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1.
Artigo em Inglês | MEDLINE | ID: mdl-32623478

RESUMO

It has been suggested that Fusobacterium nucleatum (Fn) may differentially impact tumor immune responses according to microsatellite instability (MSI) status in colorectal cancers (CRCs). We aimed to reveal the detailed relationship between intratumoral Fn and immune microenvironmental features in MSI-high CRCs. A total of 126 MSI-high CRCs were subjected to analyses for intratumoral Fn DNA load using quantitative PCR and for densities of tumor-infiltrating immune cells, including CD3+ T cells, CD4+ T cells, CD8+ T cells, FoxP3+ T cells, CD68+ macrophages, CD163+ macrophages, and CD177+ neutrophils, at invasive margin (IM) and center of tumor (CT) areas using computational image analysis of immunohistochemistry. Based on the Fn load, the 126 MSI-high CRCs were classified into Fn-high, -low, and -negative subgroups. The Fn-high subset of MSI-high CRCs was significantly correlated with larger tumor size and advanced invasion depth (p = 0.017 and p = 0.034, respectively). Compared with the Fn-low/negative subgroup, Fn-high tumors demonstrated significantly lower density of FoxP3+ cells in both IM and CT areas (p = 0.002 and p = 0.003, respectively). Additionally, Fn-high was significantly associated with elevated CD163+ cell to CD68+ cell ratio in only CT areas of MSI-high CRCs (p = 0.028). In conclusion, the Fn-enriched subset of MSI-high CRCs is characterized by increased tumor growth and invasion and distinct immune microenvironmental features, including decreased FoxP3+ T cells throughout the tumor and increased proportion of M2-polarized macrophages in the tumor center. These findings collectively support that Fn may be linked to pro-tumoral immune responses in MSI-high CRCs.

2.
Hepatol Int ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32557192

RESUMO

BACKGROUND: The association between nonalcoholic fatty liver disease (NAFLD) and renal function changes remains inconclusive. We explored whether the histological severity of NAFLD is associated with early deterioration of renal function. METHODS: Patients with biopsy-proven NAFLD were prospectively followed for renal function monitoring. A renal outcome was defined as a ≥ 50% increase in serum creatinine, a < 30% decrease in the estimated glomerular filtration rate (eGFR) or an eGFR < 45 mL/min/1.73 m2. RESULTS: Among 455 NAFLD patients, 221 (48.6%) had nonalcoholic steatohepatitis (NASH), and no difference in baseline eGFR was found between NASH and NAFL patients. During a median follow-up of 32 months, a renal outcome occurred in 15 patients; the incidence rate was 12.3 per 1,000 person-years. Compared with NAFL, NASH did not increase the risk of renal outcomes. Among the histological components of NAFLD, lobular inflammation (≥ 2), fibrosis (≥ F3), and portal inflammation (≥ 3) significantly increased the risk of renal outcomes in the crude analysis (HR 3.35, 95% CI 1.10-9.11; HR 3.25, 95% CI 1.12-8.84; and HR 7.73, 95% CI 2.86-22.22). After adjustment for risk factors for renal dysfunction, including sex, age, diabetes, hypertension, and chronic kidney disease, only portal inflammation significantly increased the risk of renal outcomes (HR 5.88, 95% CI 1.87-18.42, p = 0.002). CONCLUSIONS: Portal inflammation predicts early deterioration of renal function in patients with biopsy-proven NAFLD. Individualized monitoring of renal function based on the histological severity of NAFLD may be helpful for early identification of long-term renal outcomes.

