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AIM: To identify predictive factors for surgical site infection (SSI) in patients with type 2 diabetes and develop a prediction tool. MATERIALS AND METHODS: We retrospectively analyzed the perioperative blood glucose management of 105 patients with type 2 diabetes treated from 2016 to 2018 at Chiba University Hospital. The primary outcome was SSI onset within 30 postoperative days; moreover, predictive factors were identified using univariate analysis. Principal component analysis and logistic regression analysis were performed to prepare SSI predictive model using the identified predictive factors. The area under the receiver operating characteristic curve (AUC) was evaluated. Based on the predictive model, we developed a risk engine for SSI prediction. RESULTS: Compared with patients without SSI (n = 70), those with SSI (n = 35) had significantly higher fasting blood glucose levels at referral (169.1 ± 61.8 mg/dL vs. 140.1 ± 56.6, P = 0.036), preoperative mean blood glucose levels (178.3 ± 48.4 mg/dL vs. 155.2 ± 39.7, P = 0.009), preoperative maximum blood glucose levels (280.4 ± 87.3 mg/dL vs. 230.3 ± 92.4, P = 0.009), preoperative blood glucose fluctuations (54.9 ± 24.1 mg/dL vs. 37.7 ± 23.1, P = 0.001), percentage of hospitalization at referral (54.3% vs. 20.0, P

Background: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM),and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. Methods: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. Results: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular diseasebut not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome, than in healthy donors. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. Conclusions: Serum anti-PCK1 antibody levels were strongly associated with DM and weakly but significantly associated with cardiovascular disease. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

Background In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. Therefore, we aimed to examine the clinical significance of PCSK9 antibody (PCSK9-Ab) levels. Methods We measured blood PCSK9-Ab and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with diabetes mellitus (DM) (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. Results Although PCSK 9-Ab levels were significantly higher in the DM group than in the HDs group, PCSK9 protein levels were not significantly different. PCSK9-Ab and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, PCSK9-Ab levels were significantly associated with prognosis in patients with DM. Conclusions PCSK9-Ab may be a novel prognostic marker in patients with diabetes, and further studies are warranted to verify its usefulness.

Background In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is deeply involved in cholesterol metabolism, have also been observed. Therefore, we examined the clinical significance of PCSK9 antibody (PCSK9-Ab) levels. Methods We measured the blood PCSK9-Ab and PCSK9 protein levels in 109 healthy donors (HD) and 274 patients with diabetes mellitus (DM) (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. Results Although PCSK 9-Ab levels were significantly higher in the DM group than in the HD group, PCSK9 protein levels were not significantly different. PCSK9-Ab and PCSK9 protein levels showed no correlation in either group. We found that mortality was significantly associated with higher PCSK9-Ab levels, but not related to PCSK9 protein levels. After investigating for potential confounding factors, PCSK9-Ab levels were significantly associated with prognosis in patients with DM. Conclusions PCSK9-Ab may be a novel prognostic marker in patients with diabetes. However, further studies are warranted to verify its usefulness as a prognostic marker.

Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Background: Polyclonal autoantibodies against various proteins that do not cause autoimmune diseases have been reportedly observed in the serum. The presence of polyclonal antibodies against glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have been observed in the blood of patients who have not previously used the GLP-1 receptor agonist. Therefore, this study aimed to investigate the clinical significance of measuring anti-GIP and GLP-1 autoantibodies (Abs) in the plasma. Two groups consisted of 1healthy donors (HD) and 274 patients with diabetes mellitus (DM) were investigated. AlphaLISA was used to measure both GIP and GLP-1 Abs. This study was approved by the ethical review board of our university (approval number 21-Im-03) . Results: The serum concentration of anti-GIP Abs was significantly greater in the DM group than in the HD group (2697.6 ± 1998 vs. 2277.6 ± 821, p = 0.0001) , while the levels of anti-GLP-1 Abs were not different between the two groups. Since the concentration of anti-GIP Abs was significantly related to age, binary logistic regression analysis was perfomed for adjusting the age factor to reveal that anti-GIP Abs were greater with DM than without (OR: 1.0004; 95% CI 1.0001-1.001, p = 0.049) . Discussion: Several autoantibodies have been reportedly used as markers for various diseases, such as atherosclerosis, diabetes, and cancers. We found that the patients with DM had greater serum levels of anti-GIP Abs than those without it, indicating that the functions of GIP are inhibited in the presence of anti-GIP Abs in patients with DM. Since GIP is an insulinotropic intestinal hormone and the GLP-1/GIP dual agonist have been demonstrated to reduce both HbA1c and body weight, the functions of GIP inhibited by anti-GIP Abs may worse glucose metabolism. Conclusions: The patients with DM showed higher levels of anti-GIP autoantibodies. Disclosure H.Yamagata: None. S.Onishi: None. T.Yoshida: None. T.Hiwasa: None. M.Takemoto: None.

