Automated labelling of radiology reports using natural language processing: Comparison of traditional and newer methods.

Automated labelling of radiology reports using natural language processing allows for the labelling of ground truth for large datasets of radiological studies that are required for training of computer vision models. This paper explains the necessary data preprocessing steps, reviews the main methods for automated labelling and compares their performance. There are four main methods of automated labelling, namely: (1) rules-based text-matching algorithms, (2) conventional machine learning models, (3) neural network models and (4) Bidirectional Encoder Representations from Transformers (BERT) models. Rules-based labellers perform a brute force search against manually curated keywords and are able to achieve high F1 scores. However, they require proper handling of negative words. Machine learning models require preprocessing that involves tokenization and vectorization of text into numerical vectors. Multilabel classification approaches are required in labelling radiology reports and conventional models can achieve good performance if they have large enough training sets. Deep learning models make use of connected neural networks, often a long short-term memory network, and are similarly able to achieve good performance if trained on a large data set. BERT is a transformer-based model that utilizes attention. Pretrained BERT models only require fine-tuning with small data sets. In particular, domain-specific BERT models can achieve superior performance compared with the other methods for automated labelling.

Seahorse brood pouch morphology and control of male parturition in Hippocampus abdominalis.

INTRODUCTION: Syngnathids (seahorses, pipefishes and seadragons) are among the few vertebrates that display male pregnancy. During seahorse pregnancy, males incubate developing embryos embedded in a placenta within a fleshy brood pouch, before expelling fully developed neonates at parturition. The mechanisms underpinning seahorse parturition are poorly understood. METHODS: We examined the morphology of the brood pouch using microcomputed tomography and histological techniques, in combination with physiological assays, to examine how male pot-bellied seahorses (Hippocampus abdominalis) control labour. In female-pregnant vertebrates, nonapeptide hormones (such as vasopressin- and oxytocin-like hormones) produce contractions of gestational smooth muscle to produce labour. RESULTS: Histological analysis of the seahorse brood pouch reveals only scattered small smooth muscle bundles in the brood pouch, and in-vitro application of isotocin (a teleost nonapeptide hormone) to the brood pouch do not produce measurable muscle contractions. Micro-computed tomography shows differences in size and orientation of the anal fin assembly between male and female pot-bellied seahorses, and histological analysis reveals large skeletal muscle bundles attached to the anal fin bones at the male brood pouch opening. DISCUSSION: We conclude that seahorse parturition may be facilitated by contraction of these muscles, which, in combination with body movements, serves to gape open the pouch and expel the neonates. Future biomechanical studies are needed to test this hypothesis.

The biological feasibility and social context of gene-edited, caffeine-free coffee.

Coffee, especially the species Coffea arabica and Coffea canephora, is one of the world's most consumed beverages. The consumer demand for caffeine-free coffee is currently being met through chemical decaffeination processes. However, this method leads to loss of beverage quality. In this review, the feasibility of using gene editing to produce caffeine-free coffee plants is reviewed. The genes XMT (7-methylxanthosine methyltransferase) and DXMT (3,7-dimethylxanthine methyltransferase) were identified as candidate target genes for knocking out caffeine production in coffee plants. The possible effect of the knock-out of the candidate genes was assessed. Using Agrobacterium tumefaciens-mediated introduction of the CRISPR-Cas system to Knock out XMT or DXMT would lead to blocking caffeine biosynthesis. The use of CRISPR-Cas to genetically edit consumer products is not yet widely accepted, which may lead to societal hurdles for introducing gene-edited caffeine-free coffee cultivars onto the market. However, increased acceptance of CRISPR-Cas/gene editing on products with a clear benefit for consumers offers better prospects for gene editing efforts for caffeine-free coffee.

A meta-analysis on the presentation of Unicystic Ameloblastoma in the jaws and the consequences for their treatment.