3.
BMC Cancer ; 20(1): 589, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576177

RESUMO

BACKGROUND: We examined the association between obesity and prostate cancer based on both body mass index (BMI) and waist circumference (WC) using the National Health Insurance System (NHIS) database for the entire male population of Korea. METHODS: A total of 1,917,430 men who underwent at least one health examination in 2009 without a previous diagnosis of any other cancer were tracked through December 2015. The hazard ratio (HR) and 95% confidence interval (CI) value for the association between prostate cancer and obesity were analyzed using multiple Cox regression model. Since there was a statistically significant interaction between WC and BMI, a multiple HR for prostate cancer was estimated with stratifying both WC and BMI to control the interaction between WC and BMI. RESULTS: Without considering WC as an adjustment factor, very weak association between BMI and prostate cancer development risk was observed. When WC was considered as an adjustment factor, no significant change in the HRs for prostate cancer development beyond the reference BMI was observed in the group with WC < 85 cm in the multivariable-adjusted models. However, in the group with WC ≥ 85 cm, the HRs for prostate cancer increased as the BMI increased beyond the reference BMI. In addition, there was a discrepancy in the trend of prostate cancer development according to BMI among the groups with different categories for WC. CONCLUSION: In groups with abdominal obesity, a significant linear relationship was observed between increasing BMI and prostate cancer risk. Higher the WC category, the stronger was the association with BMI, signifying that the association of BMI with risk of prostate cancer development depends on abdominal obesity.

4.
J Pathol Transl Med ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32580537

RESUMO

Here, we provide an up-to-date review of the histopathology and molecular pathology of serrated colorectal lesions. First, we introduce the updated contents of the 2019 World Health Organization classification for serrated lesions. The sessile serrated lesion (SSL) is a new diagnostic terminology that replaces sessile serrated adenoma and sessile serrated polyp. The diagnostic criteria for SSL were revised to require only one unequivocal distorted serrated crypt, which is sufficient for diagnosis. Unclassified serrated adenomas have been included as a new category of serrated lesions. Second, we review ongoing issues concerning the morphology of serrated lesions. Minor morphologic variants with distinct molecular features were recently defined, including serrated tubulovillous adenoma, mucin-rich variant of traditional serrated adenoma (TSA), and superficially serrated adenoma. In addition to intestinal dysplasia and serrated dysplasia, minimal deviation dysplasia and not otherwise specified dysplasia were newly suggested as dysplasia subtypes of SSLs. Third, we summarize the molecular features of serrated lesions. The critical determinant of CpG island methylation development in SSLs is patient age. Interestingly, there may be ethnic differences in BRAF/KRAS mutation frequencies in SSLs. The molecular pathogenesis of TSAs is divided into KRAS and BRAF mutation pathways. SSLs with MLH1 methylation can progress into favorable prognostic microsatellite instability-positive (MSI+)/CpG island methylator phenotype-positive (CIMP+) carcinomas, whereas MLH1-unmethylated SSLs and BRAF-mutated TSAs can be precursors of poor-prognostic MSI-/CIMP+ carcinomas. Finally, based on our recent data, we propose an algorithm for stratifying risk subgroups of non-dysplastic SSLs.

5.
J Intensive Care Med ; : 885066620933245, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515272

RESUMO

BACKGROUND: Recently, a new scoring system was developed that uses the red blood cell distribution width (RDW), delta neutrophil index (DNI), and platelet count (PC) to predict mortality in patients with sepsis. We investigated whether a modified simple scoring system based on the RDW, DNI, and mean platelet volume-to-PC (MPV/PC) ratio could predict the mortality of patients with sepsis, and compared it to the previous scoring system. METHODS: We conducted a retrospective cohort study of 264 adults who had been treated for sepsis in an emergency department between January 2016 and February 2019. Each patient was rated on a scale of 0 to 3 according to the modified scoring system. Point values were assigned based on RDW > 14.5%, DNI > 5.0%, and MPV/PC ratio >10.1. RESULTS: The 28-day mortality rate was 14.4%. Those who died had higher scores than those who survived (mean: 1.55 ± 0.92 vs 0.93 ± 0.78, P < .001). The area under the curve for the new scoring system was higher than that of the previous scoring system (0.685 vs 0.645). CONCLUSION: The modified scoring system was a good predictor of the 28-day mortality and was more useful than the previous scoring system for predicting mortality in patients with sepsis.

6.
J Pathol Transl Med ; 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32580539

RESUMO

Recent advances in immuno-oncology have increased understanding of the tumor immune microenvironment (TIME), and clinical trials for immune checkpoint inhibitor treatment have shown remission and/or durable response in certain proportions of patients stratified by predictive biomarkers. The TIME in colorectal cancer (CRC) was initially evaluated several decades ago. The prognostic value of the immune response to tumors, including tumor-infiltrating lymphocytes, peritumoral lymphoid reaction, and Crohn's-like lymphoid reaction, has been well demonstrated. In this review, we describe the chronology of TIME research and review the up-to-date high-dimensional TIME landscape of CRC. We also summarize the clinical relevance of several biomarkers associated with immunotherapy in CRC, such as microsatellite instability, tumor mutational burden, POLE/POLD mutation, consensus molecular subtype, and programmed death-ligand 1 expression.

