be selectively enriched in most immune cells at the transcript level. In addition, a detailed analysis of the 4.1G 'docking site' within Fc gamma RI is provided by examining Fc gamma RI-CY-truncated and alanine-substituted mutants. These pointed to an Fc gamma RI membrane-proximal core motif of HxxBxxxBB (H represents hydrophobic residues, B basic residues and x represents any residue), followed by hydrophobic and (potentially) negatively charged residues to be central for interaction with protein 4.1G. (C) 2007 Elsevier Ltd. All rights reserved