INTRODUCTION: This meta-analysis provides reliable data on the prevalence of unicystic ameloblastomas (UA's) among solid/multicystic ameloblastomas (SMA's), as well the ratio of their presence in the maxilla and mandible and in the tooth-bearing area versus the posterior regions of the mandible, including the third molar region and ascending ramus. MATERIAL AND METHODS: A systematic review and meta-analysis was performed according to PRISMA guideline using the strategy ((unicystic ameloblastoma) OR (((ameloblastoma) OR (solid ameloblastoma)) OR (multicystic ameloblastoma))) NOT ((((systematic review) OR (literature review)) OR (case report)) OR (Immunohistochemical)). DISCUSSION: The study included 3856 SMA's and 1537 UA's, which amounted to 28.5% UA's. Of the 380 cases of UA from twelve articles that mentioned the involved jaws, 355 were in the mandible and 25 in the maxilla. The preponderance for the mandible is much higher than reports from previous studies of smaller series. Only five articles mentioned the location within the mandible. The vast majority was in the posterior area. CONCLUSION: The consequences for treatment were discussed, with an emphasis on the approach to unicystic lesions in the posterior part of the mandible for which a protocol is suggested.

Cyst or Tumor? A systematic review and meta-analysis on the expression of p53 marker in Odontogenic Keratocysts.

The odontogenic keratocyst (OKC) is a potentially aggressive odontogenic lesion and there is an ongoing debate regarding its biological behavior and classification. The present systematic review aims to assess the expression of the p53 protein in the odontogenic keratocyst in comparison to the dentigerous cyst and ameloblastoma. We searched MEDLINE, Web of Science and Scopus for immunohistochemical studies reporting OKC's, dentigerous cysts and solid/multicystic ameloblastomas. The Risk Difference between the lesions expressing the p53 was the effect measure and a P value < 0.05 was considered to provide evidence to the effect estimates. Results: The first hit retrieved 126 records. After duplicates removal, there were 84 articles, of which eighteen were assessed for eligibility. Thirteen articles were included in the meta-analysis, showing that OKC's have an estimated difference of 23% (P < 0.003) in the probability to express the p53 over dentigerous cysts, and an estimated difference of 4% (P = 0.28) in the probability to express the p53 over ameloblastomas. OKCs seem to behave more similarly to a tumor rather than an odontogenic cyst regarding its p53 expression and the classification of this lesion into Keratocystic Odontogenic Tumor should be carefully revaluated.

Characterization of the Habitat- and Season-Independent Increase in Fungal Biomass Induced by the Invasive Giant Goldenrod and Its Impact on the Fungivorous Nematode Community.

Outside its native range, the invasive plant species giant goldenrod (Solidago gigantea) has been shown to increase belowground fungal biomass. This non-obvious effect is poorly characterized; we don't know whether it is plant developmental stage-dependent, which fractions of the fungal community are affected, and whether it is reflected in the next trophic level. To address these questions, fungal assemblages in soil samples collected from invaded and uninvaded plots in two soil types were compared. Although using ergosterol as a marker for fungal biomass demonstrated a significant increase in fungal biomass, specific quantitative PCR (qPCR) assays did not point at a quantitative shift. MiSeq-based characterization of the belowground effects of giant goldenrod revealed a local increase of mainly Cladosporiaceae and Glomeraceae. This asymmetric boost in the fungal community was reflected in a specific shift in the fungivorous nematode community. Our findings provide insight into the potential impact of invasive plants on local fungal communities.

Percutaneous Cervical Cordotomy for the Treatment of Cancer Pain: A Prospective Case Series of 52 Patients with a Long-Term Follow-Up.

