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BACKGROUND: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018. METHODS: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021. RESULTS: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories. CONCLUSIONS: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan.
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BACKGROUND: Serum levels of stratifin (SFN), a member of the 14-3-3 protein family, increase in patients with drug-induced lung injury associated with diffuse alveolar damage. Therefore, we hypothesised that SFN levels would be higher in those experiencing acute exacerbation of interstitial lung disease (AE-ILD). A secondary analysis was also planned to determine whether SFN levels could discriminate survival in those with AE. METHODS: Thirty-two patients with clinically stable ILD (CS-ILD) and 22 patients with AE-ILD were examined to assess whether high serum SFN levels were associated with AE-ILD and whether SFN levels reflected disease severity or prognosis in patients with AE-ILD. RESULTS: Serum SFN levels were higher in the AE-ILD group than in the CS-ILD group (8.4 ± 7.6 vs. 1.3 ± 1.2 ng/mL, p < 0.001). The cut-off value of the serum SFN concentration for predicting 90-day and 1-year survival was 6.6 ng/mL. SFN levels were higher in patients who died within 90 days and 1 year than in patients who survived beyond these time points (13.5 ± 8.7 vs. 5.6 ± 5.3 ng/mL; p = 0.011 and 13.1 ± 7.5 vs. 3.1 ± 1.9 ng/mL; p < 0.001, respectively) in the AE-ILD group. When this cut-off value was used, the 90-day and 1-year survival rates were significantly better in the population below the cut-off value than in those above the cut-off value (p = 0.0017 vs. p < 0.0001). CONCLUSIONS: High serum SFN levels are associated with AE-ILD and can discriminate survival in patients with AE-ILD.
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Proteínas 14-3-3 , Progresión de la Enfermedad , Exorribonucleasas , Enfermedades Pulmonares Intersticiales , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Anciano , Exorribonucleasas/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/diagnóstico , Estudios Retrospectivos , Proteínas 14-3-3/sangre , Persona de Mediana Edad , Pronóstico , Biomarcadores/sangre , Anciano de 80 o más AñosRESUMEN
Several large longitudinal studies on myotonic dystrophy type 1 (DM1) patients have revealed that proximal muscles show more gradual muscle weakness than distal muscles and that the progression of muscle weakness might differ between the sexes. However, these longitudinal studies were based on two follow-up time points. The present report aimed to verify the longitudinal characteristics of muscle strength and various movement abilities in a case of DM1 by examining the results of 44 repeated evaluations for approximately two years. A 40-year-old male patient with DM1 could walk independently without any aid. We recorded the longitudinal changes in his muscle strength and movement ability during outpatient rehabilitation. During follow-up, he had a fall and was diagnosed with a right ankle sprain. To evaluate the effects of the fall, we examined his recorded data. He had a significant decrease in right knee extensor muscle strength after the fall, suggesting muscle weakness due to disuse syndrome. Although his right knee extensor muscle strength and walking speed decreased, the timed up-and-go test score was improved, and walking endurance in the 2-minute walk test was maintained. In the present case, there were some motor tasks in which the movement ability was maintained or improved, likely due to the use of compensation by residual function, even when muscle weakness was present. Regular and repeated evaluations of patients with DM1 lead to reveal longitudinal characteristics of their dysfunction and movement ability.
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The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC90, 0.5 mg/L, and MIC50, and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.
