ABSTRACT
BACKGROUND: The risk of stroke increases with age, and although previous reports have suggested that infection risk may increase with antipsychotic use, relevant studies after stroke are scarce. We aimed to investigate whether antipsychotics increase post-stroke infection risk in the acute stroke period. METHODS: This propensity score matching study included adults diagnosed with first-ever stroke between 2011 and 2020 at five university hospitals. In-hospital antipsychotic exposure was defined as any administration during hospitalisation for stroke. The primary outcome was post-stroke infection after the first 2 days of hospitalisation, and the secondary outcome was the presence of pneumonia, bacteraemia and/or bacteriuria. RESULT: Among 23,885 first-ever stroke patients, 2,773 antipsychotic users (age 71.6 ± 12.4, male 54.6%) and 2,773 non-users (age 71.2 ± 13.2, male 54.6%) were selected as matched cohorts. After adjusting for propensity score, antipsychotics were not associated with an increased risk of post-stroke infection (odds ratio 0.99, 95% confidence interval 0.87-1.14). CONCLUSION: While our study did not find conclusive evidence linking antipsychotic medication to an increased risk of post-stroke infection, prescribing these medications should still be approached with prudence. Until further research can provide more definitive insights, clinicians should carefully weigh the potential infection risks when considering antipsychotic treatment during the acute stroke care period.
Subject(s)
Antipsychotic Agents , Propensity Score , Stroke , Humans , Male , Aged , Female , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Stroke/epidemiology , Aged, 80 and over , Risk Factors , Middle Aged , Risk AssessmentABSTRACT
IMPORTANCE: Patient-reported outcome measures provide insights into intervention effects on patients. The Canadian Occupational Performance Measure (COPM) emphasizes identifying priorities in daily activity engagement and evaluating an individual's perception of changes over time. OBJECTIVE: To assess the responsiveness of the COPM and the minimal clinically important difference (MCID) among patients with frozen shoulders. DESIGN: Prospective, single-blind, randomized controlled trial. SETTING: Two physical medicine and rehabilitation clinics. PARTICIPANTS: Ninety-four patients with frozen shoulders enrolled in a previous study. OUTCOMES AND MEASURES: Baseline and 3-mo evaluations of the COPM and other measures. Responsiveness was assessed using effect size (ES) and standardized response mean (SRM). The MCID values were determined through a distribution-based approach, which used the 0.5 standard deviation and ES methods, and an anchor-based approach, which used the receiver operating characteristic curve method. RESULTS: The ES and SRM results indicated that the COPM had high responsiveness. The distribution-based MCID values for COPM Performance and COPM Satisfaction were 1.17 and 1.44, respectively. The anchor-based MCID values were 2.5 (area under the curve [AUC] = 0.78, 95% confidence interval [CI] [0.64-0.91]) and 2.1 (AUC = 0.76, 95% CI [0.60-0.91]), respectively. CONCLUSIONS AND RELEVANCE: The findings suggest that the COPM is a responsive outcome measure for patients with frozen shoulder. The established MCID values for the COPM can be valuable for interpreting changes in patient performance and satisfaction, thus aiding clinical interventions and research planning. Plain-Language Summary: This is the first study to review the effectiveness of the Canadian Occupational Performance Measure (COPM) to determine the success of occupational therapy interventions for people with a frozen shoulder. The findings suggest that the COPM is an effective and valuable tool for clients with a frozen shoulder to understand their experiences and treatment priorities and to detect meaningful changes in their performance and satisfaction after an occupational therapy intervention.