AIM: The aim of this study is to describe the effects of percutaneous cervical cordotomy (PCC) on pain, opioid consumption, adverse events, and satisfaction in palliative care patients with cancer pain after PCC until end of life. METHODS: This is a prospective observational case series of 58 PCCs in 52 consecutive patients. Indication for PCC was unilateral cancer pain with a maximum numeric rating scale (NRS) of pain above 5 despite maximal conservative treatment. The PCC was fluoroscopy guided. A radiofrequency lesion was made at 95°C for 20 seconds. The pain location and pain scores, analgesic medication, the cranial and caudal borders of dermatomes hypoesthetic for pin pricks, dysesthesia, urinary retention, Horner's syndrome, muscle strength, Karnofsky performance scale (KPS) score, patient satisfaction, hospital anxiety and distress score (HADS), and RAND 36 score were evaluated at 1 day; 1 and 6 weeks; and 3, 6, 9, 12 18, and 24 months after PCC, or until death if death occurred during the follow-up period. RESULTS: Pain relief after PCC was intense (change in median maximum NRS from 9 to 0) and persistent. Median opioid use per day was 240 mg (145 to 565 mg) before PCC and 55 mg (0 to 120 mg) after PCC. The upper and lower borders of dermatomes hypoesthetic for pin pricks were stable over time. The most common side effects were short-term (< 1 week) neck pain (28%), dysesthesia (40%), and mild loss of muscle strength (11%). Approximately 83% of the patients were satisfied or very satisfied with the results of PCC 1 week after the procedure, and this percentage remained high in the long term. There was no significant change in the KPS score, HADS, and RAND 36 score. CONCLUSION: Percutaneous cervical cordotomy is an effective treatment for unilateral cancer pain. The reduction in pain, reduction in opioid consumption, and hypoesthetic area remain stable until death.

The presentation of odontogenic keratocysts in the jaws with an emphasis on the tooth-bearing area: a systematic review and meta-analysis.

PURPOSE: This study was conducted in order to gain insight in the actual ratio of odontogenic keratocysts occurring in the tooth-bearing area as compared to the posterior region of the jaws in order to come up with reliable data to base upon a rational treatment policy. METHODS: We searched MEDLINE, Web of Science, Scopus, and Cochrane databases for studies reporting on the location of mandibular and maxillary odontogenic keratocysts. All records were independently assessed and a meta-analysis was performed. Risk difference with a confidence interval of 95% of having the lesion in the posterior region versus the tooth-bearing area was the effect measure. P value for the summary effect of < 0.05 was considered statistically significant. RESULTS: The 2615 records retrieved were reduced to 34 studies to be qualitatively/quantitatively assessed. The pooled values showed that the difference in the clinical risk of having keratocysts in the posterior region of the mandible and in the tooth-bearing area of the maxilla is 21 and 43%, respectively (P < 0.02 and P < 0.00001). CONCLUSIONS: A substantial amount of keratocysts occur in the tooth-bearing area of the jaws, requiring attention.

Recurrence of nonsyndromic odontogenic keratocyst after marsupialization and delayed enucleation vs. enucleation alone: a systematic review and meta-analysis.

PURPOSE: This study was conducted in order to determine whether marsupialization before definitive enucleation of nonsyndromic odontogenic keratocysts (OKCs) is capable of decreasing the recurrence rate more effectively than just enucleation. METHODS: We searched MEDLINE, Web of Science, Scopus, and Cochrane Library, until August 5th of 2017 for original studies reporting on the treatment of OKCs with and without previous marsupialization and the related recurrence rate. All records and data were independently assessed, meta-analysis was performed, and the odds ratio of recurrence was the effect measure; P value for the summary effect of < 0.05 was considered statistically significant. RESULTS: The 748 records retrieved were reduced to 6 studies to be qualitatively assessed and 5 studies were included in the meta-analysis. The overall odds ratio of 0.57 [0.25-1.28] of the pooled values pointed that marsupialization reduced the recurrence rate in comparison to just enucleation; however, the P value showed that there is no strong evidence to support this statement. CONCLUSIONS: Marsupialization followed by enucleation after 12 to 18 months reduces the recurrence rate, but more studies are necessary to support this statement.

