Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Prospective evaluation of intra-observer variability of the hydronephrosis index in sonographic examination of 44 patients with acute renal colic

Purpose

The aim of our prospective designed study was to confirm the intra-observer agreement of assessments of the hydronephrosis index (HI) with a sonographic technique that potentially provides additional information in patients with acute renal colic (ARC).

Methods

Sonographic measurement of HI and valuation of common clinical criteria were performed in 44 consecutive patients presenting with unilateral stone-related ARC. HI of colic side was recorded twice in predefined time intervals. Intra-observer agreement was evaluated with the Spearman’s rank correlation/rho (ρ) for attributive-metric characteristics. Data of HI-measurement on the colic side were compared with data of the unaffected side using t test.

Results

Intra-observer agreement was significant for HI in the colic side (ρ = 0.918, p < 0.001) and in the unaffected side (ρ = 0.826, p < 0.001). The mean HI between colic and unaffected side differed significantly on the first evaluation (85.2 vs. 93.7, respectively; p < 0.001) and on the second evaluation (85.1 vs. 93.6, respectively; p < 0.001) as well.

Conclusions

The HI method is a slightly feasible examination method in patients presenting with stone-related renal colic. Moreover, it offers a solid discrimination between obstruction and non-obstruction. Our prospective trial illustrates HI as a reproducible method with a high-grade intra-observer agreement. However, potential change of values under medical expulsive therapy and coherency with the functionality of the obstructed kidney may lead to bias and therefore remain to be analyzed. Further studies to specify exact thresholds for this method and to state our findings are required.     

The Outcome of Modified Extended Trochanteric Osteotomy in Revision THA for Vancouver B2/B3 Periprosthetic Fractures of the Femur

We hypothesised that a modified ETO in patients undergoing revision total hip arthroplasty (THA) for treatment of Vancouver B2/B3 peri-prosthetic fractures would be associated with good clinical outcomes. A retrospective review was conducted of 34 patients (mean age 73 years). At mean follow-up of 57 months, the ETO had healed in all patients. Two patients had subsidence of the femoral stem at two and three years postoperatively requiring revision, and one patient had a dislocation 3 months after surgery. The mean Harris Hip Score at the time of the final follow-up was 76.9 (range, 46–95); 23/34 patients had an excellent result, 7/34 a good result, and 4/34 a poor result. We conclude that satisfactory outcomes can be obtained using this technique.     

Treatment of Failed Allograft Prosthesis Composites Used for Hip Arthroplasty in the Setting of Severe Proximal Femoral Bone Defects

This study assessed failures of allograft prosthesis composites (APC) and revisions with a new APC. Twenty-one patients with failed APC’s after revision hip arthroplasty with severe proximal femoral bone loss underwent revision with a new APC. Causes of failure were aseptic loosening (18 patients), infection (3 patients). Of these 21 APC revisions, two patients failed (after 60, 156 months). The 5 and 10 year survival rates were 83.5% (95% CI, 79–100%, number at risk 12 and 6 accordingly). In addition, two patients had non-union at the host-allograft bone junction and were augmented with bone autograft and plate. These results suggest that failed APCs may be revised to a new APC with a predictable outcome.     

Impact of tutorial assistance in laparoscopic sigmoidectomy for acute recurrent diverticulitis

Purpose

Adequate training and close supervision by an experienced surgeon are crucial to assure the patient safety during laparoscopic training. This study evaluated the impact of tutorial assistance on the duration of surgery and postoperative complications after laparoscopic sigmoidectomy.

Methods

The data from 235 patients undergoing laparoscopic sigmoidectomy were collected. Operating surgeons were classified as either residents/registrars (group A, tutorial assistance) or consultants operating autonomously (group B). Groups were compared concerning the duration of surgery and in-hospital complications using a multivariable regression model accounting for the most relevant confounders.

