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1.
Tech Coloproctol ; 27(6): 481-490, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37160596

RESUMO

PURPOSE: To evaluate the potential benefits associated with the short-term (6 months) treatment with transanal irrigation (TAI) in patients suffering from functional constipation (FC), functional fecal incontinence (FI), and low anterior resection syndrome (LARS). METHODS: A multicenter observational study (12 centers; 369 patients) was conducted to assess the following primary and secondary objectives: to evaluate the level of satisfaction regarding bowel control and quality of life (QoL); to evaluate bowel symptoms severity and dropout frequency and reason. To this aim, validated questionnaires were provided to the patients at baseline (T0) and after 6 months of TAI treatment (T6) performed with the medical device Peristeen® Plus (Coloplast A/S, Denmark). Statistical analyses were conducted to compare the outcomes obtained at T0 and T6. RESULTS: A 6-month treatment with TAI enabled a statistically significant (p < 0.05) improvement of QoL scores, satisfaction scores regarding bowel control, and severity indexes of disorder-related symptoms in patients suffering from FC, FI, and LARS. Globally, 8.0% of patients discontinued the treatment after 6 months as a result of occurrence of symptoms (2.4%) or other justifications (3.8%) such as personal reasons. None of the dropouts were due to treatment inefficacy. CONCLUSION: Results of the present study suggest that short-term TAI treatment is beneficial for patients suffering from functional bowel disorders and LARS. Future analysis of prospective data will focus on the clinical outcomes associated with the long-term use (up to 24 months) of TAI when dealing with these types of medical conditions.


Assuntos
Síndrome do Intestino Irritável , Neoplasias Retais , Humanos , Qualidade de Vida , Complicações Pós-Operatórias , Estudos Prospectivos , Síndrome do Intestino Irritável/terapia , Síndrome de Ressecção Anterior Baixa
2.
Ned Tijdschr Geneeskd ; 1672023 04 17.
Artigo em Holandês | MEDLINE | ID: mdl-37078561

RESUMO

BACKGROUND: Orbital cellulitis is a potentially life-threatening condition. Compression of the optical nerve can cause total or partial loss of vision. Early diagnosis is crucial to prevent complications. In case of a unilateral sinusitis as cause of a unilateral orbital cellulitis complete clinical and dental examination combined with imaging are essential in diagnostics. CASE DESCRIPTION: A 53-year-old man presented with left eye movement impairment, intermittent diplopia and moderate swelling of the left lower eyelid. His diagnosis was post septal orbital cellulitis and despite administration of oral antibiotics no clinical improvement was observed. Orbital imaging by CT could not exclude a dental cause of his unilateral maxillary sinusitis. He was referred to the department of oral and maxillofacial surgery where clinical examination showed a dental cause. After removal of two decayed upper molars a complete recovery was accomplished. CONCLUSION: Odontogenic causes for unilateral orbital cellulitis should always be considered in diagnostics in adults. Clinical presentation and dental examination combined with adequate imaging can confirm the diagnosis.


Assuntos
Celulite Orbitária , Sinusite , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Celulite Orbitária/diagnóstico , Celulite Orbitária/etiologia , Sinusite/complicações , Diplopia , Antibacterianos/uso terapêutico , Exame Físico/efeitos adversos , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/etiologia
3.
Front Chem ; 10: 963701, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277347

RESUMO

Coronavirus disease (COVID-19), which is caused by SARS-CoV-2, is the biggest challenge to the global public health and economy in recent years. Until now, only limited therapeutic regimens have been available for COVID-19 patients, sparking unprecedented efforts to study coronavirus biology. The genome of SARS-CoV-2 encodes 16 non-structural, four structural, and nine accessory proteins, which mediate the viral life cycle, including viral entry, RNA replication and transcription, virion assembly and release. These processes depend on the interactions between viral polypeptides and host proteins, both of which could be potential therapeutic targets for COVID-19. Here, we will discuss the potential medicinal value of essential proteins of SARS-CoV-2 and key host factors. We summarize the most updated therapeutic interventions for COVID-19 patients, including those approved clinically or in clinical trials.

4.
Cell Stem Cell ; 29(6): 873-875, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35659872

RESUMO

Using an automatic microfluidics droplet platform, Ding et al. successfully replicated the tumor micro-environment by generating micro-organospheres, which were then used to predict the response to anti-tumor drugs. These miniature models could be obtained within an extremely short time frame of 14 days, amplifying their role in facilitating cancer treatment decisions.


