RESUMO
Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.
Assuntos
Histona Desacetilases , Fibrose Peritoneal , Animais , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/patologia , Camundongos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Peritônio/metabolismoRESUMO
This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.
Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Ligantes , Rim , Células Epiteliais , Artéria Renal , Hipóxia , Receptores CCR6/genética , Quimiocina CCL20/genéticaRESUMO
BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed. Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. RESULTS: The mean follow-up duration was 27.5 months (range, 4.1-43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3-20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = -1.746) and those of PD-L1 and EZH1 (R2 linear = -2.118); these relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. CONCLUSION: These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.
Assuntos
Glioblastoma , Histonas , Humanos , Antígeno CTLA-4/genética , Antígeno B7-H1 , Lisina , Prognóstico , Antígenos CD28 , Glioblastoma/diagnóstico , Glioblastoma/genética , Epigênese Genética , Estudos Retrospectivos , Linfócitos TRESUMO
Signal transducer and activator of transcription 3 (STAT3) is a pivotal mediator of IL-6-type cytokine signaling. However, the roles of its full-length and truncated isoforms in acute kidney injury (AKI) and its transition to chronic kidney disease (CKD) remain elusive. Herein, the role of STAT3 isoforms in the AKI-to-CKD transition was characterized using an ischemia-reperfusion injury (IRI) mouse model. The STAT3 inhibitor Stattic was administered to C57BL/6 mice 3 h before IRI. Intrarenal cytokine expression was quantified using real-time PCR and FACS. The effect of Stattic on human tubular epithelial cells cultured under hypoxic conditions was also evaluated. Phosphorylated (p)STAT3 isoforms were detected by Western blot analysis. Stattic treatment attenuated IRI-induced tubular damage and inflammatory cytokine/chemokine expression while decreasing macrophage infiltration and fibrosis in mouse unilateral IRI and unilateral ureteral obstruction models. Similarly, in vitro STAT3 inhibition downregulated fibrosis and apoptosis in 72-h hypoxia-induced human tubular epithelial cells and reduced pSTAT3α-mediated inflammation. Moreover, pSTAT3 expression was increased in human acute tubular necrosis and CKD tissues. STAT3 activation is associated with IRI progression, and STAT3α may be a significant contributor. Hence, STAT3 may affect the AKI-to-CKD transition, suggesting a novel strategy for AKI management with STAT3 inhibitors.NEW & NOTEWORTHY We found that IRI increased expression of STAT3 in murine kidneys, along with inflammation markers. Through the investigation of the role of STAT3 in the AKI-to-CKD transition mechanism using mouse unilateral IRI and unilateral ureteral obstruction models and 24- or 72-h hypoxic induction of primary cultured human tubular epithelial cells, we found that STAT3 could affect the AKI-to-CKD transition. We also observed different degrees of expression in STAT3 isoforms in these processes.
Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Traumatismo por Reperfusão , Obstrução Ureteral , Injúria Renal Aguda/patologia , Animais , Citocinas/metabolismo , Fibrose , Inflamação/metabolismo , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência Renal Crônica/patologia , Traumatismo por Reperfusão/patologia , Fator de Transcrição STAT3/metabolismo , Obstrução Ureteral/patologiaRESUMO
Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-α. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.
Assuntos
Biomarcadores/metabolismo , Glomerulonefrite por IGA/patologia , Glicina/urina , Metaboloma , Adulto , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: This study aimed to compare the characteristics of patients with spontaneous thalamic hemorrhage (STH) accompanied by intraventricular hemorrhage (IVH) with those of patients without IVH. METHODS: The medical records of consecutive patients with STH admitted to our institute between January 2000 and December 2018 were reviewed retrospectively. The laboratory and radiological results, mortality, and functional recovery were compared between the STH patients with IVH and those without IVH. RESULTS: Among 2,389 patients with spontaneous intracerebral hemorrhage, 233 (9.8%) patients were included in this study. Concurrent IVH was detected in 159 (68.2%) patients with STH, and more frequently in those with body mass index ≥ 25, Glasgow Coma Scale score of 3-8, underlying disease, family history of stoke, posterior/medial/global location of hematoma, ventriculomegaly, large volume of hemorrhage, and midline shift ≥ 5 mm. The 3-month mortality was 25.8% and 8.1% (P = 0.039), the rate of good functional recovery at 6 months was 52.2% and 31.0% (P = 0.040), and incidence of delayed normal pressure hydrocephalus (NPH) at 12 months was 10.8% and 24.5% (P = 0.062) in the STH patients with IVH and those without IVH, respectively. At 12 months, delayed NPH developed in 28 of 47 (59.6%) patients who received external ventricular drainage (EVD)-based treatment, 5 of 45 (11.1%) patients who underwent endoscopic evacuation-based treatment, and 8 of 45 (17.8%) patients who underwent other surgeries. CONCLUSION: Concurrent IVH is strongly associated with mortality in patients with STH. Delayed NPH may develop more frequently in STH patients with IVH who were treated with EVD.
