Dutch Criteria Research Articles

Correlation of Clinical and Electrophysiological Criteria in the Diagnosis of Guillain-Barré Syndrome: A Prospective Observational Study.

There are many criteria for diagnosing Guillain-Barré syndrome (GBS), and the yield of these diagnostic criteria varies. Each criterion requires some laboratory data and nerve conduction studies (NCS). Although supportive laboratory data are reassuring when present in suspected cases of GBS, when absent, they can potentially cause further delay in diagnosis and treatment. There is no gold standard test for the diagnosis of GBS, and there are multiple diagnostic criteria for GBS to date. The aim of the study is to know the sensitivity of different criteria, clinical and electrophysiological, for the diagnosis of GBS and to study the clinical spectrum and electrophysiological spectrum of GBS in our cohort of patients. We studied a total of 43 cases who presented with one or more of the following symptoms: relatively symmetrical and progressive flail-type weakness of more than one limb, with or without ataxia and/or ophthalmoplegia, and were diagnosed with GBS according to clinical criteria at the time of admission to Government Stanley Medical College Hospital. GBS mimics were ruled out. In all patients, the demographic data, cerebrospinal fluid (CSF) analysis (if done), and electrophysiological findings fitting into the diagnostic criteria of National Institute of Neurological Disorders and Stroke (NINDS), Dutch, and Brighton criteria were recorded. The need for assisted mechanical ventilation, neurology intensive care unit (NICU) stay, any complications, and treatment outcome details were recorded in a structured proforma. Most of the patients in our study were in their fourth decade of life, with a mean age of 41.37 years, similar to previous studies from India. Men are more frequently affected compared to women, similar to what has been observed in most studies done previously worldwide. In our study, electrophysiological criteria by Dutch criteria (87.5%), Brighton criteria (87.5%), and NINDS criteria (85.6%) had low sensitivity compared to the clinical criteria. In the present study, electrophysiological criteria proposed by the NINDS, Dutch, and Brighton criteria are less sensitive compared to clinical criteria in diagnosing GBS at early stages. Clinical criteria alone may be useful in resource-poor countries and at peripheral healthcare systems where NCS are not always readily available.

Contents and Spatial Distribution of Arsenic in Vineyard Soils in Mediterranean Environment

This study presents the contents and spatial distribution of arsenic (As) in vineyard soils from the Valdepeñas Protected Designation Origin (PDO) in central Spain. As content varies within the 108.40–0.03 mg·kg−1 range in surface horizons, and within 151.00–0.03 mg·kg−1 in subsurface horizons. The mean value of both horizons is similar: 4.25 and 4.88 mg·kg−1, respectively. Based on optimal spatial interpolation, the spatial distribution of As in soils was mapped by the IDV method. A simple data and map analysis suggests that pedogeogenic sources are the main sources for As (the As distribution tends to match the lithology and soil types), which indicates minor anthropogenic sources, mainly by agricultural sector activities. Only a high As concentration appears in the NE area, where sporadic moderate contamination is estimated based on Dutch criteria. The data obtained from the study area provide a broader view of the concentration, distribution, enrichment, sources, and the potential environmental contamination by As in the vineyard soils of this large winegrowing zone. The assessment of the results indicates that As does not affect agriculture (vineyards) in the study area because its concentrations are low in the soil types used by agriculture. These data can be employed as a guide to learn the range of values in vineyard soils in the European Mediterranean Region that are relatively unpolluted from industrial sources to make comparisons to more polluted areas.

1391P Tumor-first mutation-specific risk approach to trigger germline testing in castration-resistant prostate cancer

The prevalence of hereditary prostate cancer (PCa) in the Netherlands appears lower than previously reported, and routine germline testing is not advocated as standard of care. Current referral strategies are based on a positive family history (FH) for high-risk penetrating cancer predisposition genes, on presence of metastatic disease (DISCOVER-study), or on a tumor-first approach in patients (pts) with castration-resistant PCa (CRPC) with cascade germline testing in those with an alteration in predefined genes. Here we compare referral based on FH with the tumor-first approach. The PROMPT trial (NCT04746300) prospectively studies the impact of routine molecular tumor profiling with broad next-generation sequencing (NGS) in recently diagnosed CRPC pts. All results were discussed within the Radboudumc Molecular Tumor Board to guide precision medicine and for germline testing by geneticists per protocol. FH was taken at screening. The presence of familial and hereditary PCa by Dutch criteria for included pts was retrospectively assessed. High-risk homologous recombination deficiency (HRD) genes studied were BRCA1, BRCA2 and PALB2. Data on ATM and CHEK2 (lower-risk) will also be presented. In the 307 evaluable pts at least one pathogenic HRD alteration was found in 24 pts (8%), in BRCA1 (n=1), BRCA2 (n=21) and PALB2 (n=2) respectively. 17 pts (6%) were referred for germline testing; in 11 pts a germline variant was found. In 7/11 families the genetic predisposition was unknown, with pts not fulfilling Dutch referral criteria. FH was reported in 305 pts. Based on FH 53 pts would have been eligible for referral to clinical genetics and germline testing. In these pts, 48 pts did not have a pathogenic aberration in BRCA1/BRCA2 or PALB2 in tumor DNA. Based on reported FH, 18% of the pts would meet the Dutch criteria for genetic testing. In the majority of them the chance of a germline mutation is estimated to be low based on tumor test results, and 7 families with a germline mutation would have been missed. A tumor-first approach for high risk genes led to referral of 6%, with a germline variant in 53% of pts. Routine tumor-first DNA testing in CRPC efficiently identifies pts eligible for germline testing.

Genetic Architecture and Cardiovascular Risk of Familial Combined Hyperlipidemia

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Familial combined hyperlipidemia (FCHL) is one of most common inherited lipid phenotypes and is characterized by elevated plasma concentrations of apolipoprotein B-100 and triglycerides. However, many aspects of FCHL remain incompletely understood, such as its genetic basis and the magnitude of cardiovascular risk with which it is associated. <h3>Objective/Purpose</h3> The goals of this study were to investigate the genetic architecture and cardiovascular risk associated with FCHL. <h3>Methods</h3> We identified individuals with a FCHL phenotype among 349,222 unrelated participants of European ancestry in the UK Biobank using modified versions of 5 different diagnostic criteria. The prevalence of the FCHL phenotype was 11.44% (n=39,961), 5.01% (n=17,485), 1.48% (n=5,153), 1.10% (n=3,838), and 0.48% (n=1,688) according to modified versions of the Consensus Conference, Dutch, Mexico, Brunzell, and Goldstein clinical criteria, respectively. We performed discovery, case-control genome-wide association studies for these different FCHL criteria. <h3>Results</h3> We identified 175 independent loci associated with FCHL at genome-wide significance. All loci have known associations with plasma lipid levels. We investigated the combined impact of genetic and environmental risk on FCHL and found that the combination of polygenic susceptibility to hypercholesterolemia or hypertriglyceridemia and features of metabolic syndrome was associated wa ith greater prevalence of FCHL. Lastly, we observed that individuals with an FCHL phenotype had a comparable risk of incident coronary artery disease compared to individuals with monogenic Familial Hypercholesterolemia (FH) (adjusted hazard ratio vs controls [95% confidence interval]: 2.72 [2.31-3.21] and 1.90 [1.30-2.78]) <h3>Conclusions</h3> Our results suggest that, rather than being a single genetic entity, the FCHL phenotype represents a polygenic susceptibility to dyslipidemia in combination with metabolic abnormalities. Importantly, the cardiovascular of the FCHL phenotype is similar to that of monogenic FH, despite being at least 5 times more common.

Evaluating the sensitivity and specificity of the UK and Dutch growth referral criteria in predicting the diagnosis of pathological short stature

ObjectiveThe aim of this observational study was to evaluate the UK and Dutch referral criteria for short stature to determine their sensitivity and specificity in predicting pathological short stature. Adherence...

Prenatal antibiotic exposure, asthma, and the atopic march: Asystematic review and meta-analysis.

