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1.
Neuropathol Appl Neurobiol ; 49(1): e12866, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36519297

RESUMO

AIM: Analysis of cerebrospinal fluid (CSF) is essential for diagnostic workup of patients with neurological diseases and includes differential cell typing. The current gold standard is based on microscopic examination by specialised technicians and neuropathologists, which is time-consuming, labour-intensive and subjective. METHODS: We, therefore, developed an image analysis approach based on expert annotations of 123,181 digitised CSF objects from 78 patients corresponding to 15 clinically relevant categories and trained a multiclass convolutional neural network (CNN). RESULTS: The CNN classified the 15 categories with high accuracy (mean AUC 97.3%). By using explainable artificial intelligence (XAI), we demonstrate that the CNN identified meaningful cellular substructures in CSF cells recapitulating human pattern recognition. Based on the evaluation of 511 cells selected from 12 different CSF samples, we validated the CNN by comparing it with seven board-certified neuropathologists blinded for clinical information. Inter-rater agreement between the CNN and the ground truth was non-inferior (Krippendorff's alpha 0.79) compared with the agreement of seven human raters and the ground truth (mean Krippendorff's alpha 0.72, range 0.56-0.81). The CNN assigned the correct diagnostic label (inflammatory, haemorrhagic or neoplastic) in 10 out of 11 clinical samples, compared with 7-11 out of 11 by human raters. CONCLUSIONS: Our approach provides the basis to overcome current limitations in automated cell classification for routine diagnostics and demonstrates how a visual explanation framework can connect machine decision-making with cell properties and thus provide a novel versatile and quantitative method for investigating CSF manifestations of various neurological diseases.


Assuntos
Aprendizado Profundo , Humanos , Inteligência Artificial , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos
2.
BMB Rep ; 56(2): 202-207, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36443003

RESUMO

We investigated the neuroprotective effects of deca nano-graphene oxide (daNGO) against reactive oxygen species (ROS) and inflammation in the human neuroblastoma cell line SH-SY5Y and in the 6-hydroxydopamine (6-OHDA) induced Parkinsonian rat model. An MTT assay was performed to measure cell viability in vitro in the presence of 6-OHDA and/or daNGO. The intracellular ROS level was quantified using 2',7'-dichlorofluorescein diacetate. daNGO showed neuroprotective effects against 6-OHDA-induced toxicity and also displayed ROS scavenging properties. We then tested the protective effects of daNGO against 6-OHDA induced toxicity in a rat model. Stepping tests showed that the akinesia symptoms were improved in the daNGO group compared to the control group. Moreover, in an apomorphine-induced rotation test, the number of net contralateral rotations was decreased in the daNGO group compared to the control group. By immunofluorescent staining, the animals in the daNGO group had more tyrosine hydroxylase-positive cells than the controls. By anti-Iba1 staining, 6-OHDA induced microglial activation showed a significantly decrease in the daNGO group, indicating that the neuroprotective effects of graphene resulted from anti-inflammation. In conclusion, nanographene oxide has neuroprotective effects against the neurotoxin induced by 6-OHDA on dopaminergic neurons. [BMB Reports 2023; 56(3): 202-207].


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Apoptose , Oxidopamina/toxicidade , Fármacos Neuroprotetores/farmacologia , Linhagem Celular Tumoral , Neuroblastoma/metabolismo
3.
J Surg Res ; 279: 453-463, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35841814

