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1.
Sensors (Basel) ; 24(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38931713

RESUMO

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.


Assuntos
Inteligência Artificial , Unidades de Terapia Intensiva , Humanos , Síndrome do Desconforto Respiratório/terapia
2.
Crit Care ; 26(1): 253, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996117

RESUMO

BACKGROUND: Although lung protective strategy and adjunctive intervention are associated with improved survival in patients with acute respiratory distress syndrome (ARDS), the implementation of effective therapies remains low. This study aimed to evaluate whether the use of business intelligence (BI) for real-time data visualization is associated with an improvement in lung protective strategy and adjunctive therapy. METHODS: A retrospective observational cohort study was conducted on patients with ARDS admitted between September 2020 and June 2021 at two intensive care units (ICUs) of a tertiary referral hospital in Taiwan. BI was imported for data visualization and integration to assist in clinical decision in one of the ICUs. The primary outcomes were the implementation of low tidal volume ventilation (defined as tidal volume/predicted body weight ≤ 8 mL/kg) within 24 h from ARDS onset. The secondary outcomes included ICU and hospital mortality rates. RESULTS: Among the 1201 patients admitted to the ICUs during the study period, 148 (12.3%) fulfilled the ARDS criteria, with 86 patients in the BI-assisted group and 62 patients in the standard-of-care (SOC) group. Disease severity was similar between the two groups. The application of low tidal volume ventilation strategy was significantly improved in the BI-assisted group compared with that in the SOC group (79.1% vs. 61.3%, p = 0.018). Despite their ARDS and disease severity, the BI-assisted group tended to achieve low tidal volume ventilation. The ICU and hospital mortality were lower in the BI-assisted group. CONCLUSIONS: The use of real-time visualization system for data-driven decision support was associated with significantly improved compliance to low tidal volume ventilation strategy, which enhanced the outcomes of patients with ARDS in the ICU.


Assuntos
Síndrome do Desconforto Respiratório , Humanos , Unidades de Terapia Intensiva , Pulmão , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Volume de Ventilação Pulmonar
3.
Int J Mol Sci ; 23(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35216156

RESUMO

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of immature testicular tissues (ITT) from transgenic donor, to wild-type recipient mice. Donors and recipients were age-mismatched (from 20-week-old donors to 3-week-old recipients, and vice versa) and the transplantation sites involved the abdomen, skin of the head, back muscle, and scrotum. The application of poly-l-lactic acid (PLLA) scaffold was also evaluated in age-matched donors and recipients (both 3-weeks-old). To quantitively evaluate the process of spermatogenesis after ITT transplantation and scaffold application, bioluminescence imaging (BLI) was employed. Our result showed that ITT from 3-week-old mice had the best potential for spermatogenesis, and the optimal transplantation site was in the scrotum. Spermatogenesis was observed in recipient mice up to 51 days after transplantation, and up to the 85th day if scaffold was used. The peak of spermatogenesis occurred between the 42nd and 55th days in the scaffold group. This animal model may serve as a framework for further studies in prepubertal male fertility preservation.


Assuntos
Preservação da Fertilidade/métodos , Infertilidade Masculina/terapia , Espermatogênese , Testículo/citologia , Engenharia Tecidual/métodos , Animais , Infertilidade Masculina/etiologia , Masculino , Camundongos , Poliésteres/química , Lesões Experimentais por Radiação/complicações , Testículo/crescimento & desenvolvimento , Testículo/fisiologia , Alicerces Teciduais/química
4.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36293000

RESUMO

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.


Assuntos
Preservação da Fertilidade , Masculino , Camundongos , Animais , Preservação da Fertilidade/métodos , Camundongos Transgênicos , Testículo/metabolismo , Espermatogênese , Engenharia Tecidual , Modelos Animais de Doenças , Criopreservação
5.
Int J Mol Sci ; 22(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34638663

RESUMO

Decellularization has emerged as a potential solution for tracheal replacement. As a fully decellularized graft failed to achieve its purposes, the de-epithelialization partial decellularization protocol appeared to be a promising approach for fabricating scaffolds with preserved mechanical properties and few immune rejection responses after transplantation. Nevertheless, a lack of appropriate concurrent epithelialization treatment can lead to luminal stenosis of the transplant and impede its eventual success. To improve re-epithelialization, autologous nasal epithelial cell sheets generated by our cell sheet engineering platform were utilized in this study under an in vivo rabbit model. The newly created cell sheets have an intact and transplantable appearance, with their specific characteristics of airway epithelial origin being highly expressed upon histological and immunohistochemical analysis. Subsequently, those cell sheets were incorporated with a partially decellularized tracheal graft for autograft transplantation under tracheal partial resection models. The preliminary results two months post operation demonstrated that the transplanted patches appeared to be wholly integrated into the host trachea with adequate healing of the luminal surface, which was confirmed via endoscopic and histologic evaluations. The satisfactory result of this hybrid scaffold protocol could serve as a potential solution for tracheal reconstructions in the future.