Assuntos
Hemorragia Cerebral/patologia , Hemorragia Cerebral Intraventricular/patologia , Adulto , Índice de Massa Corporal , Hemorragia Cerebral/complicações , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral Intraventricular/complicações , Hemorragia Cerebral Intraventricular/mortalidade , Hemorragia Cerebral Intraventricular/cirurgia , Drenagem , Feminino , Escala de Coma de Glasgow , Humanos , Hidrocefalia/complicações , Hidrocefalia/diagnóstico , Hidrocefalia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Background and Objective: Procedural thromboembolism after a mechanical thrombectomy (MT) for an acute ischemic stroke (AIS) has rarely been studied. It may occur from the artery-to-artery embolization of atherosclerotic plaque in the aortic arch. We investigated the relationship between aortic arch calcification (AoAC) on a chest X-ray and procedural thromboembolism on diffusion-weighted imaging (DWI) after an MT. Materials and Methods: From January 2017 to December 2020, 131 patients underwent DWI within two days following an MT for an AIS. Procedural thromboembolism was defined as new DWI-positive lesions in other territories from the occluded artery on DWI within two days after MT. Results: Procedural thromboembolism was observed in 30 (22.9%) patients. Procedural thromboembolism was associated with old age (72.3 ± 9.44 vs. 65.7 ± 12.8 years, p = 0.003), a longer procedural time (77.6 ± 37.6 vs. 60.1 ± 29.7 min, p = 0.024), and AoAC (calcification (73.3%) vs. no calcification (29.7%), p < 0.001). Multivariable logistic regression analysis showed that procedural thromboembolism was independently associated with AoAC (adjusted odds ratio (OR): 6.107, adjusted 95% confidence interval (CI): 2.374-15.705, p < 0.001) and a longer procedural time (adjusted OR: 1.015, adjusted 95% CI: 1.001-1.030, p = 0.031). Conclusions: Procedural thromboembolism after an MT for an AIS was related to AoAC on a chest X-ray and a longer procedural time. Our results suggest that although rapid recanalization is the most crucial goal of an MT for an AIS, the importance of the careful advance of the guiding catheter through the aortic arch should not be underestimated to reduce the risk of procedural thromboembolism, especially in patients with AoAC on a chest X-ray.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Tromboembolia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Trombectomia , Tromboembolia/etiologia , Resultado do Tratamento , Raios XRESUMO
Chemokine receptor 5 (CCR5) is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade. We investigated the role of CCR5 in experimental ischaemic-reperfusion injury (IRI) pathogenesis. To establish IRI, we clamped the bilateral renal artery pedicle for 30 min and then reperfused the kidney. We performed adoptive transfer of lipopolysaccharide (LPS)-treated RAW 264.7 macrophages following macrophage depletion in mice. B6.CCR5-/- mice showed less severe IRI based on tubular epithelial cell apoptosis than did wild-type mice. CXCR3 expression in CD11b+ cells and inducible nitric oxide synthase levels were more attenuated in B6.CCR5-/- mice. B6.CCR5-/- mice showed increased arginase-1 and CD206 expression. Macrophage-depleted wild-type mice showed more injury than B6.CCR5-/- mice after M1 macrophage transfer. Adoptive transfer of LPS-treated RAW 264.7 macrophages reversed the protection against IRI in wild-type, but not B6.CCR5-/- mice. Upon knocking out CCR5 in macrophages, migration of bone marrow-derived macrophages from wild-type mice towards primary tubular epithelial cells with recombinant CCR5 increased. Phospho-CCR5 expression in renal tissues of patients with acute tubular necrosis was increased, showing a positive correlation with tubular inflammation. In conclusion, CCR5 deficiency favours M2 macrophage activation, and blocking CCR5 might aid in treating acute kidney injury.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Antagonistas dos Receptores CCR5/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Receptores CCR5/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/patologia , Transferência Adotiva , Animais , Biomarcadores , Biópsia , Citocinas/metabolismo , Imuno-Histoquímica , Imunofenotipagem , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Knockout , Células RAW 264.7 , Receptores CCR5/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Background and objective: Procedural thromboembolisms after mechanical thrombectomy (MT) for acute ischemic stroke has rarely been studied. We retrospectively evaluated factors associated with procedural thromboembolisms after MT using diffusion-weight imaging (DWI) within 2 days of MT. Materials and Methods: From January 2018 to March 2020, 78 patients with acute ischemic stroke who underwent MT were evaluated