Unveiling a Biomarker Signature of Meningioma: the Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation in grades classified from I to III. Meningiomas tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningioma, with a focus on Neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in preoperative and postoperative decision-making. Discovery of novel biomarkers will allow more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.This research is funded by a grant from Morehouse School of Medicine to Firas Kobeissy and a grant from Qatar University to Abdullah A. Shaito

Viral metagenomics analysis of stool specimens from children with unresolved gastroenteritis in Qatar

Acute gastroenteritis (AGE) is associated with significant global morbidity and mortality, especially among children under five years of age. Viruses are well established as etiologic agents of gastroenteritis since they are the most common pathogens that contribute to the disease burden in developing countries. Despite the advances in molecular diagnosis, a substantial proportion of AGE etiology remain unresolved. We implemented a viral metagenomics pipeline to determine the potential viral etiology associated with AGE among children under the age of five years in Qatar with undiagnosed etiology. Following enriching for the viral genome, ∼1.3 billion sequences were generated from 89 stool specimens using the Illumina HiSeq platform, of which 7% were mapped to viral genomes. Human viruses were detected in 34 specimens (38.2%); 14 were adenovirus, nine coxsackievirus A16, five rotavirus (G9P[8] and G4P[8]), four norovirus (GII), one influenza A virus (H3), and one respiratory syncytial virus A (RSVA). In conclusion, the viral metagenomics approach is useful for determining AGE's etiology when routine molecular diagnostic assays fail.This study was supported by Qatar National Research Fund (QNRF) funding, grant # NPRP 9–133–1-025, and partial funding from Hamad Medical Corporation, grant # 16173/16

L'impact de la sérologie pré-greffe sur le risque re réactivation du BKPyV après une transplantation rénale

Background: BK polyomavirus associated nephropathy (BKPyVAN), is a troublesome disease induced by BK polyomavirus (BKPyV) reactivation in immunocompromised renal graft recipients. BKPyVAN can progress to graft dysfunction and has no current treatment, making immunosupression reduction the only management choice. Thus predictive BKPyV infection reactivation markers are needed for high-risk patient identification. Methods: we conducted a retrospective study to assess the correlation between the BKPyV pre-transplant serostatus and post transplant BKPyV infection incidence. Sera from 329 recipients and 222 matched donors were tested for anti-BKV antibodies against four BKPyV serotypes by a VLPs- based IgG ELISA, and BKPyV DNA load was monitored for at least 1 year post transplantation. Results: 80 (24%) recipients were viruric and 59 (18%) recipients were viremic post transplantation. An elevated BKPyV viremia risk was observed for recipients who had a mean antibody titer for all serotypes ≤400 before transplantation (odd ratio [OR], 5.58; 95% confidence interval [CI], 2.60-11.79; P4 months). Conclusions: Both donor and recipient mean BKPyV antibody titer may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high reactivation riskContexte: La néphropathie associée au virus polyomavirus BK (BKPyVAN) est une maladie incommodante observée chez les receveurs de greffe rénale immunodéprimés suite à une réactivation du polyomavirus BK (BKPyVV). BKPyVAN peut évoluer vers un dysfonctionnement de la greffe et n'a actuellement aucun traitement, rendant la réduction de l'immunosuppression comme seul choix de gestion. Cependant, cette réduction s'avère inadaptée ou non applicable conduisant à une augmentation du risque de rejet aigu. Ainsi, des marqueurs prédictifs de réactivation de l'infection à BKPyV sont nécessaires pour l'identification des patients à haut risque. Méthodes: nous avons mené une étude rétrospective pour évaluer la corrélation entre le statut sérologique du BKPyV en pré-transplantation et l'incidence de l'infection par BKPyV en post-transplantation. Des sérums de 329 receveurs et 222 donneurs appariés ont été testés pour les anticorps anti-BKV contre quatre sérotypes de BKV par un test IgG ELISA à base de VLPs, et la charge d'ADN du BKPyV a été surveillée pendant au moins 1 an après la transplantation par PCR. Résultats: 80 (24%) receveurs étaient viruriques et 59 (18%) receveurs étaient virémiques en post-transplantation. Un risque élevé de virémie à BKPyV a été observé pour les receveurs qui avaient un titre moyen d'anticorps pour tous les sérotypes ≤ 400 avant la transplantation (Odds ratio [OR], 5.58; intervalle de confiance à 95% [IC], 2.60-11.79; P 4 mois). Conclusions: Le titre moyen d'anticorps anti-BKPyV du donneur et du receveur peut servir d'outil prédictif pour gérer l'infection clinique avec BKPyV, en identifiant les patients à haut risque de réactivation du viru

