Hematologic parameters pinpointed a group of hospitalized patients who were most likely to benefit from baricitinib.
In the ACTT-2 study, patients hospitalized with COVID-19 who received remdesivir plus the immunomodulator baricitinib recovered sooner than those who received remdesivir alone (NEJM JW Infect Dis Dec 17 2020 and N Engl J Med Mar 4 2021; 384:795) Now, investigators report a post hoc analysis of ACTT-2 to assess whether a risk profile based on hematologic parameters (low absolute lymphocyte count, high absolute neutrophil count, and low platelet count at baseline) identifies a group most likely to benefit from baricitinib. This “ACTT risk profile” was derived from the ACTT-1 study, in which the profile predicted risk for clinical progression among hospitalized patients.
A total of 999 participants from ACTT-2 were included. Among participants at high risk for progression based on ACTT risk profile, baricitinib plus remdesivir was associated with lower mortality and better clinical outcomes than placebo plus remdesivir, even after adjustment for baseline oxygen requirements. Participants who received baricitinib had more-favorable changes in their hematologic parameters than those who received placebo.
COMMENT
Guidelines recommend adding baricitinib to dexamethasone in patients hospitalized with COVID-19 who have rapidly increasing oxygen requirements or who need high-flow oxygen, non-invasive ventilation, or mechanical ventilation. The current study finds that hematologic biomarkers provide information on which patients are most likely to benefit from baricitinib; it also highlights the need for discovering and incorporating patient-specific characteristics that go beyond oxygen requirement in making treatment decisions. However, because ACTT-2 did not include participants who received glucocorticoids for COVID-19 — now the standard of care for hospitalized patients requiring oxygen — we need more information on performance of biomarker-based approaches in patients receiving current therapies.
In patients with HFpEF compared to patients without HF, levels of the biomarker myeloperoxidase may be significantly higher.
Myeloperoxidase (MPO) levels are significantly higher in patients with heart failure with preserved ejection fraction (HFpEF) compared with those in individuals without HF, according to a study in the International Journal of Cardiology.
The meta-analysis evaluated metabolomic studies in HFpEF with a focus on MPO, derivatives of reactive oxidative metabolites (DROMs), and carnitine to determine whether they can differentiate HFpEF from HF with reduced ejection fraction (HFrEF) or non-HF.
A systematic search was performed in the Medline and PubMed databases for relevant clinical studies published in English from inception through May 25, 2023. The meta-analysis included 12 articles.
MPO levels were evaluated in 5 studies and were significantly (P <.001) increased in patients with HFpEF compared with non-HF individuals, with a pooled effect size of 0.705 (95% CI, 0.426-0.983) in the random effects meta-analysis. MPO levels were similar in the patients with HFpEF compared with patients with HFrEF, with a pooled effect size of 0.014 (95% CI, -0.123 to 0.152; P =.838).
Using a metabolomic ‘lens’ to evaluate HFpEF, this meta-analysis found that MPO is a significant biomarker of HF compared to non-HF.
Carnitine levels were evaluated in 4 studies, and the random effects meta-analysis showed that they were similar between the non-HF group and the HFpEF group, with a pooled effect size of 0.155 (95% CI, -0.241 to 0.550; P =.443). Carnitine levels were significantly increased (P <.0001) among patients with HFrEF compared with those with HFpEF.
Summary: Researchers discovered a biomarker that can predict the impact of early toxic stress on infant cognitive development and health. The study used F2-isoprostane, a marker for oxidative stress, to assess the effects of adversity on mothers and infants.
This biomarker, previously used in adults, showed a strong correlation with cognitive development in infants as young as one year old. This breakthrough provides a critical tool for early intervention in at-risk infants, potentially altering life trajectories.
Key Facts:
F2-isoprostane levels in mothers and infants can indicate the impact of toxic stress from early adversity on infant development.
High levels of this biomarker in infants correlate with lower cognitive development scores at one year old.
This discovery enables early detection and intervention for infants exposed to high levels of toxic stress, offering new insights into child development.
Source: Children’s Hospital of Los Angeles
While multiple studies have shown a relationship between adversity in early childhood and negative lifelong health effects on groups of people, no reliable measures exist to measure the impact of early adversity on the risk of individual children.
A joint exploratory study conducted by researchers at Children’s Hospital Los Angeles and Boston Children’s Hospital found that a standard biomarker could predict the risk of early toxic stress on the cognitive development and overall health of individual infants.
Their findings are published in PLOS Global Public Health.
An overload of toxic stress can disrupt and damage cell function.
