Tree demographic strategies largely overlap across succession in Neotropical wet and dry forest communities.

Secondary tropical forests play an increasingly important role in carbon budgets and biodiversity conservation. Understanding successional trajectories is therefore imperative for guiding forest restoration and climate change mitigation efforts. Forest succession is driven by the demographic strategies-combinations of growth, mortality and recruitment rates-of the tree species in the community. However, our understanding of demographic diversity in tropical tree species stems almost exclusively from old-growth forests. Here, we assembled demographic information from repeated forest inventories along chronosequences in two wet (Costa Rica, Panama) and two dry (Mexico) Neotropical forests to assess whether the ranges of demographic strategies present in a community shift across succession. We calculated demographic rates for >500 tree species while controlling for canopy status to compare demographic diversity (i.e., the ranges of demographic strategies) in early successional (0-30 years), late successional (30-120 years) and old-growth forests using two-dimensional hypervolumes of pairs of demographic rates. Ranges of demographic strategies largely overlapped across successional stages, and early successional stages already covered the full spectrum of demographic strategies found in old-growth forests. An exception was a group of species characterized by exceptionally high mortality rates that was confined to early successional stages in the two wet forests. The range of demographic strategies did not expand with succession. Our results suggest that studies of long-term forest monitoring plots in old-growth forests, from which most of our current understanding of demographic strategies of tropical tree species is derived, are surprisingly representative of demographic diversity in general, but do not replace the need for further studies in secondary forests.

A Novel Fibrin Matrix Derived from Platelet-Rich Plasma: Protocol and Characterization.

Although fibrin matrices derived from Platelet-Rich Plasma (PRP) are widely used in regenerative medicine, they have some limitations that can hinder their application. Modifying the composition of the PRP-derived fibrin matrix may improve its properties, making it suitable for certain medical uses. Three types of fibrin matrices were obtained: a PRP-derived fibrin matrix (FM), a PRP-derived fibrin matrix with a high fibrinogen content and platelets (FM-HFP) and a PRP-derived fibrin matrix with a high fibrinogen content (FM-HF). The fibrinogen levels, biomechanical properties and cell behavior were analyzed. The presence of platelets in the FM-HFP generated an inconsistent fibrin matrix that was discarded for the rest of the analysis. The fibrinogen levels in the FM-FH were higher than those in the FM (p < 0.0001), with a concentration factor of 6.86 ± 1.81. The values of clotting and swelling achieved using the FM-HF were higher (p < 0.0001), with less clot shrinkage (p < 0.0001). The FM had a significantly higher stiffness and turned out to be the most adherent composition (p = 0.027). In terms of cell viability, the FM-HF showed less cell proliferation but higher live/dead ratio values (p < 0.01). The increased fibrinogen and platelet removal in the FM-HF improved its adhesion and other biomechanical properties without affecting cell viability.

Derotational high tibial osteotomy in cases of anterior knee pain and/or patellofemoral instability: a systematic review.

IMPORTANCE: Derotational high tibial osteotomy (HTO) is a surgical intervention for correcting rotational malalignments in the lower limb, which may contribute to anterior knee pain (AKP) and/or patellofemoral instability (PFI). This surgical technique is not yet widely implemented and requires a systematic evaluation of its outcomes. AIM: To assess the effectiveness of derotational HTO in correcting rotational malalignments of the lower limb in patients with AKP and/or PFI through radiological, clinical, and patient-reported outcome measures. EVIDENCE REVIEW: Searches were conducted in the PubMed, Embase, and Web of Science databases up to March 3, 2023, to identify studies utilizing derotational HTO in patients with AKP and/or PFI. The primary outcome measures of interest were measurements of lower limb angular correction. Other radiological, clinical, and patient-reported outcome measures were also analyzed. The risk of bias was judged with the RoBANS tool. FINDINGS: A total of 8 studies were included, comprising 215 patients (27.0 â€‹± â€‹3.9 years) and 245 knees. The most reported angle was tibial torsion (k â€‹= â€‹6 studies, n â€‹= â€‹173 knees), with a mean difference between postoperative and preoperative values (postsurgical correction) ranging from -37.8° to -10.8°. Patient-reported outcome measures showed significant improvements in the postoperative moment, exceeding the minimal clinically important difference in almost all cases, and with high patient satisfaction (93.6%). CONCLUSIONS AND RELEVANCE: Derotational HTO allows the correction of rotational malalignments of the lower limb (tibial torsion) and promotes patient satisfaction. LEVEL OF EVIDENCE: Level IV.

