Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients

Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p <0.05) as well as in later stages of CKD (p <0.05). CVD was also more common in patients in early stage CKD. In early stages CKD, Cat S and CVD were positively correlated. Conclusion: These findings suggest that serum Cat S might be useful as an early biomarker for CVD in CKD patients.

Deficits in color detection in patients with Alzheimer disease

Deficits in color vision and related retinal changes hold promise as early screening biomarkers in patients with Alzheimer’s disease. This study aimed to determine a cut-off score that can screen for Alzheimer’s dementia using a novel color vision threshold test named the red, green, and blue (RGB) modified color vision plate test (RGB-vision plate). We developed the RGB-vision plate consisting of 30 plates in which the red and green hues of Ishihara Plate No.22 were sequentially adjusted. A total of 108 older people participated in the mini-mental state examination (MMSE), Ishihara plate, and RGB-vision plate. For the analyses, the participants were divided into two groups: Alzheimer’s dementia (n = 42) and healthy controls (n = 38). K-means cluster analysis and ROC curve analysis were performed to identify the most appropriate cut-off score. As a result, the cut-off screening score for Alzheimer’s dementia on the RGB-vision plate was set at 25, with an area under the curve of 0.773 (p<0.001). Moreover, there was a negative correlation between the RGB-vision plate thresholds and MMSE scores (r = -0.36, p = 0.02). In conclusion, patients with Alzheimer’s dementia had a deficit in color vision. The RGB-vision plate is a potential early biomarker that may adequately detect Alzheimer’s dementia.

Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial

ClinicalTrials.gov identifier (NCT number): NCT03852537, Registered February 25, 2019.

Ocular Vascular Changes: Choroidal Thickness as an Early Biomarker for Alzheimer’s Disease?

Alzheimer’s disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia among the elderly [...]

The effect of two different types of forces on possible root resorption in relation to dentin phosphoprotein levels: a single-blind, split-mouth, randomized controlled trial

Background The purpose of this 2-arm-parallel split-mouth trial was to evaluate and compare the extent of possible root resorption using dentin phosphoprotein levels in gingival crevicular fluid between controlled continuous and intermittent orthodontic force groups. Materials and methods A sample of 16 maxillary first premolars from 8 patients requiring bilateral extractions of the upper first premolars as part of their orthodontic treatment were recruited. A buccally directed continuous force of 150 g, reactivated after 28 days, was applied to the upper first premolar on one side for 8 weeks. On the contralateral first premolar, a buccally directed intermittent force (21 days on, 7 days off) of the same magnitude was applied for the same period. Gingival crevicular fluid samples were collected at the beginning of the study, 1st, 3rd, 4th and 5th week, and at the end of the study to quantify and compare dentin phosphoprotein levels in both groups. Results Dentin phosphoprotein levels showed a higher concentration in the continuous force group than the intermittent force group in week 4 and 8 of sample collection; where the differences were statistically significant (95% CI 0.007–0.14; P < .04) and (95% CI 0.02–0.17; P < .04) respectively. No harm was observed. Conclusions Dentin phosphoprotein was found to be a useful early biomarker to detect and monitor root resorption, showing that the application of an intermittent orthodontic force caused less root resorption than a continuous force. Trial registration NCT04825665 ClinicalTrials.gov. Registered 1 April 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04825665.

Older adults show biomarker evidence of PICS after sepsis

Background Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in a) older (versus young) adults and b) older CCI (versus older RAP) patients to gain insight into underlying pathobiology of CCI in older adults. Methods Prospective longitudinal study with young (≤ 45 years) and older (≥ 65 years) septic adults who were characterized by a) baseline predisposition, b) hospital outcomes, c) serial SOFA organ dysfunction scores over 14 days, d) Zubrod Performance status at three, six and 12-month follow-up and e) mortality over 12 months. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS. Results Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status and mortality over 12 months. Additionally, older (versus young) and older CCI (versus older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism and anti-angiogenesis over 14 days after sepsis. Conclusion Older (versus young) and older CCI (versus older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS.

Early and rapid identification of COVID-19 patients with neutralizing type I-interferon auto-antibodies by an easily implementable algorithm

Purpose Six-19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions. Methods We analysed sera of 430 COVID-19 patients with severe and critical disease from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome. Results The prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected, predominantly male (83%) patients (7.6% IFN-α and 4.6% IFN-ω in 207 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with higher mortality (92.3% versus 19.1 % in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE. Conclusion IFN-AABs may serve as early biomarker for development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients according to our algorithm for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.

Cystatin C and Iris: Advances in the Evaluation of Kidney Function in Critically Ill Dog

Critically ill hospitalized dogs are subject to certain complications, being acute kidney injury (AKI) a common one. Early diagnosis is crucial, and Cystatin C (CysC) is a reliable and early biomarker. The International Society of Renal Interest (IRIS) states that AKI severity can be assessed by mild changes in creatinine serum levels or reduction of urine output that cannot be considered biomarkers of renal injury but failure or insufficiency. Twenty-eight dogs admitted to the Intensive Care Unit under risk factors for the development of AKI were evaluated. Blood samples were collected for determination of sCr and CysC at admission and after 24, 48, and 72 h. Urine output was measured by daily monitoring, measured by collection in a closed system. The results showed the incidence of AKI was 67.9% based on the IRIS criteria and 78.6% based on cystatin C in critically ill patients' dogs. The measurement of serum cystatin C immediately on admission to the ICU was superior in the early identification of patients with AKI when compared to the IRIS classification and serum creatinine in critically ill dogs.