A Necessary Step Toward Kidney Donor Safety: The Transition From Locking Polymer Clips to Transfixion Techniques in Laparoscopic Donor Nephrectomy

Donor safety is of paramount importance in addressing end-stage renal failure through living kidney transplantation. The United States Food and Drug Administration (FDA) issued a Class II recall on the use of Hem-o-lok (Teleflex, Limerick, Pennsylvania, United States) polymer clips on the renal artery in laparoscopic donor nephrectomy (LDN) in June 2006 following 3 reported cases of donor deaths secondary to slipped ligature. The National University Hospital of Singapore made the transition regarding hilar control in minimally invasive donor nephrectomy, from using polymer and titanium clips to transfixion techniques (pure or hand-assisted laparoscopic) via laparoscopic staples or intracorporeal suturing, respectively. This study assessed safety during the transition in arterial transfixion techniques in minimally invasive donor nephrectomy for both donors and recipients. Forty-five consecutive kidney donors underwent donor nephrectomy over a 2-year period starting from June 2010. A total of 37 donors who underwent LDN (pure laparoscopic or hand-assisted laparoscopic) were included in the analysis. Of the 37 patients, 23 kidney donors had renal arterial control using Hem-o-lok while 14 patients from November 2011 onward underwent transfixion of the renal artery. The 2 groups of donor who underwent renal arterial control by either clips ligature or transfixion technique were comparable. The outcomes for the recipients in each group were similar with no statistical difference between postoperative creatinine level, incidence of delayed graft function, or graft survival at 1 year. We conclude that the transition in renal arterial control technique to transfixion techniques in LDN in line with FDA recommendation is feasible and affords equivalent donor and recipient outcomes.     

Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype

A 20-year-old woman with high-risk acute myelogenous leukaemia was transplanted with granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood CD34+ haematopoietic stem cells and bone-marrow-derived mesenchymal stem cells (MSC) from her human leucocyte antigen haplotype-mismatched father after myeloablative conditioning therapy. The patient engrafted rapidly and had no acute or chronic graft-versus-host disease. Since transplantation, the patient has shown an enduring trilineage haematological complete response without any evidence of leukaemia relapse at 31 months. We suggest that MSC can be used effectively for genetically haploidentical haematopoietic stem cell transplantation for acute leukaemia.     

Determination of Secondary and Tertiary Structural Features of Transfer RNA Molecules in Solution by Nuclear Magnetic Resonance

High-resolution 300-MHz proton nuclear magnetic resonance spectra of the hydrogen-bounded protons in three different purified tRNA molecules are presented. The resonances in the region between -11 and -15 ppm from 2,2-dimethyl-2-silapentane-5-sulfonate (DSS) are assigned to the ring NH protons of specific base pairs by two approaches. First, intrinsic positions of -14.8 ppm and -13.7 ppm are taken for the AU and GC ring NH protons, respectively, and the spectra are calculated by including ring current shifts from the nearest neighbors. The spectra calculated in this way on the basis of the cloverleaf are in good agreement with the observed. Second, fragments of yeast tRNA(Phe) were obtained, which helped in assignments of the spectrum of intact molecules. The close agreement strongly supports the cloverleaf model.Tertiary structural features were determined in a few cases where the ring currents at the terminal base pairs of helical regions depended upon stacking of the helices. In this way, we were able to show that in Escherichia coli tRNA(Glu) the CCA stem forms a continuous helix with the TPsiC stem, which is in accord with the preliminary x-ray structure of yeast tRNA(Phe), suggesting that this stacking is observed in solution and may be a general property of different tRNA molecules. Similar reasoning suggests that in E. coli tRNA(fMet) G-27 is stacked upon the dihydrouridine helix.     

Comparison of the Framingham Risk Score,SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population

Background

Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.

Methods

Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.

Results

Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC = 0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ² goodness-of-fit, p = 0.097). The SCORE-low model was statistically acceptable for men (χ² goodness-of-fit, p = 0.067). Both SCORE-models underestimated risk in women (p < 0.001).