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Antibacterianos , Cefazolina , Escherichia coli , Pruebas de Sensibilidad Microbiana , Nefrectomía , Prostatectomía , Humanos , Cefazolina/farmacocinética , Cefazolina/sangre , Cefazolina/uso terapéutico , Masculino , Antibacterianos/farmacocinética , Antibacterianos/sangre , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Femenino , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Adulto , Unión Proteica , Anciano de 80 o más AñosRESUMEN
Nature is filled with materials that are both strong and light, such as bones, teeth, bamboo, seashells, arthropod exoskeletons, and nut shells. The insights gained from analyzing the changing chemical compositions and structural characteristics, as well as the mechanical properties of these materials, have been applied in developing innovative, durable, and lightweight materials like those used for impact absorption. This research concentrates on the involucres of Job's tears (Coix lacryma-jobivar.lacryma-jobi), which are rich in silica, hard, and serve to encase the seeds. The chemical composition and structural characteristics of involucres were observed using scanning electron microscopy and energy-dispersive x-ray spectroscopy and optical microscopy with safranin staining. The hardness of the outer and inner surfaces of the involucre was measured using the micro-Vickers hardness test, and the Young's modulus of the involucre's cross-section was measured using nanoindentation. Additionally, the breaking behavior of involucres was measured through compression test and three-point bending tests. The results revealed a smooth transition in chemical composition, as well as in the orientation and dimensions of the tissues from the outer to the inner layers of involucres. Furthermore, it was estimated that the spatial gradient of the Young's modulus is due to the gradient of silica deposition. By distributing the hard, brittle silica in the outer layer and elastoplastic organic components in the middle and inner layers, the involucres effectively respond to compressive and tensile stresses that occur when loads are applied to the outside of the involucre. Furthermore, the involucres are reinforced in both meridional and equatorial directions by robust fibrovascular bundles, fibrous bundles, and the inner layer's sclerenchyma fibers. From these factors, it was found that involucres exhibit high toughness against loads from outside, making it less prone to cracking.
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Artrópodos , Coix , Diente , Animales , Coix/química , Dióxido de SilicioRESUMEN
Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among various positions of the lesions, the recovery from USN during recovery periods (postoperative day; POD 10-18) tended to be slower in cases with more rostral lesions in the AGm (r = - 0.302; p = 0.028). Moreover, the total number of arm entries and maximum moving speed did not significantly differ between before and after AGm infarction. According to these results, the anterior lesions may slowly recover from USN-like behavior, and there may be a weak association between the AGm infarct site and recovery rate. In addition, all unilateral focal infarctions in the AGm induced USN-like behavior without motor deficits.
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Modelos Animales de Enfermedad , Trastornos de la Percepción , Animales , Trastornos de la Percepción/fisiopatología , Trastornos de la Percepción/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Lateralidad Funcional/fisiología , Percepción Espacial/fisiología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/complicaciones , Corteza Cerebral/fisiopatologíaRESUMEN
Two anti-fibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells (PBMCs) are immunocompetent cells that could orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in the bulk PBMCs of patients with IPF and the effects of anti-fibrotic drugs on these signatures. Differentially expressed genes (DEGs) between "patients with IPF and healthy controls" and "before and after anti-fibrotic treatment" were analyzed. Enrichment analysis suggested that fatty acid elongation interferes with TGF-ß/Smad signaling and the production of oxidative stress since treatment with NTD upregulates the fatty acid elongation enzymes ELOVL6. Treatment with PFD downregulates COL1A1, which produces wound-healing collagens because activated monocyte-derived macrophages participate in the production of collagen, type I, and alpha 1 during tissue damage. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinase activation, and the inhibition of PAI-1 activity attenuates lung fibrosis. DEG analysis suggested that both the PFD and NTD upregulate SERPINE1, which regulates PAI-1 activity. This study embraces a novel approach by using RNA sequencing to examine PBMCs in IPF, potentially revealing systemic biomarkers or pathways that could be targeted for therapy.