Assuntos
Células Epiteliais/citologia , Nariz/citologia , Traqueia/citologia , Animais , Estudos Transversais , Matriz Extracelular/fisiologia , Masculino , Coelhos , Procedimentos de Cirurgia Plástica/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Transplante Autólogo/métodos
6.
Eur Arch Otorhinolaryngol ; 274(1): 399-404, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27395068

RESUMO

While conservative approaches for chronic sialoadenitis are in current use, the utility of intraductal injection therapy remains unclear. The purpose of this study is to provide evidence that substances delivered through intraductal injection of the salivary gland are able to be effectively distributed throughout the gland. Methylene blue dye (0.1 %) was injected intraductally into a porcine parotid gland (5 ml) of one group and the porcine submandibular gland (1 or 2 ml, n = 6 for each preparation) of another group. After the injection, the ductal systems were evaluated, sectioned, and observed microscopically. Color area analysis was performed on submandibular gland sections, and the infiltration ratio of the dye was calculated. The papillae of both Stensen's and Wharton's duct openings were easily identified with intraductally delivered methylene blue dye. The dye infiltration began from the central ductal region of the gland and could be easily observed to gradually disperse to the peripheral regions in each acinar. There were no statistically significant differences in infiltration ratios between anterior, midline, and posterior section of the submandibular gland. Also, there were no statistically significant differences in the ratios between 1 and 2 ml injections at all the three section positions. This study demonstrated that desired substances can be evenly delivered throughout the salivary gland through intraductal injections. The use of intraductal injections might serve as a potential therapeutic procedure in the management of salivary gland diseases.


Assuntos
Corantes/administração & dosagem , Azul de Metileno/administração & dosagem , Glândula Parótida , Glândula Submandibular , Animais , Sistemas de Liberação de Medicamentos , Injeções , Masculino , Ductos Salivares , Suínos
7.
Eur Arch Otorhinolaryngol ; 273(8): 2027-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26335291

RESUMO

It is important to have a standardized tympanic membrane (TM) perforation platform to evaluate the various myringoplasty materials that have been studied and developed extensively during recent years. However, currently there are no cellular models specifically designed for this purpose, and animal models remain unsatisfactory. The purpose of this study is to propose an inexpensive, readily available, well-controlled, and easy-to-create cellular model as a substitute for use in the evaluation of TM repairing materials. A trans-well model was created using a cell culture insert with a round hole created at the center of the polycarbonate membrane. HaCaT cells were cultured on the fenestrated culture insert, and the desired myringoplasty graft was placed at the center of the window for one week and observed by fluorescent microscopy under vital staining. Under this cellular model, there was notable migration of HaCaT cells onto the positive control graft (rabbit fascia), while only a few cell clusters were observed on the negative control graft (paper). Model validation showed that the cell migration ratio for the PLLA + 1% hyaluronic acid (HA) graft is significantly higher than using myringoplasty paper, poly L-lactide (PLLA), or PLLA + 0.5% HA (p < 0.05). This trans-well-based cellular model might be a useful pre-evaluation platform for the evaluation of TM repairing materials. The model is inexpensive, readily available, easy to create, and standardized for use.


Assuntos
Ácido Hialurônico/uso terapêutico , Miringoplastia , Resinas Acrílicas/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Animais , Técnicas de Cultura de Células , Fáscia/transplante , Humanos , Masculino , Teste de Materiais , Modelos Estruturais , Miringoplastia/instrumentação , Miringoplastia/métodos , Cimento de Policarboxilato/uso terapêutico , Coelhos , Membrana Timpânica/cirurgia , Perfuração da Membrana Timpânica/cirurgia
8.
Surg Today ; 44(5): 927-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24218008

