Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study

This study was performed to determine the safety and tolerability of injecting autologous bone marrow stem cells (BMC) (CD34+) into four patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony stimulating factor (G-CSF) mobilized blood and autologous bone marrow contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated the CD34+ stem cell population from the bone marrow. The potential of the BMC to differentiate into hepatocytes and other cell lineages has already been reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into hepatocytes. Recently Sakaida demonstrated reduction in fibrosis in chemically induced liver cirrhosis following BMC transplantation. From a therapeutic point of view, chronic liver cirrhosis is one of the targets for BMC transplantation. In this condition, there is excessive deposition of extracellular matrix and hepatocyte necrosis. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte-like elements, four patients with liver insufficiency were given G-CSF to mobilize stem cells. CD34+ cells (0.1 x 10(8)) were injected into the hepatic artery. No complications or specific side effects related to the procedure were observed; four patients showed improvements in serum albumin, bilirubin and ALT after one month from the cell infusion.     

Identification of rare hepatitis C virus genotype 5a among Indian population

In Indian population, hepatitis C virus (HCV) genotypes 1 and 3 are prevalent and predominant with the highest frequency. However, other genotypes are seldom reported, and among them the HCV genotype 5a is exceptionally rare. The presented case had no history for either blood transfusion or using any type of IV drugs and never traveled to any other country. He was serologically positive with HCV antibodies and HCV RNA. 5′UTR-specific amplification and sequencing of infected viral genome confirmed that he had been infected with HCV genotype 5a which is not closely related to other common prevalent genotypes like 1a, 1b, 3a, and 3b in India. Patient’s wife and children tested negative for anti-HCV and HCV-RNA. This unique case report could be attributed to circulation of HCV genotype 5a from other geographic area at very low frequency in India as determined by phylogenetic analysis and nucleic acid-sequencing methods.     

A Snapshot of Lipid-Reporting Practices in Canadian Clinical Laboratories: An Urgent Need for Harmonisation

To effectively implement the Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia management into clinical laboratories, clear recommendations for lipid reporting are essential. In this study, the Canadian Society of Clinical Chemists Working Group on Reference Interval Harmonisation surveyed Canadian laboratories on adult lipid reporting practices to set a foundation for the development and implementation of harmonised lipid reporting across Canada. Key aspects of the survey asked laboratories: what reporting parameters were in place to assess lipid results; what interpretative comments were provided; whether nonfasting lipids were permitted and, if so, what strategy was used to document fasting status; and whether there was interest in implementing a harmonised lipid report. A total of 101 laboratories were represented by 24 respondents, as many responses were submitted by laboratory networks that included more than 1 laboratory. There was at least 1 response from 9 Canadian provinces and representation across 5 testing platforms. Upper and lower limits for lipid parameters and referenced source of limits varied substantially across laboratories, with only 56% of laboratories (9 respondents) referencing the 2016 CCS guidelines. Eighty-six percent of laboratories (19 respondents) report nonfasting lipids, although the method of documenting nonfasting status varied. Overall, 36% of laboratories (8 respondents) reported interest in implementing a harmonised lipid report. Assessment of current lipid-reporting practices supports the need for harmonised lipid reporting across Canada. Development of a harmonised lipid report for the adult population, consistent with up-to-date Canadian guidelines, will improve continuity of lipid test interpretation across Canada and improve clinical decision making.     

Occurrence of virulence genes, 16S rRNA methylases,and plasmid-mediated quinolone resistance genes in CTX-M-producing Escherichia coli from Pakistan