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Fibrosis Pulmonar Idiopática , Inhibidor 1 de Activador Plasminogénico , Humanos , Leucocitos Mononucleares , Transcriptoma , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/genética , Ácidos GrasosRESUMEN
BACKGROUND: The study introduces the application of negative pressure wound therapy (NPWT) in pediatric stoma closure, emphasizing the importance of enhancing aesthetics and minimizing surgical site infections (SSI). CASE PRESENTATION: The case series involves four infants undergoing non-umbilical stoma closure with a combination of purse-string closure (PSC) and NPWT, focusing on aesthetic outcomes and infection prevention. NPWT was initiated immediately after surgery, and patients were monitored every 3-4 days. Notably, none of the four infants experienced SSI or other complications. The patients adequately tolerated NPWT, with no significant adverse events. Furthermore, Manchester Scar Scale (MSS) was 9 [7-10], and Patient and Observer Scar Assessment Scale (POSAS) (observer) was 12.5 [12-19], POSAS (patient) was 12.5 [11-16] (all median values [minimum-maximum]), indicating that excellent aesthetic outcomes were achieved. DISCUSSION: We emphasizes the significance of aesthetics in pediatric patients; in addition, our findings demonstrate that four infants who received NPWT combined with PSC achieved superior outcomes that did the most recent four infants who underwent PSC only at our institution. It also addresses the risk of SSI in stoma closure and discusses the pros and potential cons of using NPWT in pediatric cases, underlining the need for further research and the accumulation of additional reports. CONCLUSIONS: This is the inaugural report of prophylactic NPWT for pediatric stoma closure, emphasizing the effectiveness of combining PSC and NPWT for SSI prevention and improved aesthetics. The study calls for additional research and reports on NPWT in pediatric cases to further solidify its benefits in this patient population.
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Background: We assessed damaged anterior capsulolabral motion during axial shoulder rotation in patients with anterior shoulder instability. Methods: Twenty-nine shoulders of 28 patients with anterior shoulder instability who underwent cine-magnetic resonance imaging during axial rotation of the adducted arm were included. The motion was captured after an intra-articular injection of saline solution (10-20 mL). During imaging, the shoulder was rotated passively from maximum internal rotation to maximum external rotation in the first 10 s and then back to maximum internal rotation in the subsequent 10 s. We assessed the rotational angles of the damaged labrum during compressing and pulling the humeral head against the glenoid. Evaluation of the rotational angles was performed on a series of axial images through the humeral head center. Results: The mean angles that damaged labrum compressed and pulled off against the glenoid were 12.0 ± 19.1° and 2.8 ± 21.2°, respectively. Additionally, seven of the 29 shoulders showed that the damaged labrum compressed on the glenoid rim before the rotational angle exceeded 0° during external rotation. In 13 shoulders, the damaged labrum could remain repositioned on the glenoid rim over the neutral position during internal rotation. In two shoulders, the damaged labrum was not compressed against the glenoid at the maximum external rotation. The injected saline moved from the posterior to the anterior side of the glenohumeral joint during internal rotation in each shoulder. Conclusion: The damaged labrum could be positioned on the glenoid when the arm was in a traditional internal immobilization.
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OBJECTIVE: To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. RESULTS: Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan-Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. CONCLUSION: The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.
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Pleuroparenchymal fibroelastosis (PPFE) progresses slowly but sometimes relatively quickly, leading to decreased activities of daily living (ADL) and muscle weakness. Skeletal muscle atrophy and muscle weakness in chronic obstructive pulmonary disease (COPD) patients may be caused by cachexia and are associated with reduced ADLs and increased risk of death. However, the association between skeletal muscle mass and the prognosis of PPFE patients remains unknown. We retrospectively analysed the clinical significance of the cross-sectional area of the erector spinae muscle (ESMCSA), a skeletal muscle index, and predictors of mortality within 3 years in PPFE 51 patients, idiopathic pulmonary fibrosis (IPF) 52 patients and COPD 62 patients. PPFE patients had significantly lower ESMCSA than IPF or COPD patients, and lower ESMCSA (< 22.57 cm2) was associated with prognosis within 3 years (log-rank test; p = 0.006), whereas lower body mass index (BMI) showed no association. Multivariate analysis showed that ESMCSA was an independent predictor of mortality within 3 years in PPFE patients (hazard ratio, 0.854; 95% confidence interval: 0.737-0.990, p = 0.036). These results suggest the importance of monitoring ESMCSA in PPFE patients and that assessing ESMCSA in PPFE patients could be a more useful prognostic indicator than BMI.