RESUMO

INTRODUCTION: Burns can cause multiple organ systemic derangements, particularly in respiratory systems. The prognostic nutritional index (PNI) can predict postoperative outcomes. We evaluated the incidence and risk factors, including PNI, for postoperative pulmonary complications (PPCs) in patients with major burns. METHODS: PNI was calculated as 10 × (serum albumin level) + 0.005 × (total lymphocyte count). Major burn patients admitted to the ICU without burn-induced lung injuries were retrospectively included. The incidence of PPCs was measured within 1 wk of burn surgery. A multivariable logistic regression analysis was performed to evaluate the risk factors for PPCs. Receiver operating characteristic curve analysis and propensity-score matched analysis were conducted to estimate the influence of PNI on PPCs. Outcomes after burn surgery were also assessed. RESULTS: Of 444 major burn patients, 138 (31.1%) showed PPCs. Risk factors for PPCs were PNI, gender, total body surface area burned, interval between burn and surgery, and red blood cell transfusion rate. The area under the curve of PNI for predicting PPCs was 0.709 (cutoff value = 31.5). The incidence of PPCs was significantly higher in the PNI ≤ 31.5 group than in the PNI > 31.5 group (55.7% versus 22.8%, P < 0.001) after propensity-score matching. The intensive care unit stay duration was longer and 90-d mortality was higher in patients who developed PPCs (19 [9-27] d versus 8 [4-17] d, P < 0.001; 11.6% versus 0.3%, P < 0.001). CONCLUSIONS: The prevalence of PPCs in patients with major burns was 31.1% and preoperative PNI was a predictor of PPCs in these patients. PNI ≤ 31.5 was significantly related to a higher incidence of PPCs.


Assuntos
Queimaduras , Avaliação Nutricional , Queimaduras/complicações , Queimaduras/cirurgia , Humanos , Estado Nutricional , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica
4.
Front Cell Infect Microbiol ; 12: 861915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558103

RESUMO

Colletotrichum scovillei is the major anthracnose fungus of sweet pepper and chili pepper (Capsicum annuum L.), causing significant losses in the yield and quality of the pepper fruits. Molecular mechanisms governing development and pathogenicity have been widely studied in many foliar fungal pathogens, but the information on fruit diseases is still limited. In this study, we determined the functional roles of the dual-specificity tyrosine phosphorylation-regulated kinase CsPOM1 in C. scovillei. Knockout mutant for CsPOM1 gene was obtained via homology-dependent gene replacement. The ΔCspom1 mutant exhibited a reduction in vegetative growth on osmotic stress, surface hydrophobicity, and conidiation compared with wild-type. Conidia of the ΔCspom1 mutant were already two-celled before inoculation on an induction surface, indicating that CsPOM1 negatively regulates conidial cell division. The ΔCspom1 mutant, similar to wild-type, formed appressoria on the plant surface, but was significantly reduced on hydrophobic coverslips, probably due to a defect in the recognition of surface hydrophobicity. Treatment of conidia with cutin monomers restored appressorium formation on hydrophobic coverslips in the ΔCspom1 mutant. On pepper fruits, the ΔCspom1 mutant exhibited delayed penetration and invasive growth, leading to significantly reduced virulence. Collectively, the results showed that CsPOM1 is important for stress tolerance, conidiation, surface hydrophobicity, appressorium formation, and virulence in C. scovillei.


Assuntos
Capsicum , Colletotrichum , Capsicum/genética , Capsicum/microbiologia , Colletotrichum/genética , Doenças das Plantas/microbiologia , Esporos Fúngicos , Virulência
5.
Cell Death Discov ; 8(1): 153, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35368019

RESUMO

Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by ß-amyloid (Aß) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigger AD pathological features, including Aß and p-Tau expression. AD-related phenotypes in brain organoids were upregulated via endoplasmic reticulum (ER) stress and unfolded protein response (UPR) after ZIKV infection in brain organoids. Under persistent ER stress, activated-double stranded RNA-dependent protein kinase-like ER-resident (PERK) triggered the phosphorylation of Eukaryotic initiation factor 2 (eIF2α) and then BACE, and GSK3α/ß related to AD. Furthermore, we demonstrated that pharmacological inhibitors of PERK attenuated Aß and p-Tau in brain organoids after ZIKV infection.

