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The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.

Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid‐β (Aβ) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross‐sectional BioFINDER cohort. In a further population‐based longitudinal cohort (ESTHER), the blood biomarker detected AD several years before clinical diagnosis in baseline samples with a positive likelihood ratio of 7.9; that is, those who were diagnosed with AD over the years were 7.9 times more likely to test positive. This assay may open avenues for blood screening of early AD stages as a funnel for further more invasive and expensive tests. Synopsis Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection. The amyloid‐β (Aβ) secondary structure distribution in blood plasma can be directly determined by the secondary structure sensitive amide I band. Prodromal AD cases (BioFINDER study) showed significant correlations between the amide I frequency shift and PET scanning results or CSF biomarker values. Early AD identification (Esther) yielded in 71% sensitivity, 91% specificity, and a LR + of 7.9–8 years before clinical symptoms appeared, in agreement with the BioFINDER study. The plasma biomarker may be used as a routine minimal‐invasive, low‐cost funnel to pre‐select individuals which should undergo lumbar puncture or PET scanning. Graphical Abstract Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology with a variable and unpredictable course. The aim of this study was to identify and validate plasma proteins that are predictive of outcome in IPF. Plasma samples were available for 241 patients with IPF (140 derivation and 101 validation). In the derivation cohort, concentrations of 92 proteins were analyzed using a multiplex bead-based immunoassay and concentrations of matrix metalloproteinase (MMP)-7, MMP-1, and surfactant protein D were assessed by ELISA. In the validation cohort concentrations of intercellular adhesion molecule (ICAM)-1, IL-8, and vascular cell adhesion molecule (VCAM)-1 were assessed by bead-based multiplex assay, and S100A12 and MMP-7 by ELISA. Associations of biomarkers with mortality, transplant-free survival, and disease progression were tested in the derivation and validation cohorts using nonparametric methods of survival analysis and the Cox proportional hazards model, and an integrated risk prediction score was derived and tested. High concentrations of MMP-7, ICAM-1, IL-8, VCAM-1, and S100A12 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the derivation cohort. In the independent validation cohort high concentrations of all five were predictive of poor transplant-free survival; MMP-7, ICAM-1, and IL-8 of overall survival; and ICAM-1 of poor progression-free survival. The personal clinical and molecular mortality prediction index derived in the derivation cohort was highly predictive of mortality in the validation cohort. Our results suggest that plasma proteins should be evaluated as a tool for prognosis determination in prioritization of patients for lung transplantation and stratification in drug studies.

Lipidomics analysis for large-scale studies aiming at the identification and quantification of natural lipidomes is often performed using LC–MS-based data acquisition. However, the choice of suitable LC–MS method for accurate lipid quantification remains a matter of debate. Here, we performed the systematic comparison between two HRAM-MS-based quantification workflows based on HILIC and RPLC MS by quantifying 191 lipids from five lipid classes in human blood plasma using deuterated standards in the “one ISTD-per-lipid class” approach. Lipid quantification was performed considering all necessary isotopic corrections, and obtained correction factors are illustrated. Concentrations of lipids in NIST® SRM® 1950 human blood plasma determined by the two methods were comparable for most of the studied lipid species except for highly unsaturated phosphatidylcholines (PC). A comparison of lipid concentrations to consensus values determined in a previously published multi-laboratory study illustrated possible “overestimation” of concentrations for these highly unsaturated lipids by HILIC MS. We evaluated the influence of lipid loading amounts as well as the difference between quantified lipid and internal standard concentrations on the HILIC MS quantification results. We conclude that both HILIC and RPLC HRAM-MS workflows can be equally used for accurate lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM) lipid quantification, despite significant differences in the concentration of highly unsaturated PC lipids which need to be addressed by establishing response factors to account for the differences in degree of lipid unsaturation.

Through enabling whole blood detection in point-of-care testing (POCT), sedimentation-based plasma separation promises to enhance the functionality and extend the application range of lateral flow assays (LFAs). To streamline the entire process from the introduction of the blood sample to the generation of quantitative immune-fluorescence results, we combined a simple plasma separation technique, an immunoreaction, and a micropump-driven external suction control system in a polymer channel-based LFA. Our primary objective was to eliminate the reliance on sample-absorbing separation membranes, the use of active separation forces commonly found in POCT, and ultimately allowing finger prick testing. Combining the principle of agglutination of red blood cells with an on-device sedimentation-based separation, our device allows for the efficient and fast separation of plasma from a 25-µL blood volume within a mere 10 min and overcomes limitations such as clogging, analyte adsorption, and blood pre-dilution. To simplify this process, we stored the agglutination agent in a dried state on the test and incorporated a filter trench to initiate sedimentation-based separation. The separated plasma was then moved to the integrated mixing area, initiating the immunoreaction by rehydration of probe-specific fluorophore-conjugated antibodies. The biotinylated immune complex was subsequently trapped in the streptavidin-rich detection zone and quantitatively analyzed using a fluorescence microscope. Normalized to the centrifugation-based separation, our device demonstrated high separation efficiency of 96% and a yield of 7.23 µL (= 72%). Furthermore, we elaborate on its user-friendly nature and demonstrate its proof-of-concept through an all-dried ready-to-go NT-proBNP lateral flow immunoassay with clinical blood samples.

