RESUMO
Background: This study addresses the gap in knowledge regarding the long-term mortality implications of postoperative acute kidney injury (PO-AKI) utilizing advanced machine learning techniques to predict outcomes more accurately than traditional statistical models. Methods: A retrospective cohort study was conducted using data from seven institutions between March 2009 and December 2019. Machine learning models were developed to predict all-cause mortality of PO-AKI patients using 23 preoperative variables and one postoperative variable. Model performance was compared to a traditional statistical approach with Cox regression analysis. The concordance index was used as a predictive performance metric to compare prediction capabilities among different models. Results: Among 199,403 patients, 2,105 developed PO-AKI. During a median follow-up of 144 months (interquartile range, 99.61-170.71 months), 472 in-hospital deaths occurred. Subjects with PO-AKI had a significantly lower survival rate than those without PO-AKI (p < 0.001). For predicting mortality, the XGBoost with an accelerated failure time model had the highest concordance index (0.7521), followed by random survival forest (0.7371), multivariable Cox regression model (0.7318), survival support vector machine (0.7304), and gradient boosting (0.7277). Conclusion: XGBoost with an accelerated failure time model was developed in this study to predict long-term mortality associated with PO-AKI. Its performance was superior to conventional models. The application of machine learning techniques may offer a promising approach to predict mortality following PO-AKI more accurately, providing a basis for developing targeted interventions and clinical guidelines to improve patient outcomes.
RESUMO
Background: Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. Methods: We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. Results: The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.853ï0.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although they underestimated the external validation cohort risks. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.
RESUMO
Successful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize TB therapy have exploited Mtb chemical genetics to identify pathways influencing antibiotic efficacy, novel mechanisms of antibiotic action, and new targets for TB drug discovery. However, the influence of the complex host environment on these interactions remains largely unknown, leaving the therapeutic potential of the identified targets unclear. In this study, we leveraged a library of conditional mutants targeting 467 essential Mtb genes to characterize the chemical-genetic interactions (CGIs) with TB drugs directly in the mouse infection model. We found that these in vivo CGIs differ significantly from those identified in vitro . Both drug-specific and drug-agnostic effects were identified, and many were preserved during treatment with a multidrug combination, suggesting numerous strategies for enhancing therapy. This work also elucidated the complex effects of pyrazinamide (PZA), a drug that relies on aspects of the infection environment for efficacy. Specifically, our work supports the importance of coenzyme A synthesis inhibition during infection, as well as the antagonistic effect of iron limitation on PZA activity. In addition, we found that inhibition of thiamine and purine synthesis increases PZA efficacy, suggesting novel therapeutically exploitable metabolic dependencies. Our findings present a map of the unique in vivo CGIs, characterizing the mechanism of PZA activity in vivo and identifying novel targets for TB drug development. Significance: The inevitable rise of multi-drug-resistant tuberculosis underscores the urgent need for new TB drugs and novel drug targets while prioritizing synergistic drug combinations. Chemical-genetic interaction (CGI) studies have delineated bacterial pathways influencing antibiotic efficacy and uncovered druggable pathways that synergize with TB drugs. However, most studies are conducted in vitro , limiting our understanding of how the host environment influences drug-mutant interactions. Using an inducible mutant library targeting essential Mtb genes to characterize CGIs during infection, this study reveals that CGIs are both drug-specific and drug-agnostic and differ significantly from those observed in vitro . Synergistic CGIs comprised distinct metabolic pathways mediating antibiotic efficacy, revealing novel drug mechanisms of action, and defining potential drug targets that would synergize with frontline antitubercular drugs.
