Novità nel mondo di Medicina di Laboratorio

Circular RNAs in Urine of Kidney Transplant Patients with Acute T Cell-Mediated Allograft Rejection [Molecular Diagnostics and Genetics]

Clinical Chemistry - Ultimo numero - Lun, 30/09/2019 - 18:00
BACKGROUND:

Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection.

METHODS:

A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection.

RESULTS:

A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation.

CONCLUSIONS:

CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-L-Ribitol Pyrophosphorylase A Muscular Dystrophy [Molecular Diagnostics and Genetics]

Clinical Chemistry - Ultimo numero - Lun, 30/09/2019 - 18:00
BACKGROUND:

Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for cytidine diphosphate (CDP)-l-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required.

METHODS:

An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues.

RESULTS:

CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA myopathy, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker–Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD.

CONCLUSIONS:

Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.

Amplicon Sequencing-Based Noninvasive Fetal Genotyping for RHD-Positive D Antigen-Negative Alleles [Molecular Diagnostics and Genetics]

Clinical Chemistry - Ultimo numero - Lun, 30/09/2019 - 18:00
BACKGROUND:

To avoid hemolytic disease of the fetus and newborn resulting from maternal alloantibodies against fetal Rh antigens, anti-D immunoglobulin is routinely administered to RhD-negative pregnant women in Japan. Fetal RHD genotyping using cell-free DNA may prevent unnecessary antibody administration; however, current PCR-based methods, which detect RHD deletion, do not address the higher rates of RHD-positive D antigen-negative alleles in nonwhite populations without additional inspections.

METHODS:

We developed an amplicon-sequencing method that could estimate the type of paternally inherited fetal RHD allele from 4 major RHD alleles in the Japanese population: the D antigen-positive allele (RHD*01, 92.9%) and 3 D antigen-negative alleles (RHD*01N.01, 6.6%; RHD*01EL.01, 0.3%; RHD*01N.04, 0.1%) using cell-free DNA obtained from the blood plasma of pregnant women.

RESULTS:

The method correctly determined the fetal RhD type even when RhD-negative pregnant women possessed an RHD-positive D antigen-negative allele: RHD*01EL.01 or RHD*01N.04.

CONCLUSIONS:

This method is a reliable noninvasive fetal RHD genotyping method for Japanese and other East Asian populations. The genotyping principle of amplifying 2 different regions using the same primer pair and distinguishing them by their sequence difference during the subsequent mapping procedure is also theoretically applicable to RHD-positive D antigen-negative alleles prevalent in Africans. Therefore, this method offers an opportunity to consider targeted administration of anti-D immunoglobulin to RhD-negative pregnant women in East Asian and African countries and to increase the specificity of the fetal RHD genotyping implemented nationwide in several European countries.

Reference Values for 30 Common Biochemistry Analytes Across 5 Different Analyzers in Neonates and Children 30 Days to 18 Years of Age [Pediatric Clinical Chemistry]

Clinical Chemistry - Ultimo numero - Lun, 30/09/2019 - 18:00
BACKGROUND:

Age-specific reference intervals (RIs) have been developed for biochemistry analytes in children. However, the ability to interpret results from multiple laboratories for 1 individual is limited. This study reports a head-to-head comparison of reference values and age-specific RIs for 30 biochemistry analytes for children across 5 analyzer types.

METHODS:

Blood was collected from healthy newborns and children 30 days to <18 years of age. Serum aliquots from the same individual were analyzed on 5 analyzer types. Differences in the mean reference values of the analytes by the analyzer types were investigated using mixed-effect regression analysis and by comparing maximum variation between analyzers with analyte-specific allowable total error reported in the Westgard QC database. Quantile regression was used to estimate age-specific RIs using power variables in age selected by fractional polynomial regression for the mean, with modification by sex when appropriate.

RESULTS:

The variations of age-specific mean reference values between analyzer types were within allowable total error (Westgard QC) for most analytes, and common age-specific reference limits were reported as functions of age and/or sex. Analyzer-specific reference limits for all analytes on 5 analyzer types are also reported as functions of age and/or sex.

CONCLUSIONS:

This study provides quantitative and qualitative measures of the extent to which results for individual children can or cannot be compared across analyzer types, and the feasibility of RI harmonization. The reported equations enable incorporation of age-specific RIs into laboratory information systems for improving evidence-based clinical decisions in children.

CIED Infections Have Risen Over the Past 2 Decades

Pathology & Lab Medicine - Medscape - Dom, 29/09/2019 - 07:23
Although the overall incidence of CIED infections is low for new implants, the risk for infection is significantly increased for generator replacement and device upgrade procedures.
Medscape Medical News

High-Intensity Surveillance Decreases CRC Risk After Adenoma

Pathology & Lab Medicine - Medscape - Sab, 28/09/2019 - 06:23
A modeling study predicts benefit for high-intensity surveillance in these patients; experts emphasize the need for high-quality studies to establish evidence-based surveillance policies.
Medscape Medical News

Torrent Recalls More Tainted Losartan

Pathology & Lab Medicine - Medscape - Sab, 28/09/2019 - 06:23
It's the fifth recall by Torrent of losartan-containing medicines due to detection of unacceptable levels of a potential carcinogen.
News Alerts

Plain Water Better Than Hand Sanitizer for Influenza A

Pathology & Lab Medicine - Medscape - Sab, 28/09/2019 - 06:23
Handwashing with plain water was better at killing the influenza A virus than ethanol-based disinfectants, a study found.
Medscape Medical News

Options for Publishing Research Without Any P-values

Pathology & Lab Medicine - Medscape - Ven, 27/09/2019 - 05:23
This article presents statistical approaches that can be used instead of (or in addition to) P-values in designing and presenting clinical research.
European Heart Journal

Acute Migraine Pain Relief With Oral Rimegepant Yields Lasting Benefits

Pathology & Lab Medicine - Medscape - Ven, 27/09/2019 - 05:23
The acute treatment of migraine with rimegepant can provide lasting reduction in migraine-related disability and improved quality of life, according to new data presented earlier this month at the International Headache Conference (IHC) in Dublin, Ireland.
Reuters Health Information

MS Risk Nearly Doubles 15 Years Following Teen Concussion

Pathology & Lab Medicine - Medscape - Ven, 27/09/2019 - 05:23
An association between concussion during adolescence and long-term, elevated risk for multiple sclerosis grew stronger with new evidence from a large study.
Medscape Medical News

Trump Executive Order Aims to Speed Flu Vaccine Development

Pathology & Lab Medicine - Medscape - Ven, 27/09/2019 - 05:23
The order creates a new task force charged with coming up with a 5-year plan.
Medscape Medical News
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