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1.
Kaohsiung J Med Sci ; 40(5): 445-455, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593276

RESUMO

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.


Assuntos
Movimento Celular , Proteínas Proto-Oncogênicas c-akt , Receptor trkC , Transdução de Sinais , Humanos , Receptor trkC/metabolismo , Receptor trkC/genética , Feminino , Linhagem Celular Tumoral , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Pessoa de Meia-Idade , Idoso , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Estimativa de Kaplan-Meier , Neoplasias Urológicas/genética , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/patologia
2.
Molecules ; 29(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38398564

RESUMO

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Humanos , Fármacos Neuroprotetores/farmacologia , Lipopolissacarídeos/farmacologia , Hericium
3.
Thorac Cardiovasc Surg ; 72(2): 96-104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36812923

RESUMO

BACKGROUND: The effect of continuous myocardial perfusion (CMP) on the surgical results of acute type A aortic dissection (ATAAD) remains unclear. METHODS: From January 2017 to March 2022, 141 patients who underwent ATAAD (90.8%) or intramural hematoma (9.2%) surgery were reviewed. Fifty-one patients (36.2%) received proximal-first aortic reconstruction and CMP during distal anastomosis. Ninety patients (63.8%) underwent distal-first aortic reconstruction and were placed in traditional cold blood cardioplegic arrest (CA; 4°C, 4:1 blood-to-Plegisol) throughout the procedure. The preoperative presentations and intraoperative details were balanced using inverse probability of treatment weighting (IPTW). Their postoperative morbidity and mortality were analyzed. RESULTS: The median age was 60 years. The incidence of arch reconstruction in the unweighted data was higher in the CMP compared with the CA group (74.5 vs 52.2%, p = 0.017) but was balanced after IPTW (62.4 vs 58.9%, p = 0.932, standardized mean difference = 0.073). The median cardiac ischemic time was lower in the CMP group (60.0 vs 130.9 minutes, p < 0.001), but cerebral perfusion time and cardiopulmonary bypass time were similar. The CMP group did not demonstrate any benefit in the reduction of the postoperative maximum creatine kinase-MB ratio (4.4 vs 5.1% in CA, p = 0.437) or postoperative low cardiac output (36.6 vs 24.8%, p = 0.237). Surgical mortality was comparable between groups (15.5% in CMP vs 7.5% in the CA group, p = 0.265). CONCLUSION: Application of CMP during distal anastomosis in ATAAD surgery, irrespective of the extent of aortic reconstruction, reduced myocardial ischemic time but did not improve cardiac outcome or mortality.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Parada Cardíaca Induzida/efeitos adversos , Parada Cardíaca Induzida/métodos , Perfusão/métodos , Anastomose Cirúrgica , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Estudos Retrospectivos
4.
Viruses ; 15(10)2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37896791

RESUMO

Cervical cancer, a major health concern among women worldwide, is closely linked to human papillomavirus (HPV) infection. This study explores the evolving landscape of HPV molecular epidemiology in Taiwan over a decade (2010-2020), where prophylactic HPV vaccination has been implemented since 2007. Analyzing data from 40,561 vaginal swab samples, with 42.0% testing positive for HPV, we reveal shifting trends in HPV genotype distribution and infection patterns. The 12 high-risk genotypes, in order of decreasing percentage, were HPV 52, 58, 16, 18, 51, 56, 39, 59, 33, 31, 45, and 35. The predominant genotypes were HPV 52, 58, and 16, accounting for over 70% of cases annually. The proportions of high-risk and non-high-risk HPV infections varied across age groups. High-risk infections predominated in sexually active individuals aged 30-50 and were mixed-type infections. The composition of high-risk HPV genotypes was generally stable over time; however, HPV31, 33, 39, and 51 significantly decreased over the decade. Of the strains, HPV31 and 33 are shielded by the nonavalent HPV vaccine. However, no reduction was noted for the other seven genotypes. This study offers valuable insights into the post-vaccine HPV epidemiology. Future investigations should delve into HPV vaccines' effects and their implications for cervical cancer prevention strategies. These findings underscore the need for continued surveillance and research to guide effective public health interventions targeting HPV-associated diseases.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Papillomavirus Humano , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Epidemiologia Molecular , Papillomaviridae/genética , Genótipo , Papillomavirus Humano 31/genética , Prevalência
5.
J Cachexia Sarcopenia Muscle ; 14(5): 2226-2238, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562939

