Impact of Long-Term Exercise-Based Cardiac Rehabilitation in Patients With Chronic Heart Failure　- A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to clarify the effects of exercise-based cardiac rehabilitation (CR) on patients with heart failure.Methods and Results: Patients were divided into groups according to intervention duration (<6 and ≥6 months). We searched for studies published up to July 2023 in Embase, MEDLINE, PubMed, and the Cochrane Library, without limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of CR and usual care on mortality, prehospitalization, peak oxygen uptake (V̇O2), and quality of life. Seventy-two studies involving 8,495 patients were included in this review. It was found that CR reduced the risk of rehospitalization for any cause (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.70-0.92) and for heart failure (RR 0.88; 95% CI 0.78-1.00). Furthermore, CR was found to improve exercise tolerance (measured by peak V̇O2and the 6-min walk test) and quality of life. A subanalysis performed based on intervention duration (<6 and ≥6 months) revealed a similar trend. CONCLUSIONS: Our meta-analysis showed that although CR does not reduce mortality, it is effective in reducing rehospitalization rates and improving exercise tolerance and quality of life, regardless of the intervention duration.

High-intensity interval training versus moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis.

The effects of high-intensity interval training (HIIT) in patients with heart failure (HF) remain controversial. This systematic review and meta-analysis aimed to examine the efficacy of HIIT versus moderate-intensity continuous aerobic training (MCT) on exercise tolerance in patients with HF. We searched for studies published up to 4 March 2022 in Embase, MEDLINE, PubMed, and the Cochrane Library with no limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. We identified 15 randomized controlled trials with 557 patients. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; participants = 557; studies = 15; I2 = 65.7%; very low-quality evidence). The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the difference in peak VO2 between HIIT and MCT was inversely associated with body mass index (r = - 0.508, p = 0.028, 95% confidence interval - 0.95 to - 0.07). Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with HF. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum.

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER-MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER-MII.

New Stethoscope With Extensible Diaphragm.

BACKGROUND: This study compared the diagnostic efficacy of the common suspended diaphragm stethoscope (SDS) with a new extensible diaphragm stethoscope (EDS) for low-frequency heart sounds. METHODS AND RESULTS: The EDS was developed by using an ethylene propylene diene monomer diaphragm. The results showed that the EDS enhanced both the volume and quality of low-frequency heart sounds, and improved the ability of examiners to auscultate such heart sounds. CONCLUSIONS: Based on the results of the sound analysis, the EDS is more efficient than the SDS. (Circ J 2016; 80: 2047-2049).

Pharmacological Profile of GPD-1116, an Inhibitor of Phosphodiesterase 4.

We have previously reported that GPD-1116, an inhibitor of phosphodiesterase (PDE) 4, exhibits anti-inflammatory effects in a model of cigarette smoke-induced emphysema in senescence-accelerated P1 mice. In the present study, we further characterized the pharmacological profile of GPD-1116 in several experiments in vitro and in vivo. GPD-1116 and its metabolite GPD-1133 predominantly inhibited not only human PDE4, but also human PDE1 in vitro. Moreover, GPD-1116 was effective in several disease models in animals, including acute lung injury, chronic obstructive pulmonary disease (COPD), asthma and pulmonary hypertension; the effective doses of GPD-1116 were estimated to be 0.3-2 mg/kg in these models. With regard to undesirable effects known as class effects of PDE4 inhibitors, GPD-1116 showed suppression of gastric emptying in rats and induction of emesis in dogs, but showed no such suppression of rectal temperature in rats, and these side effects of GPD-1116 seemed to be less potent than those of roflumilast. These results suggested that GPD-1116 could be a promising therapeutic agent for the treatment of inflammatory pulmonary diseases. Furthermore, the inhibitory effects of GPD-1116 for PDE1 might be associated with its excellent pharmacological profile. However, the mechanisms through which PDE1 inhibition contributes to these effects should be determined in future studies.

Embryological outcomes in cycles with human oocytes containing large tubular smooth endoplasmic reticulum clusters after conventional in vitro fertilization.