RESUMO
Experiments are increasingly performed in vitro; therefore, cell culture technology is essential for scientific progress. Fetal bovine serum (FBS) is a key cell culture supplement providing growth factors, amino acids, and hormones. However, FBS is not readily available on the market, has contamination risks, and has ethical concerns. This study aimed to investigate Haematococcus pluvialis extracts (HE) as a potential substitute for FBS. Therefore, we assessed the effects of HE on cell maintenance, growth, and cycle progression in human lung fibroblasts (MRC-5). Cell progression and monosaccharide, fatty acid, and free amino acid compositions were analyzed using cell cycle analysis, bio-liquid chromatography, gas chromatography, and high-performance liquid chromatography, respectively. The results of nutritional profiles showed that the extracts contained essential amino acids required for synthesizing non-essential amino acids and other metabolic intermediates. Furthermore, most of the components present in HE were consistent with those found in FBS. HE enhanced cell viability and regulated cell cycle phases. Additionally, the interaction between growth factor cocktails and HE significantly improved cell viability, promoted cell cycle progression, and activated key cell cycle regulators, such as cyclin A and cyclin-dependent kinases 1 (CDK1). Our findings suggest that HE have considerable potential to substitute FBS in MRC-5 cell cultures and have functional and ethical advantages.
RESUMO
The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.
Assuntos
Proliferação de Células , Microalgas , Animais , Cães , Microalgas/química , Células Vero , Chlorocebus aethiops , Meios de Cultura Livres de Soro/química , Proliferação de Células/efeitos dos fármacos , Células Madin Darby de Rim Canino , Técnicas de Cultura de Células/métodos , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND/AIMS: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events, including endocrine dysfunctions, which can have serious consequences on patient health and quality of life. The clinical course and characteristics of immune-related hypophysitis (irH) are not well established. This study aimed to analyze the clinical course and characteristics of irH. METHODS: This single-center, retrospective study analyzed data from electronic medical records of Asan Medical Center, spanning January 2017 through June 2021. It included adult patients with solid tumors who underwent thyroid and adrenal function tests, along with gonadotropin and/or growth hormone evaluations, following the initiation of ICI treatment within the same period. The study explored the clinical characteristics of ICI-treated patients with and without irH, the incidence of irH, the time to irH onset, and the associated hormonal changes. RESULTS: Twenty-one patients were included in this analysis. Clinical characteristics did not differ significantly between the irH (n = 13) and non-irH (n = 8) groups. Deficiency rates in the irH group were 23.1% for thyroid-stimulating hormone (n = 3), 76.9% for adrenocorticotropic hormone (n = 10), 61.5% for gonadotropin (n = 8), and 15.4% for growth hormone (n = 2). The overall incidence was 0.9 per person-year, with 6-month and 1-year cumulative incidences of 38.8% and 57.1%, respectively. The median time from ICI initiation to irH diagnosis was 7.7 months. Time to levothyroxine replacement was shorter in the irH group. CONCLUSION: The findings provide evidence that could facilitate the prediction of ICI-induced irH based on clinical course and characteristics.
Assuntos
Hipofisite , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Hipofisite/induzido quimicamente , Hipofisite/epidemiologia , Hipofisite/diagnóstico , Idoso , Adulto , Incidência , Fatores de Tempo , Hormônio Adrenocorticotrópico/sangue , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Fatores de RiscoRESUMO
Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and 'Omics' data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL.
Assuntos
Biomarcadores Tumorais , Meduloblastoma , Proteômica , Humanos , Meduloblastoma/líquido cefalorraquidiano , Biomarcadores Tumorais/líquido cefalorraquidiano , Proteômica/métodos , Feminino , Masculino , Criança , Proteína Tumoral 1 Controlada por Tradução , Pré-Escolar , Adolescente , Neoplasias Cerebelares/líquido cefalorraquidiano , Proteoma , Vesículas Extracelulares/metabolismoRESUMO
This study explores the potential of producing bioethanol from seaweed biomass and reusing the residues as antioxidant compounds. Various types of seaweed, including red (Gelidium amansii, Gloiopeltis furcata, Pyropia tenera), brown (Saccharina japonica, Undaria pinnatifida, Ascophyllum nodosum), and green species (Ulva intestinalis, Ulva prolifera, Codium fragile), were pretreated with dilute acid and enzymes and subsequently processed to produce bioethanol with Saccharomyces cerevisiae BY4741. Ethanol production followed the utilization of sugars, resulting in the highest yields from red algae > brown algae > green algae due to their high carbohydrate content. The residual biomass was extracted with water, ethanol, or methanol to evaluate its antioxidant activity. Among the nine seaweeds, the A. nodosum bioethanol residue extract (BRE) showed the highest antioxidant activity regarding the 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity, ferric reducing antioxidant power (FRAP), and reactive oxygen species (ROS) inhibition of H2O2-treated RAW 264.7 cells. These by-products can be valorized, contributing to a more sustainable and economically viable biorefinery process. This dual approach not only enhances the utilization of marine resources but also supports the development of high-value bioproducts.