For the purpose of examining the characteristics of dyslipidemia and fatty liver in patients with Werner syndrome in Japan in recent years, we searched all case reports of Japanese Werner syndrome reported on Medical Online and PubMed since 1996, and collected and examined the data and clinical features described in these reports. In addition, as there are few descriptions of treatment methods in these reports from Medical Online and PubMed, we analyzed 12 cases for which detailed data on treatment methods are available at Chiba University. Geriatr Gerontol Int 2021; 21: 133-138.

BackgroundWerner syndrome (WS) is an autosomal recessive progeroid syndrome caused by variants inWRN. The International Registry of Werner Syndrome has identified biallelic pathogenic variants in 179/188 cases of classical WS. In the remaining nine cases, only one heterozygous pathogenic variant has been identified.MethodsTargeted long-read sequencing (T-LRS) on an Oxford Nanopore platform was used to search for a second pathogenic variant inWRN. Previously, T-LRS was successfully used to identify missing variants and analyse complex rearrangements.ResultsWe identified a second pathogenic variant in eight of nine unsolved WS cases. In five cases, T-LRS identified intronic splice variants that were confirmed by either RT-PCR or exon trapping to affect splicing; in one case, T-LRS identified a 339 kbp deletion, and in two cases, pathogenic missense variants. Phasing of long reads predicted all newly identified variants were on a different haplotype than the previously known variant. Finally, in one case, RT-PCR previously identified skipping of exon 20; however, T-LRS did not detect a pathogenic DNA sequence variant.ConclusionT-LRS is an effective method for identifying missing pathogenic variants. Although limitations with computational prediction algorithms can hinder the interpretation of variants, T-LRS is particularly effective in identifying intronic variants.

Context The syndrome of inappropriate antidiuresis (SIAD) with euvolemic hyponatremia may occur in patients with pulmonary tuberculosis (PTB), but little is known about the clinical characteristics of SIAD-associated hyponatremia in PTB patients. Objective This study aimed to investigate the frequency and risk factors of hyponatremia in PTB patients. Methods In this retrospective chart review, we examined the incidence and severity of hyponatremia in PTB patients. Multivariate analysis was conducted to identify risk factors for hyponatremia in PTB patients. Results Of the 161 patients who were screened, after excluding patients with hyperglycemia and renal failure, we enrolled and analyzed data from 113 participants. Hyponatremia occurred in 40.7% patients ( Conclusions Hyponatremia was less frequently associated with hyperglycemia, heart failure, renal failure, and other diseases that cause euvolemic hyponatremia; thus, PTB patients may have euvolemic hyponatremia due to SIAD. Administration of hypertonic saline or fluid restriction should be considered in PTB patients with hyponatremia.

Introduction To compare the effects of ipragliflozin, a sodium-glucose transporter 2 inhibitor, with those of metformin on visceral fat (as well as muscles and bones) in Japanese elderly patients with type 2 diabetes (T2D), we conducted a sub-analysis of a prospective, multicenter, blinded-endpoint randomized-controlled study. Methods In total, 103 patients with T2D (body mass index ≥ 22 kg/m2; glycated hemoglobin, 7–10%) and being treated with sitagliptin (a dipeptidyl peptidase-4 inhibitor) were included and randomized to receive ipragliflozin or metformin. The primary outcome was the change in visceral fat area measured using computed tomography 24 weeks following treatment. The secondary outcomes included changes in subcutaneous and total fat area, muscle volume, bone density measured using computed tomography, handgrip strength, bone markers, plasma glucose, insulin, homeostasis model assessment (HOMA)2-beta, HOMA2-R, glycated hemoglobin, lipid panel, uric acid, blood pressure, adiponectin, and high-sensitivity C-reactive protein. All patients aged 65–74 years were selected for sub-analysis. Results The sub-analysis included 15 and 14 patients in the ipragliflozin and metformin groups, respectively. The patients’ backgrounds were well balanced. Visceral fat area reduction was greater in the ipragliflozin group than in the metformin group (− 10.58% vs. − 6.93%; P = 0.034). There were significant differences in the changes in bone absorption markers, uric acid, and total cholesterol levels between the groups. Conclusion Ipragliflozin significantly reduced the visceral fat area compared with metformin when added to sitagliptin in elderly patients with T2D. Long-term and large-scale studies are required to elucidate whether ipragliflozin is suitable for elderly patients. Trial Registration The study was registered at https://www.umin.ac.jp/ctr/ (UMIN-ID: UMIN 000015170). Electronic supplementary material The online version of this article (10.1007/s13300-020-00949-0) contains supplementary material, which is available to authorized users.