There have been no studies analyzing the effect of large aggregates of tubular smooth endoplasmic reticulum (aSERT) after conventional in vitro fertilization (cIVF). The aim of this study was to investigate whether aSERT can be identified after cIVF and the association between the embryological outcomes of oocytes in cycles with aSERT. This is a retrospective study examining embryological data from cIVF cycles showing the presence of aSERT in oocytes 5-6 h after cIVF. To evaluate embryo quality, cIVF cycles with at least one aSERT-metaphase II (MII) oocyte observed (cycles with aSERT) were compared to cycles with normal-MII oocytes (control cycles). Among the 4098 MII oocytes observed in 579 cycles, aSERT was detected in 100 MII oocytes in 51 cycles (8.8%). The fertilization rate, the rate of embryo development on day 3 and day 5-6 did not significantly differ between cycles with aSERT and control group. However, aSERT-MII oocytes had lower rates for both blastocysts and good quality blastocysts (p < 0.05). aSERT can be detected in the cytoplasm by removing the cumulus cell 5 h after cIVF. However, aSERT-MII oocytes do not affect other normal-MII oocytes in cycles with aSERT.

A CASE OF ADVANCED NON-SEMINOMATOUS TESTICULAR GERM CELL TUMOR ACCOMPANIED PANIC DISORDER.

We report a 33-year-old male with a left advanced non-seminomatous testicular germ cell tumor (NSGCT) accompanied panic disorder. He had experienced palpitation and hyperpnea in crowds in his twenties. He was admitted to the Department of Otorhinolaryngology with the chief complaint of left neck swelling. 18F-fluorodeoxy glucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated left neck, left supraclavicular, left axillary, and paraaortic lymph node (LN) swelling and left testicular swelling. He was referred to our department. The left testis had enlarged to the size of a fist. He rejected admission at that time, but next day, he was taken to our hospital by an ambulance because he lost consciousness at home. No abnormalities were found in the brain CT and electrocardiogram. He was admitted and left high orchiectomy was performed. The human chorionic gonadotropin (HCG) level had elevated to 9,717 IU/L and alpha fetoprotein level (AFP) had elevated to 427 ng/ml. The histopathological diagnosis was tumors of more than one histological type, mixed forms: seminoma and embryonal carcinoma.He had palpitation and hyperpnea after admission and was diagnosed with panic disorder by a psychiatrist. Psychotropic drugs (fluvoxamine maleate 50 mg/day, alprazolam 0.8 mg/day) were prescribed and the panic attacks disappeared afterwards. The psychiatric social worker supported his mind side. Bleomycin, etoposide, and cisplatin (BEP) therapy was performed for 4 courses. He put on a blanket to his face and came to avoid a conversation with other people during the chemotherapy. He was diagnosed with depression and psychotropic drugs were increased (fluvoxamine maleate 50→75 mg/day, alprazolam 0.8→1.2 mg/day) in quantity.Lymphadenectomies for LN metastases were performed and their histopathological examination revealed the existence of viable embryonal carcinoma in the supraclavicular LN. Etoposide, ifosfamide, and cisplatin (VIP) therapy was performed for 2 courses.The pateint has remained alive without tumor recurrence. Psychotropic drugs were reduced and the recent drug is fluvoxamine maleate 25 mg/day.

Birth of nine normal healthy babies following transfer of blastocysts derived from human single-pronucleate zygotes.

