Cardiomyopathy and cell therapy: ejection fraction improvement and cardiac muscle mass increasing, after a year of bone marrow stem cells transplantation, by magnetic resonance image

The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction – LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed - up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients.

Oral changes in individuals undergoing hematopoietic stem cell transplantation

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression. OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation. METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients); B (autologous transplant, 31 patients). A total of three dental status assessments were performed: in the pre-transplantation period (moment 1), one week after stem cell infusion (moment 2), and 100 days after transplantation (moment 3). In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks. RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression. CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.

Outcome of pigs with short gut syndrome submitted to orthotopic intestinal transplantation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Quantified power Doppler as a predictor of delayed graft function after renal transplantation

No safe ultrasound (US) parameters have been established to differentiate the causes of graft dysfunction.To define US parameters and identify the predictors of normal graft evolution, delayed graft function (DGF), and rejection at the early period after kidney transplantation.Between June 2012 and August 2013, 79 renal transplant recipients underwent US examination 1-3 days posttransplantation. Resistive index (RI), power Doppler (PD), and RI + PD (quantified PD) were assessed. Patients were allocated into three groups: normal graft evolution, DGF, and rejection.Resistive index of upper and middle segments and PD were higher in the DGF group than in the normal group. ROC curve analysis revealed that RI + PD was the index that best correlated with DGF (cutoff = 0.84). In the high RI + PD group, time to renal function recovery (6.33 +/- A 6.5 days) and number of dialysis sessions (2.81 +/- A 2.8) were greater than in the low RI + PD group (2.11 +/- A 5.3 days and 0.69 +/- A 1.5 sessions, respectively), p = 0.0001. Multivariate analysis showed that high donor final creatinine with a relative risk (RR) of 19.7 (2.01-184.7, p = 0.009) and older donor age (RR = 1.17 (1.04-1.32), p = 0.007) correlated with risk DGF.Quantified PD (RI + PD) was the best DGF predictor. PD quantification has not been previously reported .

Do anticoagulant and antiplatelet agents prevent acute graft thrombosis in renal transplantation? A meta-analysis of case series studies

Introduction & Objectives: Thrombosis of the renal allograft is expected to occur in 1–6% of kidney transplants, and graft loss is expected in almost all cases. Anticoagulant and anti-platelet agents could serve as an adjunctive preventive measure, but sound evidence of benefits are still lacking, in this setting. We therefore assessed the efficacy and safety of anticoagulant and anti-platelet agents, in reducing the rate of renal allograft thrombosis. Methods: A review of the literature was carried out in major databases (MEDLINE, EMBASE and LILACS), with a comprehensive search strategy, to locate all available case series studies of anticoagulant and/or anti-platelet prophylaxis of thrombosis in renal transplantation. The date of the last search was 11 August 2014. We pooled all case series in a proportional meta-analysis. Statistical significance was achieved if the 95% confidence intervals obtained for each intervention did not overlap. Results: Our search strategy retrieved 7160 titles, from which 21 case series were chosen for analysis. A total of 3246 patients were identified (1718 treated with antiplatelet and/or anticoagulant agents, and 1528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention, compared to 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%), in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. Bleeding complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin + anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. Conclusions: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher haemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.

Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Safety of kidney transplantation using anti-HBc-positive donors

Background. Prospective studies evaluating the risk of hepatitis B virus (HBV) transmission in transplants of kidneys from hepatitis B core antibody (anti-HBc)-positive/ hepatitis B surface antibody (anti-HBs) negative donors are still lacking. The objective of this study was to assess the safety of kidney transplantation with the use of anti-HBc positive donors.Methods. This prospective case series study included 50 kidney transplant recipients from anti-HBc positive donors with or without anti-HBs positivity. Recipients were required to test positive for anti-HBs (titers >10 mUI/mL), regardless of anti-HBc status, and negative for hepatitis B surface antigen (HBsAg). Recipient and donor data were retrieved from medical records, databases, and organ procurement organization sheets. Liver function tests were performed at progressively increasing post-transplantation intervals. Complete serologic tests for HBV were performed before transplantation, 3 and 6 months after transplantation, and annually thereafter.Results. Six months after transplantation, all recipients were negative for HBsAg, HBeAg, anti-HBe, and anti-HBcIgM. No seroconversion was observed among the 20 patients who received kidneys from anti-HBc positive/anti-HBs negative donors. No patient showed elevated liver enzymes during follow-up.Conclusions. Kidney transplantation using organs from anti-HBeIgG positive donors (even when they are concurrently anti-HBs negative) in anti-HBs positive recipients is a safe procedure and may be considered as a way to expand the donor pool.

Islet of Langerhans transplantation. A comparative study of two different methods for isolating islet cells from rat pancreas

Two different methods for isolation of islet of Langerhans on control of metabolic abnormalities of alloxan-induced diabetic rat were tested. Sixty rats were randomly assigned to four experimental groups: GI included 10 non-diabetic control rats, GII included 10 diabetic control rats, without treatment, GIII included 20 diabetic rats (10 inbred and 10 outbred rats) that received islet of Langerhans transplantation (ILT) using islet cells prepared by collagenase, and GIV included 20 diabetic rats (10 inbred and 10 outbred rats) submitted to ILT using islet cells prepared by nonenzymatic method. Clinical and laboratory parameters at beginning and 4, 7, 14, 21 and 30 days of follow-up were recorded. Outbred rats were immunosuppressed with cyclosporin A, diabetes was induced by e.v. alloxan administration, and islet cells were isolated from normal donor Lewis rats and injected into the portal vein. ILT corrected the body weight gain, polyuria, polydipsia, polyphagia, and the high levels of blood and urine glucose in 73.7% of rats treated by enzymatic method and in 64.7% of those ones treated by nonenzymatic method. However, there was no significantly difference between the two methods (P > 0.50). We did not also observe significantly difference between the two methods when ILT was performed either in inbred or outbred rats. We concluded that ILT performed by nonenzymatic method may be an alternative treatment for diabetes due to be less expensive and to have possible advantages in the isolation process.