RESUMO

BACKGROUND: Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID-19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance. METHODS: The effects of Sanghuangporus sanghuang SS-MN4 mycelia were tested on two groups of 6-week-old male mice-one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub-groups: a control group, a group that underwent hind limb casting for 7 days and then recovered for 7 days and a group that was administered with SS-MN4 orally for 14 days, underwent hind limb casting for 7 days and then recovered for 7 days. The fatigue group was divided into two sub-groups: a control group that received no SS-MN4 intervention and an experimental group that was administered with SS-MN4 orally for 39 days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA-seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS-MN4 treatment. RESULTS: In a disuse atrophy model induced by hind limb casting, supplementing with 250 mg/kg of SS-MN4 for 14 days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill (P < 0.05). In a fatigue animal model, equivalent SS-MN4 dosage improved swimming (178.7%) and running (162.4%) activities (P < 0.05) and reduced blood urea nitrogen levels by 18% (P < 0.05). SS-MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA-seq and western blot studies from the C2C12 myotube showed that SS-MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage. CONCLUSIONS: Supplementation of SS-MN4 (250-mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast-twitch fibre regrowth and fatigue resistance.

6.
Antioxidants (Basel) ; 12(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36979011

RESUMO

BACKGROUND: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of Antrodia cinnamomea, is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on cancer cells, especially in human colorectal cancer (CRC), remain unclear. METHODS: The cell death and ROS of the antrodin-C-treated HCT-116 cells were measured by annexin V-FITC/propidium iodide staining, DCFDA, and Fluo-3 fluorescence staining assays. Moreover, signaling molecules regulating TNFα cell death pathways and ROS/AKT/ERK/P38 pathways were also detected in cells treated with antrodin C by Western blotting and chromatin immunoprecipitation. The effects of antrodin C were determined in HCT-116 cell xenograft animal models in terms of tumor volumes and histopathological evaluation. RESULTS: Treatment with antrodin C triggered the activation of extrinsic apoptosis pathways (TNFα, Bax, caspase-3, and -9), and also suppressed the expression of anti-apoptotic molecules Bcl-2 in HCT-116 cells in a time-dependent manner. Antrodin C also decreased cell proliferation and growth through the inactivation of cyclin D1/cyclin for the arrest of the cell cycle at the G1 phase. The activation of the ROS/AKT/ERK/P38 pathways was involved in antrodin-C-induced transcriptional activation, which implicates the role of the histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFα promoters. Immunohistochemical analyses revealed that antrodin C treatment significantly induced TNFα levels, whereas it decreased the levels of PCNA, cyclin D1, cyclin E, and MMP-9 in an in vivo xenograft mouse model. Thus, antrodin C induces cell apoptosis via the activation of the ROS/AKT/ERK/P38 signaling modules, indicating a new mechanism for antrodin C to treat CRC in vitro and in vivo.

7.
J Am Chem Soc ; 144(28): 12613-12618, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35793702

RESUMO

Polyolefins represent the largest class of commodity materials due to their excellent material properties; however, they have limited pathways to chemical recycling and are often difficult to mechanically recycle. Here we demonstrate a new catalyst for the isoselective copolymerization of propylene and butadiene capable of favoring 1,4-insertion over 1,2-insertion while maintaining good molecular weights and turnover frequencies. This isotactic propylene copolymer with main-chain unsaturation was depolymerized to a telechelic macromonomer using an olefin metathesis catalyst and 2-hydroxyethyl acrylate. After hydrogenation, the telechelic macromonomer was repolymerized to form an ester-linked polypropylene material. This polymer shows thermal and mechanical properties comparable to linear low-density polyethylene. Finally, the telechelic macromonomer could be regenerated through the depolymerization of the ester-linked polypropylene material, which allows for the chemical recycling to macromonomer. This process provides a route to transform partially unsaturated polyolefins to chemically recyclable materials with similar properties to their parent polymers.