PURPOSE: The purpose of this study is to examine the clinical outcomes of blastocysts derived from human single-pronucleate (1PN) embryos after conventional in vitro fertilization (cIVF) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: This was a retrospective study at a reproductive center of a hospital. To evaluate embryo quality and clinical outcomes, cIVF or ICSI cycles with one or more 1PN embryos were compared with same cycles with 2PN embryos (control cycles). RESULTS: A total of 623 cycles (426 cIVF cycles and 197 ICSI cycles) were treated with cIVF or ICSI. The single pronuclear status rate was similar between cIVF (22.1 %) and ICSI (25.1 %) cycles. Although the development rates of 1PN embryos on day 3 and day 5/6 in cIVF were significantly higher than those in ICSI, those of 1PN embryos in cIVF were significantly lower compared to 2PN embryos (p < 0.01). Nonetheless, the ongoing pregnancy rates achieved with 1PN blastocysts in 1PN embryos did not significantly differ from the control group. Thirty-three transfer cycles with 33 blastocysts derived from 1PN embryos in cIVF resulted in nine deliveries with no newborn malformations; however, no implantation was observed in three ICSI cycles. CONCLUSION: Although the blastocyst formation rate of 1PN embryos was significantly lower than 2PN embryos in cIVF and ICSI cycles, 1PN blastocysts in cIVF, and not from ICSI, demonstrated an adequate ongoing pregnancy rate. These results suggested that 1PN blastocysts in cIVF are available for clinical use and may lead to an increase in the chance of pregnancy in patients receiving assisted reproductive technology with 1PN embryos.

α-1,6-Fucosyltransferase (FUT8) inhibits hemoglobin production during differentiation of murine and K562 human erythroleukemia cells.

Erythropoiesis results from a complex combination of the expression of several transcription factor genes and cytokine signaling. However, the overall view of erythroid differentiation remains unclear. First, we screened for erythroid differentiation-related genes by comparing the expression profiles of high differentiation-inducible and low differentiation-inducible murine erythroleukemia cells. We identified that overexpression of α-1,6-fucosyltransferase (Fut8) inhibits hemoglobin production. FUT8 catalyzes the transfer of a fucose residue to N-linked oligosaccharides on glycoproteins via an α-1,6 linkage, leading to core fucosylation in mammals. Expression of Fut8 was down-regulated during chemically induced differentiation of murine erythroleukemia cells. Additionally, expression of Fut8 was positively regulated by c-Myc and c-Myb, which are known as suppressors of erythroid differentiation. Second, we found that FUT8 is the only fucosyltransferase family member that inhibits hemoglobin production. Functional analysis of FUT8 revealed that the donor substrate-binding domain and a flexible loop play essential roles in inhibition of hemoglobin production. This result clearly demonstrates that core fucosylation inhibits hemoglobin production. Third, FUT8 also inhibited hemoglobin production of human erythroleukemia K562 cells. Finally, a short hairpin RNA study showed that FUT8 down-regulation induced hemoglobin production and increase of transferrin receptor/glycophorin A-positive cells in human erythroleukemia K562 cells. Our findings define FUT8 as a novel factor for hemoglobin production and demonstrate that core fucosylation plays an important role in erythroid differentiation.

[Construction and usefulness of the dose management system using DICOM radiation dose structured report (Dose SR) in angiography].

The International Commission on Radiological Protection recommends diagnostic reference levels (DRL) in each radiological examination for justification and optimization of patients' dose in medicine. The aim of our study was to propose the dose management system by utilizing dose information in diagnostic X-ray radiation dose structured report (Dose SR) in The Digital Imaging and Communications in Medicine to optimize radiation dose in institutions. Our dose management system is able to organize dose information obtained from various angiography systems and CTs. It is possible to provide this information to operators for justification and optimization of patient dose. Our system would be useful for the estimation of organ dose and could be used for the determination of local DRL (LDRL) for each radiological practice. In addition, the optimization became possible to compare LDRL with national DRL.

Early mobilization for acute heart failure: A scoping and a systematic review.