7.
ACS Nano ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32539339

RESUMO

Domain morphology plays a pivotal role not only for the synthesis of high-quality 2D transition metal dichalcogenides (TMDs) but also for the further unveiling of related physical and chemical properties, yet little has been divulged to date, especially for metallic TMDs. In addition, solid precursor as a transition metal source has been conventionally introduced for the synthesis of TMDs, which leads to an inhomogeneous distribution of local domains with the substrate position, making it difficult to obtain a reliable film. Here, we tailor the domain morphologies of metallic NbSe2 and NbSe2/WSe2 heterostructures using liquid-precursor chemical vapor deposition (CVD). We find that triangular, hexagonal, tripod-like, and herringbone-like NbSe2 flakes are constructed through control of growth temperature and promoter and precursor concentration. Liquid-precursor CVD ensures domain morphologies that are highly reproducible over repeated growth and uniform along the gas-flow direction. A domain coverage of ∼80% is achieved at a high precursor concentration, starting with tripod-like NbSe2 domain and evolving to the herringbone fractal. Furthermore, mixing liquid W and Nb precursors results in sea-urchin-like heterostructure domains with long-branch-shaped NbSe2 at low temperature, whereas protruded hexagonal heterostructure domains grow at high temperature. Our liquid precursor approach provides a shortcut for tailoring the domain morphologies of metallic TMDs as well as metal/semiconductor heterostructures.

8.
J Korean Med Sci ; 35(19): e189, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419401

RESUMO

BACKGROUND: When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis. METHODS: This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed. RESULTS: During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols. CONCLUSION: Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.


Assuntos
Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência , Fechamento de Instituições de Saúde , Pneumonia Viral/epidemiologia , Adulto , Betacoronavirus , Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Surtos de Doenças/prevenção & controle , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , República da Coreia/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Triagem
9.
Antibiotics (Basel) ; 9(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32414054

RESUMO

Implementation of antibiotic stewardship is difficult in patients with sepsis because of severity of disease. We evaluated the impact of glycopeptide discontinuation (GD) in patients with culture negative severe sepsis or septic shock who received glycopeptides as initial empiric antibiotic therapy at admission. We conducted a single center retrospective cohort study between January 2010 and March 2018. GD was defined as discontinuation of initial empiric glycopeptides on availability of culture results, revealing the absence of identified pathogens. In 92 included patients, the leading causes of sepsis were pneumonia (34.8%) and intra-abdominal infection (23.9%); 28-day mortality and overall mortality were 14% and 21%, respectively. Glycopeptides were discontinued in 42/92 patients. After propensity score matching, baseline characteristics were not significantly different between the GD and non-GD (GND) groups. GND was associated with development of acute kidney injury (OR 5.54, 95% CI 1.49-20.6, P = 0.011). GD did not increase the 7-day, 14-day, and 28-day mortality compared with GND. The length of hospital stay was shorter in the GD group than in GND group (16.33 ± 17.11 vs. 25.05 ± 14.37, P = 0.082), though not statistically significant. GD may be safe and reduce adverse events of prolonged antibiotic use in patients with culture negative severe sepsis or septic shock receiving glycopeptides as initial empiric antibiotic therapy.

10.
Breast Cancer Res Treat ; 182(1): 97-105, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418044

RESUMO

PURPOSE: Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC). METHODS: After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed. RESULTS: pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). CONCLUSIONS: Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.