Conclusions

The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.     

Role of induction and consolidation chemotherapy in elderly acute myeloid leukemia patients

The present study sought to elucidate the role of induction and consolidation therapy in elderly patients. We retrospectively collected data of 477 patients who were aged over 60 years at the time of acute myeloid leukemia (AML) diagnosis. The median overall survival (OS) was 339 days in the induction group (n = 266) and 86 days in the best supportive care group (n = 211) (P < 0.001). In the induction group, the complete remission (CR) rate was 58.3 %, and treatment-related death was 15.4 %. Successful induction was related to good performance [Eastern Cooperative Oncology Group (ECOG <2)] [hazard ratio (HR) 3.215; P = 0.002]. Mortality correlated with failure to achieve CR (HR 4.059; P < 0.001) and poor performance status (ECOG >2) (HR 2.731; P = 0.035). In CR patients, poor karyotype and absence of consolidation (HR 2.313; P = 0.003) correlated with mortality. More than one cycle of consolidation was associated with better OS (P < 0.001). Lack of salvage therapy was associated with mortality in patients who did not achieve CR (HR 3.223; P = 0.005). Intensive induction in patients with good performance and >1 cycle of consolidation after CR may be the best strategy for improving OS in elderly AML patients.     

CuFeO2–NiFe2O4 hybrid electrode for lithium-ion batteries with ultra-stable electrochemical performance

Stable electrode materials with guaranteed long-term cyclability are indispensable for advanced lithium-ion batteries. Recently, delafossite CuFeO₂ has received considerable attention, due to its relative structural integrity and cycling stability. Nevertheless, the low conductivity of delafossite and its relatively low theoretical capacity prevent its use as feasible electrodes for next-generation batteries that require higher reversible capacities. In this work, we suggest a simple and straightforward approach to prepare CuFeO₂–NiFe₂O₄ by introducing Ni precursor into Cu and Fe precursor to form NiFe₂O₄, which exhibits higher capacity but suffers from capacity fading, through sol–gel process and subsequent heat treatments. The presence of both NiFe₂O₄ and CuFeO₂ is apparent, and the heterostructure arising from the formation of NiFe₂O₄ within CuFeO₂ renders some synergistic effects between the two active materials. As a result, the CuFeO₂–NiFe₂O₄ hybrid sample exhibits excellent cycling stability and improved rate capability, and can deliver stable electrochemical performance for 800 cycles at a current density of 5.0 A g⁻¹. This work is an early report on introducing a foreign element into the sol–gel process to fabricate heterostructures as electrodes for batteries, which open up various research opportunities in the near future.

Novel NiFe₂O₄–CuFeO₂ heterostructures were synthesized by sol–gel process and subsequent heat treatments, which exhibit excellent long-term high-rate cyclability.     

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases – Relationships and comparisons with vascular markers of atherosclerosis

Background

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain.

Methods

We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits.

Results

After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P < 0.01). BPV significantly correlated with all of the vascular assessments (P < 0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P < 0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P < 0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P < 0.01).

Conclusions

Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases.     

Holographic Characterization of Protein Aggregates in the Presence of Silicone Oil and Surfactants

Characterizing protein aggregates in the presence of silicone oil is a long standing challenge for the pharmaceutical industry. Silicone oil is often used as a lubricant in devices that deliver and store therapeutic protein products and has been linked to protein aggregation, which can compromise a drug’s effectiveness or cause autoimmune responses in patients. Most traditional technologies cannot quantitatively distinguish protein aggregates and silicone oil in their native formulations for sizes less than 5 μm. We use holographic video microscopy to study protein aggregation to demonstrate its capability to quantitatively distinguish protein aggregates and silicone oil in the presence of varying amounts of the surfactants SDS and polysorbate 80 in the size range of 0.5-10 μm without the need for dilution or special sample preparation. We show that SDS denatures proteins and stabilizes silicone oil. We also show that polysorbate 80 may limit protein aggregate formation if it is added to an IgG solution before introducing silicone oil.