Cancer history and physical function in patients with cardiovascular disease.

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61-77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan-Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4-5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis.

Predictive value of cholinesterase in patients with heart failure: A new blood biochemical marker of undernutrition.

BACKGROUND AND AIMS: This study was conducted to verify whether serum cholinesterase (ChE) is useful in predicting prognosis and discriminating undernutrition status compared to existing low-nutrition indices of blood chemical tests in patients with heart failure (HF). METHODS AND RESULTS: A total of 1617 patients (1204 older patients) with HF who evaluated ChE during hospitalization were recruited for this study. The primary outcome was all-cause death, and multivariate survival analysis was performed. We drew a receiver operating characteristic curve for all-cause death, some undernutrition status, such as low body mass index, thin mid-upper arm circumference, low grip strength, and slow gait speed. The area under the curve was used to compare the predictive ability of ChE with some existing nutritional parameters, such as blood biochemical tests, controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI). After adjusting for 29 variables, higher ChE significantly decreased the risk of all-cause death (per 10 increase, hazard ratio: 0.975, 95% confidence interval: 0.952-0.998), and this trend was maintained for older patients (per 10 increase, hazard ratio: 0.972, 95% confidence interval: 0.947-0.997). ChE was moderately correlated with CONUT and GNRI, but the predictive ability for all-cause death was higher for ChE relative to both scores. ChE tended to have an almost consistently high predictive ability compared with other blood biochemical tests. CONCLUSIONS: ChE was associated with all-cause death and an almost consistently higher predictive ability for all-cause death and undernutrition status in comparison to existing blood chemical tests and nutritional scores.

Relationship between the spread of COVID-19, social frailty, and depressive symptoms in patients with heart failure.

In community-dwelling older people, coronavirus disease 2019 (COVID-19) has been reported to be associated with the development of frailty and depressive symptoms. We aimed to investigate whether the spread of COVID-19 is associated with the development of frailty in patients with heart failure (HF). The presence of the multi-domain of frailty in 257 patients with HF was assessed at hospital discharge. The spread of COVID-19 was significantly associated with the development of social frailty and depressive symptoms. Evaluation of these symptoms during hospitalization would support disease management and understanding of their social and psychological conditions.

Effects of Acute Phase Intensive Physical Activity (ACTIVE-PA) Monitoring and Education for Cardiac Patients: Pilot Study of a Randomized Controlled Trial.

BACKGROUND: Although physical activity (PA) decreases dramatically during hospitalization, an effective intervention method has not yet been established for this issue. We recently developed a multiperson PA monitoring system using information and communication technology (ICT) that can provide appropriate management and feedback about PA at the bedside or during rehabilitation. This ICT-based PA monitoring system can store accelerometer data on a tablet device within a few seconds and automatically display a graphical representation of activity trends during hospitalization. OBJECTIVE: This randomized pilot study aims to estimate the feasibility and effect size of an educational PA intervention using our ICT monitoring system for in-hospital patients undergoing cardiac rehabilitation. METHODS: A total of 41 patients (median age 70 years; 24 men) undergoing inpatient cardiac rehabilitation were randomly assigned to 2 groups as follows: wearing an accelerometer only (control) and using both an accelerometer and an ICT-based PA monitoring system. Patients assigned to the ICT group were instructed to gradually increase their step counts according to their conditions. Adherence to wearing the accelerometer was defined as having enough wear records for at least 2 days to allow for adequate analysis during the lending period. An analysis of covariance was performed to compare the change in average step count during hospitalization as a primary outcome and the 6-minute walking distance at discharge. RESULTS: The median duration of wearing the accelerometer was 4 days in the ICT group and 6 days in the control group. Adherence was 100% (n=22) in the ICT group but 83% (n=20) in the control group. The ICT group was more active (mean difference=1370 steps, 95% CI 437-2303) and had longer 6-minute walking distances (mean difference=81.6 m, 95% CI 18.1-145.2) than the control group. CONCLUSIONS: Through this study, the possibility of introducing a multiperson PA monitoring system in a hospital and promoting PA during hospitalization was demonstrated. These findings support the rationale and feasibility of a future clinical trial to test the efficacy of this educational intervention in improving the PA and physical function of in-hospital patients. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000043312; http://tinyurl.com/m2bw8vkz.