Women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men.

PURPOSE: The purpose of this study was to evaluate the impact of gender on the efficacy of platelet-rich plasma (PRP) in patients with knee osteoarthritis (KOA), comparing their short-term response between men and women. METHODS: Four hundred-eighteen patients (529 knees) were included. Patients were treated with three injections of PRP on a weekly basis. Blood and PRP samples were randomly tested. Patients were asked to complete the knee injury and osteoarthritis outcome score (KOOS) and 12-item short form survey (SF-12), at baseline and 6 months. Success rates were calculated according to a reduction in the pain score of at least 9.3 points [minimal clinically important improvement (MCII)]. Comparative tests and multivariate regression were performed. RESULTS: The PRP had a platelet concentration factor of 2.0X compared to blood levels, with no leucocytes or erythrocytes. KOOS scores showed an increase from baseline to 6 months (p < 0.0001). There was an increase in the physical component summary (PCS) (p < 0.0001) and mental component summary (MCS) (p < 0.01) of the SF-12. The number of knees of women with MCII was 156 out of 262 (59.6%), whereas the number of knees of men was 136 out of 267 (50.9%) (p = 0.0468). Women had worse baseline scores on pain (p = 0.009), PCS (p < 0.0001) and MCS (p < 0.0001). CONCLUSION: Although the symptomatology generated by KOA was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women providing comparable final follow-up outcomes between men and women. LEVEL OF EVIDENCE: Level IV.

Method to obtain a plasma rich in platelet- and plasma-growth factors based on water evaporation.

Platelet-Rich Plasma, also known as PRP, is an autologous biologic product used in medicine as a treatment for tissue repair. Nowadays, the majority of PRP obtention methods enrich only platelets, not considering extraplatelet biomolecules, which take part in several cell processes. In the present work, a novel PRP preparation method was developed to obtain a PRP rich in both platelet and plasma extraplatelet molecules. The method is based on the evaporation of the water of the plasma using a rotary evaporator. With this new methodology an increase in plasmatic growth factors and, as a consequence, a better dermal fibroblast cell viability was achieved, compared to a standard PRP formulation. This novel PRP product obtained with this new methodology showed promising results in vitro as an improved PRP treatment in future application.

Derotational distal femoral osteotomy corrects excessive femoral anteversion in patients with patellofemoral instability: A systematic review.

PURPOSE: Patellofemoral instability (PFI) is a common condition that can be caused from multiple factors, including lower limb rotational malalignments. Determining precise criteria for performing corrective torsional osteotomy can be a daunting task due to the lack of consensus on normal and excessive values and the limited evidence-based data in the postoperative results. The purpose was to assess the clinical, functional and imaging outcomes following derotational distal femoral osteotomy (DDFO) in patients with PFI and/or anterior knee pain (AKP) associated with lower limb rotational malalignments. METHODS: Searches were conducted on PubMed, EMBASE and Web of Science databases up to October 2023. Studies reporting outcomes after DDFO in patients with PFI and/or AKP were eligible for the systematic review. The primary outcome was imaging metrics, especially femoral anteversion. Secondary outcomes included the patient-reported outcome measures (PROMs) (clinical and functional). Quantitative synthesis involved the use of weighted averages to calculate pre- to postoperative mean differences (MD) and compare them against the minimal clinically important difference (MCID). RESULTS: Ten studies (309 knees) were included with a mean follow-up of 36.1 ± 11.7 months. Imaging outcomes consistently indicated the correction of femoral anteversion (MD = -19.4 degrees, 95% confidence interval: -20.1 to -18.7) following DDFO. PROMs showed significant improvements in most studies, exceeding the MCID. Patient satisfaction with the DDFO was high (93.3%). CONCLUSIONS: The DDFO was an effective treatment option for correcting excessive femoral anteversion in patients with PFI associated with clinically relevant functional and clinical improvement and a high satisfaction rate. LEVEL OF EVIDENCE: Level IV, systematic review of level II-IV studies.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial.

