Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Department.

BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Simian varicella virus infection and reactivation in rhesus macaques trigger cytokine and Aß40/42 alterations in serum and cerebrospinal fluid.

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aß42/Aß40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aß42/Aß40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aß42/Aß40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.

Treatment of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review and meta-analysis.

The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.

Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Clinical Significance of Apela in Acute Cardiorenal Insuffiency of Chronic Heart Failure.

INTRODUCTION: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. METHODS: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. RESULTS: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = -0.374) and 6-min walk distance (r = -0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. CONCLUSION: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

AIM: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. METHODS: In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. RESULTS: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. CONCLUSION: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Reference intervals for CTX and P1NP in a multi-ethnic Malaysian cohort.

BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

BACKGROUND: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS. METHODS: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants. RESULTS: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis. CONCLUSIONS: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. OBJECTIVES: The study aimed to identify predictors of end­stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. PATIENTS AND METHODS: A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin­3 [Gal­3], extracellular matrix metalloproteinases [MMP­2 and MMP­9], N­terminal pro-B­type natriuretic peptide [NT­proBNP], and high­sensitivity troponin T [hs­TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter­defibrillator intervention. RESULTS: During the median (interquartile range) follow­up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT­proBNP concentration (≥890.3 pg/ml), greater right ventricular end­diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. CONCLUSIONS: An NT­proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers.

The formation of toxic Amyloid ß-peptide (Aß) oligomers is one of the earliest events in the molecular pathology of Alzheimer's Disease (AD). These oligomers lead to a variety of downstream effects, including impaired neuronal signaling, neuroinflammation, tau phosphorylation, and neurodegeneration, and it is estimated that these events begin 10 to 20 y before the presentation of symptoms. Toxic Aß oligomers contain a nonstandard protein structure, termed α-sheet, and designed α-sheet peptides target this main-chain structure in toxic oligomers independent of sequence. Here we show that a designed α-sheet peptide inhibits the deleterious effects on neuronal signaling and also serves as a capture agent in our soluble oligomer binding assay (SOBA). Pre-incubated synthetic α-sheet-containing Aß oligomers produce strong SOBA signals, while monomeric and ß-sheet protofibrillar Aß do not. α-sheet containing oligomers were also present in cerebrospinal fluid (CSF) from an AD patient versus a noncognitively impaired control. For the detection of toxic oligomers in plasma, we developed a plate coating to increase the density of the capture peptide. The proof of concept was achieved by testing 379 banked human plasma samples. SOBA detected Aß oligomers in patients on the AD continuum, including controls who later progressed to mild cognitive impairment. In addition, SOBA discriminated AD from other forms of dementia, yielding sensitivity and specificity of 99% relative to clinical and neuropathological diagnoses. To explore the broader potential of SOBA, we adapted the assay for a-synuclein oligomers and confirmed their presence in CSF from patients with Parkinson's disease and Lewy body dementia.

Serum stratifin and presepsin as candidate biomarkers for early detection of COVID-19 disease progression.

The prognosis of patients with severe cases of COVID-19 is poor; thus, biomarkers for earlier prediction of COVID-19 progression are vital. We measured levels of five lung injury-related biomarkers, SP-D, KL-6, presepsin, kallistatin and stratifin, in serum samples collected serially during hospitalization from 31 patients with mild/moderate or severe/critical COVID-19 pneumonia, and their predictive performances were compared. Like the previously reported presepsin, a new biomarker candidate, stratifin, was significantly elevated with the onset of severe or critical symptoms in COVID-19 patients and decreased with symptom improvement. Notably, changes in stratifin and presepsin levels were distinctly earlier than those in SP-D, KL-6 and even SpO2/FiO2 values. Furthermore, serum levels of these biomarkers were significantly higher at the pre-severe stage (before the start of oxygen support) of patients who eventually advanced to severe/critical stages than in the patients who remained at the mild/moderate stage. These results were confirmed in an independent cohort, including 71 mild/moderate and 14 severe/critical patients, for whom the performance of stratifin and presepsin in discriminating between mild/moderate and pre-severe conditions of COVID-19 patients was superior to that of the SpO2/FiO2 ratio. Therefore, we concluded that stratifin and presepsin could be used as prognostic biomarkers for severe COVID-19 progression.

Study of the Role of Plasma NT-proBNP in the Diagnosis of Heart Failure.