6.
Cell Death Discov ; 8(1): 1, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013145

RESUMO

Mitochondrial dysfunction is associated with familial Alzheimer's disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to disease progression. In the amyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by ß-secretase to generate a C-terminal fragment, which is then cleaved by γ-secretase to produce amyloid-beta (Aß). The accumulation of Aß and its detrimental effect on mitochondrial function are well known, yet the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) contributing to this pathology have rarely been reported. We demonstrated the effects of APP-CTFs-related pathology using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs accumulation was demonstrated to mainly occur within mitochondrial domains and to be both a cause and a consequence of mitochondrial dysfunction. APP-CTFs accumulation also resulted in mitophagy failure, as validated by increased LC3-II and p62 and inconsistent PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) recruitment to mitochondria and failed fusion of mitochondria and lysosomes. The accumulation of APP-CTFs and the causality of impaired mitophagy function were also verified in AD patient-iNSCs. Furthermore, we confirmed this pathological loop in presenilin knockout iNSCs (PSEN KO-iNSCs) because APP-CTFs accumulation is due to γ-secretase blockage and similarly occurs in presenilin-deficient cells. In the present work, we report that the contribution of APP-CTFs accumulation is associated with mitochondrial dysfunction and mitophagy failure in AD patient-iNSCs as well as PSEN KO-iNSCs.

7.
Burns Trauma ; 10: tkab050, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35097135

RESUMO

BACKGROUND: Red cell distribution width (RDW) and serum albumin concentration are associated with postoperative outcomes. However, the usefulness of the RDW/albumin ratio in burn surgery remains unclear. Therefore, we evaluated the association between RDW/albumin ratio and 90-day mortality after burn surgery. METHODS: Between 2013 and 2020, a retrospective review of patients in a burn intensive care unit (ICU) was performed. Receiver operating characteristic curve, multivariate Cox logistic regression, multivariate logistic regression and Kaplan-Meier analyses were conducted to evaluate the association between RDW/albumin ratio and 90-day mortality after burn surgery. Additionally, prolonged ICU stay rate (>60 days) and ICU stay were assessed. RESULTS: Ninety-day mortality was 22.5% (210/934) in burn patients. Risk factors for 90-day mortality were RDW/albumin ratio at postoperative day 1, age, American Society of Anesthesiologists physical status, diabetes mellitus, inhalation injury, total body surface area burned, hypotensive event and red blood cell transfusion volume. The area under the curve of the RDW/albumin ratio at postoperative day 1 to predict 90-day mortality, after adjusting for age and total body surface area burned, was 0.875 (cut-off value, 6.8). The 90-day mortality was significantly higher in patients with RDW/albumin ratio >6.8 than in those with RDW/albumin ratio ≤6.8 (49.2% vs 12.3%, p < 0.001). Prolonged ICU stay rate and ICU stay were significantly higher and longer in patients with RDW/albumin ratio >6.8 than in those with RDW/albumin ratio ≤6.8 (34.5% vs 26.5%; 21 [11-38] vs 18 [7-32] days). CONCLUSION: RDW/albumin ratio >6.8 on postoperative day 1 was associated with higher 90-day mortality, higher prolonged ICU stay rate and longer ICU stay after burn surgery.

8.
J Burn Care Res ; 43(4): 942-950, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34927687

RESUMO

Burn injuries can cause significant malnutrition, leading to cardiovascular impairments. The prognostic nutritional index (PNI) predicts postoperative complications. We evaluated the impact of preoperative PNI on major adverse cardiac events (MACE) after burn surgery. PNI was calculated using the equation, 10×(serum albumin level)+0.005×(total lymphocyte count). Multivariable logistic regression analysis was conducted to evaluate the predictors for MACE at 6 months after burn surgery. Receiver operating characteristic curve and propensity score matching analyses were conducted. Additionally, Kaplan-Meier analysis was conducted to compare postoperative 1-year mortality between MACE and non-MACE groups. MACE after burn surgery occurred in 184 (17.5%) of 1049 patients. PNI, age, American Society of Anesthesiologists physical status, and TBSA burned were significantly related to MACE. The area under the receiver operating characteristic curve of PNI was 0.729 (optimal cutoff value = 35). After propensity score matching, the incidence of MACE in the PNI <35 group was higher than that in the PNI ≥35 group (20.1% vs 9.6%, P < .001). PNI <35 was related to an increased incidence of MACE (odds ratio = 2.373, 95% confidence interval = 1.499-3.757, P < .001). The postoperative 1-year mortality was higher in the MACE group than in the non-MACE group (54.9% vs 9.1%, P < .001). Preoperative PNI was a predictor for MACE after burn surgery. PNI <35 was significantly related to an increased incidence of MACE. Moreover, MACE was related to higher postoperative 1-year mortality.