Assuntos
Ésteres , Polipropilenos , Peso Molecular , Polimerização , Polímeros/química
8.
J Transl Med ; 20(1): 324, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864526

RESUMO

Kidney transplantation is a lifesaving option for patients with end-stage kidney disease. In Taiwan, urothelial carcinoma (UC) is the most common de novo cancer after kidney transplantation (KT). UC has a greater degree of molecular heterogeneity than do other solid tumors. Few studies have explored genomic alterations in UC after KT. We performed whole-exome sequencing to compare the genetic alterations in UC developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). After mapping and variant calling, 18,733 and 11,093 variants were identified in patients with UCKT and UCHD, respectively. We excluded known single-nucleotide polymorphisms (SNPs) and retained genes that were annotated in the Catalogue of Somatic Mutations in Cancer (COSMIC), in the Integrative Onco Genomic cancer mutations browser (IntOGen), and in the Cancer Genome Atlas (TCGA) database of genes associated with bladder cancer. A total of 14 UCKT-specific genes with SNPs identified in more than two patients were included in further analyses. The single-base substitution (SBS) profile and signatures showed a relative high T > A pattern compared to COMSIC UC mutations. Ingenuity pathway analysis was used to explore the connections among these genes. GNAQ, IKZF1, and NTRK3 were identified as potentially involved in the signaling network of UCKT. The genetic analysis of posttransplant malignancies may elucidate a fundamental aspect of the molecular pathogenesis of UCKT.


Assuntos
Carcinoma de Células de Transição , Transplante de Rim , Neoplasias da Bexiga Urinária , Humanos , Mutação/genética , Neoplasias da Bexiga Urinária/patologia , Sequenciamento do Exoma
9.
Acta Cardiol Sin ; 38(2): 159-168, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35273437

RESUMO

Background: The optimal level of hypothermia and safe time of unilateral antegrade cerebral perfusion (uACP) in acute type A aortic dissection (ATAAD) repair remain controversial. Objectives: To analyze the association of uACP time and circulatory arrest temperature with surgical outcomes of ATAAD. Methods: We retrospectively analyzed 263 patients who had undergone ATAAD repair between 2006 and 2020 using uACP. The patients were stratified by three chronologically equivalent periods (period 1, 2006 to 2010; period 2, 2011 to 2015; period 3, 2016 to 2020) to demonstrate the decade-long evolution of surgical strategy and outcomes. Results: The mean age of the patients was 59.4 ± 12.5 years, and 68.8% were male. The hospital mortality rates were 15.1%, 12.9%, and 11.0% from period 1 to 3 (p = 0.740). The median circulatory arrest temperatures were 20, 23, and 25 °C (p < 0.001), respectively, and the median uACP times were 72, 59, and 41 minutes (p < 0.001). The incidence rates of postoperative permanent neurologic deficits were 13.2%, 10.9%, and 18.3% (p = 0.312), and those of transient neurologic deficits were 9.4%, 10.9%, and 11.9% (p = 0.936), respectively. Multivariate logistic regression analysis showed that uACP time ≥ 60 minutes was an independent predictor of hospital mortality rather than postoperative stroke. ROC curve analysis estimated an optimal cutoff value of 52 minutes of uACP time when the circulatory arrest temperature was ≥ 25 °C to predict hospital mortality (area under the curve: 0.72). Conclusions: Unilateral antegrade cerebral perfusion time was associated with hospital mortality after ATAAD surgery. A safe threshold of 50 to 60 minutes of uACP should be considered.

10.
Oncol Lett ; 23(4): 128, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35251348

RESUMO

Gemcitabine (GEM) is a typical chemotherapeutic drug used to treat pancreatic cancer, but GEM resistance develops within weeks after chemotherapy. Hence, the development of a new strategy to overcome drug resistance is urgent. 4-Acetylantroquinonol B (4-AAQB), a ubiquinone derived from Taiwanofungus camphoratus, has hepatoprotective, anti-obesity, and antitumor activities. However, the role of 4-AAQB in enhancing GEM sensitivity is unclear. This study aimed to determine the underlying mechanisms by which 4-AAQB enhances cytotoxicity and GEM sensitivity. Cell viability was dramatically reduced by 4-AAQB (2 and 5 µM) treatment in the MiaPaCa-2 and GEM-resistant MiaPaCa-2 (MiaPaCa-2GEMR) human pancreatic cancer cells. 4-AAQB led to cell cycle arrest, upregulated the levels of reactive oxygen species (ROS), promoted apoptosis, and inhibited autophagy, which subsequently enhanced GEM chemosensitivity by suppressing the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1)-initiated PI3K/Akt/multidrug resistance protein 1 (MDR1) signaling pathway in both cell lines. Vascular endothelial growth factor A (VEGFA) expression, cell migration, and invasion were also inhibited by the 4-AAQB incubation. Overall, this combination treatment strategy might represent a novel approach for GEM-resistant pancreatic cancer.

