From biochemical markers to molecular endotypes of osteoarthritis: a review on validated biomarkers

\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Introduction: Osteoarthritis (OA) affects over 500 million people worldwide. OA patients are symptomatically treated, and current therapies exhibit marginal efficacy and frequently carry safety-risks associated with chronic use. No disease-modifying therapies have been approved to date leaving surgical joint replacement as a last resort. To enable effective patient care and successful drug development there is an urgent need to uncover the pathobiological drivers of OA and how these translate into disease endotypes. Endotypes provide a more precise and mechanistic definition of disease subgroups than observable phenotypes, and a panel of tissue- and pathology-specific biochemical markers may uncover treatable endotypes of OA. Areas covered: We have searched PubMed for full-text articles written in English to provide an in-depth narrative review of a panel of validated biochemical markers utilized for endotyping of OA and their association to key OA pathologies. Expert opinion: As utilized in IMI-APPROACH and validated in OAI-FNIH, a panel of biochemical markers may uncover disease subgroups and facilitate the enrichment of treatable molecular endotypes for recruitment in therapeutic clinical trials. Understanding the link between biochemical markers and patient-reported outcomes and treatable endotypes that may respond to given therapies will pave the way for new drug development in OA

Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis. Materials and Methods: We included 780 PWH with suppressed viral replication (<50 copies/mL) and absence of hepatitis B and hepatitis C co-infection and 65 uninfected controls from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study. Flow cytometry was used to determine T-cell activation (CD38+HLA-DR+), senescence (CD28-CD57+), and apoptosis (CD28-CD95+). T-cell subsets are reported as proportions of CD4+ and CD8+ T-cells. We defined an elevated proportion of a given T-cell subset as above the 75th percentile. Regression models were used to determine the association between HIV status and T-cell subset and in PWH to determine the association between age or HIV-specific risk factors and T-cell subsets. Furthermore, an interaction between HIV status and age on T-cell subsets was investigated with an interaction term in models including both PWH and controls. Models were adjusted for age, sex, BMI, and smoking status. Results: In adjusted models a positive HIV status was associated with elevated proportions of CD8+ activated (p = 0.009), CD4+ senescent (p = 0.004), CD4+ apoptotic (p = 0.002), and CD8+ apoptotic (p = 0.003) T-cells. In PWH a 10-year increase in age was associated with higher proportions of CD4+ and CD8+ senescent (p = 0.001 and p < 0.001) and CD4+ and CD8+ apoptotic T-cells (p < 0.001 and p < 0.001). However, no interaction between HIV status and age was found. Furthermore, in PWH a CD4+/CD8+ ratio < 1 was associated with elevated proportions of T-cell activation, senescence, and apoptosis. Discussion: We found evidence of residual T-cell immune dysfunction in well-treated PWH without HBV or HCV co-infection, and age was associated with T-cell senescence and apoptosis. Our data supports that HIV infection has similar effects as aging on T-cell subsets. However, since no interaction between HIV status and age was found on these parameters, we found no evidence to support accelerated immunological aging in PWH

Assessing Medicare Part D Claim Completeness Using Medication Self-Reports: The Role of Veteran Status and Generic Drug Discount Programs

Medicare Part D claims are commonly used for research, but missing claims could compromise their validity. This study assessed two possible causes of missing claims: veteran status and Generic Drug Discount Programs (GDDP)

Medication Adherence Based on Part D Claims for Patients With Heart Failure After Hospitalization (from the Atherosclerosis Risk in Communities Study)

Medication non-adherence is a common precipitant of heart failure (HF) hospitalization and is associated with poor outcomes. Recent analyses of national data focus on long-term medication adherence. Little is known about adherence of HF patients immediately following hospitalization. Hospitalized HF patients were identified from the Atherosclerosis Risk in Communities (ARIC) study. ARIC data were linked to Medicare inpatient and Part D claims from 2006–2009. Inclusion criteria were: a chart adjudicated diagnosis of acute decompensated or chronic HF; documentation of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), beta-blocker (BB), or diuretic prescription at discharge; Medicare Part D coverage. Proportion ambulatory days covered (PADC) was calculated for up to twelve 30-day periods after discharge. Adherence was defined as ≥80% PADC. We identified 402 participants with Medicare Part D: mean age 75, 30% male, 41% black. Adherence at 1, 3 and 12 months was 70%, 61%, 53% for ACEI/ARB, 76%, 66%, 62% for BB, and 75%, 68%, 59% for diuretic. Adherence to any single drug class was positively correlated with being adherent to other classes. Adherence varied by geographic site/race for ACEI/ARB and BB but not diuretics. In conclusion, despite having Part D coverage, medication adherence post discharge for all three medication classes declined over 2–4 months after discharge, followed by a plateau over the subsequent year. Interventions should focus on early and sustained adherence