Subject(s)
Bursitis , Minimal Clinically Important Difference , Patient Reported Outcome Measures , Humans , Bursitis/rehabilitation , Male , Female , Middle Aged , Single-Blind Method , Prospective Studies , Occupational Therapy/methods , Canada , Aged , Activities of Daily Living , Adult , Disability EvaluationABSTRACT
Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Most patients with RA face a barrier to participation in social activities or exercise due to joint pain, despite the beneficial effects of exercise and physical activity. Thus, RA may be a risk factor for sarcopenia in the clinical field. Bioelectrical impedance analysis-derived phase angle (PhA) reflects cellular health and is correlated with the prognosis of various diseases. However, its association with physical function in non-sarcopenic RA female patients remains unclear. We evaluated the association between PhA values and various physical function measures in female patients with non-sarcopenic RA. Methods: Thirty-five participants with RA were screened. One met the criteria for sarcopenia. Finally, 34 patients with non-sarcopenic RA were enrolled. This cross-sectional retrospective study evaluated upper- and lower-extremity strengths, cross-sectional area of rectus femoris, 6 min walking test, Borg scale score, sit-to-stand test, and physical function and mental health from 36-Item Short Form Health Survey scores. Results: In total, 34 female participants (mean age = 49.74 ± 8.15 years) were enrolled. In non-sarcopenic RA patients, PhA was significantly correlated with BMI and ASM/(height)2. Multicollinearity was not detected among the independent variables (VIF < 5). The final multivariable regression model identified ASM/height2 as a significant predictor of PhA among non-sarcopenic RA patients. Conclusion: Multivariable linear regression analyses identified appendicular skeletal muscle mass as a significant predictor of PhA. Bioelectrical impedance analysis-derived PhA is a valuable guidance tool for RA management. PhA can be a useful clinical biomarker of muscle status in non-sarcopenic RA patients.
Subject(s)
Arthritis, Rheumatoid , Sarcopenia , Humans , Female , Adult , Middle Aged , Retrospective Studies , Arthritis, Rheumatoid/complications , Risk Factors , ExerciseABSTRACT
INTRODUCTION/AIMS: There are two conventional needle electromyography (EMG) approaches to the serratus anterior (SA), both of which can result in erroneous insertion into adjacent structures such as the latissimus dorsi (LD), teres major, or external oblique abdominis muscles and pose a risk of long thoracic nerve (LTN) injury. Therefore, we identified a novel needle insertion point for the SA in cadavers that avoids other muscles and LTN injury. METHODS: This study included 17 cadavers: 12 to devise the new method and 5 to verify its accuracy. Novel landmarks were the inferior angle of the scapula (I), sternal notch (S), and xiphoid process (X). The relationships of the LD, pectoralis major (PM), SA, and LTN were determined relative to these landmarks. RESULTS: When inserting a needle into the proximal one third along the line connecting points I and X, there were adequate safety margins around the LD, PM, and LTN, and the new method had excellent accuracy. DISCUSSION: Compared to the conventional midaxillary method, our novel method improved the accuracy of needle EMG of the SA. Follow-up studies using clinical imaging techniques are needed to verify whether above findings are equally applicable in living subjects.
Subject(s)
Muscle, Skeletal , Superficial Back Muscles , Humans , Electromyography/methods , Scapula/innervation , Axilla , Pectoralis Muscles/diagnostic imagingABSTRACT
Introduction: Limited range of motion (ROM) of the shoulder occurs commonly after breast cancer surgery, resulting in reduced quality of life and difficulty with activities of daily living. Physical exercise is effective in postoperative breast cancer patients, but no study has assessed the effects of augmented reality (AR)-based telerehabilitation. Therefore, this study aimed to investigate the effect of hospital-home linked rehabilitation therapy using an AR-based digital health care system (UINCARE Home+) in postoperative patients with breast cancer. Methods: This study was a prospective, multicenter, assessor-blinded, randomized controlled trial. Patients who underwent breast cancer surgery were assigned to either the UINCARE Home+ (intervention) group or the brochure-based home rehabilitation (control) group for an 8-week intervention. The study outcomes were the change in ROM of the affected shoulder, pain in the affected shoulder (Numerical Rating Scale [NRS]), functional outcomes (Disabilities of the Arm, Shoulder, and Hand questionnaire [QuickDASH] score), and quality of life (Functional Assessment of Cancer Therapy-Breast [FACT-B] and EuroQoL 5-Dimension 5-Level [EQ-5D-5L] scores), all of which were measured at enrollment and at 4, 8, and 12 weeks thereafter. Results: A total of 100 participants were enrolled in the study (n = 50 in each groups). In both groups, active and passive ROM, NRS, and the QuickDASH, FACT-B, and EQ-5D-5L scores showed significant improvements from baseline to 12 weeks (p < 0.001), but no group differences were detected. Discussion: A home-based exercise program with an AR system improved shoulder dysfunction in breast cancer patients and could be used in conjunction with a traditional hospital-based rehabilitation program. Trial Registration: ClinicalTrials.gov ID: NCT04316156.
