Children with high-risk neuroblastoma have a poor prognosis with chemotherapy alone, and hematopoietic stem cell transplantation offers improved survival. As a dose-escalation strategy, tandem transplants have been used, but are associated with persistent immunocompromise. This study evaluated the provision of an autologous costimulated, activated T-cell product to support immunologic function.

Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

A prospective, randomized double-blind study comparing the effects of irradiated and unirradiated white blood cells was conducted in 108 acute leukemia patients with life-threatening infections, refractory to antibiotics. The study demonstrated no significant improvement in 30-day survival or overall survival. Transfusion of unirradiated white cells did not compromise the patient's opportunity to undergo allogeneic stem cell transplant, nor the success rate or overall survival after allogeneic transplant. The important positive finding in this study was that the unirradiated white cells produced a significantly higher increment in circulating granulocytes and in a higher proportion of patients granulocyte count exceeded 1000 per microliter, approaching normal concentrations. The increase in the number and the improved survival of the unirradiated granulocytes suggest that this procedure might potentially be a method to improve the utility of granulocyte transfusions and merits further investigation. The study demonstrated non-inferiority for unirradiated white cells. There were no harmful effects such as graft-versus-host disease, indicating that such studies would be safe to conduct in the future.

CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.

To evaluate the role of dexamethasone therapy in neonatal meningitis in a randomized placebo controlled trial.

Device-related bloodstream infections are associated with a significant increase in patient morbidity and mortality in multiple health care settings. Recently, intraoperative bacterial contamination of conventional open-lumen 3-way stopcock sets has been shown to be associated with increased patient mortality. Intraoperative use of disinfectable, needleless closed catheter devices (DNCCs) may reduce the risk of bacterial injection as compared to conventional open-lumen devices due to an intrinsic barrier to bacterial entry associated with valve design and/or the capacity for surface disinfection. However, the relative benefit of DNCC valve design (intrinsic barrier capacity) as compared to surface disinfection in attenuation of bacterial injection in the clinical environment is untested and entirely unknown. The primary aim of the current study was to investigate the relative efficacy of a novel disinfectable stopcock, the Ultraport zero, with and without disinfection in attenuating intraoperative injection of potential bacterial pathogens as compared to a conventional open-lumen stopcock intravascular device. The secondary aims were to identify risk factors for bacterial injection and to estimate the quantity of bacterial organisms injected during catheter handling.

Thiazolidinedione (TZD) therapy has been associated with an increased risk of bone fractures. Studies in rodents have led to a model in which decreased bone quality in response to TZDs is due to a competition of lineage commitment between osteoblasts (OBs) and adipocytes (ADs) for a common precursor cell, resulting in decreased OB numbers. Our goal was to investigate the effects of TZD exposure on OB-AD lineage determination from primary human bone marrow stromal cells (hBMSCs) both in vitro and in vivo from nondiabetic subjects and patients with type 2 diabetics. Our experimental design included 2 phases. Phase 1 was an in vitro study of TZD effects on the differentiation of hBMSCs into OBs and ADs in nondiabetic subjects. Phase 2 was a randomized, placebo-controlled trial to determine the effects of 6-month pioglitazone treatment in vivo on hBMSC differentiation using AD/OB colony forming unit assays in patients with type 2 diabetes. In vitro, TZDs (pioglitazone and rosiglitazone) enhanced the adipogenesis of hBMSCs, whereas neither altered OB differentiation or function as measured by alkaline phosphatase activity, gene expression, and mineralization. The ability of TZDs to enhance adipogenesis occurred at a specific time/stage of the differentiation process, and pretreating with TZDs did not further enhance adipogenesis. In vivo, 6-month TZD treatment decreased OB precursors, increased AD precursors, and increased total colony number in patients with type 2 diabetes. Our results indicate that TZD exposure in vitro potently stimulates adipogenesis but does not directly alter OB differentiation/mineralization or lineage commitment from hBMSCs. However, TZD treatment in type 2 diabetic patients results in decreased osteoblastogenesis from hBMSCs compared with placebo, indicating an indirect negative effect on OBs and suggesting an alternative model by which TZDs might negatively regulate bone quality.

Previous studies have indicated that supplementation with probiotic bacteria may improve lipid metabolism. The present study was aimed at investigating the effects of a mixture of three strains of Lactobacillus plantarum (CECT 7527, CECT 7528 and CECT 7529) on cholesterol-lowering efficacy in hypercholesterolaemic patients. A total of sixty volunteers (thirty participants in the placebo group and thirty counterparts in the L. plantarum group), aged 18–65 years old, participated in a controlled, randomised, double-blind trial. The study group received one capsule daily containing 1·2 × 10(9) colony-forming units of Lactobacillus strains in a unique dose; the placebo group consumed the same product without bacteria for 12 weeks. A significant reduction of 13·6 % in plasma total cholesterol (TC) levels was observed after 12 weeks of consumption in the L. plantarum group when compared with the placebo group. The lipidic outcomes were also analysed based on TC values at baseline: low initial values (LIV, 2000-2500 mg/l) v. high initial values (HIV, 2510–3000 mg/l). In the HIV group, the L. plantarum treatment showed a reduction after 12 weeks of consumption compared with the placebo group in TC, LDL-cholesterol (LDL-C) and oxidised LDL-C (17·4, 17·6 and 15·6 %, respectively). In the LIV, the L. plantarum treatment only showed a reduction after 12 weeks of consumption when compared with the placebo group in TC (9·4 %). The present results showed that the biofunctionality of L. plantarum (CECT 7527, CECT 7528 and CECT 7529) is proportional to the cardiovascular risk of the patient, having a better effect in patients with higher levels of cholesterol.