Oral Administration of Lipopolysaccharide Enhances Insulin Signaling-Related Factors in the KK/Ay Mouse Model of Type 2 Diabetes Mellitus.

Lipopolysaccharide (LPS), an endotoxin, induces systemic inflammation by injection and is thought to be a causative agent of chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). However, our previous studies found that oral LPS administration does not exacerbate T2DM conditions in KK/Ay mice, which is the opposite of the response from LPS injection. Therefore, this study aims to confirm that oral LPS administration does not aggravate T2DM and to investigate the possible mechanisms. In this study, KK/Ay mice with T2DM were orally administered LPS (1 mg/kg BW/day) for 8 weeks, and blood glucose parameters before and after oral administration were compared. Abnormal glucose tolerance, insulin resistance progression, and progression of T2DM symptoms were suppressed by oral LPS administration. Furthermore, the expressions of factors involved in insulin signaling, such as insulin receptor, insulin receptor substrate 1, thymoma viral proto-oncogene, and glucose transporter type 4, were upregulated in the adipose tissues of KK/Ay mice, where this effect was observed. For the first time, oral LPS administration induces the expression of adiponectin in adipose tissues, which is involved in the increased expression of these molecules. Briefly, oral LPS administration may prevent T2DM by inducing an increase in the expressions of insulin signaling-related factors based on adiponectin production in adipose tissues.

Trends and Outcomes of Early Rehabilitation in the Intensive Care Unit for Patients With Cardiovascular Disease: A Cohort Study With Propensity Score-Matched Analysis.

BACKGROUND: The effectiveness of acute-phase cardiovascular rehabilitation (CR) in intensive care settings remains unclear in patients with cardiovascular disease (CVD). This study aimed to investigate the trends and outcomes of acute-phase CR in the intensive care unit (ICU) for patients with CVD, including in-hospital and long-term clinical outcomes. METHOD: This retrospective cohort study reviewed a total of 1,948 consecutive patients who were admitted to a tertiary academic ICU for CVD treatment and underwent CR during hospitalisation. The endpoints of this study were the following: in-hospital outcomes: probabilities of walking independence and returning home; and long-term outcomes: clinical events 5 years following hospital discharge, including all-cause readmission or cardiovascular events. It evaluated the associations of CR implementation during ICU treatment (ICU-CR) with in-hospital and long-term outcomes using propensity score-matched analysis. RESULTS: Among the participants, 1,092 received ICU-CR, the rate of which tended to increase with year trend (p for trend <0.001). After propensity score matching, 758 patients were included for analysis (pairs of n=379 ICU-CR and non-ICU-CR). ICU-CR was significantly associated with higher probabilities of walking independence (rate ratio, 2.04; 95% CI 1.77-2.36) and returning home (rate ratio, 1.22; 95% CI 1.05-1.41). These associations were consistently observed in subgroups aged >65 years, after surgery, emergency, and prolonged ICU stay. ICU-CR showed significantly lower incidences of all-cause (HR 0.71; 95% CI 0.56-0.89) and cardiovascular events (HR 0.69; 95% CI 0.50-0.95) than non-ICU-CR. CONCLUSIONS: The implementation of acute-phase CR in ICU increased with year trend, and is considered beneficial to improving in-hospital and long-term outcomes in patients with CVD and various subgroups.

Characteristics of Elderly Patients with Heart Failure and Impact on Activities of Daily Living: A Registry Report from Super-Aged Society.

