Claudio Beretta

Long‐term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia: a prospective study

Summary. Infectious and thrombotic complications limit the long‐term use of subcutaneous ports as venous accesses for children with haemophilia. This study has evaluated for the first time the safety and feasibility of internal arteriovenous fistulae (AVF) as alternative accesses. During the 3‐year study period, 27 severe haemophiliacs, 14 with factor VIII inhibitors (52%), underwent the creation of 31 proximal AVF in the forearm. Mild forearm haematomas were observed after five procedures (16%) in five patients who had or developed inhibitors after surgery. Inadequate AVF maturation was observed after five of 31 procedures (16%) in four children. AVF were first accessed after a median of 42 d and regularly used at home by 26 patients (96%) for a median follow‐up period of 29 months. Thrombosis of a venous branch occurred in one AVF (3%) after 9 months of uncomplicated use in a child with inhibitor who spontaneously recovered from the symptoms and still used AVF for nine additional months. Mild symptoms, referable to distal ischaemia, were transiently reported by two children (7%) who needed no remedial intervention. This study demonstrates that the use of AVF in haemophiliacs enabled long‐term treatment at home in all patients but one.

Improved treatment feasibility in children with hemophilia using arteriovenous fistulae: the results after seven years of follow-up

Whilst the benefits of prophylactic replacement therapy for children with hemophilia and of immune tolerance for those with inhibitors are both generally accepted, venous access can be a limiting problem in their delivery. In this paper, Mancuso and coworkers report on their extensive experience using arterio-venous fistulae to deal with this problem and suggest they could be more widely adopted. Background An easy and stable venous access is essential in hemophilic children who receive regular prophylaxis or immune tolerance induction treatment. Central venous access devices improve treatment feasibility, but their use is complicated by infection and/or thrombosis. Arteriovenous fistula (AVF) has been evaluated as an alternative to central venous access devices in hemophilic children since 1999. Design and Methods This study provides results obtained in a large series after seven years of follow-up. Results From 1999 to 2008, 43 procedures were performed in 38 children (median age: 2.7 years). Thirty-five AVFs (81%) achieved maturation after a median of 58 days and were used for a median of five years (range: 0.4–8.5). A brachial artery caliber larger than 1.2 mm was associated with successful maturation (p<0.05). Complications with some impact on arteriovenous fistula use or duration were observed in 14/43 procedures (32%) and in 13/38 children (34%). Age at arteriovenous fistula creation was younger in children who lost arteriovenous fistula patency (p<0.05) and aneurysms were more frequent in children who were on daily treatment regimen and thus had a greater cumulative number of arteriovenous fistula accesses (p<0.05). At the end of the follow-up period, 22 AVFs were still in use and 9 had been surgically dismantled. Arteriovenous fistula use allowed long-term prophylaxis (up to 8.5 years) in 11 children and the completion of immune tolerance induction without interruptions in 18 children. Conclusions This study confirms the feasibility of arteriovenous fistula with an acceptable rate of complications and suggests that its use is particularly favorable in children with inhibitors in whom it should be considered as first-choice venous access.

Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the rat

We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9( 11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is characterized by an inhibitory activity against iron-dependent lipid peroxidation, on ischemia-reperfusion renal injury in a rat model. After either 60 or 90 min of ischemia, plus 2 or 24 h of reperfusion, kidneys were assayed for glutathione, adenine nucleotides and lipid peroxidation products. 60 min of ischemia produced too little oxidative stress and/or too much spontaneous recovery to allow visualization of the protective effect of the drug. 90 min of ischemia followed by reperfusion induced significant glutathione oxidation, the free oxidized glutathione to total glutathione redox ratio (%) being enhanced from 4.6 +/- 0.7% before kidney clamping to 11 +/- 1 and 8.6 +/- 1.4% at 2 and 24 h reperfusion, respectively. Treatment with the lazaroid provided significant protection against this oxidation (4.9 +/- 1.05% at 24 h reperfusion). Results of lipid peroxidation confirmed the antioxidant effect of the lazaroid. In conclusion this study provides evidence for a protective role of the tested lazaroid against ischemia-reperfusion renal injury in the rat.

Further studies of the action on smooth muscle of eledoisin-fragments and eledoisin-like hepta-and hexapeptides

Abstract The effect of eledoisin fragments and eledoisin-related peptides was studied in vivo on dog, rabbit and cock blood pressure, on rabbit uterus and on guinea pig brocchospasm, and in vitro on guinea pig seminal vesicles. The following conclusions were drawn: (1) At least six amino acids are necessary for the biological activity. (2) The nona-and decapeptides are in general more active than eledoisin. (3) The substitution of some amino acids in the hepta-and hexapeptide chain can yield more specific and more active compounds. Thus the presence of lysine instead of alanine in the hexapeptide increased the affinity of the new peptides for vascular smooth muscle and the replacement of the methioninamide residue with the ethioninamide residue caused a considerable enhancement of all activity except that on the guinea pig bronchial muscles.

Living Donor Transplantation of Kidneys with Fibromuscular Dysplasia: Indications, Surgical Techniques and Long Term Results in 11 Cases

The incidence of FMD in potential LDs is observed in a range from 2% to 6.6% with a female predominance [1]; it is the second most common anatomical abnormality after multiple renal arteries. FMD still represents a challenge for any decision to harvest the kidney, particularly from a LD, due to the potential risk to develop a renovascular hypertension and/or FMD either in the remnant kidney after donation [2,3,1,4] or in the recipient’s graft [5-7]. Moreover, the problem may only arise at the operative stage since early forms of FMD give rise to no or mild radiographic evidence. This ‘mild’ radiographic evidence has been described by Indudhara [2] as irregularity of the arterial wall without significant stenosis.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

Background Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. Methods Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. Results HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). Conclusions Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.