11.
Molecules ; 26(19)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34641562

RESUMO

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Polyporales/química , Adulto , Idoso , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micélio/química , Organoides , Ratos , Células Tumorais Cultivadas
12.
Acta Cardiol Sin ; 37(1): 18-29, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33488024

RESUMO

BACKGROUND: Very limited therapeutic strategies exist to prevent the primary failure of arteriovenous (AV) fistulas in patients with diabetes. OBJECTIVES: To investigate whether rosuvastatin could improve the primary patency of AV fistulas in diabetic patients with stage 5 chronic kidney disease (CKD). METHODS: This was a double-blind randomized clinical trial. From July 2012 to September 2018, patients aged between 18 and 65 years with type 2 diabetes and stage 5 CKD were randomized to receive placebo or rosuvastatin (5 mg/day) for 7 days prior to the creation of an AV fistula on the forearm until the 21st day after surgery. Patients were followed up for 180 days after the operation. The primary composite endpoint was the development of fistula immaturity or stenosis. The secondary endpoints were changes in inflammatory markers, oxidative stress, and occurrence of postoperative complications. RESULTS: A total of 60 patients were enrolled in the study. Rosuvastatin resulted in a 20% reduction in total cholesterol from postoperative day 0 to 28 (p = .0006). The overall rate of AV fistula failure (immaturity or stenosis) was 30%, with no significant difference between patients receiving rosuvastatin and those receiving the placebo (33.3% vs. 26.7%, p = .5731). Although not statistically significant, the administration of rosuvastatin might have increased the incidence of postoperative complications (2.99 vs. 2.39 event rate per 1000 patient-days; odds ratio, 1.33; p = .5986). CONCLUSIONS: Rosuvastatin showed no significant beneficial effects on the primary patency of AV fistulas in diabetic patients with stage 5 CKD, but might have been associated with the risk of drug-related complications.

13.
Ann Thorac Surg ; 111(3): 923-929, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32738223

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used in patients with circulatory collapse or extremely unstable hemodynamics caused by acute massive pulmonary embolism (PE). The effectiveness of simultaneous thrombolytic therapy has been rarely investigated in these patients after being stabilized with ECMO. METHODS: From January 2008 to December 2018 consecutive patients with acute massive PE requiring ECMO supported in a tertiary medical center were included for retrospective analysis. RESULTS: Thirteen patients with PE underwent ECMO implantation and received subsequent thrombolytic therapy as a definite treatment for PE. All patients survived their ECMO courses to a successful decannulation, with a mean ECMO support duration of 6.23 ± 4.69 days. Eleven patients (84.62%) survived to hospital discharge. All survivors were alive during follow-up, although 2 patients (18.2%) had permanent dysfunctional neurologic complications. Major bleeding complications occurred in 4 patients (30.77%), whereas no patient had intracranial hemorrhage. Systemic thrombolysis showed comparable outcomes of catheter-directed thrombolysis in our patients who underwent ECMO. CONCLUSIONS: Thrombolysis-based therapeutic strategy under ECMO could be a relatively safe and effective definitive treatment for patients with acute massive PE, even for those who were resuscitated. Bleeding complications remain a major concern and should be monitored and managed immediately.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Fibrinolíticos/administração & dosagem , Embolia Pulmonar/terapia , Terapia Trombolítica/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
JAMA Netw Open ; 3(8): e2011768, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32821921

RESUMO

Importance: A tool for precisely stratifying postoperative patients with advanced oral cancer is crucial for the treatment plan, such as intensifying or deintensifying the regimen to improve their quality of life and prognosis. Objective: To develop and validate a machine learning-based algorithm that can provide survival risk stratification for patients with advanced oral cancer who have comprehensive clinicopathologic and genetic data. Design, Setting, and Participants: In this prognostic cohort study, the elastic net penalized Cox proportional hazards regression-based risk stratification model was developed and validated using single-center data collected between January 1, 1996, and December 31, 2011. In total, comprehensive clinicopathologic and genetic data (including clinical, pathologic, and 44 cancer-related gene variant profiles) of 334 patients with stage III or IV oral squamous cell carcinoma were used to develop and validate the algorithm in this 15-year cohort study. Data analysis was conducted between February 1, 2018, and May 6, 2020. Main Outcomes and Measures: The main outcomes were cancer-specific survival, distant metastasis-free survival, and locoregional recurrence-free survival. Model performance was compared in terms of the Akaike information criterion and the Harrell concordance index (C index). Results: Complete data were available for 334 patients (315 men; median age at onset, 48 years [interquartile range, 42-56 years]). The predictive models using comprehensive clinicopathologic and genetic data outperformed those using clinicopathologic data alone. In the groups of postoperative patients receiving adjuvant concurrent chemoradiotherapy, the models demonstrated higher classification performance than those using clinicopathologic data alone in cancer-specific survival (mean [SD] C index, 0.689 [0.050] vs 0.673 [0.051]; P = .02) and locoregional recurrence-free survival (mean [SD] C index, 0.693 [0.039] vs 0.678 [0.035]; P = .004). The classification performance in distant metastasis-free survival was not different (mean [SD] C index, 0.702 [0.056] vs 0.688 [0.048]; P = .09). Conclusions and Relevance: A risk stratification model using comprehensive clinicopathologic and genetic data accurately differentiated the high-risk group from the low-risk group in cancer-specific survival and locoregional recurrence-free survival for postoperative patients with advanced oral cancer. This algorithm could be used through an online calculator to provide additional personalized information for postoperative management of patients with advanced oral squamous cell carcinoma.