Some cancers are related to atherosclerotic diseases; therefore, these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay‐linked immunosorbent assay (AlphaLISA) method, which incorporates glutathione donor beads and anti‐human IgG acceptor beads, was used to evaluate serum antibody levels. SEREX screening identified low‐density lipoprotein receptor–related protein–associated protein 1 (LRPAP1) as a target antigen of serum IgG antibodies in the sera of patients with ESCC or AIS. Antigens, including recombinant glutathione S‐transferase–fused LRPAP1 protein, were prepared to examine serum antibody levels. AlphaLISA revealed significantly higher antibody levels against the LRPAP1 protein in patients with solid cancers such as ESCC and colorectal carcinoma and some atherosclerosis‐related diseases such as AIS and diabetes mellitus compared with healthy donors. Correlation analysis revealed that the elevated serum antibody levels against LRPAP1 were associated with smoking, a well‐known risk factor for both cancer and atherosclerosis. Serum LRPAP1 antibody is therefore a common marker for the early diagnosis of some cancers and atherosclerotic diseases and may reflect diseases caused by habitual smoking., Some cancers and arteriosclerosis may share some antibody biomarkers in common. To investigate this, a first screening of sera was performed from patients with esophageal squamous cell carcinoma for SEREX. Serum LRPAP1 antibody is a useful marker for the early diagnosis of some cancers and atherosclerotic diseases.

Red yeast rice contains monacolin K, an inhibitor of cholesterol synthesis, and gamma-aminobutyric acid, a neurotransmitter. The daily dose of red yeast rice and monacolin K in previous studies was relatively high; therefore, there were safety concerns. We aimed to examine the effects of low daily dose red yeast rice on arteriosclerosis in patients with mild dyslipidemia.Eighteen patients without known cardiovascular disease and unsatisfactory low-density lipoprotein cholesterol (3.96±0.19 mmol/L) controlled only by diet therapy were randomly allocated to receive low dose red yeast rice (200 mg/day) containing 2 mg monacolin K or diet therapy alone for 8 weeks. The primary outcome was the absolute change in low-density lipoprotein cholesterol. Secondary outcomes included total cholesterol, apolipoprotein B, and blood pressure.Low-density lipoprotein cholesterol decreased significantly in the red yeast rice group than in the diet therapy group (median [interquartile range]: control -0.20 [-0.62, 1.19] mmol/L vs. red yeast rice -0.96 [-1.05, -0.34] mmol/L, p=0.030). The red yeast rice group also exhibited significant decreases in total cholesterol, apolipoprotein B, and blood pressure. No severe treatment-related adverse effects on muscles, liver, or renal function were observed.We found that patients in the red yeast rice group exhibited significant reductions in lowdensity lipoprotein cholesterol, total cholesterol, apolipoprotein B, and blood pressure without any recognised adverse effect. This suggests that low daily dose red yeast rice could reduce cardiovascular risk in patients with dyslipidemia.

Aim To clarify the diagnostic value of the calcification in the Achilles tendon for Werner syndrome. Methods Calcification of the Achilles tendon in the plain radiograph was investigated in 92 patients with Werner syndrome provided from the nationwide secondary survey in 2010. And the same investigation was performed for 2151 feet in 1853 patients without Werner syndrome, who underwent foot and ankle surgeries at the department of orthopaedic surgery in Nara Medical University from 2004 to 2015. Result and conclusion Achilles tendon calcification was observed in 70 (76.1%) out of 92 patients with Werner syndrome, whereas that was observed only in 19 feet (0.88%) without Werner syndrome, accompanied by 1 to 4 calcified masses with a maximum diameter ranging from 9.7mm to 63.2mm. The frequency of Achilles tendon calcification in patients with Werner syndrome is far higher than that of patients without Werner syndrome. Achilles tendon calcification could be included in the diagnostic criteria for Werner syndrome. Geriatr Gerontol Int 2020; ••: ••-••.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke, transient ischemic attack , diabetes mellitus (DM), cardiovascular disease , chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than that of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

