Outcomes of Octogenarians and Nonagenarians in a Contemporary Cardiac Care Unit　- Insights From 2,242 Patients Admitted Between 2019 and 2021.

Background: The number of octo- and nonagenarians admitted to cardiac care units (CCUs) has been increasing in the context of an aging society; however, clinical details and outcomes for these patients are scarce. Methods and Results: Data from 2,242 consecutive patients admitted to the CCU between 2019 and 2021 (age <80 years, 1,390 [62%]; octogenarians, 655 [29%]; nonagenarians, 197 [8.7%]) were reviewed using the in-hospital database for the Tokyo CCU Network. The primary cause of admission was acute coronary syndrome in younger patients and octogenarians (58% and 49%, respectively) and acute heart failure (AHF) in nonagenarians (42%). The proportions of females, underweight, hypertension, atrial fibrillation, myocardial infarction, stroke, previous heart failure, anemia, and malnutrition were higher among octo- and nonagenarians than among younger patients. In-hospital and 1-year mortality rates were greater in octo- and nonagenarians (younger vs. octogenarian vs. nonagenarian, 2.0% vs. 3.8% vs. 5.6% and 4.1% vs. 11.9% vs. 19.0%, respectively). Multivariate analysis revealed that 1-year mortality was associated with octo-/nonagenarian status (odds ratio [OR] 2.24 and 2.64), AHF (OR 2.88), body mass index (OR per 1-kg/m2 0.91), and albumin concentration (OR per 1-g/dL 0.27). Conclusions: Approximately 40% of patients admitted to the CCU were octo- or nonagenarians, and being an octo- or nonagenarian, having AHF, a lower body mass index, and lower albumin concentrations were associated with 1-year mortality after CCU admission.

The Anti-Inflammatory Effects and Clinical Potential of Dexmedetomidine in Pulmonary Arterial Hypertension.

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective α-2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions. We investigated the hypothesis that anti-inflammatory characteristics of DEX could lessen PAH that monocrotaline (MCT) causes in rats. In vivo, male Sprague-Dawley rats aged 6 weeks were subcutaneously injected with MCT at a dose of 60 mg/kg. Continuous infusions of DEX (2 µg/kg per hour) were started via osmotic pumps in one group (MCT plus DEX group) at day 14 following MCT injection but not in another group (MCT group). Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), and survival rate significantly improved in the MCT plus DEX group compared with the MCT group [RVSP, 34 mmHg ± 4 mmHg versus 70 mmHg ± 10 mmHg; RVEDP, 2.6 mmHg ± 0.1 mmHg versus 4.3 mmHg ± 0.6 mmHg; survival rate, 42% versus 0% at day 29 (P < 0.01)]. In the histologic study, the MCT plus DEX group showed fewer phosphorylated p65-positive PASMCs and less medial hypertrophy of the pulmonary arterioles. In vitro, DEX dose-dependently inhibited human PASMC proliferation. Furthermore, DEX decreased the expression of interleukin-6 mRNA in human PASMCs treated with fibroblast growth factor 2 (FGF2). These consequences suggest that DEX improves PAH by inhibiting PASMC proliferation through its anti-inflammatory properties. Additionally, DEX may exert anti-inflammatory effects via blocking FGF2-induced nuclear factor κ B activation. SIGNIFICANCE STATEMENT: Dexmedetomidine, a selective α-2 adrenergic receptor agonist utilized as a sedative in the clinical setting, improves pulmonary arterial hypertension (PAH) by inhibiting pulmonary arterial smooth muscle cell proliferation through its anti-inflammatory effect. Dexmedetomidine may be a new PAH therapeutic agent with vascular reverse remodeling effect.

Factors Related to Hospitalisation-Associated Disability in Patients after Surgery for Acute Type A Aortic Dissection: A Retrospective Study.