Assuntos
Aprendizado de Máquina , Neoplasias Bucais/mortalidade , Medição de Risco/métodos , Adulto , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Prognóstico , Estudos Retrospectivos
15.
J Med Internet Res ; 22(8): e20261, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32763879

RESUMO

BACKGROUND: Colorectal cancer screening by fecal occult blood testing has been an important public health test and shown to reduce colorectal cancer-related mortality. However, the low participation rate in colorectal cancer screening by the general public remains a problematic public health issue. This fact could be attributed to the complex and unpleasant operation of the screening tool. OBJECTIVE: This study aimed to validate a novel toilet paper-based point-of-care test (ie, JustWipe) as a public health instrument to detect fecal occult blood and provide detailed results from the evaluation of the analytic characteristics in the clinical validation. METHODS: The mechanism of fecal specimen collection by the toilet-paper device was verified with repeatability and reproducibility tests. We also evaluated the analytical characteristics of the test reagents. For clinical validation, we conducted comparisons between JustWipe and other fecal occult blood tests. The first comparison was between JustWipe and typical fecal occult blood testing in a central laboratory setting with 70 fecal specimens from the hospital. For the second comparison, a total of 58 volunteers were recruited, and JustWipe was compared with the commercially available Hemoccult SENSA in a point-of-care setting. RESULTS: Adequate amounts of fecal specimens were collected using the toilet-paper device with small day-to-day and person-to-person variations. The limit of detection of the test reagent was evaluated to be 3.75 µg of hemoglobin per milliliter of reagent. Moreover, the test reagent also showed high repeatability (100%) on different days and high reproducibility (>96%) among different users. The overall agreement between JustWipe and a typical fecal occult blood test in a central laboratory setting was 82.9%. In the setting of point-of-care tests, the overall agreement between JustWipe and Hemoccult SENSA was 89.7%. Moreover, the usability questionnaire showed that the novel test tool had high scores in operation friendliness (87.3/100), ease of reading results (97.4/100), and information usefulness (96.1/100). CONCLUSIONS: We developed and validated a toilet paper-based fecal occult blood test for use as a point-of-care test for the rapid (in 60 seconds) and easy testing of fecal occult blood. These favorable characteristics render it a promising tool for colorectal cancer screening as a public health instrument.


Assuntos
Aparelho Sanitário/provisão & distribuição , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Sangue Oculto , Testes Imediatos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Voluntários
16.
Thorac Cardiovasc Surg ; 68(8): 706-713, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31891949

RESUMO

BACKGROUND: Coronary artery bypass grafting (CABG) is frequently performed in patients with end-stage renal disease (ESRD) together with severe coronary artery disease, after which, patients with ESRD have higher surgical risk and poorer long-term outcomes. We report our experience in patients with ESRD who survived in CABG and identify predictors of long-term outcomes. METHODS: We retrospectively investigated 93 consecutive patients with ESRD who survived to discharge after isolated CABG between January 2005 and December 2016 at our institution. Long-term outcomes, including all-cause mortality after discharge, readmission due to major adverse cardiac events, and reintervention, were evaluated. Predictors affecting long-term outcomes were also analyzed. RESULTS: The rates of freedom from all-cause mortality after discharge in 1, 3, 5, and 10 years were 92.1, 81.3, 71.9, and 34.9%, respectively. The rates of freedom from readmission due to major adverse cardiac events in 1, 3, 5, and 10 years were 90.7, 79.1, 69.9, and 55.6%, respectively. The rates of freedom from reintervention in 1, 3, 5, and 10 years were 95.3, 86.5, 79.0, and 66.6%, respectively. Postoperative ß-blocker and statin use significantly improved overall long-term survival (ß-blocker, p = 0.013; statin, p = 0.009). After case-control matching, patients who received statins showed better long-term survival than those without statins. The comparison of long-term survival between patients with and without ß-blockers showed no significant difference after matching. CONCLUSIONS: After CABG, dialysis patients who survived to discharge had acceptable long-term overall survival. Post-CABG statin use in dialysis patients is a predictor of better long-term survival.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Falência Renal Crônica/terapia , Diálise Renal , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
ACS Macro Lett ; 9(8): 1161-1166, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35653207

