Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts.

BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study.

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.

BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

BACKGROUND: Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF. METHODS: The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination. RESULTS: On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema). CONCLUSIONS: Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.

Clinical effect of hyperbaric oxygen therapy in adhesive postoperative small bowel obstruction.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is a controversial treatment for adhesive postoperative small bowel obstruction, with only a few small studies reported. The aim of this study was to assess the clinical value of HBO therapy in the treatment of adhesive postoperative small bowel obstruction. METHODS: Between April 2006 and March 2012, all patients with adhesive postoperative small bowel obstruction were treated using either decompression therapy or HBO. Patients undergoing HBO therapy were treated once a day at a pressure of 2·0 atmospheres absolute and received 100 per cent oxygen. Patients showing no clinical and radiological improvement with HBO therapy were converted to decompression therapy by means of a long tube. Medical records were reviewed and outcomes analysed. RESULTS: A total of 305 patients were treated, of whom 142 underwent tube decompression therapy during the first 3 years and the remaining 163 had HBO therapy during the last 3 years. The median number of HBO treatments was 3 (range 1-7). A total of 143 patients (87·7 per cent) were treated successfully with HBO without long-tube decompression. HBO therapy was associated with earlier resumption of oral intake (mean 4·7 versus 6·5 days; P = 0·001) and a shorter hospital stay (mean 10·3 versus 14·1 days; P = 0·001). The rate of operation was 7·4 per cent in the HBO group and 14·8 per cent in group treated by decompression alone (P = 0·037). CONCLUSION: In this study, HBO therapy was safe for the treatment of adhesive postoperative small bowel obstruction. It reduced the need for surgery and time to recovery as well as the hospital stay.

Preliminary study for the assessment of physical activity using a triaxial accelerometer with a gyro sensor on the upper limbs of subjects with paraplegia driving a wheelchair on a treadmill.

OBJECTIVE: This study aimed to examine whether, on the basis of the relationship between sensors attached on the upper limbs and energy expenditure (EE) at the time of wheelchair propulsion, there are differences in the measurement of EE depending on the sensor attachment site and whether addition of the angular velocity information to the acceleration value is advantageous. We also aimed to clarify the variables used to estimate EE as well as the estimated error. SETTING: Laboratory of the National Hospital Organization Murayama Medical Center, Japan. METHODS: Six male subjects with spinal cord injuries participated in the study. Each wore sensors at the wrist and the middle upper arm on both sides while driving a wheelchair on a treadmill at three levels: very, very light; very light; and fairly light. Triaxial acceleration, triaxial angular velocity and EE were measured during driving. We analyzed the correlation between EE and acceleration, angular velocity and synthesized values of acceleration and angular velocity at each location using regression, multiple regression and Bland-Altman analyses. RESULTS: The determination coefficients between EE and the acceleration, angular velocity and synthesized values of acceleration and angular velocity varied from 0.68 to 0.87 at each location. The mean difference between the measured and estimated EE varied from 0.0028 (s.d., 0.0027) kcal min(-1) kg(-1) on the right upper arm. CONCLUSION: These findings suggest that combining the synthesized values of angular velocity and acceleration of the motion sensors on the upper limbs might reflect EE during a wheelchair driving activity on a treadmill.

An observational, prospective study of monthly adalimumab therapy for disease maintenance in psoriasis patients: a possible new therapeutic option for good responders to the initial induction treatment.

BACKGROUND: While adalimumab is a mainstay of treatment for moderate to severe chronic plaque psoriasis, the data regarding optimal treatment intervals for therapeutic maintenance are limited. OBJECTIVE: We compared the clinical efficacy of biweekly maintenance administration of adalimumab with that of monthly treatment. METHODS: 17 psoriasis patients treated with adalimumab 40 mg every other week with initial loading dose of 80 mg until week 24 were assigned to the maintenance therapy with adalimumab 40 mg either every other week (n = 7), or every month (n = 10). The treatment efficacy was evaluated by the proportion of patients who achieved PASI 75 from the baseline at weeks 36, 48 and 60. There was no selection bias between the two groups. RESULTS: At week 24, all the patients except for one in each group achieved PASI 75. In both groups, all the patients who achieved PASI 75 at week 24 maintained PASI 75 responses at week 60. Regarding two patients who did not achieve PASI 75 at week 24, one biweekly treated patient experienced a gradual increase in therapeutic response while one monthly treated patient showed exacerbation after week 24. CONCLUSION: Monthly adalimumab treatment seems to be a reasonable treatment option for patients who responded well to initial standard adalimumab treatment for 24 weeks. Since there are several limitations in this study, including the number of patients, observation period, and patients' characteristics, large randomized controlled trials are needed to confirm these results.

Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.

PURPOSE: The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK). MATERIALS AND METHODS: Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined. RESULTS: Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells. CONCLUSION: This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.

Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, in B cells.

Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1; previously named HCP, PTP1C, SH-PTP1, and SHP) is a cytosolic protein tyrosine phosphatase that contains two SH2 domains. Recent data have demonstrated that the gene encoding SHP-1 is mutated in motheaten (mc) and viable motheaten (mc') mice resulting in autoimmune disease. More recently, SHP-1 has been shown to negatively regulate B cell antigen receptor (BCR)-initiated signaling. To elucidate potential mechanisms of SHP-1 action in BCR signal transduction, we studied proteins that interact with SHP-1 in B cells. Both anti-SHP-1 antibody and the two SH2 domains of SHP-1 expressed as glutathione S-transferase fusion proteins precipitated at least three phosphoproteins of approximately 75, 110, and 150 kD upon anti-immunoglobulin M stimulation of the WEHI-231 immature B cell line. Binding of SHP-1 to the 75- and 110-kD proteins appeared to be mediated mainly by the NH2-terminal SH2 domain of SHP-1, whereas both the NH2- and COOH-terminal SH2 domains are required for maximal binding to the 150-kD protein. Immunoprecipitation and Western blot analysis revealed that the SHP-1-associated 75-kD protein is the hematopoietic cell-specific, SH2-containing protein SLP-76. Further, this protein-protein association was constitutively observed and stable during the early phase of BCR signaling. However, significant tyrosine phosphorylation of SLP-76 as well as of SHP-1 was observed after BCR ligation. Constitutive association of SHP-1 with SLP-76 could also be detected in normal splenic B cells. Collectively, these results suggest possible mechanisms by which SHP-1 may modulate signals delivered by BCR engagement.

STAT3 is required for the gp130-mediated full activation of the c-myc gene.

The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter- driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.

Analyses of amino acid sequences in hypervariable region-1 of hepatitis C virus (HCV) in sera from chimpanzees infected three times with the same HCV strain.

BACKGROUND: To investigate whether or not the same strain of hepatitis C virus (HCV) can twice re-infect the same chimpanzee, we analyzed nucleic and amino acid sequences in HCV hypervariable region-1 (HVR1). Two chimpanzees were inoculated, three times each, with the same HCV strain during the 1983-1991. After each inoculation, chimpanzees developed acute hepatitis C, and then recovered. METHODS: Using sera, HVR1 cloning and antibody to HVR1 major clone measurement were performed. RESULTS: Clones from the first inoculum were divisible into major and minor types. Clones from the second and third inocula, as well as all post-inoculation sera, were essentially identical to the major type. Titers of antibody to HVR1 major clone were consistently low in pre- and post-inoculation sera. CONCLUSIONS: Both chimpanzees were re-infected twice with the same strain of HCV. The sequences from the second and third infections were similar to the major sequences in the first inoculum.

Maturational changes in the feeding behaviour of infants - a comparison between breast-feeding and bottle-feeding.

AIM: To obtain a better understanding of the changes in feeding behaviour from 1 to 6 months of age. By comparing breast- and bottle-feeding, we intended to clarify the difference in longitudinal sucking performance. METHODS: Sucking variables were consecutively measured for 16 breast-fed and eight bottle-fed infants at 1, 3 and 6 months of age. RESULTS: For breast-feeding, number of sucks per burst (17.8 +/- 8.8, 23.8 +/- 8.3 and 32.4 +/- 15.3 times), sucking burst duration (11.2 +/- 6.1, 14.7 +/- 8.0 and 17.9 +/- 8.8 sec) and number of sucking bursts per feed (33.9 +/- 13.9, 28.0 +/- 18.2 and 18.6 +/- 12.8 times) at 1, 3 and 6 months of age respectively showed significant differences between 1 and 6 months of age (p < 0.05). The sucking pressure and total number of sucks per feed did not differ among different ages. Bottle-feeding resulted in longer sucking bursts and more sucks per burst compared with breast-feeding in each month (p < 0.05). CONCLUSION: The increase in the amount of ingested milk with maturation resulted from an increase in bolus volume per minute as well as the higher number of sucks continuously for both breast- and bottle-fed infants.

Pharmacokinetics of 5-fluorouracil in elderly Japanese patients with cancer treated with S-1 (a combination of tegafur and dihydropyrimidine dehydrogenase inhibitor 5-chloro-2,4-dihydroxypyridine).

