Proenkephalin for the early detection of acute kidney injury in hospitalized patients with chronic kidney disease

Background

The early detection of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is an unmet clinical need. Proenkephalin (PENK) might improve the early detection of AKI.

Methods

One hundred and eleven hospitalized CKD patients undergoing radiographic contrast procedures were enrolled. PENK was measured in a blinded fashion at baseline (before contrast media administration) and on day 1 (after contrast media administration). The potential of PENK levels to predict contrast‐induced AKI was the primary endpoint.

Results

Baseline creatinine and baseline PENK were similar in AKI and no‐AKI patients. In AKI patients, day 1 PENK (198 pmol/L vs 121 pmol/L, P < 0.01) was significantly higher compared to no‐AKI patients. The area under the curve (AUC) for the prediction of AKI by day 1 PENK was 0.79, 95% CI: 0.70‐0.87, similar to serum creatinine: 0.78, 95% CI: 0.61‐0.95. Delta PENK was significantly higher in AKI compared to no‐AKI patients (53 pmol/L vs 1 pmol/L, P < 0.01). The AUC for the prediction of AKI by delta PENK was high (0.92, 95%CI 0.82‐1.00) and remained high for creatinine‐blind AKI (0.94, 95% CI: 0.87‐0.97).

Conclusion

Delta PENK levels improve the early detection of contrast‐induced AKI in CKD patients over serial creatinine sampling. Delta PENK accelerates the detection of creatinine‐blind AKI by 24 hours.     

Sonochemical preparation of alumina-spheres loaded with Pd nanoparticles for 2-butyne-1,4-diol semi-hydrogenation in a continuous flow microwave reactor

A novel protocol for microwave-assisted alkyne semi-hydrogenation under heterogeneous catalysis in a continuous flow reactor is reported herein. This challenging task has been accomplished using a multifaceted strategy which includes the ultrasound-assisted preparation of Pd nanoparticles (average Ø 3.0 ± 0.5 nm) that were synthesized on the μ-metric pores of sintered alumina spheres (Ø 0.8 mm) and a continuous flow reaction under H₂ (flow rate 7.5 mL min⁻¹) in a microwave reactor (counter-pressure 4.5 bar). The semi-hydrogenation of 2-butyne-1,4-diol in ethanol was chosen as a model reaction for the purposes of optimization. The high catalyst efficiency of the process, in spite of the low Pd loading (Pd content 111.15 mg kg⁻¹ from ICP-MS), is due to the pivotal role of ultrasound in generating a regular distribution of Pd nanoparticles across the entire support surface. Ultrasound promotes the nucleation, rather than the growth, of crystalline Pd nanoparticles and does so within a particularly narrow Gaussian size distribution. High conversion (>90.5%) and selectivity to (Z)-2-butene-1,4-diol (95.20%) have been achieved at an alkyne solution flow rate of 10 mL min⁻¹. The lead-free, alumina-stabilized Pd catalyst was fully characterized by TEM, HR-TEM, EDX, IR, XRPD and AAS. Highly dispersed Pd nanoparticles have proven themselves to be stable under the reaction conditions employed. The application of the method is subject to the dielectric properties of substrates and solvents, and is therefore hardly applicable to apolar alkynes. Considering the small volume of the reaction chamber, microwave-assisted flow hydrogenation has proven itself to be a safe procedure and one that is suitable for further scaling up to industrial application.

A novel protocol for microwave-assisted alkyne semi-hydrogenation under heterogeneous catalysis in a continuous flow reactor is reported herein.     

Nutritional status: its influence on the outcome of patients undergoing liver transplantation

Background: Malnutrition is frequently present in case of end‐stage liver diseases, and in cirrhotic patients, a poor nutritional status is considered to be one of the predictive factors for increased morbidity and mortality rates after surgery. The impact of the recipients' malnutrition on the outcome of liver transplantation (LT) is still under debate and recent studies have shown controversial results. Patients and methods: We prospectively analysed the nutritional status of 38 consecutive patients undergoing LT in our University Hospital. Subjective global nutritional assessments (SGA) and anthropometry were used for the evaluation of the nutritional status. Energy expenditure, dietary intake and energy balance were also evaluated. After LT, multiple short‐term outcomes that could be influenced by the nutritional status, such as number of episodes of infections (bacterial, viral and fungal) until discharge from hospital, length of stay in intensive care unit (ICU), length of hospital stay and in‐hospital graft and patient's survival, were recorded. Results: Malnutrition was identified in 53% of cases according to the SGA. Pretransplant nutritional status, haemoglobin levels and disease severity were independently associated with the number of infection episodes during the hospital stay. The presence of malnutrition was the only independent risk factor for the length of stay in the ICU and the total number of days spent in hospital. Conclusion: The present data suggest that recipients' malnutrition should be taken into account as a factor that increases complications and costs after LT.     

Genomic lesions associated with a different clinical outcome in diffuse large B‐Cell lymphoma treated with R‐CHOP‐21

Despite recent therapeutic improvements, the clinical course of diffuse large B‐cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi‐centre study to evaluate the impact of genomic aberrations detected using a high‐density genome wide‐single nucleotide polymorphism‐based array on clinical outcome in a population of DLBCL patients treated with R‐CHOP‐21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R‐CHOP‐21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p‐ and 15q‐. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R‐CHOP, have been identified by arrayCGH.     

