Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

Effects of infectious complications on patients' survival in peritoneal dialysis.

AIM: To investigate the impacts of infectious complications on mortality and morbidity; and to identify the other potential factors effective in mortality in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: We included patients who initiated therapy between 2001-2011. Patients were divided into two groups regarding to presence or absence of infectious complications. Socio-demographic data and clinical courses were compared and the reasons for PD withdrawal were obtained. Survival analysis of all patients was performed and the effects of infectious complications on mortality were investigated. RESULTS: 301 patients were included in this retrospective study. 214 patients (mean follow-up time 28.7±16.5 months) had infection history, 87 patients (mean follow-up time 48.9±29.6 months) had no infection history. There were no statistically significant difference in comparison of the groups in terms age, gender, education levels, hemodialysis history. In patients with infection history, 465 peritonitis and 213 catheter exit site infection attacks were diagnosed. The most frequently agent was methicillin-sensitive Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus in both conditions, while 25% of catheter exit site infection and 25% of peritonitis attacks were culture negative. During follow-up period, 60 patients transferred to hemodialysis, 58 patients died, 18 patients had renal transplantation in patients with infection history. In other group, 27 patients died, 23 patients had renal transplantation and 11 patients transferred to hemodialysis. Mean survival times were 56.3±2.8 months in patients with infection history and 86.8±6.1 months in other group. Mortality rate was found higher in patients with infection history (long-rank: 0.030). PD preference (OR: 5.213, p < 0.001), pretreatment low serum albumin (OR: 0.378, p = 0.001), low hemoglobin levels (OR: 0.810, p = 0.029) were found as predictors of survival in patients with infection history. CONCLUSIONS: Infectious complications have negative effects on patient survival. Nature of PD preference, initial hypoalbuminemia and anemia were found to increase the mortality rate. The major causes of deaths were peritonitis and/or sepsis in patients with infectious complications, while the major cause of death was cardiac reasons in patients without infectious complications.

Investigation of the protective effect of anzer propolis in cerebral ischemia-reperfusion injury.

OBJECTIVE: Globally, stroke is the leading cause of disability and death. With the use of thrombolytic therapy, reperfusion injury, and its consequences came to the fore. We aimed to find out how anzer propolis, which can only be obtained in Turkey's Eastern Black Sea region, affected ischemia-reperfusion injury using biochemical and histological techniques. MATERIALS AND METHODS: 32 female Wistar albino rats were divided into 4 groups, including a control group. Three of the groups underwent 30 minutes of induced ischemia via clamping of the common carotid artery, followed by ischemia-reperfusion injury through the release of the clamp. One group received no treatment, another received oral administration of 100 mg/kg of anzer propolis one hour before surgery, and the third group received oral administration of 40 mg/kg of acetylsalicylic acid just before surgery. Histopathological examination assessed apoptosis and tissue necrosis, while serum and brain tissue were evaluated for levels of nerve growth factor (NGF), Interlokin 1ß (IL-1ß), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAS), and total oxidant capacity (TOS). RESULTS: Anzer propolis and acetylsalicylic acid significantly reduced hyperemia in vessels, vacuolization in neurons, glial cell infiltration, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity. The anzer propolis group had the highest NGF levels. The anzer propolis and acetylsalicylic acid groups had lower levels of TNF-a and IL-6 in the brain tissue than the ischemia-reperfusion group, while TAS levels were higher. CONCLUSIONS: The findings obtained in this study suggest that anzer propolis has a neuroprotective effect against ischemia-reperfusion injury and will have beneficial effects on neurodegeneration. We believe our findings will contribute to the clinical treatment of ischemia-reperfusion injury.

Correlation between the resistive index values of renal and orbital arteries.