Pre-transplantation assessment of BK virus serostatus: Significance, current methods, and obstacles.

International audienceThe immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field)

Pre-transplantation assessment of BK virus serostatus: Significance, current methods, and obstacles.

The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques' advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field)

Impact, obstacles and boundaries of patient partnership: A qualitative interventional study in Lebanon.

The patient as partner approach is a modern ‎model of patient engagement that integrates the patients' knowledge and skills into managing their own health. This study aims to evaluate the benefits and barriers of patient partnership in a healthcare setting. It is a qualitative and interventional study that implemented a patient and family partnership committee (PFPC) at a Lebanese hospital during the COVID-19 pandemic. A purposeful guided approach was used for sampling, and data was collected by structured questionnaire ‎interviews. Seven PFPC team dynamics building blocks were generated: transparency, support, motivation, comfortable communication, mutual understanding, equity in positions and empowerment to participate. Both the patient partners (94%) and healthcare professionals (90%) were satisfied with the PFPC experience. The majority of the healthcare professionals (HP) reported a noticeable change in the quality improvement process (QIP) (89%) and approved to standardize the PFPC (93%). The patient partnership benefits were clear, and the PFPC was perceived positively by both patient partners (PP) and HP. PP experienced distress relief (37%), gained ideas (41%) and felt that their opinion was heard (27%) after PFPC participation. PP reported benefits to hospitalized patients, including respect and care (63%) and patient satisfaction (20%). The main challenges for PFPC implementation were time availability and conflicts. Lessons from patient partnership can be utilized to improve the patient care policies in the Lebanese healthcare system. Moreover, developing countries can benefit from the patient partnership approach in their healthcare settings

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study

Abstract Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes

The impact of pre-graft serology on the risk of BKPyV infection post-renal transplantation

International audienceAbstract Objectives BK polyomavirus associated nephropathy, is a troublesome disease induced by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients with no effective available treatment, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for high-risk viremia patient identification. Methods we conducted a retrospective study to assess the correlation between the BKPyV pre-transplant serostatus and post-transplant BKPyV infection incidence. Sera from 329 recipients and 222 matched donors were tested for anti-BKV antibodies against BKPyV serotypes I and IV by a VLPs-based IgG ELISA, and BKPyV DNA load was monitored for at least 1 year post transplantation. Results 80 recipients were viruric and 59 recipients were viremic post transplantation. In the post-transplant period, the probability of developing viremia for serotype I was increasing from 4.3% for the D-/R + group to 12.1% for the D+/R + group and climbing to 37.5% for the D+/R- group (p < 0.05). When calculating the recipient mean titers for serotypes I and IV, we observed a clear difference in the proportions of viremia passing from 50% for mean titers < 400 to 13.5% for titers ≥ 400 (p < 0.001) with also a higher proportion of presumptive nephropathy (50% vs 23.1%, p < 0.05). In univariate analysis this parameter has an odds ratio of 6.41 for the risk of developing post-transplant BKPyV viremia (95% CI: 3.16–13.07; p < 0.0001). Conclusions Both donor and recipient BKPyV seropositivity determination before transplantation and antibody titer may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk

The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of aspirin and clopidogrel treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with aspirin and/or clopidogrel for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or clopidogrel treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients