Japanese Ministry Of Health And Welfare Research Articles

Abstract 9231: Contribution of Echocardiographic Abnormalities to Cardiac Sarcoidosis Diagnosis According to Past and Contemporary Diagnostic Criteria

Introduction: Cardiac sarcoidosis (CS) guidelines were originally published in 1993 by the Japanese Ministry of Health and Welfare (JMHW) and updated in 2006 and 2017. The updated guidelines consider several echocardiographic abnormalities as major diagnostic CS criteria. Contribution of this change to CS diagnosis has not been well investigated. Methods: A case control, single tertiary medical center study included 571 sarcoidosis patients (52.7% females, 58.9+/-12.6 years old) with documented extracardiac sarcoidosis and completed electrocardiogram and imaging assessment. Echocardiographic abnormalities consistent with CS were left ventricular (LV) dilation (LVD), LV aneurysms (LVA), LV wall motion abnormalities (LVWMA), LV hypertrophy (LVH), right ventricular hypertrophy (RVH), focal thinning of the anterior septum, and LV ejection fraction (EF) less than 50%. Frequency of echocardiographic abnormalities according to 1993, 2006 and 2017 CS diagnostic criteria were compared. Results: Most common echocardiographic abnormalities were reduced LVEF and LVH, occurring in more than 14 and 12% of CS patients. LVD and LVWMA occurred 8 and 7%, followed by uncommon RVH, LVA, and septal thinning (Table). Despite being common in CS, only LVD, LWMA, and reduced LVEF significantly (p<0.001) contributed to the CS diagnosis, while LVH did not (p=0.609). Alternatively, while LV aneurysm and septal thinning were uncommon, they significantly contributed to CS diagnosis (p<0.001). RVH was very uncommon and did not affect CS diagnosis. Conclusions: CS diagnostic criteria highlights the importance of cardiac imaging in suspected CS. Commonly seen echocardiographic findings of CS include EF<50%, LVWMA, and LV dilation significantly contribute to CS diagnosis. Of less commonly seen abnormalities, RVH utility appears to be low, while LVA and septal thinning may be helpful. Echocardiography remains an integral part in evaluating individuals with suspected CS.

The Role of Fibrin-Related Markers in Disseminated Intravascular Coagulation Due to Sepsis

Sepsis leads to local and systemic activation of different response systems, including coagulation and fibrinolysis. An overwhelming inflammatory response may lead to organ failure, and the coagulation and fibrinolysis involvement may lead to Disseminated Intravascular Coagulation (DIC). Special regard is given to the diagnosis of DIC by the use of scoring systems, which are, APACHE II, SAPS II, International Society of Thrombosis and Hemostasis (ISTH), and Japanese Ministry of Health and Welfare (JMHW). A large variety of fibrin compounds can be detected in plasma from septic patients with intravascular coagulation activation. Coagulation activation is indicated by elevated plasma levels of D-dimer, prothrombin fragments, and Thrombin-Antithrombin (TAT) complexes. Fibrin-Related Markers (FRMs) identified in sepsis are D-dimer, fibrinogen, Soluble Fibrin Monomer (SFM), and Fibrin Degradation Products (FDP). Hemostatic molecular markers, such as TAT, Plasmin-Plasmin Inhibitor Complex (PPIC), D-dimer, and SFM are better for the diagnosis of pre-DIC. No single biomarker of sepsis may be ideal, but many are helpful in terms of at least identifying critically ill patients who need more careful monitoring. As each biomarker has limited sensitivity and specificity, it may be interesting to combine several biomarkers. The purpose of this literature review was to increase knowledge about laboratory tests of FRMs and provide current knowledge and insight into these biomarkers related to DIC-sepsis. The method used in this literature review was a traditional review. Search, identify, and select relevant literature on PubMed–CBI and Google Scholar based on keywords, 30 journals were obtained from the two search engines.

Feasibility of Applying Novel FDP Threshold Criteria to DIC Diagnostic Scoring Systems in Japanese Women with Placental Abruption