Induction of short gut syndrome and transplantation in a porcine model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Is bone transplantation the gold standard for repair of alveolar bone defects?

New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate), compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7) defects were repaired with autogenous bone grafts; Group 2 (n = 5) defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5) defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5) defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6) defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2-5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01) and 38.35% ± 19.59% (p = 0.06) of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30) and 61.80% ± 2.14% (p = 0.88) of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

Analysis of the feasibility of early hospital discharge after autologous hematopoietic stem cell transplantation and the implications to nursing care

Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in this process. Guidance may contribute to long-term goals through patients' short-term needs. To analyze the results of early hospital discharge on the treatment of patients submitted to autologous transplantation and the influence of nursing care on this conduct. A retrospective, quantitative, descriptive and transversal study was conducted. The hospital records of 112 consecutive patients submitted to autologous transplantation in the period from January to December 2009 were revisited. Of these, 12 patients, who remained in hospital for more than ten days after transplantation, were excluded from the study. The medical records of 100 patients with a median age of 48.5 years (19-69 years) were analyzed. All patients were mobilized and hematopoietic stem cells were collected by leukapheresis. The most common conditioning regimes were BU12Mel100 and BEAM 400. Toxicity during conditioning was easily managed in the outpatient clinic. Gastrointestinal toxicity, mostly Grades I and II, was seen in 69% of the patients, 62% of patients had diarrhea, 61% of the patients had nausea and vomiting and 58% had Grade I and II mucositis. Ten patients required hospitalization due to the conditioning regimen. Febrile neutropenia was seen in 58% of patients. Two patients died before Day +60 due to infections, one with aplasia. The median times to granulocyte and platelet engraftment were 12 days and 15 days, respectively, with median red blood cell and platelet transfusions until discharge of three and four units, respectively. Twenty-three patients required rehospitalization before being discharged from the outpatient clinic. The median time to granulocyte engraftment was 12 days and during the aplasia phase few patients were hospitalized or suffered infections. The toxicity of the conditioning was the leading cause of rehospitalization. The nursing staff participated by providing guidance to patients and during the mobilization, transplant and outpatient follow-up phases, thus helping to successfully manage toxicity.

One-hundred days of monitoring of patients undergoing hematopoietic stem cell transplantation: events of metabolic syndrome

Objective This study assessed early manifestations of metabolic syndrome determinants in patients submitted to hematopoietic stem cell transplantation. Methods Twenty-seven individuals participated in the study (20 with autologous and 7 with allogeneic hematopoietic stem cell transplantation). Anthropometric variables and biochemical indicators of lipid and glucose metabolism were determined before and 100 days after hematopoietic stem cell transplantation.Results The mean total cholesterol (p=0.086), very low density lipoprotein-cholesterol (p=0.069) and triglycerides (p=0.086) of all patients did not change significantly between the two study periods, but when the patients were separated by type of hematopoietic stem cell transplantation, triglycerides and very low density lipoprotein-cholesterol were close to the critical level of significance for individuals with allogeneic hematopoietic stem cell transplantation (p=0.060) and total cholesterol was significant in individuals with autologous hematopoietic stem cell transplantation (p=0.027). Anthropometric variables did not change significantly between before and 100 days after hematopoietic stem cell transplantation. Conclusion Metabolic syndrome risk factors may be associated with lipid metabolism in the early phase of allogeneic and autologous hematopoietic stem cell transplantation.

Patients on the Waiting List for Liver Transplantation: Caregiver Burden and Stress

Over the last few decades, informal caregivers of patients with chronic diseases have received more attention, and there is a growing volume of studies demonstrating high rates of burden, stress, and mental disorders in this group of individuals. The objective of this study was to evaluate the burden, stress, and psychosocial characteristics of informal caregivers of liver transplantation candidates. Participants were assessed by individual evaluations with the following instruments: a semi-structured interview, the Caregiver Burden Scale, the Inventario de Sintomas de Stress para Adultos de Lipp, and the Beck Depression Inventory. The Mann-Whitney test was used for statistical analysis with a significance level of 0.05. The characteristics of the study group (n = 61) were similar to those of groups in other studies with respect to gender (82% were women), kinship (64% were spouses), and age (the mean age was 47.6 years). The main stressors identified by the participants were as follows: doubts about ways to react in a crisis or in emergency situations (42.6%), mood swings of the patient (29.5%), and care involving food and medications (27.9%). Approximately 25% of the caregivers reported that they felt unprepared to adequately perform their roles. Data analysis indicated a greater burden overall on caregivers when the patient`s Model for End-Stage Liver Disease score was greater than or equal to 15 points (P = 0.041). Furthermore, caregivers of patients with alcoholic liver disease showed higher depression (P = 0.034) and overall burden scores (P = 0.031) versus caregivers of patients with liver disease due to other etiologies. In conclusion, the participants showed significantly high levels of burden, stress, and depression. Support measures and caregiver preparation should be implemented by health care providers. Liver Transpl 16: 1164-1168, 2010. (C) 2010 AASLD.