The aim of the study was to conduct a comprehensive molecular characterization of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli collected from Pakistan. Genetic relatedness among 98 ESBL-producing E. coli was measured by pulsed-field gel electrophoresis (PFGE). The presence of genes encoding ESBLs, virulence factors (VFs), 16S rRNA methylases, plasmid-mediated quinolone resistance (PMQR) encoding elements, plasmid replicon types, phylogenetic groups of E. coli, prevalence of the worldwide disseminated clone E. coli ST131, and phylogrouping of CTX-M enzymes was investigated by polymerase chain reaction (PCR). All isolates carried bla _CTX-M genes and, except for one isolate from CTX-M phylogroup 9, they all belonged to CTX-M phylogroup 1. The isolates were genetically diverse with PFGE. Phylogenetic group D (36 %) was most abundant in this collection of E. coli, whereas isolates belonging to B2 (22 %) had the highest content of virulence genes. PMQR genes were found in 84.6 % of the isolates; among them, 93 % isolates were positive for variants of acetyltransferases (aac(6′)-lb-cr), whereas qnrB, qepA, and qnrS were present in 11 %, 5 %, and 4 % of the isolates, respectively. Only 3 % of the isolates contained genes encoding 16S rRNA methylases. The most abundant replicon type was IncF (96 %), and 18 % of the isolates belonged to the ST131 clone. Out of 34 investigated VFs, 24 genes encoding different types of adhesins, protectins, toxins, siderophores, and other VFs were found. Although the isolates in this collection were highly resistant to many antimicrobials, susceptibility to amikacin and meropenem was retained.     

Effect of 200 μG/day of vitamin k1 on the variability of anticoagulation control in patients on warfarin: A randomized controlled trial

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.     

Enhanced care for primary hip arthroplasty: factors affecting length of hospital stay

Background

Enhanced care in joint replacement requires identification and correction of the causes of delay in discharge while ensuring practice remains safe. We conducted prospective studies of factors delaying discharge following hip replacement in 2006 and 2010.

Methods

Daily data were twice collected prospectively in 100 consecutive unselected primary cemented THR, by an independent observer. Reasons for delays in discharge and variation from the patient pathway were identified and addressed.

Results

The mean length of stay (LOS) in 2006 was 4.3 days and in 2010, 3.56 days (target for discharge 4 days). In 2006, 31 patients had a stay of more than 4 days, 17 due to inadequate physiotherapy provision, 10 for medical and 4 for other reasons. In 2010, 15 patients had a stay of more than 4 days, 1 patient had inadequate physiotherapy provision, in 7 cases discharge was delayed because of need for blood transfusion and 7 because of need for catheterisation. Women aged more than 70 with preoperative haemoglobin of <12 g/dL were at particularly high risk of requiring transfusion. Catheterisation was also identified as a factor causing significant increase in LOS. Patients going home in less than 4 days were more likely to have had their operation in the morning.

Conclusion

Patient LOS is multifactorial and can be reduced by regular review of the care pathway to effect incremental changes that have a significant impact on reducing stay.     

Modification of Serum Galectin-3 and Reversal of Cardiac Remodeling Following Pediatric Transcatheter Atrial Septal Defect Closure

Objectives: We aimed to evaluate the effect of percutaneous atrial septal defect (ASD) closure in children using right heart indices and serum galectin-3 (Gal-3), as potential biomarkers of right heart remodeling. Methods: This case–control prospective study included 40 children with ASD and 25 control subjects. An echocardiographic evaluation was performed before the procedure, as well as 24 h, 1 month, and 6 months after intervention. Serum Gal-3 was measured before, and 1 month after the procedure. Results: Serum Gal-3 concentration, right atrial (RA) dimensions, right ventricular (RV) dimensions, indexed RA area, and right index of myocardial performance (RIMP) were significantly increased in children with ASD compared with control subjects while tricuspid annular plane systolic excursion (TAPSE) was significantly decreased. Six months after closure, RA, and RV dimensions significantly decreased and RV function improved (RIMP decreased and TAPSE increased). Gal-3 oncentration significantly decreased 1 month after ASD closure, but it did not reach normal range compared with control subjects. A positive correlation between Gal-3 and age at closure, RA area, RV dimensions, and RIMP was observed. A positive correlation was observed between the decrease in Gal-3 concentration and the decrease in RA area and RV dimensions 1 month after ASD closure. A significant negative correlation was observed between TAPSE and Gal-3 concentration before and after intervention. Conclusions: Percutaneous ASD closure can improve right-sided indices and decrease serum Gal-3 concentration. Gal-3 can be used as a sensitive biomarker of right heart remodeling, with a decrease in Gal-3 concentration suggesting reversal of maladaptive remodeling.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.