Rekonstruktion der anterioren Schädelbasis bei spontaner Rhinoliquorrhoe

Objective/Hypothesis: Spontaneous rhinoliquorrhea often occurs due to defects of the skull base. It is often misinterpreted as rhinitis and is surgically the most difficult rhinoliquorrhea entity to close.Methods: We conducted a retrospective chart analysis of patients that were diagnosed with spontaneous rhinoliquorrhea at the University Hospital Bonn between 2001 and 2017.Results: Overall, twelve patients were included in this study. On average, the time between occurrence of nasal discharge and diagnoses of rhinoliquorrhea was 123 days. In ten patients, the localization of the skull base defect could be localized by computed tomography or MRI cisternography. Ten patients underwent surgery, of which 9 remained recurrence free. One patient underwent revision surgery and from thereon was recurrence free.Conclusion: Spontaneous rhinoliquorrhea still remains a diagnostic and therapeutic challenge. Whenever persistent watery nasal discharge appears in a patient, rhinoliquorrhea must be considered. Endoscopic surgical reconstruction of the skull base is the therapeutic gold standard and should be attempted as soon as the diagnosis is secured.Hypothese: Rhinoliqurrhoe tritt häufig als Folge von spontanen Schädelbasisläsionen auf; diese Form der Rhinoliqurrhoe ist die am schwierigsten zu beherrschende.Methoden: Wir haben eine retrospektive Analyse aller Patienten durchgeführt, welche mit der Diagnose einer spontanen Rhinoliquorrhoe im Uniklinikum Bonn behandelt wurden.Ergebnisse: Insgesamt wurden zwölf Patienten in dieser Studie eingeschlossen. Im Mittel betrug die Zeit zwischen dem ersten Auftreten einer wässerigen Rhinorrhoe und der Diagnose einer spontanen Rhinoliqurrhoe 123 Tage. In zehn dieser Patienten konnte der Defekt mittel Computertomographie oder MR-Zisternographie dargestellt werden. Zehn Patienten wurden aufgrund der spontanen Rhinoliqurrhoe operiert, von denen neun auch im weiteren Verlauf beschwerdefrei blieben. Ein Patient benötigt einen Revisionseingriff, war hernach jedoch ebenfalls ohne weitere Episoden von Rhinoliqurrhoe.Schlussfolgerung: Spontane Rhinoliqurrhoe ist nach wie vor sowohl diagnostisch wie therapeutisch eine Herausforderung. Bei jedem Patienten, der sich mit wässriger Rhinorrhoe vorstellt, muss eine spontane Rhinoliqurrhoe in Betracht gezogen werden. Die endoskopische Rekonstruktion der Schädelbasis ist bis heute der therapeutische Goldstandard und sollte bei Diagnosestellung geplant werden

A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women

Objective: Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new biomarkers to correctly identify early knee OA. Method: We have created an analytics pipeline based on machine learning to identify small models (having few variables) that predict the 30-months incidence of knee OA (using multiple clinical and structural OA outcome measures) in overweight middle-aged women without knee OA at baseline. The data included clinical variables, food and pain questionnaires, biochemical markers (BM) and imaging-based information. Results: All the model

Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria.

OBJECTIVE: To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015. METHODS: PubMed was used as searching machine: Time period 2014/04/01-2015/05/01, MeSH term [Biomarker] AND [Osteoarthritis], Language; English, Full text available. Reviews were excluded. Only papers describing protein based biomarkers measured in human body fluids from OA patients were included. RESULTS: Biomarkers of joint tissue turnover, cytokines, chemokines and peptide arrays were measured in different cohorts and studies. Amongst those were previously tested biomarkers such as osteocalcin, Carboxy-terminal cross-linked fragment of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP). A majority of the biomarker were classified as I, B or B biomarkers according to the BIPED criteria. Work is continuing on testing biomarkers in OA. There is still a huge, unmet medical need to identify, test, validate and qualify novel and well-known biomarkers. A pre-requisite for this is better characterization and classification of biomarkers to their needs, which may not be reached before higher understanding of OA phenotypes has been gained. In addition, we provide some references to some recent guidelines from Food and Drug Administration (FDA) and European Medicines Agency (EMA) on qualification and usage of biomarkers for drug development and personalized medicine, which may provide value to the field