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BACKGROUND: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. METHODS: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. RESULTS: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. CONCLUSION: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.
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BACKGROUND: We previously identified ezetimibe, an inhibitor of Niemann-Pick C1-like intracellular cholesterol transporter 1 and European Medicines Agency-approved lipid-lowering agent, as a potent autophagy activator. However, its efficacy against pulmonary fibrosis has not yet been evaluated. This study aimed to determine whether ezetimibe has therapeutic potential against idiopathic pulmonary fibrosis. METHODS: Primary lung fibroblasts isolated from both humans and mice were employed for mechanistic in vitro experiments. mRNA sequencing of human lung fibroblasts and gene set enrichment analysis were performed to explore the therapeutic mechanism of ezetimibe. A bleomycin-induced pulmonary fibrosis mouse model was used to examine in vivo efficacy of the drug. Tandem fluorescent-tagged microtubule-associated protein 1 light chain 3 transgenic mice were used to measure autophagic flux. Finally, the medical records of patients with idiopathic pulmonary fibrosis from three different hospitals were reviewed retrospectively, and analyses on survival and lung function were conducted to determine the benefits of ezetimibe. RESULTS: Ezetimibe inhibited myofibroblast differentiation by restoring the mechanistic target of rapamycin complex 1-autophagy axis with fine control of intracellular cholesterol distribution. Serum response factor, a potential autophagic substrate, was identified as a primary downstream effector in this process. Similarly, ezetimibe ameliorated bleomycin-induced pulmonary fibrosis in mice by inhibiting mechanistic target of rapamycin complex 1 activity and increasing autophagic flux, as observed in mouse lung samples. Patients with idiopathic pulmonary fibrosis who regularly used ezetimibe showed decreased rates of all-cause mortality and lung function decline. CONCLUSION: Our study presents ezetimibe as a potential novel therapeutic for idiopathic pulmonary fibrosis.
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Anticolesterolemiantes , Autofagia , Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos , Ezetimiba , Fibrosis Pulmonar Idiopática , Ezetimiba/uso terapéutico , Ezetimiba/farmacología , Animales , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Humanos , Ratones , Autofagia/efectos de los fármacos , Masculino , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/farmacología , Femenino , Ratones Transgénicos , Bleomicina , Pulmón/patología , Pulmón/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Ratones Endogámicos C57BL , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Colesterol/metabolismoRESUMEN
Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.
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Neoplasias Gastrointestinales , Neoplasias Pancreáticas , Humanos , Pronóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/mortalidad , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Tracto Gastrointestinal/patologíaRESUMEN
Background: This study aimed to develop a machine learning-based 2-year risk prediction model for early identification of patients with rapid progressive immunoglobulin A nephropathy (IgAN). We also assessed the model's performance to predict the long-term kidney-related outcome of patients. Methods: A retrospective cohort of 1,301 patients with biopsy-proven IgAN from two tertiary hospitals was used to derive and externally validate a random forest-based prediction model predicting primary outcome (30% decline in estimated glomerular filtration rate from baseline or end-stage kidney disease requiring renal replacement therapy) and secondary outcome (improvement of proteinuria) within 2 years after kidney biopsy. Results: For the 2-year prediction of primary outcomes, precision, recall, area-under-the-curve, precision-recall-curve, F1, and Brier score were 0.259, 0.875, 0.771, 0.242, 0.400, and 0.309, respectively. The values for the secondary outcome were 0.904, 0.971, 0.694, 0.903, 0.955, and 0.113, respectively. From Shapley Additive exPlanations analysis, the most informative feature identifying both outcomes was baseline proteinuria. When Kaplan-Meier analysis for 10-year kidney outcome risk was performed with three groups by predicting probabilities derived from the 2-year primary outcome prediction model (low, moderate, and high), high (hazard ratio [HR], 13.00; 95% confidence interval [CI], 9.52-17.77) and moderate (HR, 12.90; 95% CI, 9.92-16.76) groups showed higher risks compared with the low group. From the 2-year secondary outcome prediction model, low (HR, 1.66; 95% CI, 1.42-1.95) and moderate (HR, 1.42; 95% CI, 0.99-2.03) groups were at greater risk for 10-year prognosis than the high group. Conclusion: Our machine learning-based 2-year risk prediction models for the progression of IgAN showed reliable performance and effectively predicted long-term kidney outcome.