BACKGROUND: To assess the health care burden of elderly patients with heart failure (HF) in an aging Japanese community-based hospital, we investigated the outcomes of cardiac rehabilitation. METHODS AND RESULTS: We enrolled all patients with HF aged ≥65 years admitted to 3 hospitals in the Niigata Prefecture. We prospectively collected data on their hospital stays and for 2 years postdischarge. The cohort comprised 617 patients (46.5% men; mean age 84.7 years), 76.2% of whom were aged ≥80 years. Among these patients, 15.6% were nursing home residents, 57.7% required long-term care insurance, only 37.6% could walk unaided at the time of admission, and 70.5% required cardiac rehabilitation; age had no significant rehabilitative effect on the degree of improvement in activities of daily living (ADLs). Two years postdischarge, all-cause mortality, and HF rehospitalization were 41.1% and 38.6%, respectively. The ADL score at discharge was an independent prognostic factor for mortality. The incidence of mortality and rehospitalization was lower in elderly patients with preserved ADLs at discharge. CONCLUSIONS: Elderly patients with HF in our super-aged society were mainly octogenarians who required disease management and personalized care support. Although their ADL scores increased with comprehensive cardiac rehabilitation, improved scores at discharge were closely associated with prognosis.

Low skeletal muscle density combined with muscle dysfunction predicts adverse events after adult cardiovascular surgery.

BACKGROUND AND AIMS: Although muscle dysfunctions are widely known as a poor prognostic factor in patients with cardiovascular disease, no study has examined whether the addition of low skeletal muscle density (SMD) assessed by computed tomography (CT) to muscle dysfunctions is useful. This study examined whether SMDs can strengthen the predictive ability of muscle dysfunctions for adverse events in patients who underwent cardiovascular surgery. METHODS AND RESULTS: We retrospectively reviewed 853 patients aged ≥40 years who had preoperative CT for risk management purposes and who measured muscle dysfunctions (weakness: low grip strength and slowness: slow gait speed). Low SMD based on transverse abdominal CT images was defined as a mean Hounsfield unit of the psoas muscle <45. All definitions of muscle dysfunction (weakness only, slowness only, weakness or slowness, weakness and slowness), the addition of SMDs was shown to significantly improve the continuous net reclassification improvement and integrated discrimination improvement for adverse events in all analyses (p < 0.05). Low SMDs combined with each definition of muscle dysfunction had the highest risk of all-cause death (hazard ratio: lowest 3.666 to highest 6.002), and patients with neither low SMDs nor muscle dysfunction had the lowest risk of all-cause and cardiovascular-related events. CONCLUSION: The addition of SMDs consistently increased the predictive ability of muscle dysfunctions for adverse events. Our results suggest that when CT is performed for any clinical investigation, the addition of the organic assessment of skeletal muscle can strengthen the diagnostic accuracy of muscle wasting.

Multidomain Frailty in Heart Failure: Current Status and Future Perspectives.

PURPOSE OF REVIEW: With a worldwide aging population, frailty and heart failure (HF) have become issues that need to be addressed urgently in cardiovascular clinical practice. In this review, we outline the clinical implications of frailty in HF patients and the potential therapeutic strategies to improve the clinical outcomes of frail patients with HF. RECENT FINDINGS: Frailty has physical, psychological, and social domains, each of which is a prognostic determinant for patients with HF, and each domain overlaps with the other, although there are no standardized criteria for diagnosing frailty. Frailty can be targeted for treatment with various interventions, and recent studies have suggested that multidisciplinary intervention could be a promising option for frail patients with HF. However, currently, there is limited data, and further research is needed before its clinical implementation. Frailty and HF share a common background and are strongly associated with each other. More comprehensive assessment and therapeutic interventions for frailty need to be developed to further improve the prognosis and quality of life of frail patients with HF.

Prognostic value of instrumental activity of daily living in initial heart failure hospitalization patients aged 65 years or older.

Although the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) is useful to assess decline of instrumental activities of daily living (IADL) in Japanese individuals, limited data are available in patients with heart failure (HF). This study was performed to investigate the prognostic value of IADL evaluated by TMIG-IC in initial HF hospitalization patients aged ≥ 65 years. We reviewed 297 elderly HF patients with independent basic ADL before hospitalization. Patients with prior HF were excluded. Five TMIG-IC items were investigated as IADL parameters. Patients with full IADL scores were defined as "independent" and others were defined as "dependent". The endpoint was all-cause mortality, and multivariable analysis was performed to identify IADL risk. The median age was 76 years, and 55% of the patients were male. Forty-one deaths occurred over a median follow-up period of 1.01 years. After adjusting for existing risk factors, including Seattle Heart Failure Score, dependent patients had higher mortality risk than independent patients [hazard ratio 3.64, 95% confidence interval (CI) 1.57-8.43], and mortality risk decreased by 16% for each 1-point increase in IADL score (hazard ratio 0.84, 95% CI 0.71-0.99). In conclusion, limited IADL indicated by TMIG-IC was associated with poorer long-term mortality rate in elderly patients with HF. This inexpensive and easily applicable tool will support decision making in cardiac rehabilitation.

