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Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH., Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality., Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test)., Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Mpox, caused by the mpox virus (MPXV), produces symptoms similar to those of smallpox when transmitted to humans. Since 1970, this disease has been endemic, particularly in Africa. However, since May 2022, the number of patients without a history of travel to endemic areas has increased rapidly globally. Under these circumstances, in July 2022, two different real-time PCR methods were used on specimens brought to the Tokyo Metropolitan Institute of Public Health. MPXV was detected in the skin samples, and it was inferred that the virus was a West African strain. Furthermore, a more detailed analysis of the genetic characteristics of the detected MPXV using next-generation sequencing revealed that the MPXV detected in Tokyo was strain B.1, which corresponds to the same strain that is prevalent in Europe and the USA. This suggests that mpox reported for the first time in Japan was imported and related to outbreaks in Europe and the USA. Therefore, it is necessary to continue monitoring outbreaks in Japan in conjunction with global epidemics.

Objective Treatment for uncomplicated diverticulitis (UD) is not well established. We evaluated the strategy of reviewing intravenous antibiotics for hospitalized Japanese patients with UD. Methods Treatment was based on the physician's choice until August 2018; the indications for hospitalization and treatment have been standardized since September 2018. In this study, we monitored the use of intravenous antibiotics administered to patients hospitalized for UD and then reviewed the need for them on hospital day 3. We compared patients' length of antibiotic use, hospital stay, health care cost, and complications via the review strategy from September 2018 to December 2020 and via the previous physicians' choice strategy from January 2016 to August 2018. Results Two hundred and forty-seven patients were admitted to our hospital because of acute colonic diverticulitis from January 2016 to December 2020. After excluding complicated cases, 106 individuals were enrolled during the period of physician's choice; 87 were enrolled when treatment review was employed. There were no significant differences in age, sex, inflammation site, or severity during the first hospital visit. The median duration of antibiotic use was significantly reduced from 5 to 4 days (p=0.0075), with no marked increase in rates of transfer to surgery, mortality, or readmission due to recurrence. A more significant proportion of patients completed 3-day antibiotic treatment with the review strategy than with the physician's choice strategy (6.6% vs. 25.3%, p=0.0004). However, the length of hospital stay and total medical costs did not decrease. Conclusion The strategy of reviewing treatment on day 3 after hospitalization for UD safety reduced the duration of antibiotic use, but the hospital stay and health care costs did not decrease.

Introduction: The ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19., Methods: This cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay., Results: IgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer., Conclusion: Older participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In order to tackle the COVID-19 pandemic, a COVID-19 convalescent plasma (CCP) procurement program was initiated in Japan in April 2020. The program was a collaboration between a government-managed national hospital, an infectious disease research institute, and a blood banking organization. Each party assumed different responsibilities: recruitment, SARS-CoV-2 antibody profiling, and plasmapheresis; conduction of screening tests; and SARS-CoV-2 blood testing, respectively., Methods: We adopted a two-point screening approach before the collected CCP was labeled as a CCP product for investigational use, for which we mainly tested anti-SARS-CoV-2 antibody eligibility and blood product eligibility. Anti-SARS-CoV-2 spike protein titer was measured using enzyme-linked immunosorbent assay, and the IC 50 value was denoted as the neutralizing activity. Blood donor eligibility was extended beyond the normal blood donation guidelines to include a broader range of participants. After both eligibility criteria were confirmed, participants were asked to revisit the hospital for blood donation, which is a unique aspect of the Japanese CCP program, as most donations are taking place in normal blood donation venues in other countries. Some donors were re-scheduled for repeat plasma donations. As public interest in anti-SARS-CoV-2 antibodies increased, test results were given to the participants., Results: As of September 17, 2020, our collection of CCP products was sufficient to treat more than 100 patients. As a result, projects for administration and distribution are also being conducted., Conclusions: We successfully implemented a CCP procurement scheme with the goal to expand to other parts of the country to improve treatment options for COVID-19., (© 2021 AABB.)