Site and Burden of Lower Limb Atherosclerosis Predicts Long-term Mortality in a Cohort of Patients With Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Lower limb peripheral arterial disease (PAD) is becoming increasingly common. Lower limb perfusion, as determined by the ankle brachial pressure index (ABPI), is a recognised predictor of overall mortality. The increasing role of non-invasive imaging in patient assessment may aid in the ability to predict poor patient outcomes. METHODS: This study included all patients undergoing a lower limb arterial duplex over a period of 20 months. The site and burden of atherosclerosis within the lower limb was determined using the well validated Bollinger score. Patient demographic data were also collated. The primary outcome measure was all cause mortality. RESULTS: A total of 678 patients were included (median age 74 years). The overall median follow up period was 69.9 months. Of these, 307 patients reached the primary end point, which was death. Independent predictors of all cause mortality included total Bollinger score (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.18 [p < .001]; OR per 10 points), femoropopliteal Bollinger score (OR 1.34, 95% CI 1.11-1.08 [p = .05]; OR per 10 points), and crural Bollinger score (OR 1.03, 95% CI 1.01-1.03 [p = .03]). There was also a significant association between mortality and age, a prior history of ischaemic heart disease, a history of congestive cardiac failure and chronic renal failure (chronic kidney disease ≥ 3). Statin and antiplatelet therapy were protective. CONCLUSION: This contemporary study confirms poor long-term outcomes still exist in patients with PAD. The site and severity of lower limb atherosclerosis are independent predictors of long-term mortality.

Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial.

Importance: Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium. Objective: To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017. Interventions: Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride. Main Outcome and Measures: The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. Results: All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 [0.3%] for the 2-mg haloperidol group vs 1 [0.1%] for the placebo group). Conclusions and Relevance: Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults. Trial Registration: clinicaltrials.gov Identifier: NCT01785290.

Validation of an automated surveillance approach for drain-related meningitis: a multicenter study.

OBJECTIVE Manual surveillance of healthcare-associated infections is cumbersome and vulnerable to subjective interpretation. Automated systems are under development to improve efficiency and reliability of surveillance, for example by selecting high-risk patients requiring manual chart review. In this study, we aimed to validate a previously developed multivariable prediction modeling approach for detecting drain-related meningitis (DRM) in neurosurgical patients and to assess its merits compared to conventional methods of automated surveillance. METHODS Prospective cohort study in 3 hospitals assessing the accuracy and efficiency of 2 automated surveillance methods for detecting DRM, the multivariable prediction model and a classification algorithm, using manual chart review as the reference standard. All 3 methods of surveillance were performed independently. Patients receiving cerebrospinal fluid drains were included (2012-2013), except children, and patients deceased within 24 hours or with pre-existing meningitis. Data required by automated surveillance methods were extracted from routine care clinical data warehouses. RESULTS In total, DRM occurred in 37 of 366 external cerebrospinal fluid drainage episodes (12.3/1000 drain days at risk). The multivariable prediction model had good discriminatory power (area under the ROC curve 0.91-1.00 by hospital), had adequate overall calibration, and could identify high-risk patients requiring manual confirmation with 97.3% sensitivity and 52.2% positive predictive value, decreasing the workload for manual surveillance by 81%. The multivariable approach was more efficient than classification algorithms in 2 of 3 hospitals. CONCLUSIONS Automated surveillance of DRM using a multivariable prediction model in multiple hospitals considerably reduced the burden for manual chart review at near-perfect sensitivity.

The extraordinary career of Professor Dr. Simon van Creveld.