11.
BMC Gastroenterol ; 20(1): 117, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306900

RESUMO

BACKGROUND: The majority of colonic obstructions result from colorectal cancer. However, malignancies of extra-colonic origin can also disrupt colorectal patency, and the efficacy of self-expanding metal stents (SEMS) insertion as a bridge to surgery in these patients are still in debate. The aim of this study is to evaluate the efficacy of endoscopic stenting as a bridge to surgery (BTS) for extra-colonic malignancy (ECM)-induced colonic obstruction. METHODS: Thirty-three patients with colonic obstruction due to ECM who received self-expanding metal stents (SEMS) insertion at a single academic tertiary medical center between 2004 and 2015 were included. The purpose of SEMS insertion was determined based on whether the patient's medical records indicated any surgical plans before SEMS insertion. Technical success was defined as a patent SEMS covering the entire length of the obstruction. Bridging success was defined as elective surgical procedures after the first SEMS insertion. RESULTS: Among the 33 patients who underwent SEMS insertion for colorectal obstruction due to ECM, nine underwent SEMS as a BTS. Technical success was achieved in 100% (9/9). Seven patients underwent elective surgery after successful decompression with the first SEMS, and the bridging success rate was 77.8% (7/9). Two patients needed secondary stent insertion before elective surgery. However, none of them required emergent surgery. No major complications occurred, including death related to colorectal endoscopic procedures, perforation, or bleeding. CONCLUSION: SEMS insertion as a BTS is a good treatment option to avoid emergent surgery in patients with colonic obstruction caused by extra-colonic malignancy.

12.
J Korean Med Sci ; 35(14): e149, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281317

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Idoso , Feminino , Humanos , Imunização Passiva , Masculino , Pandemias , República da Coreia , Síndrome do Desconforto Respiratório do Adulto/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-32267568

RESUMO

BACKGROUND AND AIM: Generally, colonoscopy is less effective for detecting colorectal adenomas in the right-sided colon compared with the distal colon. Repeat forward-view (RF) examination of the right-sided colon has been suggested to increase the adenoma detection rate (ADR). However, studies investigating the efficacy of RF examination are lacking. Thus, the aim of this study was to determine whether RF examination in the right-sided colon enhances right-sided ADR. METHODS: We performed a prospective, randomized controlled trial, including asymptomatic subjects who underwent screening colonoscopy. Subjects were randomized to the RF group, in which the right-sided colon was examined twice in the forward view, or to the standard forward-view (SF) group, in which the right-sided colon was examined once in the forward view. The primary outcome was the right-sided ADR on RF examination of the right-sided colon. RESULTS: A total of 640 subjects completed the study protocol (RF group, n = 320; SF group, n = 320). The right-sided ADR in the RF group was significantly higher than that in the SF group (17.5% vs 11.9%, respectively; P = 0.044). In the RF group, an additional 31 adenomas were found, resulting in an increased detection rate of adenomas of 38.3% compared with the first forward view. The ADR of the whole colon was similar between the groups. CONCLUSIONS: In our prospective randomized controlled trial, RF examination of the right-sided colon, which can be easily performed in clinical practice, was associated with an increased rate of detection of right-sided ADR.

14.
Medicina (Kaunas) ; 56(3)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168799

RESUMO

Background and objective: Although obesity is associated with an increased risk of peptic ulcer disease (PUD), no study has evaluated the association of PUD with sarcopenia. The aim of this study was to evaluate the association of sarcopenia and obesity with PUD. Material and Methods: Data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV and V for 2007-2012 were used. PUD history, dietary, alcohol consumption, smoking, physical activity patterns, and other socioeconomic factors were analyzed. Sarcopenia index (appendicular skeletal muscle mass (kg) ÷ body mass index (kg/m2)) and body fat mass were determined by dual-energy X-ray absorptiometry. Univariate and multivariate analyses were performed to evaluate the association of sarcopenia with the prevalence of PUD. Results: The 7092 patients were divided into the sarcopenic obesity (SO, n = 870), sarcopenic non-obesity (n = 2676), non-sarcopenic obesity (NSO, n = 2698), and non-sarcopenic non-obesity (NSNO, n = 848) groups. The prevalence of PUD in these groups was 70 (7.9%), 170 (7.4%), 169 (6.3%), and 47 (3.8%), respectively (p < 0.001). A crude analysis revealed that the prevalence of PUD was 2.2-fold higher in the SO group than in the NSNO group (odds ratio (OR), 2.2; 95% confidence interval (CI), 1.5-3.2), the significance of which remained after adjustment for age, sex, body mass index, and HOMA-IR (homeostatic model assessment insulin resistance) score (OR, 1.9; 95% CI, 1.3-2.7). Conclusion: In conclusion, in this nationally representative cohort, the combination of muscle and fat mass, as well as obesity, was associated with an increased risk of PUD.

