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BACKGROUND/AIM: The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear. PATIENTS AND METHODS: In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m2) and low- (<25 kg/m2) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated. RESULTS: Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS). CONCLUSION: Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.
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Composición Corporal , Índice de Masa Corporal , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Composición Corporal/efectos de los fármacos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Anciano de 80 o más Años , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Autoantibody-mediated glomerulonephritis (AGN) arises from dysregulated renal inflammation, with urgent need for improved treatments. IL-17 is implicated in AGN and drives pathology in a kidney-intrinsic manner via renal tubular epithelial cells (RTECs). Nonetheless, downstream signaling mechanisms provoking kidney pathology are poorly understood. A noncanonical RNA binding protein (RBP), Arid5a, was upregulated in human and mouse AGN. Arid5a-/- mice were refractory to AGN, with attenuated myeloid infiltration and impaired expression of IL-17-dependent cytokines and transcription factors (C/EBPß, C/EBPδ). Transcriptome-wide RIP-Seq revealed that Arid5a inducibly interacts with conventional IL-17 target mRNAs, including CEBPB and CEBPD. Unexpectedly, many Arid5a RNA targets corresponded to translational regulation and RNA processing pathways, including rRNAs. Indeed, global protein synthesis was repressed in Arid5a-deficient cells, and C/EBPs were controlled at the level of protein rather than RNA accumulation. IL-17 prompted Arid5a nuclear export and association with 18S rRNA, a 40S ribosome constituent. Accordingly, IL-17-dependent renal autoimmunity is driven by Arid5a at the level of ribosome interactions and translation.
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Autoanticuerpos , Proteínas de Unión al ADN , Glomerulonefritis , Interleucina-17 , Ratones Noqueados , Factores de Transcripción , Animales , Interleucina-17/metabolismo , Glomerulonefritis/inmunología , Glomerulonefritis/genética , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Humanos , Ratones , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Autoanticuerpos/inmunología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/genética , Proteína delta de Unión al Potenciador CCAAT/metabolismo , Proteína delta de Unión al Potenciador CCAAT/genética , Ratones Endogámicos C57BL , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Endoscopic variceal ligation and sclerotherapy are recommended for esophagogastric variceal bleeding (EGVB) in cirrhosis but can be complicated by early rebleeding and death. This study aimed to identify noninvasive markers accurately predicting early rebleeding and mortality after endoscopic hemostasis for EGVB. METHODS: Among 116 patients with endoscopically confirmed EGVB and endoscopic hemostasis, various noninvasive markers were calculated, and their predictive accuracy was compared by receiver-operating characteristic curve analysis. Endpoints included 5-day rebleeding, 5-day mortality, 6-week rebleeding, and 6-week mortality. RESULTS: The median age was 63 years. Child-Pugh class B and C patients accounted for 40.5% and 34.5%, respectively. Only the aspartate aminotransferase-to-platelet ratio index (APRI) significantly predicted 5-day rebleeding, with an area under the curve (AUC) of 0.777 (95% confidence interval [CI]: 0.537-1). The model for end-stage liver disease-Na (MELD-Na) score showed good predictive accuracy for 5-day mortality (AUC: 0.839, 95% CI: 0.681-0.997), 6-week rebleeding (AUC: 0.797, 95% CI: 0.663-0.932), and 6-week mortality (AUC: 0.888, 95% CI: 0.797-0.979). CONCLUSIONS: Patients with cirrhosis with a high APRI and MELD-Na score were at high risk of early rebleeding and death after EGVB. Allocating appropriate monitoring and care for those patients is necessary.
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INTRODUCTION: A specialized device equipped with a sharp blade filter has been developed to enable more efficient purification of a micronized cellular adipose matrix (MCAM) containing stem cells. The aim of this study is to compare the characteristics and functions of the population of stromal cells (mSVF) and cultured cells (mASCs) purified using this device with those of cSVF and cASCs obtained through conventional enzymatic purification. METHODS: Cell viability, proliferation capacity and yield were assessed. Characterization of stem cell potency was performed by analyzing cell surface markers including CD34, a marker of activated adipose-derived stem cells. The trilineage differentiation potential was evaluated using RT-PCR and histology. RESULTS: The yield rate of mSVF obtained from MCAM was significantly higher than that with the conventional method, although use of the device resulted in a slight decrease in cell viability. After culture, mASCs exhibited a remarkable clonogenic potential and significantly higher cell proliferation potential than cASCs. The mASCs also displayed a distinct pattern of ASC cell surface markers, increased expression of genes related to CD34, high pluripotency, and a high trilineage differentiation ability. CONCLUSION: The specialized device enhanced the yield of SVF and produced cells with high proliferation rates and characteristics that include expression of stem cell markers.