RESUMO

The compatibilization of polyethylene (PE) and isotactic polypropylene (iPP) blends is of particular interest due to the challenges associated with recycling these plastics from mixed waste streams. Polyethylene-graft-iPP copolymers (PE-g-iPP) were prepared using a grafting-through strategy by copolymerization of ethylene with allyl-terminated iPP macromonomers in the presence of a hafnium pyridylamido catalyst. Graft copolymers with a variety of graft lengths (Mn = 6-28 kg/mol), graft numbers, and graft spacings were prepared. These graft copolymers were melt-blended with high-density polyethylene (HDPE) and iPP (iPP/HDPE = 30/70 w/w), and the blend properties were evaluated by tensile testing. The blends showed enhanced tensile strength at 5 and 1 wt % loading, with higher tensile strength observed for larger block numbers and graft lengths. These results indicate that graft copolymers are efficient compatibilizers for blends of HDPE and iPP.

19.
Gen Thorac Cardiovasc Surg ; 67(11): 1001-1005, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31152378

RESUMO

Cabrol shunt and several of its modifications have been used as adjunctive procedures to control inaccessible bleeding occurring after aortic root surgeries. Nevertheless, the hemostatic effect of the shunt is suboptimal when the reconstructive procedure extends to the aortic arch and coronary arteries. We propose a "Mantle-style" modified Cabrol shunt to facilitate hemostasis of the exsanguination from the neo-root after aortic root replacement with concomitant arch and coronary reconstruction.


Assuntos
Aorta/cirurgia , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Hemorragia/prevenção & controle , Hemostasia Cirúrgica/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Vasos Coronários/cirurgia , Humanos , Masculino
20.
Ann Thorac Surg ; 107(5): 1333-1341, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30552885

RESUMO

BACKGROUND: A bloodstream infection in patients undergoing cardiovascular operations is crucial because it can result in significantly worse outcomes. However, microbiological patterns have rarely been investigated in these patients. METHODS: We retrospectively reviewed the data of 1,041 adult patients who underwent cardiovascular operations using cardiopulmonary bypass from January 2013 to December 2017 at the National Cheng Kung University Hospital, Tainan, Taiwan. The microbiological pattern and associated variables were analyzed in patients with early postoperative primary bloodstream infection. RESULTS: Primary bloodstream infection developed in 28 patients (2.7%) within 7 days after cardiovascular operations using cardiopulmonary bypass. In patients with early primary bloodstream infection, 36 microorganisms were isolated, and a gram-negative bacillus was identified to be the predominant pathogen (28 of 36 [77.8%]). The most common microorganisms comprised the Enterobacter (n = 8) and Acinetobacter (n = 7) species, and 16 of the 28 gram-negative bacilli belonged to the Enterobacteriaceae family. Compared with those without postoperative bloodstream infection, patients with Enterobacteriaceae family-related early postoperative bloodstream infections had a significantly longer cardiopulmonary bypass time and also worse early and late survival rates. CONCLUSIONS: Most patients with early primary bloodstream infection after cardiovascular operations using cardiopulmonary bypass were infected with gram-negative bacilli, and the Enterobacteriaceae family was the most common microorganism observed. Endogenous bacterial translocation after prolonged cardiopulmonary bypass is a possible mechanism of Enterobacteriaceae family-related early primary bloodstream infection in these patients. Prophylactic use of an antibiotic regimen with broader gram-negative bacteria coverage in cardiovascular surgical patients with prolonged cardiopulmonary bypass should be considered.


Assuntos
Bacteriemia/epidemiologia , Ponte Cardiopulmonar/efeitos adversos , Infecções por Enterobacteriaceae/epidemiologia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Taiwan
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