Early mobilization of hospitalized patients is beneficial under certain circumstances. This has been applied in clinical practice for patients with acute heart failure (HF). However, its current definition, effectiveness, and safety are not well established. This review aimed to clarify the current definition of "early mobilization," and summarize its effectiveness and safety in acute HF. We conducted a scoping review to define early mobilization (Part 1) and a systematic review and meta-analysis (Part 2) to evaluate its effectiveness and safety. For Part 1, we searched MEDLINE (Ovid), and for Part 2, we searched the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), Embase (ProQuest Dialog), CINAHL, and PEDro. We included 12 studies in Part 1 and defined early mobilization as protocol-based interventions or walking within 3 days of admission. Based on this definition, two observational studies were included in Part 2, with no randomized controlled trials. Early mobilization may result in a large reduction in the readmission rate compared with that of the control (two studies, 283 participants: odds ratio 0.25, 95 % confidence interval 0.14 to 0.42; I2 = 0 %; low certainty evidence). We could not define frequency, intensity, or quantity because many of the included studies did not describe them. In conclusions, our review suggests that early mobilization, defined as protocol-based interventions or walking within 3 days of admission, may be associated with a low readmission rate in patients with acute HF. Future studies are essential, to investigate the causal relationship between early mobilization and possible outcomes.

Inhibition of Notch4 using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium.

Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade can interfere with tumor vessel function but causes tissue hypoxia and gastrointestinal toxicity. Notch4 is primarily expressed in endothelial cells, where it may promote angiogenesis; however, effective therapeutic targeting of Notch4 has not been successful. We developed highly specific Notch4-blocking antibodies, 6-3-A6 and humanized E7011, allowing therapeutic targeting of Notch4 to be assessed in tumor models. Notch4 was expressed on tumor endothelial cells in multiple cancer models, and endothelial expression was associated with response to E7011/6-3-A6. Anti-Notch4 treatment significantly delayed tumor growth in mouse models of breast, skin, and lung cancer. Enhanced tumor inhibition occurred when anti-Notch4 treatment was used in combination with chemotherapeutics. Endothelial transcriptomic analysis of murine breast tumors treated with 6-3-A6 identified significant changes in pathways of vascular function but caused only modest change in canonical Notch signaling. Analysis of early and late treatment timepoints revealed significant differences in vessel area and perfusion in response to anti-Notch4 treatment. We conclude that targeting Notch4 improves tumor growth control through endothelial intrinsic mechanisms.

[Display Performance of X-ray Image Output from DICOM-embedded Printer to Paper-based Hard Copy Print: Comparison with X-ray Image on LCD].

PURPOSE: We have been using a paper-based hard copy print (paper print) system of X-ray images, in which digital imaging and communications in medicine (DICOM) data can be directly output on papers from medical imaging systems or from a picture archiving and communication system (PACS) server, and they are utilized as patient referral materials or for preoperative planning. The purpose of this study was to compare the display performance of X-ray images on the printed paper and that on the liquid crystal display (LCD). METHODS: We measured contrast response to verify consistency of image appearance on both display systems. The contrast resolution was assessed by a CDRAD phantom. The spatial resolution was assessed by an X-ray test chart. RESULTS: The contrast response of the paper printer was not concordant with the grayscale standard display function (GSDF). The difference between the measured contrast response and the ideal GSDF on the paper was large in the high-density area. The low-contrast resolution on the paper was inferior to that on the LCD. The spatial resolving power on the paper was superior to that on the LCD. CONCLUSION: The display performance of the paper printer for X-ray images was clarified. X-ray images printed on the paper should be used carefully taking account of their characteristics of display performance.

Optimization of Microchannels and Application of Basic Activation Functions of Deep Neural Network for Accuracy Analysis of Microfluidic Parameter Data.

The fabrication of microflow channels with high accuracy in terms of the optimization of the proposed designs, minimization of surface roughness, and flow control of microfluidic parameters is challenging when evaluating the performance of microfluidic systems. The use of conventional input devices, such as peristaltic pumps and digital pressure pumps, to evaluate the flow control of such parameters cannot confirm a wide range of data analysis with higher accuracy because of their operational drawbacks. In this study, we optimized the circular and rectangular-shaped microflow channels of a 100 µm microfluidic chip using a three-dimensional simulation tool, and analyzed concentration profiles of different regions of the microflow channels. Then, we applied a deep learning (DL) algorithm for the dense layers of the rectified linear unit (ReLU), Leaky ReLU, and Swish activation functions to train and test 1600 experimental and interpolation of data samples which obtained from the microfluidic chip. Moreover, using the same DL algorithm, we configured three models for each of these three functions by changing the internal middle layers of these models. As a result, we obtained a total of 9 average accuracy values of ReLU, Leaky ReLU, and Swish functions for a defined threshold value of 6×10-5 using the trial-and-error method. We applied single-to-five-fold cross-validation technique of deep neural network to avoid overfitting and reduce noises from data-set to evaluate better average accuracy of data of microfluidic parameters.

