Different reconstitution of peripheral blood lymphocytes and dendritic cells in liver and kidney transplant patients

T cells and dendritic cells are responsible for immune alloreactivity or tolerance after transplantation. In this study, we compared the levels of circulating T, B, and NK lymphocytes, as well as monocytes, plasmacytoid dendritic cells, and myeloid dendritic cells, in adult patients undergoing a liver transplant or kidney transplant. Our findings show that candidates for liver transplant had significantly lower levels of circulating T, B, and dendritic cells than candidates for kidney transplant. Nevertheless, liver transplant patients showed a greater T-cell recovery, despite the use of thymoglobulin, as compared with kidney transplant patients who were induced with Daclizumab. In four kidney transplant patients with allograft rejection we observed a dramatic drop of circulating T and dendritic cells at the time of rejection, and while myeloid dendritic cells and CD4(+) and CD8(+) cells rapidly recovered after 1 month, plasmacytoid dendritic cells and CD4(+)CD25(+) T-cell numbers remained significantly lower than in patients without rejection. Future studies will evaluate the monitoring of circulating CD4(+)CD25(+) T cells and myeloid dendritic cell:plasmacytoid dendritic cell ratio as potential biomarkers for rejection or, alternatively, for withdrawal of immune suppression.     

Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy

BACKGROUND: Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. PATIENTS AND METHODS: Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group (P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. CONCLUSION: Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.     

Hypercytokinemia-induced metabolic encephalopathy in a multiple myeloma patient on hemodialysis undergoing autologous stem cell transplantation: Clinical response after plasma exchange

We report here a 50-years old female with multiple myeloma-associated chronic renal failure who underwent high-dose chemotherapy supported by autologous hematopoietic stem cell transplantation. She developed progressive encephalopathy on day 5 progressing to coma despite hemodialysis and no obvious organ failure. She finally recovered after a single 1-liter plasma exchange. The final diagnosis was metabolic encephalopathy due to hypercytokinemia, particularly high serum TNF levels. We discuss here the pathogenesis and raise an alert for monitoring cytokine levels in patients with renal failure undergoing high-dose chemotherapy.     

Combined treatment with renin-angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: a randomized controlled trial

Background. Currently, several therapeutic protocols exist forIgA nephropathy (IgAN); results in slowing the progression toend-stage renal disease (ESRD) are variable, but 30–40%of patients require replacement therapy (dialysis or renal transplantation)by 20 years from the onset. The adverse effects brought by thechronic assumption of drugs can be a potential limit. Actually,the most used therapies for IgAN are renin–angiotensinsystem blockers (RASB), glucocorticoids and immunosuppressiveagents. Trials with polyunsaturated fatty acids (PUFA) in IgANhave been done since the first successful attempt by Hamazakiin 1984, resulting in alternate answers, but no trials haveever been done testing the efficacy of combined therapy withRASB and PUFA. Methods. We tested the effect of a 6-month course of PUFA (3grams/day) in a group of 30 patients with biopsy-proven IgANand proteinuria already treated with RASB randomized to receivePUFA supplementation or to continue their standard therapy.The primary end-point was the percent reduction of proteinuriafrom the baseline. Secondary end-points were modifications inglomerular filtration rate (GFR), blood pressure, serum triglyceridesand erythrocyturia. Results. At the end of the 6-month trial, the percent reductionof proteinuria was 72.9% in the PUFA group and 11.3% in theRASB group (P < 0.001). A reduction of 50% of baseline proteinuriawas achieved in 80.0% of PUFA patients and 20.0% of RASB patients(P = 0.002). Erythrocyturia was significantly lower in the PUFAgroup (P = 0.031). No significant changes in renal function,blood pressure and triglycerides were observed. Conclusions. PUFA associated with RASB reduced proteinuria inpatients with IgAN more than RASB alone.     

Prospective, Randomized, Multi-Center Trial of Antibody Induction Therapy in Simultaneous Pancreas-Kidney Transplantation

A randomized, multicenter, prospective study was conducted at 18 pancreas transplant centers in the United States to determine the role of induction therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74 recipients were enrolled: 87 recipients each in the induction and noninduction treatment arms. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. There were no statistically significant differences between treatment groups for patient, kidney, and pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28), respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute kidney allograft rejection in the induction and noninduction treatment arms was 13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft rejection occurred later post-transplant and appeared to be less severe among recipients that received induction therapy. The highest rate of Cytomegalovirus (CMV) viremia/syndrome was observed in the subgroup of recipients who received T-cell depleting antibody induction and received organs from CMV serologically positive donors. Decisions regarding the routine use of induction therapy in SPK transplantation must take into consideration its differential effects on risk of rejection and infection.     