Toxic stress is a prolonged, repeated and harmful overactivation of the body’s stress response. It literally can imprint itself on the body. An overload of toxic stress can disrupt and damage cell function. That can be caused by several factors, including adversity.
The groundbreaking Adverse Childhood Experiences (ACEs) study as well as several subsequent studies connected adversity— (psychological, physical or sexual abuse, parental violence, exposure to substance abuse, mentally ill or imprisoned household members) occurring in childhood as recalled by the adult—that is associated on average, with adult health-risk behaviors, chronic illness and shorter life span in a large population group.
More recent studies showed that high ACE scores in individuals did not necessarily predict worse disease risk later in life, as some may be more resilient and others more susceptible.
In children, studies have shown that early exposure to adversity-caused stressors can disrupt cognitive development, hormones and the immune system. But these studies also showed that the impacts of early adversity can be prevented by reducing the sources of stress, as well as buffered by building supportive relationships between children and their caregivers along with learning life and coping skills.
Measuring the toll of toxic stress
In this study, the researchers investigated if a standard biomarker could measure the effects of toxic stress stemming from adversity on mothers and their infants. The researchers measured levels of F2-isoprostane, a sensitive chemical biomarker that indicates cell disruption and damage from oxidative stress, in samples of blood from mothers and urine from infants.
Oxidative stress occurs when cells cannot properly process their waste products, known as free radicals, produced as the body processes food or reacts to environmental factors.
The researchers wanted to know if F2-isoprostane—which has been previously used to reliably measure the effects of oxidative stress in adults—could be used to measure the impact of stressors from adversity and connect these effects to the early development and neurocognitive outcomes of infants.
“In this exploratory study, we aimed to evaluate the individual effects from adversity experienced around the time of birth,” says Kameelah Gateau, MD, MS, neonatologist at Children’s Hospital Los Angeles and lead study author.
“We found a measure of the biological signature of toxic stress on infant brain development, something that no previous study has yet managed to accomplish. We believe that this sensitive and objective biomarker shows great promise in detecting how toxic stress affects the bodies and brains of children.”
Statistical analysis found that cumulative risk scores were correlated with higher F2-isoprostane levels in mothers and infants after six months in the study. The infants who had higher levels of this biomarker of damage from toxic stress at their two-month study visit were more likely to have lower scores on a standard test of child cognitive development when they were a year old.
The team also found that higher cumulative risk scores predicted a higher average level of the toxic-stress biomarker in the bodies of mothers during the one-year study.
The researchers suggested that the relationship between cumulative risk scores around the time of birth and higher maternal and infant stress biomarker levels at six months may reflect oxidative stress levels. The researchers also believe that this initial six-month window of development could be an optimal window of time that can reveal the physical impacts of early adversity in the body and brain.
Stress affects small bodies
The study, conducted at Children’s Hospital Los Angeles and Boston Children’s Hospital, followed 116 pairs of mothers and their infants under two months old and born after 36 weeks of gestation.
The mothers were assessed using a risk score composed of maternal mental health and demographic information including education, marital status and income. The researchers checked infant development at six and 12 months, measuring the levels of oxidative stress biomarker in samples of blood from mothers and urine from babies.
About 80% of the children in the study in Los Angeles identified as White or Latino, and in the Boston group about half identified as Black.
“The infants who had higher measures of biological stress when measured with this biomarker did worse on this learning test,” says Pat Levitt, Ph.D., Chief Scientific Officer at CHLA and study senior author.
“This could mean that the infants who had higher stress levels do worse on learning and retention. These effects are already appearing in 2-month-old infants but are even more apparent at the six-month mark.”
Abstract
Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life
Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings.
The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother.
The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks’ gestation.
Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants’ development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively.
Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04).
The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.
