Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

The combination of the low immunohistochemical expression of peroxiredoxin 4 and perilipin 2 predicts longer survival in pancreatic ductal adenocarcinoma with peroxiredoxin 4 possibly playing a main role.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients' clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC.

A new predictive tool consolidating CURB-65 with procalcitonin and albumin to assess short-term mortality in hospitalized elderly patients with infectious disease: A retrospective study of a patient cohort.

BACKGROUND: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb). METHOD: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died. RESULTS: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died. CONCLUSIONS: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease.

Orthogeriatric co-management at a regional core hospital as a new multidisciplinary approach in Japanese hip fracture operation.

BACKGROUND: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital. METHODS: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared etrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission. RESULTS: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05). CONCLUSIONS: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications.

Postoperative Urinary Retention in Japanese Elderly Males with a Femoral Neck or Trochanteric Fracture.

We assessed risk factors for postoperative urinary retention (UR) in elderly males with femoral bone fractures: 169 Japanese males (mean age 81.95 ± 1.19 years) who had undergone hip surgery at a municipal hospital (Toyama, Japan). A multiple logistic regression analysis was used to test possible risk factors for UR: age, body mass index, serum albumin, cognitive impairment, activities of daily living (ADL), and history of diabetes mellitus (DM). UR occurred in 24 (14.2%) of the 169 patients. A multivariate logistic regression analysis with age adjustment showed that ADL (odds ratio [OR] 3.88; 95% confidence interval [CI]: 1.2-12.5, p=0.023) was significantly associated with the development of UR, and a history of DM showed marginal significance for UR occurrence (OR 0.36, 95%CI: 0.11-10, p=0.064). These results suggests that ADL is a risk factor for UR development in elderly males who have undergone surgery for femoral neck or trochanter fractures.

Multidisciplinary care model for geriatric patients with hip fracture in Japan: 5-year experience.

INTRODUCTION: Japan is a super-aging society, the geriatric care system establishment for hip fractures is at an urgent task. This report described our concept of multidisciplinary care model for geriatric hip fractures and 5-year outcomes at the Toyama City Hospital, Japan. METHODS: In this retrospective cohort study, a multidisciplinary treatment approach was applied for elderly patients with hip fracture since 2014. These patients (n = 678, males: n = 143, mean age: 84.6 ± 7.5 years), were treated per the multidisciplinary care model. Time to surgery, length of hospital stays, complications, osteoporosis treatment, mortality, and medical costs were evaluated. RESULTS: The mean time to surgery was 1.7 days. Overall, 78.0% patients underwent surgery within 2 days. The mean duration of hospital stay was 21.0 ± 12.4 days. The most frequent complication was deep venous thrombosis (19.0%) followed by dysuria (14.5%). Severe complications were pneumonia 3.4%, heart failure 0.8% and pulmonary embolism 0.4%. The in-hospital mortality rate was 1.2%. The 90-day, 6-month, and 1-year mortality rates were 2.5%, 6.7%, and 12.6%, respectively. The pharmacotherapy rate for osteoporosis at discharge was 90.7%, and the continuation pharmacotherapy rate was 84.7% at 1-year follow-up. The total hospitalization medical cost per person was lower than about 400 other hospitals' average costs every year, totaled 14% less during the 5-year study period. CONCLUSION: We have organized a multidisciplinary team approach for geriatric hip fracture. This approach resulted in a shorter time to surgery and hospital stay than the national average. The incidence of severe complications and mortality was low. The multidisciplinary treatment has maintained a high rate of osteoporosis treatment after discharge and at follow-up. Furthermore, the total medical cost per person was less than the national average. Thus, the multidisciplinary treatment approach for geriatric hip fractures was effective and feasible to conduct in Japan.

Examination of Endoscopic Ultrasonographic Diagnosis for the Depth of Early Gastric Cancer.

