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The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.
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Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities. Materials and Methods This retrospective study included Korean adults (age ≥ 25 years) who underwent health screening with fluorine 18 fluorodeoxyglucose PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral and subcutaneous fat, muscle, bone density, liver fat, all normalized to height (in meters squared), and aortic calcification. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively. Results The cross-sectional and cohort analyses included 32166 (mean age, 45 years ± 6 [SD], 28833 men) and 27 298 adults (mean age, 44 years ± 5 [SD], 24 820 men), respectively. Diabetes prevalence and incidence was 6% at baseline and 9% during the 7.3-year median follow-up, respectively. Visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUC of 0.70 (95% CI: 0.68, 0.71) for men and 0.82 (95% CI: 0.78, 0.85) for women and C-index of 0.68 (95% CI: 0.67, 0.69) for men and 0.82 (95% CI: 0.77, 0.86) for women, respectively. Combining visceral fat, muscle area, liver fat fraction, and aortic calcification improved predictive performance, yielding C-indexes of 0.69 (95% CI: 0.68, 0.71) for men and 0.83 (95% CI: 0.78, 0.87) for women. The AUC for visceral fat index in identifying metabolic syndrome was 0.81 (95% CI: 0.80, 0.81) for men and 0.90 (95% CI: 0.88, 0.91) for women. CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores greater than 100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95. Conclusion Automated multiorgan CT analysis identified individuals at high risk of diabetes and other cardiometabolic comorbidities. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pickhardt in this issue.
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Diabetes Mellitus , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Transversais , República da Coreia/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Medição de Risco/métodos , Doenças Cardiovasculares/diagnóstico por imagemRESUMO
PURPOSE: A tibial cement spacer (TCS) with spikes offers better initial stability than a conventional TCS and reduces spacer-related problems in two-stage revision total knee arthroplasty (R-TKA) for infection. We compared the clinical outcomes of two-stage revision arthroplasty for infected TKA using spiked TCS with that of conventional TCS. METHODS: This retrospective cohort study included 29 patients who underwent two-stage revision arthroplasty using an articulating cement spacer and who could be followed up for at least one year. Group S comprised 14 patients using spiked TCS, whereas Group C comprised 15 patients using conventional TCS. Demographic data, the interval from first to second stage revision, motion arc, numerical rating scale (NRS), Knee Society (KS) score, serum levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and frequency of repeating the first-stage and infection recurrence after R-TKA between the groups were analyzed. RESULTS: No significant differences were observed in the female ratio and mean age between both groups. The mean interval between the first and second stage revision was significantly shorter in Group S than in Group C. The mean motion arc was significantly larger in Group S than in Group C. The mean NRS was significantly lower in Group S than in Group C. The mean KS score in Group S was significantly higher than that in Group C. Serum ESR and CRP levels did not differ between the groups. The frequency of repeating the first stage was lower in Group S than in Group C. However, the recurrence rate after R-TKA was higher in Group S than in Group C. CONCLUSION: Compared with conventional TCS, spiked TCS shortened the period until R-TKA and improved pain and function levels. However, no significant difference existed in the rate of infection recurrence after R-TKA.
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Our objective was to develop and evaluate the clinical feasibility of deep-learning-based synthetic contrast-enhanced computed tomography (DL-SynCCT) in patients designated for nonenhanced CT (NECT). We proposed a weakly supervised learning with the utilization of virtual non-contrast CT (VNC) for the development of DL-SynCCT. Training and internal validations were performed with 2202 pairs of retrospectively collected contrast-enhanced CT (CECT) images with the corresponding VNC images acquired from dual-energy CT. Clinical validation was performed using an external validation set including 398 patients designated for true nonenhanced CT (NECT), from multiple vendors at three institutes. Detection of lesions was performed by three radiologists with only NECT in the first session and an additionally provided DL-SynCCT in the second session. The mean peak signal-to-noise ratio (PSNR) and structural similarity index map (SSIM) of the DL-SynCCT compared to CECT were 43.25 ± 0.41 and 0.92 ± 0.01, respectively. With DL-SynCCT, the pooled sensitivity for lesion detection (72.0% to 76.4%, P < 0.001) and level of diagnostic confidence (3.0 to 3.6, P < 0.001) significantly increased. In conclusion, DL-SynCCT generated by weakly supervised learning showed significant benefit in terms of sensitivity in detecting abnormal findings when added to NECT in patients designated for nonenhanced CT scans.