Kihon checklist is useful for predicting outcomes in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Frailty is a major risk factor for death and disability following transcatheter aortic valve implantation (TAVI). The Kihon checklist (KCL) is a simple self-reporting yes/no survey consisting of 25 questions and is used as a screening tool to identify frailty in the primary care setting. No clinical studies have focused on frailty calculated by the KCL in the TAVI cohort. We investigated the 3-year prognostic impact of frailty evaluated by the KCL in patients who underwent TAVI. METHODS: This single-center prospective observational study included 280 consecutive patients with symptomatic severe aortic stenosis who underwent TAVI and evaluated pre-procedural physical performance focused on frailty at our institution. We assessed all patients' frailty by the KCL before TAVI, as described previously. We set the primary endpoint as the 3-year all-cause mortality after TAVI. RESULTS: The median patient age was 84 years (interquartile range, 81-87 years), and 31.1% were men. In the receiver operating characteristics curve, there were no significant differences between the KCL and Cardiovascular Health Study frailty index [area under the curve (AUC) 0.625 versus 0.628; p=0.93), KCL and Rockwood Clinical Frailty Scale (AUC 0.625 versus 0.542; p=0.15), and KCL and Short Physical Performance Battery (AUC 0.625 versus 0.612; p=0.91). The first and second tertiles of the total KCL score were 8 and 12, respectively. The multivariate Cox regression model indicated that the total KCL score [hazard ratio (HR), 1.104; 95% confidence interval (CI), 1.034-1.179; p=0.003], presence of diabetes mellitus (HR, 1.993; CI, 1.055-3.766; p=0.03), and presence of liver disease (HR, 3.007; CI, 1.067-8.477; p=0.04) were independently associated with 3-year all-cause mortality. CONCLUSIONS: The KCL is a simple and useful tool for evaluating frailty status and predicting 3-year all-cause mortality in patients undergoing TAVI.

[Case of antiamphiphysin antibody-positive stiff-person syndrome with breast cancer diagnosed by FDG-PET].

We report a case of antiamphiphysin antiboddy-positive stiff-person syndrome associated with breast cancer, which was detected only by FDG-PET. A 46-year-old woman was admitted to our hospital because of painful muscle cramp and stiffness of both legs. Laboratory results were negative for anti-GAD antibody, but highly positive for antiamphiphysin antibody (1: 61,440). She had been diagnosed as having paraneoplastic stiff-person syndrome. However, mammogram, thoracic CT, breast MRI and ultrasonic echography showed no abnormal findings. A whole-body fluorodeoxyglucose (FDG) PET was performed, showing an increased uptake in the left axillary lymph nodes. Then, the left axillary lymph nodes were resected and immunohistochemically diagnosed as breast adenocarcinoma. Treatment of stiff-person syndrome was initiated with corticosteroids followed by chemotherapy against breast cancer, which led to a remarkable improvement of her neurological symptoms. If there is possibility of paraneoplastic syndromes like stiff-person syndrome, FDG-PET is very useful for detecting the occult carcinoma.

Positron emission tomography for predicting malignancy of sinonasal inverted papilloma.

BACKGROUND: Sinonasal inverted papilloma (IP) is an uncommon nasal tumor. It is known for being locally invasive and recurrent, with a high probability of malignant transformation. Accurate initial staging and close surveillance are critical in the management of the disease. METHODS AND RESULTS: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) was performed in 5 patients with IP. High FDG uptake (maximum standardized uptake (SUVmax) value >3.0) was observed in all patients, and 2 patients with IP associated with squamous cell carcinoma (SCC) exhibited higher SUVmax values. CONCLUSION: The SUVmax value of a sinonasal tumor can warn the surgeon of the probability of an associated malignancy, even when preoperative biopsy demonstrates a purely benign papilloma.