BACKGROUND: The diagnosis of heart failure (HF) remains essentially clinical-Based. However, the history, physical examination, and chest radiograph findings are often inadequate in the diagnosis because multiple other conditions that affect the cardiopulmonary system mimic the symptoms of HF. N-terminal pro-BNP (NT-proBNP) has long been used for diagnosing HF. N-terminal pro-BNP values vary with different patient parameters. There is a scarcity of Indian studies on this topic. Especially with the use of newer drugs like angiotensin receptor neprilysin inhibitor (ARNI), it is important to have data from our own population on the same. AIMS AND OBJECTIVES: (i) To assess the role of NT-proBNP in the diagnosis of HF. (ii) Achieve diagnostic clarity in cases having cardiorespiratory symptoms and signs like acute onset dyspnea, pedal edema, and basal crepitations. (iii) To study the effect of various factors like age, body mass index (BMI), and creatinine on NT-proBNP. (iv) Establish a relation between NT-proBNP levels and left ventricular ejection fraction (LVEF), disease severity, and etiology of HF. MATERIALS AND METHODS: An observational prospective study of 50 patients presenting with acute onset breathlessness was carried out, fulfilling inclusion and exclusion criteria over a period of 10 months. Detailed history and examination of the patients were obtained. Venous sample for the measurement of NT-proBNP was collected within 24 hours of onset of symptoms. Other relevant blood and radiographic investigations were obtained. The NT-proBNP "cut-offs" set forth by the American Heart Association (AHA)/American College of Cardiology (ACC) were used to "rule in" or "rule out" HF. Two-dimensional echocardiography (2D Echo) was used to confirm the diagnosis. The correlation between NT-proBNP and various parameters like age, BMI, creatinine, and LVEF was obtained. Sensitivity and specificity tests were applied as well. RESULTS: Out of the 50 patients presenting with acute onset dyspnea, the most common cause was ischemic heart disease (IHD) (44%) followed by dilated cardiomyopathy (DCM) (32%), chronic obstructive pulmonary disease (COPD) (10%), anemia (4%), followed by other causes. The median NT-proBNP value was the highest for IHD patients (9485 pg/mL), followed by DCM (8969 pg/mL), followed by COPD (2846 pg/mL), and followed by anemia (850 pg/mL). There is a significant positive correlation between NT-proBNP and age (coefficient of correlation r = 0.4007, significance level p = 0.0389, and class interval = 0.137-0.61). There is a significant negative correlation between creatinine clearance and NT-proBNP (coefficient of correlation r = -0.372, significance level p = 0.007, and class interval = -0.58 to -0.105). There was significant negative correlation between LVEF and NT-proBNP (coefficient of correlation r = -0.36, significance level p = 0.009, and class interval = -0.58 to -0.09). Higher LVEF is associated with lower NT-proBNP values. There is marked heterogeneity in the values though. CONCLUSION: It is seen that the values of NT-proBNP vary with factors like age, BMI, and creatinine clearance in addition to LVEF. This may lead to falsely positive or falsely negative diagnosis of HF. With the above observations in mind, it can be concluded that NT-proBNP can help diagnose HF but only in addition to clinical findings.

Mid-regional proadrenomedullin, C-terminal proendothelin-1 values, and disease course are not different in critically ill SARS-CoV-2 pneumonia patients with obesity.

BACKGROUND/OBJECTIVES: Patients affected by obesity and Coronavirus disease 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have a higher risk for intensive care (ICU) admission. A state of low-grade chronic inflammation in obesity has been suggested as one of the underlying mechanisms. We investigated whether obesity is associated with differences in new inflammatory biomarkers mid-regional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and clinical outcomes in critically ill patients with SARS-CoV-2 pneumonia. SUBJECTS/METHODS: A total of 105 critically ill patients with SARS-CoV-2 pneumonia were divided in patients with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 42) and patients without obesity (BMI < 30 kg/m2, n = 63) and studied in a retrospective observational cohort study. MR-proADM, CT-proET-1 concentrations, and conventional markers of white blood count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were collected during the first 7 days. RESULTS: BMI was 33.5 (32-36.1) and 26.2 (24.7-27.8) kg/m2 in the group with and without obesity. There were no significant differences in concentrations MR-proADM, CT-proET-1, WBC, CRP, and PCT at baseline and the next 6 days between patients with and without obesity. Only MR-proADM changed significantly over time (p = 0.039). Also, BMI did not correlate with inflammatory biomarkers (MR-proADM rho = 0.150, p = 0.125, CT-proET-1 rho = 0.179, p = 0.067, WBC rho = -0.044, p = 0.654, CRP rho = 0.057, p = 0.564, PCT rho = 0.022, p = 0.842). Finally, no significant differences in time on a ventilator, ICU length of stay, and 28-day mortality between patients with or without obesity were observed. CONCLUSIONS: In critically ill patients with confirmed SARS-CoV-2 pneumonia, obesity was not associated with differences in MR-proADM, and CT-proET-1, or impaired outcome. TRIAL REGISTRATION: Netherlands Trial Register, NL8460.