Subject(s)
Breast Neoplasms , Telerehabilitation , Humans , Female , Breast Neoplasms/surgery , Activities of Daily Living , Quality of Life , Prospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Digital healthcare systems based on augmented reality (AR) show promise for postoperative rehabilitation. We compared the effectiveness of AR-based rehabilitation and conventional rehabilitation after total knee arthroplasty (TKA). MATERIALS AND METHODS: We randomly allocated 56 participants to digital healthcare rehabilitation group (DR group) and conventional rehabilitation group (CR group). Participants in the CR group performed brochure-based home exercises for 12 weeks, whereas those in the DR group performed AR-based home exercises that showed each motion on a monitor and provided real-time feedback. The primary outcome was change in 4-m gait speed. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, health-related quality of life [assessed by the EuroQoL 5-Dimension 5-Level (EQ5D5L) questionnaire], pain [measured using a numeric rating scale (NRS)], Berg Balance Scale (BBS), range of motion (ROM), and muscle strength. Outcomes were measured at baseline (T0) and 3 (T1), 12 (T2), and 24 (T3) weeks after randomization. RESULTS: There was no significant difference in baseline characteristics of participants between two groups, except age and body mass index. No group difference was observed in 4-m gait speed (0.37 ± 0.19 and 0.42 ± 0.28 for the DR and CR groups, respectively; p = 0.438). The generalized estimating equation model revealed no significant group by time interaction regarding for 4-m gait speed, WOMAC, EQ5D5L, NRS, BBS, ROM, and muscle strength score. All outcomes were significantly improved in both groups (p < 0.001). CONCLUSION: The use of a digital healthcare system based on AR improved the functional outcomes, pain, and quality of life of patients after TKA. AR-based rehabilitation may be useful treatment as an alternative to conventional rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT04513353). Registered on August 9, 2020. http://clinicaltrials.gov/ct2/show/NCT04513353 .
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Arthroplasty, Replacement, Knee/rehabilitation , Quality of Life , Treatment Outcome , Pain/surgery , Delivery of Health Care , Osteoarthritis, Knee/surgery , Range of Motion, Articular , Knee Joint/surgeryABSTRACT
BACKGROUND: We investigated the branching pattern and topographic anatomy of the nerves to the teres minor (Tm) and the long head of the triceps brachii (LHT) in relation to reference lines extending between surface landmarks, to identify the innervation patterns of, and the optimal needle placement points within, the Tm and the LHT. METHODS: The anatomical courses of the nerves to the Tm and the LHT were investigated in 37 upper limbs of fresh-frozen cadavers. Distances from the acromion to nerve penetration points, and crossing points of reference lines with the Tm and LHT were measured in 27 cadaveric upper limbs. RESULTS: The Tm was innervated by the axillary nerve in all specimens in three patterns, and the LHT was innervated exclusively by the radial nerve. Our dissection and measurements indicate that the midpoint of the reference line from the acromion to the inferior angle of the scapula is the optimal needle insertion point for the Tm. The target point for the LHT appears to be the one-third point of the reference line from the acromion to the medial epicondyle, or the two-thirds point of the reference line from the acromion to the axillary fold. CONCLUSIONS: We investigated the branching pattern of the nerves to the Tm and the LHT and propose optimal needle placement points for electromyography of the Tm and LHT.