<i>Objectiv</i>e: The diagnosis of disseminated intravascular coagulation (DIC) in obstetrics characterized by marked elevation of fibrin/fibrinogen degradation products (FDP) requires specific FDP criteria, however, no reference values are currently available. We previously reported the FDP criteria reflecting the degree of coagulation activity, determined by the quantitative relation between the distributions of FDP and fibrinogen. We aimed to evaluate the feasibility of applying the novel FDP criteria to four existing DIC diagnostic scoring systems, in a retrospective study of Japanese women with placental abruption. <i>Materials and Methods</i>: The study population was 68 pregnant women who had been diagnosed with placental abruption at Okayama Medical Center (Japan) between January 2008 and December 2020. DIC was clinically determined using the following four categories: plasma fibrinogen level < 100 mg/dl, hemorrhage amount at delivery ≥ 2000 g, blood product (red blood cells and fresh frozen plasma) transfusion, and renal dysfunction. Based on our previous report on the artificial intelligence analysis of the FDP distribution function, FDP criteria for the normal upper limit, moderate increase, and marked increase were defined as 20, 32, and 80 μg/ml, respectively. We applied the FDP criteria to compare four current and revised DIC diagnostic scoring systems: Japanese Ministry of Health and Welfare (JMHW), Japanese Association for Acute Medicine (JAAM), International Society on Thrombosis and Haemostasis (ISTH), and pregnancy-modified ISTH (PM-ISTH) DIC score. We used the Kruskal-Wallis test, Wilcoxon rank-sum test, and proportion test for statistical analysis. <i>Results</i>: Clinical DIC was observed in nine cases. Sensitivity was 1.00 in all DIC scoring systems. The current/revised sensitivity of the JMHW, JAAM, ISTH, and PM-ISTH systems was 1.00/1.00, 1.00/1.00, not available (NA)/1.00, and 1.00/NA, respectively. The current/revised specificity of the JMHW, JAAM, ISTH, and PM-ISTH systems was 0.864/0.864, 0.678/0.797, NA/0.864, and 0.424/NA, respectively. The specificity of the revised JMHW and revised ISTH systems was higher than for the current JAAM (<I>P </I>< 0.05) and current PM-ISTH (<I>P </I>< 0.0001) systems. The specificity of the revised JAAM improved from 0.678 to 0.797. <i>Conclusion</i>: Our novel proposed FDP criteria are potentially useful for diagnosis of DIC in placental abruption.

Patient profile and comparison of three diagnostic criteria for cardiac sarcoidosis in a tuberculosis endemic population.

Background:Cardiac sarcoidosis (CS) is an underdiagnosed and life-threatening condition. Histopathological diagnosis is difficult due to the risks and variable diagnostic yield of endomyocardial biopsy.Objectives:To study the clinical profile and compare the diagnostic criteria of CS in a cohort of sarcoidosis.Methods:A retrospective review of the Sarcoidosis database (375 patients) was performed to identify patients with CS. Demographic and clinical details were retrieved. We applied the available diagnostic criteria for the diagnosis of CS: The World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), Heart Rhythm Society (HRS), and Japanese Ministry of Health and Welfare (JMHW) criteria.Results:Out of the 375 patients, 15 (4%) were identified with CS. The median age was 41 years, and 53% were female. The most common symptoms were breathlessness, palpitation, and fatigue in 80%, 53.3%, and 46.6% of patients, respectively. Tuberculin positivity (≥ 10mm induration) was seen in 26.6%. 80% and 53.3% of the patients had abnormal ECG and 2D echocardiography findings, respectively. Six patients had a history of Ventricular tachycardia (40%). LV Ejection fraction was reduced in 12 subjects (80%). Cardiac-MRI showed late gadolinium enhancement in 53.3%. A definitive histopathological diagnosis for sarcoidosis was established in 86.6% (13/15) patients. Of the 15, all satisfied JMHW criteria and WASOG criteria (12 (80%) at least probable category, 3 (20%) possible CS), and 13 (86.6%) met HRS criteria for a diagnosis of CS.Conclusion:In a cohort of 375 patients with sarcoidosis in a tuberculosis endemic setting, 4% were diagnosed with cardiac sarcoidosis. Histopathological diagnosis may be obtained by sampling from extracardiac sites. JMHW and WASOG criteria perform equally well in TB endemic settings.

Agreement on Overt Disseminated Intravascular Coagulation in Sepsis Patients between International Society of Thrombosis and Haemostasis Criteria and Japanese Ministry of Health and Welfare Criteria

Disseminated Intravascular Coagulation (DIC) is an acquired syndrome characterized by the activation of intravascular coagulation which is most commonly caused by sepsis. There are two types of DIC disease: overt and non-overt DICs. The International Society of Thrombosis and Haemostasis (ISTH) criteria are more frequently used in the diagnosis of overt DIC compared to Japanese Ministry of Health and Welfare (JMHW). One of the different parameters of the two criteria is the D-Dimer element in the ISTH criteria and Fibrin Degradation Products (FDP) in the JMHW criteria. The availability of fibrin-related markers is different in each health center. This study aimed to see the agreement of the DIC diagnosis based on the ISTH and JMHW criteria and to analyze the correlation between D-Dimer and FDP in sepsis patients to help clinician decide which criteria is better to use. An analytical cross-sectional study was carried out on patients with sepsis based on the clinical diagnosis from the laboratory order forms and the DIC criteria according to the ISTH and JMHW. Patients included in this study were those visiting Dr. Hasan Sadikin General Hospital Bandung from August 2019-April 2020. Data collected were analyzed statistically using Cohen's Kappa test and Spearman test, both were performed in SPSS 17.0 program.There were 35 subjects participating in this study with overt and non-overt DIC with a composition based on the ISTH and JMHW criteria of 31 and 19 vs. 4 and 16, respectively. The Kappa coefficient between ISTH and JMHW was 0.266 (p 0.021) and the correlation between the D-Dimer and the FDP was 0.88 based on the Spearman test. There is a fair agreement on the DIC diagnosis and strong correlation between the FDP and the D-Dimer in sepsis patients when assessed using the ISTH and JMHW criteria. Both criteria are equally able to assist clinicians in determining the type of DIC depending on the type of fibrin-related markers available in the health centers.