Antibiotic use during pregnancy may increase the risk for asthma in children. We performed a meta-analysis assessing prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march. A systematic literature search protocol (PROSPERO-ID: CRD42020191940) was registered and searches were completed using Medline, Proquest, Embase, and the Cochrane central register of controlled trials. Screening for inclusion criteria: published in English, German, French, Dutch, or Arabic, intervention (use of any antibiotic at any time point during pregnancy), and disease (reporting atopic disease incidence in children with a primary outcome of asthma or wheeze), and exclusion criteria: reviews, preclinical data, and descriptive studies, yielded 27 studies. Study quality was assessed using the Newcastle-Ottawa Assessment Scale. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Our meta-analysis demonstrates that antibiotic use during pregnancy is associated with an increased relative risk (RR) of developing wheeze RR 1.51 (95% CI: 1.17-1.94) or asthma RR 1.28 (95% CI 1.22-1.34) during childhood. Assessment of the atopic march in association with asthma or wheeze revealed that antibiotic use during pregnancy also increases the risk for eczema/dermatitis RR 1.28 (95% CI: 1.06-1.53) and allergic rhinitis RR 1.13 (95% CI: 1.02-1.25). One study found an increase in food allergy RR 1.81 (95% CI: 1.11-2.95). Maternal antibiotic use during pregnancy is associated with an increased risk for wheeze or asthma development in children, as well as for diseases involved in the atopic march. There was high heterogeneity in the data, and the certainty of the evidence was determined to be low quality, highlighting the need for more high-quality studies on this topic. These results have importance for antibiotic stewardship throughout the prenatal period. This work was supported by the Deutsche Forschungsgemeinschaft and theKonrad Adenauer Foundation.

Comparison of Equations for the Calculation of LDL-Cholesterol in Familial Hypercholesterolemia: Data from Iranian Registry.

Low-density lipoprotein cholesterol is the mainstay of diagnosis, treatment, and follow-up of patients with familial hypercholesterolemia, the most prevalent autosomal domi- nant disorder among humans. Since the reference measurement method (ultracentrifugation) is time-consuming and expensive, many formulas emerged to calculate low-density lipopro- tein cholesterol levels and are commonly used in laboratories. To compare the performance of 3 low-density lipoprotein cholesterol calcula- tion equations with a direct method (enzymatic photometric assay), the lipid profiles of 1148 patients of the registry of familial hypercholesterolemia in Iran were analyzed retrospec- tively, 270 of which had a possible or definite familial hypercholesterolemia diagnosis according to Dutch criteria. While measured using the direct method, we calculated the low-density lipoprotein cholesterol levels using the Friedewald, Chen, and Anandaraja formulas. Our results showed that all 3 formulas are highly correlated with the direct method, and the Chen formula showed the highest intra-class correlation coefficient among all (0.954 among all patients with hypercholesterolemia and 0.947 among the familial hyper- cholesterolemia population). In addition, the Chen formula was the most sensitive, and the Friedewald formula was the most specific formula using a low-density lipoprotein cholesterol cut-off of 100 in familial hypercholesterolemia patients. Our findings encourage applying the Chen formula in addition to the Friedewald formula to make better clinical decisions for familial hypercholesterolemia patients.

Familial Hypercholesterolemia Due to APOE p.Leu167del Mutation, Response to Bempedoic Acid/Ezetimibe, after Failure of Both Inclisiran and Evolocumab, in a Statin Intolerant Patient: A Case Report