Assuntos
Antioxidantes , Biomassa , Etanol , Saccharomyces cerevisiae , Alga Marinha , Alga Marinha/química , Alga Marinha/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Animais , Camundongos , Saccharomyces cerevisiae/metabolismo , Células RAW 264.7 , Biocombustíveis , Espécies Reativas de Oxigênio/metabolismo , Rodófitas/química , Rodófitas/metabolismo , Phaeophyceae/químicaRESUMO
Autophagy is a cellular process that degrades damaged cytoplasmic components and regulates cell death. The homeostasis of endothelial cells (ECs) is crucial for the preservation of glomerular structure and function in aging. Here, we investigated the precise mechanisms of endothelial autophagy in renal aging. The genetic deletion of Atg7 in the ECs of Atg7flox/flox;Tie2-Cre mice accelerated aging-related glomerulopathy and tubulointerstitial fibrosis. The EC-specific Atg7 deletion in aging mice induced the detachment of EC with the disruption of glomerular basement membrane (GBM) assembly and increased podocyte loss resulting in microalbuminuria. A Transwell co-culture system of ECs and kidney organoids showed that the iron and oxidative stress induce the disruption of the endothelial barrier and increase vascular permeability, which was accelerated by the inhibition of autophagy. This resulted in the leakage of iron through the endothelial barrier into kidney organoids and increased oxidative stress, which led to ferroptotic cell death. The ferritin accumulation was increased in the kidneys of the EC-specific Atg7-deficient aging mice and upregulated the NLRP3 inflammasome signaling pathway. The pharmacologic inhibition of ferroptosis with liproxstatin-1 recovered the disrupted endothelial barrier and reversed the decreased expression of GPX4, as well as NLRP3 and IL-1ß, in endothelial autophagy-deficient aged mice, which attenuated aging-related renal injury including the apoptosis of renal cells, abnormal structures of GBM, and tubulointerstitial fibrosis. Our data showed that endothelial autophagy is essential for the maintenance of the endothelial barrier during renal aging and the impairment of endothelial autophagy accelerates renal senescence by ferroptosis and NLRP3 inflammasome signaling pathways. These processes may be attractive therapeutic targets to reduce cellular injury from renal aging.
RESUMO
Sargassum fusiforme and Sargassum fulvellum are types of brown algae used for their nutritional value and medicinal properties, including anti-inflammatory, antioxidant, and anticancer effects. Despite their importance in various industries, many seaweed byproducts containing dietary fiber and polysaccharides are discarded in landfills. These byproducts can be recycled and repurposed for different applications. In this study, we investigated the impact of S. fusiforme food processing byproducts (MbP-SFF) and S. fulvellum food processing byproducts (MbP-SFV) on improving intestinal motility and reducing inflammation in mice with constipation induced by loperamide. To evaluate this, mice were orally administered 500 mg/kg/day of the byproducts once daily for 8 days. Constipation was induced by 5 mg/kg/day of loperamide for two days after oral administration for 6 days. Each sample contained approximately 70% carbohydrates. MbP-SFF had 52.0% mannuronic acid and 18.8% guluronic acid, while MbP-SFV had 36.9% mannuronic acid and 32.9% guluronic acid. These byproducts enhanced fecal excretion and intestinal motility by modulating inflammatory responses. Furthermore, they restored the balance of the gut microbiota disrupted by loperamide, increasing beneficial Bifidobacterium and reducing harmful Staphylococcus aureus. Overall, MbP-SFF and MbP-SFV improved intestinal motility and inflammation by influencing the gut microbiota and inflammatory responses in a loperamide-induced mouse model. These byproducts show potential as ingredients in functional foods aimed at enhancing gut health, potentially reducing waste disposal costs and addressing environmental concerns associated with their utilization.