Diagnostic Performance and Prognostic Value of a Chinese Diagnostic Scoring System (CDSS) for Disseminated Intravascular Coagulation—a Multicenter Prospective Study

AbstractObjectives: To evaluate the diagnostic performance and prognostic value of a Chinese DIC Scoring System (CDSS).Methods:1076 patients suspected of DIC were enrolled in 18 hospitals located across virtually the entire China. Scores of DIC were calculated on days 1-3 and 7, when DIC were diagnosed against the CDSS, the Japanese Ministry of Health and Welfare (JMHW) criteria, and the International Society on Thrombosis and Hemostasis (ISTH) criteria respectively. Illness severity and organ failure were assessed against the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) score. 28-day all-cause mortality was taken as a major prognostic sign.Results: If 28-day all-cause mortality was used as a standard for DIC diagnosis, compared with the ISTH and JMHW criteria, the CDSS had the highest sensitivity (CDSS, 81.19%; ISTH, 71.29%; JMHW 74.26%, p<0.05) in patients without hematological malignancies and highest specificity (CDSS, 48.05%; ISTH, 32.90%; JMHW 32.90%, p<0.05) in patients with hematological malignancies. The area under the ROC curve (AUC) of the CDSS was largest in all patients. If the ISTH or JMHW criteria were taken as a standard for DIC diagnosis, the comparison between the CDSS and the other criteria yielded similar results. The odds ratios (ORs) for mortality were much higher in patients without hematological malignancies (CDSS, 14.1; ISTH, 8.6; JMHW 11.4) as compared with patients with hematological malignancies (CDSS, 3.1; ISTH, 2.5; JMHW 3.2). Moreover, in patients without hematological malignancies, the OR in the CDSS was conspicuous higher than that in ISTH and JMHW criteria. Spearman's rank test revealed that the DIC score bore a significant correlation with APACHE II and SOFA score. Besides, the survival rate of the DIC patients diagnosed against CDSS was significantly lower than that of those without DIC.Conclusions: Compared with the ISTH and JMHW criteria, the CDSS has better diagnostic performance and prognostic value in DIC patients with different underlying diseases. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and safety of plasma hemodiafiltration (PHDF) in pediatric patients with multiple organ dysfunction syndrome with shock and DIC: a preliminary study

BackgroundMultiple organ dysfunction syndrome is the leading cause of death in pediatric intensive care units and can be very critical when combined with shock and disseminated intravascular coagulation (DIC). Currently, there is no effective treatment. We developed a new hemodiafiltration (HDF) method called plasma HDF (PHDF) that uses fresh frozen plasma as replacement fluid and investigated the safety and efficacy of this treatment.MethodsWe enrolled critically ill children with (1) a Pediatric Logistic Organ Dysfunction 2 (PELOD-2) score ≥ 14, (2) a Japanese Ministry of Health and Welfare (JMHW) DIC score ≥ 7, (3) a vasoactive inotropic score (VIS) ≥ 10, and (4) a serum total protein concentration ≤ 5.0 g/dL. PHDF was performed for 5 h and then switched to continuous HDF. The primary endpoint was the 28-day mortality rate. Secondary endpoints included assessment of vital signs, blood test data, and fluid balance from PHDF start to day 7.ResultsNine patients (four males and five females) between 3 days and 40 months of age, weighing 2.1–13 kg, met the inclusion criteria. Although the median PMR was 0.94 (0.71–0.96), the 28-day mortality rate was 22.2% (2/9). One hour after the start of PHDF, there was an increase in mean arterial pressure and central venous pressure and a decrease in heart rate; by day 7, there was a significant decrease in the PELOD-2 score, the JMHW DIC score, and the VIS. Hypoproteinemia also improved the day after PHDF. Water balance was able to remain negative after day 2.ConclusionsPHDF was found to be effective in the treatment of DIC and circulatory failure by supplementing coagulation and antithrombotic factors as well as by raising colloid osmotic pressure to increase circulating blood volume. PHDF has been shown to be a safe and useful treatment for critically ill children and has the potential to improve 28-day survival.