BACKGROUND: Resistive index (RI) is an indirect measurement of blood flow resistance that can be used to evaluate vascular damage. AIMS: The purpose of this study is to evaluate the association between RI values of orbital and intrarenal arteries by means of Doppler ultrasonography (US). METHODS: We evaluated 103 diabetic patients. As a control group, 30 subjects were examined. The patients were divided into two groups. Group 1 consisted of patients with urinary albumin excretion (UAE) <300 mg/day and estimated glomerular filtration rate (eGFR) levels >90 ml/min (n = 50); Group 2 had a UAE >300 mg/day and/or eGFR levels between 89 and 60 ml/min (n = 53). The association between RI values obtained with Doppler US of the ophthalmic artery, central retinal artery, posterior ciliary artery and intrarenal arteries were calculated. RESULTS: Both orbital and intrarenal arterial RI values in Group 1 and Group 2 were higher than the control group (p = 0.001); furthermore, values were higher in Group 2 than in Group 1 (p = 0.0004/0.029/0.036, p = 0.016, respectively). A positive correlation was found between orbital and intrarenal arterial RI values in Group 2 (r = 0.475, 0.285, 0.363, p < 0.01, respectively). CONCLUSION: Both orbital and renal arterial RI values were shown to be higher than the control group. Further, a trend towards higher RI values was observed with renal disease. RI may be useful as one of the markers for early diagnosis and follow-up of diabetic nephropathy and retinopathy.

Effects of rosiglitazone treatment on insulin resistance and TNF-alpha levels in patients with chronic kidney disease: a prospective study.

AIM: The aim of the study was to investigate the effects of rosiglitazone treatment on insulin resistance (IR) and tumor necrosis factor-alpha (TNF-alpha) levels in non-diabetic chronic kidney disease (CKD) patients with IR. PATIENTS AND METHODS: Thirty non-diabetic CKD patients with IR were enrolled in the study. Patients were grouped into two: group 1 (n = 15) received rosiglitazone 4 mg tablet for 3 months and patients who did not receive rosiglitazone treatment constituted the group 2 (n = 15). Baseline and after rosiglitazone treatment, homeostatis model assessment-insulin resistance (HOMA-IR) and TNF-alpha levels were measured. RESULTS: There were no statistical differences in gender, age, HOMA-IR and TNF-alpha levels among group 1 and group 2 (p > 0.05 for all). Compared to baseline in group 1, significant differences were found in HOMA-IR and TNF-alpha levels after 3 months (p = 0.023; p = 0.001, respectively). CONCLUSIONS: Our study indicates that, rosiglitazone treatment improves the IR and decreases TNF-alpha levels in non-diabetic patients CKD with IR.

Risk factors for progression of renal disease in patient with diabetic nephropathy.

AIM: The aim of this study was to investigate the annual rate of glomerular filtration rate (GFR) decline and associated risk factors with this decline in diabetic nephropathy patients. PATIENTS AND METHODS: A total of 122 type 2 diabetes mellitus (DM) patients (66F, mean follow up time 39 +/- 19 months, mean age 56 +/- 10 years, mean duration of diabetes diagnosis 12.1 +/- 9.5 years) between 2003 and 2010 were evaluated retrospectively. Socio-demographic characteristics and blood pressure data, laboratory parameters, HbAlc, daily urine protein excretion both of the first and last visits of all patients were recorded. Patients were separated into three groups according to rate of GFR decline. Group 1 (n:35), group 2 (n:42) and group 3 (n:45) consisted of patients < 1 ml/dk/1.73 m2, 1-5 ml/dk/1.73 m2 and > 5 ml/dk/1.73 m2 annual rate of GFR decline respectively. Demographics, laboratory data and their treatments were compared in all three groups and were investigated factors that may influence the rate of GFR decline. RESULTS: The annual rate of GFR decline was 1.4 +/- 2.3 ml/sec, -2.9 +/- 1.0 ml/sec and -11.9 +/- 9.1 ml/sec in group 1, 2 and 3 respectively. Daily urine protein excretion was 0.9 +/- 1.3, 1.2 +/- 1.5 and 5.2 +/- 5.5 g in groups respectively, was found significantly higher in group 3 (p < 0.001). Serum albumin level was significantly lower in group 3 (p < 0.001). We found positive correlation between annual rate of GFR decline and last visit systolic blood pressure (SBP), daily proteinuria and parathormone levels (r: 0.339, 0.447 and 0.289 p < 0.001, < 0.001 and 0.02 respectively) and negative correlation between GFR decline and deltaSBP (delta systolic blood pressure), pretreatment albumin, calcium and hemoglobin levels (r: -0.409, -0.526, -0.233 and -0.467, p < 0.001, < 0.001, < 0.001 and 0.016 respectively). CONCLUSIONS: Proteinuria, hypoalbuminemia, anemia, and a change in SBP were found most effective in annual rate of GFR decline in patients with diabetic nephropathy. The early detection of these factors may slow the progression of nephropathy.

