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1.
Article in English | MEDLINE | ID: mdl-38895560

ABSTRACT

Objectives: Black spots (BSs) are lentiginous findings observed in the gastric body and fundus during upper gastrointestinal endoscopy and are predominantly seen in patients undergoing Helicobacter pylori eradication treatment. However, the detailed patient background and exact composition are poorly understood. This study aims to clarify the clinicopathological features of BSs, examine patient demographics, and use the NanoSuit-correlative light and electron microscopy (CLEM) method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy for elemental analysis. Methods: Patients who underwent upper gastrointestinal endoscopy between 2017 and 2022 were included. Data on age, medications, blood tests, and H. pylori infection status were retrospectively gathered from medical records. Univariate analysis was conducted to examine BS presence, with results then used in a multivariate model to identify associated risk factors. Additionally, pathological specimens from patients with BSs were analyzed for elemental composition using the NanoSuit-CLEM method combined with scanning electronmicroscopy-energy dispersive X-ray spectroscopy. Results: An analysis of 6778 cases identified risk factors for BSs, including older age and using proton pump inhibitors, statins, corticosteroids, and antithrombotic drugs. Endoscopically, BSs correlated with higher gastric atrophy and lower active H. pylori infection. Iron deposition at BS sites was specifically identified using NanoSuit-CLEM. Conclusions: BSs on gastrointestinal endoscopy may indicate an absence of active H. pylori inflammation. The discovery of iron deposition within BSs using the NanoSuit-CLEM method has offered new insights into the possible causative factors and advances our understanding of the etiology of BSs, bringing us closer to unraveling the underlying mechanisms of their formation.

2.
Medicine (Baltimore) ; 103(15): e35647, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608112

ABSTRACT

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.


Subject(s)
Crohn Disease , Humans , Crohn Disease/drug therapy , Ustekinumab/therapeutic use , C-Reactive Protein , Intestines , Albumins , Hemoglobins
3.
PLoS One ; 19(1): e0295681, 2024.
Article in English | MEDLINE | ID: mdl-38166010

ABSTRACT

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.


Subject(s)
Adalimumab , Colitis, Ulcerative , Serum Albumin , Humans , Adalimumab/therapeutic use , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Retrospective Studies , Treatment Outcome , Treatment Failure
4.
Am J Physiol Endocrinol Metab ; 326(3): E326-E340, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38294696

ABSTRACT

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.


Subject(s)
Interleukin-15 , Muscle, Skeletal , Mice , Male , Animals , Interleukin-15/genetics , Interleukin-15/metabolism , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Mice, Transgenic , Mice, Knockout , AMP-Activated Protein Kinases/metabolism , Autophagy
5.
BMC Gastroenterol ; 24(1): 13, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166726

ABSTRACT

BACKGROUND: Screening esophagogastroduodenoscopy plays an important role in the early detection of upper gastrointestinal cancer. To provide more opportunities for patients with pancreaticobiliary disease to undergo this screening, we have performed esophagogastroduodenoscopy prior to endoscopic ultrasonography. However, the usefulness of this protocol is not elucidated. This study aimed to investigate the utility of screening esophagogastroduodenoscopy in this protocol in the detection of upper gastrointestinal epithelial neoplasms. METHODS: The outcomes of screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography in patients with pancreaticobiliary disease at our hospital between April 2020 and September 2022 were investigated. A logistic regression model was used to identify factors affecting the detection of epithelial neoplasms. Additionally, we compared the detection rate of gastric epithelial neoplasms between screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography and that performed at our medical checkup center. RESULTS: A total of 615 screening esophagogastroduodenoscopies prior to endoscopic ultrasonography were performed, and 12 (2.0%) epithelial neoplasms were detected, including esophageal lesions (n = 2) and gastric lesions (n = 10). Of these lesions, 75% (9/12) underwent curative endoscopic resection. A multivariate analysis showed that open-type gastric mucosal atrophy (odds ratio, 7.7; 95% confidence interval, 1.5-38.4; p = 0.01) and the use of magnification endoscopy (odds ratio, 7.3; 95% confidence interval, 1.9-27.9; p < 0.01) independently affected the detection of epithelial neoplasms. The detection rate of gastric epithelial neoplasms was significantly higher using this protocol than that in our medical checkup center (1.6% versus 0.2%, p < 0.01). CONCLUSIONS: A protocol of screening esophagogastroduodenoscopy prior to endoscopic ultrasonography may be recommended because epithelial neoplasms could be detected at a non-negligible rate.