RESUMO

PURPOSE: We evaluated the adhesive strength of ethyl-2-cyanoacrylate and compared the findings with those of traditional monofilament synthetic sutures. We also investigated the factors that could affect the effectiveness of cyanoacrylate bonding by skin surface modifications at the adhesion site. METHODS: Using a porcine skin model, we measured the maximum load for ethyl-2-cyanoacrylate adhesive under various application conditions. RESULTS: When the application width was 5 mm, no differences were found in the maximum force load for one layer or two layers of ethyl-2-cyanoacrylate adhesive (3.3 ± 1.7 and 4.8 ± 1.5 N, p = 0.176). When the application width was extended to 10 mm, the maximum force load for one layer was 8.2 ± 0.6 N, which was significantly higher than for 5 mm (p < 0.002). The force fell to within the loads generated by 6-0 to 5-0 ETHILON™ monofilament non-absorbable synthetic sutures. Roughening of the application surface had little effect on adhesion; however, smoothing resulted in a decrease in overall adhesive strength. CONCLUSIONS: The width of the application of ethyl-2-cyanoacrylate adhesive over the skin defect was important for achieving good and stable adhesive strength. Increasing the number of layers of adhesive through repeated applications of the cyanoacrylate did not increase overall adhesive strength. Skin surface modifications other than regular cleaning should be avoided.


Assuntos
Cianoacrilatos , Suturas , Resistência à Tração , Adesivos Teciduais , Animais , Pele , Técnicas de Sutura , Suínos
9.
J Microbiol Immunol Infect ; 57(1): 184-188, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38151433

RESUMO

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %.


Assuntos
Pneumonia Viral , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Taiwan/epidemiologia , Pacientes
10.
Artigo em Inglês | MEDLINE | ID: mdl-38942661

RESUMO

BACKGROUND: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. METHODS: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. RESULTS: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results. CONCLUSIONS: In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.

11.
J Microbiol Immunol Infect ; 57(3): 480-489, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38471985

RESUMO

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Taiwan , Antibacterianos/uso terapêutico , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Adulto , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética
12.
Eur Arch Otorhinolaryngol ; 270(2): 695-704, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22673737

RESUMO

The purpose of this study was to determine the effect of all-trans retinoid acid (ATRA) on two nasopharyngeal cancer (NPC) cell lines and to evaluate the synergistic effect of ATRA used in combination with cisplatin, a standard chemotherapeutic agent for NPC. Two NPC cell lines (NPC-TW01 and NPC-TW04) were used, and the MTT assay was used to analyze cell growth inhibition under various concentrations of ATRA and cisplatin. Under low concentrations of ATRA, the growth of both cell lines was significantly inhibited. When ATRA was used in combination with cisplatin, the resulting synergistic effects were robust and significant. Only a low concentration of ATRA was required to produce a synergistic effect when combined with cisplatin, indicating the potential usefulness of a combination therapy regimen. Therefore, the combination of ATRA and cisplatin is a viable treatment option for NPC and should be further investigated.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Tretinoína/administração & dosagem , Carcinoma , Linhagem Celular Tumoral/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Inibidores do Crescimento/administração & dosagem , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Células Tumorais Cultivadas/efeitos dos fármacos
13.
Wounds ; 25(1): 15-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25867703

RESUMO

OBJECTIVE: Bulb suction drains have long been used in various surgical procedures. The purpose of this study was to evaluate 4 commonly used bulb suction devices in vitro to explore the nonlinear changes in draining ability and efficiency along with the conformation changes of the device throughout the draining processes. METHODS: Under a designed simulated scenario using pure water as the desired draining substance, the relative function of the J-VAC 100 cc (JV100) (Ethicon, Inc, Somerville, USA); the EVACUATOR 125cc (EP125) (Pacific Hospital Supply, Taiwan); the Bulb Reservoir 150 cc (BH150) (Hosmed, Inc, Miami, FL); and the HemoVac 400 cc (HV400) (Zimmer, Inc, Warsaw, IN) drains were compared. The maximum collection capacities and the dead space at maximum compression of each bulb drain were recorded and compared. The collected fluid weight was recorded along with time, and collection speeds were calculated and compared. RESULTS: The maximum collected weight of the 4 drains were 110.07 ± 0.54 g (JV100), 122.7 ± 06.51 g (EP125), 140.8 ± 03.78 g (BH150), and 335.07 ± 04.24 g (HV400). The dead spaces under maximum compression were 15.63 ± 01.32 ml, 19.80 ± 03.37 ml, 34.23 ± 06.77 ml, and 82.83 ± 05.51 ml, respectively. The collecting speed-volume curves were generated from the authors' tested devices. Although slightly different individually, typical characteristics, such as tendency to reach maximum collection speed at the very beginning of the collection phase; rapid decline to about 65% of peak collection speed when approximately 30% of the total collection volume had been achieved; and inefficient collection speed in the later collection phase were noted. CONCLUSIONS: Among all the bulb drains tested in this study, all of them performed well in vitro. Although using bulb drains continues to be an effective and economic draining method after operation, clinicians should be aware of the nonlinear features of suction efficiency during the drainage process to avoid unexpected function deterioration. .