Fungal peritonitis in peritoneal dialysis: a 10 year retrospective analysis in a single center.

INTRODUCTION: Fungal peritonitis (FP) is a rare but serious complication in patients undergoing peritoneal dialysis (PD), and is associated with higher morbidity, mortality. We aimed to analyze the predisposing factors, etiological agents, outcome and treatment of FP in patients with PD. METHODOLOGY: We evaluated retrospectively all PD patients PD center between 2001 and 2011. Sixteen patients with FP were included into the study. RESULTS: The clinical records of 16 patients with FP among 355 patients were reviewed for the clinical and laboratory data. Among 506 episodes of PD-related peritonitis in 10 years, we identified 16 episodes of FP. Median PD duration was 36.7±22.2 months. In 87.5% of patients had one or more previous episode of bacterial peritonitis that were treated with multiple broad-spectrum antibiotics. FP was primary infection in five patients, whereas eleven patients experienced FP during the course of treatment of bacterial peritonitis. Six patients died due to the fungal infection whereas others were transferred to haemodialysis. CONCLUSIONS: Treatment of bacterial peritonitis with broad spectrum antibiotics was an important risk factor predisposing to the development of FP. The catheter removal and initiation of antifungal therapy as soon as possible are obligatory in episode of FP because it is responsible from high mortality rate.

Effect of Olmesartan on serum cystatin C levels in the patients with essential hypertension.

AIM: We aimed to investigate whether Olmesartan had an effect on cystatin C levels in hypertensive patients, and evaluate its correlation with blood pressure (BP). MATERIALS AND METHODS: Seventy-two patients essential hypertension patients with a known for, at most, the last 3 years were enrolled to the study. Patients were divided in three groups (group 1; receives 20 mg/day olmesartan; group 2, receives 40 mg/day olmesartan; group 3, receives Olmesartan plus hydrochlorothiazide), according to their BP measurements. Blood samples (serum urea, creatinine, sodium, potassium and cystatin C) were collected initially and at the end of the study from all patients and the correlation of these parameters with BP and drug use was investigated. RESULTS: There were no significantly difference between the groups in terms of age, gender, serum urea, creatinine, cystatin C and diastolic BP levels (p > 0.05); while, systolic BP was significantly higher in group 3 at baseline (p = 0.001). After 3 months of olmesartan treatment, the mean serum cystatin C (p: 0.001, 0.023 and 0.018 respectively), systolic (p: 0.001, 0.001 and 0.001 respectively) and diastolic BP levels (p: 0.001, 0.001 and 0.001 respectively) decreased in all groups. However, there was no significant difference in serum creatinine levels (p > 0.05). There were not found correlation between the changes of systolic and diastolic BP and cystatin C levels. CONCLUSIONS: Cystatin C is a more sensitive marker to detect of early kidney dysfunction compared to serum creatinine level. Olmesartan treatment led to a decrease of cystatin C level. Therefore, olmesartan can be used to prevent the renal damage in patients with hypertensive and it is independent of drop in blood pressure.

EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL).

Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.

Nano-scale superhydrophobicity: suppression of protein adsorption and promotion of flow-induced detachment.

Wall adsorption is a common problem in microfluidic devices, particularly when proteins are used. Here we show how superhydrophobic surfaces can be used to reduce protein adsorption and to promote desorption. Hydrophobic surfaces, both smooth and having high surface roughness of varying length scales (to generate superhydrophobicity), were incubated in protein solution. The samples were then exposed to flow shear in a device designed to simulate a microfluidic environment. Results show that a similar amount of protein adsorbed onto smooth and nanometer-scale rough surfaces, although a greater amount was found to adsorb onto superhydrophobic surfaces with micrometer scale roughness. Exposure to flow shear removed a considerably larger proportion of adsorbed protein from the superhydrophobic surfaces than from the smooth ones, with almost all of the protein being removed from some nanoscale surfaces. This type of surface may therefore be useful in environments, such as microfluidics, where protein sticking is a problem and fluid flow is present. Possible mechanisms that explain the behaviour are discussed, including decreased contact between protein and surface and greater shear stress due to interfacial slip between the superhydrophobic surface and the liquid.