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely. FUNDING: Canadian Institutes of Health Research and Philips RS North America.

Estrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice.

Menopause is associated with cognitive deficits and brain atrophy, but the brain region and cell-specific mechanisms are not fully understood. Here, we identify a sex hormone by age interaction whereby loss of ovarian hormones in female mice at midlife, but not young age, induced hippocampal-dependent cognitive impairment, dorsal hippocampal atrophy, and astrocyte and microglia activation with synaptic loss. Selective deletion of estrogen receptor beta (ERß) in astrocytes, but not neurons, in gonadally intact female mice induced the same brain effects. RNA sequencing and pathway analyses of gene expression in hippocampal astrocytes from midlife female astrocyte-ERß conditional knock out (cKO) mice revealed Gluconeogenesis I and Glycolysis I as the most differentially expressed pathways. Enolase 1 gene expression was increased in hippocampi from both astrocyte-ERß cKO female mice at midlife and from postmenopausal women. Gain of function studies showed that ERß ligand treatment of midlife female mice reversed dorsal hippocampal neuropathology.

New Formulation of Platelet-Rich Plasma Enriched in Platelet and Extraplatelet Biomolecules Using Hydrogels.

Platelet-rich plasma (PRP) is an autologous biologic product used in several fields of medicine for tissue repair due to the regenerative capacity of the biomolecules of its formulation. PRP consists of a plasma with a platelet concentration higher than basal levels but with basal levels of any biomolecules present out of the platelets. Plasma contains extraplatelet biomolecules known to enhance its regenerative properties. Therefore, a PRP containing not only a higher concentration of platelets but also a higher concentration of extraplatelet biomolecules that could have a stronger regenerative performance than a standard PRP. Considering this, the aim of this work is to develop a new method to obtain PRP enriched in both platelet and extraplatelet molecules. The method is based on the absorption of the water of the plasma using hydroxyethyl acrylamide (HEAA)-based hydrogels. A plasma fraction obtained from blood, containing the basal levels of platelets and proteins, was placed in contact with the HEAA hydrogel powder to absorb half the volume of the water. The resulting plasma was characterized, and its bioactivity was analyzed in vitro. The novel PRP (nPRP) showed a platelet concentration and platelet derived growth factor (PDGF) levels similar to the standard PRP (sPRP), but the concentration of the extraplatelet growth factors IGF-1 (p < 0.0001) and HGF (p < 0.001) were significantly increased. Additionally, the cells exposed to the nPRP showed increased cell viability than those exposed to a sPRP in human dermal fibroblasts (p < 0.001) and primary chondrocytes (p < 0.01). In conclusion, this novel absorption-based method produces a PRP with novel characteristics compared to the standard PRPs, with promising in vitro results that could potentially trigger improved tissue regeneration capacity.

Method Based on Ultrafiltration to Obtain a Plasma Rich in Platelet and Plasma Growth Factors.

Platelet-Rich Plasma (PRP) is an autologous biological product which, due to its regenerative capacity, is currently used in different fields of medicine. This biological treatment has proven to be effective in numerous research studies due to its high content of growth factors released by platelets. However, the current systems used to obtain PRP do not enrich the growth factors and cytokines outside platelets. Considering this, the present work aims to develop a new technique by which all the biomolecules present in plasma are enriched. Thus, a new method based on ultrafiltration has been developed for the obtaining of the novel PRP. By this method, ultrafiltration of the plasma water is carried out using a 3KDa filtering unit. The results showed that the technique was able to concentrate extraplatelet factors, such as IGF-1 and HGF, in contrast with conventional plasmas. Thus, the cultured cells responded with increased viability to this new PRP. These results could provide a new approach to the treatment of injuries requiring regenerative medicine, potentially improving the outcomes of the conventional PRPs.