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Meios de Contraste , Aprendizado Profundo , Estudos de Viabilidade , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste/química , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso de 80 Anos ou mais , Radiografia Abdominal/métodos , Abdome/diagnóstico por imagemRESUMO
PURPOSE: The use of rodent models for diabetes, particularly with pancreatic islet transplantation, has been prevalent in various preclinical trials. The purpose of this study is to establish a diabetes mellitus (DM) model in Sprague Dawley (SD) rats using alloxan evaluated by assessing alloxan dosage, the induction rate of diabetes, and glucose stability through insulin treatment. METHODS: Over the course of 13 experimental rounds, diabetes was induced in 86 SD rats using alloxan at concentrations of 200 mg/kg (16 rats) or 150 mg/kg (70 rats). Various parameters, including diabetes induction rates, average insulin doses, extent of weight loss, and adverse effects such as diabetic ketoacidosis (DKA), were measured. RESULTS: The administration of 200 mg/kg of alloxan in rats resulted in severe diabetes induction, leading to DKA in three individuals, despite daily insulin glargine administration, DKA prevention was unsuccessful. The stability of alloxan decreases over time, especially when refrigeration is compromised during weighing. In the group treated with 150 mg/kg of alloxan, the diabetes induction rate was 83%. The average insulin dose was 2.21 units/kg/day. In contrast, the group treated with 200 mg/kg of alloxan exhibited a diabetes induction rate of 81% with a statistically significant higher average insulin requirement at 7.58 units/kg/day compared to 150 mg/kg of alloxan. CONCLUSION: Inducing diabetes in rats with 150 mg/kg of alloxan is considered more suitable for creating a diabetes model for xenogeneic islet transplantation compared to using 200 mg/kg of alloxan. This is due to fewer complications related to DKA or hyperglycemia and reduced need for exogenous insulin treatment.
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PURPOSE: To investigate serial changes in postoperative alignment over 5 years after open-wedge high tibial osteotomy (OWHTO) and to identify risk factors associated with alterations in the postoperative weight-bearing line WBL ratio. METHODS: Patients who underwent OWHTO during 2011-2017 were retrospectively reviewed. Inclusion criteria were (1) follow-up duration ≥5 years and (2) serial postoperative long-standing hip-to-ankle radiographs to evaluate alignment alterations. The WBL ratio was measured preoperatively and at 3 months, 6 months, 1 year, and 5 years postoperatively to evaluate serial changes. Alterations in the WBL ratio were analyzed using a linear mixed model, considering potential risk factors including International Cartilage Repair Society (ICRS) grades of each compartment, and medial meniscus extrusion (≥3 mm). Clinical outcomes were assessed using the Knee Society (KS) objective and functional scores, and the correlations between clinical outcomes and alignment alteration were examined. RESULTS: A total of 78 knees were investigated. During the study period, the overall WBL ratio decreased by 5.5 ± 7.2%, signifying varus shifting, from 58.6 ± 11.5% at 3 months post-surgery to 51.5 ± 12.7% at 5 years post-surgery. Based on univariate regression analyses, ICRS grade of the medial compartment and medial meniscus extrusion were included in a linear mixed model regarding alignment alteration. The model identified medial meniscus extrusion as a significant risk factor after adjusting for time (p <0.001). Medial meniscus extrusion also had a significant interaction with time (p <0.001), indicating greater alignment alteration in cases of medial meniscus extrusion. The extrusion was noted in 68 out of 78 knees. CONCLUSION: In the midterm following OWHTO, the overall alignment had a tendency toward varus shifting. A linear mixed model found that preoperative medial meniscus extrusion on magnetic resonance imaging is associated with the tendency.
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BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.