The in-hospital mortality rate among patients after surgery for acute type A aortic dissection (ATAAD) has improved chronologically. However, the relationship between the incidence of hospitalisation-associated disability (HAD) and acute cardiac rehabilitation in patients after surgery for ATAAD has not been reported. Therefore, this study evaluated factors related to HAD in patients after surgery for ATAAD. This single-centre retrospective observational study included 483 patients who required emergency surgery for ATAAD. HAD occurred in 104 (21.5%) patients following cardiovascular surgery. Factors associated with HAD were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.001), noninvasive positive pressure ventilation (NPPV; OR, 2.15; 95% CI, 1.10-4.19; p = 0.025), postoperative delirium (OR, 2.93; 95% CI, 1.60-5.37; p = 0.001), and timing of walking onset (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008). Furthermore, a late walking onset was associated with a higher risk of developing HAD and more severe functional decline. Early rehabilitation based on appropriate criteria has possibility of preventing HAD.

Coronary ostial angioplasty for juvenile Takayasu arteritis involving the coronary artery using external iliac artery grafts.

Takayasu arteritis can affect the coronary ostia, leading to myocardial ischemia. Coronary ostial angioplasty effectively treats coronary artery ostial lesions associated with Takayasu arteritis. We present a case of juvenile Takayasu arteritis with bilateral subclavian artery occlusions treated with a novel coronary artery ostial angioplasty using the external iliac artery.

Physical function examination at intensive care unit as predictive indicators for hospitalization-associated disability in patients after cardiovascular surgery.

BACKGROUND: Following cardiovascular surgery, patients are at high risk of requiring systemic management in the intensive care unit (ICU), resulting in hospitalization-associated disability (HAD). Predicting the risk of HAD during the postoperative course is important to prevent susceptibility to cardiovascular events. Assessment of physical function during the ICU stay may be useful as a prediction index but has not been established. METHODS: This prospective observational study conducted at a high-volume cardiovascular center included 236 patients (34% female; median age, 73 years) who required an ICU stay of at least 72 hours after surgery and underwent postoperative rehabilitation. HAD was defined as a decrease in the discharge Barthel index (BI) score of at least 5 points relative to the preadmission BI score. Physical Function ICU Test-scored (PFIT-s), Functional Status Score for the ICU (FSS-ICU), and Medical Research Council (MRC)-sumscore were used to assess physical function at ICU discharge. RESULTS: HAD occurred in 58 (24.6%) of the 236 patients following cardiovascular surgery. The cut-off points for HAD were 7.5 points for the PFIT-s (sensitivity 0.80, specificity 0.59), 24.5 points for the FSS-ICU (sensitivity 0.57, specificity 0.66), and 59.5 points for the MRC-sumscore (sensitivity 0.93, specificity 0.66). Multivariate logistic regression analysis revealed a PFIT-s of >7.5 points (odds ratio [OR], 4.84; 95% CI, 2.39-9.80; p < 0.001) and an MRC-sumscore of >59.5 points (OR, 2.43; 95% CI, 1.22-4.87; p = 0.012) as independent associated factors. CONCLUSIONS: We demonstrate that the PFIT-s and MRC-sumscore at ICU discharge may be helpful as a predictive indicator for HAD in patients having undergone major cardiovascular surgery.

[Asymptomatic Congenital Left Ventricular Aneurysm Treated with Endocardial Linear Infarct Exclusion Technique( ELIET):Report of a Case].

Surgical repair of asymptomatic congenital left ventricular aneurysm is poorly reported. A 30-yearold man presented with an asymptomatic abnormal electrocardiogram. Computed tomography (CT) and angiography revealed a congenital left ventricular aneurysm, and surgical repair was conducted with endocardial linear infarct exclusion technique (ELIET). His postoperative course was uneventful. Postoperative CT showed an elliptical cardiac shape with no recurrence of aneurysm. ELIET would serve as a surgical procedure for congenital left ventricular aneurysm.

[Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy Due to Noonan Syndrome;Report of a Case].

A 15-year-old boy with Noonan syndrome, who had been diagnosed with hypertrophic cardiomyopathy (HCM) at 4 and treated by drugs, was referred to our hospital because of progression of left ventricular outflow tract obstruction (LVOTO). Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy( LVH), LVOTO( systolic gradient:102 mmHg), and systolic anterior motion of the mitral valve( SAM) with mild mitral regurgitation(MR). We performed septal myectomy by transaortic and transapical approaches. Postoperative TTE revealed significant reduction in left ventricular outflow tract (LVOT) gradient (9 mmHg), resolution of SAM, and reduction in MR grade. The postoperative course was uneventful except for transient atrial tachyarrhythmia. Myectomy for HCM in a patient with Noonan syndrome is rare. This case suggests that myectomy is useful for the patients with Noonan syndrome.