AIM An investigator-initiated clinical study was carried out to evaluate the therapeutic potency of SR-0379 for the treatment of leg ulcers in patients with Werner syndrome. METHODS A multicenter, open-label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and

Context Hashimoto’s thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto’s thyroiditis. Case Description The patient whose case we report had a history of Hashimoto’s thyroiditis, immune thrombocytopenia, and refractory hypertension, with varying treatment resistance to the oral medications prescribed for each condition. In order to establish or exclude a genetic basis for her illness, we examined the patient’s gene expression profiles using peripheral blood leukocytes, and found that ABCG2/BCRPexpression was significantly high compared with healthy volunteers. Also, the increased daunomycin efflux capacity of our patient’s lymphocytes was successfully inhibited by fumitremorgin C, a specific ABCG2/BCRP inhibitor, and the patient’s level of thyroid-stimulating hormone increased by 248.6% after administration of intact levothyroxine tablets but decreased by 45.1% when tablets were crushed. Her average blood pressure decreased from 166.3/108.5 mmHg to 125.9/78.8 mmHg when switching from intact to crushed losartan tablets. Conclusions High expression and accelerated efflux transporter activity of ABCG2/BCRP in the small intestine are expected to contribute to the ineffectiveness of orally administered intact tablets in cases with treatment-resistant Hashimoto’s thyroiditis, and crushed tablets can be more effective for some of these patients.

A prospective, multicentre, open‐label, blinded‐endpoint, randomized controlled study was conducted to evaluate the efficacy of treatment with ipragliflozin (sodium‐dependent glucose transporter‐2 inhibitor) versus metformin for visceral fat reduction and glycaemic control among Japanese patients with type 2 diabetes treated with sitagliptin, HbA1c levels of 7%‐10%, and body mass index (BMI) ≥ 22 kg/m2. Patients were randomly assigned (1:1) to receive ipragliflozin 50 mg or metformin 1000‐1500 mg daily. The primary outcome was change in visceral fat area as measured by computed tomography after 24 weeks of therapy. The secondary outcomes were effects on glucose metabolism and lipid metabolism. Mean percentage reduction in visceral fat area was significantly greater in the ipragliflozin group than in the metformin group (−12.06% vs. −3.65%, P = 0.040). Ipragliflozin also significantly reduced BMI, subcutaneous fat area, waist circumference, fasting insulin, and homeostatic model assessment (HOMA)‐resistance, and increased HDL‐cholesterol levels. Metformin significantly reduced HbA1c and LDL‐cholesterol levels and increased HOMA‐beta. There were no severe adverse events. The use of ipragliflozin or metformin in combination with dipeptidyl peptidase‐4 inhibitors, widely used in Japan, may have beneficial effects in ameliorating multiple cardiovascular risk factors.

ObjectiveRecently, podocytes have been recognised not only as a physical barrier to prevent urinary protein loss but also as producers of proinflammatory cytokines. However, the roles of podocytes in the pathogenesis of lupus nephritis (LN) remain largely unknown. This study aims to determine the roles of suppressor of cytokine signalling (SOCS) family members expressed in glomeruli in the regulation of LN.MethodsWe investigated the expression of SOCS family members in glomeruli in murine lupus model induced by repeated epicutaneous administration of the TLR7/8 agonist imiquimod. We also investigated the roles of SOCS3 expressed in podocytes in the imiquimod-induced glomerulonephritis and systemic autoimmunity by using podocyte-specific SOCS3-deficient mice (podocin-Cre x SOCS3fl/fl mice (SOCS3-cKO mice)). Finally, we investigated the expression of proinflammatory cytokines and chemokines in SOCS3-deficient podocyte cell lines.ResultsqPCR analysis revealed that among SOCS family members, SOCS3 was preferentially induced in glomeruli on epicutaneous administration of imiquimod and that interleukin 6 (IL-6) induced SOCS3 expression in podocyte cell lines. SOCS3-cKO mice exhibited severe glomerulonephritis, high levels of serum creatinine and urine albumin and decreased survival rate compared with control SOCS3-WT mice. Levels of anti-double-strand DNA antibody, SOCS (GC) formation and the numbers of follicular helper T (Tfh) cells and GC B cells in the spleen were higher in SOCS3-cKO mice than those in SOCS3-WT mice. Serum IL-6 levels and expression of IL-6 mRNA in glomeruli were also elevated in SOCS3-cKO mice. IL-6-induced IL-6 expression was enhanced in SOCS3-deficient podocyte cell lines compared with that in SOCS3-sufficient podocyte cell lines.ConclusionSOCS3 expressed in podocytes plays protective roles for the development of glomerulonephritis and inhibits autoantibody production in the imiquimod-induced lupus model presumably by suppressing IL-6 production of podocytes.