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Antibacterianos , Gestão de Antimicrobianos , Bacteriemia , Análise de Séries Temporais Interrompida , Klebsiella pneumoniae , Humanos , Estudos Retrospectivos , Criança , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Feminino , Masculino , Pré-Escolar , Antibacterianos/uso terapêutico , Lactente , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Adolescente , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Hospitais PediátricosRESUMO
OBJECTIVE: This study investigated whether early cognitive assessment in children with developmental delay (DD) predicts cognitive development. We investigated the correlation between cognitive and language development in children with DD, cerebral palsy (CP), and autism spectrum disorder (ASD). METHODS: Data were collected from children diagnosed with DD who visited the hospital between 2015 and 2023. The assessments included the Korean Bayley Scales of Infant and Toddler Development Second Edition (K-BSID-II) and the Korean Wechsler Preschool Primary Scale of Intelligence Fourth Edition (K-WPPSI-IV). Language development was evaluated using the Sequenced Language Scale for Infants (SELSI) and Preschool Receptive-Expressive Language Scale (PRES). The statistical analysis involved a correlation analysis. RESULTS: Among 95 children in the study, a significant correlation was discovered between early cognitive assessments (the Mental Developmental Index from the K-BSID-II) and later cognitive development (the Full-Scale Intelligence Quotient from the K-WPPSI-IV) in the DD and CP groups, but not in the ASD group. The DD and CP groups exhibited significant correlations in language development between the SELSI and PRES, whereas the ASD group did not. CONCLUSION: Early cognitive assessments can predict later cognitive development in children with DD and CP, but not in those with ASD, according to this study. There was a strong correlation between language and cognitive development in the DD and CP groups, highlighting the importance of early intervention and assessment for these children. Further investigation is necessary to address these limitations and refine demographic data.
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PURPOSE: Whether the longevity of total knee arthroplasty (TKA) differs between postoperative phenotypes has not been investigated. This study aims to examine which phenotype has a worse long-term survival rate than the reference phenotype (neutral alignment-parallel joint line), and whether joint-line obliquity (JLO) affects the survivorship of TKA. METHODS: A total of 945 knees that underwent primary TKAs for primary osteoarthritis from January 2000 to January 2009 were included. These were classified into nine postoperative phenotypes based on the combined assessment of the hip-knee-ankle (HKA) angle and JLO, measured on standing radiographs. The 5-, 10- and 15-year survival rates were analysed using Kaplan-Meier methods and log-rank tests. The long-term survival rates of each phenotype were compared with the reference phenotype. RESULTS: There were 55 aseptic mechanical failures within a period of 10.4 ± 5.0 years. The most frequently observed phenotypes were the reference phenotype (n = 527), neutral alignment-lateral joint-line inclination (n = 162), varus alignment-lateral joint-line inclination (n = 104) and varus alignment-parallel joint line (n = 101). The overall failure rate for each phenotype was 3.6%, 3.7%, 18.3% and 7.9%, respectively. Only the 10- and 15-year survival rates of the varus alignment-lateral joint-line inclination phenotype were significantly different from those of the reference phenotype (97%-93% vs. 90%-69%; p = 0.017, <0.001). CONCLUSION: The lateral joint-line inclination phenotype had an inferior long-term survival rate after varus-aligned TKA. This suggested that alignment and JLO affected the long-term survival rate of patients who underwent TKA. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.
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The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.
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Regeneração Óssea , Tíbia , Alicerces Teciduais , Animais , Cães , Alicerces Teciduais/química , Tíbia/diagnóstico por imagem , Projetos Piloto , Osteogênese , Porosidade , Microtomografia por Raio-X , Durapatita , Transplante Ósseo/métodos , Substitutos ÓsseosRESUMO
Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
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BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.
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Anlodipino , Estudos Cross-Over , Combinação de Medicamentos , Ezetimiba , Voluntários Saudáveis , Losartan , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administração & dosagem , Anlodipino/farmacocinética , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Masculino , Ezetimiba/farmacocinética , Ezetimiba/administração & dosagem , Losartan/farmacocinética , Losartan/administração & dosagem , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Comprimidos , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/administração & dosagem , Área Sob a CurvaRESUMO
BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).