Cryoballoon Ablation Induced Hyperkalemia due to Possible Cold Agglutinin Disease.

Cryoballoon ablation is a well-established therapeutic tool for paroxysmal atrial fibrillation (PAF). We herein report a rare case of a 69-year-old man with PAF undergoing hemodialysis due to chronic kidney disease who developed hyperkalemia caused by possible cold agglutinin disease during cryoballoon ablation therapy. During the procedure, his electrocardiogram showed wide QRS when we finished cryoablation therapy. We detected hyperkalemia and performed urgent hemodialysis. We should bear in mind that cold agglutinin disease can occur during cryoballoon ablation.

New tailored approach using a revised assessment of fragmented potentials for persistent atrial fibrillation: Early area defragmentation by modified CFAE module.

INTRODUCTION: Pulmonary vein isolation (PVI) is widely performed for atrial fibrillation (AFib). However, it is insufficient to maintain sinus rhythm (SR) in persistent and long persistent atrial fibrillation (Per-AFib). Ablation of complex fractionated atrial electrograms (CFAEs) is currently classified as class IIb, However, the concept of length of potential was different between the current CFAE module of CARTO system and the definition of CFAE potential. The current CFAE module was configured in the shortest complex interval (SCI) mode, in which the meaning of length of potential was the interval of each component of fragmented potentials. That was a part of the potential. On the other hand, the meaning of the definition of CFAE potential was the length of fragmented potential itself. The purpose of this study was to essentially evaluate fragmented potentials by revisiting in interval confidence level (ICL) mode and express them on the map and prospectively investigate the efficacy and prognosis of a new tailored approach for defragmentation, which is called early area defragmentation (EADF). METHODS AND RESULTS: We acquired atrial potentials by modified CFAE module in ICL mode (K-CFAE potential) and visualized the distribution of K-CFAE potential (K-CFAE map). We performed PVI, and we ablated the fragmented areas based on the K-CFAE map. We enrolled 77 patients in this study (control group: 84 patients). After 24-month follow-up, 75.3% were able to maintain SR. CONCLUSIONS: K-CFAE mapping faithfully represented the distribution of fragmented areas. PVI, together with our new tailored approach, EADF, was successful in treating Per-AFib.

Beneficial effects of losartan for prevention of paroxysmal atrial fibrillation in patients with sick sinus syndrome: analysis with memory function of pacemaker.

Renin-angiotensin system (RAS) inhibitors may be useful in preventing the occurrence of paroxysmal atrial fibrillation (PAF). However, evaluation of such effect is difficult because many PAF episodes are asymptomatic and not all episodes are detected by intermittent electrocardiographic monitoring. A pacemaker has been developed with dedicated functions for AF detection and electrocardiogram storage. Accordingly, we examined the effect of losartan, an angiotensin receptor blocker on PAF occurrence using this new modality. We enrolled 70 consecutive patients who had undergone dual-chamber pacemaker implantation for sick sinus syndrome. Finally, 62 patients participated in the study. Thirty patients were randomized to the losartan group (mean 43 ± 12 mg/day) and 32 patients to the control group. They were followed up for 3 months. The frequency, the maximum duration and the total duration of PAF recorded by the stored electrocardiograms for the last 1 month during the observation period and study period were compared between the two groups. The change in the frequency of PAF from the observation period in the losartan and control groups was similar (-35 ± 25 vs. -67 ± 62 times; NS). However, the change in the maximum duration and the total duration of PAF was significantly shorter in the losartan group than in the control group (-493 ± 158 vs. -10 ± 69 min; p < 0.05, and -4007 ± 2334 vs. 1119 ± 714 min; p < 0.05, respectively). Losartan suppressed the maximum duration and the total duration of PAF in patients with sick sinus syndrome without hemodynamic changes. This is the first study to show the effect of a renin-angiotensin system inhibitor on the secondary prevention of PAF using the dedicated functions of a pacemaker for PAF detection and electrocardiogram storage.

Polymyxin B-immobilized fiber column hemoperfusion mainly helps to constrict peripheral blood vessels in treatment for septic shock.