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Fibrosis Pulmonar Idiopática , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pronóstico , Estudios Retrospectivos , Actividades Cotidianas , Músculos Paraespinales , Debilidad MuscularRESUMEN
PURPOSE: Since pediatric stomas are often temporary, their creation, management, and closure should be simple, with minimal complications and excellent cosmetic results. We began employing umbilical stomas in 2000. This study aimed to characterize the ingenuity and utility of umbilical stomas and provide a quantitative evaluation of their cosmetic outcomes. METHODS: We examined cases of stoma construction and closure surgery performed in our department from January 2000 to December 2022. The umbilical and non-umbilical stoma groups included 54 and 42 cases, respectively, and the findings for both groups were compared and analyzed. RESULTS: The two groups showed no significant differences in the incidence of complications. The Manchester Scar Scale score for the umbilical stoma group (8.42 ± 1.85) was significantly better than that for the non-umbilical stoma group (16.31 ± 2.96; P < 0.01). Likewise, in Patient and Observer Scar Assessment Scale assessments, the umbilical stoma group showed significantly better scores in both the observer scale (9.48 ± 2.50 vs. 21.78 ± 7.26; P < 0.01) and the patient scale (10.5 ± 1.39 vs. 22.40 ± 7.35; P < 0.01). CONCLUSIONS: Umbilical stomas are easy to manage and yield an inconspicuous closure incision with excellent cosmetic outcomes. Although patient selection is important, pediatric umbilical stomas are a valuable option that can be actively employed.
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Cicatriz , Estomas Quirúrgicos , Humanos , Niño , Selección de PacienteRESUMEN
BACKGROUND: The University of Wisconsin (UW) solution is the gold standard for preserving the liver, kidneys, and pancreas. For renal preservation, the addition of the flavonoid, quercetin (QE), to the preservation solution reduces damage to renal tubular cells, and the addition of sucrose (Suc) is also beneficial for preservation. The aim of this study was to investigate the protective effects of QE and Suc on porcine livers in terms of warm and cold injury and to evaluate whether their use improves ischemia-reperfusion (I/R) injury after simple cold storage (CS). METHODS: We tested porcine livers procured after 30 minutes of warm ischemia followed by preservation for 6 hours under the following 2 conditions: group 1, preserved with the CS/UW solution (n = 4); group 2, preserved with the CS/UW solution containing Que 33.1 µM and Suc 0.1 M (n = 6). All livers were evaluated using an ex vivo isolated liver reperfusion model with saline-diluted autologous blood. RESULTS: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels in group 2 were significantly lower at 30 minutes of reperfusion than in group 1. Furthermore, histologic evaluation by hematoxylin and eosin staining showed significantly fewer morphologic changes in group 2 than in group 1, as indicated by the total Suzuki score. Group 2 also had significantly better scores for sinusoidal congestion and hepatocyte cytoplasmic vacuolization. CONCLUSION: Adding Que and Suc to the UW solution can effectively prevent cold injury in livers donated after circulatory death.
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Lesión por Frío , Soluciones Preservantes de Órganos , Daño por Reperfusión , Humanos , Porcinos , Animales , Preservación de Órganos , Quercetina/farmacología , Soluciones Preservantes de Órganos/farmacología , Hígado/patología , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Glutatión/farmacología , Alopurinol/farmacología , Insulina/farmacología , Rafinosa/farmacología , Lesión por Frío/patologíaRESUMEN
BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.
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Fallo Renal Crónico , Diálisis Peritoneal , Adulto , Humanos , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Catéteres de Permanencia/efectos adversos , Japón , Cateterismo/métodos , Peritoneo , Fallo Renal Crónico/terapia , Fallo Renal Crónico/etiologíaRESUMEN
INTRODUCTION: Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP-IP) is frequently not curable by chest drainage only. A digital drainage system (DDS) provides an objective evaluation of air leakage and maintains a pre-determined negative pressure, compared to an analog drainage system (ADS). Few studies have reported the effectiveness of DDS in the treatment of SSP-IP. This study aimed to assess the usefulness of DDS for SSP-IP. METHODS: This retrospective study included patients with SSP-IP who had undergone chest drainage. We reviewed the included patients' medical records, laboratory data, computed tomography findings, and pulmonary function data. RESULTS: DDS was used in 24 patients and ADS in 49 patients. The mean duration of chest drainage was 11.4 ± 1.9 days in the DDS group and 14.2 ± 1.3 days in the ADS group, which was not significantly different (p = 0.218). Surgery, pleurodesis, and/or factor XIII administration were performed in 40 patients. Additionally, five (20.8%) patients in the DDS group and nine (18.4%) in the ADS group had a recurrence of pneumothorax within 4 weeks (p = 1.000). One patient (14%) in the DDS group and six (12.2%) in the ADS group (p = 0.414) were cured of pneumothorax but later died. CONCLUSION: DDS did not demonstrate a significant difference in the shortening of chest drainage duration. Further study is needed to validate the results of this study.