Association between sarcopenia and atherosclerosis in elderly patients with ischemic heart disease.

Compared to the general population, elderly patients with cardiovascular disease have a higher prevalence of sarcopenia, and it shows an association with increased mortality risk. Although several studies have indicated that atherosclerosis may cause sarcopenia in community dwelling elderly subjects, the association between sarcopenia and atherosclerosis is not clear in patients with ischemic heart disease (IHD). The present study was performed to examine the association between muscle function and atherosclerosis in elderly patients with IHD. We reviewed the findings of 321 consecutive patients ≥ 65 years old with IHD. Three measures of muscle function were examined, i.e., gait speed, quadriceps isometric strength, and handgrip strength, just before hospital discharge. In addition, we measured intima-media thickness (IMT) as a parameter of arteriosclerosis. To investigate the association between sarcopenia and atherosclerosis, patients were divided into Group H (high), Group M (middle), and Group L (low) according to the tertiles of muscle function, and IMT was compared between the three groups. In addition, we considered the association between IMT thickening and muscle function. The mean age of the study population was 74.1 ± 6.0 years and 73.2% of the patients were men. IMT was compared between groups stratified according to gait speed and quadriceps isometric strength, and the results indicated that IMT was significantly lower in Group H than in Groups L and M (p < 0.05). In addition, gait speed and quadriceps isometric strength were associated with IMT thickening (p < 0.05). Parameters reflecting muscle function of the lower limbs are associated with atherosclerosis in patients with IHD.

Usefulness of the Simplified Frailty Scale in Predicting Risk of Readmission or Mortality in Elderly Patients Hospitalized with Cardiovascular Disease.

The simplified frailty scale is a simple frailty assessment tool modified from Fried's phenotypic frailty criteria, which is easy to administer in hospitalized patients. The applicability of the simplified frailty scale to indicate prognosis in elderly hospitalized patients with cardiovascular disease (CVD) was examined.This cohort study was performed in 895 admitted patients ≥ 65 years (interquartile range, 71.0-81.0, 541 men) with CVD. Patients were classified as robust, prefrail, or frail based on the five components of the simplified frailty scale: weakness, slowness, exhaustion, low activity, and weight loss. The primary endpoint was the composite outcome of all-cause mortality and unplanned readmission for CVD.Patients positive for greater numbers of frailty components showed higher risk of all-cause mortality or unplanned CVD-related readmission (P for trend < 0.001). Classification as both frail (adjusted HR: 3.27, 95% confidence interval [CI]: 1.49-7.21, P = 0.003) and prefrail (adjusted HR: 2.19, 95% CI: 1.00-4.79, P = 0.049) independently predicted the composite endpoint compared with robust after adjusting for potential confounding factors. The inclusion of prefrail, frail, and number of components of frailty increased both continuous net reclassification improvement (0.113, P = 0.049; 0.426, P < 0.001; and 0.321, P < 0.001) and integrated discrimination improvement (0.007, P = 0.037; 0.009, P = 0.038; and 0.018, P = 0.002) for the composite endpoint.Higher scores on the simplified frailty scale were associated with increased risk of mortality or readmission in elderly patients hospitalized for CVD.

[Laparoscopic Resection of a Giant Lumbar Foraminal Schwannoma].