BACKGROUND: Polymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment. METHODS: We retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group). RESULTS: The inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from 0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p < 0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p < 0.05). CONCLUSIONS: The improvement group's inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.

[Procalcitonin for the differential diagnosis of infectious and non-infectious systemic inflammatory response syndrome after cardiac operation].

OBJECTIVE: To assess the value of procalcitonin (PCT) for the differential diagnosis between infectious and non-infectious systemic inflammatory response syndrome (SIRS) after cardiac operation. METHODS: Patients diagnosed with SIRS after cardiac surgery and admitted to Department of Cardiovascular Surgery of Tokyo Medical and Dental University Graduate School between April 1st, 2011 and March 31st, 2013 were retrospectively studied. A total of 142 patients with SIRS were included, and they were divided into infectious group (n =47) or non-infectious group ( n =95) according to the diagnostic criteria of the Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock: 2012 (SSCG2012). The patients with infectious SIRS were included, and there were 11 with sepsis, 12 with severe sepsis without shock, and 24 with septic shock respectively.The clinical data of patients were compared, and the receiver operating characteristic curve (ROC curve) was plotted to assess the diagnostic value of infection and non-infectious diseases for PCT, C-reactive protein ( CRP) and white blood cell count ( WBC ) , as well as the diagnosis of the severity of sepsis. RESULTS: PCT, CRP, and WBC were significantly higher in the infectious SIRS group than those in the non-infectious SIRS group [ PCT ( J.Lg/L): 2.80 ( 1.24, 10.20) vs.0.10 (0.06, 0.21), Z=-9.020, P=O.OOl; CRP (mg/L): 158.0 (120.0, 199.0) vs. 58.0 (25.0, 89.0), Z=-7.264,P=O.OOl; WBC ( x 1Q9/L): 15.5 (11.0, 22.6) vs. 9.3 (7.2, 12.6), Z=-5.792, P=O.OOl ]. PCT had the highest sensitivity ( 91.5%) and specificity ( 93.7%) for differential diagnosis, with a cut-off value for infectious SIRS of0.4 7 fLg/L, and the cut-off value of CRP and WBC were 119.5 mg/L and l 0.85 X 1 09/L, respectively. There was no significant difference in WBC among sepsis group, severe sepsis group, and septic shock group (X 109/L: 12.40 (9.10, 24.20),13.30 ( 9.93, 16.93), 20.40 ( 13.45, 28.6), x2=5.638, P=0.060], while PCT, CRP had significant difference (PCT(fLg/L): 1.37 (0.72, 1.85), 3.16 (0.48, 13.24), 3.68 (1.67, 20.96), x2 =7.422, P=0.024; CRP (mg!L): 120.0(74.0, 180.0), 135.7 (81.7, 181.3), 171.1 (151.5, 306.0), x2 =9.524, P=0.009].PCT was more reliable than CRP in diagnosing severe sepsis without shock, but it was ineffective for diagnosing septic shock. The cut-off value of PCT for diagnosing severe sepsis without shock was 2.28 fLg/L, and the sensitivity was 66.7%, specificity was 90.9%.Cut-off value of CRP for the diagnosis of septic shock was 149.5 mg/L, with the sensitivity of 83.3%, and the specificity of 66.7%. CONCLUSIONS: PCT was a useful marker for the diagnosis of infectious SIRS after cardiac operation as compared with WBC and CRP. The optimal PCT cut-off value for diagnosing infectious SIRS was 0.47 fLg/L.

Polymyxin B-immobilized fiber column hemoperfusion removes endotoxin throughout a 24-hour treatment period.

PURPOSE: The purpose of this study was to evaluate the extent of endotoxin adsorption by polymyxin B-immobilized fiber column hemoperfusion (PMX) performed for a 24-hour treatment period in patients with septic shock. MATERIALS AND METHODS: Nineteen patients with septic shock were retrospectively studied. The plasma endotoxin concentrations of blood drawn from the radial artery and from the outlet circuit of the PMX column were measured by kinetic turbidimetric limulus assay using an MT-358 Toxinometer (Wako Pure Chemical Industries, Ltd, Osaka, Japan) after 24 hours of PMX treatment. The endotoxin removal rate was defined by the following equation: ([radial artery endotoxin concentration - outlet circuit of PMX column endotoxin concentration]/radial artery endotoxin concentration) × 100%. RESULTS: The patients had a median Acute Physiology and Chronic Health Evaluation II score of 29 at intensive care unit admission and a 28-day mortality of 47%. Before the start of the PMX treatment, the median radial arterial plasma endotoxin concentration was 16.48 pg/mL. After 24 hours of PMX treatment, the median radial plasma endotoxin concentration had decreased to 1.857 pg/mL, and the concentration at the outlet circuit of the PMX column was further decreased to 0.779 pg/mL. The median endotoxin removal rate was 74.4%. CONCLUSION: These findings suggest that 24-hour PMX treatment was effective in removing endotoxin continuously throughout the entire treatment period.