Precision medicine offers enormous opportunities for the improvement of clinical outcomes in cardiovascular medicine, and this is particularly relevant for patients with non–ST-segment elevated acute coronary syndromes (NSTE-ACS).1 However, the design and deployment of such diagnostic and therapeutic strategies requires a deep understanding of the pathophysiology of NSTE-ACS. Indeed, vascular inflammation is considered to be a fundamental mechanism behind atherosclerotic plaque rupture,2,3 a concept confirmed by recent clinical trials4,5 demonstrating the reduction of cardiovascular risk by targeting specific inflammatory pathways.6,7 To optimize such therapeutic interventions, there is an unmet need for the following: 1) to discover the most important druggable therapeutic targets; and 2) to develop new ways to guide the application of high-precision treatments to the right patient, at the most appropriate time, to be effective. Although imaging of disease activity offers unique opportunities to detect the vulnerable plaque and the vulnerable patient,8 strategies that combine imaging biomarkers with clinical risk factors, and potentially plasma and/or genetic biomarkers, have the potential to revolutionize precision medicine in acute cardiovascular medicine.9-12
In search of such therapeutic targets in acute coronary syndromes, cathepsin S (CTSS) has emerged.13 CTSS is 1 of an 11-member family of cysteine proteases found to be abundant in atherosclerotic plaques, where it seems to participate in cholesterol metabolism and apoptosis in smooth muscle cells and macrophages.14 Beyond its use as a target for novel therapeutics,13 CTSS has also emerged as a rational blood biomarker of prognostic value. Indeed, clinical studies have demonstrated a positive association between circulating CTSS and the risk of cardiovascular death.15
Although clinical risk stratification scores, like the GRACE (Global Registry of Acute Coronary Events) risk score, perform well in predicting all-cause mortality and/or myocardial infarction,1 it is unclear whether their performance can improve further by adding plasma biomarkers such as CTSS.
In this issue of the Journal of the American College of Cardiology, Stamatelopoulos et al16 explored the incremental value of circulating CTSS for the prognosis of patients with NSTE-ACS over and above the GRACE risk score. The study enrolled 1,112 patients with NSTE-ACS, in which serum CTSS levels were used to risk-stratify them for the primary endpoint of all-cause mortality and a secondary endpoint of cardiovascular death over an 8-year follow-up period.17 Patients in the highest CTSS quartiles displayed an increased prevalence of type 2 diabetes mellitus and left ventricular ejection fraction with progressively increasing high-sensitivity C-reactive protein, high-sensitivity troponin-T, and GRACE risk scores across all quartiles. Multivariable analyses revealed that patients in the highest quartile of CTSS had 2.58 times higher risk for cardiovascular death and 1.89 times higher risk for all-cause mortality compared with those in the lower quartiles. Importantly, the prognostic value of CTSS remained significant even after adjustment for the GRACE score, left ventricular ejection fraction, and high-sensitivity troponin-T.
This assessment is of clear clinical value; however, there are a few areas where additional insight would have been welcome. As a single-center, retrospective study, the findings may suffer from selection bias, and external validation in completely independent and ideally prospective cohorts is essential to ensure the generalizability of the findings. Furthermore, serial CTSS measurements might have allowed us to better appreciate the temporal relationship between CTSS levels and post–NSTE-ACS outcomes. Nevertheless, these findings provide impetus for the continued assessment of CTSS as a clinically relevant biomarker in other conditions in addition to NSTE-ACS,18 including dilated cardiomyopathy,19 atrial fibrillation,20 and others.
Over the last few decades, it has become clear that singular biomarkers for cardiovascular disease often fail to effectively translate into clinical practice in part because of an incomplete capturing of disease pathophysiology and poorly implemented performance benchmarks. This has introduced the need for a more holistic approach in biomarker development, which would include networks of biomarkers in the context of multi-omic panels.9 It is likely that the value of biomarkers like CTSS would be critical if used as part of such a multi-omic approach, which may also incorporate clinical risk factors, genetic information, and advanced imaging, integrated using prognostic modelling or artificial intelligence approaches. Integration of all of these approaches is essential for the introduction of precision medicine in clinical practice (Figure 1).12
Download FigureDownload PowerPointFigure 1 Present and Future of Risk Stratification, Leading to Precision MedicineCurrent clinical practice uses fragmented data for cardiovascular risk stratification, which includes clinical information, individual biomarkers, as well as imaging, assuming that the experienced clinician will weigh and interpret these multidimensional data when making decisions about the management of the patient. In the future, artificial intelligence (AI) is expected to be used to interpret digital information about the patient, multi-omic screening, and advanced image analysis tools, which will be integrated into prognostic models that will guide clinical care. Then we will have achieved implementation of precision medicine in clinical practice. CCTA = computed tomography angiography; CKD = chronic kidney disease; CMR = cardiac magnetic resonance; CVD = cardiovascular disease; FAI = fat attenuation index; GRACE = Global Registry of Acute Coronary Events; hsTnT = high-sensitivity troponin T; LVEF = left ventricular ejection fraction; ML = machine learning; NSTE-ACS = non–ST-segment elevation acute coronary syndromes; PET = positron emission tomography; T2DM = type 2 diabetes mellitus.
