Bilirubin Removal by Plasmafiltration-Adsorption: Ex vivo Adsorption Kinetics Model and Single Case Report.

BACKGROUND: Extracorporeal removal of bilirubin in patients with severe liver dysfunction is a key blood purification strategy. We conducted an ex vivo study to assess the quantitative capacity to remove bilirubin from plasma of a novel adsorptive cartridge. METHODS: We studied a downscaled module of the BS330 Plasma Bilirubin Adsorption Column Cartridge (Jafron Biomedical, Zhuhai City, China) to minimize the plasma requirement in an ex vivo circulation using a solution of hyperbilirubinemic plasma. We measured the bilirubin concentration gap (ΔC) between inlet (Cpin) and outlet (Cpout) of the unit and we calculated the removal ratio (RR) as mass adsorbed at different time points. Moreover, we compared the ex vivo model with the bilirubin adsorption kinetics in a patient with acute on chronic liver failure treated with the BS330 cartridge. RESULTS: Bilirubin concentration change across the cartridge at 30 min was 16.5%, and cartridge saturation was reached at 750 min. We used a minimodule downscaled to 1:3 and containing approximately 131 g of BS330 sorbent beads: the device retained 759 mg of bilirubin with a RR of 78.1% and a RR of 42.6% at 120 min. Thus, the adsorption capacity was 5.76 mg of bilirubin per gram of sorbent. Bilirubin adsorption kinetics in our clinical case with a full-scale unit shows a coherent trend with a total bilirubin mass adsorbed after 180 min of 470 mg. DISCUSSION: Our findings provide the first assessment of bilirubin adsorption in an ex vivo model of plasma perfusion and can be used to design interventional studies in humans, providing guidance for an adequate prescription of treatment frequency and duration.

Introduction of day case hip and knee replacement programme at an inpatient ward is safe and may expedite shortening of hospital stays of traditional arthroplasties.

PURPOSE: We investigated the safety of primary hip and knee replacements with same day discharge (SDD) and their effect on length of stay (LOS) of traditional inpatient arthroplasties at our elective orthopaedic ward. METHODS: 200 patients underwent elective, unilateral primary day case total hip (THA, n = 94), total knee (TKA, n = 60) and unicondylar knee replacements (UKA, n = 46). SDD rates, reasons for failure to discharge, readmission, complication and satisfaction rates were recorded at 6-week follow up. Changes in LOS of inpatient arthroplasties (n = 6518) and rate of patients discharged with only one night stay treated at the same ward were tracked from 1 year prior to introduction of day case arthroplasty (DCA) program to the end of observation period. RESULTS: 166 patients (83%) had SDD while 34 (17%) needed overnight stay. Main reasons for failure to discharge were lack of confidence (4%) fainting due to single vasovagal episode (3.5%), urine retention (3%) and late resolution of spinal anaesthesia (3%). 5 patients (3%) had readmission within 6 weeks, including 1 (0.6%) with a partial and treated pulmonary embolism. 163 patients were satisfied with SDD (98%). After launching the DCA program, average LOS of inpatients was reduced from 2.3 days to 1.8 days and rate of discharge with only 1-night stay increased from 12% to around 60%. CONCLUSION: Introduction of routine SDD hip and knee arthroplasty programme at an elective orthopaedic centre is safe and also may confer wider benefits leading to shorter inpatient hospital stays.

Subclinical hypothyroidism and diabetes as risk factors for postoperative stiff shoulder.