BACKGROUND: Endoscopic ultrasonography (EUS) is one of the helpful tools to diagnose depth of early gastric cancer (EGC). In this study, we examined efficiencies of EUS for EGC such as overall accuracy, risk factors of over/under-staging, and accuracies of each invasive distance. METHODS: A total of 403 EGC lesions that could be investigated by EUS during pre-operation and histological diagnosis after endoscopic submucosal dissection (ESD) or surgery were enrolled in this study. For the 403 cases, we analyzed the accuracies of depth by conventional endoscopy (CE) and EUS retrospectively. We evaluated the clinical survey items of CE and EUS which will be described later to compare the differences between "accuracy group" and "over-staging group", and between "accuracy group" and "under-staging group", retrospectively. Additionally, 78 EGC lesions which were confined to the submucosa and for which it was possible to measure accurate invasive distance from the muscularis mucosae were examined for the relationship between preoperative diagnosis of depth by CE and EUS and invasive distance retrospectively. RESULTS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were 87.3%. For CE staging, histological classification was the factor which influenced over-staging. Gastric regions and tumor area were the factors which influenced under-staging of CE. For EUS staging, tumor area was the factor which influenced over-staging, and gastric regions were the factors which influenced under-staging. Both CE and EUS were not sufficient for predicting the lesions confined to < 500 µm from the muscularis mucosae because the accuracies of both in predicting depth were less than 50%. However, EUS has a higher accuracy than CE for the lesions confined to 500 - 2,000 µm. CONCLUSIONS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were equal, but the contributing factors for over/under-staging were different. Both CE and EUS are not sufficient at present to predict the lesions confined to < 500 µm from the muscularis mucosae. However, the accuracy of EUS in predicting them may increase if high-performance EUS systems are developed in the future.

A Case of Refractory Esophageal Ulcer Caused by Radiotherapy for Hepatocellular Carcinoma.

A 77-year-old man who underwent radiotherapy for hepatocellular carcinoma 6 months prior consulted for esophageal obstruction. Esophagogastroduodenoscopy revealed an esophageal ulcer caused by radiotherapy for hepatocellular carcinoma. He was treated with dietary counseling and vonoprazan. After 9 months, the ulcer improved but a moderate stenosis remained. Several factors such as high fraction size, history of chemotherapy, and stress associated with food intake might involve in the development of a radiation-associated ulcer. Opportunities to choose radiotherapy for hepatocellular carcinoma may increase, so we hypothesize that esophageal ulcers might be a complication that should be noted associated with this therapy.

Relationship Between Gastroesophageal Reflux Disease and Endoscopic Finding "Iodine-Unstained Streak".

BACKGROUND: Esophagogastroduodenoscopy (EGD) with iodine stain is a useful and diffused method for diagnosing esophageal cancer. We can perform the procedure easily with endoscopic system which does not comprise image-enhanced endoscopy. Several studies advocated that iodine-unstained streaks are a characteristic finding of gastroesophageal reflux disease (GERD). However, there are only a few reports about the subject. In this study, we investigated the usefulness of iodine chromoendoscopy for GERD consultation. METHODS: The study was conducted with 154 GERD cases in which EGD with iodine stain to the esophagus was performed. For the 154 cases, we analyzed the existence of reflux esophagitis finding and iodine-unstained streaks. In 47 GERD cases (proton pump inhibitor (PPI): 45 cases, histamine H2-receptor antagonist (H2-RA): two cases) where medication was started after EGD, we examined predictive factors of the symptom improvement such as sex, age, weight, reflux esophagitis finding, and iodine-unstained streak. RESULTS: An iodine-unstained streak was observed in 50/154 cases (32.5%). For 50 cases with iodine-unstained streak, there were only 24/50 cases (48.0%) that had both reflux esophagitis findings (≥ Los Angeles classification: grade M) and an iodine-unstained streak. For 47 cases in which medication was started, 34 cases showed improvement in their symptoms, and 13 cases did not show improvement. An iodine-unstained streak was observed more often in "Improved" group rather than in "Not improved" group (P < 0.01). When we supposed an iodine-unstained streak to be the predictive factor of the medication effect for GERD, sensitivity was 61.8% and specificity was 84.6%. CONCLUSIONS: No erosion was often found in the GERD cases without reflux esophagitis, and iodine-unstained streak was observed more often in "Improved" group rather than in "Not improved" group. We think that iodine-unstained streak can be useful for diagnosing of GERD and predictive factor of the medication effect.

Mortality and the Risk Factors in Elderly Female Patients With Femoral Neck and Trochanteric Fractures.