Assuntos
Queimaduras , Avaliação Nutricional , Queimaduras/complicações , Queimaduras/cirurgia , Humanos , Estado Nutricional , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
9.
Plant Pathol J ; 37(3): 307-314, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34111920

RESUMO

Pepper (Capsicum annuum L.) is an important agricultural crop worldwide. Recently, Colletotrichum scovillei, a member of the C. acutatum species complex, was reported to be the dominant pathogen causing pepper anthracnose disease in South Korea. In the present study, we isolated bacterial strains from rhizosphere soil in a pepper field in Gangwon Province, Korea, and assessed their antifungal ability against C. scovillei strain KC05. Among these strains, a strain named BS1 significantly inhibited mycelial growth, appressorium formation, and disease development of C. scovillei. By combined sequence analysis using 16S rRNA and partial gyrA sequences, strain BS1 was identified as Bacillus velezensis, a member of the B. subtilis species complex. BS1 produced hydrolytic enzymes (cellulase and protease) and iron-chelating siderophores. It also promoted chili pepper (cv. Nockwang) seedling growth compared with untreated plants. The study concluded that B. velezensis BS1 has good potential as a biocontrol agent of anthracnose disease in chili pepper caused by C. scovillei.

10.
Neuropathol Appl Neurobiol ; 47(6): 756-767, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34091929

RESUMO

AIMS: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.


Assuntos
Neoplasias da Orelha/patologia , Saco Endolinfático/patologia , Proteínas Supressoras de Tumor/metabolismo , Doença de von Hippel-Lindau/patologia , Adulto , Neoplasias da Orelha/complicações , Neoplasias da Orelha/genética , Saco Endolinfático/metabolismo , Humanos , Pessoa de Meia-Idade , Mutação/genética , Risco , Proteínas Supressoras de Tumor/genética , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética
11.
Burns ; 47(8): 1865-1872, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33832798

RESUMO

BACKGROUND: Burn is an overwhelming injury. The De Ritis ratio, defined as aspartate aminotransferase to alanine aminotransferase ratio, can be used to predict poor outcomes. We evaluated the risk factors, including the De Ritis ratio, associated with 1-year mortality after burn surgery. METHODS: Patients who underwent burn surgery from 2009 to 2019 were retrospectively evaluated. Multivariate Cox regression analysis was conducted to evaluate the risk factors for 1-year mortality after burn surgery. Receiver operating characteristic (ROC) curve analysis of the De Ritis ratio was performed to predict postoperative 1-year mortality. Kaplan-Meier survival analysis was also conducted. Other postoperative outcomes, such as durations of hospital and intensive care unit stays, acute kidney injury, and major adverse cardiac events, were evaluated. RESULTS: One-year mortality after burn surgery occurred in 247 (19.9%) of 1244 patients. The risk factors for 1-year mortality after burn surgery were the De Ritis ratio, age, American Society of Anesthesiologists physical status, diabetes mellitus, total body surface area burned, inhalation injury, serum creatinine level, and serum albumin level. The area under the ROC curve for the De Ritis ratio was 0.716 (optimal cutoff=1.9). The 1-year mortality rate after burn surgery was significantly higher in patients with a De Ritis ratio >1.9 than in those with a De Ritis ratio ≤1.9 (35.8% vs. 11.8%, P<0.001). The survival rate was significantly higher in patients with a De Ritis ratio ≤1.9 than in those with a De Ritis ratio >1.9 (log-rank test, P<0.001). Intensive care unit stay, acute kidney injury, and major adverse cardiac events were significantly higher in patients with a De Ritis ratio >1.9 than in those with a De Ritis ratio ≤1.9 (P=0.006, P<0.001, and P<0.001, respectively). CONCLUSIONS: The preoperative De Ritis ratio was a risk factor for 1-year mortality after burn surgery. The De Ritis ratio >1.9 was significantly associated with an increased 1-year mortality after burn surgery. These findings emphasized the importance of identifying burn patients with an increased De Ritis ratio to reduce the mortality after burn surgery.