PURPOSE: Postoperative stiffness can be a disabling condition after arthroscopic shoulder surgery. The purpose of this study was to analyse the potential contribution of subclinical forms of hypothyroidism and diabetes in the development of postoperative shoulder stiffness. METHODS: A prospective study was conducted on 65 consecutive patients scheduled for arthroscopic subacromial decompression or rotator cuff tear repair. Patients with preoperative stiffness were excluded. Preoperative measurements of free thyroxine, free triiodothyronine, thyroid-stimulating hormone and fasting glycaemia were taken in all patients to detect subclinical forms of diabetes and hypothyroidism. A follow-up was planned at 30, 60, 90 and 180 days after surgery. According to range of motion measurements, postoperative stiffness was classified as severe or moderate at follow-up. Univariate and logistic regression analyses were performed for the assessment of risk factors for stiffness. RESULTS: The overall incidence of postoperative stiffness was 29 % (19/65) in our cohort. Considering only the arthroscopic rotator cuff repairs, this incidence was 23 % (7/31). A new diagnosis of subclinical forms of diabetes or hypothyroidism was made in five cases. All five of these cases developed postoperative stiffness. The logistic regression analysis demonstrated that hypothyroidism was a risk factor for severe stiffness (RR = 25; p = 0.001) and that diabetes was a risk factor for moderate stiffness (RR = 5.7; p = 0.03). CONCLUSION: The postoperative stiffness in the majority of patients can be predicted by a careful analysis of past medical history and by detecting subclinical forms of hypothyroidism and diabetes. LEVEL OF EVIDENCE: Prognostic study, Level II.

Relevance of pre-analytical blood management on the emerging cardiovascular protein biomarkers TWEAK and HMGB1 and on miRNA serum and plasma profiling.

BACKGROUND: Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers. METHODS: An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0.5, 3, 6 and 9h) and centrifugation (one or two-step). Aliquots of all processed samples were immediately frozen (-80°C) before analysis. Proteins were assayed by ELISAs, miRNA expression profile by microarray and peptidome profiling by MALDI-TOF/MS. RESULTS: Temperature, time and centrifugation had no impact on TWEAK and HMGB1 results, which were significantly influenced by matrix type, TWEAK levels being significantly higher (F=194.7, p<0.0001), and HMGB1 levels significantly lower (F=36.32, p<0.0001) in serum than in any other plasma type. Unsuitable miRNA results were obtained using Heparin-plasma. Serum miRNA expression profiles depended mainly on temperature, while EDTA-plasma miRNA expression profiles were strongly affected by the centrifugation method used. MALDI-TOF/MS allowed the identification of seven features as indices of pre-analytical serum (m/z at 1206, 1350, 1865 and 2021) or EDTA-plasma (m/z 1897, 2740 and 2917) degradation. CONCLUSIONS: Serum and EDTA-plasma allow the analysis of both proteins and miRNA emerging biomarkers of heart diseases. Refrigerated storage prevents an altered miRNA expression profile also in cases of a prolonged time-interval between blood drawing and processing.

Reproducibility in urine peptidome profiling using MALDI-TOF.

MALDI-TOF profiling of low molecular weight peptides (peptidome) usage is limited due to the lack of reproducibility from the confounding inferences of sample preparation, data acquisition, and processing. We applied MALDI-TOF analysis to profile urine peptidome with the aims to: (i) compare centrifugal ultrafiltration and dialysis pretreatments, (ii) determine whether using signal LOD (sLOD), together with data normalization, may reduce MALDI-TOF variability. We also investigated the influence of peaks detection on reproducibility. Dialysis allowed to obtain better MALDI-TOF spectra than ultrafiltration. Within the 1000-4000 m/z range, we identified 120 and 129 peaks in intra- and interassay studies, respectively. To estimate the sLOD, serial dilution of pooled urines up to 1/256 were analyzed in triplicate. Six data normalization strategies were investigated-the mean, median, internal standard, relative intensity, TIC, and linear rescaling normalization. Normalization methods alone performed poorly in reducing features variability while when combined to sLOD adjustment showed an overall reduction in features CVs. Applying a feedback signal processing approach, after median normalization and sLOD adjustment, CVs were reduced from 103 to 26% and 113 to 25% for the intra- and interassay, respectively, and spectra became more comparable in terms of data dispersion.