<h3>Lead Author's Financial Disclosures</h3> M.D. has received speaker's bureau honorarium from Amgen and Esperion and for advisory board honorarium from The Medicines Company. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Both inclisiran and evolocumab have been shown to reduce LDL-C in patients with heterozygous FH. Occasional cases of nonresponse have been reported. A rare genetic form of HeFH exhibits LDL-C nonresponse to both inclisiran and evolocumab, but a robust response to bempedoic acid/ezetimibe. <h3>Objective/Purpose</h3> To describe LDL-C responses to inclisiran, evolocumab, and bempedoic acid/ezetimibe, in a patient with HeFH due the APOE p.Leu167del mutation. <h3>Methods</h3> A participant in the Orion 10 clinical trial dropped from the Open Label Extension study because of lack of inclisiran efficacy. Genetic testing was obtained. For management of his lipid disorder, the patient was treated first with evolocumab and then with bempedoic acid/ezetimibe. <h3>Results</h3> A 63-year-old statin intolerant male with definite HeFH by the Dutch Criteria, and premature ASCVD manifested by an MI at age 47 followed by multiple PCIs (12 stents), dropped from the Open Label Extension of Orion 10 for nonresponse. His baseline LDL-C at randomization had been 178 mg/dL, while his on treatment (inclisiran 300 mg every 6 months) LDL-C was 204 mg/dL, representing a 13% increase. New baseline LDL-C was 202 mg/dL when evolocumab 140 mg every 2 weeks was added. After 5 weeks, LDL-C was 195 mg/dL, a 3% decrease, and after 8 weeks, LDL-C was 190 mg/dL, a 6% decrease. Evolocumab was stopped for nonresponse. A GBinsight Comprehensive Dyslipidemia panel identified neither pathogenic nor likely pathogenic variants in the LDLR, APOB, PCSK9, or RAP1 genes, but did demonstrate that the patient is heterozygous for a very rare variant in his APOE gene, c.500_502del(p.Leu167del). Next, bempedoic acid 180 mg/ezetimibe 10 mg daily was added. 6 weeks later, LDL-C was 63 mg/dL, down from 190 mg/dL, a decrease of 67%. <h3>Conclusions</h3> This patient with HeFH due to the APOE p.Leu167del mutation exhibited nonresponse to the PCSK9-reducing drugs, inclisiran, and evolocumab. The response to bempedoic acid/ezetimibe, however, was robust. In the homozygous state, this APOE variant causes the rare disease, Sea-Blue Histiocyte Syndrome, and in the heterozygous state, this variant is a rare cause of HeFH. The reported mechanism is that VLDL carrying the mutant apo E produces LDLR down-regulation in hepatocytes, thereby raising plasma LDL-C. Subjects with the APOE p.Leu167del mutation are reported to have a higher lipid-lowering response to statins than HeFH due to LDLR mutations. In this statin intolerant patient, bempedoic acid/ezetimibe produced a similar, heightened LDL-C-lowering response.

Polygenic architecture and cardiovascular risk of familial combined hyperlipidemia

Background and aimsFamilial combined hyperlipidemia (FCHL) is one of the most common inherited lipid phenotypes, characterized by elevated plasma concentrations of apolipoprotein B-100 and triglycerides. The genetic inheritance of FCHL remains poorly understood. The goals of this study were to investigate the polygenetic architecture and cardiovascular risk associated with FCHL. Methods and resultsWe identified individuals with an FCHL phenotype among 349,222 unrelated participants of European ancestry in the UK Biobank using modified versions of 5 different diagnostic criteria. The prevalence of the FCHL phenotype was 11.44% (n = 39,961), 5.01% (n = 17,485), 1.48% (n = 5,153), 1.10% (n = 3,838), and 0.48% (n = 1,688) according to modified versions of the Consensus Conference, Dutch, Mexico, Brunzell, and Goldstein criteria, respectively. We performed discovery, case-control genome-wide association studies for these different FCHL criteria and identified 175 independent loci associated with FCHL at genome-wide significance. We investigated the association of genetic and clinical risk with FCHL and found that polygenic susceptibility to hypercholesterolemia or hypertriglyceridemia and features of metabolic syndrome were associated with greater prevalence of FCHL. Participants with an FCHL phenotype had a similar risk of incident coronary artery disease compared to participants with monogenic familial hypercholesterolemia (adjusted hazard ratio vs controls [95% confidence interval]: 2.72 [2.31–3.21] and 1.90 [1.30–2.78]). ConclusionsThese results suggest that, rather than being a single genetic entity, the FCHL phenotype represents a polygenic susceptibility to dyslipidemia in combination with metabolic abnormalities. The cardiovascular risk associated with an FCHL phenotype is similar to that of monogenic familial hypercholesterolemia, despite being ∼5x more common.

Estimated Prevalence of Familial Hypercholesterolemia Among Egyptian Patients with Acute Coronary Syndromes; Analysis from The Cardiorisk Project

Abstract Aims The prevalence of familial hypercholesterolemia (FH) in Egypt is largely un- known. We aimed to estimate the prevalence of FH among 3224 Egyptian patients with acute coronary syndromes enrolled from 2015 to 2018 in the nationwide cross- sectional cardioRisk project. Methods and Results We applied the Dutch Lipid Clinic criteria for the diagnosis of FH on the available data recorded for the patients enrolled in the CardioRisk project. Two main criteria were applied: the presence of premature CAD (given 2 points in the Dutch criteria), and the categorized low density lipoprotein cholesterol (LDL-C) lev- els (given 1, 3, 5, or 8 points in the Dutch criteria according to the level). From a total of 3224 patients, 2743 patients had available LDL-C levels. Among those patients, when applying the abovementioned 2 criteria, we estimated that 472 patients had at least ‘possible’ FH (17.2% of the total population). Specifically, 4 patients had ‘defi- nite’ FH (0.1%), 7 patients had ‘probable’ FH (0.25%), and 461 patients had ‘possi- ble’ FH (16.8%). Conclusion The estimated prevalence of at least ‘possible’ FH among Egyptian patients with ACS is 17%.