Assuntos
Queimaduras , Alanina Transaminase , Aspartato Aminotransferases , Queimaduras/cirurgia , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos
12.
Acta Neuropathol ; 141(6): 959-970, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33755803

RESUMO

Subependymomas are benign tumors characteristically encountered in the posterior fossa of adults that show distinct epigenetic profiles assigned to the molecular group "subependymoma, posterior fossa" (PFSE) of the recently established DNA methylation-based classification of central nervous system tumors. In contrast, most posterior fossa ependymomas exhibit a more aggressive biological behavior and are allocated to the molecular subgroups PFA or PFB. A subset of ependymomas shows epigenetic similarities with subependymomas, but the precise biology of these tumors and their potential relationships remain unknown. We therefore set out to characterize epigenetic traits, mutational profiles, and clinical outcomes of 50 posterior fossa ependymal tumors of the PFSE group. On histo-morphology, these tumors comprised 12 ependymomas, 14 subependymomas and 24 tumors with mixed ependymoma-subependymoma morphology. Mixed ependymoma-subependymoma tumors varied in their extent of ependymoma differentiation (2-95%) but consistently exhibited global epigenetic profiles of the PFSE group. Selective methylome analysis of microdissected tumor components revealed CpG signatures in mixed tumors that coalesce with their pure counterparts. Loss of chr6 (20/50 cases), as well as TERT mutations (21/50 cases), were frequent events enriched in tumors with pure ependymoma morphology (p < 0.001) and confined to areas with ependymoma differentiation in mixed tumors. Clinically, pure ependymoma phenotype, chr6 loss, and TERT mutations were associated with shorter progression-free survival (each p < 0.001). In conclusion, our results suggest that subependymomas may acquire genetic and epigenetic changes throughout tumor evolution giving rise to subclones with ependymoma morphology (resulting in mixed tumors) that eventually overpopulate the subependymoma component (pure PFSE ependymomas).


Assuntos
Cromossomos Humanos Par 6/genética , Ependimoma/classificação , Ependimoma/genética , Neoplasias Infratentoriais/genética , Neoplasias Infratentoriais/patologia , Mutação , Regiões Promotoras Genéticas/genética , Telomerase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Ependimoma/patologia , Feminino , Técnicas Genéticas , Humanos , Neoplasias Infratentoriais/classificação , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão
13.
Burns Trauma ; 9: tkaa043, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33709002

RESUMO

BACKGROUND: Burn injury in elderly patients can result in poor outcomes. Prognostic nutritional index (PNI) can predict the perioperative nutritional status and postoperative outcomes. We aim to evaluate the risk factors, including PNI, for one-year mortality after burn surgery in elderly patients. METHODS: Burn patients aged ≥65 years were retrospectively included. PNI was calculated using the following equation: 10 × serum albumin level (g/dL) + 0.005 × total lymphocyte count (per mm3). Cox regression, receiver operating characteristic curve and Kaplan-Meier survival analyses were performed to evaluate the risk factors for postoperative one-year mortality. RESULTS: Postoperative one-year mortality occurred in 71 (37.6%) of the 189 elderly burn patients. Risk factors for one-year mortality were PNI on postoperative day one (hazard ratio (HR) = 0.872; 95% CI = 0.812-0.936; p < 0.001), Sequential Organ Failure Assessment score (HR = 1.112; 95% CI = 1.005-1.230; p = 0.040), American Society of Anesthesiologists physical status (HR = 2.064; 95% CI = 1.211-3.517; p = 0.008), total body surface area burned (HR = 1.017; 95% CI = 1.003-1.032; p = 0.015) and preoperative serum creatinine level (HR = 1.386; 95% CI = 1.058-1.816; p = 0.018). The area under the curve of PNI for predicting one-year mortality after burn surgery was 0.774 (optimal cut-off value = 25.5). Patients with PNI ≤25.5 had a significantly lower one-year survival rate than those with PNI >25.5 (32.1% vs 75.9%, p < 0.001). CONCLUSIONS: PNI on postoperative day one was associated with postoperative one-year mortality in elderly burn patients. The postoperative one-year survival rate was lower in patients with PNI ≤25.5 than in those with PNI >25.5. These findings indicate the importance of identifying elderly burn patients with low PNI, thereby reducing the mortality after burn surgery.