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OBJECTIVES: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that arise at various sites throughout the body. The gastroenteropancreatic (GEP) tract is the most common site of NETs. We investigated the clinicopathologic features of patients with GEP-NETs and the utility of digital image analysis, which was compared to eyeball estimation, a conventional method used to determine the Ki-67 labeling index. METHODS: The clinicopathologic data of GEP-NET patients at Gangnam Severance Hospital from January 2008 to October 2019 were retrospectively analyzed. Each case was reclassified according to the 2019 World Health Organization classification system, to which the classification of grade 3 was added. Comparisons between eyeball estimation and the digital image analysis method for Ki-67 index assessment were performed by calculating Cohen's kappa (k) coefficient. RESULTS: In total, 345 patients with GEP-NETs were enrolled. The mean age was 49.3 (range 13-79) years, with more male (61.1%) than female patients. The primary tumor sites were the rectum (70.1%), pancreas (12.5%), stomach (6.7%), and duodenum (5.8%). Overall, 298 (86.4%), 35 (10.1%), 2 (0.6%), and 10 (2.9%) patients exhibited grade 1, 2, and 3 and neuroendocrine carcinoma, respectively. Statistical analysis revealed that age > 50 years, tumor size > 2 cm, and presence of lymphovascular invasion, nodal metastasis, and distant metastasis were significantly associated with short overall survival. Additionally, 283 patients underwent digital image analysis of the Ki-67 index, and substantial agreement was found between the two methods (κ value: 0.765). CONCLUSIONS: Eyeball estimation revealed non-inferior results compared with digital image analysis. Further research is needed to evaluate the possibility of using digital image analysis as an alternative analysis method.
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This study investigated whether histopathological classification and histologic lesion scores could significantly and independently predict the progression to end-stage kidney disease (ESKD) in Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis-glomerulonephritis (AAV-GN). This study included 113 patients with AAV-GN confirmed by kidney biopsy. The glomerular, tubulointerstitial, and vascular lesions were systematically assessed using a scoring system. The scoring system was adopted from the Banff scoring system but also the Oxford study and the revision of the ISN/RPS. For comparison, the scores were classified into two groups; the low, and the high, and the difference was investigated between ESKD and non-ESKD groups using Cox proportional analysis. At diagnosis, the median age was 59.0 years and 33.6% were males. Of 113 patients, 44.2% had ESKD progression during follow-up. There were significant differences in several kidney-, inflammation-, and AAV-pathogenesis-related variables between AAV-GN patients with ESKD and those without. The sclerotic class exhibited the worst renal prognosis among the four histopathological classes. Among histopathological features, high interstitial fibrosis, tubular atrophy and global glomerulitis scores were significantly associated with ESKD progression. Whereas multivariable Cox analysis revealed only a high global glomerulitis score which means global endocapillary hypercellularity in a larger number of glomeruli is an independent predictor of ESKD progression. Moreover, among clinical and histopathological features, a high global glomerulitis score could also predict ESKD progression in addition to serum blood urea nitrogen and creatinine. This study demonstrated the worst renal prognosis for the sclerotic class and first discovered that a high global glomerulitis score was an independent predictor of ESKD in patients with AAV-GN.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glomerulonefritis , Fallo Renal Crónico , Masculino , Humanos , Persona de Mediana Edad , Femenino , Riñón , Fallo Renal Crónico/etiología , Glomerulonefritis/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , República de Corea/epidemiologíaRESUMEN
BACKGROUND: Free tissue transfer is the preferred method of reconstructing head and neck defects, with a success rate of approximately 95%. Although flap failure is uncommon, it has a major impact on patient morbidity and diminishes quality of life, making it is important to investigate the causes of flap failure. METHODS: This retrospective chart review analyzed patients who underwent free tissue transfer during head and neck reconstruction at a single institution between 2016 and 2021. RESULTS: During the study period, 58 patients underwent 60 free flap procedures. Revision surgery was needed in 14 patients. Subsequent free flap surgery was performed in one patient, and three free flaps (5%) could not be salvaged. Cardiovascular disease was significantly associated with flap failure, and venous congestion (thrombosis) was the most common reason for revision surgery. CONCLUSION: Cardiovascular disease clearly emerged as a factor related to the failure of free flap surgery, and this issue warrants particular attention in patients for whom free tissue transfer is planned.