Bacillus circulans paracardiac infection in non-hodgkin lymphoma--a case report.

A case report is presented concerning Bacillus circulans paracardiac infection in a 27 year old woman with non-hodgkin lymphoma.

Posttransplant Urinary Tract Infection Rates and Graft Outcome in Kidney Transplantation for End-Stage Renal Disease Due to Reflux Nephropathy Versus Chronic Glomerulonephritis.

BACKGROUND: The goal of this study was to evaluate posttransplant urinary tract infection (UTI) rates and graft outcome in kidney transplantation for end-stage renal disease (ESRD) due to vesicoureteral reflux (VUR)-related reflux nephropathy (RN) versus chronic glomerulonephritis (CGN). METHODS: A total of 62 patients with ESRD who underwent kidney transplantation for VUR-related RN (VUR-RN group, n = 31; mean ± standard deviation age, 34.1 ± 6.0 years; 58.1% female) or CGN (CGN group, n = 31; mean age, 34.2 ± 6.8 years; 71.0% male) at our unit between January 1996 and January 2011 were included in this retrospective study. Baseline recipient and donor characteristics, renal replacement therapy, posttransplant data on serum creatinine levels, graft outcome, and UTIs were recorded. Posttransplant UTIs and graft outcome were compared between the VUR-RN and CGN groups, as well as between patients with and without pretransplant nephrectomy in the VUR-RN group. RESULTS: The frequency of overall (72 vs 18 of 90; P = .05) UTI episodes was significantly higher in the VUR-RN group than in the CGN group; Escherichia coli (64.2%) was the most common pathogen. The VUR-RN and CGN groups were similar in terms of 1-year (100.0% for each), 5-year (95.8% vs 96.8%), and 10-year (82.0% vs 96.8%) graft survival. VUR-RN patients with and without nephrectomy were similar in terms of 1-year (100.0% for each), 5-year (91.7% vs 85.7%), and 10-year (81.5% vs 85.7%) graft survival. CONCLUSIONS: Our findings indicate kidney transplantation is a safe and effective option in ESRD patients with RN secondary to VUR. It resulted in high 1-year, 5-year, and 10-year graft survival rates.

Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: potential autocrine or paracrine effectors in the Sézary syndrome.

PURPOSE: To examine interleukin-7 (IL7)- and interleukin-2 (IL2)-induced proliferation of Sézary lymphoma cells and to consider if an autocrine or paracrine growth-stimulatory circuit involving IL7 exists in the Sézary syndrome (SS). MATERIALS AND METHODS: Fresh Sézary lymphoma cells were maintained in short-term culture in the presence of cytokines, and growth was measured by incorporation of (3H)-thymidine (TdR). Expression of IL7 and IL7 and IL2 receptors (IL7-R and IL2-R, respectively) was assessed by polymerase chain amplification of first-strand complementary DNA (RT-PCR), by affinity cross-linking of radioactive iodine-125-IL7, and by dual-color fluorescence-activated cell analysis. IL-7 production was measured by immunoassay. RESULTS: Sézary lymphoma cells from seven patients showed synergistic (five of seven) or additive (two of seven) proliferation when cultured in the presence of IL2 and IL7, as compared with culture with either cytokine alone. Two patients with evidence of synergistic stimulation of [3H]-TdR incorporation showed IL7-R gene expression by RT-PCR and IL7 affinity cross-linking. Incubation of all seven patients' cells with IL7 induced coexpression to varying degrees of IL7-R and IL2-R. Sézary lymphoma cells from at least three of five patients studied expressed IL7 mRNA, and skin from three of five patients studied, as well as normal skin, expressed IL7 mRNA by RT-PCR. CONCLUSION: Sézary lymphoma cells respond by proliferation to IL7 plus IL2, and in some instances produce IL7. Therapeutic maneuvers should be pursued to take advantage of this potential autocrine or paracrine growth-stimulatory mechanism.