14.
Anesth Pain Med (Seoul) ; 15(4): 498-504, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33329855

RESUMO

BACKGROUND: Surgeries in patients with coronavirus disease 2019 (COVID-19) put medical staff at a high risk of infection. We report the anesthetic management and infection control of a mechanically ventilated COVID-19 patient who underwent exploratory laparotomy for suspected duodenal ulcer perforation. CASE: A 73-year-old man, mechanically ventilated for confirmed COVID-19, showed clinical and radiographic signs of a perforated duodenal ulcer, and he was transferred under sedation and intubation to a negative-pressure operating room. The operating and assistant staff wore personal protective equipment. High-efficiency particulate absorbing filters were inserted into the expiratory circuits of the anesthesia machine and portable ventilator. No participating staff contracted COVID-19, although the patient later died due to pneumonia. CONCLUSIONS: This report can contribute to establishing clinical guidelines for the surgical management and operation room setting of COVID-19 patients.

15.
Acta Neuropathol ; 140(6): 893-906, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32926213

RESUMO

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.


Assuntos
Cauda Equina/patologia , Neoplasias do Sistema Nervoso Central/patologia , Tumores Neuroendócrinos/patologia , Paraganglioma/genética , Paraganglioma/patologia , Neoplasias do Sistema Nervoso Central/genética , Diagnóstico Diferencial , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética , Prognóstico
16.
Acta Anaesthesiol Scand ; 63(2): 240-247, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30203468

RESUMO

BACKGROUND: Severe inflammation and acute kidney injury (AKI) are serious adverse events after burn injuries. The neutrophil/lymphocyte ratio (NLR) is a marker of inflammation. We evaluated the independent risk factors for postoperative AKI, including NLR, in burn-injured patients. METHODS: The preoperative, intraoperative, and postoperative variables of 473 burn-injured patients were collected. The risk factors for AKI after burn surgery were evaluated using univariate and multivariate logistic regression analyses. The receiver operating characteristic (ROC) curve analysis of preoperative NLR was performed. The 3-month mortality after surgery was also compared between AKI and non-AKI groups using Kaplan-Meier analysis with a log-rank test. RESULTS: Postoperative AKI occurred in 71 of 473 (15.0%) burn patients. The total body surface area burned (odds ratio (OR), 1.013; 95% confidence interval (CI), 1.001-1.026; P = 0.037), inhalation injury (OR, 1.821; 95% CI, 1.008-3.292; P = 0.047), and preoperative NLR (OR, 1.094; 95% CI, 1.064-1.125; P < 0.001) were risk factors for AKI after surgery. The area under the ROC curve was 0.767, with an optimal cut-off value of 11.7. Moreover, the 3-month mortality after surgery was significantly higher in the AKI group than in the non-AKI group (49.3% vs 14.9%, P < 0.001). CONCLUSION: Total body surface area burned, inhalation injury, and preoperative NLR are risk factors for AKI after burn surgery, which is associated with early postoperative mortality. Preoperative NLR can provide useful information for the early detection of postoperative AKI and subsequent mortality in burn-injured patients.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Queimaduras/cirurgia , Contagem de Leucócitos , Contagem de Linfócitos , Neutrófilos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/terapia , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Queimaduras por Inalação/complicações , Queimaduras por Inalação/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
17.
Medicine (Baltimore) ; 97(30): e11580, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30045286