BACKGROUND: The main purpose of this study is to exhaustively explore risk factors, including age, gender, and several clinical indices, for mortality in elderly patients with femoral neck fracture and to evaluate some of them using survival analyses. METHODS: This was a retrospective study tracking 1 year for vital prognosis. Data were collected at post-operation from medical records of the cases. Survival analysis was conducted to investigate the risk factors for death, including albumin, urinary retention, activity of daily living (ADL), and cognitive disorder. RESULTS: We recruited 318 patients with a history of hip surgery carried out at Toyama Municipal Hospital, in which 39 patients died for 1 year after discharge. The results showed a significant decrease in survival rate in low albumin, positive urinary retention, and low ADL (P < 0.01, by log-rank test). The hazard ratios (95% confidence interval) of albumin, urinary retention, ADL, and cognitive disorder were 0.36 (0.19 - 0.69), 0.4 (0.2 - 0.8), 0.29 (0.15 - 0.58) and 0.65 (0.32 - 1.29), respectively. CONCLUSIONS: This study demonstrated that albumin, urinary retention and ADL were the important risk factors for mortality, and suggested that the postoperative management of albumin, urinary retention and ADL is important, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

Risk factors for the development of aspiration pneumonia in elderly patients with femoral neck and trochanteric fractures: A retrospective study of a patient cohort.

Aspiration pneumonia (AP) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of AP in elderly patients with femoral neck fractures.We recruited 426 patients (age 84.9 ±â€Š7.4 years) with a history of hip surgery carried out at Toyama Municipal Hospital. AP occurred in 18 out of 426 cases (4.23%). Statistical test has found significant differences in age, gender, serum albumin level, and cognitive impairment, between AP and non-AP groups. Subsequently multiple logistic regression analysis was conducted to investigate the risk factors for AP, including age, gender, serum albumin, cognitive impairment, and activities of daily living (ADL). Adjusted odds ratio showed significant differences in age, gender, and serum albumin, whereas no significant differences were found in cognitive impairment and ADL.This study suggested that serum albumin seemed to be a risk factor for AP but were necessary to assess under adjustment of confounding factors, including age and gender. Monitoring serum albumin level seemed to be important for the postoperative management of AP, especially in elderly patients receiving surgery of femoral neck and trochanteric fractures.

Urinary retention as a postoperative complication associated with functional decline in elderly female patients with femoral neck and trochanteric fractures: A retrospective study of a patient cohort.

Urinary retention (UR) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of UR in elderly female patients with femoral neck fractures.We recruited 221 female patients (age 85.3 ±â€Š7.0 years) with a history of hip surgery carried out at Toyama Municipal Hospital. UR occurred in 34 out of 221 cases (15.4%). Multiple logistic regression analysis was conducted to investigate the risk factors for UR, including age, body mass index (BMI), serum albumin, cognitive impairment, and activities of daily living (ADL).The results showed significant association of UR with cognitive impairment (P = .005, odds ratio [OR] 4.11, 95% confidence interval [CI] 1.53-11.03), and ADL (P = .029, OR 2.61, 95% CI 1.11-6.18), under adjustment with age and BMI.This study demonstrated that cognitive function and ADL were the important risk factors for UR, suggested that the postoperative management of UR is important with taking account of neurofunctional assistance and nursing care in daily living, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus.

The use of glycine as a therapeutic option for improving sleep quality is a novel and safe approach. However, despite clinical evidence of its efficacy, the details of its mechanism remain poorly understood. In this study, we investigated the site of action and sleep-promoting mechanisms of glycine in rats. In acute sleep disturbance, oral administration of glycine-induced non-rapid eye movement (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core temperature. Oral and intracerebroventricular injection of glycine elevated cutaneous blood flow (CBF) at the plantar surface in a dose-dependent manner, resulting in heat loss. Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine inhibited the CBF increase caused by glycine injection into the brain. Induction of c-Fos expression was observed in the hypothalamic nuclei, including the medial preoptic area (MPO) and the suprachiasmatic nucleus (SCN) shell after glycine administration. Bilateral microinjection of glycine into the SCN elevated CBF in a dose-dependent manner, whereas no effect was observed when glycine was injected into the MPO and dorsal subparaventricular zone. In addition, microinjection of D-serine into the SCN also increased CBF, whereas these effects were blocked in the presence of L-701324. SCN ablation completely abolished the sleep-promoting and hypothermic effects of glycine. These data suggest that exogenous glycine promotes sleep via peripheral vasodilatation through the activation of NMDA receptors in the SCN shell.