14.
J Funct Biomater ; 14(3)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36976071

RESUMO

Few efforts have been made regarding the optimization of porcine small intestinal submucosa (SIS) to improve its biocompatibility. This study aims to evaluate the effect of SIS degassing on the promotion of cell attachment and wound healing. The degassed SIS was evaluated in vitro and in vivo, compared with the nondegassed SIS control. In the cell sheet reattachment model, the reattached cell sheet coverage was significantly higher in the degassed SIS group than in the nondegassed group. Cell sheet viability was also significantly higher in the SIS group than in the control group. In vivo studies showed that the tracheal defect repaired by the degassed SIS patch showed enhanced healing and reductions in fibrosis and luminal stenosis compared to the nondegassed SIS control group, with the thickness of the transplanted grafts in the degassed SIS group significantly lower than those in the control group (346.82 ± 28.02 µm vs. 771.29 ± 20.41 µm, p < 0.05). Degassing the SIS mesh significantly promoted cell sheet attachment and wound healing by reducing luminal fibrosis and stenosis compared to the nondegassed control SIS. The results suggest that the degassing processing might be a simple and effective way to improve the biocompatibility of SIS.

16.
Biomolecules ; 11(6)2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200705

RESUMO

In this study, we developed a new procedure for the rapid partial decellularization of the harvested trachea. Partial decellularization was performed using a combination of detergent and sonication to completely remove the epithelial layers outside of the cartilage ring. The post-decellularized tracheal segments were assessed with vital staining, which showed that the core cartilage cells remarkably remained intact while the cells outside of the cartilage were no longer viable. The ability of the decellularized tracheal segments to evade immune rejection was evaluated through heterotopic implantation of the segments into the chest muscle of rabbits without any immunosuppressive therapy, which demonstrated no evidence of severe rejection or tissue necrosis under H&E staining, as well as the mechanical stability under stress-pressure testing. Finally, orthotopic transplantation of partially decellularized trachea with no immunosuppression treatment resulted in 2 months of survival in two rabbits and one long-term survival (2 years) in one rabbit. Through evaluations of posttransplantation histology and endoscopy, we confirmed that our partial decellularization method could be a potential method of producing low-immunogenic cartilage scaffolds with viable, functional core cartilage cells that can achieve long-term survival after in vivo transplantation.


Assuntos
Matriz Extracelular/química , Engenharia Tecidual , Alicerces Teciduais/química , Traqueia/química , Animais , Coelhos
17.
Thorac Cancer ; 11(9): 2672-2680, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32767461

RESUMO

BACKGROUND: This study aimed to evaluate the characteristics of patients with newly diagnosed advanced lung cancer who initially presented with respiratory failure. METHODS: This was a retrospective study which analyzed patients in the intensive care unit (ICU) with newly diagnosed advanced lung cancer who were placed on mechanical ventilation (MV). We defined newly diagnosed lung cancer as pathological or molecular results for treatment decisions not yet determined when the patient was admitted to ICU. RESULTS: During the 14-year inclusion period, 845 lung cancer patients requiring MV were screened. A total of 56 newly diagnosed extensive lung cancer patients were analyzed. Cancer-related to central airway obstruction (n = 29, 51.8%) was the leading cause of respiratory failure. The significant etiologies of delay in the diagnosis of lung cancer were diagnostic error, mistaking cancer for tuberculosis, and missed hilar lesions. The six-month survival rate was only 7.1% (n = 4). The sequential organ failure assessment (SOFA) score was significantly associated with mortality (HR = 1.142, 95% CI = 1.012-1.288, P = 0.031). The six-month survival rate in patients receiving suitable targeted therapy and accepting chemotherapy and best supportive care was 40% (2/5), 0% (0/7), and 4.5% (2/44), respectively. CONCLUSIONS: Patients with newly diagnosed advanced lung cancer with acute life-threatening respiratory failure have poor outcomes. Cancer-related to central airway obstruction is a leading cause of respiratory failure. Diagnostic errors such as tuberculosis and missed hilar lesions are the two main etiologies of a delay in diagnosis. The SOFA score is correlated with mortality. Targeted therapy can raise the six-month survival rates in patients with oncogenic mutation adenocarcinoma, who survive after presentation in a critical condition.