Simon van Creveld received both the MD and PhD degrees and had a multifaceted medical and scientific education at many hospitals and research institutes in the Netherlands, Germany, and the UK. He and his wife were the first to develop insulin for the Netherlands. His major interests were in hemophilia and hemorrhagic disorders, which accounted for 87 of his publications. In 1934, van Creveld demonstrated that a dispersed protein fraction obtained from serum could reduce the clotting time of hemophilic blood. His interest in glycogen storage disease resulted in van Creveld-von Gierke disease for which van Creveld contributed four published articles. The Ellis-van Creveld syndrome, also known as chondroectodermal dysplasia, was published in 1940 and became well known to medical geneticists. During the Nazi occupation of the Netherlands, van Creveld's professorship was taken away from him because he was Jewish. His visits to hospitals of concentration camps to treat babies and give pediatric advice while wearing a Jewish Yellow Star and interacting with SS Commandants in charge, and then leaving can only be described as amazing. After the war, his professorship was returned, and in the same year as his retirement, he established a large Hemophila Treatment and Research Center now known as the Van Creveld Clinic, which celebrated its 40th anniversary in 2005.

Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio.

BACKGROUND: The preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio. METHODS: A prospective case-cohort study was performed (PREVEND cohort; no previous cardiovascular disease and no use of lipid-lowering drugs initially). Fasting serum TC/HDL-C, apoB/apoA-I, triglycerides, and common CETP variations (TaqIB [rs708272] and -629C>A [rs1800775] polymorphisms) were measured at baseline. The composite end point was incident MACE. RESULTS: A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up. The age- and sex-adjusted hazard ratio was 1.31 (95 % confidence interval 1.23-1.41) for the apoB/apoA-I ratio and 1.22 (95% confidence interval 1.26-1.39) for the TC/HDL-C ratio (both P < .001). These relationships were essentially similar within each TaqIB and -629C>A CETP genotype group. No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C>A CETP variations on incident MACE were observed (P > .20 for all). CONCLUSION: The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations. CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

SSU ribosomal DNA-based monitoring of nematode assemblages reveals distinct seasonal fluctuations within evolutionary heterogeneous feeding guilds.

Soils are among the most complex, diverse and competitive habitats on Earth and soil biota are responsible for ecosystem services such as nutrient cycling, carbon sequestration and remediation of freshwater. The extreme biodiversity prohibits the making of a full inventory of soil life. Hence, an appropriate indicator group should be selected to determine the biological condition of soil systems. Due to their ubiquity and the diverse responses to abiotic and biotic changes, nematodes are suitable indicators for environmental monitoring. However, the time-consuming microscopic analysis of nematode communities has limited the scale at which this indicator group is used. In an attempt to circumvent this problem, a quantitative PCR-based tool for the detection of a consistent part of the soil nematofauna was developed based on a phylum-wide molecular framework consisting of 2,400 full-length SSU rDNA sequences. Taxon-specific primers were designed and tested for specificity. Furthermore, relationships were determined between the quantitative PCR output and numbers of target nematodes. As a first field test for this DNA sequence signature-based approach, seasonal fluctuations of nematode assemblages under open canopy (one field) and closed canopy (one forest) were monitored. Fifteen taxa from four feeding guilds (covering ∼ 65% of the free-living nematode biodiversity at higher taxonomical level) were detected at two trophic levels. These four feeding guilds are composed of taxa that developed independently by parallel evolution and we detected ecologically interpretable patterns for free-living nematodes belonging to the lower trophic level of soil food webs. Our results show temporal fluctuations, which can be even opposite within taxa belonging to the same guild. This research on nematode assemblages revealed ecological information about the soil food web that had been partly overlooked.

Lower carotid intima media thickness is predicted by higher serum bilirubin in both non-diabetic and Type 2 diabetic subjects.