The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach

A pilot expanded newborn screening programme to detect inherited metabolic disorders by means of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) began in the Campania region, southern Italy, in 2007. By October 2009, >8,800 dried blood samples on filter paper from 11 hospitals had been screened. Within this screening programme, we identified a case of mitochondrial acetoacetyl-coenzyme A (CoA) thiolase deficiency [β-ketothiolase (β-KT) deficiency] by analysing the acylcarnitine profile from a dried blood spot with LC-MS/MS. Gas chromatography coupled with mass spectrometry analysis of urinary organic acids and LC-MS/MS analysis of urinary acylcarnitines were in line with this disorder. In fact, concentrations were well beyond the cut-off values of tiglyl carnitine, 3-hydroxybutyrylcarnitine and 2-methyl-3-hydroxybutyrylcarnitine, 2-methyl-3-hydroxybutyric acid and tiglyl glycine. The absence of 2-methylacetoacetic acid in urine may be attributed to: (i) the instability of this β-ketoacid because it undergoes spontaneous decarboxylation to 2-butanone, which is highly volatile and thus difficult to detect, and (ii) the good health of the patient in the first days of life. β-KT deficiency was subsequently diagnosed in the patient's older sister, who showed increased levels of the same metabolites but also small amounts of 2-methylacetoacetic acid, which is considered a key marker for β-KT diagnosis. Genomic analysis revealed mutation c.1189C >G in exon 12 of the ACAT1 gene, which results in a severe defect because of the p.H397D amino acid change in both alleles of both patients.     

Circulating cytochrome c as potential biomarker of impaired reperfusion in ST-segment elevation acute myocardial infarction

In patients with ST-segment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), abrupt reperfusion can induce myocardial injury and apoptotic cell death. Reperfusion-induced myocardial damage, however, cannot be easily evaluated in clinical practice because of the lack of specific biomarkers. Cytochrome c, a mitochondrial protein, is released on reperfusion into the cytosol, where it triggers the apoptotic process. It can reach the external fluid and circulating blood when cell rupture occurs. We measured the cytochrome c circulating levels in patients with STEMI undergoing pPCI, and correlated them with the clinical signs of myocardial necrosis and reperfusion. The plasma creatine kinase-MB mass and serum cytochrome c (enzyme-linked immunosorbent assay method) were serially measured in 55 patients with STEMI undergoing pPCI. The angiographic and electrocardiographic signs of myocardial reperfusion were also assessed. Cytochrome c transiently increased in all patients with STEMI, with a curve that paralleled that of creatine kinase-MB. A significant relation was found between the peak values of the 2 biomarkers (R = 0.35, p = 0.01) and between the areas under the 2 curves (R = 0.33, p = 0.02). The creatine kinase-MB peak value correlated significantly with the clinical features of infarct extension. In contrast, the cytochrome c peak value correlated inversely with the myocardial blush grade. Patients with clinical signs of myocardial reperfusion injury had a significantly greater cytochrome c peak value than patients without reperfusion injury (median 1.65 ng/ml, interquartile range 1.20 to 2.20, vs 1.1 ng/ml, interquartile range 0.65 to 1.55; p = 0.04). In conclusion, serum cytochrome c is detectable in the early phase of STEMI treated with pPCI and is associated with clinical signs of impaired myocardial reperfusion.     

Platelet gel in the treatment of cutaneous ulcers: the experience of the Immunohaematology and Transfusion Centre of Parma

Background

Platelet gel is being ever more frequently used to promote healing of cutaneous ulcers. However, the factors that determine the often variable clinical outcome of this procedure are still incompletely understood.

Aims

The aims of this study were to demonstrate that platelet gel, even when obtained under strictly controlled conditions, produces highly variable outcomes in patients with cutaneous ulcers and to propose a method for in vitro standardisation of the biological properties of platelet gel.

Material and methods.

Patients were enrolled on the basis of a pre-defined protocol. Platelet concentrate was produced with standard methods, with a variability in platelet count among the different samples of less than 10%. The platelet gel for clinical use was obtained, under strictly standardized conditions, by adding thrombin and calcium gluconate to the concentrates. For in vitro studies, platelet gel, obtained from platelet-rich plasma from four donors, was frozen and thawed twice so as to increase gel contraction. The supernatant was used to modify cell proliferation, protein synthesis, and the expression of selected genes in cultures of human diploid fibroblasts.

Results

Seventeen patients (aged 44–78 years) with ulcers (4 diabetic, 11 vascular, 1 post-traumatic, 1 decubitus) were treated with platelet gel (4 autologous, 13 homologous). Complete re-epithelialisation of four ulcers (1 diabetic, 1 post-traumatic, 2 vascular) was obtained after applications of platelet gel (2 autologous, 2 homologous); in 11 other cases there was a greater than 50% reduction in the size of the ulcer. Two patients had no benefit. The supernatant of the platelet gel was able to promote dose-dependent proliferation and changes in gene expression as well as in metabolic activities related to protein synthesis.

Conclusions

Although the use of platelet gel in the treatment of cutaneous ulcers is increasing, and conditions for its production are better standardised, very considerable variability of clinical outcomes is still observed, even within single centres, suggesting that there are differences in biological properties of platelet concentrates from individual patients which cannot be readily controlled with current techniques. The biological effects of the platelet gel supernatant described in this article may provide the basis for a simple biological validation of platelet preparations before their clinical use, so as to reduce this potentially important source of variability.