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Tejido Adiposo , Diferenciación Celular , Proliferación Celular , Células Madre , Humanos , Tejido Adiposo/citología , Células Madre/citología , Células Madre/metabolismo , Supervivencia Celular , Separación Celular/métodos , Células Cultivadas , Adipocitos/citología , Adipocitos/metabolismo , Antígenos CD34/metabolismo , Células del Estroma/citología , Células del Estroma/metabolismoRESUMEN
Increasing evidence suggests that, in addition to a loss of tolerance, bile acid (BA) modulates the natural history of primary biliary cholangitis (PBC). We focused on the impacts of dietary changes on the immunopathology of PBC, along with alterations in BA composition and gut microbiota. In this study, we have taken advantage of our unique PBC model, a Cyp2c70/Cyp2a12 double knockout (DKO), which includes a human-like BA composition, and develops progressive cholangitis following immunization with the PDC-E2 mimic, 2-octynoic acid (2OA). We compared the effects of a ten-week high-fat diet (HFD) (60 % kcal from fat) and a normal diet (ND) on 2OA-treated DKO mice. Importantly, we report that 2OA-treated DKO mice fed HFD had significantly exacerbated cholangitis, leading to cirrhosis, with increased hepatic expression of Th1 cytokines/chemokines and hepatic fibrotic markers. Serum lithocholic acid (LCA) levels and the ratio of chenodeoxycholic acid (CDCA)-derived BAs to cholic acid-derived BAs were significantly increased by HFD. This was also associated with downregulated expression of key regulators of BA synthesis, including Cyp8b1, Cyp3a11, and Sult2a1. In addition, there were increases in the relative abundances of Acetatifactor and Lactococcus and decreases in Desulfovibrio and Lachnospiraceae_NK4A136_group, which corresponded to the abundances of CDCA and LCA. In conclusion, HFD and HFD-induced alterations in the gut microbiota modulate BA composition and nuclear receptor activation, leading to cirrhotic change in this murine PBC model. These findings have significant implications for understanding the progression of human PBC.
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Ácidos y Sales Biliares , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Cirrosis Hepática Biliar , Ratones Noqueados , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Microbioma Gastrointestinal/inmunología , Cirrosis Hepática Biliar/etiología , Cirrosis Hepática Biliar/metabolismo , Cirrosis Hepática Biliar/inmunología , Ácidos y Sales Biliares/metabolismo , Humanos , Hígado/metabolismo , Hígado/patología , Esteroide 12-alfa-Hidroxilasa/metabolismo , Esteroide 12-alfa-Hidroxilasa/genética , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/inmunología , Familia 2 del Citocromo P450/metabolismo , Familia 2 del Citocromo P450/genética , Colangitis/etiología , Colangitis/metabolismo , Colangitis/inmunología , Ratones Endogámicos C57BL , Ácidos Grasos MonoinsaturadosRESUMEN
BACKGROUND/AIM: The porous glass membrane pumping emulsification device enhances local therapeutic effects of transarterial chemoembolization for hepatocellular carcinoma (HCC); however, limited clinical outcomes have been reported. This study aimed to investigate the efficacy and safety of transarterial chemoembolization using the glass membrane pumping emulsification device for HCC. PATIENTS AND METHODS: Between 2019 and 2023, 58 patients (median age=73 years) with unresectable HCC underwent 73 transarterial chemoembolizations using the glass membrane pumping emulsification device at the Nagoya University Hospital. Treatment effects were assessed using contrast-enhanced computed tomography 1-3 months after therapy and every 2-3 months thereafter. RESULTS: The median size of treated tumors was 25.5 mm (45 solitary nodules). The median dosage of ethiodized oil mixed with the epirubicin solution was 3 ml. Complete and partial response were observed in 73% and 11% of patients, respectively. Local control rates at 6 and 12 months were 82.8% and 59.8%, respectively. The median time to recurrence after treatment was 581 days. No major treatment-related complications occurred. The number of tumors and therapeutic effects of the initial transarterial chemoembolization were significantly associated with better local control. CONCLUSION: The glass membrane pumping emulsification device facilitated the accumulation of more concentrated ethiodized oil within the tumor and effective local control.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Vidrio , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/instrumentación , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Porosidad , Epirrubicina/administración & dosificación , Emulsiones , Aceite Etiodizado/administración & dosificación , AdultoRESUMEN
Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.