Subject(s)
Carcinoma , Stomach Neoplasms , Humans , Endosonography , Early Detection of Cancer/methods , Stomach Neoplasms/pathology , Endoscopy, Gastrointestinal
6.
J Am Med Dir Assoc ; 25(1): 98-103, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37353205

ABSTRACT

OBJECTIVES: Muscle weakness, assessed by grip strength, has been shown to predict postoperative mortality in older patients with cancer. Because lower extremity muscle strength well reflects physical performance, we examined whether lower knee extension muscle strength predicts postoperative mortality better than grip strength in older patients with gastrointestinal cancer. DESIGN: Prospective, observational study in a single institution. SETTING AND PARTICIPANTS: A total of 813 patients (79.0 ± 4.2 years, 66.5% male) aged 65 years or older with gastrointestinal cancer who underwent preoperative evaluation of grip strength and isometric knee extension muscle strength between April 2012 and April 2019 were included. METHODS: The study participants were prospectively followed up for postoperative mortality. Muscle weakness was defined as the lowest quartile of grip strength or knee extension strength (GS-muscle weakness and KS-muscle weakness, respectively). RESULTS: Among the study participants, 176 patients died during a median follow-up of 716 days. In the Kaplan-Meier analysis, we found that patients with both GS-muscle weakness and KS-muscle weakness had a lower survival rate than those without muscle weakness. As expected, higher clinical stages and abdominal and thoracic surgeries compared with endoscopic surgery were associated with increased all-cause mortality. In addition, we found that KS-muscle weakness, but not GS-muscle weakness, was an independent prognostic factor after adjusting for sex, body mass index, cancer stage, surgical technique, and surgical site in the Cox proportional hazard model. CONCLUSIONS AND IMPLICATIONS: In older patients with gastrointestinal cancer, muscle weakness based on knee extension muscle strength can be a better predictor of postoperative prognosis than muscle weakness based on grip strength.


Subject(s)
Gastrointestinal Neoplasms , Lower Extremity , Humans , Male , Aged , Female , Prospective Studies , Muscle Strength/physiology , Hand Strength , Muscle Weakness , Gastrointestinal Neoplasms/surgery
7.
J Gastroenterol Hepatol ; 39(1): 55-65, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37788676

ABSTRACT

BACKGROUND AND AIM: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients. METHODS: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks. RESULTS: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients. CONCLUSION: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.


Subject(s)
Crohn Disease , Humans , Crohn Disease/drug therapy , Antibodies, Monoclonal/adverse effects , Remission Induction , Interleukin-23/therapeutic use , Double-Blind Method , Treatment Outcome
8.
Medicine (Baltimore) ; 102(38): e35022, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37746995

ABSTRACT

Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.


Subject(s)
Adenocarcinoma , Carcinoma, Medullary , Colorectal Neoplasms , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/surgery , Mutation , Genetic Testing , MutL Protein Homolog 1/genetics
9.
J Prosthodont Res ; 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37648481

ABSTRACT

PURPOSE: Individuals with impaired masticatory function tend to prefer soft foods, which results in decreased masticatory muscle activity. This study examined the association between the oral condition (number of teeth, occlusal force, and occlusal contact area) and dietary hardness using a daily dietary questionnaire. METHODS: This cross-sectional study evaluated 1841 participants aged 69-71 and 79-81 years. Registered dentists examined the number of teeth, occlusal force, and occlusal contact area. Dietary hardness was defined as the estimated masticatory muscle activity required for a habitual diet. Habitual diet during the preceding month was assessed using a brief self-administered diet history questionnaire. Confounding factors, such as age, sex, socioeconomic status, smoking habits, history of chronic diseases (hypertension, hyperlipidemia, and diabetes), and cognitive function were also evaluated. Multivariate linear regression analyses were performed to assess the association between dietary hardness and each oral condition. RESULTS: Occlusal force (standardized regression coefficients [ß]=0.08, P < 0.01) and occlusal contact area (ß=0.06, P < 0.01) were significantly associated with dietary hardness after adjusting for the confounding factors. Number of teeth was not significantly associated with dietary hardness. In addition, the associations between dietary hardness, sex, and a history of diabetes were stronger than those between dietary hardness and oral factors. CONCLUSIONS: Occlusal force and contact area were significantly associated with dietary hardness as estimated from the masticatory muscle activity using a daily diet questionnaire.