The present study was designed to determine whether exclusion of the gingival connective tissue (CT) and periosteum with contained stem cells has a positive or negative effect on periodontal regeneration by comparing the use of a novel modified perforated collagen membrane with a traditional cell occlusive barrier membrane.

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

To investigate the inhibiting effects of multi-target anti-microRNA antisense oligonucleotide (MTg-AMOs) on proliferation and migration of human gastric cancer cells.

SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results.

Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined.

The incorporation of high-dose therapy/autologous stem cell transplantation (HDT/ASCT) and novel agents has significantly improved survival in patients with multiple myeloma (MM), but whether this improvement also benefits patients harboring poor prognostic features, such as nonhyperdiploid MM (NH-MM) and a high proliferation index, remains largely unknown. We analyzed the DNA content and proliferation index of bone marrow plasma cells (PCs) by multiparameter flow cytometry in 595 newly diagnosed transplant-eligible patients with MM included in two consecutive PETHEMA/GEM trials: GEM2000 [VBMCP/VBAD (vincristine, carmustine, melphalan, cyclophosphamide, prednisone/vincristine, bischloroethylnitrosourea, adriamycin, and dexamethasone) followed by HDT/ASCT; n = 319] and GEM2005<65y (randomized induction with VBMCP/VBAD/bortezomib or thalidomide/dexamethasone or bortezomib/thalidomide/dexamethasone followed by HDT/ASCT; n = 276). Of the 595 patients, 295 were classified as NH-MM (49.6%) and 336 (56.5%) as high-proliferative MM (≥1% PCs in S-phase). Detection of NH-MM DNA content and ≥1% PCs in S-phase were of independent prognostic value for overall survival. Treatment with bortezomib-based regimens abrogated the inferior overall survival of patients with ≥1% PCs in S-phase but not of patients with NH-MM. Finally, a comparative analysis of PC proliferation index at diagnosis versus disease progression showed a twofold increase at relapse in 44 of 52 patients (85%) analyzed at both time points. NH-MM and a high proliferation index assessed by multiparameter flow cytometry remain as independent prognostic factors in MM, but the latter may be overcome by incorporating novel agents in the HDT/ASCT setting.

Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of exercise in the hematological and immunological recovery of children undergoing hematopoietic stem cell transplant. The primary objective of this randomized-controlled trial (RCT) is to study the effect of an exercise program (in- and outpatient) on immune cell recovery in patients undergoing an autologous stem cell transplantation. The secondary objective is to determine if an exercise intervention diminishes the usual deterioration in quality of life, physical fitness, and the acquisition of a sedentary lifestyle.

To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM).

Influenza infection after allogeneic hematopoietic cell transplantation (allo-HCT) can result in severe complications. The effectiveness of the annual vaccine depends on age, immune competence, and the antigenic potential of the 3 strains included. We hypothesized that a second vaccine dose, the standard of care for vaccine-naïve children, might improve post hematopoietic cell transplantation (HCT) immune responses. Patients >60 days post-HCT were randomized to receive either 1 (n = 33) or 2 (n = 32) influenza vaccine doses separated by 1 month. The primary endpoint was whether 2 vaccinations induced superior immunity; however, we found no difference. Secondary endpoints were to identify variables associated with responses. Both hemagglutination inhibition (HI; P < .005) and ELISpot responses (P = .03) were greater for patients vaccinated ≥ 1 year posttransplantation. Umbilical cord blood (UCB) recipients showed less IFN-γ responses (P < .001). Interestingly, there was a positive correlation between the total number of CD19(+) cells before vaccination and seroconversion (P = .01) and an inverse correlation for IFN-γ responses (P = .05). Variables not associated with vaccine responses included prevaccine CD4(+) cell counts (total, naïve, or memory), steroid usage at vaccination, age, or conditioning intensity. Time from transplantation to vaccination and absolute CD19(+) cell counts were the strongest predictors of vaccine responses. Methods to improve influenza vaccine responses after allo-HCT are needed.

This cross-over study was conducted to assess the germ-killing efficacy of an essential oil mouthrinse (EOM) by determining the blood levels of microorganisms associated with induced bacteremia and investigating the prevalence of this event in Brazilians with mild-to-moderate gingivitis. Thirty four (31.19%) subjects positive for bacteremia induced by chewing a ration of apple were enrolled out of 109 screened subjects (50 males and 59 females). A difference of at least 10 colony forming units between the pre- and post-insult blood samples was defined as a positive result. For the following two weeks patients underwent a toothbrush plus fluoride dentifrice normalization period, and were then scheduled for the Phase I protocol as follows. At baseline I, subjects were instructed to chew a new apple ration, had new blood samples taken before and after this oral stimulus, and were randomly assigned to an experimental essential oil (n = 17) or placebo (P) mouthrinse (n = 17) treatment for 2 weeks. These procedures were repeated at the end of Phase I and then followed by a two-week wash-out period (tooth brushing with fluoride dentifrice). Bacteremia was again induced at baseline and at the end of Phase II, when subjects were crossed-over to the other EOM or placebo groups. Bacterial count differences between baseline and 2-week post-treatment (EOM versus P) in the blood samples collected were assessed by analysis of covariance. Mean aerobic counts decreased by 45.8%, whereas mean anaerobic counts decreased by 63.3% after EOM treatment. After the P treatment, aerobic bacteria increased by 28.4% and anaerobic bacteria decreased by 18.5%. This study validated this novel methodology and showed that the germ-killing action of EOM significantly reduced bacteremia.

The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.