Subject(s)
Anatomic Landmarks , Arm/innervation , Brachial Plexus/anatomy & histology , Muscle, Skeletal/innervation , Radial Nerve/anatomy & histology , Rotator Cuff/innervation , Acromion/anatomy & histology , Aged , Aged, 80 and over , Axilla/anatomy & histology , Cadaver , Electromyography , Female , Humans , Humerus/anatomy & histology , Male , Scapula/anatomy & histologyABSTRACT
INTRODUCTION: Identification of Baxter's nerve (BN) has proven challenging for less experienced practitioners using ultrasonography due to a lack of adequate landmarks. This study aimed to establish novel, user-friendly anatomical landmarks and to describe useful structures to localize BN. MATERIALS AND METHODS: We examined 10 fresh cadaveric feet and identified the interobserver agreement of measuring three surface landmarks: the most medially protruded point on the medial malleolus (P), the navicular tuberosity (Q), and the center of the calcaneus (B). Next, 24 fresh cadaveric feet were used to identify the point of BN entry into the quadratus plantae (QP) muscle, which corresponds to the proximal BN impingement site. The rectangular coordinate system consisted of the origin (point P), X-axis, extension line P-Q, and Y-axis (the perpendicular line to the X-axis). To consider various foot sizes, the X and Y values were divided by the P-Q length and were designated as the ratios X and Y. RESULTS: Points P and Q showed smaller interobserver differences than that of point B. Ratios X and Y were 61.25 and 99.80%, respectively, for the QP. BN arose from the lateral plantar nerve in 20 of 24 specimens. The adjacent vessel was <3 mm from the entrapment site of BN in 20 of 24 specimens. CONCLUSION: New landmarks will improve the precision of localizing the entrapment site of BN and will provide advanced guidelines for podiatric patients.
Subject(s)
Anatomic Landmarks , Foot/innervation , Peripheral Nerves/anatomy & histology , Aged , Aged, 80 and over , Cadaver , Female , Humans , Male , Middle AgedABSTRACT
Interferon (IFN)-ß and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secreted by adipose tissue-derived mesenchymal stem cells (ASCs) have been proposed as key mechanistic factors in anti-cancer efficacy in lung cancer and breast cancer cells, where they act through paracrine signaling. We hypothesized that IFN-ß and TRAIL produced by ASCs suppress proliferation of hepatocellular carcinoma cells (HCCs). The present study evaluated the anti-cancer effects of ASCs on HCCs in vitro. We found that indirect co-culture with ASCs diminished growth of Huh7 hepatocellular carcinoma cells with increased protein levels of p53/p21 and phosphorylated STAT1 (pSTAT1), without apoptosis. Treatment with ASC-conditioned medium (ASC-CM) also decreased growth of Huh7 cells through elevated p53/p21 and pSTAT1 signaling. ASC-CM-mediated inhibition of cell growth was neutralized in Huh7 cells treated with anti-IFN-ß antibody compared to that in ASC-CM-treated Huh7 cells incubated with an anti-TRAIL antibody. Treatment with JAK1/JAK2 inhibitors recovered inhibition of growth in Huh7 cells incubated in ASC-CM or IFN-ß via down-regulation of pSTAT1/p53/p21. However, treatment of IFN-ß resulted in no alterations in resistance of Huh7 cells to TRAIL. Our findings suggest that ASCs decrease growth through activated STAT1-mediated p53/p21 by IFN-ß, but not TRAIL, in Huh7 cells.
Subject(s)
Carcinoma, Hepatocellular/therapy , Interferon-beta/metabolism , Liver Neoplasms/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , TNF-Related Apoptosis-Inducing Ligand/metabolism , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Humans , Janus Kinases/metabolism , Liver Neoplasms/metabolism , Mesenchymal Stem Cells/cytology , STAT1 Transcription Factor/metabolism , Signal Transduction , Tumor Suppressor Protein p53/metabolismABSTRACT
BACKGROUND: Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. METHODS: This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival. FINDINGS: Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9-22), median progression-free survival was 20·1 months (95% CI 14·2-21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1-17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen. FUNDING: Pfizer, Shinpoong, and Daewoong Korea and Takeda.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Gonadotropin-Releasing Hormone/agonists , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Androstadienes/administration & dosage , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Capecitabine/administration & dosage , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Piperazines/administration & dosage , Prognosis , Pyridines/administration & dosage , Survival RateABSTRACT