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OBJECTIVE: To establish the Minimal Clinically Important Differences (MCIDs) for lower limb strength measured by the Motricity Index (LLMI) and trunk function assessed by the Trunk Control Test (TCT) in the acute phase of stroke in older patients. Further, the study sought to determine the cutoff values predicting functional prognosis at discharge for both the LLMI and TCT. METHODS: This prospective cohort study was conducted for older patients (≥65 years) admitted for acute stroke, receiving guideline-based stroke care that includes early rehabilitation. The LLMI and TCT were measured within 7 days of admission and at discharge. The MCID was derived from receiving operating characteristic curves, based on a ≥ 1 point shift in the modified Rankin Scale (mRS) from admission to discharge. A good functional prognosis at discharge was defined as an mRS score of ≤ 3. RESULTS: A total of 201 older patients with acute stroke were included. The TCT achieved an MCID of 13 (area under the curve [AUC] = 0.704, 95% confidence interval [CI]: 0.633-0.775), whereas the LLMI lacked the precision to produce a significant MCID. The optimal cutoff points for predicting a good outcome were found to be an LLMI score of 65 (AUC = 0.770, 95% CI: 0.705-0.835) and a TCT score of 25 (AUC = 0.827, 95% CI: 0.768-0.887) upon admission. CONCLUSIONS: This study identified a valid MCID for the TCT, failed to do so for the LLMI, and established cutoff values for both the LLMI and TCT that can predict good outcomes in older patients with acute stroke.
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BACKGROUND & AIMS: Steatotic liver disease (SLD) is often detected in health examinations. However, although individuals with metabolic dysfunction-associated SLD (MASLD) may have decreased bone mineral density (BMD), the specific risk factors remain unclarified. The objective of this study was to identify the factors associated with decreased BMD in patients with MASLD. METHODS: Individuals who underwent abdominal ultrasonography and BMD measurements at our healthcare center were included. The BMD of the calcaneus was assessed using an AOS-10SA bone densitometer. Decreased BMD was defined as a T-score below -1.0 SD or the administration of osteoporosis treatment. SLD was diagnosed based on specific ultrasonographic criteria. RESULTS: A total of 1410 patients were diagnosed with MASLD. The median age was 52 years. Multivariate analysis using a logistic regression model revealed that the independent predictors of decreased BMD were a low body mass index (BMI) or a small waist circumference (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.34-0.67), hypertriglyceridemia (OR: 1.29, 95% CI: 1.00-1.65), and a weak grip strength (OR: 0.98, 95% CI: 0.97-1.00). Subgroup analyses of individuals aged 50 years or older, men, and individuals with a FIB-4 index of 1.3 or greater revealed that the absence of a high BMI or a large waist circumference was associated with decreased BMD. The subgroup analysis of men revealed that a weaker grip strength was associated with decreased BMD. CONCLUSION: The present study suggested several potential risk factors for decreased BMD in patients with MASLD. Individuals with the abovementioned risk factors should be encouraged to undergo BMD measurement from the perspective of preventive medicine.
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Índice de Masa Corporal , Densidad Ósea , Hígado Graso , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Transversales , Factores de Riesgo , Hígado Graso/fisiopatología , Hígado Graso/complicaciones , Adulto , Anciano , Osteoporosis/fisiopatología , Osteoporosis/etiología , Osteoporosis/epidemiología , Circunferencia de la Cintura , Ultrasonografía/métodos , Hipertrigliceridemia/complicaciones , Fuerza de la Mano , Absorciometría de FotónRESUMEN
BACKGROUND: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. AIMS: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. METHODS: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. RESULTS: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. CONCLUSIONS: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.