A Conformational Variant of p53 (U-p53AZ) as Blood-Based Biomarker for the Prediction of the Onset of Symptomatic Alzheimer's Disease.

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer's disease (AD). OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years. DESIGN: Retrospective Longitudinal Prognostic biomarker study. SETTING: Single-center study based on the AIBL cohort. PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses. MEASUREMENTS: The AlzoSure® Predict test, consisting of immunoprecipitation (IP) followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS), was performed to quantify the AZ 284® peptide as readout of U-p53AZ and compared with an independent neuropsychological diagnosis. The amyloid load via amyloid ß-positron emission tomography (Aß-PET) and supporting clinical information were included where possible. RESULTS: U-p53AZ diagnostic and prognostic performance was assessed in both time-independent and time-dependent (36, 72 and 90 months following initial sampling) analyses. Prognostic performance of Aß-PET and survival analyses with different risk factors (gender, Aß-PET and APOE ε4 allele status) were also performed. U-p53AZ differentiated neuropsychologically graded AD from non-AD samples, and its detection at intermediate/high levels precisely identified present and future symptomatic AD. In both time-independent and time-dependent prognostic analyses U-p53AZ achieved area under the curve (AUC) >98%, significantly higher than Aß-PET AUCs (between 84% and 93%, P respectively <0.0001 and <0.001). As single factor, U-p53AZ could clearly determine the risk of AD neuropsychological diagnosis over time (low versus intermediate/high U-p53AZ hazard ratio=2.99). Proportional hazards regression analysis identified U-p53AZ levels as a major independent predictor of AD onset. CONCLUSIONS: These findings support use of U-p53AZ as blood-based biomarker predicting whether individuals would reach neuropsychologically-defined AD within six years prior to AD diagnosis. Integration of U-p53AZ in screening processes could support refined participant stratification for interventional studies.

Plasma presepsin level predicts acute kidney injury in patients with sepsis in the emergency department.

Acute kidney injury (AKI) is a common complication in patients with sepsis. We evaluated the potential prognostic value of plasma presepsin to predict AKI in patients with sepsis in the emergency department. A total of 193 patients diagnosed with sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in this observational study. AKI was defined according to the Kidney Disease Improving Global Outcomes clinical practice guideline. Plasma presepsin levels were measured on admission to the emergency department. We compared plasma presepsin levels between patients who did and those who did not develop AKI. AKI occurred in 100 (51.8%) patients. The median plasma presepsin level was significantly higher in patients with AKI than in those without AKI (1061 pg/mL vs 495 pg/mL, P <.001). Plasma presepsin levels were significantly increased in patients with AKI stage 3 compared with those with AKI stages 1 and 2 (P =.001). The area under the curve of presepsin for predicting AKI was 0.793 (95% confidence interval: 0.729-0.848). The optimal presepsin cutoff value for predicting AKI was >572 pg/mL, with a sensitivity of 77.0% and specificity of 81.7%. Plasma presepsin level is a valuable biomarker for the prediction of AKI in patients with sepsis in the emergency department.

Association between obstructive sleep apnea and Alzheimer's disease-related blood and cerebrospinal fluid biomarkers: A meta-analysis.

INTRODUCTION: Recent studies indicate that Alzheimer's disease- (AD) related biomarkers, including amyloid ß (Aß40 and Aß42) and tau proteins (P-tau and T-tau), in blood and cerebrospinal fluid (CSF) are associated with obstructive sleep apnea (OSA). However, the results have been inconsistent. Therefore, the primary purpose of this meta-analysis was to determine the relationship between blood and CSF AD-related biomarkers and OSA. METHODS: We searched the Embase, PubMed, Scopus, and Cochrane Library databases for relevant articles till February 2022. RESULTS: Eight articles were finally included after the literature screening, including 446 patients with OSA and 286 controls. Pooled analysis showed that CSF Aß42 (SMD = -0.220, P = 0.136), T-tau (SMD = 0.012, P = 0.89), and P-tau (SMD = 0.099, P = 0.274) levels were not different between patients with OSA and controls. In patients with moderate to severe OSA, CSF Aß42 (SMD = -0.482, P = 0.031) were significantly lower than in controls. Blood T-tau (SMD = 0.560, P = 0.026), P-tau (SMD = 0.621, P < 0.001), and Aß40 (SMD = 0.656, P < 0.001) levels were significantly higher in patients with OSA than in controls. Blood Aß42 (SMD = 0.241, P = 0.232) were not different between patients with OSA and controls. CONCLUSION: OSA is associated with changes in AD-related markers. Higher OSA severity may be associated with the development of AD. AD-related biomarkers, especially in the blood, are clinically efficient, less invasively assessed and monitored, and may be useful for detecting OSA and related cognitive impairments. Further studies are needed to confirm these results.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.