We investigated the effect of the modulation of Na/H exchanger 1 (NHE1) on apoptosis, differentiation, and chemoresistance in acute myeloid leukemia (AML) cells to evaluate the possibility of NHE1 modulation as a novel therapeutic strategy for AML. The pHi of leukemia cell lines except KG1a was higher than that of normal bone marrow mononuclear cells (BM MNCs). Notably, in K562, cytarabine (AraC)-resistant OCI-AML2, and primary leukemia cells, pHi was significantly higher than that of normal BM MNCs. Western blotting and real-time quantitative PCR confirmed that the increased NHE1 expression was responsible for the higher pHi. Specifically, compared to CD34+CD38+ leukemia cells, the mean fluorescence intensity of NHE1 was significantly higher in CD34+CD38- leukemic stem cells. The out of range in pHi by treatment with an NHE inhibitor, the amiloride analogue 5-(N,N-hexamethylene) amiloride (HMA), or an NHE activator, phorbol 12-myristate 13-acetate (PMA), resulted in dose- and time-dependent inhibition of leukemia cell proliferation. PMA induced CD14+ differentiation of leukemia cells, whereas HMA induced cell cycle arrest at the G1 phase. HMA could induce apoptosis of leukemia cells even in AraC-resistant cells and showed an additive effect on apoptosis in AraC-sensitive cells. Our result revealed that AML cells prefer more alkalic intracellular moiety than normal BM MNCs following increased NHE1 expression and that NHE1 modulation can induce apoptosis and differentiation of AML cells. These findings imply that NHE1 is a potential target in cytotoxic or differentiation-induction treatment for AML.
Subject(s)
Amiloride/pharmacology , Apoptosis/drug effects , Cell Differentiation/drug effects , Sodium-Hydrogen Exchanger 1/antagonists & inhibitors , Tetradecanoylphorbol Acetate/pharmacology , Acute Disease , Amiloride/chemistry , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , K562 Cells , Leukemia, Myeloid/genetics , Leukemia, Myeloid/metabolism , Leukemia, Myeloid/pathology , Sodium-Hydrogen Exchanger 1/genetics , Sodium-Hydrogen Exchanger 1/metabolismABSTRACT
Background: Recently, the application of smartphone in medical field has received great attention.Introduction: The objective of this study was to compare the effectiveness of smartphone-based and conventional pedometer-based exercise monitoring systems in promoting home exercise among prostate cancer patients.Methods: Prostate cancer patients who have undergone surgery or androgen deprivation therapy were recruited. All participants were provided with physical activity goals based on their activities and were advised to achieve these goals during their home exercise period. The intervention group was instructed to use smartphone application to record their activities; they also received weekly remote consultations based on the activity record from the application, without visiting a clinic. The control group was instructed to keep a written record of their daily activities based on pedometer readings; these records were checked by clinicians during follow-up visits. The uptake, adherence, and completion rates of two groups were compared by intention-to-treat analysis. Changes in physical function during the exercise period were analyzed.Results: In total, 100 patients were recruited (smartphone: 5 and pedometer: 50). No significant differences were detected between groups in rates of uptake (80.0% vs. 88.0%, p = 0.28), adherence (92.5% vs. 79.5%, p = 0.12), or completion (76.0% vs. 86.0%, p = 0.20). Physical functions were significantly improved in both groups.Conclusions: The smartphone-based exercise monitoring system and the pedometer yielded comparable results in promoting physical activity, as assessed by rates of uptake, adherence, and completion. Exercise monitoring was effective in improving physical functions, in both methods.
Subject(s)
Exercise , Health Promotion/methods , Prostatic Neoplasms/rehabilitation , Smartphone , Wearable Electronic Devices , Aged , Humans , Male , Middle Aged , Patient Compliance , Prospective Studies , Republic of KoreaABSTRACT
BACKGROUND: Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin's lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature. CASE PRESENTATION: An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence. CONCLUSIONS: In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin's lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.