Risk evaluation of early-stage hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients: a population-based study from Taiwan

To assess the prognostic value of the Dutch criteria for patients with early-stage hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer from the Taiwan Cancer RegistryDatabase. We included 8295 patients with early-stage node-negative breast cancer who underwent surgery during January 2008-December 2012. Patients were stratified into low- and high-risk groups based on the Dutch criteria. The Kaplan-Meier method and log-rank test were used to estimate the difference in breast cancer-specific survival (BCSS) and overall survival (OS) between groups. Multivariable analysis was used to evaluate the prognostic value of the Dutch criteria. Overall, the low-risk and high-risk groups comprised 5375 and 2920 patients, respectively. In the low- and high-risk groups, the 5-year BCSS rate was 99.6% and 98.2% (P < 0.0001) and the 5-year OS rate was 98.3% and 96.8% (P < 0.0001), respectively. The hazard ratio for BCSS was 4.18 (95% confidence interval [CI] 2.63-6.63, P < 0.0001), and the hazard ratio for OS was 1.94 (95% CI 1.48-2.55); both were significantly poorer in the high-risk group than in the low-risk group. In the low-risk group, the 5-year BCSS and OS of patients who did and did not receive adjuvant chemotherapy were similar (99.5% versus 99.6% [P = 0.927] and 98.8% and 98.1% [P = 0.0683], respectively). The prognosis of low-risk patients as classified using the Dutch criteria is excellent with or without adjuvant chemotherapy. The benefit of multi-gene testing for chemotherapy decision-making might be minimal in these patients.

Analysis of Soil Quality Status and Accumulation of Potentially Toxic Element in Food Crops Growing at Fecal Sludge Dumpsite in Ubakala, Nigeria

This study investigated the magnitude of potentially toxic element (PTE) in fecal sludge and the level of contamination of soil and food crops at Ubakala, Abia State, Nigeria. Soil samples were collected in four cardinal points at north (N), south (S), east (E) and west (W) of 1 m, 5 m, 15 m and 30 m from the edge of the fecal sludge dumpsite and standards (2 ppm, 4 ppm and 6 ppm) were prepared from 1000 ppm stock solution of the metals and used to plot the calibration curve with Atomic Absorption Spectrometer. Commonly consumed Carica papaya, Telfairia occidentalis and Manihot esculenta leaf samples were collected and analyzed to measure the concentrations of PTEs such as Cd, Zn Cr, Mn, Pb and Cu. The concentrations of Zn (12.41±0.30 mg/kg), Cd (0.07±0.00 mg/kg), Cr (4.47±0.34 mg/kg), Cu (2.12±0.03 mg/kg), Mn (8.13±0.03 mg/kg) and Pb (0.01±0.00 mg/kg) in dried fecal sludge are below the permitted limits of European Union. Concentrations of PTEs in soil and plants were Zn (13.40±1.20 to 100.80±1.40 and 1.24±0.06 to 56.02±5.02 mg/kg), Cd (0.07±0.01 to 0.92±0.02 and 0.0000±0.000 to 0.085±0.01 mg/kg), Cu (6.27±0.31 to 31.39±1.04 and 0.002±0.001 to 10.80±2.01 mg/kg), Mn (36.00±1.56 to 188.57±2.25 and 0.11±0.00 to 17.21±2.01 mg/kg), Cr (2.40±0.40 to 21.03±1.43 and 0.000±0.00 to 9.60±1.13 mg/kg) and Pb (0.09±0.02 to 0.35±0.03 and &lt;0.00001±0.00 to 0.008±0.00 mg/kg), respectively. Zinc in soil is higher than FAO/WHO permissible limit while Cd in soil is higher than FAO/WHO limit and Dutch criteria for soil. Zinc and Cr in food crops are higher than FAO/WHO permissible limit. Strong positive relationship exist between Zn in soil and food crops (r = 0.616, p&lt;0.05). Based on the findings, it is recommended that the fecal sludge should be treated with lime to precipitate PTE content of sludge and lowering the corresponding environmental risks.