RESUMO
Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.
Assuntos
Carcinoma , Neoplasias do Plexo Corióideo , Papiloma do Plexo Corióideo , Humanos , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/metabolismo , Feminino , Masculino , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/patologia , Criança , Pré-Escolar , Carcinoma/genética , Carcinoma/patologia , Metilação de DNA , Lactente , Adolescente , MultiômicaRESUMO
BACKGROUND: Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. METHODS: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. RESULTS: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71-0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73-0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. CONCLUSION: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.
RESUMO
BACKGROUND: Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. METHODS: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65-74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. RESULTS: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99-1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30-0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18-10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02-2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36-0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28- day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. CONCLUSION: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.
RESUMO
INTRODUCTION: Primary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes. METHODS: Fifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis. RESULTS: CAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020). CONCLUSIONS: Immunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.
Assuntos
Biomarcadores Tumorais , Hemangioendotelioma Epitelioide , Hemangiossarcoma , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Biomarcadores Tumorais/análise , Hemangioendotelioma Epitelioide/patologia , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/mortalidade , Prognóstico , Adulto , Idoso , Hemangiossarcoma/patologia , Hemangiossarcoma/mortalidade , Hemangiossarcoma/diagnóstico , Imuno-Histoquímica , Antígeno Ki-67/análise , Adulto Jovem , Proteínas de Ligação ao Cálcio , TransativadoresRESUMO
Acute kidney injury (AKI) is characterized by an abrupt decline of excretory kidney function. The incidence of AKI has increased in the past decades. Patients diagnosed with AKI often undergo diverse clinical trajectories, such as early or late recovery, relapses, and even a potential transition from AKI to chronic kidney disease (CKD). Although recent clinical studies have demonstrated a strong association between AKI and progression of CKD, our understanding of the complex relationship between AKI and CKD is still evolving. No cohort study has succeeded in painting a comprehensive picture of these multi-faceted pathways. To address this lack of understanding, the idea of acute kidney disease (AKD) has recently been proposed. This presents a new perspective to pinpoint a period of heightened vulnerability following AKI, during which a patient could witness a substantial decline in glomerular filtration rate, ultimately leading to CKD transition. Although AKI is included in a range of kidney conditions collectively known as AKD, spanning from mild and self-limiting to severe and persistent, AKD can also occur without a rapid onset usually seen in AKI, such as when kidney dysfunction slowly evolves. In the present review, we summarize the most recent findings about AKD, explore the current state of biomarker discovery related to AKD, discuss the latest insights into pathophysiological underpinnings of AKI to CKD transition, and reflect on therapeutic challenges and opportunities that lie ahead.