Assuntos
Neoplasias Pulmonares/complicações , Insuficiência Respiratória/etiologia , Idoso , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Respiratória/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
18.
Int J Cancer ; 124(9): 2210-9, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19123483

RESUMO

Phloretin (Ph), a natural product found in apples and pears with glucose transporter (GLUT) inhibitory activity, exerts antitumor effects. However, little is known about its effects on human liver cancer. The purpose of this study is to test the cytotoxic effects of Ph on HepG2 cells and to identify the underlying molecular pathways. Human hepatocellular carcinoma specimens and HepG2 show a high level of GLUT2 transporter activity in the cell membrane. Real-time PCR and MTT assays demonstrate that Ph-induced cytotoxicity correlates with the expression of GLUT2. Flow cytometry and DNA fragmentation studies show that 200 microM Ph induces apoptosis in HepG2, which was reversed by glucose pretreatment. GLUT2 siRNA knockdown induced HepG2 apoptosis, which was not reversed by glucose. Western blot analysis demonstrates that both intrinsic and extrinsic apoptotic pathways in addition to Akt and Bcl-2 family signaling pathways are involved in Ph-induced cell death in HepG2 cells. Furthermore, using flow cytometry analysis, a mitochondrial membrane potential assay and Western blot analysis, we show that cytochalasin B, a glucose transport inhibitor, enhances the Ph-induced apoptotic effect on HepG2 cells, which was reversed by pretreatment with glucose. Furthermore, we found significant antitumor effects in vivo by administering Ph at 10 mg/kg intraperitoneally to severe combined immune deficiency mice carrying a HepG2 xenograft. A microPET study in the HepG2 tumor-bearing mice showed a 10-fold decrease in (18)F-FDG uptake in Ph-treated tumors compared to controls. Taken together, these results suggest that Ph-induced apoptosis in HepG2 cells involves inhibition of GLUT2 glucose transport mechanisms.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Transportador de Glucose Tipo 2/antagonistas & inibidores , Neoplasias Hepáticas/patologia , Floretina/farmacologia , Animais , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocalasina B/farmacologia , Citometria de Fluxo , Imunofluorescência , Glucose/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Técnicas Imunoenzimáticas , Técnicas In Vitro , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos SCID , Tomografia por Emissão de Pósitrons , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Transplante Heterólogo
19.
J Biomed Biotechnol ; 2009: 917837, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20069129

RESUMO

Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-alpha-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-alpha stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-alpha induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.


Assuntos
Quimiocina CCL2/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Interleucina-8/metabolismo , Ticlopidina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Quimiocina CCL2/genética , Quimiotaxia/efeitos dos fármacos , Células Endoteliais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-8/genética , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição RelA/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
20.
Exp Ther Med ; 17(4): 2907-2912, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30936960

RESUMO

Obstructive salivary gland diseases are common conditions that arise following the disruption of the secretary ductal system and usually results in the swelling and pain of the affected gland(s). There has been an increase in the use of sialendoscopy for the treatment and diagnosis of obstructive salivary gland infection. If damage occurs to a duct or papilla following sialendoscopy, a stent may be necessary to prevent restenosis and for maintaining the salivary duct open after complete sialendoscopy. Currently, there are only non-biodegradable salivary duct stents available. The aim of the current study was to establish a methodology for the fabrication of a biodegradable poly-L-lactide (PLLA) salivary duct stent and to examine its function in an animal model. In the current study, PLLA was used to fabricate a salivary duct stent, which was compared with other commercially available non-biodegradable products. The mechanical tests revealed that the tensile strength of the PLLA stent was similar to that of the commercially available non-biodegradable stents. The Young's modulus, which measures the stiffness of a solid material, was significantly higher for the PLLA stent compared with the commercially available non-biodegradable stents. In addition, the current study demonstrated that the PLLA salivary duct stent was easily used with current sialendoscopy techniques, allowing accurate stent placement in an animal model.

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