Lumbar foraminal schwannomas occasionally present as giant lesions in the retroperitoneal cavity. Here, we report a case of a L5 giant foraminal schwannoma that was laparoscopically excised. A 26-year-old man visited our hospital with the complaint of numbness of the left leg that had persisted for 2 years. Magnetic resonance imaging scans revealed a dumbbell tumor originating from the left L5/L6 intervertebral foramen. The tumor mass in the retroperitoneum extended to 6 cm and was buried in the iliopsoas, pressing superiorly on the L4 nerve root. During the surgical procedure, the ventral portion of the tumor was first excised outside the intervertebral foramen, using the anterior approach to laparoscopically enter the retroperitoneum. Postoperatively, the left leg pain disappeared. The residual tumor in the posterior portion was resected microsurgically with the Wiltse paraspinal approach. The tumor was a schwannoma originating from the dorsal ramus of the L5 nerve root. Postoperatively, the patient resumed ambulation and was discharged with no exacerbation of the neurological symptoms.

Mathematical modeling of septic shock based on clinical data.

BACKGROUND: Mathematical models of diseases may provide a unified approach for establishing effective treatment strategies based on fundamental pathophysiology. However, models that are useful for clinical practice must overcome the massive complexity of human physiology and the diversity of patients' environmental conditions. With the aim of modeling a complex disease, we choose sepsis, which is highly complex, life-threatening systemic disease with high mortality. In particular, we focused on septic shock, a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Our model includes cardiovascular, immune, nervous system models and a pharmacological model as submodels and integrates them to create a sepsis model based on pathological facts. RESULTS: Model validation was done in two steps. First, we established a model for a standard patient in order to confirm the validity of our approach in general aspects. For this, we checked the correspondence between the severity of infection defined in terms of pathogen growth rate and the ease of recovery defined in terms of the intensity of treatment required for recovery. The simulations for a standard patient showed good correspondence. We then applied the same simulations to a patient with heart failure as an underlying disease. The model showed that spontaneous recovery would not occur without treatment, even for a very mild infection. This is consistent with clinical experience. We next validated the model using clinical data of three sepsis patients. The model parameters were tuned for these patients based on the model for the standard patient used in the first part of the validation. In these cases, the simulations agreed well with clinical data. In fact, only a handful parameters need to be tuned for the simulations to match with the data. CONCLUSIONS: We have constructed a model of septic shock and have shown that it can reproduce well the time courses of treatment and disease progression. Tuning of model parameters for each patient could be easily done. This study demonstrates the feasibility of disease models, suggesting the possibility of clinical use in the prediction of disease progression, decisions on the timing of drug dosages, and the estimation of time of infection.

Short-Term Change in Gait Speed and Clinical Outcomes in Older Patients With Acute Heart Failure.

BACKGROUND: Evidence for the prognostic value of gait speed is largely based on a single measure at baseline, so we investigated the prognostic significance of change in gait speed in hospitalized older acute heart failure (AHF) patients.Methods and Results:This retrospective study was performed in a cohort of 388 AHF patients ≥60 years old (mean age: 74.8±7.8 years, 228 men). Routine geriatric assessment included gait speed measurement at baseline and at discharge. The primary outcome of this study was all-cause death. Gait speed increased from 0.74±0.25 m/s to 0.98±0.27 m/s after 13.5±11.0 days. Older age, shorter height and lower hemoglobin level at admission, prior HF admission, and higher baseline gait speed were independently associated with lesser improvement in gait speed. A total of 80 patients died and 137 patients were readmitted for HF over a mean follow-up period of 2.1±1.9 years. In multivariate analyses, change in gait speed showed inverse associations with all-cause death (hazard ratio [HR] per 0.1 m/s increase: 0.83; 95% confidence interval [CI]: 0.73 to 0.95; P=0.006) and with risk of readmission for HF (HR: 0.91; 95% CI: 0.83 to 0.99; P=0.036). CONCLUSIONS: Short-term improvement in gait speed during hospitalization was associated with reduced risks of death and readmission for HF in older patients with AHF.

Facile preparation of highly active casein kinase 1 using Escherichia coli constitutively expressing lambda phosphatase.