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Anticuerpos Monoclonales , Enfermedad de Crohn , Células Caliciformes , Interleucina-18 , Interleucina-18/metabolismo , Interleucina-18/inmunología , Animales , Células Caliciformes/inmunología , Células Caliciformes/patología , Células Caliciformes/efectos de los fármacos , Humanos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Ratones , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Masculino , Modelos Animales de Enfermedad , Colitis/inmunología , Colitis/tratamiento farmacológico , Adulto , Ratones Endogámicos C57BLRESUMEN
Background: No actual data on spinal fusion and management of osteoporosis in Japan have been reported. The aim of the survey was to investigate pre- and post-operative management of osteoporosis, including testing and prescription, in elderly patients undergoing spinal fusion in Japan. Methods: Medical data on patients aged 65 years or older undergoing spinal fusion from April 2018 to March 2022 were extracted from the medical data vision (MDV) database containing health insurance claims data from Japanese acute care hospitals to investigate fusion area, pre- and post-operative osteoporosis tests (bone mineral density and osteoporosis markers), prescriptions of osteoporosis medications, and other information. Results: The analysis set consisted of 26,959 patients. Annual pre-operative BMD testing rates and osteoporosis markers testing rates were higher than the post-operative rates without significant annual changes. The post-operative prescription rate of osteoporosis medications throughout the target period was approximately two times higher than the preoperative rate. The drug with highest pre- and post-operative prescription rates was teriparatide (TPTD) followed by bisphosphonates, showing that the prescription rate of TPTD proportionally increased with the length of fusion area. Conclusions: It was suggested that patients aged 65 years or older undergoing spinal fusion might receive insufficient osteoporosis tests. Despite no trend in the testing rate with the length of fusion area, some tendency was observed in the selection of osteoporosis medications. In patients with osteoporosis undergoing spinal fusion, early examination, diagnosis, and therapeutic intervention may improve the prognoses, and solid testing and prescriptions are therefore expected.
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The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder (n = 28) and non-responder (n = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of Bacteroides stercoris and Parabacteroides merdae was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
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Silver nanoparticles (AgNPs) hold great promise for several different applications, from colorimetric sensors to antimicrobial agents. Despite their widespread incorporation in consumer products, limited understanding of the detrimental effects and cellular antioxidant responses associated with AgNPs at sublethal concentrations persists, raising concerns for human and ecological well-being. To address this gap, we synthesized AgNPs of varying sizes and evaluated their cytotoxicity against human dermal fibroblasts (HDF). Our study revealed that toxicity of AgNPs is a time- and size-dependent process, even at low exposure levels. AgNPs exhibited low short-term cytotoxicity but high long-term impact, particularly for the smallest NPs tested. Raman microspectroscopy was employed for in-time investigations of intracellular molecular variations during the first 24 h of exposure to AgNPs of 35 nm. Subtle protein and lipid degradations were detected, but no discernible damage to the DNA was observed. Signals associated with antioxidant proteins, such as superoxide dismutase (SOD), catalase (CAT) and metallothioneins (MTs), increased over time, reflecting the heightened production of these defense agents. Fluorescence microscopy further confirmed the efficacy of overexpressed antioxidant proteins in mitigating ROS formation during short-term exposure to AgNPs. This work provides valuable insights into the molecular changes and remedial strategies within the cellular environment, utilizing Raman microspectroscopy as an advanced analytical technique. These findings offer a novel perspective on the cytotoxicity mechanism of AgNPs, contributing to the development of safer materials and advice on regulatory guidelines for their biomedical applications.
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Antioxidantes , Fibroblastos , Nanopartículas del Metal , Plata , Espectrometría Raman , Superóxido Dismutasa , Plata/química , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/citología , Superóxido Dismutasa/metabolismo , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Metalotioneína/metabolismo , Especies Reactivas de Oxígeno/metabolismoAsunto(s)
Cálculos , Colangiopancreatografia Retrógrada Endoscópica , Enfermedades Pancreáticas , Conductos Pancreáticos , Humanos , Conductos Pancreáticos/cirugía , Conductos Pancreáticos/diagnóstico por imagen , Cálculos/cirugía , Cálculos/diagnóstico por imagen , Cálculos/terapia , Enfermedades Pancreáticas/cirugía , Enfermedades Pancreáticas/diagnóstico por imagen , Dilatación/instrumentación , Masculino , Femenino , Persona de Mediana EdadRESUMEN
AIM: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. METHODS: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). RESULTS: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. CONCLUSION: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.