2',3'-Dideoxyadenosine killing of TdT-positive cells is due to a trace contaminant.

We have previously reported that the chain-terminating nucleoside analogue 2',3'-dideoxyadenosine (ddA) is specifically cytotoxic for TdT-positive cells in the co-presence of the adenosine deaminase (ADA) inhibitor coformycin (CF). Further studies with ddA/CF revealed that cytotoxicity occurs only if ddA is supplied from the Calbiochem or Fluka companies. ddA supplied from other commercial sources (Pharmacia, Sigma) or the NCI Pharmaceutical Resources Branch is non-cytotoxic. To explore the basis for this difference, ddA from various sources was subjected to reverse-phase high-pressure liquid chromatography (HPLC) analysis. The Calbiochem and Fluka ddA had a unique HPLC peak, with a retention time of 12.8 min, representing a contaminant of less than 0.1% of the bulk material applied to the C-18 HPLC column. Study of all HPLC peaks resolved from the bulk material showed cytotoxic activity in only the 12.8 min peak. To identify the nature of the unknown compound, we compared HPLC characteristics of the synthetic intermediates and byproducts of ddA synthesis to the peak eluting at 12.8 min. Of these, only 3'-deoxyadenosine (cordycepin) had similar HPLC characteristics. In addition, in the co-presence of CF, cordycepin was specifically cytotoxic (IC50 < 0.5 microM) for all TdT-positive cell lines tested. Cytotoxicity was seen in TdT-negative cells only at concentrations 10-100-fold higher. We conclude that our previous report on ddA/CF as a TdT-specific cytotoxic combination was due to contamination of the ddA supplied by Calbiochem by cordycepin. ddA itself is non-cytotoxic for TdT-positive cells. Cordycepin in the co-presence of an ADA inhibitor may be effective in the treatment of TdT-positive hematological malignancies.

Arginine butyrate downregulates p210 bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells.

Downregulation of bcr-abl expression in the chronic myelogenous leukemia cell line K562 using antisense oligonucleotides has been shown to enhance the sensitivity of the cells to apoptotic stimuli, suggesting that p210 bcr-abl, like bcl-2 functions as an anti-apoptosis factor (McGahon A et al, Blood 1994, 83: 1179). In these experiments, the inhibition of p210 bcr-abl expression alone was not sufficient to induce apoptosis. We demonstrated that exposure to low doses (0.5 mM) of a butyric acid analog, arginine butyrate, was capable of inducing apoptosis in selected leukemia cell lines, including K562 cells, and in fresh leukemia cells from patients with chronic myelogenous leukemia. To further explore the mechanisms of this effect, we examined expression of p210 bcr-abl after butyrate exposure and found a dose-related inhibition of p210 bcr-abl protein without concordant change in other phosphoproteins, including the JAK-1 kinase. Further analysis revealed that the inhibition of bcr-abl expression occurs due to transcriptional regulation of the bcr-abl gene by arginine butyrate. These results suggest that arginine butyrate and other butyrate analogs alone or in combination may be useful in the therapy of patients with chronic myelogenous leukemia or bcr-abl expressing acute leukemias.

Induction of apoptosis by cordycepin in ADA-inhibited TdT-positive leukemia cells.

The nucleoside analogue cordycepin (3'-deoxyadenosine), when protected against ADA deamination, is specifically cytotoxic for TdT-positive leukemia cells. Cordycepin-treated, ADA-inhibited, TdT-positive cells undergo the classic changes associated with drug-induced apoptosis: reduction in cell volume, chromatin clumping, membrane blebbing, and 180-bp multimer DNA laddering on agarose gels. In common with the apoptosis seen in normal TdT-positive thymocytes, following exposure to various agents, apoptosis induced by cordycepin in TdT-positive leukemia cells was associated with increased protein kinase A (PK-A) activity. Unlike thymocyte apoptosis however, no elevation in cAMP levels was seen preceding the rise in PK-A activity. Ex vivo we show that cordycepin monophosphate can activate PK-A as efficiently as cAMP. On this basis we speculate that cordycepin monophosphate in TdT-positive cells may be able to activate PK-A in place of cAMP, and that PK-A may phosphorylate TdT, augmenting its activity as an endonuclease. In cell-free experiments, the activity of recombinant TdT as an endonuclease digesting supercoiled plasmid DNA into linear fragments was dramatically increased following phosphorylation of TdT by PK-A. A role for TdT as an apoptotic endonuclease in TdT-positive leukemia cells following cordycepin exposure is now the subject of on-going work.