Assuntos
Injúria Renal Aguda , Progressão da Doença , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Injúria Renal Aguda/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , BiomarcadoresRESUMO
OBJECTIVE: Craniosynostosis involves early closure of one or more sutures, which is known to limit normal cranium growth and interfere with normal brain development. Various surgical methods are used, ranging from minimally invasive strip craniectomy to more extensive whole-vault cranioplasty. This study aimed to evaluate neurocognitive outcomes 5 years after surgical treatment in children with craniosynostosis and to evaluate relevant clinical factors. METHODS: After exclusion of genetically confirmed syndromic craniosynostosis patients, a retrospective review was conducted on 112 nonsyndromic craniosynostosis patients who underwent surgical treatment and follow-up neurocognitive assessment. Ninety-seven patients underwent strip craniectomy with postoperative orthotic helmet therapy, and 15 received other surgical treatment: 4 with distraction osteotomy and 11 with craniofacial reconstruction. Neurocognitive assessment using the Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), was performed 5 years postoperatively. Clinical factors were assessed regarding neurocognitive outcomes. RESULTS: The mean age at surgery was significantly younger in the strip craniectomy group (strip craniectomy 4.6 months vs other surgical treatment 18.6 months, p < 0.01). Patients with 2 or more sutures involved were more likely to receive more extensive surgical treatment (16.5% in the strip craniectomy group vs 53.8% in the other group, p < 0.01). Four (3.5%) patients who showed evidence of increased intracranial pressure (ICP) also underwent more extensive surgical treatment. Multivariable linear regression revealed a significant correlation of age at neurocognitive testing (-3.18, 95% CI -5.95 to -0.40, p = 0.02), increased ICP (-34.73, 95% CI -51.04 to -18.41, p < 0.01), and the level of maternal education (6.11, 95% CI 1.01-11.20, p = 0.02) with the Full-Scale Intelligence Quotient (FSIQ). Age at surgery, involvement of 2 or more sutures, and type of operation demonstrated no correlation with FSIQ. Among the 97 patients who underwent strip craniectomy, the FSIQ ranged from mean ± SD 100.2 ± 10.2 (bicoronal) to 110.1 ± 12.7 (lambdoid), and there was no significant difference between the suture groups (p = 0.41). The 5 index scores were all within average ranges based on their age norms. CONCLUSIONS: Age at neurocognitive assessment, increased ICP, and maternal education level showed significant correlations with the neurocognitive function of craniosynostosis patients. Although children with craniosynostosis exhibited favorable 5-year postoperative neurocognitive outcomes across various synostosis sutures, longer follow-up is needed to reveal the incidence of neurocognitive dysfunction in these patients.
Assuntos
Craniossinostoses , Humanos , Craniossinostoses/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Lactente , Pré-Escolar , Resultado do Tratamento , Seguimentos , Craniotomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Testes Neuropsicológicos , Criança , Dispositivos de Proteção da CabeçaRESUMO
Background and Objectives: Traumatic vascular injuries of the head and neck pose significant treatment challenges due to the complex anatomy, diverse clinical presentation, and mostly emergent nature. Endovascular treatment increasingly complements traditional surgical approaches. This study aimed to report our 10-year experience in treating traumatic vascular injuries of the head and neck with endovascular therapy and to determine the effectiveness of endovascular treatment. Materials and Methods: A retrospective analysis of 21 patients treated for head and neck vascular injuries between May 2011 and April 2021 was performed. Patients' medical histories, clinical presentations, imaging findings, treatment materials, and clinical outcomes were reviewed. Treatments included stenting, coil embolization, and other endovascular techniques focused on hemostasis and preservation of the parent vessel. Results: The most common injuries involved the internal maxillary artery branches (n = 11), followed by the common or internal carotid artery (n = 6), vertebral artery (n = 3), and others. Endovascular treatment achieved successful hemostasis in all but one case. In five of six carotid artery injuries and two of three vertebral artery injuries, we achieved successful hemostasis while preserving the parent vessel using covered and bare stents, respectively. Conclusions: Endovascular therapy might be a useful treatment modality for traumatic vascular injuries in the head and neck region, offering efficacy, safety, and a minimally invasive approach.