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Aims: The aim of this study was to investigate the distribution of phenotypes in Asian patients with end-stage osteoarthritis (OA) and assess whether the phenotype affected the clinical outcome and survival of mechanically aligned total knee arthroplasty (TKA). We also compared the survival of the group in which the phenotype unintentionally remained unchanged with those in which it was corrected to neutral. Methods: The study involved 945 TKAs, which were performed in 641 patients with primary OA, between January 2000 and January 2009. These were classified into 12 phenotypes based on the combined assessment of four categories of the arithmetic hip-knee-ankle angle and three categories of actual joint line obliquity. The rates of survival were analyzed using Kaplan-Meier methods and the log-rank test. The Hospital for Special Surgery score and survival of each phenotype were compared with those of the reference phenotype with neutral alignment and a parallel joint line. We also compared long-term survival between the unchanged phenotype group and the corrected to neutral alignment-parallel joint line group in patients with Type IV-b (mild to moderate varus alignment-parallel joint line) phenotype. Results: The most common phenotype was Type I-b (mild to moderate varus alignment-medial joint line; 27.1% (n = 256)), followed by Type IV-b (23.2%; n = 219). There was no significant difference in the clinical outcomes and long-term survival between the groups. In Type IV-b phenotypes, the neutrally corrected group showed higher 15-year survival compared with the unchanged-phenotype group (94.9% (95% confidence interval (CI) 92.0 to 97.8) vs 74.2% (95% CI 98.0 to 100); p = 0.020). Conclusion: Constitutional varus was confirmed in more than half of these patients. Mechanically aligned TKA can achieve consistent clinical outcomes and long-term survival, regardless of the patient's phenotype. The neutrally corrected group had better long-term survival compared with the unchanged phenotype group.
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Artroplastia do Joelho , Povo Asiático , Osteoartrite do Joelho , Fenótipo , Humanos , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Falha de Prótese , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.
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Antiparkinsonianos , Levodopa , Oxidiazóis , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Levodopa/uso terapêutico , Levodopa/administração & dosagem , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Oxidiazóis/uso terapêutico , Oxidiazóis/administração & dosagem , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores de Catecol O-Metiltransferase/farmacologia , Inibidores de Catecol O-Metiltransferase/administração & dosagem , República da Coreia , Resultado do TratamentoRESUMO
AIMS/INTRODUCTION: To investigate the long-term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. MATERIALS AND METHODS: Donor porcine islets were obtained from wild-type, α1,3-galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate-chitosan (AC), alginate-perfluorodecalin (A-PFD) and AC-perfluorodecalin (AC-PFD) encapsulated porcine islets were transplanted into diabetic mice. RESULTS: In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC-PFD capsules showed the most favorable long-term outcomes, maintaining normal blood glucose levels for 180 days. A-PFD capsules showed comparable results to AC-PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild-type porcine islets. CONCLUSION: The AC-PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long-term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.
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Diabetes Mellitus Experimental , Transplante das Ilhotas Pancreáticas , Transplante Heterólogo , Transplante das Ilhotas Pancreáticas/métodos , Animais , Suínos , Camundongos , Transplante Heterólogo/métodos , Diabetes Mellitus Experimental/terapia , Alginatos , Galactosiltransferases/genética , Sobrevivência de Enxerto , Ilhotas Pancreáticas , Glicemia/análise , Masculino , Genótipo , Doadores de TecidosRESUMO
Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.
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Disfunção Cognitiva , Colite , Eucommiaceae , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Receptor 4 Toll-Like , Colite/induzido quimicamente , Colite/tratamento farmacológico , Ácido Clorogênico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológicoRESUMO
OBJECTIVE: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson's disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog). METHODS: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test-retest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. Spearman's rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. RESULTS: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). CONCLUSION: Our. RESULTS: demonstrate that the K-SCOPA-Cog has good reliability and validity.
RESUMO
This study was investigated to examine the neuroprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced-dementia mice. Consumption of FPB by mice resulted in improved memory dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. FPB significantly decreased oxidative stress by regulating levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in brain tissues. In addition, FPB restored cerebral mitochondrial dysfunction by modulating levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP. In addition, FPB enhanced the cholinergic system via the regulation of acetylcholine (ACh) content, acetylcholinesterase (AChE) activity, and expressions of AChE and choline acetyltransferase (ChAT) in brain tissues. FPB ameliorated neuronal apoptosis through modulation of the protein kinase B (AKT)/B-cell lymphoma (BCL)-2 signaling pathway. Also, FPB improved inflammation response by down-regulating the toll-like receptor (TLR)-4/nuclear factor (NF)-κB pathway. Additionally, FPB ameliorated synaptic plasticity via the increase of the expressions of synaptophysin (SYP), postsynaptic density protein (PSD)-95, and growth-associated protein (GAP)-43. Treatment with FPB also reinforced the blood-brain barrier by increasing tight junctions including zonula occludens (ZO)-1, occludin, and claudin-1. In conclusion, these results show that FPB can improve cognitive impairment via AKT/NF-κB pathways in ethanol-induced-dementia mice.