Relationships of elevated systemic pentraxin-3 levels with high-risk coronary plaque components and impaired myocardial perfusion after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

BACKGROUND: We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0-1) (log-rank test χ(2)=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

Procalcitonin for the differential diagnosis of infectious and non-infectious systemic inflammatory response syndrome after cardiac surgery.

BACKGROUND: This study was performed to assess the value of procalcitonin (PCT) for the differential diagnosis between infectious and non-infectious systemic inflammatory response syndrome (SIRS) after cardiac surgery. METHODS: Patients diagnosed with SIRS after cardiac surgery between April 1, 2011 and March 31, 2013 were retrospectively studied. A total of 142 patients with SIRS, infectious (n = 47) or non-infectious (n = 95), were included. The patients with infectious SIRS included 11 with sepsis, 12 with severe sepsis without shock, and 24 with septic shock. RESULTS: PCT, C-reactive protein (CRP), and the white blood cell (WBC) count were significantly higher in the infectious SIRS group than in the non-infectious SIRS group. PCT had the highest sensitivity and specificity for differential diagnosis, with a cut-off value for infectious SIRS of 0.47 ng/mL. PCT was more reliable than CRP in diagnosing severe sepsis without shock, but it was not useful for diagnosing septic shock. The PCT cut-off value for diagnosing severe sepsis without shock was 2.28 ng/mL. CONCLUSIONS: PCT was a useful marker for the diagnosis of infectious SIRS after cardiac surgery. The optimal PCT cut-off value for diagnosing infectious SIRS was 0.47 ng/mL.

Procalcitonin for the differential diagnosis of infectious and non-infectious systemic inflammatory response syndrome after cardiac operation / 中华危重病急救医学

Objective To assess the value of procalcitonin (PCT) for the differential diagnosis between infectious and non-infectious systemic inflammatory response syndrome (SIRS) after cardiac operation.Methods Patients diagnosed with SIRS after cardiac surgery and admitted to Department of Cardiovascular Surgery of Tokyo Medical and Dental University Graduate School between April 1st,2011 and March 31st,2013 were retrospectively studied.A total of 142 patients with SIRS were included,and they were divided into infectious group (n =47) or non-infectious group (n =95) according to the diagnostic criteria of the Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock:2012 (SSCG2012).The patients with infectious SIRS were included,and there were 11 with sepsis,12 with severe sepsis without shock,and 24 with septic shock respectively.The clinical data of patients were compared,and the receiver operating characteristic curve (ROC curve) was plotted to assess the diagnostic value of infection and non-infectious diseases for PCT,C-reactive protein (CRP) and white blood cell count (WBC),as well as the diagnosis of the severity of sepsis.Results PCT,CRP,and WBC were significantly higher in the infectious SIRS group than those in the non-infectious SIRS group [PCT (μg/L):2.80 (1.24,10.20) vs.0.10 (0.06,0.21),Z=-9.020,P=0.001; CRP (mg/L):158.0 (120.0,199.0) vs.58.0 (25.0,89.0),Z=-7.264,P=0.001; WBC (× 109/L):15.5 (11.0,22.6) vs.9.3 (7.2,12.6),Z=-5.792,P=0.001].PCT had the highest sensitivity (91.5％) and specificity (93.7％) for differential diagnosis,with a cut-off value for infectious SIRS of 0.47 μg/L,and the cut-offvalue of CRP and WBC were 119.5 mg/L and 10.85 × 109/L,respectively.There was no significant difference in WBC among sepsis group,severe sepsis group,and septic shock group [× 109/L:12.40 (9.10,24.20),13.30 (9.93,16.93),20.40 (13.45,28.6),x2=5.638,P=0.060],while PCT,CRP had significant difference [PCT(μg/L):1.37 (0.72,1.85),3.16 (0.48,13.24),3.68 (1.67,20.96),x2=7.422,P=0.024; CRP (mg/L):120.0(74.0,180.0),135.7 (81.7,181.3),171.1 (151.5,306.0),x2=9.524,P=0.009].PCT was more reliable than CRP in diagnosing severe sepsis without shock,but it was ineffective for diagnosing septic shock.The cut-off value of PCT for diagnosing severe sepsis without shock was 2.28 μg/L,and the sensitivity was 66.7％,specificity was 90.9％.Cut-off value of CRP for the diagnosis of septic shock was 149.5 mg/L,with the sensitivity of 83.3％,and the specificity of 66.7％.Conclusions PCT was a useful marker for the diagnosis of infectious SIRS after cardiac operation as compared with WBC and CRP.The optimal PCT cut-off value for diagnosing infectious SIRS was 0.47 μg/L.