using DWI. Procedural thromboembolisms were defined as new cerebral infarctions in other territories from the occluded artery on DWI after MT. Results: Procedural thromboembolisms were observed on DWI in 16 patients (20.5%). Procedural thromboembolisms were associated with old age (73.8 ± 8.18 vs. 66.8 ± 11.2 years, p = 0.021), intravenous (IV) thrombolysis (12 out of 16 (75.0%) vs. 25 out of 62 (40.3%), p = 0.023), heparinization (4 out of 16 (25.0%) vs. 37 out of 62 (59.7%), p = 0.023), and longer procedural time (90.9 ± 35.6 vs. 64.4 ± 33.0 min, p = 0.006). Multivariable logistic regression analysis revealed that procedural thromboembolisms were independently associated with procedural time (adjusted odds ratio (OR); 1.020, 95% confidence interval (CI); 1.002-1.039, p = 0.030) and IV thrombolysis (adjusted OR; 4.697, 95% CI; 1.223-18.042, p = 0.024). The cutoff value of procedural time for predicting procedural thromboembolisms was ≥71 min (area under the curve; 0.711, 95% CI; 0.570-0.851, p = 0.010). Conclusions: Procedural thromboembolisms after MT for acute ischemic stroke are significantly associated with longer procedural time and IV thrombolysis. This study suggests that patients with IV thrombolysis and longer procedural time (≥71 min) are at a higher risk of procedural thromboembolisms after MT for acute ischemic stroke.
Assuntos
AVC Isquêmico/cirurgia , Trombectomia/efeitos adversos , Tromboembolia/etiologia , Idoso , Feminino , Humanos , AVC Isquêmico/complicações , Masculino , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/métodos , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Trombectomia/métodos , Resultado do TratamentoRESUMO
Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 in PF using patient samples along with mouse and cell-based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure (P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate-induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human peritoneal mesothelial cells (HPMCs), transforming growth factor-ß treatment increased ST2, fibronectin, ß-galactosidase and Snail protein levels and decreased E-cadherin level. Anti-ST2 antibody administration reversed the up-regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose (100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.
Assuntos
Glucose/toxicidade , Proteína 1 Semelhante a Receptor de Interleucina-1/antagonistas & inibidores , Fibrose Peritoneal/patologia , Fator de Crescimento Transformador beta/toxicidade , Animais , Células Cultivadas , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Epitélio/patologia , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Diálise Peritoneal , Peritônio/patologia , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
OBJECTIVE: The Act on Life-Sustaining Treatment (LST) decisions for end-of-life patients has been effective since February 2018. An increasing number of patients and their families want to withhold or withdraw from LST when medical futility is expected. This study aimed to investigate the status of the Act on LST decisions for patients with acute cerebrovascular disease at a single hospital. METHODS: Between January 2017 and December 2021, 227 patients with acute cerebrovascular diseases, including hemorrhagic stroke (n=184) and ischemic stroke (n=43), died at the hospital. The study period was divided into the periods before and after the Act. RESULTS: The duration of hospitalization decreased after the Act was implemented compared to before (15.9±16.1 vs. 11.2±18.6 days, p=0.127). The rate of obtaining consent for the LST plan tended to increase after the Act (139/183 [76.0%] vs. 27/44 [61.4%], p=0.077). Notably, none of the patients made an LST decision independently. Ventilator withdrawal was more frequently performed after the Act than before (52/183 [28.4%] vs. 0/44 [0%], p<0.001). Conversely, the rate of organ donation decreased after the Act was implemented (5/183 [2.7%] vs. 6/44 [13.6%], p=0.008). Refusal to undergo surgery was more common after the Act was implemented than before (87/149 [58.4%] vs. 15/41 [36.6%], p=0.021) among the 190 patients who required surgery. CONCLUSION: After the Act on LST decisions was implemented, the rate of LST withdrawal increased in patients with acute cerebrovascular disease. However, the decision to withdraw LST was made by the patient's family rather than the patient themselves. After the execution of the Act, we also observed an increased rate of refusal to undergo surgery and a decreased rate of organ donation. The Act on LST decisions may reduce unnecessary treatments that prolong end-of-life processes without a curative effect. However, the widespread application of this law may also reduce beneficial treatments and contribute to a decline in organ donation.