RESUMO

Percutaneous nephrolithotomy (PNL) is a minimally invasive technique for renal stone removal but can cause renal parenchymal injury. Renal stones can also affect renal function. We evaluated the risk factors for acute kidney injury (AKI) after PNL.The study cohort included 662 patients who underwent PNL. Patient characteristics, preoperative laboratory values, intraoperative data, and stone characteristics were collected. Univariate and multivariate logistic regression analyses were performed to identify risk factors for AKI after PNL. Postoperative outcomes such as hospitalization, intensive care unit admission rate and stay duration, and chronic kidney disease were also evaluated.Of the total study series, there were 107 (16.2%) cases of AKI after PNL (AKI group), and 555 (83.8%) patients who showed no injury (no-AKI group). The risk factors for AKI after PNL were found to be a higher preoperative serum uric acid level [odds ratio (OR) = 1.228; 95% confidence interval (95% CI) = 1.065-1.415; P = .005], longer operation time (OR = 1.009; 95% CI = 1.004-1.014; P < .001), and intraoperative hypotension (OR = 12.713; 95% CI = 7.762-20.823; P < .001). Hospitalization and intensive care unit stay duration were significantly longer in the AKI group (8.7 ±â€Š5.2 vs 6.6 ±â€Š2.8 days, P < .001; 0.34 ±â€Š1.74 vs 0.07 ±â€Š0.48 days, P = .002, respectively). Chronic kidney disease was also significantly higher in the AKI group (63.6% vs 32.7%, P = .024).As intraoperative hypotension is an important risk factor for AKI after PNL, which leads to poor postoperative outcomes, it should be prevented or managed vigorously during PNL.


Assuntos
Injúria Renal Aguda , Hipotensão , Complicações Intraoperatórias/epidemiologia , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Feminino , Humanos , Hipotensão/epidemiologia , Hipotensão/etiologia , Cálculos Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/métodos , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco
18.
Medicine (Baltimore) ; 97(26): e11338, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29953025

RESUMO

Mannitol, an osmotic diuretic, has been used to prevent acute kidney injury (AKI). However, studies have found divergent effects of intraoperative mannitol administration on postoperative AKI. We therefore evaluated the effects of intraoperative mannitol administration on AKI after robot-assisted laparoscopic radical prostatectomy (RALP) in prostate cancer patients.A total of 864 patients who underwent RALP were divided into mannitol (administered at 0.5 g/kg) and no-mannitol groups. Demographics, cancer-related data, preoperative laboratory values, intraoperative data, and postoperative outcomes such as AKI, chronic kidney disease at 12 months postoperation, duration of hospital stay, and intensive care unit admission rate and duration of stay were compared between the 2 groups using propensity score matching analysis. To determine the risk factors for AKI after RALP, univariate and multivariate logistic regression analyses were performed. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria.After performing 1:1 propensity score matching, the mannitol and no-mannitol groups included 234 patients each. The overall incidence of AKI after RALP was 5.1% and was not significantly different between the no-mannitol and mannitol groups in the propensity score-matched patients (13 [5.6%] vs. 11 [4.7%], P = .832). Univariate logistic regression analysis revealed that body mass index and operative time were associated with AKI in 864 patients who underwent RALP. However, intraoperative mannitol administration was not associated with AKI after RALP (P = .284). Multivariate logistic regression analysis revealed that operative time was significantly associated with AKI after RALP (odds ratio = 1.013, P = .001). The incidence of chronic kidney disease (13 [5.6%] vs. 12 [5.1%], P = 1.000) and other postoperative outcomes were not also significantly different between the no-mannitol and mannitol groups in the propensity score-matched patients.Intraoperative mannitol administration has no beneficial effect on the prevention of AKI after RALP in prostate cancer patients. This result provides useful information for clinical practice guidelines regarding intraoperative mannitol use.