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BACKGROUND: The modified Rankin scale (mRS) is extensively used for premorbid evaluation in patients with stroke; however, its limited capacity to assess functional status highlights the need for additional indicators such as frailty. AIMS: This study aimed to assess the impact of the premorbid mRS score and frailty on daily living (ADL) activities at hospital discharge, focusing on varying stroke severities. METHODS: This single-centre, prospective cohort study included patients with acute stroke aged ≥60 years. Key metrics included the frailty index for frailty assessment or mRS for functional status premorbid and the functional independence measure of the motor domain (FIM-M) at discharge for ADL outcomes. The patients were categorized into mild (0-4), moderate (5-15), and severe (16-42) groups based on the National Institute of Health Stroke Scale. Multiple hierarchical linear regression analyses were performed for each group to evaluate the influence of mRS and frailty on FIM-M scores. RESULTS: In the mild stroke group, significant associations were observed with premorbid mRS3 (ß = -0.183, p = 0.004), mRS4 (ß = -0.234, p < 0.001), and frailty status (ß = -0.227, p = 0.005) and FIM-M scores. Premorbid frailty did not show a significant association with the FIM-M scores in the moderate or severe stroke group. Frailty status notably contributed to changes in R², particularly in the mild stroke group (R² change = 0.031, p = 0.002). However, such changes were not evident in the other stroke severity groups. CONCLUSION: This study emphasizes the importance of incorporating frailty assessments into premorbid evaluations, particularly when considering ADL outcomes in patients with mild stroke. Conversely, the significance of frailty in moderate-to-severe stroke was less evident.
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Actividades Cotidianas , Fragilidad , Evaluación Geriátrica , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular , Humanos , Anciano , Masculino , Femenino , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Persona de Mediana Edad , Evaluación Geriátrica/métodos , Anciano de 80 o más Años , Rehabilitación de Accidente Cerebrovascular/métodos , Estado Funcional , Anciano Frágil/estadística & datos numéricosRESUMEN
We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.
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Novel functional biomaterials are expected to bring about breakthroughs in developing immunotherapy and regenerative medicine through their application as drug delivery systems and scaffolds. Nanogels are defined as nanoparticles with a particle size of 100 nm or less and as having a gel structure. Nanogels have a three-dimensional network structure of cross-linked polymer chains, which have a high water content, a volume phase transition much faster than that of a macrogel, and a quick response to external stimuli. As it is possible to transmit substances according to the three-dimensional mesh size of the gel, a major feature is that relatively large substances, such as proteins and nucleic acids, can be taken into the gel. Furthermore, by organizing nanogels as a building block, they can be applied as a scaffold material for tissue regeneration. This review provides a brief overview of the current developments in nanogels in general, especially drug delivery, therapeutic applications, and tissue engineering. In particular, polysaccharide-based nanogels are interesting because they have excellent complexation properties and are highly biocompatible.
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AIM: How possible sarcopenia affects functional prognosis in patients with premorbid disability remains unclear. This study aimed to compare and investigate the impact of possible sarcopenia at admission on functional outcomes at discharge in patients with acute stroke with and without premorbid disability. METHODS: This cohort study enrolled patients who were consecutively admitted to a single center for acute stroke. Calf circumference and grip strength were measured within 7 days of admission, and possible sarcopenia was determined using the Asian Working Group for Sarcopenia 2019 criteria. The Functional Independence Measure (FIM) score at discharge during the acute phase was the primary outcome. To examine the impact of possible sarcopenia on FIM scores at discharge, patients were divided into two groups according to being with or without premorbid disability according to the modified Rankin Scale, and multiple linear regression analysis was performed in each group. RESULTS: This study included 456 patients with acute stroke (median age, 80 years). In the premorbid-disability group (n = 166), possible sarcopenia was present in 140 patients (84%). Patients without possible sarcopenia had significantly higher FIM scores at discharge compared with those with possible sarcopenia (P < 0.001). However, multiple linear regression analysis showed that possible sarcopenia was not associated with FIM scores at discharge in the premorbid-disability group (ß = -0.054, P = 0.346). CONCLUSIONS: The results of this study demonstrated that a high rate of possible sarcopenia was observed in patients with stroke with premorbid disability; however, this did not affect functional prognosis. Geriatr Gerontol Int 2024; 24: 359-363.