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RATIONALE: The World Health Organization defines a perivascular epithelioid cell tumor (PEComa) as a mesenchymal neoplasia composed of perivascular epithelioid cells with characteristic morphological and immunohistochemical features. Although PEComas have the potential to behave in a malignant fashion, malignant PEComas are extremely rare. PATIENT CONCERNS: An 83-year-old man visited our clinic presented with palpable, painless, and movable mass in the right knee area. DIAGNOSES: Malignant PEComa was diagnosed by incisional biopsy. No metastases was confirmed by radiologic imaging including PET/CT, magnetic resonance imaging, high resolution computed tomography. INTERVENTIONS: We performed wide excision of the mass and used an anterolateral thigh free flap to reconstruct the defect on the right knee. OUTCOMES: The permanent histopathology showed malignant PEComa was totally resected. The flap which was performed to cover the defect was survived and the patient discharge without any complications. LESSONS: PEComa can metastasize to various anatomical regions. Although there is no established standardized treatment, radical resection is still considered the cornerstone of treatment. Rapid and appropriate defect coverage is important to improve the patient's prognosis.
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Colgajos Tisulares Libres , Neoplasias de Células Epitelioides Perivasculares , Masculino , Humanos , Anciano de 80 o más Años , Tomografía Computarizada por Tomografía de Emisión de Positrones , Articulación de la Rodilla/patología , Pronóstico , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirugía , Neoplasias de Células Epitelioides Perivasculares/patologíaRESUMEN
AIM: The prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and conflicting. The present study aims to investigate the potential role of CD274 (PD-L1) immunohistochemical overexpression as a prognostic marker in malignant tumours. METHODS: We searched PubMed, Embase and Web of Science from inception to December 2021 to identify potentially eligible studies. The pooled HRs with 95% CIs were calculated to identify the association between CD274 (PD-L1) overexpression and overall survival (OS), cancer-specific survival, disease-free survival, recurrence-free survival and progression-free survival in 10 lethal malignant tumours. Heterogeneity and publication bias were also analysed. RESULTS: The study included 57 322 patients from 250 eligible studies (241 articles). The meta-analysis by tumour type using multivariate HR revealed worse OS in non-small cell lung cancer (HR 1.41, 95% CI 1.19 to 1.68), hepatocellular carcinoma (HR 1.75, 95% CI 1.11 to 2.74), pancreatic cancer (HR 1.84, 95% CI 1.12 to 3.02), renal cell carcinoma (HR 1.55, 95% CI 1.12 to 2.14) and colorectal cancer (HR 1.46, 95% CI 1.14 to 1.88). Estimated HRs showed associations between CD274 (PD-L1) overexpression and worse prognosis across different types of tumours in various survival endpoints, but no inverse correlation was identified. The heterogeneity for most of the pooled results was high. CONCLUSIONS: This large meta-analysis suggests that CD274 (PD-L1) overexpression is a potential biomarker for multiple types of cancers. However, further studies are needed to reduce high heterogeneity. PROSPERO REGISTRATION NUMBER: CRD42022296801.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/análisis , PronósticoRESUMEN
The National Institutes of Health (NIH) lupus nephritis activity and chronicity indices, which comprise six activity scores and four chronicity scores, have a long development history. The 2018 revised International Society of Nephrology/Renal Pathology Society classification for lupus nephritis adopted the most recent NIH indices to replace subclasses A, C, and A/C. Although an evidence-based approach should further evaluate the clinical significance of the modified NIH indices, recent validation studies demonstrated that the modified chronicity indices have a strong correlation with kidney outcome of lupus nephritis.