Assuntos
Injúria Renal Aguda/prevenção & controle , Manitol/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Índice de Massa Corporal , Humanos , Laparoscopia/métodos , Modelos Logísticos , Masculino , Duração da Cirurgia , Período Pós-Operatório , Fatores de Risco , Fatores Socioeconômicos
19.
Cardiovasc J Afr ; 29(1): 16-21, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29582878

RESUMO

INTRODUCTION: This study aimed to evaluate the value of transluminal attenuation gradient (TAG) of stress coronary computed tomography angiography (CCTA), using a wide-area detector CT in patients with coronary artery disease, compared to stress perfusion cardiac magnetic resonance (CMR) imaging. METHODS: This prospective study from May 2012 to January 2015 included 21 patients with moderate coronary stenosis on invasive coronary angiography. All patients underwent adenosine stress single-shot CCTA with a rest CCTA scan using a wide-area detector CT. Coronary artery stenosis was evaluated on both stress and rest CCTA images, and TAG was manually obtained for all vessels. Stress perfusion CMR was used as a reference standard. A TAG cut-off value of -15.1 HU/10 mm was applied for diagnosing haemodynamically significant stenosis. The diagnostic accuracies of TAG and CMR were estimated and compared. RESULTS: TAG of stress CCTA in all coronary arteries had a sensitivity, specificity, and positive and negative predictive values of 90.5, 90.0, 86.4 and 93.1%, respectively. Corresponding values for TAG of rest CCTA in all coronary arteries were 42.9, 83.3, 64.3 and 67.6%, respectively, whereas those for TAG of coronary arteries with moderate stenosis on stress CCTA were 93.3, 100, 100 and 92.3%, respectively. Mean effective radiation doses for stress and rest CCTA were 10.6 ± 2.6 mSv and 2.3 ± 1.3 mSv, respectively. CONCLUSION: TAG of CCTA provided high diagnostic accuracy for detecting haemodynamically significant coronary artery stenosis. TAG of stress CCTA was more diagnostically accurate, especially in coronary arteries with moderate stenosis.


Assuntos
Angiografia por Tomografia Computadorizada/instrumentação , Angiografia Coronária/instrumentação , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Hemodinâmica , Imageamento por Ressonância Magnética , Imagem de Perfusão do Miocárdio/instrumentação , Tomógrafos Computadorizados , Adenosina/administração & dosagem , Idoso , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Vasodilatadores/administração & dosagem
20.
J Thorac Dis ; 8(7): 1524-31, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27499939

RESUMO

BACKGROUND: Identifying markers for predicting the course and outcome of chronic obstructive pulmonary disease (COPD) remains important. The relative pulmonary artery enlargement to aorta ratio (PA-A ratio), which is measured using computed tomography (CT), is a reported predictor for COPD exacerbation and mortality. However, little is known about the implications of the PA-A ratio in patients with mild COPD. METHODS: We investigated the utility of the PA-A ratio as a biomarker in patients with relatively mild COPD. A total of 131 patients with mild to moderate COPD [post-bronchodilator forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) 61.6±6.4, mean post-bronchodilator FEV1 83%±17.8% of predicted value] were selected from a Korean COPD cohort (from 2012 until the end of 2014) and analyzed retrospectively. We determined the correlation between the PA-A ratio and clinical parameters using a linear regression model. RESULTS: The COPD assessment test (P=0.04), FEV1 (P=0.03), and a history of exacerbation in the last year (P=0.03) were significant factors in the univariate linear regression analysis. Post-bronchodilator FEV1 was most significantly associated with the PA-A ratio in the multivariate analysis (P=0.01). CONCLUSIONS: The PA-A ratio evaluated by CT imaging was independently correlated with a representative pulmonary function factor (FEV1) in patients with relatively mild COPD. The results suggest that the PA-A ratio may be an important biomarker for clinical outcome in patients with mild COPD.

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