Assuntos
Lesões das Artérias Carótidas , Procedimentos Endovasculares , Lesões do Sistema Vascular , Humanos , Lesões do Sistema Vascular/etiologia , Estudos Retrospectivos , Lesões das Artérias Carótidas/cirurgia , Lesões das Artérias Carótidas/etiologia , Pescoço , Procedimentos Endovasculares/métodos , Stents , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is largely unknown and a rare subtype of HCC with immune-rich stroma. Tertiary lymphoid structures (TLS), frequently observed in LR-HCC, are known to be prognostically significant in various malignancies; however, their significance in HCC remains unevaluated. METHODS: Clinicopathologic data of 191 cases of surgically resected conventional HCC (C-HCC, n = 160) and LR-HCC (n = 31) were retrieved. Immunohistochemistry, multiplex immunofluorescence staining, RNA sequencing and proteomic analysis were conducted. Differences between the subtypes were statistically evaluated. RESULTS: LR-HCC was significantly correlated to larger tumour size, higher Edmondson-Steiner grade, presence of TLS and higher CD3-, CD8- and FOXP3-positive T cell, high PD-1 and PD-L1 expression (p < .001 for all) compared to C-HCC. Patients with LR-HCC exhibited significantly better overall survival (OS) (p = .044) and recurrence-free survival (RFS) (p = .025) than C-HCC. LR-HCC demonstrated TLS signatures with significantly higher proteomic-based immune scores in 14 of 17 types of tumour-infiltrating immune cells. Furthermore, C-HCC with secondary follicles, the most mature form of TLS, exhibited significantly better OS (p = .031) and RFS (p = .033) than those without. Across the global proteome, LR-HCC was well-differentiated from C-HCC and a map of protein-protein interactions between tumour-infiltrating lymphocytes and HCC in tumour microenvironment was completed. CONCLUSION: LR-HCC is clinicopathologically and molecularly distinct and shows better prognosis compared to C-HCC. Also, the presence of secondary follicle can be an important prognostic marker for better prognosis in both LR-HCC and C-HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Estruturas Linfoides Terciárias , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Neoplasias Hepáticas/patologia , Estruturas Linfoides Terciárias/patologia , Proteômica , Biomarcadores Tumorais/análise , Linfócitos do Interstício Tumoral , Microambiente TumoralRESUMO
This study examined the experiences and the perceptions of elder mistreatment (EM), as well as help-seeking knowledge and behaviors, particularly about Adult Protective Services (APS), among community samples of Asian American older adults, including Koreans, Chinese, and others (N = 288). Approximately 27% of the study participants experienced at least one EM incident in the past year. Between 27% and 38% of the participants reported that they were likely to seek help from APS for different types of EM. Significant differences were found across the three Asian groups in their perceptions toward EM and intention to seek help from APS in the event of EM. However, many Asian American older adults in the study did not know about APS prior to participating in the study (75.5%) and other formal sources of help (66.3%). Implications for helping professionals, particularly APS and community-based organizations serving Asian Americans, are discussed.
Assuntos
Abuso de Idosos , Comportamento de Busca de Ajuda , Idoso , Humanos , AsiáticoRESUMO
PURPOSE: The present study aimed to evaluate the role of early and delayed surgery in congenital brain tumors and analyze the clinical outcomes of infantile brain tumors. MATERIALS AND METHODS: We performed a retrospective cohort study on 69 infantile brain tumors at a single institution from January 2008 to June 2023. Outcomes were assessed as early mortality (within 30 days following surgery) to evaluate the risk of early surgery in congenital brain tumors. Outcomes of recurrence and overall survival were analyzed in infantile brain tumors. RESULTS: Surgery-related early mortality appeared to occur in young and low-body-weight patients. Cut-off values of age and body weight were found to be 1.3 months and 5.2 kg to avoid early mortality. Three patients (3/10, 30%) showed early mortality in the early surgery group, and early mortality occurred in one patient (1/14, 7.14%) in the delayed surgery group, whose tumor was excessively enlarged. Younger age at diagnosis (< 3 months of age; hazard ratios [HR], 7.1; 95% confidence intervals [CI], 1.4 to 35.6; p=0.018) and leptomeningeal seeding (LMS; HR, 30.6; 95% CI, 3.7 to 253.1; p=0.002) were significant independent risk factors for high mortality in infantile brain tumors. CONCLUSION: We suggest delaying surgery until the patient reaches 1.3 months of age and weighs over 5.2 kg with short-term imaging follow-up unless tumors grow rapidly in congenital brain tumors. Younger ages and the presence of LMS are independent risk factors for high mortality in infantile brain tumors.