Background: Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD), and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders such as angiogenesis and atherosclerosis, and DM is a risk factor for certain cancers. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected by a common biomarker.Methods: We employed the protein array method for the initial screening of antigens and employed the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) to evaluate antibody levels in serum samples.Results: The protein array identified KIAA0513 as an antigen recognized by serum IgG antibodies in the sera of patients with atherosclerosis. We then prepared recombinant glutathione S-transferase-fused KIAA0513 protein. AlphaLISA showed significantly higher serum antibody levels against KIAA0513 protein in patients with AIS, transient ischemic attack, DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD, and solid cancers, such as esophageal, gastric, colon, lung, and breast cancer, than in healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were for esophageal cancer, nephrosclerosis-type CKD, and DM. Spearman’s correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis.Conclusion: Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD, and solid cancers and might reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

Background: Atherosclerosis has been considered as the main cause of morbidity, mortality, premature incapacity, and disability worldwide. For early and sensitive diagnosis, development of novel biomarkers is expected and of significant practical importance.Methods: The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning (SEREX). Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen.Results: SEREX screening has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. As per the results of AlphaLISA, it was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack (TIA), diabetes mellitus (DM), cardiovascular disease (CVD), chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were noted to be higher than that of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The Japan Public Health Center-based Prospective Study results have verified that the serum antibody levels against AP3D1 showed significantly higher odds ratios with the risk of AIS for persons with the third quartiles and the highest quartiles versus the lowest quartile, indicating that this antibody marker is deemed useful as risk factors for AIS.Conclusions: Serum anti-AP3D1 antibodies, which are broad-spectrum biomarkers of atherosclerotic diseases and digestive organ cancers, could be useful in predicting the onset of AIS.

Patients with Werner syndrome present with diverse signs of aging that begin in adolescence. A Japanese nationwide survey was conducted to establish a registry that could clarify the disease profile of patients with Werner syndrome. The questionnaires were sent to 7888 doctors. The survey identified 116 patients diagnosed with Werner syndrome based on the diagnosis criteria. Forty patients were enrolled in the registry. Data on clinical symptoms, treatment information, and laboratory examination from patients who provided informed consent were collected. The data at enrollment were analyzed. The patients' average age at enrollment was 50.1±7.5 years. The mean onset age was 26.1±9.5 years, but the mean age at diagnosis was 42.5±8.6 years. Average height and weight of the study patients were lower than those of Japanese individuals. Almost all patients experienced hair change and cataracts. More than 60% of patients presented with glycolipid abnormalities. Overall, 15% of patients had a history of foot amputation. Approximately 30% of the patients' parents had a consanguineous marriage. The average grip strength, walking speed, and skeletal muscle mass index met the diagnostic criteria for sarcopenia. The registry revealed that there are opportunities for early diagnosis and intervention; therefore, sensitization about the disease is needed.

Aim Sarcopenia is defined as a condition that combines decreased skeletal muscle mass with weakness or decreased physical function. It is well known that in older adults, the presence of sarcopenia is a risk of frailty, falls and physical dysfunction. Patients with Werner syndrome are characterized by visceral fat accumulation and thin limbs, but the prevalence of sarcopenia in patients with Werner syndrome has not been investigated. Methods A literature search was conducted using Werner syndrome and skeletal muscle as keywords. We also analyzed data from our 7 Werner syndrome patients. Results A literature search on the relationship between Werner syndrome and skeletal muscle yielded only one article reported from Japan. According to this paper, a decrease in skeletal muscle mass (appendicular skeletal muscle index) was observed in all 9 Werner syndromes investigated. On the other hand, in our 7 Werner syndrome patients, their appendicular skeletal muscle indexes were below the standard value except for one male patient who had continued resistance exercise. Conclusion The decrease in skeletal muscle mass frequently occurs in patients with Werner syndrome. However, resistance exercise may prevent the appearance of sarcopenia and requires early intervention in patients with Werner syndrome. Geriatr Gerontol Int 2021; 21: 139-141.