RESUMO
Mitochondrial dysfunction is linked to degenerative diseases, resulting from cardiolipin (CL)-induced disruption of cristae structure in the inner mitochondrial membrane (IMM); therefore, preserving cristae and preventing CL remodeling offer effective strategies to maintain mitochondrial function. To identify reactive oxygen species (ROS)-blocking agents against mitochondrial dysfunction, a library of cyclohexylamine-containing cell-penetrating α-helical amphipathic "bundle" peptides were screened. Among these, CMP3013 is selectively bound to abnormal mitochondria, preserving the cristae structure impaired by mitochondria-damaging agents. With a stronger affinity for CL compared with other IMM lipid components, CMP3013 exhibited high selectivity. Consequently, it protected cristae, reduced ROS production, and enhanced adenosine triphosphate (ATP) generation. In mouse models of acute kidney injury, a 1 mg/kg dose of CMP3013 demonstrated remarkable efficacy, highlighting its potential as a therapeutic agent for mitochondrial dysfunction-related disorders. Overall, CMP3013 represents a promising agent for mitigating mitochondrial dysfunction and associated diseases.
Assuntos
Cardiolipinas , Peptídeos Penetradores de Células , Fenilalanina/análogos & derivados , Camundongos , Animais , Cardiolipinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rim/metabolismoRESUMO
The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.
RESUMO
OBJECTIVE: With the recent increase in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the role of neurosurgeons in AIS treatment has become increasingly important. This study aimed to assess the outcomes of patients with AIS treated by neurosurgeons and neurologists in the emergency room (ER) of a tertiary hospital in South Korea. METHODS: From January 2020 to June 2021, 536 patients with AIS within 24 hours of symptom onset were admitted to our hospital via the ER. Based on the type of doctors who provided initial care for AIS in the ER, patients were divided into two groups : (a) neurosurgeon group (n=119, 22.2%) and (b) neurologist group (n=417, 77.8%). RESULTS: Intravenous tissue plasminogen activator (tPA) was administered in 82 (15.3%) of 536 patients (n=17 [14.3%] in the neurosurgeon group and n=65 [15.6%] in the neurologist group). The door-to-tPA time was not significantly different between both groups (median, 53 minutes; interquartile range [IQR], 45-58 vs. median, 54 minutes; IQR, 46-74; p=0.372). MT was performed in 69 patients (12.9%) (n=25, 36.2% in the neurosurgeon group and n=44, 63.8% in the neurologist group). The neurosurgeon group achieved a shorter door-to-puncture time than the neurologist group (median, 115 minutes; IQR, 107-151 vs. median, 162 minutes; IQR, 117-189; p=0.049). Good clinical outcomes (3-month modified Rankin Scale 0-2) did not differ significantly between the two groups (96/119 [80.7%] vs. 322/417 [77.2%], p=0.454). CONCLUSION: The neurosurgeon group showed similar door-to-treatment time and clinical outcomes to the neurologist group in patients with AIS in the ER. This study suggests that neurosurgeons have comparable abilities to care for patients with AIS in the ER.