Casein kinase 1 (CK1) is a widely expressed Ser/Thr kinase in eukaryotic organisms that is involved in various cellular processes (e.g., circadian rhythm and apoptosis). Therefore, preparing highly active CK1 and investigating its properties in vitro have important implications for understanding the biological roles of the kinase. However, recombinant CK1 undergoes autoinactivation via autophosphorylation in Escherichia coli cells and thus is undesirably prepared as a phosphorylated and inactivated kinase. To circumvent this problem, we established a protein expression system using E. coli strain BL21(DE3)pλPP in which λ protein phosphatase (λPPase) is constitutively expressed. Using this system, recombinant CK1 isoforms (α, δ and ε) were readily prepared as unphosphorylated forms. Furthermore, we found that CK1s prepared using BL21(DE3)pλPP showed markedly higher activity than those prepared by the conventional BL21(DE3). Finally, we demonstrated that the kinase activity of CK1δ from BL21(DE3)pλPP was higher than that prepared by a conventional method consisting of troublesome steps such as in vitro λPPase treatment. Thus, this simple method using BL21(DE3)pλPP is valuable for preparing highly active CK1s. It may also be applicable to other kinases that are difficult to prepare because of phosphorylation in E. coli cells.

A mathematical model of type 1 diabetes involving leptin effects on glucose metabolism.

Leptin, a hormone released from fat cells in adipose tissues, was recently found to be capable of normalizing glucose metabolism in animals. Clinical data on patients with lipodystrophy indicates that leptin may have a positive effect on glucose metabolism in individuals with diabetes. There are growing expectations that leptin can improve the current insulin treatment for patients with type 1 diabetes. We investigated this possibility through in silico experiments based on a mathematical model of diabetes, which is currently the only mode of research that eliminates human risk. A model of the brain-centered glucoregulatory system, in which leptin plays a central role, was constructed and integrated within a conventional model of insulin/glucose dynamics. The model has been validated using experimental data from animal studies. The in silico combination experiments showed excellent therapeutic performance over insulin monotherapy.

Characterization of CoPK02, a Ca2+/calmodulin-dependent protein kinase in mushroom Coprinopsis cinerea.

We surveyed genome sequences from the basidiomycetous mushroom Coprinopsis cinerea and isolated a cDNA homologous to CMKA, a calmodulin-dependent protein kinase (CaMK) in Aspergillus nidulans. We designated this sequence, encoding 580 amino acids with a molecular weight of 63,987, as CoPK02. CoPK02 possessed twelve subdomains specific to protein kinases and exhibited 43, 35, 40% identity with rat CaMKI, CaMKII, CaMKIV, respectively, and 40% identity with CoPK12, one of the CaMK orthologs in C. cinerea. CoPK02 showed significant autophosphorylation activity and phosphorylated exogenous proteins in the presence of Ca2+/CaM. By the CaM-overlay assay we confirmed that the C-terminal sequence (Trp346-Arg358) was the calmodulin-binding site, and that the binding of Ca2+/CaM to CoPK02 was reduced by the autophosphorylation of CoPK02. Since CoPK02 evolved in a different clade from CoPK12, and showed different gene expression compared to that of CoPK32, which is homologous to mitogen-activated protein kinase-activated protein kinase, CoPK02 and CoPK12 might cooperatively regulate Ca2+-signaling in C. cinerea.

Baseline data collections of lipopolysaccharide content in 414 herbal extracts and its role in innate immune activation.

Some herbal extracts contain relatively high amounts of lipopolysaccharide (LPS). Because orally administered LPS activates innate immunity without inducing inflammation, it plays a role as an active ingredient in herbal extracts. However, the LPS content in herbal extracts remains extensively unevaluated. This study aimed to create a database of LPS content in herbal extracts; therefore, the LPS content of 414 herbal extracts was measured and the macrophage activation potential was evaluated. The LPS content of these hot water extracts was determined using the kinetic-turbidimetric method. The LPS concentration ranged from a few ng/g to hundreds of µg/g (Standard Escherichia coli LPS equivalent). Twelve samples had a high-LPS-content of > 100 µg/g, including seven samples from roots and three samples from leaves of the herbal extracts. These samples showed high phagocytosis and NO production capacity, and further investigation using polymyxin B, an LPS inhibitor, significantly inhibited macrophage activation. This study suggests that some herbal extracts contain sufficient LPS concentration to activate innate immunity. Therefore, a new approach to evaluate the efficacy of herbal extracts based on their LPS content was proposed. A database listing the LPS content of different herbal extracts is essential for this approach.