[Vitamin D in relation to frailty and locomotive syndrome].

Frailty is an extremely common and serious health problem in the elderly. Frailty has been described as "a biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse health outcomes" by Fried and colleagues. Frailty is associated with incident falls, functional limitation, disability, and mortality. There are many reports that vitamin D deficiency may play roles in diabetes mellitus, cancers, multiple sclerosis, and other autoimmune diseases, and was associated with poorer physical performance, falls and fractures, and a greater risk of nursing home admission. Recently, researches suggest that vitamin D may provide treatment and prevention from these diseases lead to frailty. Vitamin D is expected to be a treatment for frailty in an aging society.

[Frontiers in vitamin D; basic research and clinical application. Activated vitamin D in psoriasis].

Psoriasis is a chronic immune-mediated disease that appears on the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Activated vitamin D3 is the first-line treatment for psoriasis. Psoriasis is often treated with combination therapy of activated vitamin D3 and other treatment. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Thus, the goal for the treatment of psoriasis is to control the signs and symptoms over a long period and to ameliorate the quality of life of psoriasis patients.

Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice.

STUDY OBJECTIVE: Caffeine, an adenosine A1 and A2a receptor antagonist, is a widely consumed stimulant and also used for the treatment of hypersomnia; however, the wake-promoting potency of caffeine is often not strong enough, and high doses may induce side effects. Caffeine is metabolized to paraxanthine, theobromine, and theophylline. Paraxanthine is a central nervous stimulant and exhibits higher potency at A1 and A2 receptors, but has lower toxicity and lesser anxiogenic effects than caffeine. DESIGN: We evaluated the wake-promoting efficacy of paraxanthine, caffeine, and a reference wake-promoting compound, modafinil, in a mice model of narcolepsy, a prototypical disease model of hypersomnia. Orexin/ataxin-3 transgenic (TG) and wild-type (WT) mice were subjected to oral administration (at ZT 2 and ZT14) of 3 doses of paraxanthine, caffeine, modafinil, or vehicle. RESULTS: Paraxanthine, caffeine, and modafinil significantly promoted wakefulness in both WT and narcoleptic TG mice and proportionally reduced NREM and REM sleep in both genotypes. The wake-promoting potency of 100 mg/kg p.o. of paraxanthine during the light period administration roughly corresponds to that of 200 mg/kg p.o. of modafinil. The wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine, when the drugs were administered during the light period. The wake-promotion by paraxanthine, caffeine, and modafinil are associated with an increase in locomotor activity and body temperature. However, the higher doses of caffeine and modafinil, but not paraxanthine, induced hypothermia and reduced locomotor activity, thereby confirming the lower toxicity of paraxanthine. Behavioral evaluations of anxiety levels in WT mice revealed that paraxanthine induced less anxiety than caffeine did. CONCLUSIONS: Because it is also reported to provide neuroprotection, paraxanthine may be a better wake-promoting agent for hypersomnia associated with neurodegenerative diseases.

[A ninety-eight-year-old woman with ruptured pancreatic anaplastic mucinous cystadenocarcinoma].

A 98-year-old woman was admitted to our hospital complaining of anorexia, epigastralgia, and vomiting. An elastic hard tumor was palpable in her epigastric region. CT and US examination revealed a huge cystic lesion adjacent to the left lobe of the liver and the stomach. Her serum levels of CEA (13.6 ng/ml), CA19-9 (95 U/ml) and CA125 (99 U/ml) were high. She suffered from aspiration pneumonia on the 10th day of admission, which progressed to acute respiratory distress syndrome. On the 20th day of admission, the epigastric tumor suddenly disappeared. She passed away on the 31st day due to respiratory failure. Autopsy revealed that she had a ruptured pancreatic anaplastic mucinous cystadenocarcinoma. To the best of our knowledge, this is the oldest reported case of ruptured pancreatic cystadenocarcinoma in the world.

Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.

OBJECTIVES: To examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP). BACKGROUND: The Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque. METHODS: Thirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study. RESULTS: Plasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells. CONCLUSIONS: This demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.