Abstract PS6-51: Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing

Abstract Purpose: Dutch clinical risk criteria (low-risk definition: age &amp;gt; 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Materials and methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n=2679) and 5-year OS (n=2636) between low-risk and high-risk groups (in both endpoints, P &amp;lt; 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusion: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective. Citation Format: Lei Lei, Han-Ching Chan, Tzu-Pin Lu, Xian-Yuan Miao, Zi-Yan Yang, Jia-Huan Huang, Xiao-Jia Wang, Hung-Chun Skye Cheng. Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-51.

Verification of the Dutch criteria for familial hypercholesterolemia among a contingent of patients in Southern Bulgaria

Background and Aims: The Dutch criteria for FH are routinely used in everyday practice in Bulgaria. The goal of the study was to detect patients with Familial hypercholesterolemia in the outpatient care system through application of the Dutch criteria and to verify that with genetic analysis.

Recurrence risk stratification by Dutch clinical risk criteria for early-stage luminal breast cancer patients in Taiwan: A population-based analysis.

e12509 Background: Dutch clinical risk criteria (low-risk definition: age &gt; 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P &lt; 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.

Diagnostic discordance between the dutch lipid criteria network and simon broome phenotypic diagnostic test for familial hypercholesterolaemia

Diagnostic discordance between the dutch lipid criteria network and simon broome phenotypic diagnostic test for familial hypercholesterolaemia

Abstract 243: Familial Hypercholesterolemia Screening at a Large Corporate Clinic in Japan

Background and Aims: Familial hypercholesterolemia (FH) is a high risk of developing premature coronary artery disease even in heterozygotes. It is reported that the diagnostic rate in Japan and the United States is extremely low compared with the Netherlands and a few countries. The diagnostic criteria of FH vary from country to country. Using the JASb(Japan Atherosclerosis Society) diagnostic criteria, it has been shown that sensitivity and specificity in patients who visited lipid clinics are high, but those in the general population are not clear. In this study, we tried to screen FH in a clinic of a large Japanese corporation. Methods: During the period from July 1, 2014 to October 31, 2017, we extracted patients suspected of FH with LDL-C≧180mg/dL or with a family history of CAD at annual and follow-up medical checkup. In the extracted patients, family history of premature CAD and Achilles tendon thickening were evaluated. For patients to which additional information was added, FH diagnosis by JAS diagnostic criteria and by Dutch criteria were performed. Results: A total of 3,3136 medical checkups were set for about 6,300 subjects, and a total of 2,8108 visits were made (the examination rate was 84.8%). Among them, 328 patients with suspected FH were extracted due to LDL-C of 180 mg/dL or more, or family history of CAD. Among subjects additional information was obtained as of November 2017, 43 (19.6%) were diagnosed as FH on JAS criteria, and the number was higher than predicted from the estimated prevalence of FH. On the other hand, there were 24 patients who were "Definite" or "Probably" in Dutch criteria and 211 patients with LDL-C≧190 mg/dL. LDL-C of patients diagnosed as FH by JAS diagnostic criteria was 206.6 (45.3) mg/dL, while patients who did not meet the criteria also had high LDL-C values as 201.4 (18.6) mg/dL. 26.8% of patients who met the diagnostic criteria of FH had not received statin at the time of evaluation. Conclusion: The number of patients satisfying the JAS criteria was more than predicted from the prevalence, suggesting the possibility of over-diagnosis. On the other hand, there were many patients who do not satisfy the diagnostic criteria even when LDL-C is very high.

IDENTIFICATION OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA IN THE RUSSIAN POPULATION USING THE EXAMPLE OF MOSCOW CITY AND MOSCOW REGION