Overall, this elegant work by Stamatelopoulos et al16 provides the first clear evidence of the superiority of CTSS in stratifying long-term mortality risk in patients with NSTE-ACS beyond the GRACE risk score. This is in line with our current mechanistic understanding of the relationship between CTSS and atherosclerotic disease and paves the way for further investigations into the validity of CTSS as a prognostic biomarker in acute coronary syndromes, both as a stand-alone biomarker as well as part of multi-omic, multifactorial prognostic models that could transform clinical care in the near future.
Hi. I’m David Kerr, professor of cancer medicine from the University of Oxford.
As you know, I’ve believed for some time that ploidy (the number of sets of chromosomes in a cell) measurements have been largely overlooked in terms of the relative importance of prognostic markers for the whole range of different cancer types. One of my friends and colleagues, Prof Håvard Danielsen, from the University of Oslo, has established what I consider one of the best assays in the world for measuring ploidy and DNA content in tumors, and characterizing it from paraffin-embedded tissue. ‘It’s a very available system.
New Data on an Overlooked Biomarker
To this end, a really interesting study was recently reported in Science by Teresa Davoli and colleagues,[1] who looked at ploidy across a whole range of tumor types and tried to relate ploidy measurements to the hallmarks of cancer. A ploidy is also known as somatic copy number alterations (SCNAs), and [the authors] refined the definition of ploidy a little, into [SCNAs] that were predominantly focal or [SCNAs] that mainly correlated with whole-arm ploidy, or changes in DNA content in that way.
This was a fascinating study, in which they found that ploidy was indeed associated with prognosis, but also with signatures associated with proliferation, increased expression of the gene’s enzymes involved in control of proliferation and cell cycle—this was mainly for the focal SCNAs. The larger, long-arm, and chromosomal ploidy tended to be associated with reduced expression of immune signature and immune infiltration.
This is an important first step in showing that ploidy does correlate with drivers or hallmarks of cancer. There are some subtle differences that lead you toward increased proliferation or increased immune invasion, both of which work in terms of establishing the cancer.
The researchers then retrospectively analyzed ploidy levels in melanoma tumor specimens saved from two large trials using immune checkpoint inhibitors. What they showed was that aneuploid tumors (eg, elevated levels of SCNA) were indeed more resistant to immune blockade.
It’s a really fascinating new potential use of ploidy, which has been around for decades and has been much overlooked. Not only is it a prognostic marker and therefore gives us important information about the biological behavior of our patients’ tumors, but it may also be a predictive factor in that aneuploid tumors may be relatively resistant to immune checkpoint blockade.
[Because this study was conducted] retrospectively, there’s much work yet to be done. [However, it offers] a really interesting insight for a marker, which I think could be delivered relatively easily in a sophisticated way in every pathology lab in the world. It surprises me that we don’t measure ploidy more. [It is] another interesting insight—some beautiful basic science uncovering the subtle differences in ploidy, how it links to the different hallmarks of cancer, and how it may aid us in selecting patients who may benefit less from immune checkpoint inhibitors.
Thank you for listening. It will be really keen for you to have a look at the Science paper and post any comments that you may care to talk about. This is an unfinished story but one that must be followed up prospectively.
There are a large number of biomarkers with potential utility for early cancer detection from blood samples
Few biomarkers have been studied sufficiently with clinical validation to allow their use in combination for screening in the general population.
We used an iterative mapping review of 20,000 references, retrieving 3,990 relevant papers, and identified 788 markers in blood of potential use
Screening for cancer can save lives, but it is difficult to justify individual screening programmes for many cancer types. However, cancers of different types share many attributes, and markers of cancer biology found in the blood. We surveyed the literature to identify known biomarkers using a new mapping approach. With nearly 20,000 papers on the subject, we retrieved 3990 papers, and identified 788 markers in blood of potential use. Most have not been studied enough to justify their use in clinical practice. This evidence based approach should help us to develop a blood-based cancer screening test in the general population.
Abstract
Background
The Early Cancer Detection Consortium is developing a blood-test to screen the general population for early identification of cancer, and has therefore conducted a systematic mapping review to identify blood-based biomarkers that could be used for early identification of cancer.
Methods
A mapping review with a systematic approach was performed to identify biomarkers and establish their state of development. Comprehensive searches of electronic databases Medline, Embase, CINAHL, the Cochrane library and Biosis were conducted in May 2014 to obtain relevant literature on blood-based biomarkers for cancer detection in humans. Screening of retrieved titles and abstracts was performed using an iterative sifting process known as “data mining”. All blood based biomarkers, their relevant properties and characteristics, and their corresponding references were entered into an inclusive database for further scrutiny by the Consortium, and subsequent selection of biomarkers for rapid review. This systematic review is registered with PROSPERO (no. CRD42014010827).