Assuntos
Neoplasias , Humanos , Microfluídica , Neoplasias/diagnóstico , Medicina de Precisão , Microambiente Tumoral
5.
Anal Chem ; 94(19): 6939-6947, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35503862

RESUMO

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivo metabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivo by REIMS during four glossectomies. Complementary desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivo REIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivo tissue recognition during oral cavity cancer surgeries.


Assuntos
Metabolômica , Neoplasias Bucais , Humanos , Espectrometria de Massas/métodos , Neoplasias Bucais/cirurgia , Análise Multivariada , Espectrometria de Massas por Ionização por Electrospray/métodos
6.
J Appl Clin Med Phys ; 23(1): e13449, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34708923

RESUMO

Despite medical physics becoming a more patient-facing part of the radiation oncology team, medical physics graduate students have no training in patient communication. An introductory patient communication training for medical physics graduate students is presented here. This training exposes participants to foundational concepts and effective communication skills through a lecture and it allows them to apply these concepts through realistic simulated patient interactions. The training was conducted virtually, and eight students participated. The impact of the training was evaluated based on changes in both confidence and competence of the participants' patient communication skills. Participants were asked to fill out a survey to assess their confidence on communicating with patients before and after the training. They also underwent a simulated patient interaction pre- and postlecture. Their performance during these was evaluated by both the simulated patient actors and the participants themselves using a rubric. Each data set was paired and analyzed for significance using a Wilcoxon rank-sum test with an alpha of 0.05. Participants reported significantly higher confidence in their feeling of preparedness to interact with patients (mean = 2.38 vs. 3.88, p = 0.008), comfort interacting independently (mean = 2.00 vs. 4.00, p = 0.002), comfort showing patients they are actively listening (mean = 3.50 vs. 4.50, p = 0.005), and confidence handling challenging patient interactions (mean = 1.88 vs. 3.38, p = 0.01), after the training. Their encounter scores, as evaluated by the simulated patient actors, significantly increased (mean = 77% vs. 91%, p = 0.022). Self-evaluation scores increased, but not significantly (mean = 62% vs. 68%, p = 0.184). The difference between the simulated patient and self-evaluation scores for the postinstruction encounter was statistically significant (p = 0.0014). This patient communication training for medical physics graduate students is effective at increasing both the confidence and the competence of the participants in the subject. We propose that similar trainings be incorporated into medical physics graduate training programs prior to students entering into residency.


Assuntos
Comunicação , Simulação de Paciente , Competência Clínica , Humanos , Física , Estudantes
7.
Cell Chem Biol ; 28(3): 257-270, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33651977

RESUMO

The high-throughput phenotypic screen (HTPS) has become an emerging technology to discover synthetic small molecules that regulate stem cell fates. Here, we review the application of HTPS to identify small molecules controlling stem cell renewal, reprogramming, differentiation, and lineage conversion. Moreover, we discuss the use of HTPS to discover small molecules/polymers mimicking the stem cell extracellular niche. Furthermore, HTPSs have been applied on whole-animal models to identify small molecules regulating stem cell renewal or differentiation in vivo. Finally, we discuss the examples of the utilization of HTPS in stem cell-based disease modeling, as well as in the discovery of novel drug candidates for cancer, diabetes, and infectious diseases. Overall, HTPSs have provided many powerful tools for the stem cell field, which not only facilitate the generation of functional cells/tissues for replacement therapy, disease modeling, and drug screening, but also help dissect molecular mechanisms regulating physiological and pathological processes.


Assuntos
Ensaios de Triagem em Larga Escala , Células-Tronco/citologia , Biologia Celular , Diferenciação Celular , Humanos , Fenótipo
8.
Oncotarget ; 11(28): 2686-2701, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32733642

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. New animal models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs and advance standard-of-care therapeutics. This study utilized the Oncopig Cancer Model to develop a translational porcine HCC model which can serve as a bridge between murine studies and human clinical practice. Reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug metabolizing enzyme expression. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous (SQ) injection into immunodeficient mice and Oncopigs. Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers. Whole-genome sequencing demontrated intrahepatic tumor tissue resembled human HCC at the genomic level. Finally, Oncopig HCC cells are amenable to gene editing for development of personalized HCC tumors. This study provides a novel, clinically-relevant porcine HCC model which holds great promise for improving HCC outcomes through testing of novel therapeutic approaches to accelerate and enhance clinical trials.