Introduction: "Re-infection" with COVID-19 is a growing concern; re-infection cases have reported worldwide. However, the clinical characteristics of SARS-CoV-2 re-infection, including the levels and role of anti-SARS-CoV-2 Spike protein IgG antibodies and the half-maximal concentration (IC 50 ) of neutralizing antibodies remain unknown., Methods: Both the epidemiological and clinical information has been collected during two episodes of COVID-19 in a patient. Laboratory results, including RT-PCR, Ct values, anti-SARS-CoV-2 Spike protein IgG antibodies, and the IC 50 of neutralizing antibodies levels were analyzed on the patient., Results: The patient was a 58-year-old man who developed moderate COVID-19 pneumonia with oxygen demand (cannula 2 L/min) in the first episode. By day 30, he recuperated and was discharged after testing negative for SARS-CoV-2. After two and a half months, his three family members showed COVID-19 symptoms and tested positive for SARS-CoV-2. He tested positive for SARS-CoV-2 once again and was asymptomatic (the second episode). The IC 50 of neutralizing antibodies against SARS-CoV-2 greatly increased from 50.0 μg/mL (after the first episode) to 14.8 μg/mL (after the second episode), and remained strongly reactive (20.1 μl/mL) after 47 days of the second episode., Conclusions: Epidemiological, clinical, and serological analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest that SARS-CoV-2 re-infection may manifest as asymptomatic with increased neutralizing antibody levels. Further studies such as the virus characteristics, immunology, and epidemiology on SARS-CoV-2 re-infection are needed., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Abstract: The subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rate in hospitals during the pandemic remains unclear. To evaluate the effectiveness of our hospital's current nosocomial infection control measures, we conducted a serological survey of anti-SARS-CoV-2 antibodies (immunoglobulin [Ig] G) among the staff of our hospital, which is treating coronavirus disease 2019 (COVID-19) patients.The study design was cross-sectional. We measured anti-SARS-CoV-2 IgG in the participants using a laboratory-based quantitative test (Abbott immunoassay), which has a sensitivity and specificity of 100% and 99.6%, respectively. To investigate the factors associated with seropositivity, we also obtained some information from the participants with an anonymous questionnaire. We invited 1133 staff members in our hospital, and 925 (82%) participated. The mean age of the participants was 40.0 ± 11.8 years, and most were women (80.0%). According to job title, there were 149 medical doctors or dentists (16.0%), 489 nurses (52.9%), 140 medical technologists (14.2%), 49 healthcare providers (5.3%), and 98 administrative staff (10.5%). The overall prevalence of seropositivity for anti-SARS-CoV-2 IgG was 0.43% (4/925), which was similar to the control seroprevalence of 0.54% (16/2970) in the general population in Osaka during the same period according to a government survey conducted with the same assay. Seropositive rates did not significantly differ according to job title, exposure to suspected or confirmed COVID-19 patients, or any other investigated factors.The subclinical SARS-CoV-2 infection rate in our hospital was not higher than that in the general population under our nosocomial infection control measures., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The factors predicting the progression of coronavirus disease-2019 (COVID-19) from mild to moderate to critical are unclear. We retrospectively evaluated risk factors for disease progression in Japanese patients with COVID-19. Seventy-four patients with laboratory-confirmed COVID-19 were hospitalized in our hospital between February 20, 2020, and June 10, 2020. We excluded asymptomatic, non-Japanese, and pediatric patients. We divided patients into the stable group and the progression group (PG; requiring mechanical ventilation). We compared the clinical factors. We established the cutoff values (COVs) for significantly different factors via receiver operating characteristic curve analysis and identified risk factors by univariate regression. We enrolled 57 patients with COVID-19 (median age 52 years, 56.1% male). The median time from symptom onset to admission was 8 days. Seven patients developed critical disease (PG: 12.2%), two (3.5%) of whom died; 50 had stable disease. Univariate logistic analysis identified an elevated lactate dehydrogenase (LDH) level (COV: 309 U/l), a decreased estimated glomerular filtration rate (eGFR; COV: 68 ml/min), lymphocytopenia (COV: 980/μl), and statin use as significantly associated with disease progression. However, in the Cox proportional hazards analysis, lymphocytopenia at admission was not significant. We identified three candidate risk factors for progression to critical COVID-19 in adult Japanese patients: statin use, elevated LDH level, and decreased eGFR., (© 2020 Wiley Periodicals LLC.)