Pathophysiological roles of nuclear factor kappaB (NF-kB) in pulmonary arterial hypertension: effects of synthetic selective NF-kB inhibitor IMD-0354.

AIMS: Proliferation of pulmonary arterial smooth muscle cells (PASMCs) is one histological sign of pulmonary arterial hypertension (PAH). We hypothesized that a signalling cascade from fibroblast growth factor 2 (FGF2) to plasminogen activator inhibitor 1 (PAI-1) and monocyte chemotactic protein-1 (MCP-1) via nuclear transcription factor nuclear factor kappaB (NF-kB) play a critical role in progression of PAH, and tested this hypothesis both in vivo and in vitro using a synthetic selective NF-kB inhibitor, N-(3,5-Bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide (IMD-0354). METHODS AND RESULTS: Monocrotaline (MCT) was injected into 75 Sprague-Dawley rats. Starting at day 14 after MCT injection, we administered IMD-0354 (MCT + IMD group) or vehicle (MCT group) daily. At day 32, 65% of the MCT + IMD group were alive compared with 0% of the MCT group. IMD-0354 prevented increase of right ventricular pressure, and suppressed proliferation and induced apoptosis of PASMCs. mRNA transcript levels of FGF2, PAI-1, and tissue plasminogen activator (t-PA) were lower in MCT + IMD compared with MCT. In in vitro experiments, IMD-0354 inhibited p65 translocation to the nucleus promoted by FGF2 in PASMCs. Furthermore, the time courses of extracellular signal-regulated kinase (Erk) 1/2, MCP-1, and PAI-1 stimulated with FGF2 were each markedly shortened by IMD-0354. CONCLUSIONS: We speculate that the positive-feedback loop (Erk1/2-NF-kB-MCP-1-Erk1/2) is associated with progression of PAH by causing FGF2-induced inflammation in MCT rats. IMD-0354 has potential as a new therapeutic tool for PAH.

Diagnosis and assessment of Takayasu arteritis by multiple biomarkers.

BACKGROUND: Patients with Takayasu arteritis (TA) often show recurrence under steroid treatment without an elevation of C-reactive protein (CRP). There is a report that matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and pentraxin3 (PTX3) could be sensitive biomarkers, but the characteristics of these biomarkers have not been established. METHODS AND RESULTS: We enrolled 45 consecutive patients; 28 were grouped in an active phase as evidenced by clinical recurrence within 2 years of blood sampling. Circulating levels of high-sensitivity (hs)CRP, MMPs, and PTX3 were determined. Patients in an active phase showed higher levels of hsCRP, MMP-9, and PTX3. Area under the receiving operating characteristics curves of hsCRP and PTX3 were significantly higher than that of MMP-9. Among the 28 patients with active TA, 71% was positive for hsCRP and 82% for PTX3. Patients without recurrence showed significantly higher plasma levels of MMP-9. There was a positive correlation between the plasma MMP-3 level and the prednisolone dose. However, PTX3 and MMP-9 levels did not have such a correlation. CONCLUSIONS: PTX3 and MMP-9, which are not affected by prednisolone, could be sensitive biomarkers for assessing TA activity. Evaluation of MMP-9 may suggest prior existence of TA.