9.
AJR Am J Roentgenol ; 214(4): 893-899, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045307

RESUMO

OBJECTIVE. The aim of this study is to evaluate the ability of dual-energy CT (DECT) to identify bone marrow edema (BME) in the head and neck region in comparison with MRI as the standard of reference. MATERIALS AND METHODS. A total of 33 patients who underwent imaging between February 2016 and February 2018 were included in this retrospective study. All patients underwent both DECT and MRI for head and neck abnormalities. Two radiologists independently visually assessed virtual noncalcium (VNCa) reconstructions with color-coded maps for the presence of BME. STIR or T2-weighted MRI reconstructions with fat suppression were used as the standard of reference for BME. Subjective quality assessment and severity of metal artifacts were scored on both imaging modalities. RESULTS. BME was detected in 18 patients on DECT compared with 20 patients on MRI. Most BME seen on DECT was located in the mandible. VNCa DECT images had a sensitivity, specificity, positive predictive value, and negative predictive value for BME of 85%, 92%, 94%, and 80% respectively, using MRI as the reference. The quality of the images was rated as excellent to moderate in 94% of the patients for VNCa DECT compared with 82% of the patients for MRI, but this difference was not statistically significant. Significantly more metal artifacts were scored on the mixed DECT images than on the MR images, but these artifacts did not interfere with diagnosis. CONCLUSION. BME detection in the head and neck region seems possible with VNCa DECT images and has the potential to provide an alternative for MRI in clinical practice.


Assuntos
Doenças da Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Tech Coloproctol ; 24(2): 127-143, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31974827

RESUMO

Perianal sepsis is a common condition ranging from acute abscess to chronic anal fistula. In most cases, the source is considered to be a non-specific cryptoglandular infection starting from the intersphincteric space. Surgery is the main treatment and several procedures have been developed, but the risks of recurrence and of impairment of continence still seem to be an unresolved issue. This statement reviews the pertinent literature and provides evidence-based recommendations to improve individualized management of patients.


Assuntos
Doenças do Ânus , Fístula Retal , Sepse , Dermatopatias , Abscesso/etiologia , Abscesso/cirurgia , Doenças do Ânus/etiologia , Doenças do Ânus/cirurgia , Humanos , Fístula Retal/etiologia , Fístula Retal/cirurgia , Resultado do Tratamento
11.
J Clin Lipidol ; 13(2): 287-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30797720

RESUMO

BACKGROUND: There is a lack of information on the health care of familial hypercholesterolemia (FH). OBJECTIVE: The objective of this study was to compare the health care of FH in countries of the Asia-Pacific region and Southern Hemisphere. METHODS: A series of questionnaires were completed by key opinion leaders from selected specialist centers in 12 countries concerning aspects of the care of FH, including screening, diagnosis, risk assessment, treatment, teaching/training, and research; the United Kingdom (UK) was used as the international benchmark. RESULTS: The estimated percentage of patients diagnosed with the condition was low (overall <3%) in all countries, compared with ∼15% in the UK. Underdetection of FH was associated with government expenditure on health care (Ï° = 0.667, P < .05). Opportunistic and systematic screening methods, and the Dutch Lipid Clinic Network criteria were most commonly used to detect FH; genetic testing was infrequently used. Noninvasive imaging of coronary calcium and/or carotid plaques was underutilized in risk assessment. Patients with FH were generally not adequately treated, with <30% of patients achieving guideline recommended low-density lipoprotein cholesterol targets on conventional therapies. Treatment gaps included suboptimal availability and use of lipoprotein apheresis and proprotein convertase subtilsin-kexin type 9 inhibitors. A deficit of FH registries, training programs, and publications were identified in less economically developed countries. The demonstration of cost-effectiveness for cascade screening, genetic testing, and specialized treatments were significantly associated with the availability of subsidies from the health care system (Ï° = 0.571-0.800, P < .05). CONCLUSION: We identified important gaps across the continuum of care for FH, particularly in less economically developed countries. Wider implementation of primary and pediatric care, telehealth services, patient support groups, education/training programs, research activities, and health technology assessments are needed to improve the care of patients with FH in these countries.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Hiperlipoproteinemia Tipo II/epidemiologia , Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/complicações , LDL-Colesterol/sangue , Atenção à Saúde/economia , Dietoterapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Educação em Saúde , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/economia , Hiperlipoproteinemia Tipo II/terapia , Reembolso de Seguro de Saúde , Internacionalidade , Inibidores de PCSK9 , Sistema de Registros , Medição de Risco , Inibidores de Serina Proteinase/farmacologia , Inibidores de Serina Proteinase/uso terapêutico
12.
Transl Res ; 207: 19-29, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30620888

RESUMO

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.