Utility of updated diagnositc criteria to detect isolated cardiac sarcoidosis

Abstract Background Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS. Purpose We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines. Methods We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy. Results The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P&amp;lt;0.05 for all). Compared with clinical diagnosis group, patients with isolated CS showed higher incident of regional wall motion abnormality (WMA) or left ventricular (LV) dysfunction (p=0.023). In the subgroup of 45 patients with serial FDG-PET evaluation, only updated CS criteria was associate with improvement in myocardial inflammation by FDG-PET (p&amp;lt;0.001). Conclusions Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines. Diagnostic criteria for CS Funding Acknowledgement Type of funding source: None

P1805Troponin-T, NT-proBNP and creatinine at presentation predict outcomes in patients with cardiac sarcoidosis

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative inflammatory condition defined by infiltration of noncaseating granulomas into the heart. Based on the location of sarcoid lesion involvement, patients can present with symptoms of congestive heart failure, arrhythmias, and even sudden cardiac death. Purpose Diagnosis of CS has been somewhat challenging, with the Heart Rhythm Society (HRS) and Japanese Ministry of Health and Welfare (JMHW) being the 2 widely accepted diagnostic guidelines. Endomyocardial biopsy is the gold standard to prove definite CS but has a low sensitivity. Imaging studies have been helpful as non-invasive methods to diagnose probable CS but these can be logistically difficult and expensive. Thus, investigating for laboratory biomarkers that can act as both diagnostic and prognostic can be crucial in how we diagnose and manage CS in the future. Methods Patients meeting HRS for CS were evaluated at a single institution (n=217). Biomarkers of interest included angiotensin-converting enzyme (ACE), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin-T, 1,25 dihydroxyvitamin D (1,25-OHVit-D), and creatinine. Biomarkers were stratified by clinical variables of interest and their association with prognosis was examined. The primary endpoint was LVAD implantation, transplantation, or death. Results Mean values on presentation were: ACE 32.9±28, ESR 12±13, CRP 7.4±19, NT-proBNP 1630±2923, Troponin-T 0.03±0.1, 1,25-OHVit-D 55.5±20, and creatinine 1.12±0.3. None of the biomarkers differed by sex, definite or probable CS, or a history of immunosuppression. ACE levels were associated with the presence of cardiac fibrosis on cardiac MRI (mean difference 14.7, p=0.032). Troponin-T (p=0.006; HR 1.06 per 0.01 ng/mL), NT-proBNP (p=0.0003; HR 1.31 per 1,000 pg/mL), and creatinine (p=0.01; HR 4.02 per mg/dL) were each associated with the primary endpoint (52/217 patients). Biomarkers associated with long term outcomes in patients with cardiac sarcoidosis Biomarker Hazard ratio P value Troponin-T 1.06 (1.02–1.11)* 0.006 NT-pro BNP 1.31 (1.15–1.48)** 0.0003 Creatinine 4.02 (1.41–9.94)*** 0.01 *Per 0.01 ng/mL change; 99th percentile upper reference limit &lt;0.01 ng/mL; **per 1,000 pg/mL change; ***per 1 mg/dL change. Conclusion Troponin-T, NT-proBNP, and creatinine at presentation predict outcomes in patients with CS. Further investigation on the utility of biomarkers for assessment of disease activity and treatment response is warranted.

Impact of Antithrombin Supplementation and Concomitant Anticoagulation Therapy in Pediatric Patients With Disseminated Intravascular Coagulation

We aimed to evaluate the efficacy and safety of antithrombin (AT) supplementation and concomitant anticoagulation therapy in 65 children who met the Japanese Ministry of Health and Welfare (JMHW) disseminated intravascular coagulation (DIC) criteria and had received AT concentrate and/or other concomitant anticoagulants. The primary efficacy end point was to determine standardized mortality ratio (SMR). The secondary efficacy end points were DIC resolution rate and pediatric sequential organ failure assessment (pSOFA) score on day 3. The 28-day mortality rate was 6.8%; SMR was 0.55. Disseminated intravascular coagulation resolution rate on day 3 was 54.5%. The JMHW DIC scores at day 0 (P = .005) and pSOFA scores at day 3 (P = .018) were significantly lower in patients with resolution of DIC than in those without resolution of DIC. The target cutoff value for JMHW DIC score on day 0 was 6. No bleeding-related adverse events were associated with AT administration. In children with DIC, AT supplementation and concomitant anticoagulation therapy can be safely used as initial treatment when JMHW DIC score is 6; it may improve DIC resolution, organ failure, and mortality rates.

Cardiac Magnetic Resonance Imaging for Diagnosis of Cardiac Sarcoidosis: A Meta-Analysis.