Background/aim: The present study aimed to examine the therapeutic efficacy of ramucirumab compared with that of sorafenib as subsequent systemic therapy for patients with hepatocellular carcinoma (HCC) and serum α-fetoprotein (AFP) levels ≥400 ng/ml., Patients and Methods: In our prospectively registered, real-world cohort, 13 and 11 patients treated with ramucirumab or sorafenib, respectively, were analyzed. Progression-free survival (PFS) was primarily compared between the ramucirumab and sorafenib groups., Results: The PFS was significantly longer in the ramucirumab group than in the sorafenib group (median, 2.7 vs. 0.9 months, respectively; p=0.005). There were no significant differences in the objective response rates or the disease control rates between the ramucirumab and sorafenib groups (9.1% and 54.5% vs. 0.0% and 22.2%, respectively)., Conclusion: Subsequent systemic therapy with ramucirumab showed a better ability to control tumor progression than sorafenib in HCC patients with serum AFP levels ≥400 ng/ml., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Recently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan., Methods and Analysis: This is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose-area product (Gycm 2 ) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement., Ethics and Dissemination: Approval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the opt-out method of each hospital website., Trial Registration Number: The UMIN Clinical Trials Registry, UMIN000036525., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: It is unclear why colonic diverticular bleeding and diverticulitis rarely coexist. This study compared the characteristics of these conditions., Methods: This single-center retrospective study examined 310 consecutive patients hospitalized with an episode of diverticular disease (cases) and outpatients without a diverticular episode (controls) from January 2012 to December 2015. We investigated distinct clinical factors in hospitalized patients with diverticular bleeding and diverticulitis., Results: We identified 183 patients with 263 episodes of diverticular bleeding and 127 patients with 135 episodes of diverticulitis during the study period. Patients with diverticular bleeding were significantly older than those with diverticulitis (median age 76 vs. 56 years) and had more cardiovascular disease, hypertension, diabetes, cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer performance status. Significantly more diverticular bleeding patients were taking antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and antiplatelet agent use (OR 7.29) were more significant risk factors for diverticular bleeding than for diverticulitis., Conclusions: Elderly people using antiplatelet drugs may be more susceptible to diverticular bleeding than diverticulitis., (© 2018 S. Karger AG, Basel.)

Background & Aims: In patients with chronic hepatitis C virus (HCV) infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although many pretreatment factors are known to affect HCC incidence, less is known about post-treatment factors-many change during the course of interferon therapy., Methods: We performed a prospective study, collecting data from 2659 patients with chronic hepatitis C without a history of HCC who had been treated with pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals in Japan. Biopsy specimens were collected before treatment; all patients received Peg-IFN plus ribavirin for 48 to 72 weeks (HCV genotype 1) or 24 weeks (HCV genotype 2). Hematologic, biochemical, and virologic data were collected every 4 weeks during treatment and every 6 months after treatment. HCC was diagnosed based on angiography, computed tomography, and/or magnetic resonance imaging findings., Results: HCC developed in 104 patients during a mean observation period of 40 months. Older age, male sex, lower platelet counts and higher levels of α-fetoprotein at baseline, and lack of an SVR were significant risk factors for HCC. The cumulative incidence of HCC was significantly lower in patients without SVRs who relapsed than those with no response to treatment. Levels of α-fetoprotein 24 weeks after the end of treatment (AFP24) were significantly lower than levels of α-fetoprotein at baseline in patients with SVRs and those who relapsed, but not in nonresponders. Post-treatment risk factors for HCC among patients with SVRs included higher AFP24 level and older age; among those without SVRs, risk factors included higher AFP24 level, integrated level of alanine aminotransferase, older age, and male sex. AFP24 (≥10 ng/mL, 10-5 ng/mL, and then <5 ng/mL) was a better predictor of HCC incidence than pretreatment level of AFP among patients with and without SVRs., Conclusions: In patients with chronic HCV infection, levels of α-fetoprotein decrease during interferon therapy. High post-treatment levels of α-fetoprotein predict HCC, regardless of whether patients achieve an SVR. University Hospital Medical Information Network Clinical Trials Registry: C000000196, C000000197., (Copyright © 2014. Published by Elsevier Inc.)

