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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.
Yu Chen, H, Dina, C, Small, AM, Shaffer, CM, Levinson, RT, Helgadóttir, A, Capoulade, R, Munter, HM, Martinsson, A, Cairns, BJ, et al
European heart journal. 2023;44(21):1927-1939
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Aortic stenosis (AS) is a form of heart disease that is an abnormal narrowing of the aortic valve in the heart, which restricts blood flow. Although being over the age of 75 appears to increase the risk for development, it is unclear as to who else may be at risk. A better understanding of genetic factors, which may be involved in its development could better help to identify those at risk. This meta-analysis of 10 cohort studies aimed to determine genetic contributors to AS and possible mechanisms involved. The results showed that 15 different gene variations were strongly associated with AS including those in the CELSR2-SORT1, NLRP6, LPA and SMC2 genes. Interestingly some of these genes were also identified in individuals with African and Latin American ancestry. It was concluded that these genes, many of which are associated with hardening of the arteries, altered lipid metabolism, excess storage of fat, and inflammation may all contribute to AS. This study could be used by healthcare professionals to understand that there are specific genetic contributors to the development of AS and that in the future we may be able to target these to identify high-risk individuals and use them in therapeutic management.
Abstract
AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
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Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.
Al-Horani, RA, Kar, S
Viruses. 2020;12(10)
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The covid-19 pandemic has required the identification of therapies to prevent infection and limit severity. A previous paper by the same authors reviewed therapies that block the virus in the early stages of its lifecycle. This very large review of over 300 papers aimed to summarise therapeutics which are aimed at blocking the lifecycle of the virus after it has entered the body’s cells. The authors began by reviewing the lifecycle of the covid-19 virus explaining how it enters the body’s cells, replicates inside and then is released to infect new cells. Several antivirals, antimalarials and natural products were then reviewed. Of note, Remdesivir is being trialled in covid-19 patients, with mixed results, however, is being recommended in the US for the treatment of hospitalised covid-19 patients with severe disease. Ribavirin, which is being trialled in combination with other antivirals is also showing promising results in shortening hospitalisation times in covid-19 patients. It was concluded that any stage of the covid-19 lifecycle could be a target for therapeutics and combining therapies is likely to be more successful than monotherapy. This paper could be used by health care professionals to understand the most recent therapeutic research for covid-19.
Abstract
The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.
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COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.
Thomas, T, Stefanoni, D, Reisz, JA, Nemkov, T, Bertolone, L, Francis, RO, Hudson, KE, Zimring, JC, Hansen, KC, Hod, EA, et al
JCI insight. 2020;5(14)
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There is increasing urgency for the development of Covid-19 therapies. Treatments preventing infection and decreasing the amount of virus in the body have largely been unsuccessful and so the focus has turned to host biological pathways, which may be altered by Covid-19 infection. This observational study of forty-nine Covid-19 positive and negative individuals aimed to determine alterations in the hosts metabolism. The results showed that Covid-19 infection was associated with disrupted host inflammatory and immune pathways. Markers for kidney dysfunction were also increased alongside raised blood sugar levels and fatty acids in the blood. It was concluded that inflammatory markers may be an indicator for disease severity and a target for Covid-19 therapy. Dietary therapy could be used to target blood fatty acid changes brought about by Covid-19 infection. This study could be used by healthcare professionals to understand that inflammation is increased in Covid-19 patients and in lieu of approved therapies, dietary intervention may be of benefit.
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.
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Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Heneka, MT, Golenbock, D, Latz, E, Morgan, D, Brown, R
Alzheimer's research & therapy. 2020;12(1):69
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Covid-19 may cause brain dysfunction evidenced by symptoms individuals experience once they have contracted the disease. Loss of smell, taste and confusion have all been reported by patients and a number of severe cases have reported incidences of stroke. These are all of concern, as Covid-19 can severely affect the elderly who ordinarily are the most likely to suffer from brain disorders. This small review paper of 27 studies stated that there are four possible ways in which Covid-19 may affect the brain, which put Covid-19 sufferers at an increased risk of long-term brain disorders. This was supported by findings, which showed one third of Covid-19 patients leave hospital with evidence of brain dysfunction. Inflammation was heavily reviewed by the authors as a possible causal factor. It was concluded that patients who survive Covid-19 infection are at an increased risk for developing brain disorders such as Alzheimer's disease, however it was acknowledged that further studies are required. Clinicians could use this study to understand the possible need for both short-term and long-term monitoring of brain function in individuals who have survived Covid-19, especially if they are elderly.
Abstract
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.
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Effects of Roux-en-Y Gastric Bypass on Osteoclast Activity and Bone Density in Morbidly Obese Patients with Type 2 Diabetes.