15.
Sci Rep ; 10(1): 5270, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210254

RESUMO

Human epidermal growth factor receptor 2 (HER2) is implicated in several cancers, including gastric cancer. However, limited data are available regarding its clinical significance in early gastric cancer (EGC). We evaluated the clinical significance of HER2 overexpression in patients with EGC. We retrospectively reviewed 727 patients who underwent surgical treatment for EGC between October 2010 and August 2017. HER2 expression was analysed in 680 EGC cases by immunohistochemistry and classified as negative (0 and 1+), equivocal (2+), or positive [overexpression (3+)]. Among patients with differentiated EGC, the number of patients with HER2 overexpression was not significantly different from that of HER2-negative patients in terms of age, sex, tumour size, location, gross type, depth of invasion, presence of lymphovascular invasion (LVI), and presence of lymph node metastasis (LNM). However, in patients with undifferentiated EGC, HER2 overexpression was significantly correlated with LVI and presence of LNM compared with HER2-negative patients. Multivariate analysis indicated HER2 overexpression as a good predictive marker of LNM in patients with undifferentiated EGC. HER2 expression is associated with LNM in undifferentiated EGC. Therefore, the importance of HER2 overexpression in EGC should not be overlooked, and further studies are needed to identify its clinical significance.

16.
Adv Mater ; 32(14): e1906989, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32103565

RESUMO

Biomolecular piezoelectric materials are considered a strong candidate material for biomedical applications due to their robust piezoelectricity, biocompatibility, and low dielectric property. The electric field has been found to affect tissue development and regeneration, and the piezoelectric properties of biological materials in the human body are known to provide electric fields by pressure. Therefore, great attention has been paid to the understanding of piezoelectricity in biological tissues and its building blocks. The aim herein is to describe the principle of piezoelectricity in biological materials from the very basic building blocks (i.e., amino acids, peptides, proteins, etc.) to highly organized tissues (i.e., bones, skin, etc.). Research progress on the piezoelectricity within various biological materials is summarized, including amino acids, peptides, proteins, and tissues. The mechanisms and origin of piezoelectricity within various biological materials are also covered.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32062042

RESUMO

BACKGROUND & AIMS: There are no biomarkers of nonalcoholic steatohepatitis (NASH) that are ready for routine clinical use. We investigated whether an analysis of PNPLA3 and TM6SF2 genotypes (rs738409 and rs58542926) can be used to identify patients with nonalcoholic fatty liver disease (NAFLD), with and without diabetes, who also have NASH. METHODS: We collected data from the Boramae registry in Korea on 453 patients with biopsy-proven NAFLD with sufficient clinical data for calculating scores. Patients enrolled from May 2011 through March 2016 were assigned to cohort 1 (n = 302; discovery cohort) and patients enrolled thereafter were assigned to cohort 2 (n = 151; validation cohort). DNA samples were obtained from all participants and analyzed for the PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, SREBF2 rs133291 C>T, MBOAT7-TMC4 rs641738 C>T, and HSD17B13 rs72613567 adenine insertion (A-INS) polymorphisms. We used multivariable logistic regression analyses with stepwise backward selection to build a model to determine patients' risk for NASH (NASH PT) using the genotype and clinical data from cohort 1 and tested its accuracy in cohort 2. We used the receiver operating characteristic (ROC) curve to compare the diagnostic performances of the NASH PT and the NASH scoring systems. RESULTS: We developed a NASH PT scoring system based on PNPLA3 and TM6SF2 genotypes, diabetes status, insulin resistance, and levels of aspartate aminotransferase and high-sensitivity C-reactive protein. NASH PT scores identified patients with NASH with an area under the ROC (AUROC) of 0.859 (95% CI, 0.817-0.901) in cohort 1. In cohort 2, NASH PT scores identified patients with NASH with an AUROC of 0.787 (95% CI, 0.715-0.860), which was significantly higher than the AUROC of the NASH score (AUROC, 0.729; 95% CI, 0.647-0.812; P = .007). The AUROC of the NASH PT score for detecting NASH in patients with NAFLD with diabetes was 0.835 (95% CI, 0.776-0.895) and in patients without diabetes was 0.809 (95% CI, 0.757-0.861). The negative predictive value of the NASH PT score <-0.785 for NASH in patients with NAFLD with diabetes reached 0.905. CONCLUSIONS: We developed a scoring system, based on polymorphisms in PNPLA3 and TM6SF2 and clinical factors that identifies patients with NAFLD, with or without diabetes, who have NASH, with an AUROC value of 0.787. This system might help clinicians better identify NAFLD patients at risk for NASH.