High sensitivity c-reactive protein and circulating biomarkers of endothelial dysfunction in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of patients with chronic myelogenous leukemia (CML); however, they may cause cardiovascular (CV) toxicities. In this cross-sectional study, we explored whether high-sensitivity C-reactive protein (hsCRP) and novel markers of vascular dysfunction were associated with exposure to specific TKIs, in 262 CML patients. Hs-CRP level was not associated with CML disease activity or treatment with a specific TKI. Body mass index (OR: 1.15, 95% CI: 1.108-1.246; p < 0.001) and CML duration (OR: 1.004, 95% CI: 1.001-1.008; p = 0.024) were independently associated with higher hs-CRP. In exploratory analyses, novel endothelial-centric markers (e.g. ET-1 and VCAM-1) were differential across the various TKIs, particularly amongst nilotinib- and ponatinib-treated patients. While Levels of hs-CRP do not appear to be correlated with specific TKIs, circulating markers of vascular dysfunction were altered in patients treated with specific TKIs and should be explored as potential markers of TKI-associated CV risk.

High survival rate after the combination of intrameniscal and intraarticular infiltrations of platelet-rich plasma as conservative treatment for meniscal lesions.

PURPOSE: To evaluate the efficacy of applying a combination of intrameniscal and intraarticular infiltrations of Platelet-Rich Plasma (PRP) in patients with meniscal tears, analyzing its failure rate and clinical evolution, as well as factors that may influence the positive response to this treatment. METHODS: Three hundred and ninety-two cases out of 696 met the inclusion criteria and were included in this work. Survival and patient-reported outcome measure (PROM) were collected and analyzed. Survival rate was defined as the percentage of patients who did not undergo meniscus surgery during their follow-up time. Patients were asked to complete the Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6 months and 18 months. Other patient- and pathology-related variables were collected. Blood and PRP samples were randomly tested as a quality control measure. Survival and comparative statistical tests, and multivariate regression were performed for the analysis of the variables. RESULTS: The PRP applied had a platelet concentration factor of 1.9X in respect to blood levels, with no leukocytes or erythrocytes. Thirty-eight patients required surgical intervention after treatment reaching a survival rate of 90.3% with an estimated mean survival time of 54.4 months. The type of injury (P = 0.002) and the presence of chondropathy were risk factors for surgical intervention after PRP treatment (P = 0.043). All KOOS scores showed a significant statistical increase from baseline to 6 months (N = 93) and 18 months (N = 66) (P < 0.0001). The number of cases with minimal clinically important improvement (MCII) at 6 months and 18 months post-treatment was 65 (69.9%) and 43 (65.2%), respectively. CONCLUSION: The combination of intrameniscal and intraarticular PRP infiltrations is a valid conservative treatment for meniscal injuries avoiding the need for surgical intervention. Its efficacy is higher in horizontal tears and decreases when joint degeneration is present. LEVEL OF EVIDENCE: Level IV.

Regulatory T Cell Biomarkers Identify Patients at Risk of Developing Acute Cellular Rejection in the First Year Following Heart Transplantation.

BACKGROUND: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk. METHODS: We used a CD4+ T cell gene signature (TGS) panel that tracks CD4+ conventional T cells (Tconv) and regulatory T cells (Treg) on longitudinal samples from 94 adult heart transplant recipients. We evaluated combined diagnostic performance of the TGS panel with a previously developed biomarker panel for ACR diagnosis, HEARTBiT, while also investigating TGS' prognostic utility. RESULTS: Compared with nonrejection samples, rejection samples showed decreased Treg- and increased Tconv-gene expression. The TGS panel was able to discriminate between ACR and nonrejection samples and, when combined with HEARTBiT, showed improved specificity compared with either model alone. Furthermore, the increased risk of ACR in the TGS model was associated with lower expression of Treg genes in patients who later developed ACR. Reduced Treg gene expression was positively associated with younger recipient age and higher intrapatient tacrolimus variability. CONCLUSIONS: We demonstrated that expression of genes associated with CD4+ Tconv and Treg could identify patients at risk of ACR. In our post hoc analysis, complementing HEARTBiT with TGS resulted in an improved classification of ACR. Our study suggests that HEARTBiT and TGS may serve as useful tools for further research and test development.

The effect of short-term cryopreservation on the properties and functionality of platelet-rich plasma.