BACKGROUND: Higher serum bilirubin levels may be implicated cardiovascular protection. It is unknown whether the impact of serum bilirubin on carotid artery intima media thickness (IMT), a marker of subclinical atherosclerosis, is different in diabetic subjects compared to non-diabetic subjects. We assessed relationships of IMT with serum total bilirubin in non-diabetic and Type 2 diabetic subjects without clinically manifest cardiovascular disease. METHODS: IMT, total bilirubin, transaminases, C-reactive protein (CRP) and lipid levels were measured in 40 predominantly middle-aged non-diabetic and 80 diabetic subjects. RESULTS: IMT was higher in diabetic subjects compared to non-diabetic subjects (unadjusted, p<0.001), whereas bilirubin was not different (p=0.82). In both non-diabetic and in diabetic subjects, IMT was negatively related to bilirubin (ß=-0.316, p=0.045 and ß=-0.247 p=0.014, respectively) taking account of age, sex and mean arterial pressure. In the combined subjects, IMT remained independently related to bilirubin (ß=-0.183, p=0.028) after additional adjustment for diabetes status, alcohol intake, transaminases, CRP and lipid levels. There was no interaction of bilirubin with the presence of diabetes on IMT (p=0.98). CONCLUSION: Carotid artery IMT relates negatively to bilirubin in non-diabetic and Type 2 diabetic subjects. The association of subclinical atherosclerosis with bilirubin appears to be unaltered in the diabetic state.

The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study.

OBJECTIVE: The plasma leptin/adiponectin (L/A) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone. We determined the extent to which the L/A ratio predicts incident cardiovascular disease (CVD) taking account of clinical risk factors, microalbuminuria, the total cholesterol/HDL cholesterol (TC/HDL-C ratio), triglycerides, high sensitive C-reactive protein (hs-CRP) and insulin sensitivity (homeostasis model assessment (HOMA(ir))). METHODS: A community-based prospective nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event (cases) and 106 male control subjects (no clinically manifest CVD and no lipid lowering drug use at baseline; median follow-up of 3.0 and 10.5 years, respectively). Plasma leptin, adiponectin, the leptin/adipnectin (L/A) ratio, as well as hs-CRP, HOMA(ir) and the TC/HDL-C ratio were determined at baseline. RESULTS: Plasma leptin levels and the L/A ratio were higher in cases vs. controls (p=0.002 for both), but the difference in adiponectin was not significant (p=0.10). Age-adjusted incident CVD was associated with plasma leptin, adiponectin and the L/A ratio (p=0.045 to p=0.001). The relationships of incident CVD with plasma leptin (p=0.19) and adiponectin (p=0.073) lost statistical significance after additional adjustment for smoking, waist circumference, hypertension, microalbuminuria, the TC/HDL-C ratio, hs-CRP and HOMA(ir). In this fully adjusted analysis, the L/A ratio remained predictive of incident CVD (hazard ratio: 1.40 (95% CI 1.05-1.87), p=0.024). CONCLUSION: This study suggests that the L/A ratio may be a preferential marker of a first cardiovascular event in men compared to plasma leptin and adiponectin levels alone.

Plasma lipoprotein-associated phospholipase A2 is inversely correlated with proprotein convertase subtilisin-kexin type 9.

BACKGROUND AND AIMS: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a pro-atherogenic phospholipase A(2), which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA(2) mass. METHODS: Lp-PLA(2) mass (turbidimetric immunoassay), PCSK9 (enzyme-linked immunosorbent assay) and (apo) lipoproteins were measured in 53 nondiabetic subjects (27 women) with body mass index <30 kg/m(2). RESULTS: Lp-PLA(2) and PCSK9 levels were both correlated positively with LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol (r = 0.330 to r = 0.382, p ≤0.02). Remarkably, Lp-PLA(2) was inversely related to PCSK9 (r = -0.388, p = 0.004). The Lp-PLA(2)/apolipoprotein B ratio, as a measure of the Lp-PLA(2) content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r = -0.575, p <0.001). The inverse relationships of Lp-PLA(2) (p = 0.023) and the Lp-PLA(2)/apolipoprotein B ratio (p = 0.001) with PCSK9 levels remained significant after controlling for age, gender, triglycerides and HDL cholesterol. CONCLUSIONS: Despite increasing effects on LDL cholesterol, higher PCSK9 levels are unlikely to confer impaired Lp-PLA(2) metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA(2) regulation and vice versa to determine effects of Lp-PLA(2) inhibitors on the PCSK9 pathway.