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Enfermedades Pulmonares Intersticiales , Neumotórax , Humanos , Tubos Torácicos , Drenaje/métodos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/terapia , Pleurodesia/métodos , Neumotórax/terapia , Neumotórax/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. METHODS: Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n = 5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n = 4). After 4 h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2 h. RESULTS: In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). CONCLUSIONS: The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.
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Soluciones Preservantes de Órganos , Preservación de Órganos , Animales , Porcinos , Soluciones Preservantes de Órganos/farmacología , Hígado , Glutatión/farmacología , Insulina , PerfusiónRESUMEN
Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the "Hematopoietic cell lineage" pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs. The differentially expressed genes (DEGs) upregulated in PBMCs reflected the disease state of non-emphysematous COPD. Upregulated DEGs such as XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 activate T lymphocytes and eosinophils. Upregulating keratan sulfate biosynthesis and metabolic processes is associated with protection against the destruction of the distal airways. ITGA3 upregulation augments interactions with extracellular matrix proteins, and COL6A1 augments the profibrotic mast cell phenotype during alveolar collagen VI deposition. Upregulating HSPG2, PDGFRB, and PAK4 contributes to the thickening of the airway wall, and upregulating SERPINF1 expression explains the better-preserved vascular bed. Therefore, gene expression and pathway analysis in PBMCs in patients with non-emphysematous COPD represented type 2 immune responses and airway remodeling features. Therefore, these patients have asthmatic potential despite no clinical signs of asthma, in contrast to those with emphysematous COPD.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Transcriptoma , Leucocitos Mononucleares , Enfermedad Pulmonar Obstructiva Crónica/genética , Genes Reguladores , Quinasas p21 ActivadasRESUMEN
Objective: Approximately two-thirds of patients with history of shoulder dislocation may develop osteoarthritis (OA) of the glenohumeral joint. However, the biochemical mechanisms underlying the association between dislocation and OA are largely unknown. This study aimed to investigate macrophage markers and inflammatory cytokine expression associated with shoulder instability (SI) in comparison to rotator cuff tears (RCTs). Design: This study included 30 patients with SI and 30 patients with RCTs. Synovial membrane samples were harvested from the rotator interval during the arthroscopic anatomical repair for both groups. The localization of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and cluster of differentiation (CD) 68 in synovial membranes was determined by immunohistochemistry. Transcript-level expressions of the inflammatory cytokines (TNFA and IL1B) and macrophage markers pan-CD68 and -M1 (CD80 and CD86) were quantified. CD80 and CD86 expression in macrophages from the SI group was confirmed using flow cytometry. Results: TNF-α, IL-1ß, and CD68 were expressed in the synovial lining layer of the synovial tissue in both groups. In addition, the mRNA expressions of TNFA, IL1B, CD68, and CD80 were significantly higher in the SI group compared to the RCT group (P â= â0.012, 0.014, 0.022, 0.003, respectively). In samples from the SI group, 96.3% of CD68+/CD14+ macrophages were CD86-positive, whereas 2.5% of CD68+/CD14+/CD86+ cells were CD80-positive. Conclusions: Patients with SI had higher mRNA levels of TNFA, IL1B, CD68, and CD80 than those with RCTs. These findings may partially explain the biochemical mechanism underlying the frequent development and progression of osteoarthritis in patients with SI.
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Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.
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OBJECTIVES: There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined. METHODS: Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients. RESULTS: The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL. CONCLUSIONS: The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.