RESUMO
BACKGROUND: Vascular conditions can affect the recanalization rates after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Chest radiography can assess the conditions of the aortic arch based on the presence or absence of aortic arch calcification (AoAC). The aim of this study was to investigate the relationship between AoAC on chest radiography and first-pass successful recanalization (modified thrombolysis in cerebral infarction 2b/3 after the first-pass). METHODS: We compared the rate of first-pass successful recanalization between patients with and without AoAC. A total of 193 patients with anterior circulation occlusion who underwent EVT between January 2017 and December 2021 were included. RESULTS: AoAC was observed in 80 (41.5%) patients. Patients with AoAC were older (74.5 ± 7.78 vs. 63.9 ± 12.4 years, p < 0.001), had more EVT attempts (3.04 ± 1.95 vs. 2.01 ± 1.34 times, p < 0.001), and a longer procedural time (71.7 ± 31.2 vs. 48.7 ± 23.1 min, p < 0.001) than those without AoAC. Moreover, Patients with AoAC showed a lower incidence of first-pass successful recanalization (18.8% vs. 47.8%, p < 0.001) and a higher incidence of postprocedural hemorrhage (45.0% vs. 27.7%, p = 0.015) than those without AoAC. On multivariate analysis, AoAC was independently associated with first-pass successful recanalization (odds ratio: 0.239 [0.121-0.475], p < 0.001). CONCLUSIONS: AoAC on chest radiography can be used as a preoperative predictor of successful first-pass recanalization in patients undergoing EVT for AIS.
RESUMO
AIM: To compare an antiplatelet-preparation group with a no-preparation group to evaluate the effect of the antiplatelet preparation on procedural thromboembolism during endovascular thrombectomy (EVT) with diffusion-weighted imaging (DWI), retrospectively. MATERIAL AND METHODS: From January 2017 to April 2020, EVT was performed in 60 patients with cerebral infarction. Patients were categorized into the antiplatelet-preparation group (n=25) or the no-preparation group (n=35). Procedural thromboembolism was defined as new DWI-positive lesions in other areas of the occluded artery after EVT. RESULTS: The antiplatelet-preparation and no-preparation groups did not differ in the rate of procedural thromboembolism occurrence (6/25 [24.0%] vs. 6/35 [17.1%]; p=0.532). Procedural thromboembolism was associated with age (74.4 ± 6.95 years vs. 65.7 ± 12.9 years; p=0.028), atherosclerotic occlusion (66.7% vs. 29.2%; p=0.022), and procedural time (97.4 ± 45.7 min vs. 60.1 ± 28.8 min; p=0.001). Multivariable logistic regression analysis showed that factors affecting procedural thromboembolism during EVT for cerebral infarction were old age (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.009-1.273; p=0.035), atherosclerotic occlusion (OR, 7.434; 95% CI, 1.272-43.431; p=0.026), and longer procedural time (OR, 1.023; 95% CI, 1.001 - 1.046; p=0.006). CONCLUSION: The antiplatelet preparation had no significant protective effect on procedural thromboembolism during EVT for cerebral infarction. Old age, atherosclerotic occlusion, and longer procedural time were independent risk factors for procedural thromboembolism during EVT for cerebral infarction.
Assuntos
Procedimentos Endovasculares , Acidente Vascular Cerebral , Tromboembolia , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Procedimentos Endovasculares/efeitos adversos , Humanos , Estudos Retrospectivos , Trombectomia , Tromboembolia/diagnóstico por imagem , Resultado do TratamentoRESUMO
Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-ß, CCL8 was upregulated by rTGF-ß treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-ß-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.
Assuntos
Anticorpos Monoclonais , Quimiocina CCL8 , Insuficiência Renal Crônica , Obstrução Ureteral , Anticorpos Monoclonais/farmacologia , Células Cultivadas , Quimiocina CCL8/antagonistas & inibidores , Células Epiteliais , Fibrose , Humanos , Túbulos Renais/citologia , Insuficiência Renal Crônica/patologia , Obstrução Ureteral/complicaçõesRESUMO
OBJECTIVE: Microembolic infarcts are frequently observed on diffusion-weighted imaging (DWI) following endovascular treatment. We investigated DWI-positive lesions and symptomatic ischemic complications (SICs) in patients with ruptured and unruptured aneurysms following coiling and the relationship between DWI-positive lesions and antithrombotic drugs. METHODS: Between January 2016 and December 2020, 83 patients underwent DWI within 48 h following endovascular treatment for ruptured (n=30) and unruptured (n=53) aneurysms. RESULTS: The overall rate of DWI-positive lesions was 55.4%. There were no significant differences in the occurrence rate (45.3% vs. 43.3%, p=1.000) and the number of lesions (2.7±4.6 vs. 4.0±5.3, p=0.237) between unruptured and ruptured aneurysms. SIC occurred more frequently in patients with ruptured aneurysms than unruptured ones (20.0% vs. 1.9%, p=0.015). The cutoff value of DWI-positive lesions for predicting SIC was 5 (sensitivity 100%, specificity 78.9%). The procedure time was significantly longer in patients with DWI-positive lesions ≥5 than those with DWI-positive lesions <5 (104.1±43.8 vs. 85.1±30.8 min, p=0.030). Patients with DWI-positive lesions <5 were more frequently observed in the postprocedural heparinization group than in the no heparinization group (85.7% vs. 58.5%, p=0.012). CONCLUSIONS: The incidence of DWI-positive lesions did not differ significantly between the ruptured and unruptured aneurysms. However, SIC occurred more frequently in patients with ruptured aneurysms. Longer procedure time is a risk factor for DWI-positive lesions, and postprocedural heparinization seems to reduce the incidence of DWI-positive lesions.