Objective: Oxaliplatin-induced chronic neuropathy is cumulative and dose-limiting; reliable predictors and determination of the mechanism of this toxic effect are needed., Methods: We retrospectively studied 51 Japanese adults with colorectal cancer who had received oxaliplatin-based chemotherapy to explore the pharmacogenetic association between oxaliplatin-induced neuropathy and polymorphisms of the excision repair cross-complementation Group 1 (ERCC1) and glutathione-S-transferases pi 1 (GSTP1) genes., Results: For the ERCC1 C118T polymorphism, Grade 1 chronic neuropathy developed earlier in patients with C/T and T/T genotypes (median number of treatment cycles at onset = 6) than in those with the reference C/C genotype (7 cycles; p = 0.0162 by the generalized Wilcoxon test). For the GSTP1 Ile105Val polymorphism, chronic neuropathy developed earlier in patients with the reference Ile/Ile genotype (6 cycles) than in those with Ile/Val and Val/Val genotypes (9 cycles; p = 0.0321). ERCC1 C118T and GSTP1 Ile105Val polymorphisms were not significantly associated with an increased risk of developing Grade 2 or more severe chronic neuropathy., Conclusions: Our results suggest that ERCC1, C118T and GSTP1 Ile105Val polymorphisms are more strongly related to the time until onset of neuropathy than to the grade of neuropathy. Most likely these polymorphisms influence patients' sensitivity to neuropathy.

We aimed to assess whether circulating sex steroids would influence bone density and bone loss, whether part of this influence could be explained by genetic variation measured as polymorphisms in candidate genes affecting circulating hormone levels, or whether gene polymorphisms would have direct effects on bone in 229 postmenopausal Japanese women aged 46 years and over who had been followed for eight years (Yokohama Cohort). Bone mineral density (BMD) in the lumbar spine (L), femoral neck (FN), total hip (T) and distal radius (R) was measured every year, and endogenous sex steroid levels were determined at the start of the study. We investigated the polymorphisms of estrogen-metabolizing enzyme gene, CYP17; estrogen biosynthesis (high activity, A2/A2), CYP1A1; hydroxylation (high inducibility, vt/vt) and COMT; inactivation (low activity, L/L) with PCR-based restriction fragment length polymorphism assays. Dehydroepiandrosterone (DHEA) and androstenedione (AND) levels significantly correlated with bone density in both the axial (L) and the appendicular skeleton (FN, T and R) (r=0.194-0.229; P<0.05) whereas estradiol (E2) and AND showed significant correlations with bone change only at the axial skeleton (r=0.205 and r=-0.139, respectively; P<0.05) on the total cohort. These correlations remained significant in thin/normal-weight women [body mass index (BMI) <25 kg/m2)] even after adjustment for years since menopause (YSM) and BMI or age and BMI, suggesting an interaction of BMI and sex steroid/BMD association. On the total cohort, a difference in endogenous DHEA levels between CYP17 homozygote A2 and non-homozygote A2; an increasing trend in AND levels from COMT L/L, L/H, to H/H; and a difference in TS level between COMT homozygote L and non-homozygote L were separately observed. All observations were significant for unadjusted and adjusted analysis, except for COMT and TS. In thin/normal-weight women (BMI <25 kg/m2), the same effects of CYP17 genotypes on DHEA were observed as on the total cohort. CYP17 and COMT genes showed some direct influence on bone density. Mean percent change in T-BMD was negative for CYP17 non-homozygote A2 in contrast to a positive value for homozygote A2. Mean percent change in R-BMD showed the difference between COMT homozygote L and non-homozygote L with a larger decrease for the homozygote L. Together, CYP17 and COMT genotypes might have some effect on bone both directly and indirectly through their effects on endogenous sex steroids in postmenopausal Japanese women.