Assuntos
Fatores de Crescimento Endotelial/sangue , Pré-Eclâmpsia/sangue , Adulto , Proteínas de Ligação ao Cálcio , Família de Proteínas EGF , Endoglina/sangue , Análise Fatorial , Feminino , Humanos , Modelos Logísticos , Análise Multivariada , Fator de Crescimento Placentário/sangue , Gravidez , Análise de Componente Principal , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
13.
Tech Coloproctol ; 22(12): 933-939, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30535666

RESUMO

BACKGROUND: Laser closure is a novel sphincter-saving technique for the treatment of anal fistula. The aim of this study was to report middle term results of laser treatment without closure of the internal orifice and to identify prognostic factors to improve selection criteria and maximize healing. METHODS: A retrospective observational study was conducted on patients treated with laser for transphinteric anal fistula. A diode laser emitting laser energy of 12W at a wavelength of 1470 nm was used. The relationship between fistula healing and age, sex, previous fistula surgery, location of fistula, and length of fistula tract was investigated. A successful outcome was defined by the complete healing of the surgical wound and external opening for at least 6 months. RESULTS: Thirty patients (16 males, median age 52 years, range 26-72 years) underwent laser fistula closure between January 2015 and December 2016. Cure was achieved in 10 patients (33.3%). The mean follow-up was 11.30 months (range 6-24 months). Patients with persistent or recurrent fistula were offered repeat surgery. Eventually 4 underwent laser treatment once more. Two patients were cured leading to an overall healing rate of 40% (12 out of 30). Only 4 minor complications occurred (13.3%). No worsening of anal continence was registered. Only fistula length had a statistically significant correlation with successful treatment. Fistula tracts shorter than 30 mm were associated with a primary healing rate of 58.3% while tracts longer than 30 mm were cured in only 16.6% of cases (p < 0.02). CONCLUSIONS: Laser closure is a safe and effective treatment for transphinteric anal fistula. The fistula length is the only significant prognostic factor when closing anal fistulas exclusively with laser: shorter fistulas have a better outcome.


Assuntos
Lasers Semicondutores/uso terapêutico , Fístula Retal/patologia , Fístula Retal/cirurgia , Adulto , Idoso , Canal Anal/patologia , Canal Anal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Cicatrização
14.
Sci Rep ; 8(1): 12548, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135483

RESUMO

Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to humans, we engineered transgenic sus scrofa expressing a LSL-KRASG12D-TP53R167H cassette. By applying Adeno-Cre to pancreatic duct cells in vitro, cells self-immortalized and established tumors in immunocompromised mice. When Adeno-Cre was administered to the main pancreatic duct in vivo, pigs developed extensive PDAC at the injection site hallmarked by excessive proliferation and desmoplastic stroma. This serves as the first large animal model of pancreatic carcinogenesis, and may allow for insight into new avenues of translational research not before possible in rodents.


Assuntos
Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Sus scrofa/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Animais Geneticamente Modificados , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Integrases , Camundongos SCID , Mutação , Neoplasias Experimentais , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Vasc Interv Radiol ; 29(8): 1194-1202.e1, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29887183

RESUMO

PURPOSE: This study used the Oncopig Cancer Model (OCM) to develop alcohol-induced fibrosis in a porcine model capable of developing hepatocellular carcinoma. MATERIALS AND METHODS: Liver injury was induced in 8-week-old Oncopigs (n = 10) via hepatic transarterial infusion of 0.75 mL/kg ethanol-ethiodized oil (1:3 v/v). Feasibility was assessed in an initial Oncopig cohort (n = 5) by histologic analysis at 8 weeks after induction, and METAVIR results were compared to age- and sex-matched healthy controls (n = 5). Liver injury was then induced in a second OCM cohort (n = 5) for a time-course study, with post-induction disease surveillance via biweekly physical exam, lab analysis, and liver biopsies until 20 weeks after induction. RESULTS: In Cohort 1, 8-week post-induction liver histologic analysis revealed median METAVIR F3 (range, F3-F4) fibrosis, A2 (range, A2-A3) inflammation, and 15.3% (range, 5.0%-22.9%) fibrosis. METAVIR and inflammation scores were generally elevated compared to healthy controls (F0-F1, P = 0.0013; A0-A1, P = .0013; median percent fibrosis 8.7%, range, 5.8%-12.1%, P = .064). In Cohort 2, histologic analysis revealed peak fibrosis severity of median METAVIR F3 (range, F2-F3). However, lack of persistent alcohol exposure resulted in liver recovery, with median METAVIR F2 (range, F1-F2) fibrosis at 20 weeks after induction. No behavioral or biochemical abnormalities were observed to indicate liver decompensation. CONCLUSIONS: This study successfully validated a protocol to develop METAVIR F3-F4 fibrosis within 8 weeks in the OCM, supporting its potential to serve as a model for hepatocellular carcinoma in a fibrotic liver background. Further investigation is required to determine if repeated alcohol liver injury is required to develop an irreversible METAVIR grade F4 porcine cirrhosis model.