RESUMO
OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic is affecting the characteristics of patients with head injuries. This study aimed to evaluate the effect of the COVID-19 pandemic on patients with head injuries at a regional emergency medical center in South Korea. METHODS: From April 2019 to November 2020, 350 patients with head injuries were admitted to our hospital. The study period was divided into the pre-COVID-19 (n=169) and COVID-19 (n=181) eras (10 months each). Patients with severe head injuries requiring surgery (n=74) were categorized into those who underwent surgery (n=41) and those who refused surgery (n=33). RESULTS: Head injuries in pediatric patients (<3 years) were more frequent in the COVID-19 era than in the pre-COVID-19 era (8.8% vs. 3.6%, p=0.048). More patients refused surgery in the COVID-19 era than in the pre-COVID-19 era (57.9% vs. 30.6%, p=0.021). Refusal of surgery was associated with old age (67.7±14.5 vs. 52.4±19.1, p<0.001), marital status (married, 84.8% vs. 61.0%, p=0.037), unemployment (42.4% vs. 68.3%, p=0.034), COVID-19 era (66.7% vs. 39.0%, p=0.021), and lower Glasgow coma scale scores (6.12±3.08 vs. 10.6±3.80, p<0.001). Multivariable logistic regression analysis revealed that refusal of surgery was independently associated with old age (adjusted odds ratio [OR], 1.084; 95% confidence interval [CI], 1.030-1.140; p=0.002), COVID-19 era (adjusted OR, 6.869; 95% CI, 1.624-29.054; p=0.009), and lower Glasgow coma scale scores (adjusted OR, 0.694; 95% CI, 0.568-0.848; p<0.001). CONCLUSION: We observed an increased prevalence of head injuries in pediatric patients (<3 years) during the COVID-19 pandemic. Additionally, among patients with severe head injuries requiring surgery, more patients refused to undergo surgery during the COVID-19 pandemic.
RESUMO
Procedural thromboembolism after coil embolization of a cerebral aneurysm can occur because of fragmented atherosclerotic plaques in the aortic arch. The purpose of this study was to investigate the relationship between aortic arch calcification (AoAC) observed using preoperative chest X-ray and procedural thromboembolisms after coil embolization of cerebral aneurysms. Between January 2019 and December 2020, 66 patients underwent coil embolization for cerebral aneurysms at our hospital. AoAC was assessed based on the presence of calcification using a preoperative chest X-ray. A procedural thromboembolism was defined as a new positive lesion on diffusion-weighted imaging within 7 days post-procedure. A procedural thromboembolism occurred in 34 (51.5%) patients. The thromboembolism was associated with AoAC (calcification [52.9%] vs. no calcification [6.3%], p < 0.001), aneurysm type (aneurysm with incorporated branches [63.9%] vs. sidewall aneurysm [36.7%], p = 0.047), and a longer procedural time (100.2 ± 34.1 min vs. 79.7 ± 24.9 min, p = 0.007). Multivariable logistic regression analysis showed that AoAC (adjusted odds ratio [OR], 23.566; adjusted 95% confidence interval [CI], 3.921-141.654; p = 0.001) and aneurysm type (adjusted OR, 5.501; adjusted 95% CI, 1.455-20.799; p = 0.012) were independent risk factors for procedural thromboembolism. AoAC on preoperative chest X-ray was associated with a significant increase in the procedural thromboembolism rate. Our study suggests that a procedural thromboembolism after coil embolization of cerebral aneurysms might result primarily from fragmented atherosclerotic plaques in the aortic arch. Preoperative chest X-ray could be a useful tool to predict the risk of procedural thromboembolisms.