Platelet Rich Plasma (PRP) is a biological treatment which, thanks to its enhanced growth factors content, is widely used in the field of regenerative medicine for its reparative effects. Although it is usually used fresh immediately after preparation, its freezing for preservation for future usage could be key in increasing its versatility and new applications. To assess the suitability of freezing, after collecting PRP and platelet lysates (PL) from 6 patients, they were preserved for 1 or 3 months at temperatures of -20ºC and -80°C. Measurements were then made on platelet number and integrity, growth factor levels, biomechanical properties of the clot and its bioactivity on cultured cells. Fresh PRP and PL were used as controls. The results showed an increase in platelet size (p < .01) and clot elasticity (p < .01), as well as decrease in levels of PDGF (P < .05) and VEGF (p < .05), though the overall bioactivity was not affected as culture cells showed the same responsiveness to both frozen and fresh PRP and PL in terms of cell viability. Based on these results, it could be assumed that preservation of PRP by freezing is a feasible and suitable option for its further use.

What is the context? Platelet-Rich Plasma (PRP) is a biological treatment widely used in regenerative medicine as a result of its high content of growth factors.In its routine use, PRP has autologous character, since it is obtained from the same patient and its infiltration in the affected area takes place immediately after it is obtained.Its storability would give PRP versatility in use, which could enable a potential allogeneic use and even significantly reduce the number of blood draws for each patient.It is necessary to establish a PRP storage protocol where its properties are not affected.What is new? PRP was stored at two time points (1 and 3 months) and temperatures (−20ºC and −80ºC) in activated and unactivated states. Afterwards, platelet number, size and activation were measured. Furthermore, the biomechanical properties of the resulting clot, the growth factor content and PRP's impact on cell viability were analyzed.The limiting factor was not having used aggregometry or other techniques that measure other cellular processes, as well as the limited sample size.The results showed that freezing affected platelet size, the levels of platelet-derived GFs and the biomechanical properties of the clot. However, plasmatic levels of growth factors or its capacity to boost cellular proliferation were not affected.What is the impact?The clinical impact of this work is the ability to preserve PRP by freezing. This is especially relevant as it allows a possible use of PRP as an allogeneic treatment. Moreover, its preservation significantly reduces the number of blood draws for each patient, especially in those with puncture difficulties or with apprehension.

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report.

Introduction and Objective: Amyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes. In September 2021, the Canadian Onco-Nephrology Interest Group hosted a symposium to discuss diagnostic challenges and recent advances in the management of amyloidosis from the perspectives of the nephrologist, cardiologist, and onco-hematologist. Methods and Sources of Information: Through structured presentations, the group discussed a series of cases highlighting the varied clinical presentations of amyloidoses affecting the kidney and heart. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient-related and treatment-related considerations in the diagnosis and management of amyloidoses. Key findings: (1) Overview of the clinical presentation of amyloidoses and the role of specialists in performing timely and accurate diagnostic workup; (2) review of best practices for multidisciplinary management of amyloidosis, including prognostic variables and determinants of treatment response; and (3) update on new and emerging treatments in the management of light chain and amyloid transthyretin amyloidoses. Limitations: This conference featured multidisciplinary discussion of cases, and learning points reflect the assessments by the involved experts/authors. Implications: Identification and management of amyloidoses can be facilitated with a multidisciplinary approach and higher index of suspicion from cardiologists, nephrologists, and hemato-oncologists. Increased awareness of clinical presentations and diagnostic algorithms for amyloidosis subtyping will lead to more timely interventions and improved clinical outcomes.