Assuntos
Carcinoma Hepatocelular/etiologia , Transformação Celular Neoplásica/patologia , Etanol , Óleo Etiodado , Cirrose Hepática Alcoólica/etiologia , Neoplasias Hepáticas/etiologia , Fígado/patologia , Animais , Animais Geneticamente Modificados , Biópsia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Progressão da Doença , Feminino , Genes p53 , Genes ras , Cirrose Hepática Alcoólica/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Índice de Gravidade de Doença , Sus scrofa , Fatores de Tempo
16.
Oncotarget ; 8(38): 63620-63634, 2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28969016

RESUMO

Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology. Human HCC transcriptional hallmarks were detected in pHCC cells using RNA-seq, including TERT reactivation, apoptosis evasion, angiogenesis activation, and Wnt signaling activation. Master regulators of gene expression were conserved across Oncopig and 18 human HCC cell lines. pHCC injection into SCID mice resulted in tumors recapitulating human HCC characteristics, including thick trabeculae formation, pseudoacini patterning, and sheets of well-vascularized stroma. Finally, autologous injection of pHCC cells subcutaneously yielded a tumor histologically characterized as Edmondson Steiner (HCC nuclear grade assessment system) grade 2 HCC with trabecular patterning and T-lymphocyte infiltration. These data demonstrate the Oncopig HCC model's utility for improving detection, treatment, and biomarker discovery relevant to human HCC.

17.
J Craniomaxillofac Surg ; 45(9): 1464-1471, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28756966

RESUMO

Oral squamous cell carcinoma (OSCC) is a growing problem globally. OSCC often arises in close anatomical relation to the jaws and may invade the bone. Bone invasion by OSCC has major implications on tumor staging, choice of treatment, outcome, and quality of life. The difference in cortical or medullary bone invasion has implications for these factors. Treatment protocols used for cortical and medullary invasion differ worldwide. By researching possible pathways a more molecular-based clinical staging and tailor-made therapy can be useful for patients with bone invasion by OSCC. An important molecular step in bone invasion seems to be the activation of osteoclasts. Several direct and indirect pathways can activate osteoclasts. Microbial infections, hypoxia, and the immune system could be of interest.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma de Células Escamosas/secundário , Neoplasias Bucais/patologia , Osteogênese/fisiologia , Neoplasias Ósseas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Invasividade Neoplásica/fisiopatologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoclastos/fisiologia , Receptor Ativador de Fator Nuclear kappa-B/metabolismo
18.
J Gen Intern Med ; 32(9): 990-996, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28550609