Aim . To estimate the prevalence of familial hypercholesterolemia (FH) in a sample of Moscow city and Moscow region patients with hypercholesterolemia (HCh) based on lipid spectrum and instrumental methods. Material and methods . The study included two samples of patients (age >18 years), with total cholesterol (TCh) level ≥7.5 mmol/l and/or low-density lipoprotein (LDL) cholesterol level ≥4.9 mmol/l. First sample (n=60) was included to determine secondary hyperlipidemia frequency in newly diagnosed HCh, with measurement of thyroid hormone, glucose and glycated hemoglobin (HbA1c) levels. Patients of the second sample (n=432) from Russian registry of FH (RuFH) were studied by drug therapy assessment, lipid profile measurements, calculation of FH probability according to Dutch and British criteria, carotids duplex scanning (CDS), cardiac perfusion single-photon emission computed tomography (SPECT/CT) using rest/stress protocol. Results . The incidence of secondary dyslipidemia due to diabetes or hypothyroidism in patients with severe HCh was 18.3%. Monotherapy with atorvastatin (34.2%) or rosuvastatin (31.8%), combined therapy with statins and other lipid-lowering drugs (24.4%) prevails in the structure of lipidlowering therapy in patients with severe HCh. The frequency of FH according to Dutch criteria in HCh patients was 15.3%, – 18.1%. Patients with definite FH diagnosis showed higher level of TCh (p<0.001), LDL cholesterol (p<0.001), proprotein convertase subtilisin/kexin type 9 (p<0.001), lower high-density lipoprotein (HDL; p=0.02), and triglycerides (p<0.001). At that HDL cholesterol levels differed only in patients treated with lipid-lowering drugs. Patients with lipid-lowering therapy had significantly higher values of total stenosis percent, the number of plaques, intima-media complex thickness (p<0.001). Patients with lipid-lowering therapy with a definite and probable FH diagnosis had significantly worse values of CDS parameters. CDS parameters correlated with age in both therapeutic groups, and with maximal TCh levels in history in lipid-lowering therapy group (p<0.01). Patients with HCh and established ischemic heart disease showed higher frequency of positive exercise test result, higher values of left ventricle myocardial perfusion heterogeneity and defect severity parameters according to SPECT. Conclusion . Patients with severe HCh and suspected FH in Moscow city and region demonstrate satisfactory awareness, but low adherence to therapy, which is also extremely rarely sufficient to achieve target LDL levels and reduce coronary risks. This leads to early manifestations of atherosclerosis, including characteristic progressive impairments of myocardial perfusion. Despite the ongoing work on primary prevention, it is advisable to recommend sending such patients to specialized clinics for more qualified consultations and selection of optimal lipid-lowering therapy with mandatory further monitoring of its effectiveness.

Heavy Metals in Soil and Accumulation in Medicinal Plants at an Industrial Area in Enyimba city, Abia State, Nigeria

The study assessed heavy metals in the soil and subsequent accumulation in plants at an industrial site at Enyimba city, Abia State, Nigeria. Soil and medicinal plant samples were analyzed for zinc (Zn), lead (Pb) and cadmium (Cd). The highest concentration of Zn (142.06 ± 2.91 mg/kg), Pb (18.06 ± 1.30 mg/kg) and Cd (27.055 ± 2.468 mg/kg) were obtained at the sampling points of 2, 7 and 5, respectively. The highest concentrations of Zn (27.09 ± 1.44 mg/kg) and Cd (2.000 ± 0.156 mg/kg) were accumulated by Azadiractha indica while the highest concentration of Pb (4.58 ± 0.51 mg/kg) was accumulated by Mangifera indica. The levels of Zn and Cd in soil were 13.77 ± 1.35 to 142.06 ± 2.91 and 0.695 ± 0.106 to 27.055 ± 2.468, and their concentrations in Azadiractha indica were 5.06 ± 0.35 to 27.09 ± 1.44 and 0.002 ± 0.001 to 2.000 ± 0.156 mg/kg, respectively. The concentrations of Zn and Cd in soil and Cd in Azadiractha indica reflected a state of pollution relative to Dutch criteria for soil and the FAO/WHO Codex Alimentarius Commission for soil and herbal plants.

CLINICAL CASE OF A PATIENT WITH HETEROZYGOUS FAMILY HYPERCHOLESTEROLEMIA

The article presents the clinical case of a patient with heterozygous family hypercholesterolemia with a retro-spective review of the disease progression. The patient with severe lipid metabolism disorder was referred to the Center of Lipid Disorders at the Kemerovo Regional Clinical Cardiac Dispensary n. a. Academician L.S. Barbarash. The patient underwent selective screening according to the Dutch diagnostic criteria comprising of hypercho lesterolemia phenotype, personal and family history, as well as genetic factors. For patient N. the total cumulative score by the Dutch criteria was 30. The diagnosis of familial hypercholesterolemia (CGS) was confirmed. The patient was given maximum tolerated doses of statins. However, the statin therapy was switched to combined lipidlowering therapy due to its low effectiveness.