Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation.

Immunoincompetence after allogeneic hematopoietic stem cell transplantation (HSCT) affects in particular the T-cell lineage and is associated with an increased risk for infections, graft failure and malignant relapse. To generate large numbers of T-cell precursors for adoptive therapy, we cultured mouse hematopoietic stem cells (HSCs) in vitro on OP9 mouse stromal cells expressing the Notch-1 ligand Delta-like-1 (OP9-DL1). We infused these cells, together with T-cell-depleted mouse bone marrow or purified HSCs, into lethally irradiated allogeneic recipients and determined their effect on T-cell reconstitution after transplantation. Recipients of OP9-DL1-derived T-cell precursors showed increased thymic cellularity and substantially improved donor T-cell chimerism (versus recipients of bone marrow or HSCs only). OP9-DL1-derived T-cell precursors gave rise to host-tolerant CD4+ and CD8+ populations with normal T-cell antigen receptor repertoires, cytokine secretion and proliferative responses to antigen. Administration of OP9-DL1-derived T-cell precursors increased resistance to infection with Listeria monocytogenes and mediated significant graft-versus-tumor (GVT) activity but not graft-versus-host disease (GVHD). We conclude that the adoptive transfer of OP9-DL1-derived T-cell precursors markedly enhances T-cell reconstitution after transplantation, resulting in GVT activity without GVHD.

Effects of Individualized Dialysate Sodium Prescription in Hemodialysis - Results from a Prospective Interventional Trial.

INTRODUCTION: Individualized dialysate sodium prescription does affect weight gain, blood pressure (BP), and intradialytic complications. A prospective interventional trial (Dialysate Individualised Sodium (DISO) trial) was conducted to study this issue in Indian patients. METHODS: Forty patients on thrice-weekly maintenance hemodialysis (HD) for at least 6 weeks were enrolled. The study was performed in two different phases. In the first phase, 12 consecutive HD sessions were done with a standard dialysate sodium concentration of 140 mEq/L. In the second phase, 12 consecutive HD sessions were done with dialysate sodium concentration set to individualized value (mean of pre-HD sodium concentration multiplied by Donnan coefficient of 0.95). Differences in pre- and post-HD sodium, interdialytic weight gain (IDWG), pre- and post-HD BP, thirst scores, and intradialytic adverse events during both phases were assessed. RESULTS: The mean age of patients was 45.65 years (24 males, 16 females). The mean serum pre-HD sodium level was 138.7 ± 1.7 meq/L in the standard phase and 138.2 ± 2.6meq/L in the individualized phase (P = 0.229). In the standard phase, the mean IDWG was 2.64 ± 1.56 kg and 2.13 ± 0.99 kg in the individualized phase (P = 0.008). The mean pre-HD systolic BP was 138 ± 18 mmHg and 134 ± 17 mmHg in the standard and individualized phases (P = 0.008). There was no difference in intradialytic symptoms, hypotensive episodes or requirement of interventions. Hypertension episodes occurred at a mean value of 2.2 and 1.2 in the standard and individualized phases, respectively (P = 0.010). CONCLUSION: The use of individualized dialysate sodium level is safe and results in lower IDWG, pre-HD systolic BP, and intradialytic hypertension in patients on HD.

"Why I Chose Hemodialysis Over Peritoneal Dialysis": An Opinion Survey Among In-Center Hemodialysis Patients.

Peritoneal dialysis (PD) penetration in India remains low despite the huge chronic kidney disease burden and unmet need for renal replacement therapy (RRT). In order to understand the socioeconomic reasons that govern patients' preference for hemodialysis (HD), we carried out an opinion survey among prevalent in-center HD patients at our institution using a multiple response questionnaire that was verbally administered to them at the dialysis facility by the investigators. Close to 80% were self-financed and 49.5% were on twice weekly HD. Despite the majority (95%) receiving RRT education from a nephrologist, 43.4% were not aware of PD as an RRT modality. The treating nephrologist's recommendation was the most important reason given for choosing HD (77.8%) and not choosing PD (69.7%). Other reasons for not choosing PD included lack of a dedicated caregiver or "clean area" at home (15.1%), fear of infection (15.1%), disruption of work (14.1%), and the high cost of PD (7%). The perceived advantages of HD over PD were greater convenience because of need for only twice or thrice weekly sessions (61%), supervised care received in a hospital setting (28.8%), and less disruption of the patient's and family's routine (22%). We discuss the implications of these findings and what policy makers and nephrologists in India and other developing countries can do to improve PD penetration and utilization.

The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era.

Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.

Rituximab-induced urticarial dermatitis during the treatment of membranous nephropathy.

Rituximab is a monoclonal antibody directed against B cells and is being increasingly used for various renal indications. Acute dermatologic manifestations such as urticaria are well known to occur during rituximab infusion. Here, we report the case of a 53- year-old female who was treated with rituximab for membranous nephropathy and developed an exanthematous rash, which progressed with a further dose of rituximab and was diagnosed as urticarial dermatitis. A review of literature showed that urticarial dermatitis following rituximab therapy has been seldom reported and identification of this complication is very important to avoid giving further doses and thus, increasing the severity of lesions.

Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease for which stem cell research has created hope in the last few years. Seven PD patients aged 22 to 62 years with a mean duration of disease 14.7+/-7.56 years were enrolled to participate in the prospective, uncontrolled, pilot study of single-dose, unilateral transplantation of autologous bone-marrow-derived mesenchymal stem cells (BM-MSCs). The BM-MSCs were transplanted into the sublateral ventricular zone by stereotaxic surgery. Patients were followed up for a period that ranged from 10 to 36 months. The mean baseline "off" score was 65+/-22.06, and the mean baseline "on" score was 50.6+/-15.85. Three of 7 patients have shown a steady improvement in their "off"/"on" Unified Parkinson's Disease Rating Scale (UPDRS). The mean "off" score at their last follow-up was 43.3 with an improvement of 22.9% from the baseline. The mean "on" score at their last follow-up was 31.7, with an improvement of 38%. Hoehn and Yahr (H&Y) and Schwab and England (S&E) scores showed similar improvements from 2.7 and 2.5 in H&Y and 14% improvement in S&E scores, respectively. A subjective improvement was found in symptoms like facial expression, gait, and freezing episodes; 2 patients have significantly reduced the dosages of PD medicine. These results indicate that our protocol seems to be safe, and no serious adverse events occurred after stem-cell transplantation in PD patients. The number of patients recruited and the uncontrolled nature of the trial did not permit demonstration of effectiveness of the treatment involved. However, the results encourage future trials with more patients to demonstrate efficacy.