Results

The median duration of the operation in group A (n = 75) was 221 min, and that in group B (n = 160) 189 min (p < 0.001). The risk of developing any in-hospital complication (Clavien–Dindo classification I–V) was 36.0 % in Group A and 32.5 % in group B (95 % CI ?16.6, 9.6 %). The risk of developing moderate to severe surgical complications (Clavien–Dindo classification II-V) was 16.0 % in group A and 12.5 % in group B (95 % CI ?13.3, 6.3 %).

Conclusions

We were unable to demonstrate a clear impact of tutorial assistance on the risk of postoperative complications. Although associated with a longer duration of surgery, laparoscopic sigmoidectomy for acute recurrent sigmoid diverticulitis conducted by a junior supervised surgeon appears to be a safe surgical modality.     

Critical Dynamics of Defects and Mechanisms of Damage-Failure Transitions in Fatigue

An experimental methodology was developed for estimating a very high cycle fatigue (VHCF) life of the aluminum alloy AMG-6 subjected to preliminary deformation. The analysis of fatigue damage staging is based on the measurement of elastic modulus decrement according to “in situ” data of nonlinear dynamics of free-end specimen vibrations at the VHCF test. The correlation of fatigue damage staging and fracture surface morphology was studied to establish the scaling properties and kinetic equations for damage localization, “fish-eye” nucleation, and transition to the Paris crack kinetics. These equations, based on empirical parameters related to the structure of the material, allows us to estimate the number of cycles for the nucleation and advance of fatigue crack.     

Laser-driven structural transformations in dextran-graft-PNIPAM copolymer/Au nanoparticles hybrid nanosystem: the role of plasmon heating and attractive optical forces

Laser induced structural transformations in a dextran grafted-poly(N-isopropylacrylamide) copolymer/Au nanoparticles (D-g-PNIPAM/AuNPs) hybrid nanosystem in water have been observed. The laser induced local plasmonic heating of Au NPs leads to Lower Critical Solution Temperature (LCST) phase transition in D-g-PNIPAM/AuNPs macromolecules accompanied by their shrinking and aggregation. The hysteresis non-reversible character of the structural transformation in D-g-PNIPAM/AuNPs system has been observed at the decrease of laser intensity, i.e. the aggregates remains in solution after the turn-off the laser illumination. This is an essential difference comparing to the case of usual heating–cooling cycles when there is no formation of aggregates and structural transformations are reversible. Such a fundamental difference has been rationalized as the result of action of attractive optical forces arising due to the excitation of surface plasmons in Au NPs. The attractive plasmonic forces facilitate the formation of the aggregates and counteract their destruction. The laser induced structural transformations have been found to be very sensitive to matching conditions of the resonance of the laser light with surface plasmon resonance proving the plasmonic nature of observed phenomena.

Structural transformations in D-g-PNIPAM/AuNPs hybrid nanosystem arise from the synergetic action of plasmonic heating and attractive optical plasmonic forces.     

Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy

An unresolved question in cardiac biology is whether distinct signaling pathways are responsible for the development of pathological and physiological cardiac hypertrophy in the adult. Physiological hypertrophy is characterized by a normal organization of cardiac structure and normal or enhanced cardiac function, whereas pathological hypertrophy is associated with an altered pattern of cardiac gene expression, fibrosis, cardiac dysfunction, and increased morbidity and mortality. The elucidation of signaling cascades that play distinct roles in these two forms of hypertrophy will be critical for the development of more effective strategies to treat heart failure. We examined the role of the p110alpha isoform of phosphoinositide 3-kinase (PI3K) for the induction of pathological hypertrophy (pressure overload-induced) and physiological hypertrophy (exercise-induced) by using transgenic mice expressing a dominant negative (dn) PI3K(p110alpha) mutant specifically in the heart. dnPI3K transgenic mice displayed significant hypertrophy in response to pressure overload but not exercise training. dnPI3K transgenic mice also showed significant dilation and cardiac dysfunction in response to pressure overload. Thus, PI3K(p110alpha) appears to play a critical role for the induction of physiological cardiac growth but not pathological growth. PI3K(p110alpha) also appears essential for maintaining contractile function in response to pathological stimuli.