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Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Animales , Ratones , Riñón , Transducción de Señal , Macrófagos , Factores de Transcripción NFATCRESUMEN
Current treatment strategies for autoimmune diseases may not sufficiently control aberrant metabolism in B-cells. To address this concern, we investigated a biguanide derivative, IM156, as a potential regulator for B-cell metabolism in vitro and in vivo on overactive B-cells stimulated by the pro-inflammatory receptor TLR-9 agonist CpG oligodeoxynucleotide, a mimic of viral/bacterial DNA. Using RNA sequencing, we analyzed the B-cell transcriptome expression, identifying the major molecular pathways affected by IM156 in vivo. We also evaluated the anti-inflammatory effects of IM156 in lupus-prone NZB/W F1 mice. CD19+B-cells exhibited higher mitochondrial mass and mitochondrial membrane potential compared to T-cells and were more susceptible to IM156-mediated oxidative phosphorylation inhibition. In vivo, IM156 inhibited mitochondrial oxidative phosphorylation, cell cycle progression, plasmablast differentiation, and activation marker levels in CpG oligodeoxynucleotide-stimulated mouse spleen B-cells. Interestingly, IM156 treatment significantly increased overall survival, reduced glomerulonephritis and inhibited B-cell activation in the NZB/W F1 mice. Thus, our data indicated that IM156 suppressed the mitochondrial membrane potentials of activated B-cells in mice, contributing to the mitigation of lupus activity. Hence, IM156 may represent a therapeutic alternative for autoimmune disease mediated by B-cell hyperactivity.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Ratones , Animales , Potencial de la Membrana Mitocondrial , Fosforilación Oxidativa , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfocitos B , Ratones Endogámicos NZB , Oligodesoxirribonucleótidos/farmacologíaRESUMEN
Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. The association of LOXL2 with epithelial-mesenchymal transformation-related molecules was also evaluated in vitro using HK-2 cells. The present data demonstrated that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro-sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023-treated group although it was not statistically significant. Following transforming growth factor-ß (TGF-ß) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-ß/Smad signalling pathway.
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BACKGROUND: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX). METHODS: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of DEX, respectively. Histological ALI score and pulmonary edema were assessed after 48 h. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1ß, IFN-γ, and TNFα were also assessed. RESULTS: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P < 0.001 for both) and SAH+DEX25 groups (P = 0.001 and P < 0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group. CONCLUSIONS: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.
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Lesión Pulmonar Aguda , Dexmedetomidina , Edema Pulmonar , Hemorragia Subaracnoidea , Animales , Masculino , Ratas , Lesión Pulmonar Aguda/prevención & control , Lesión Pulmonar Aguda/complicaciones , Autofagia , Dexmedetomidina/farmacología , Interleucina-6/uso terapéutico , FN-kappa B/metabolismo , Edema Pulmonar/prevención & control , Edema Pulmonar/complicaciones , Ratas Wistar , Transducción de Señal , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 9/metabolismoRESUMEN
BACKGROUND: Although the transcatheter closure of atrial septal defect was established as the treatment of choice several decades ago, the process of device neoendothelialization (NE) in humans is not well understood. We aimed to measure the extent of device NE using cardiac computed tomography angiography and analyze its risk factors. METHODS: Between January 2005 and February 2021, we retrospectively reviewed 164 devices of 112 patients on cardiac computed tomography angiography. We investigated device shape, contrast opacification within the device that differentiated device NE, and device-related thrombosis or vegetation. Risk factor analysis for major adverse cardiovascular events and incomplete NE according to the postprocedural period was performed. RESULTS: Seventy patients (62.5%) were women, with a median (range) age at the time of device closure of 44.5 (0.6-79.2) years. The mean (±SD) defect size was 16.6 (±7.8) mm, and patients were followed for 35.9±33.9 months. After 6 months of device implantation, 35% of the devices (42/120) had incomplete NE. The intensity of intradevice opacification shifted from complete to partial or nonopacification over time (P<0.001), and a similar pattern was observed in the shunt flow (P<0.001). The bulkiness of devices also decreased in proportion to the postprocedural period (P<0.001). Risk analysis revealed device diameter (hazard ratio, 1.18 [95% CI, 1.04-1.27]; P<0.001) as the only significant factor of incomplete NE and major adverse events. CONCLUSIONS: Incomplete NE of atrial septal defect devices was identified on cardiac computed tomography angiography in significant numbers after 6 months of the procedure. The device diameter was related to incomplete NE and major adverse events. Further prospective and multicenter studies are warranted to validate this new assessment of device NE.