Subject(s)
Constriction, Pathologic/complications , Hepatic Duct, Common/pathology , Jaundice, Obstructive/complications , Klatskin Tumor/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Aged, 80 and over , Constriction, Pathologic/pathology , Diagnosis, Differential , Female , Humans , Jaundice, Obstructive/pathology , Klatskin Tumor/etiology , Lymphoma, B-Cell, Marginal Zone/etiology , PrognosisABSTRACT
l-ascorbic acid 2-phosphate (Asc-2P) acts as an antioxidant and a stimulator of hepatocyte growth factor (HGF) production. Previously, we reported that depletion of growth factors such as fibroblast growth factor (FGF)-2, epidermal growth factor (EGF), FGF-4 and HGF during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF). In this study, we investigated the proliferation and differentiation potential of BMSCs by FGF-2 and Asc-2P. Co-treatment with FGF-2 and Asc-2P induced optimal proliferation of BMSCs and increased the accumulation rate of BMSC numbers during a 2-month culture period. Moreover, differentiation potential was maintained by co-treatment with FGF-2 and Asc-2P via HGF expression. Adipogenic differentiation potential by FGF-2 and Asc-2P was dramatically suppressed by c-Met inhibitors (SU11274). These data suggest that co-treatment with FGF-2 and Asc-2P would be beneficial in obtaining BMSCs that possess "stemness" during long-term culture.
Subject(s)
Ascorbic Acid/analogs & derivatives , Bone Marrow Cells/drug effects , Fibroblast Growth Factor 2/administration & dosage , Hepatocyte Growth Factor/metabolism , Mesenchymal Stem Cells/drug effects , Adipocytes/cytology , Adult , Ascorbic Acid/administration & dosage , Autophagy , Cell Differentiation , Cell Proliferation , Cells, Cultured , Cellular Senescence , Healthy Volunteers , Humans , Reactive Oxygen Species/metabolism , Young AdultABSTRACT
Mesenchymal stem cells (MSCs) can exhibit a marked tropism towards site of tumors. Many studies have reported that tumor progression and metastasis increase by MSCs. In contrast, other studies have shown that MSCs suppress growth of tumors. MSCs contribute to tumor growth promotion by several mechanisms: (1) transition to tumor-associated fibroblasts; (2) suppression of immune response; (3) promotion of angiogenesis; (4) stimulation of epithelial-mesenchymal transition (EMT); (5) contribution to the tumor microenvironment; (6) inhibition of tumor cell apoptosis; and (7) promotion of tumor metastasis. In contrast to the tumor-promoting properties, MSCs inhibit tumor growth by increasing inflammatory infiltration, inhibiting angiogenesis, suppressing Wnt signaling and AKT signaling, and inducing cell cycle arrest and apoptosis. In this review, we will discuss potential mechanisms by which MSC mediates tumor support or suppression and then the possible tumor-specific therapeutic strategies using MSCs as delivery vehicles, based on their homing potential to tumors.
Subject(s)
Mesenchymal Stem Cells/metabolism , Neoplasms/pathology , Tumor Suppressor Proteins/metabolism , Carcinogenesis/pathology , Cell Proliferation , Humans , Mesenchymal Stem Cell Transplantation , Neoplasms/therapyABSTRACT
[Purpose] We evaluated the relationship between knee alignment and the electromyographic (EMG) activity of the vastus medialis (VM) to the vastus lateralis (VL) muscles in patients with knee osteoarthritis (OA) in a cross-sectional study. [Subjects and Methods] Forty subjects with knee OA were assessed by anatomic radiographic knee alignment and the VM/VL ratio was calculated. Surface EMG from both the VM and VL muscles were evaluated during maximal isometric contraction at 60° knee flexion. Simultaneously, peak quadriceps torque was assessed using an isokinetic dynamometer. Subjects were categorized into low, moderate, and high varus groups according to knee malalignment. The peak quadriceps torque and VM/VL ratio across groups, and their relationships with varus malalignment were analyzed. [Results] All subjects had medial compartment OA and the VM/VL ratio of all subjects was 1.31 ± 0.28 (mean ± SD). There were no significant differences in the peak quadriceps torque or VM/VL ratios across the groups nor were there any significant relationships with varus malalignment. [Conclusion] The VM/VL ratio and peak quadriceps torque were not associated with the severity of knee varus malalignment.
ABSTRACT
Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2month) cultures. Taken together, depletion of growth factors during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF) through suppression of AKT and ERK signaling.