10.
Clin Nutr ; 42(8): 1454-1461, 2023 08.
Article in English | MEDLINE | ID: mdl-37451157

ABSTRACT

BACKGROUND & AIMS: This study aimed to investigate the associations of pre-existing sarcopenia with swallowing function, oral intake level, and aspiration pneumonia in patients with acute stroke. METHODS: This observational study included patients (≥60 years of age) with acute ischemic stroke or intracerebral hemorrhage within 7 days of onset who were screened for sarcopenia, malnutrition, and swallowing difficulties in a stroke-care unit within 48 h of admission. Sarcopenia was defined by the Asian Working Group on Sarcopenia 2019 as having a low calf circumference, handgrip strength, and appendicular muscle mass index. The primary outcome was impaired oral intake (functional oral intake scale <5 points) at 3, 7, and 14 days after admission, and the secondary outcome was aspiration pneumonia during hospitalization. RESULTS: We enrolled 350 patients (median age of 77 years; 63% males) who underwent the aforementioned screening. Sarcopenia was diagnosed in 34% of patients, and malnutrition was found in 66% of patients with sarcopenia. When compared with the comparison group (defined as patients with either or both normal calf circumference and handgrip strength), the sarcopenia group had significantly lower tongue pressure and a higher prevalence of dysphagia. Sarcopenia was associated with functional oral intake scale <5 at 7 days (adjusted odds ratio [OR], 4.72; 95% confidence interval [CI], 1.91-11.71); p = 0.002) and 14 days (adjusted OR, 3.93; 95% CI, 1.47-10.53; p = 0.006) and with aspiration pneumonia during hospitalization (adjusted OR, 6.12; 95% CI, 1.63-22.94; p = 0.007). CONCLUSION: Acute stroke patients with sarcopenia may have weakness of the swallowing-related muscles which may lead to impaired oral intake and aspiration pneumonia.


Subject(s)
Deglutition Disorders , Ischemic Stroke , Malnutrition , Pneumonia, Aspiration , Sarcopenia , Stroke , Aged , Female , Humans , Male , Deglutition , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Deglutition Disorders/diagnosis , Hand Strength , Ischemic Stroke/complications , Malnutrition/complications , Malnutrition/epidemiology , Pneumonia, Aspiration/etiology , Pneumonia, Aspiration/complications , Pressure , Sarcopenia/etiology , Sarcopenia/complications , Stroke/complications , Stroke/epidemiology , Tongue , Middle Aged , Aged, 80 and over
11.
World J Gastrointest Surg ; 15(6): 1224-1231, 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37405109

ABSTRACT

BACKGROUND: Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY: We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION: Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

12.
Aging (Albany NY) ; 15(9): 3273-3294, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37130431

ABSTRACT

Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and were observed in approximately 30% of patients during the 3-year survey period. Regarding renal function, the mean estimated glomerular filtration rate calculated from serum creatinine (eGFRcre) and eGFRcys, which were calculated from cystatin C in the first year, were 98.3 and 83.2 mL/min/1.73 m2, respectively, and differed depending on the index used. In longitudinal analysis, the average eGFRcre for the first and fourth years was 74.8 and 63.4 mL/min/1.73 m2, showing a rapid decline. Secular changes in Werner syndrome in multiple patients were identified. The prevalence of malignant neoplasms is high, and renal function may decline rapidly. It is, therefore, necessary to carry out active and detailed examinations and pay attention to the type and dose of the drugs used.


Subject(s)
Cardiovascular Diseases , Kidney Diseases , Neoplasms , Sarcopenia , Werner Syndrome , Humans , Kidney , Follow-Up Studies , Werner Syndrome/complications , Werner Syndrome/epidemiology , Cross-Sectional Studies , Neoplasms/complications , Neoplasms/epidemiology , Creatinine
14.
J Clin Med ; 12(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37176551

ABSTRACT

Vonoprazan (VPZ) inhibits gastric acid secretion more potently than proton pump inhibitors. Recently, attention has been focused on the dual therapy with VPZ and amoxicillin (AMOX) for the eradication of H. pylori. The dual VPZ/AMOX therapy attains the sufficient eradication rate with lowering the risk of adverse events in comparison with the triple therapy and quadruple therapy. Therefore, the dual VPZ/AMOX therapy is considered a useful eradication regimen for H. pylori infection.