Islet Transplantation for Brittle Type 1 Diabetes: The UIC Protocol

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1–3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460   080 ± 418   330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537   495 ± 190   968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2–3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets .     

Rotational Position of Femoral and Tibial Components in TKA Using the Femoral Transepicondylar Axis

Proper femoral and tibial component rotational positioning in TKA is critical for outcomes. Several rotational landmarks are frequently used with different advantages and limitations. We wondered whether coronal axes in the tibia and femur based on the transepicondylar axis in the femur would correlate with anteroposterior deformity. We obtained computed tomography scans of 100 patients with arthritis before they underwent TKA. We measured the posterior condylar angle on the femoral side and the angle between Akagi’s line and perpendicular to the projection of the femoral transepicondylar axis on the tibial side. On the femoral side, we found a linear relationship between the posterior condylar angle and coronal deformity with valgus knees having a larger angle than varus knees, ie, gradual external rotation increased with increased coronal deformity from varus to valgus. On the tibial side, the angle between Akagi’s line and the perpendicular line to the femoral transepicondylar axis was on average approximately 0°, but we observed substantial interindividual variability without any relationship to gender or deformity. A preoperative computed tomography scan was a useful, simple, and relatively inexpensive tool to identify relevant anatomy and to adjust rotational positioning. We do not, however, recommend routine use because on the femoral side, we found a relationship between rotational landmarks and coronal deformity. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Total knee replacement versus osteochondral allograft in proximal tibia bone tumours

Total knee modular megaprosthesis or osteochondral allograft are used to preserve joint movement in bone tumours of the proximal tibia. The aim of this study was to compare two groups of patients with total knee modular megaprosthesis and osteochondral allograft through an objective analysis. Eighteen patients, ten treated with prosthesis (TKR group) and eight with osteochondral allografts (AL group), were included in the study. X-ray, muscular strength measurements, and studies of gait analysis including electromyography (EMG) were used to compare functional results of patients. In the TKR group a higher incidence of knee extension lag was found. While the TKR group had a prevalent knee stiff/hyperextension pattern with reduced rectus femoris activity, the AL group had a higher percentage of normal knee pattern. Knee extensor muscular strength was reduced in the TKR group. TKR functional performance during gait is in most cases abnormal, consistent with the weakness of the extensor apparatus and knee extension lag. Although a greater rate of normal walking was found in the AL group, problems related to a short patellar tendon, knee instability, and joint mismatching were considered to be responsible for abnormal knee kinematics. An allograft, when optimal reconstruction is performed, gives better functional results.     

One-year follow-up of tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of female stress urinary incontinence: a prospective randomised trial

OBJECTIVES: To compare tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of stress urinary incontinence (SUI) for complications (primary end point) and success rate (secondary end point). METHODS: Seventy-two consecutive patients, with a mean age of 53.2 yr (range: 38-69 yr) and affected by SUI, were included in this randomised controlled trial. After preoperative assessment, patients were randomly allocated to the TVT or TVT-O procedure. Operative time, perioperative complications, and hospital stay were prospectively recorded. Cure of SUI was defined as no leakage of urine during the stress test at urodynamic testing at the 12-mo evaluation. The Wilcoxon signed rank sum test, Mann-Whitney U test, McNemar test, and Fisher exact test were used to verify statistical significance, set at p<0.05. RESULTS: All patients were evaluable at the 12-mo follow-up. The characteristics of patients were well balanced between groups after randomisation. The mean operative time was significantly shorter in the TVT-O group. Perioperative complications were significantly more common after the retropubic approach (5% and 27% in TVT-O and TVT groups, respectively, p<0.04). The groups did not differ significantly in intraoperative blood loss, hospital stays, and time to return to normal activities. Sixty-five patients (90%) were successfully treated for SUI 12 mo after the operation (89% and 91% for TVT-O and TVT groups, respectively). CONCLUSIONS: Both techniques appear to be equally effective in the surgical treatment of SUI. However, TVT-O had a shorter operative time and lower overall perioperative complication rate.