Background Cardiac magnetic resonance imaging (CMR) is an effective technique for the diagnosis of cardiac sarcoidosis (CS). The efficacy of CMR versus the Japanese Ministry of Health and Welfare (JMHW) guidelines considered as standard criterion for the diagnosis of CS remains to be elucidated. Methods In this systematic review and meta-analysis, we aimed at assessing the diagnostic accuracy of CMR in cardiac sarcoidosis. We searched on PubMed from January 1, 1980, to March 28, 2018, on Embase from January 1, 1980, to March 29, 2018, and on the Cochrane Library from January 1, 1980, to April 1, 2018, using a strategy based on the search terms (sarcoidosis and magnetic resonance imaging) independently. We analyzed the data obtained with Revman 5.3 and Stata 14.0 software. Results Eight studies with a total of 649 participants met the inclusion criteria, and data were extracted. CMR had an overall sensitivity of 0.93 (95% confidence interval (CI), 0.87–0.97) and specificity of 0.85 (95% CI, 0.68–0.94) for the diagnosis of cardiac sarcoidosis. The area under the summary receiver operating characteristic (SROC) curve was 0.95 (95% CI, 0.93–0.97). The subgroup analysis via public year showed that studies between 2011 and 2017 had an overall sensitivity of 0.95 (95% CI, 0.88–0.98) and specificity of 0.92 (95% CI, 0.49–0.99), with an area under the SROC curve being 0.96. Conclusions The results of this meta-analysis suggest that CMR could be used for the diagnosis of cardiac sarcoidosis and screening of patients suspected of CS. With the improvement of the technique, the diagnostic accuracy of MRI has improved.

A multicenter, prospective evaluation of the Chinese Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation

IntroductionDisseminated intravascular coagulation (DIC) is a severe complication of critical conditions. There are several scoring systems used for the diagnosis of DIC, including the International Society on Thrombosis and Hemostasis (ISTH) Overt-DIC criteria, the Japanese Ministry of Health and Welfare (JMHW) criteria and the Chinese Society of Thrombosis and Hemostasis scoring system for DIC (CDSS). The objective of this prospective study was to evaluate the accuracy and predictive value of the CDSS. Materials and methods1318 patients, aged 18–70 years old and suspected of DIC were enrolled from 18 hospitals across China. Participants were divided into two groups for analysis (group 1, non-hematological diseases; group 2, hematological diseases). 242 patients were excluded because of incomplete data collection and failure to follow-up. Results and conclusionsThe rates of concordance of diagnosis of DIC between the CDSS and two other scoring systems were close to 80%. The area under ROC curves of CDSS had a slight advantage when using the ISTH, JMHW criteria or prognosis as gold standard, respectively. The CDSS DIC was an independent predictor of mortality, and its odds-ratio was superior or comparable to that of the ISTH and JMHW criteria in the two groups. The CDSS DIC score also had a significant correlation with the APACHE II and SOFA score (p < 0.05). In summary, as a quantification standard of the Chinese experts' consensus, the CDSS is conducive to the standardized diagnosis of DIC because of its favorable diagnostic and prognostic utility.

Performance of 5 disseminated intravascular coagulation score systems in predicting mortality in patients with severe trauma.

The present study aimed to analyze and compare the prognostic performances of the Japanese Ministry of Health and Welfare (JMHW) score, the Korean Society on Thrombosis and Hemostasis (KSTH) score, the International Society on Thrombosis and Haemostasis (ISTH) score, the Japanese Association for Acute Medicine (JAAM) score, and the revised JAAM (rJAAM) score, for 28-day mortality in severe trauma.This retrospective observational study included patients admitted for severe trauma between 2012 and 2015. Receiver operating characteristics analysis was performed to examine the prognostic performance of the 5 different DIC score systems. The primary outcome was 28-day mortality following an injury.Of the 1266 patients included in the study, 28-day mortality rate was 19.7% (n = 249). The area under the curves (AUCs) of JMHW, KSTH, ISTH, JAAM, and rJAAM scores for 28-day mortality were 0.751 [95% confidence interval (95% CI), 0.726–0.775], 0.726 (95% CI, 0.701–0.750), 0.700 (95% CI, 0.674–0.725), 0.673 (95% CI, 0.646–0.699), and 0.676 (95% CI, 0.649–0.701), respectively. The AUC of JMHW score was significantly different from those of the other score systems. Fibrinogen levels ≤1.0 g/L [odds ratio (OR), 1.824; 95% CI, 1.029–3.232] and 1.0 to 1.5 g/L (OR, 1.697; 95% CI, 1.058–2.724) were independently associated with 28-day mortality compared with fibrinogen level above 1.5 g/L.JMHW score has the highest prognostic performance for 28-day mortality among DIC score systems in severe trauma. Fibrinogen level seemed to have a role in greater discrimination of JMHW scores than the other DIC score systems.

Clinical evaluation of Chinese disseminated intravascular coagulation scoring system (version 2017) in patients with acute promyelocytic leukemia