RESUMO

BACKGROUND: The Tobacco, Alcohol, Prescription Medication, and Other Substance use (TAPS) tool is a combined two-part screening and brief assessment developed for adult primary care patients. The tool's first-stage screening component (TAPS-1) consists of four items asking about past 12-month use for four substance categories, with response options of never, less than monthly, monthly, weekly, and daily or almost daily. OBJECTIVE: To validate the TAPS-1 in primary care patients. DESIGN: Participants completed the TAPS tool in self- and interviewer-administered formats, in random order. In this secondary analysis, the TAPS-1 was evaluated against DSM-5 substance use disorder (SUD) criteria to determine optimal cut-points for identifying unhealthy substance use at three severity levels (problem use, mild SUD, and moderate-to-severe SUD). PARTICIPANTS: Two thousand adult patients at five primary care sites. MAIN MEASURES: DSM-5 SUD criteria were determined via the modified Composite International Diagnostic Interview. Oral fluid was used as a biomarker of recent drug use. KEY RESULTS: Optimal frequency-of-use cut-points on the self-administered TAPS-1 for identifying SUDs were ≥ monthly use for tobacco and alcohol (sensitivity = 0.92 and 0.71, specificity = 0.80 and 0.85, AUC = 0.86 and 0.78, respectively) and any reported use for illicit drugs and prescription medication misuse (sensitivity = 0.93 and 0.89, specificity = 0.85 and 0.91, AUC = 0.89 and 0.90, respectively). The performance of the interviewer-administered format was similar. When administered first, the self-administered format yielded higher disclosure rates for past 12-month alcohol use, illicit drug use, and prescription medication misuse. Frequency of use alone did not provide sufficient information to discriminate between gradations of substance use problem severity. Among those who denied drug use on the TAPS-1, less than 4% had a drug-positive biomarker. CONCLUSIONS: The TAPS-1 can identify unhealthy substance use in primary care patients with a high level of accuracy, and may have utility in primary care for rapid triage.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Usuários de Drogas/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Inquéritos e Questionários/normas , Produtos do Tabaco/estatística & dados numéricos , Adulto , Revelação/estatística & dados numéricos , Feminino , Humanos , Programas de Rastreamento/métodos , Atenção Primária à Saúde/métodos , Transtornos Relacionados ao Uso de Substâncias/classificação , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
19.
Curr Radiol Rep ; 5(5): 19, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435761

RESUMO

PURPOSE OF REVIEW: To explain the technique of Dual-energy CT (DECT) and highlight its applications and advantages in head and neck radiology. RECENT FINDINGS: Using DECT, additional datasets can be created next to conventional images. In head and neck radiology, three material decomposition algorithms can be used for improved lesion detection and delineation of the tumor. Iodine concentration measurements can aid in differentiating malignant from nonmalignant lymph nodes and benign posttreatment changes from tumor recurrence. Virtual non-calcium images can be used for detection of bone marrow edema. Virtual mono-energetic imaging can be useful for improved iodine conspicuity at lower keV and for reduction of metallic artifacts and increase in signal-to-noise ratio at higher keV. SUMMARY: DECT and its additional reconstructions can play an important role in head and neck cancer patients, from initial diagnosis and staging, to therapy planning, evaluation of treatment response and follow-up. Moreover, it can be helpful in imaging of infections and inflammation and parathyroid imaging as supplementary reconstructions can be obtained at lower or equal radiation dose compared with conventional single energy scanning.

20.
Ann Intern Med ; 165(10): 690-699, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27595276

RESUMO

BACKGROUND: Substance use, a leading cause of illness and death, is underidentified in medical practice. OBJECTIVE: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical workflows. The goal of this study was to assess the performance of the TAPS tool in primary care patients. DESIGN: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693). SETTING: 5 adult primary care clinics. PARTICIPANTS: 2000 adult patients consecutively recruited from clinic waiting areas. MEASUREMENTS: Interviewer- and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD). RESULTS: Interviewer- and self-administered versions of the TAPS tool had similar diagnostic characteristics. For identifying problem use (at a cutoff of 1+), the TAPS tool had a sensitivity of 0.93 (95% CI, 0.90 to 0.95) and specificity of 0.87 (CI, 0.85 to 0.89) for tobacco and a sensitivity of 0.74 (CI, 0.70 to 0.78) and specificity of 0.79 (CI, 0.76 to 0.81) for alcohol. For problem use of illicit and prescription drugs, sensitivity ranged from 0.82 (CI, 0.76 to 0.87) for marijuana to 0.63 (CI, 0.47 to 0.78) for sedatives; specificity was 0.93 or higher. For identifying any SUD (at a cutoff of 2+), sensitivity was lower. LIMITATIONS: The low prevalence of some drug classes led to poor precision in some estimates. Research assistants were not blinded to participants' TAPS tool responses when they administered the CIDI. CONCLUSION: In a diverse population of adult primary care patients, the TAPS tool detected clinically relevant problem substance use. Although it also may detect tobacco, alcohol, and marijuana use disorders, further refinement is needed before it can be recommended broadly for SUD screening. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse.


Assuntos
Programas de Rastreamento , Atenção Primária à Saúde/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Relacionados ao Uso de Álcool/diagnóstico , Feminino , Humanos , Masculino , Abuso de Maconha/diagnóstico , Pessoa de Meia-Idade , Medicamentos sob Prescrição , Sensibilidade e Especificidade , Tabagismo/diagnóstico , Adulto Jovem
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