Short- to long-term follow-up of total femoral replacement in non-oncologic patients.

BACKGROUND: Compromised bone stock and heavily impaired structural integrity after multiple endoprosthetic revision surgeries can lead to a comparable condition as encountered in musculoskeletal tumor surgery. Total femoral replacement (TFR) can restore femoral integrity and allow patients to resume ambulation. Even though several authors reported their results of TFR, so far many questions are still on debate: Which patients are at risk to experience low functional outcome? Do complications and clinical outcome after TFR depend on the indication for the surgery (e.g. periprosthetic fractures or aseptic loosening) or the age of the patients? The purpose of the present study was to compare complication rates after TFR performed with modular total femur prosthesis MML (Fa. ESKA/Orthodynamics) in patients without malignant disease. METHODS: We conducted a retrospective chart review and functional investigation of patients treated with a TFR for non-oncologic conditions from 1995 to 2015 and a minimum follow-up of 2 years. Complications were recorded according to the Henderson-Classification; outcome was evaluated with established clinical scores. The indication for TFR was periprosthetic fracture (Group A, n = 11) or aseptic loosening (Group B, n = 7) with massive bone defect of the femur deemed unsuitable for conventional arthroplastic or biologic reconstruction. RESULTS: Eighteen patients matched the inclusion criteria and could be investigated clinically after a mean follow-up of 80 months (range: 28-132). Before TFA, all patients had previously undergone multiple operations (range: 1-8). The overall failure rate for any reason was 72% (n = 13/18), leading to a total of 37 surgical revisions with total exchange of TFR in 22% (n = 4/18). Most common failure mechanism was Type I (soft tissue), followed by Type IV (infection) and Type III (mechanical failure). According to Enneking's functional evaluation method (MSTS-Score), the function ranged from 1 to 15 with a mean of 10 ± 4 out of 30. CONCLUSION: TFR is a salvage procedure to restore mechanical integrity and regain functional ability after extensive femoral bone loss. Outcome of the patients in the present study did mainly depend on the age at reconstruction and not on the indication for TFR.

Reduced CD40L expression on ex vivo activated CD4+ T-lymphocytes from patients with excellent renal allograft function measured with a rapid whole blood flow cytometry procedure.

BACKGROUND: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. MATERIALS AND METHODS: Whole blood from recipients of renal allografts was stimulated with PMA and ionomycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. RESULTS: The median percentage +/- SEM of CD4+/CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation (groups 2a and 3a) revealed a higher percentage of CD4+CD40L+ cells than patients showing a gradual increase over time (groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. CONCLUSION: After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy.

Non-invasive monitoring of renal transplant recipients: urinary excretion of soluble adhesion molecules and of the complement-split product C4d.

BACKGROUND: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. METHODS: Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: GROUP 1: acute steroid-sensitive rejection (ASSR, n = 14), GROUP 2: acute steroid-resistant rejection (ASRR, n = 12), GROUP 3: chronic allograft dysfunction (CAD, n = 20) and GROUP 4: stable graft function (SGF, n = 29). RESULTS: All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p < 0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p < 0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p < 0.05). CONCLUSION: The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment.

Gadolinium as an alternative contrast agent for diagnostic and interventional angiographic procedures in patients with impaired renal function.

BACKGROUND: The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy. METHODS: Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12). RESULTS: Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases. CONCLUSIONS: Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.