Tangalakis, LL, Tabone, L, Spagnoli, A, Muehlbauer, M, Omotosho, P, Torquati, A
Obesity surgery. 2020;30(1):290-295
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Gastric surgery and the resultant weight loss can improve an individual’s outcomes in a number of diseases, such as heart disease and type 2 diabetes, however an unfortunate side effect is bone loss. Roux-en-Y gastric bypass is a process whereby the size of your stomach is significantly reduced, and it is unclear as to the effect this type of surgery has on bone density. This cohort study of sixty-one individuals who underwent Roux-en-Y gastric bypass aimed to determine the effect on bone density one year post surgery. The results showed that following surgery, bone resorption was increased compared to control and although bone density was similar between the two groups, bone mineral content and bone surface area were decreased. Women who were post-menopausal demonstrated diminished bone health, although this was not significant. It was concluded that Roux-en-Y gastric bypass surgery results in a negative impact on bone health. This study could be used by healthcare professionals to understand the importance of considering bone health when recommending surgery, especially in those at high-risk of bone loss such as post-menopausal women.
Abstract
INTRODUCTION Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown. OBJECTIVE Determine the changes in osteoclast function and bone density 1 year after RYGB as compared with a control group undergoing a diabetes support and education program (DSE). DESIGN A prospective cohort study with patients matched for weight and age assigned to RYGB or DSE. SETTING Large academic institution. PATIENTS OR OTHER PARTICIPANTS Patients with type 2 diabetes mellitus and morbid obesity (body mass index greater than 35 kg/m2). INTERVENTION Subjects either received laparoscopic RYBG or DSE, which consisted of nutritional, exercise, and dietary counseling performed by a certified diabetic educator and a nutritionist three times over a year. MAIN OUTCOME MEASURE Osteoclast activity, bone mineral density. RESULTS One year after, intervention subjects undergoing RYGB have a 280% increase in osteoclast activity as compared with a 7.6% increase in the DSE control group (P < 0.001). Furthermore, there was a statistically significant increase in sclerostin levels in subjects undergoing RYGB compared with an increase in the control group. The total bone mineral density was statistically unchanged within 1 year of intervention in both groups. A statistically significant decrease in bone mineral density in the left ribs (decrease of 6.8%, P < 0.05) and lumbar spine (decrease of 4.0%, P < 0.05) was seen 1 year after RYGB. CONCLUSIONS There is a significant increase in osteoclast activity observed 1 year after RYGB; the long-term clinical implications of this increased bone metabolism are unknown.
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Plant-Based Diets Are Associated With a Lower Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality in a General Population of Middle-Aged Adults.
Kim, H, Caulfield, LE, Garcia-Larsen, V, Steffen, LM, Coresh, J, Rebholz, CM
Journal of the American Heart Association. 2019;8(16):e012865
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Plant based diets have been associated with better health outcomes, however mixed results have been shown on their relationship with death by any cause and death due to heart disease. This cohort study of 15792 middle aged people aimed to determine if plant-based diets are associated with a lower risk of heart disease, death due to heart disease or death due to any cause and whether this was on a sliding scale depending on adherence to a healthful plant-based diet. The results showed that individuals following a plant-based diet had a 16% lower risk of heart disease, 32% lower risk of death due to heart disease and a 25% lower risk of death by any cause and individuals who followed a healthier plant-based diet were at an even lower risk of heart disease, death due to heart disease and death due to any cause. Interestingly when margarine was included in an individual’s diet, the decreased risk of heart disease was attenuated. It was concluded that higher adherence to a healthy plant-based diet was associated with a lower risk of heart disease, death due to heart disease and death by any cause. This study could be used by healthcare practitioners to recommend a plant-based diet to those at an increased risk of heart disease.
Abstract
Background Previous studies have documented the cardiometabolic health benefits of plant-based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community-based cohort of middle-aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants' diet was classified using 4 diet indexes. In the overall plant-based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant-based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant-based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant-based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant-based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all-cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant-based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population.
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Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis.
Jutras, BL, Lochhead, RB, Kloos, ZA, Biboy, J, Strle, K, Booth, CJ, Govers, SK, Gray, J, Schumann, P, Vollmer, W, et al
Proceedings of the National Academy of Sciences of the United States of America. 2019;116(27):13498-13507
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Lyme disease is a varied, multisystem disorder caused by the spiral-shaped bacteria Borrelia burgdorferi (Bb). Advanced stages of the disease can present with oligoarthritis, most commonly involving the knee joints. Peptidoglycan (PG) is a compound that makes up the cell envelope of Bb and other bacteria. It acts as a microbe-associated molecular pattern, which can trigger the immune system and induces pro-inflammatory responses. This article summarises a series of cell, human, and animal studies supporting the theory that PG is a contributor to persistent Lyme’s arthritis (LA) far beyond the eradication of the pathogen. Significantly elevated inflammatory markers as well as antibodies to PG and Bb itself have been found in patients with LA before and after antibiotic therapy. The inflammatory response to Bb PG seems to be particularly high when compared to other bacteria. In summary, the authors suggest that PG accumulation in the joints and subsequent persistent inflammation contribute to LA and that targeting the specific inflammatory pathways involved may yield potential therapeutic interventions. This article could be of interest to those looking to understand more about the mechanisms and specific inflammatory responses involved in LA.