Findings
The searches retrieved 19,724 records after duplicate removal. The data mining approach retrieved 3990 records (i.e. 20% of the original 19,724), which were considered for inclusion. A list of 814 potential blood-based biomarkers was generated from included studies. Clinical experts scrutinised the list to identify miss-classified and duplicate markers, also volunteering the names of biomarkers that may have been missed: no new markers were identified as a result. This resulted in a final list of 788 biomarkers.
Interpretation
This study is the first to systematically and comprehensively map blood biomarkers for early detection of cancer. Use of this rapid systematic mapping approach found a broad range of relevant biomarkers allowing an evidence-based approach to identification of promising biomarkers for development of a blood-based cancer screening test in the general population.
Scientists have discovered a unique protein that gives away the presence of inactive HIV in the body.
Sniffing out these hidden caches of the virus is something researchers have been trying to do for decades. Now that we have a lead, the finding could speed up research on a cure.
Thanks to modern antiretroviral therapies, for many people, HIV is not the death sentence it once was. But we still don’t have a reliable way of permanently flushing it out of someone’s system.
Drugs can keep the virus in check, but unfortunately HIV has a major weapon – it stows away in secret reservoirs in the immune system. There it lies dormant until conditions are more suitable to re-emerge.
That’s why people infected with HIV have to spend a lifetime on expensive drugs, because the virus can take only weeks to come back from its latent state if drug treatment is stopped.
Those nasty secret reservoirs HIV creates are located in long-lived immune cells known as resting T cells. Because the virus hijacks these cells and integrates its genetic material into the DNA of the patient, it makes reservoir T cells extremely hard to track down.
Now a team of French scientists has managed to achieve this important milestone in HIV research by discovering a biomarker that exists only on the surface of T cells that harbour the latent virus.
“Since 1996, the dream has been to kill these nasty cells in hiding, but we had no way to do it because we had no way to recognise them,” says virologist Monsef Benkirane from University of Montpellier in France.
Benkirane’s team discovered that a specific protein, called CD32a, hangs out on the surface of T cells with a latent HIV infection, but is not found on uninfected T cells, or even T cells with active HIV.
This is huge. Having CD32a as a biomarker for HIV reservoirs means scientists have a better chance to track them down in a patient’s blood. This paves the way for more research into the mechanisms that allow HIV to create such reservoirs in the first place.
Armed with such knowledge, scientists could then find ways to actually get rid of these HIV nests for good.
The team first detected the protein in a lab-made model of HIV infection, before moving on to test it as a biomarker in actual blood samples from 12 people who live with HIV and are receiving treatment.
They separated T cells with CD32a from other T cells in the blood samples, and found that the cells with this particular protein indeed had latent HIV harboured inside them.
Unfortunately, it’s not a smoking gun in every case, since the protein was found only on about half of all latently infected T cells.
Douglas Richman from University of California San Diego, who wasn’t involved in the research, writes that “the eradication of latent HIV would require a much greater reduction in the number of latently infected cells in the body.”
But it’s an extremely encouraging first step in the long search for a marker that could help us track down the nasty virus once it goes into hiding.
Tony Fauci, director of the US National Institute of Allergies and Infectious Disease, toldNature that a good next step would be to replicate the findings in more blood samples from a larger variety of patients who have the virus.
It’s still way too soon to say that we’re on the path to an actual HIV cure, but the news is super-exciting to researchers who have been hammering away at this problem for decades.
“I really hope this is correct,” says Fauci. “The fact that this work has been done by such competent investigators, and the data looks good, makes me optimistic.”
In a world where HIV continues to be a major health issue, this discovery indeed gives cause for optimism.
About 36.7 million people around the world live with HIV, but only 17 million have access to antiretroviral therapy, according to data from the US CDC.
The scientists have already filed a patent for the diagnostic and therapeutic use of the new biomarker.
What are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimize the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. “The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,” states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. “The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.” Dr. Osuch explains, “This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.”
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients. The hope is that one day there could be a definitive biological marker which could help differentiate the two disorders, leading to a faster diagnosis and optimal care.
In using a co-relative approach, a novel method in the field, Dr. Osuch uncovered results in patients that extend beyond verbal history and observation. These results may go on to change the way mental health is diagnosed, and subsequently treated, worldwide.
We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation.
RESULTS
Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P<0.001 for both comparisons). Plasma ST2 values at day 14 after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen.
CONCLUSIONS
ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation.
In patients with HFpEF compared to patients without HF, levels of the biomarker myeloperoxidase may be significantly higher.
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