15.
Diabetes Ther ; 14(7): 1175-1192, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37195511

ABSTRACT

INTRODUCTION: This study aimed to understand the actual status of multimorbidity and polypharmacy among patients with type 2 diabetes using glucose-lowering drugs, and to assess the effects of patient characteristics on severe hypoglycemia and glycemic control. METHODS: We designed a retrospective cohort study using health insurance claims and medical checkup data in Japan from April 2016 to February 2021 and identified patients with type 2 diabetes who were prescribed glucose-lowering drugs. We analyzed data on patient characteristics, including multimorbidity and polypharmacy, calculated the incidence rate for severe hypoglycemic events, applied a negative binomial regression model to explore factors that affected severe hypoglycemia, and analyzed the status of glycemic control in the subcohort for which HbA1c data were available. RESULTS: Within the analysis population (n = 93,801), multimorbidity was present in 85.5% and mean ± standard deviation for oral drug prescriptions was 5.6 ± 3.5 per patient, while for those aged 75 years or older these numbers increased to 96.3% and 7.1 ± 3.5, respectively. The crude incidence rate for severe hypoglycemia was 5.85 (95% confidence interval 5.37, 6.37) per 1000 person-years. Risk factors for severe hypoglycemia included younger and older age, prior severe hypoglycemia, use of insulin, sulfonylurea, two-drug therapy including sulfonylurea or glinides, three-or-more-drug therapy, excessive polypharmacy, and comorbidities including end-stage renal disease (ESRD) requiring dialysis. Subcohort analysis (n = 26,746) showed that glycemic control is not always maintained according to guidelines. CONCLUSION: Patients with type 2 diabetes, particularly older patients, experienced high multimorbidity and polypharmacy. Several risk factors for severe hypoglycemia were identified, most notably younger age, ESRD, history of severe hypoglycemia, and insulin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry (UMIN000046736).

16.
J Clin Biochem Nutr ; 72(3): 248-255, 2023 May.
Article in English | MEDLINE | ID: mdl-37251965

ABSTRACT

Diabetes mellitus is recognized as a risk factor for sarcopenia. Luseogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces inflammation and oxidative stress by improving hyperglycemia, subsequently improving hepatosteatosis or kidney dysfunction. However, the effects of SGLT2 inhibitor on the regulation of skeletal muscle mass or function in hyperglycemia are still unknown. In this study, we investigated the effects of luseogliflozin-mediated attenuation of hyperglycemia on the prevention of muscle atrophy. Twenty-four male Sprague-Dawley rats were randomly divided into four groups: control, control with SGLT2 inhibitor treatment, hyperglycemia, and hyperglycemia with SGLT2 inhibitor treatment. The hyperglycemic rodent model was established using a single injection of streptozotocin, a compound with preferential toxicity toward pancreatic beta cells. Muscle atrophy in streptozotocin-induced hyperglycemic model rats was inhibited by the suppression of hyperglycemia using luseogliflozin, which consequently suppressed hyperglycemia-mediated increase in the levels of advanced glycation end products (AGEs) and activated the protein degradation pathway in muscle cells. Treatment with luseogliflozin can restore the hyperglycemia-induced loss in the muscle mass to some degree partly through the inhibition of AGEs-induced or homeostatic disruption of mitochondria-induced activation of muscle degradation.

17.
Cancer Med ; 12(12): 13007-13018, 2023 06.
Article in English | MEDLINE | ID: mdl-37096775

ABSTRACT

BACKGROUND: Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile-derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application. METHODS: Bile samples from seven patients with malignant diseases (hilar CCA = 4, distal CCA = 3) and eight patients with benign diseases (gallstones = 6, primary sclerosing cholangitis = 1, autoimmune pancreatitis = 1) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker. RESULTS: Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98-fold higher in the malignant group than in the benign group (P = 0.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643-1.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1 µg/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620-1.000). CONCLUSION: PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Extracellular Vesicles , Humans , Bile/chemistry , Phosphatidylcholines/analysis , Cholangiocarcinoma/diagnosis , Biomarkers/analysis , Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic , Extracellular Vesicles/chemistry , Biomarkers, Tumor/analysis
18.
J Geriatr Oncol ; 14(5): 101485, 2023 06.
Article in English | MEDLINE | ID: mdl-37062639