S-1 is an oral anticancer agent that combines tegafur, a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase. We examined the effects of aging on the pharmacokinetics of the components of S-1. The median area under the concentration-time curve (AUC) of active 5-FU did not significantly differ between 10 patients 75 years or older and 53 patients younger than 75 years (P = 0.598, Mann-Whitney U test). It is interesting to note that the median oral clearance of tegafur in patients 75 years or older was significantly lower than that in patients younger than 75 years (P = 0.011). Furthermore, the median AUC of CDHP was significantly higher in patients 75 years or older than in those younger than 75 years (P = 0.004). This effect was caused by reduced renal function in the elderly, because CDHP is excreted in the urine by glomerular filtration. The opposing effects of aging on the oral clearance of tegafur and the AUC of CDHP may offset each other, leading to unchanged systemic exposure of 5-FU.

Protein tyrosine phosphatase epsilon is a negative regulator of FcepsilonRI-mediated mast cell responses.

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase epsilon (PTPepsilon; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (FcepsilonRI). Bone marrow-derived mast cells (BMMC) from Ptpre(-/-) mice exhibited enhanced FcepsilonRI-induced Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca(2+) mobilization revealed that the absence of PTPepsilon leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPepsilon. In the event, Syk but not Lyn was hyperphosphorylated in PTPepsilon-deficient BMMC. Thus, PTPepsilon most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca(2+). Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre(-/-) mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTPepsilon negatively regulates FcepsilonRI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.

Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures.

We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. elegans atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607--3614]. Together with the fact that aPKC and a mammalian PAR-3 homologue, aPKC-specific interacting protein (ASIP), colocalize at the tight junctions of polarized epithelial cells (Izumi, Y., H. Hirose, Y. Tamai, S.-I. Hirai, Y. Nagashima, T. Fujimoto, Y. Tabuse, K.J. Kemphues, and S. Ohno. 1998. J. Cell Biol. 143:95--106), this suggests a ubiquitous role for aPKC in establishing cell polarity in multicellular organisms. Here, we show that the overexpression of a dominant-negative mutant of aPKC (aPKCkn) in MDCK II cells causes mislocalization of ASIP/PAR-3. Immunocytochemical analyses, as well as measurements of paracellular diffusion of ions or nonionic solutes, demonstrate that the biogenesis of the tight junction structure itself is severely affected in aPKCkn-expressing cells. Furthermore, these cells show increased interdomain diffusion of fluorescent lipid and disruption of the polarized distribution of Na(+),K(+)-ATPase, suggesting that epithelial cell surface polarity is severely impaired in these cells. On the other hand, we also found that aPKC associates not only with ASIP/PAR-3, but also with a mammalian homologue of C. elegans PAR-6 (mPAR-6), and thereby mediates the formation of an aPKC-ASIP/PAR-3-PAR-6 ternary complex that localizes to the apical junctional region of MDCK cells. These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells.

Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.

The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.

SARC-F Validation and SARC-F+EBM Derivation in Musculoskeletal Disease: The SPSS-OK Study.

OBJECTIVES: To validate the SARC-F questionnaire for sarcopenia screening in musculoskeletal disease setting, and to assess improvements in diagnostic accuracy by adding "EBM" (elderly and body mass index information) to the SARC-F. DESIGN: Diagnostic accuracy study. SETTING AND PARTICIPANTS: The center involved in this study was located in an urban area of Kobe City, Japan. People with musculoskeletal disease in the knee, hip, or spine who were scheduled for surgical treatment were included. MEASUREMENTS: Sarcopenia was evaluated using the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP2), which included bioimpedance, handgrip strength, and gait speed. Patients answered the SARC-F questionnaire and their body mass index was measured. SARC-F and "EBM" information were combined into an original score. The sensitivities, specificities, and areas under the receiver operating characteristic curve (AUC) were estimated and compared to identify sarcopenia. RESULTS: A total of 959 patients were included. Sarcopenia by AWGS criteria was identified in 36 (3.8%) patients. SARC-F had a sensitivity of 41.7% and specificity of 68.5%. SARC-F+EBM had a sensitivity of 77.8% and specificity of 69.6%, with substantial improvement in sensitivity (P<0.001). The AUCs for SARC-F and SARC-F+EBM were 0.557 (95% confidence interval [CI] 0.452-0.662) and 0.824 (95% CI 0.762-0.886), respectively (P<0.001). Similar results were obtained when EWGSOP2 criteria were used as the reference standard. CONCLUSION: The SARC-F alone is not adequate for finding cases in musculoskeletal disease settings. SARC-F+EBM significantly improved the sensitivity and overall diagnostic accuracy of the SARC-F for screening sarcopenia. SARC-F+EBM is potentially useful for screening sarcopenia in different ethnic and disease settings.