We recently identified vasopressin type 2 receptor gene mutations in two unrelated Japanese families with X-linked nephrogenic diabetes insipidus, which were a missense mutation from Arg143 to Pro (R143P) and a single amino acid deletion of Val278 or 279 (delta V278). To investigate the mechanism by which the mutations cause arginine vasopressin (AVP) resistance in this disorder, we expressed them in mammalian cells and analyzed their functional properties. Stable expression study with Chinese hamster ovary (CHO) cells demonstrated that the R143P mutation reduced receptor binding capacity to 10% of normal. However, the R143P mutant itself had a normal affinity for AVP and stimulated adenylyl cyclase production at up to 50% of the wild-type level, suggesting that the mutant receptors could function normally despite their reduced surface expression. In contrast, the delta V278 mutation totally abolished receptor-ligand binding and subsequent adenylyl cyclase stimulation, indicating that delta V278 mutant is virtually nonfunctional receptor. Northern blotting revealed that mutant CHO cell lines produced levels of receptor mRNA similar to the wild-type cell line. Our results suggest that the two mutations impair binding activity of the receptor without affecting mRNA accumulation, thereby causing AVP resistance through a posttranscriptional mechanism.

Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder exhibiting renal resistance to the antidiuretic action of arginine vasopressin (AVP). Recent elucidation of the vasopressin V2 (renal type) receptor gene structure has enabled us to test the hypothesis that the genetic defect in the V2 receptor is the likely molecular basis of NDI. By using the polymerase chain reaction (PCR)-direct sequencing, we identified novel V2 receptor gene mutations in two unrelated Japanese kindreds with NDI. In the male patients of kindred A, a single codon deletion in one of two consecutive GTC triplets (nucleotide 832 to 837) was detected. This base change resulted in the loss of a valine residue in the 6th transmembrane domain. In the affected males of kindred B, a G to C substitution was found at nucleotide 428, altering codon 143 from arginine (CGT) to proline (CCT) in the second cytoplasmic domain. PCR-single strand conformation polymorphism (SSCP) analysis of family members demonstrated that the mutations cosegregated with clinically affected individuals and were absent in normal subjects. Our results suggest that different V2 receptor defects could be responsible for AVP resistance in individual NDI kindreds.

Ventricular late potentials are obtained by signal-averaged surface electrocardiography. Late potentials have been reported to be affected by body characteristics or left ventricular mass. To evaluate late potentials in relation to body characteristics, 52 healthy Japanese young volunteers (21 girls, 31 boys) aged 15-16 years were studied. QRS duration in men was significantly longer than in women. There were no significant differences in low-amplitude signal and root mean square voltage between women and men. When relations between signal-averaged electrocardiographic parameters and body characteristics were examined, QRS duration had positive linear correlations with weight and body mass index. The slope of QRS duration and weight relation, and QRS duration and body mass index relation was significantly steeper in men compared to those in women; a prolongation of QRS duration in men compared to women as weight and body mass index increased. Our results indicated that QRS duration in teenage healthy subjects should be used with caution because it is affected by gender.

Several investigators demonstrated that severe reduction of colloid osmotic pressure (COP) predicts a fatal outcome in patients with cardiopulmonary failure. To evaluate the clinical significance of COP in relation to pulmonary edema, we studied 117 patients with unstable angina admitted in the hospital within 24 h after the chest pain. The mean COP of all 117 patients was 24.8 +/- 3.7 mmHg. COP was significantly lower in patients with pulmonary edema, according to the chest x-ray findings, compared with the patients without it. Among 26 patients with emergency coronary arteriography, a fairly good correlation was observed between coronary jeopardy score and COP (r = -0.57, p less than 0.005). Furthermore, COP in patients who survived 26 months after the hospital discharge was significantly higher than that of the nonsurvivors. Thus, measurement of COP is advised for monitoring patients with unstable angina.