ABSTRACT

INTRODUCTION: The number of older patients with cancer is expected to continue to increase owing to the aging population. Recently, the usefulness of geriatric assessment (GA) conducted by multiple staff members from different medical backgrounds has been reported; however, a consensus on the effectiveness of GA has not yet been achieved. MATERIALS AND METHODS: We, as the Japanese Geriatric Oncology Guideline Committee for elderly patients with cancer, conducted a literature search of randomized controlled trials published before August 2021 that used GA or comprehensive GA (CGA) as an intervention for patients with cancer undergoing chemotherapy. As the key outcomes for answering the clinical question, we focused on survival benefit, adverse events, and quality of life (QOL). After a systematic review of these studies, the expert panel member developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: For older patients with cancer, GA or CGA is suggested during or before chemotherapy (weakly recommended). Chemotherapy-induced adverse events were significantly reduced by GA/CGA interventions without any adverse effects on survival. Health-related QOL tended to improve with the GA/CGA interventions. DISCUSSION: Although, in our opinion, GA/CGA does require time and resources, it poses no harm patients. Therefore, we suggest expanding the human resources and educating skills of medical providers for clinical implementation of GA/CGA.


Subject(s)
Geriatric Assessment , Neoplasms , Aged , Humans , Aging , East Asian People , Neoplasms/epidemiology , Quality of Life , Randomized Controlled Trials as Topic
19.
Geriatr Gerontol Int ; 23(5): 334-340, 2023 May.
Article in English | MEDLINE | ID: mdl-36958816

ABSTRACT

AIM: The aging-related increase in the incidence of anemia potentially affects the mortality risk. Lower cognitive function is common among older adults, and anemia is one of the causes of cognitive decline. However, to the best of our knowledge, no study has investigated whether cognitive decline is a risk factor for anemia in older people. Therefore, in this study, we used a 3-year longitudinal evaluation to examine the association of cognitive function with anemia in community-dwelling older adults. METHODS: This longitudinal study enrolled participants without anemia (diagnosed based on the World Health Organization's criteria) at baseline. Cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment. Multiple logistic regression models were used to examine the association between cognitive function at baseline and the presence of anemia 3 years later. RESULTS: Participants were in the 69-71 and 79-81 years age groups, and 974 older people (48.6% men) were enrolled, of whom 126 (12.9%) had anemia after 3 years. After adjusting, cognitive function at baseline was associated with anemia in women, but not in men. CONCLUSIONS: Older Japanese women with lower cognitive function have an increased risk for anemia 3 years later. The adoption of a lifestyle that utilizes or improves cognitive function might be important to prevent anemia in older women. Geriatr Gerontol Int 2023; 23: 334-340.


Subject(s)
Anemia , Cognitive Dysfunction , Aged , Female , Humans , Male , Anemia/complications , Anemia/epidemiology , Anemia/prevention & control , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , East Asian People , Independent Living , Longitudinal Studies , Risk Factors , Aged, 80 and over
20.
PLoS One ; 18(1): e0280279, 2023.
Article in English | MEDLINE | ID: mdl-36608042

ABSTRACT

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most serious complications of ERCP. Various procedures can reduce the incidence of PEP, such as wire-guided cannulation, prophylactic pancreatic stent placement, and pretreatment anal insertion of NSAIDs. Recently, iso-osmolar contrast media (IOCM) have been used for ERCP in several hospitals to reduce the risk of PEP in Japan. However, the effect of IOCM is uncertain because few reports have examined IOCM in relation to PEP. AIM: This study aimed to investigate the relationship between contrast media used and the incidence of PEP. METHODS: This retrospective study included all qualifying patients who had undergone ERCP at Hamamatsu University Hospital between January 2012 and January 2020. This study examined whether there was a difference in the onset of PEP between patients administered IOCM and high osmolar contrast medium (HOCM). Propensity score matching was used to analyze patient characteristics and ERCP procedures. Amidotrizoic acid was used as HOCM and iodixanol as IOCM. RESULTS: ERCP was performed on 458 patients, and 830 procedures were conducted. After propensity score matching, 162 patients from the amidotrizoic acid group and 162 patients from the iodixanol group were selected. The incidence of PEP was 10.5% (17) in the amidotrizoic acid group and 9.3% (15) in the iodixanol group (P = 0.71). Changes in serum amylase levels post- and pre-ERCP were 240.6 ± 573.8 U/L and 142.7 ± 382.1 U/L in the amidotrizoic acid and iodixanol groups, respectively (P = 0.072). CONCLUSION: Iodixanol had no prophylactic effect on PEP and clinical outcomes.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Contrast Media , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods , Contrast Media/adverse effects , Retrospective Studies , Diatrizoate Meglumine , Risk Factors
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