Acute dural venous sinus thrombosis without brain parenchymal abnormality: assessment with cerebral blood volume using dynamic susceptibility contrast magnetic resonance imaging.

We report results applying the dynamic susceptibility contrast (DSC) magnetic resonance (MR) technique to a patient with dural venous sinus thrombosis (DVST) of the right transverse-sigmoid sinus without brain parenchymal abnormality. The DSC-MR technique clearly demonstrated increased regional cerebral blood volume of the right temporo-parieto-occipital region adjacent to a right transverse-sigmoid sinus thrombosis in a patient with DVST without cerebral edema or hemorrhage.

Cardiac sympathetic denervation modulates the sympathoexcitatory response to acute myocardial ischemia.

OBJECTIVES: This study was designed to elucidate the influence of cardiac sympathetic denervation on the sympathoexcitatory response to acute myocardial ischemia during balloon coronary occlusion (BCO) in humans. BACKGROUND: Alterations of cardiac sympathetic nerve function could modulate sympathetic reflexes originating from the ischemic area. METHODS: In 23 patients with angina pectoris, we quantified the baseline cardiac sympathetic denervation of the ischemia-related area by iodine-123 metaiodobenzylguanidine ((123)I-MIBG), and transient changes in sympathetic activity during BCO by wavelet analysis of RR interval variability. RESULTS: Balloon coronary occlusion resulted in a transient augmentation of low-frequency (LF: 0.04 to 0.14 Hz) spectral components of RR interval variability in 4 of 12 patients with cardiac denervation and in 8 of 11 patients without denervation (p < 0.01 by the chi-square test). Consequently, the increase in LF components was significantly less during BCO in patients with cardiac denervation (34%) than in those without denervation (273%) (interaction: p < 0.05). In seven patients with severe ischemia provoked by a fall of > or = 10% in the left ventricular ejection fraction, LF components increased by 506% during BCO, regardless of the condition of cardiac denervation. In contrast, in patients with mild ischemia provoked by a fall of <10% in the ejection fraction, changes of LF components during BCO were significantly less in patients with denervation than in those without denervation (84 vs. 344%, p < 0.05). CONCLUSIONS: These findings suggest that if the provoked ischemia is not severe, cardiac sympathetic denervation could prevent ischemia-induced sympathoexcitation.

Soluble elastin fragments in serum are elevated in acute aortic dissection.

OBJECTIVE: We aimed to establish an enzyme-linked immunosorbent assay for measuring soluble elastin fragments (sELAF) in serum and to reveal its usefulness in diagnosing acute aortic dissection (AAD). METHODS AND RESULTS: An enzyme-linked immunosorbent assay to measure sELAF in serum was developed by using the newly created double monoclonal antibodies, which recognize the different epitopes of human aortic elastin. Twenty-five AAD patients, 50 patients with acute myocardial infarction (AMI), and 474 healthy individuals were enrolled in the study. The sELAF levels from healthy subjects gradually increased with aging. When the cutoff point for positivity was set at the mean+3 SD (ie, 3 SD above the mean in healthy subjects at each age), 16 AAD patients (64.0%) were found be positive, whereas only 1 AMI patient was found to be positive (2.0%). AAD patients with either an open or a partially open pseudolumen were found be 88.9% positive for sELAF, whereas those with its early closure were 0% positive. The difference in the sELAF levels between AAD patients with and without a thrombotic closure of false lumen was significant (60.3+/-15.6 versus 135.4+/-53.2 ng/mL, respectively; P<0.005). CONCLUSIONS: The sELAF level in serum may be a useful marker for helping in the diagnosis and screening of AAD and may also help to distinguish AAD from AMI.