The last two decades witnessed a significant advancement in the field of diluted and whole blood plasma separation. This is one of the common procedures used to diagnose, cure and treat numerous acute and chronic diseases. For this separation purpose, various types of geometries of microfluidic devices, such as T-channel, Y-channel, trifurcation, constriction–expansion, curved/bend/spiral channels, a combination of any of the two geometries, etc., are being exploited, and this is detailed in this review article. The evaluation of the performance of such devices is based on the several parameters such as separation efficiency, flow rate, hematocrits, channel dimensions, etc. Thus, the current extensive review article endeavours to understand how particular geometry influences the separation efficiency for a given hematocrit. Additionally, a comparative analysis of various geometries is presented to demonstrate the less explored geometric configuration for the diluted and whole blood plasma separation. Also, a meta-analysis has been performed to highlight which geometry serves best to give a consistent separation efficiency. This article also presents tabulated data for various geometries with necessary details required from a designer’s perspective such as channel dimensions, targeted component, studied range of hematocrit and flow rate, separation efficiency, etc. The maximum separation efficiency that can be achieved for a given hematocrits and geometry has also been plotted. The current review highlights the critical findings relevant to this field, state of the art understanding and the future challenges.

Numerous in-depth studies continue to reveal the many benefits of gut microbiota and young blood plasma administration. Dysbiosis, which occurs in the intestinal microbiota, especially in the aging process, is associated with many metabolic and cognitive disorders. Therefore, many studies aim to reverse the dysbiosis that occurs. There are also studies showing that young blood plasma application reverses the effects of aging at the level of many tissues and organs. Today, while research continues to reveal all the benefits of young blood plasma application in terms of health, blood plasma centers are also being established. In this study, we aimed to reveal the impact of young blood plasma, administered for 1 month, on the intestinal microbiota of middle-aged rats. After detailed metagenome analysis, alpha diversity indices demonstrated greater bacterial richness in the microbiota of plasma-administered rats compared with control rats. In addition, the Firmicutes/Bacteroidetes ratio was significantly diminished in plasma group microbiota, confirming possible rejuvenation properties of young plasma. Furthermore, increased counts of Bifidobacterium longum, Coprococcus catus, and Romboutsia ilealis species were measured in plasma-administered rats. The study revealed many fluctuations in different bacterial taxonomic units of the microbiota that could be valuable in future research on blood-based anti-aging treatments.

Abstract Rationale Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Objectives Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Methods Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. Measurements and Main Results There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0–0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01–0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). Conclusions The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required. Clinical trial registered with www.controlled-trials.com (ISRCTN92422949).

Abstract Rationale Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH. Objectives To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted lungs of patients with idiopathic PAH versus healthy donor lungs and to demonstrate functional relevance by blocking stromal-derived factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary hypertension in rats. Methods Immunohistochemistry was performed on lung tissue sections from patients with idiopathic PAH and healthy donors. All positively stained cells in whole-lung tissue sections, surrounding the vessels, and in the different compartments of the vessels were counted. To study the effects of blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration. Measurements and Main Results We found a significant increase of the perivascular number of macrophages (CD68+), macrophages/monocytes (CD14+), mast cells (toluidine blue+), dendritic cells (CD209+), T cells (CD3+), cytotoxic T cells (CD8+), and helper T cells (CD4+) in vessels of idiopathic PAH lungs compared with control subjects. FoxP3+ mononuclear cells were significantly decreased. In the monocrotaline model, the NOX-A12–induced reduction of mast cells, CD68+ macrophages, and CD3+ T cells was associated with improvement of hemodynamics and pulmonary vascular remodeling. Conclusions Our findings reveal altered perivascular inflammatory cell infiltration in pulmonary vascular lesions of patients with idiopathic pulmonary arterial hypertension. Targeting attraction of inflammatory cells by blocking stromal-derived factor-1 may be a novel approach for treatment of PAH.

Abstract Rationale Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells. Objectives We tested whether this outcome correlates with protection against childhood TB disease after newborn vaccination with bacillus Calmette-Guérin (BCG). Methods Whole blood from 10-week-old infants, routinely vaccinated with BCG at birth, was incubated with BCG for 12 hours, followed by cryopreservation for intracellular cytokine analysis. Infants were followed for 2 years to identify those who developed culture-positive TB—these infants were regarded as not protected against TB. Infants who did not develop TB disease despite exposure to TB in the household, and another group of randomly selected infants who were never evaluated for TB, were also identified—these groups were regarded as protected against TB. Cells from these groups were thawed, and CD4, CD8, and γδ T cell–specific expression of IFN-γ, TNF-α, IL-2, and IL-17 measured by flow cytometry. Measurements and Main Results A total of 5,662 infants were enrolled; 29 unprotected and two groups of 55 protected infants were identified. There was no difference in frequencies of BCG-specific CD4, CD8, and γδ T cells between the three groups of infants. Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants. Conclusions The frequency and cytokine profile of mycobacteria-specific T cells did not correlate with protection against TB. Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-γ production, may not necessarily translate into immune correlates of protection against TB disease.