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Angiografía por Tomografía Computarizada , Defectos del Tabique Interatrial , Cateterismo Cardíaco , Femenino , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/cirugía , Humanos , Masculino , Prótesis e Implantes , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Nephrin is a type-1 transmembrane protein and a component of the slit diaphragm renal-filtration barrier. It has several functions in actin remodeling and cell-cell adhesion. Nephrin is principally located in the kidney glomerulus, but several studies have reported that nephrin is found in the pancreas, brain, and placenta. However, nephrin expression and its role in human skin have not yet been reported. First, using single-cell RNA sequencing, immunohistochemistry, and immuno-electron microscopy, nephrin expression was confirmed in human-skin epidermal keratinocytes. Nephrin expression colocalized with the expression of zonula occludens-1 in keratinocytes and was closely related to keratinocyte cell density, proliferation, and migration. High glucose treatment decreased nephrin expression and compromised keratinocyte cell migration without yes-associated protein nuclear entry. This reduced cell migration under high glucose conditions was improved in nephrin-overexpressing keratinocytes. Nephrin was highly expressed on the margins of re-epithelized epidermis based on in vivo mice and ex vivo human skin wound models. The results demonstrate that nephrin is expressed in human-skin keratinocytes and functions in cell adhesion, proliferation, and migration. In conclusion, this study suggests that nephrin may have a variety of physiological roles in human skin.
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Epidermis , Queratinocitos , Animales , Movimiento Celular/fisiología , Epidermis/metabolismo , Glucosa/metabolismo , Humanos , Queratinocitos/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , RatonesRESUMEN
BACKGROUND: The International IgA Nephropathy Prediction Tool has been recently developed to estimate the progression risk of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the clinical performance of this prediction tool in a large IgAN cohort in Korea. METHODS: The study cohort was comprised of 2,064 patients with biopsy-proven IgAN from four medical centers between March 2012 and September 2021. We calculated the predicted risk for each patient. The primary outcome was occurrence of a 50% decline in estimated glomerular filtration rate (eGFR) from the time of biopsy or end-stage kidney disease. The model performance was evaluated for discrimination, calibration, and reclassification. We also constructed and tested an additional model with a new coefficient for the Korean race. RESULTS: During a median follow-up period of 3.8 years (interquartile range, 1.8-6.6 years), 363 patients developed the primary outcome. The two prediction models exhibited good discrimination power, with a C-statistic of 0.81. The two models generally underestimated the risk of the primary outcome, with lesser underestimation for the model with race. The model with race showed better performance in reclassification compared to the model without race (net reclassification index, 0.13). The updated model with the Korean coefficient showed good agreement between predicted risk and observed outcome. CONCLUSION: In Korean IgAN patients, International IgA Nephropathy Prediction Tool had good discrimination power but underestimated the risk of progression. The updated model with the Korean coefficient showed acceptable calibration and warrants external validation.
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Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) is receiving more attention as a biomarker for eligibility for immune checkpoint inhibitors in advanced diseases. However, due to high costs and resource limitations, MSI/dMMR testing is not widely performed. Some attempts are in progress to predict MSI/dMMR status through histomorphological features on H&E slides using artificial intelligence (AI) technology. In this study, the potential predictive role of this new methodology was reviewed through a systematic review. Studies up to September 2021 were searched through PubMed and Embase database searches. The design and results of each study were summarized, and the risk of bias for each study was evaluated. For colorectal cancer, AI-based systems showed excellent performance with the highest standard of 0.972; for gastric and endometrial cancers they showed a relatively low but satisfactory performance, with the highest standard of 0.81 and 0.82, respectively. However, analyzing the risk of bias, most studies were evaluated at high-risk. AI-based systems showed a high potential in predicting the MSI/dMMR status of different cancer types, and particularly of colorectal cancers. Therefore, a confirmation test should be required only for the results that are positive in the AI test.