Subject(s)
Bone Marrow Cells/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Mesenchymal Stem Cells/drug effects , Adult , Blotting, Western , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cells, Cultured , Dose-Response Relationship, Drug , Epidermal Growth Factor/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 4/pharmacology , Hepatocyte Growth Factor/pharmacology , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Young AdultABSTRACT
AIMS: Urinary cystatin C has been suggested as a useful biomarker for diagnosis of acute kidney injury (AKI). Multiple myeloma is often complicated by AKI. Therefore, we investigated whether the urinary cystatin C was available for diagnosis of AKI in multiple myeloma. MATERIALS AND METHODS: This study included 39 patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. We reviewed the medical records retrospectively and investigated whether urinary γ-globulin and myeloma progression had effects on urinary cystatin C excretion. RESULTS: Spearman's correlation analysis showed that serum ß2-microglobulin and serum cystatin C had a significant positive correlation with the urinary cystatin C excretion (r = 0.513, p = 0.001, r = 0.659, p < 0.001) and FEcystatinC (r = 0.585, p = 0.002, r = 0.711, p < 0.001). The GFRcr also had a significant negative correlation with the urinary cystatin C excretion (r = -0.582, p < 0.001) and FEcystatinC (r = -0.474, p = 0.002). In addition, the urinary γ-globulin had a significant positive correlation with the urinary cystatin C excretion (r = 0.678, p < 0.001) and FEcystatinC (r = 0.731, p < 0.001). Urinary γ-globulin was the most significant factor to influence urinary cystatin C excretion in multiple regression test. CONCLUSION: These results indicate that urinary γ-globulin and myeloma progression can increase the fractional and total excretion of urinary cystatin C. Therefore, it is believed that the urinary cystatin C can be affected by urinary γ-globulin and myeloma progression in the diagnosis of AKI in multiple myeloma. In addition, urinary γ-globulin is believed to be the most significant factor to influence on urinary cystatin C.
Subject(s)
Acute Kidney Injury/urine , Cystatin C/urine , Multiple Myeloma/urine , gamma-Globulins/urine , Acute Kidney Injury/diagnosis , Aged , Disease Progression , Glomerular Filtration Rate , Humans , Middle Aged , Multiple Myeloma/pathology , Neoplasm Staging , beta 2-Microglobulin/bloodABSTRACT
Fringing reefs play an important role in protecting the coastal area by inducing wave breaking and wave energy dissipation. However, modeling of wave transformation and energy dissipation on this topography is still difficult due to the unique structure. In the present study, two-dimensional laboratory experiments were conducted to investigate the cross-shore variations of wave transformation, setup, and breaking phenomena over an idealized fringing reef with the 1/40 reef slope and to verify the Boussinesq model under monochromatic wave conditions. One-layer and two-layer model configurations of the Boussinesq model were used to figure out the model capability. Both models predicted well (r (2) > 0.8) the cross-shore variation of the wave heights, crests, troughs, and setups when the nonlinearity is not too high (A 0/h 0 < 0.07 in this study). However, as the wave nonlinearity and steepness increase, the one-layer model showed problems in prediction and stability due to the error on the vertical profile of fluid velocity. The results in this study revealed that one-layer model is not suitable in the highly nonlinear wave condition over a fringing reef bathymetry. This data set can contribute to the numerical model verification.
Subject(s)
Algorithms , Anthozoa/physiology , Coral Reefs , Models, Theoretical , Water Movements , Animals , Conservation of Natural Resources , Hydrodynamics , Oceans and Seas , SeawaterABSTRACT
This study presents wave height distribution in terms of stem wave evolution phenomena on partially perforated wall structures through three-dimensional laboratory experiments. The plain and partially perforated walls were tested to understand their effects on the stem wave evolution under the monochromatic and random wave cases with the various wave conditions, incident angle (from 10 to 40 degrees), and configurations of front and side walls. The partially perforated wall reduced the relative wave heights more effectively compared to the plain wall structure. Partially perforated walls with side walls showed a better performance in terms of wave height reduction compared to the structure without the side wall. Moreover, the relative wave heights along the wall were relatively small when the relative chamber width is large, within the range of the chamber width in this study. The wave spectra showed a frequency dependency of the wave energy dissipation. In most cases, the existence of side wall is a more important factor than the porosity of the front wall in terms of the wave height reduction even if the partially perforated wall was still effective compared to the plain wall.