目的探索2017年版中国DIC诊断积分系统（CDSS）在急性早幼粒细胞白血病（APL）DIC诊断中的适用性。方法回顾性分析2004年1月至2018年2月就诊于中国医学科学院血液病医院并行诱导治疗的220例APL患者病历资料，采用CDSS、国际血栓与止血协会（ISTH）DIC积分系统和日本卫生福利部（JMHW）DIC积分系统分别进行评价及比较分析。结果220例APL患者中，男114例，女106例，中位年龄38.5（12~70）岁，其中低/中危组173例，高危组47例。11例患者诱导治疗期死亡。CDSS、ISTH、JMHW三种标准诊断DIC阳性率分别为62.27%、54.09%、69.09%。CDSS和ISTH诊断DIC的一致率为78.10%，CDSS和JMHW诊断DIC的一致率为88.32%。ROC曲线比较三者互为参照的敏感度及特异度，敏感度JMHW>CDSS>ISTH，特异度ISTH>CDSS>JMHW。CDSS DIC（+）和DIC（−）组患者PT、APTT、纤维蛋白原（FIB）、D-二聚体及纤维蛋白原/纤维蛋白降解产物（FDP）之间差异均有统计学意义（P值均<0.05）；但采用ISTH诊断积分系统时DIC（−）组的D-二聚体水平高于DIC（+）组[26.3（0.6~488.7）mg/L对21.9（1.2~477.1）mg/L，χ2=1.871，P=0.002]；采用JMHW诊断积分系统时DIC（+）与DIC（−）组的APTT差异无统计学意义[27.05（18.0~181.0）s对26.15（18.2~35.5）s，χ2=1.162，P=0.134]。CDSS DIC（+）和DIC（−）组患者的年龄及性别差异无统计学意义（P>0.05）；单因素Logistic回归显示患者起病时WBC、骨髓中异常早幼粒细胞比例对DIC的发生存在影响（P<0.05），而多因素分析显示在CDSS中起病时WBC>3×109/L是DIC发生的独立危险因素（OR=3.525，95%CI 1.875~6.629，P<0.001）。结论2017年版CDSS诊断DIC的敏感度高于ISTH DIC积分系统，特异度优于JMHW DIC积分系统。CDSS较ISTH、JMHW对于DIC相关指标具有较好区分度，适用于中国APL患者的DIC诊断。

Evaluation of the new Chinese Disseminated Intravascular Coagulation Scoring System in critically ill patients: A multicenter prospective study

Disseminated intravascular coagulation (DIC) is a common life-threatening complication in critically ill patients. The diagnostic scoring systems of DIC enable a more prompt and accurate diagnosis of DIC, such as the International Society on Thrombosis and Haemostasis (ISTH), the Japanese Association for Acute Medicine (JAAM) and the Japanese Ministry of Health and Welfare (JMHW). This study prospectively evaluated the newly proposed Chinese DIC Scoring System (CDSS), which was conducted at 18 centers in China during a one-year period. Receiver operating characteristic (ROC) curves showed that, for diagnosis of DIC and for prediction of the 28-day all-cause mortality, the CDSS had larger areas under the ROC curve (AUCs) than the ISTH and the JAAM in different groups. The CDSS also had larger AUC than the JMHW for the ISTH DIC in non-infectious diseases. All of the AUCs of the CDSS were greater than 0.8, accompanied with both high sensitivity and high specificity. Furthermore, the CDSS score was an independent predictor of mortality (odds ratio, 1.882; p < 0.001), and could reflect the illness severity (p < 0.001 for Spearman’s rank correlations with the scores of severity). In conclusion, the CDSS is worthy of promotion with a better diagnostic and prognostic value for DIC.

Increased Levels of Histone in Human Plasma in Septic Patients with DIC

<Background and Methods>Sepsis is a life-threatening condition that is characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome, SIRS). Histones are essential for packing DNA into the cell nucleus and also play role in regulating gene expression but the new study (Jun Xu et al, Nature Medicine 15. 1318, 2009) have shown histones released into blood stream at the onset of sepsis can have devastating effects (endothelial damage and organ failure etc). However, plasma levels of histone are unclear in septic patients with DIC. Therefore, We developed a sandwich ELISA to quantify serum or plasma histone H3 levels and measured plasma levels of histone H3 in septic patients with DIC (n=30).<Results>DIC was diagnosed on the Japanese Ministry of Health and Welfare (JMHW) DIC diagnostic criteria. The thrombin antithrombin complexes (TAT) levels were higher in septic patients with DIC as reported by others. The working range of this ELISA was 3-1000 ng/ml. In healthy volunteers, plasma levels of histone (H3) were not detectable. We detected high levels of extracellular hisotone (H3) in the plasma of all septic patients with DIC by sandwich ELISA. Mean plasma levels of hisotone (H3) were 70.5 ± 63.2 (12.9-336.5) ng/ml in septic patients with DIC. However, plasma levels of extracellular histone (H3) were negative in acute promyelocytic leukemia (APL)-induced DIC (n=5). Also, Plasma levels of histone were 10 ng/ml or less by sandwich ELISA in septic patients without DIC (n=8).<Conclusion>These results suggest that assess of extracellular hisotones in the plasma may be helpful in the making the diagnosis in septic patients with DIC. Also, it appears that extracellular hisotones in the plasma may contribute to develop DIC in septic patients. DisclosuresNo relevant conflicts of interest to declare.

Retrospective Evaluation of New Chinese Diagnostic Scoring System for Disseminated Intravascular Coagulation.