Introduction et objectifs: Les amyloïdoses sont un groupe hétérogène de troubles résultant du dépôt de fibrilles amyloïdes dans les tissus extracellulaires. Les reins sont un des sites les plus fréquents de dépôts amyloïdes, mais ces derniers peuvent également affecter un large éventail de systèmes et d'organes, notamment le cœur, le foie, le tractus gastro-intestinal et les nerfs périphériques. Le pronostic de l'amyloïdose, en particulier en cas d'atteinte cardiaque, est mauvais. Les résultats peuvent cependant être améliorés par une approche collaborative utilisant de nouveaux outils de diagnostic et de prise en charge. En septembre 2021, le Canadian Onco-Nephrology Interest Group (groupe canadien d'intérêt en onco-néphrologie) a organisé un symposium pour discuter des défis liés au diagnostic de l'amyloïdose et des récents progrès dans la gestion de cette maladie du point de vue du néphrologue, du cardiologue et de l'hémato-oncologue. Méthodologie et sources de l'information: Au moyen de présentations structurées, le groupe a discuté d'une série de cas mettant en évidence les diverses présentations cliniques d'amyloïdoses affectant les reins et le cœur. Les opinions d'experts, les résultats des essais cliniques et les résumés des publications ont été utilisés pour illustrer les facteurs liés au patient et au traitement à considérer dans le diagnostic et la prise en charge des amyloïdoses. Principaux résultats: 1) Aperçu de la présentation clinique des amyloïdoses et du rôle des spécialistes dans la réalisation d'un bilan diagnostic précis et en temps opportun (2) Examen des meilleures pratiques de gestion multidisciplinaire de l'amyloïdose, y compris des variables pronostiques et des déterminants de la réponse au traitement (3) Mise à jour sur les traitements nouveaux et émergents dans la prise en charge des amyloïdoses à chaîne légère (AL) et à transthyrétine (ATTR). Limites: Ce symposium a donné lieu à une discussion multidisciplinaire de cas; les points d'apprentissage reflètent les évaluations des experts/auteurs concernés. Conclusion: L'identification et la prise en charge des amyloïdoses peuvent être facilitées par une approche multidisciplinaire et un indice de suspicion plus élevé de la part des cardiologues, des néphrologues et des hémato-oncologues. Une meilleure connaissance des présentations cliniques et des algorithmes de diagnostic pour le sous-typage de l'amyloïdose permettra d'intervenir plus rapidement et d'améliorer les résultats cliniques.

Action of Platelet-Rich Plasma on In Vitro Cellular Bioactivity: More than Platelets.

Platelet-rich plasma (PRP) is a biological therapy in which one of the mechanisms of action is the stimulation of biological processes such as cell proliferation. The size of PRP's effect depends on multiple factors, one of the most important being the composition of PRP. The aim of this study was to analyze the relationship between cell proliferation and the levels of certain growth factors (IGF-1, HGF, PDGF, TGF-ß and VEG) in PRP. First, the composition and effect on cell proliferation of PRP versus platelet-poor plasma (PPP) were compared. Subsequently, the correlation between each growth factor of PRP and cell proliferation was evaluated. Cell proliferation was higher in cells incubated with lysates derived from PRP compared to those cultured with lysates derived from PPP. In terms of composition, the levels of PDGF, TGF-ß, and VEGF were significantly higher in PRP. When analyzing the PRP growth factors, IGF-1 was the only factor that correlated significantly with cell proliferation. Of those analyzed, the level of IGF-1 was the only one that did not correlate with platelet levels. The magnitude of PRP's effect depends not only on platelet count but also on other platelet-independent molecules.

Donor and recipient human leukocyte antigen-G polymorphisms modulate the risk of adverse immunologic events following lung transplantation.

The long-term benefits of lung transplantation (LTx) are limited by pathogenic alloimmune responses that drive injury, inflammation, and chronic dysfunction. Human leukocyte antigen-G (HLA-G) plays a key role in the modulation of these pathways. This study assesses the impact of the HLA-G genotype on immunologic risk and survival following LTx. This retrospective cohort study included 289 bilateral LTx. Recipient and donor HLA-G genotypes were analyzed to identify associations with de novo donor-specific antibodies, acute rejection, chronic lung allograft dysfunction, and allograft survival. We further assessed these associations, both individually and in paired analysis, based on a grouped haplotype classification of HLA-G expression. Donor HLA-G single nucleotide polymorphisms were associated with allograft injury, the onset of chronic lung allograft dysfunction following injury, and allograft survival. Recipient HLA-G single nucleotide polymorphisms were associated with allograft injury, cellular rejection, and donor-specific antibody formation. "Low HLA-G expression" donor haplotypes were associated with impaired allograft survival, as were "low HLA-G expression" donor-recipient haplotype pairs. This study provides compelling evidence for the role of HLA-G in modulating immunologic risk after LTx. Our results highlight the importance of both donor and recipient HLA-G genotypes on the overall risk profile and underscore the lasting influence of donor genotype on lung transplant outcomes.