Renal Damage Frequency in Patients with Solitary Kidney and Factors That Affect Progression.

Background. The aim of this study is to assess renal damage incidence in patients with solitary kidney and to detect factors associated with progression. Methods. Medical records of 75 patients with solitary kidney were investigated retrospectively and divided into two groups: unilateral nephrectomy (group 1) and unilateral renal agenesis/dysplasia (group 2). According to the presence of kidney damage, each group was divided into two subgroups: group 1a/b and group 2a/b. Results. Patients in group 1 were older than those in group 2 (p = 0.001). 34 patients who comprise group 1a had smaller kidney size (p = 0.002) and higher uric acid levels (p = 0.028) than those in group 1b at presentation. Uric acid levels at first and last visit were associated with renal damage progression (p = 0.004, 0.019). 18 patients who comprise group 2a were compared with those in group 2b in terms of presence of DM (p = 0.038), HT (p = 0.003), baseline proteinuria (p = 0.014), and uric acid (p = 0.032) levels and group 2a showed higher rates for each. Progression was more common in patients with DM (p = 0.039), HT (p = 0.003), higher initial and final visit proteinuria (p = 0.014, for both), and higher baseline uric acid levels (p = 0.047). Conclusions. The majority of patients with solitary kidney showed renal damage at presentation. Increased uric acid level is a risk factor for renal damage and progression. For early diagnosis of renal damage and reducing the risk of progression, patients should be referred to a nephrologist as early as possible.

A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia.

The use of unmanipulated graft is increasingly adopted in the setting of allogeneic hematopoietic stem cell transplantation from haploidentical family donors (haplo-SCT) in acute leukemia (AL). We analyzed the outcome of 229 adult patients with de novo AL, who received an unmanipulated haploidentical transplant as their first allo-SCT between 2007 and 2011. Median follow-up was 30 months. Disease status at transplant was: first complete remission (CR1) for 77, second CR (CR2) for 56, and advanced for 96 patients. One hundred and seventy-one patients received in vivo T-cell depletion by monoclonal antibodies (75%). The 60-day cumulative incidence (CI) of engraftment was 93±2%. The 100-day CI of acute graft-versus-host disease (GvHD) was 32±3% for grade II-IV, 12±3% for grade III-IV. The 3-year CI of chronic GvHD was 34±3%. The 3-year CI of non-relapse mortality was 31±4% with in vivo T-cell depletion and 17±5% without. At 3 years, for patients transplanted in CR1, CR2 or advanced disease leukemia-free survival was 44±6, 42±7 and 12±3%, overall survival was 55±6, 51±7 and 14±4% and CI of relapse was 32±6, 24±6 and 61±5%, respectively. These data suggest that unmanipulated haplo-SCT is a valid treatment option for adult AL patients in complete remission lacking a matched donor.

Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia.

Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.

Miniaturised nucleic acid analysis.

The application of micro total analysis systems has grown exponentially over the past few years, particularly diversifying in disciplines related to bioassays. The primary focus of this review is to detail recent new approaches to sample preparation, nucleic acid amplification and detection within microfluidic devices or at the microscale level. We also introduce some applications that have as yet to be explored in a miniaturised environment, but should benefit from improvements in analytical efficiency and functionality when transferred to planar-chip formats. The studies described in this review were published in commonly available journals as well as in the proceedings of three major conferences relevant to microfluidics (Micro Total Analysis Systems, Transducers and The Nanotechnology Conference and Trade Show). Although an emphasis has been placed on papers published since 2002, pertinent articles preceding this publication year have also been included.