ObjectivesTo retrospectively validate the new Chinese DIC scoring system (CDSS).MethodsThis study retrospectively collected the information of 619 patients (371 cases with non-hematologic malignancies, 248 cases with hematologic malignancies) who suspected of DIC in Wuhan Union Hospital during 2013-4 to 2014-6. We validated CDSS by comparing it with three leading scoring systems, from International Society on Thrombosis and Haemostasis (ISTH), Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW), and evaluated its prognostic value by 28 days mortality, APACHE II and SOFA score.ResultsIn non-hematologic malignancies, CDSS was more specific than JAAM (72.55% vs. 50.49%, p<0.05) and more sensitive than ISTH (77.07% vs. 62.03%, p<0.05). In hematologic malignancies, the area under the ROC curve of CDSS was larger than ISTH and JMHW (0.933 vs. 0.889, p<0.01 with ISTH, 0.944 vs. 0.845, p<0.01 with JMHW). In addition, the 28-day mortality rate, SOFA scores, APACHE II scores of DIC patients diagnosed by CDSS were significantly greater than non-DIC (P <0.05).ConclusionsWe are the first group to propose CDSS. It emphasized the values of the clinical manifestations, the rapidly declining platelet count, APTT in the diagnosis of DIC and used D-dimer as the fibrin-related maker. DIC with hematological malignancies was treated as a special part. In this study we can see that CDSS displayed an acceptable property for the diagnosis of DIC with appropriate sensitivity and specificity, and also had a good prognostic value for DIC patients.

Role of plasma high mobility group box-1 in disseminated intravascular coagulation with leukemia

IntroductionHigh mobility group box 1(HMGB1) is a DNA-binding protein which can act as a proinflammatory cytokine when released by necrotic cells, monocytes or macrophages. It also plays a role in the coagulation activation and several tumors including leukemia. The objective of this study was to investigate the role of HMGB1 in the diagnosis of DIC with leukemia. Methods89 subjects with leukemia in Wuhan Union Hospital were prospectively recruited. Among them, 83 cases were suspected of DIC, while the other 6 were the negative controls. Their clinical data, laboratory tests and plasma samples were collected or measured respectively. Accordingly, we made scores for these subjects by the Japanese Ministry of Health and Welfare (JMHW) criteria. ResultsThis study demonstrated that the plasma levels of HMGB1 were higher in the DIC group than non-DIC (115.16 ng/ml vs. 63.94 ng/ml, p=0.003). The similar results were achieved in infected or non-infected groups. And along with the increase of DIC scores, the levels of HMGB1 increased gradually (p=0.006). In addition, HMGB1 was an independent factor in the diagnosis of DIC with leukemia(p<0.05). The diagnostic sensitivity of HMGB1 was high (Se=90.32%), and there was a tendency of increased HMGB1 levels in the pre-DIC patients. Three of these six pre-DIC patients were diagnosed as DIC by the new revised scoring system which contained HMGB1. Finally, the HMGB1 levels were significantly higher in patients with organ failures (SOFA≥2) than those without (118.76 vs. 72.75, p=0.032). ConclusionThe increased plasma levels of HMGB1 were related tightly to the diagnosis and severity of DIC in leukemia patients. Furthermore, the diagnostic sensitivity of HMGB1 was high. So HMGB1 in plasma is a helpful molecular marker, and can be added in the scoring system for the early diagnosis of DIC with leukemia.

Recombinant Human Thrombomodulin in the Treatment of Acute Myeloid Leukemia Patients Complicated By Disseminated Intravascular Coagulation: Results of a Multicenter, Retrospective Epidemiologic Study in Japan