Abstract
Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of the B. burgdorferi cell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show that B. burgdorferi has a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBb fragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient. We also detect PGBb in 94% of synovial fluid samples (32 of 34) from patients with LA, many of whom had undergone oral and intravenous antibiotic treatment. These same synovial fluid samples contain proinflammatory cytokines, similar to those produced by human peripheral blood mononuclear cells stimulated with PGBb In addition, systemic administration of PGBb in BALB/c mice elicits acute arthritis. Altogether, our study identifies PGBb as a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.
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Inflammaging and the Lung.
Kovacs, EJ, Boe, DM, Boule, LA, Curtis, BJ
Clinics in geriatric medicine. 2017;33(4):459-471
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Characteristic of ageing is the presence of inflammatory markers in the blood and lead to the term inflammageing being coined. Inflammatory markers may contribute to chronic disease such as diseases of the lung. This review of 122 papers aimed to address the role of inflammageing on the lungs. The paper discussed the changes that the lungs immune cells go through with ageing and the impairment that they experience, with inflammageing playing a role. Causes of inflammageing were discussed and gut permeability, the halting of cell division and the stimulation of larger molecules in the body to release inflammatory markers were all implicated. Gut permeability which is a newer area of research with regards to inflammageing, was extensively discussed and allows more bacteria and pathogens into the body causing an inflammatory reaction. It was concluded that reducing inflammageing is a target for treatments in the elderly, whether these directly target inflammation or the underlying cause, requires more research. This paper could be used by healthcare professionals as a basis to understand inflammageing and where it may be appropriate to target inflammation in the elderly.
Abstract
With the coming of the "silver tsunami," expanding the knowledge about how various intrinsic and extrinsic factors affect the immune system in the elderly is timely and of immediate clinical need. The global population is increasing in age. By the year 2030, more than 20% of the population of the United States will be older than 65 years of age. This article focuses on how advanced age alters the immune systems and how this, in turn, modulates the ability of the aging lung to deal with infectious challenges from the outside world and from within the host.
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Tracking post-infectious fatigue in clinic using routine Lab tests.
Harvey, JM, Broderick, G, Bowie, A, Barnes, ZM, Katz, BZ, O'Gorman, MRG, Vernon, SD, Fletcher, MA, Klimas, NG, Taylor, R
BMC pediatrics. 2016;16:54
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Chronic fatigue syndrome (CFS) is a complex disease with many different symptoms and there are no definitive tests for diagnosis. This cohort study of 301 adolescents, who had suffered a viral infection, aimed to analyse several commonly used biological markers to determine who may experience CFS symptoms. The results showed variations in several biomarkers, however, decreases in hormones related to the stress response were highly predictive of CFS. Sex hormones and the proportion of immune cells were also markedly disrupted. It was concluded that assessing stress hormones, sex hormones and the proportion of immune cells could be used to diagnose CFS following a viral infection. This study could be used by healthcare professionals to understand that several commonly tested biomarkers could be potentially used to diagnose post-viral CFS.
Abstract
BACKGROUND While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis. Classification models separating PI-CFS from controls were constructed at each time point using stepwise subset selection. RESULTS Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM.
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Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study.
Wesa, KM, Cunningham-Rundles, S, Klimek, VM, Vertosick, E, Coleton, MI, Yeung, KS, Lin, H, Nimer, S, Cassileth, BR
Cancer immunology, immunotherapy : CII. 2015;64(2):237-47
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Myelodysplastic syndromes (MDS) are a group of bone marrow stem cell disorders characterized by ineffective red blood cell production, a reduction in mature blood cells and may progress to acute myelogenous leukaemia (AML). Low levels and poor function of white blood cells, a key part of the immune system, are a common feature of MDS and this increases the risk of serious infection, the most common cause of death in lower-risk MDS patients. Maitake had previously been shown to enhance blood forming cells and was therefore thought to be of potential benefit for MDS patients. The aim of this phase II, open-label, non-randomized, safety and efficacy trial was to assess white blood cells function in lower-risk MDS patients. 18 untreated patients received Maitake extract at 6 mg/kg daily for 12 weeks. The function of two types of white blood cells, neutrophils and monocytes,increased after 12 weeks of maitake administration. Maitake was generally well tolerated although a mild increase in eosinophils, a type of white blood cells associated with allergies, was noted in four patients, and two of these patients also experienced mild diarrhoea. The authors concluded that maitake beta-glucan consumption improves white blood cell (neutrophil and monocyte) function in lower-risk MDS patients and may enhance immune responses against bacterial infection. They point out that one limitation of their trial was a lack of control group and that larger studies are needed to confirm the potential benefits of maitake.
Abstract
BACKGROUND Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS. METHODS Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated. RESULTS Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant. CONCLUSIONS Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.