18.
Ophthalmic Epidemiol ; 27(2): 105-114, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31672074

RESUMO

Purpose: Work-related eye injuries have been reported with a variety of epidemiologic and clinical characteristics. We aimed to identify epidemiologic characteristics of work-related eye injuries and risk factors associated with severe injury in a large metropolitan city.Methods: This multicentre, retrospective, observational study used a prospective eye injury registry. We included patients with work-related eye injuries at four tertiary teaching hospitals in Daegu, South Korea, between August 2016 and July 2018. Severe injuries were defined as subjects fulfilled one or more of the following criteria: 1) presented with open globe injury; 2) required emergency eye surgery or observation after hospitalization; 3) developed eye injury-associated complications or 4) impaired final visual acuity.Results: The study included 1,424 patients. One hundred seventy-three patients (12.1%) had severe injuries. The median age and interquartile range (IQR; 25th and 75th percentiles) of the subjects were 48.0 years (IQR, 36.0-57.0), and the majority (91.9%) were male. Among the subjects, 61 patients (4.2%) suffered eye injuries despite the use of protective eyewear at the time of injury. Multivariable logistic regression analysis revealed age ≥70 years (odds ratio: 4.02, 95% confidence interval: 1.77-9.15), hammering/nailing (6.80, 2.80-16.53), and mowing (4.87, 1.77-9.15) as activities that conferred a high risk of ocular trauma with severe injury.Conclusion: Age over 70 years, hammering/nailing, and mowing were risk factors for severe injury from work-related ocular trauma. Severe eye injury could occur in spite of the use of protective eyewear; appropriate, well-fitting protective eyewear should be emphasized in the future.

19.
J Gastroenterol ; 55(3): 330-341, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31535207

RESUMO

BACKGROUND AND AIMS: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis. METHODS: Our cross-sectional study included 559 subjects (mean age of 53 years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25 kg/m2) or non-obese (< 25 kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+ , (3) obese MS-, and (4) obese MS+. RESULTS: Obese MS- and non-obese MS+ groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+ group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+ group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+ groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis. CONCLUSION: The non-obese MS+ group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+ individuals who develop NASH with significant hepatic fibrosis. CLINICAL TRIAL NUMBER: NCT02206841.

20.
Clin Cancer Res ; 26(4): 870-881, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31757879

RESUMO

PURPOSE: Despite the well-known prognostic value of the tumor-immune microenvironment (TIME) in colorectal cancers, objective and readily applicable methods for quantifying tumor-infiltrating lymphocytes (TIL) and the tumor-stroma ratio (TSR) are not yet available. EXPERIMENTAL DESIGN: We established an open-source software-based analytic pipeline for quantifying TILs and the TSR from whole-slide images obtained after CD3 and CD8 IHC staining. Using a random forest classifier, the method separately quantified intraepithelial TILs (iTIL) and stromal TILs (sTIL). We applied this method to discovery and validation cohorts of 578 and 283 stage III or high-risk stage II colorectal cancers patients, respectively, who were subjected to curative surgical resection and oxlaliplatin-based adjuvant chemotherapy. RESULTS: Automatic quantification of iTILs and sTILs showed a moderate concordance with that obtained after visual inspection by a pathologist. The K-means-based consensus clustering of 197 TIME parameters that showed robustness against interobserver variations caused colorectal cancers to be grouped into five distinctive subgroups, reminiscent of those for consensus molecular subtypes (CMS1-4 and mixed/intermediate group). In accordance with the original CMS report, the CMS4-like subgroup (cluster 4) was significantly associated with a worse 5-year relapse-free survival and proved to be an independent prognostic factor. The clinicopathologic and prognostic features of the TIME subgroups have been validated in an independent validation cohort. CONCLUSIONS: Machine-learning-based image analysis can be useful for extracting quantitative information about the TIME, using whole-slide histopathologic images. This information can classify colorectal cancers into clinicopathologically relevant subgroups without performing a molecular analysis of the tumors.

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