Background: Thrombomodulin is a thrombin receptor that acts an important regulator of coagulation. Recombinant human thrombomodulin (rTM) is a promising anticoagulant that activates protein C, which leads to the inactivation of factor (F) Va and FVIIIa and decreased formation of thrombin. rTM has also been identified as a novel anticoagulant with a long half-life. When compared with heparin therapy, rTM therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients. However, it is unknown as to whether or not the treatment with rTM affects patient’s outcome. Therefore, we retrospectively analyzed 88 patients with acute myeloid leukemia (AML) (except adult acute promyelocytic leukemia), who suffered from DIC and compared the outcomes between the patients with low molecular weight heparin (LMWH) therapy and with rTM in multi-center.Methods: The diagnosis of de novo AML patients was based on the morphology, histopathology, cytogenetics, expression of leukocyte-differentiation antigens, and the French-American-British (FAB) classification. The patients examined in the current study (aged 18–84 years) were diagnosed with AML from January 2004 to March 2013. Patients younger than 65 years of age were treated with idarubicin (12 mg/m2 per day) for 3 days (days 1–3) and cytarabine (100 mg/m2 per day) by continuous infusion for 7 days (days 1–7). Patients 65 years of age or older were treated with daunorubicin (40 mg/m2 per day) for 3 days (days 1–3) and 200 mg/m2 per day behenoyl cytarabine for 8 days (days 1–8). The continuous infusion of dalteparin sodium (75 IU/kg per day) or recombinant human thrombomodulin (380 U/kg per day) was used to treat DIC.The diagnostic criteria for DIC previously proposed by the Japanese Ministry of Health and Welfare (JMHW) were employed in this study. The criteria are based on a scoring system including the presence of underlying disease (0 or 1 points), organ failure (0 or 1 points), and the results of coagulation tests of fibrinogen (0 to 2 points), fibrin/fibrinogen degradation products (FDP, 0 to 3 points), and the prothrombin time (0 to 2 points). DIC is diagnosed when the DIC score is greater than 4.Comparisons between the qualitative variables were carried out using the Chi-square test. The survival probabilities were estimated by the Kaplan-Meier method, and differences in the survival distributions were evaluated using the log-rank test. These statistical analyses were performed with the software package Stata version 11 (StataCorp LP, College Station, TX, USA). For all analyses, the P values were 2-tailed, and a P value less than.05 was considered to be significant.Results: DIC developed in 88 patients. Median age of patients was 60 years (from 15 to 85) and median duration was 699 days (from 15 to 2552 days). 30 patients were treated with dalteparin sodium and 58 patients were treated with recombinant human thrombomodulin. The FAB subtypes, age distribution, major laboratory data (CBC, LDH, and CRP) were not significantly different between two groups. The duration of DIC treatment with rTM was significant shorter than that with LMWH (6.3 days vs 15.1 days, p <0.0001). The overall survival was superior in the rTM group compared with dalteparin sodium group (P=0.0425).Discussion: Patients with DIC resulting from sepsis or hematological malignancies can be successfully treated if sufficient treatments are offered. However, additional anti-coagulant treatments may be required in many cases because of life-threatening abnormal coagulation states. In Japan, LMWH has been recommended by the Japanese Society of Thrombosis Hemostasis/DIC subcommittee for the treatment of DIC because patients were less likely to bleed when treated with LMWH than with unfractionated heparin (UFH) (Level 2b). On the other hand, a randomized controlled study reported that rTM therapy improved DIC and relieved bleeding complications in DIC patients more significantly than UFH therapy. To the best of our knowledge, very few institutes compared rTM with heparin as a therapy for DIC during AML induction therapy. Here, we demonstrate that if patients develop DIC, their prognosis will be improved by the administration of rTM.Conclusion: We conclude that treatment with rTM is safe and efficient, when compared with LMWH. Based on this retrospective study, randomized control study could be attempted in the future. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CLINICAL IMPLICATIONS OF FDG-PET IN SUSPECTED CARDIAC SARCOIDOSIS

An optimal strategy for diagnosing cardiac sarcoidosis (CS) and monitoring treatment response is lacking. FDG-PET is a highly sensitive and specific test for CS that assesses disease activity, but its additive value to other modalities in the clinical setting remains unclear. To determine the impact of FDG-PET in relation to biopsy, cardiac MRI, and the Japanese Ministry of Health and Welfare (JMHW) criteria on the course of patients with suspected CS. Retrospective cohort study of suspected CS patients who were offered FDG-PET through a limited access feasibility study in the Province of British Columbia. Baseline characteristics, sequence of diagnostic testing, and treatment decisions were examined for patients who underwent FDG-PET between January 2013 and March 2014. Clinical data and FDG-PET results for 20 patients who underwent the scans were available for analysis. Median age was 58 years, and men comprised 60% of the cohort. Nine (45%) patients presented with low EF, 4 (20%) with VT, 4 (20%) with advanced heart block, 2 (10%) with SVT, and 1 (5%) with acute myocarditis. Median EF on echo was 45%, and 12 (60%) patients required ICD, mostly for secondary prevention (9 patients). Of the 13 (65%) patients who underwent cardiac biopsy, 5 (38%) were consistent with sarcoidosis. All biopsy positive patients had normal FDG uptake, however 4 of these patients were already treated prior to their scan. Six (30%) patients had abnormal cardiac FDG uptake, including 2 that had received prior steroid therapy. Five out of 8 patients with negative cardiac biopsy had abnormal cardiac FDG uptake. While 13 (65%) patients had confirmed or high suspicion of CS after multimodality testing and biopsy, only 2 (10%) met the JMHW diagnostic criteria. FDG-PET influenced management in 14 (70%) patients: by helping initiate, continue, or change steroid dosage in 3 (15%) patients, and by allowing discontinuation or lack of initiation of treatment in 11 (55%) patients on the basis of negative FDG-PET. Of the remaining 6 (30%) patients, either no treatment was given despite an abnormal FDG uptake in 2 patients due to clinically silent disease, or treatment decisions were not yet finalized. In our series, FDG-PET aided in treatment decisions in patients suspected of CS. Due to its ability to assess disease activity and monitor response to therapy, FDG-PET adds value beyond conventional testing, and its use is advocated in cases with high suspicion of CS.