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1.
Eur J Contracept Reprod Health Care ; 29(2): 69-75, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651645

RESUMO

OBJECTIVE: To compare the performance of the abdominal handheld point-of-care ultrasonography (POCUS) Butterfly-iQ to gold standard transvaginal ultrasonography (US) in identifying the position of intrauterine devices (IUDs) in the hands of a medical doctor specialised in ultrasonography. METHODS: In this diagnostic accuracy study, a single operator conducted abdominal POCUS followed by conventional transvaginal US. Seventy patients utilising copper or hormonal IUDs were assessed between June 2021 and October 2022. IUDs were categorised as entirely within the uterine cavity or malpositioned. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for detecting malpositioned IUDs, with conventional US results serving as the reference standard. Concordance rate and Kappa coefficient were computed to assess the agreement between the two ultrasound modalities. RESULTS: Among the 70 patients, 46 (65.7%) used copper IUDs, and 24 (34.3%) used hormonal IUDs. Conventional transvaginal US showed IUDs entirely within the uterine cavity in 56 (80%) patients and 14 (20%) IUDs were malpositioned. Of the 14 malpositioned IUDs seen by conventional US, POCUS identified 13 demonstrating a sensitivity of 92.9% (66.1-99.8). Of the 56 IUDs entirely within the uterine cavity shown by conventional US, only two cases were considered malpositioned by POCUS demonstrating a specificity of 96.4% (87.7-99.6). The concordance rate was 95.7%, and the Kappa value was 0.87 in differentiating between IUDs entirely within the uterine cavity and those that were malpositioned. CONCLUSION: Abdominal POCUS using Butterfly-iQ, when administered by an imaging specialist, exhibited excellent performance in confirming IUDs entirely within the uterine cavity.


Through a smartphone-based handheld point-of-care ultrasonography it was possible to correctly evaluate the position of intrauterine devices (IUDs) in a sample of 70 patients (46 using copper and 24 using hormonal IUDs).


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Humanos , Feminino , Ultrassonografia/métodos , Adulto , Sensibilidade e Especificidade , Dispositivos Intrauterinos/efeitos adversos , Pessoa de Meia-Idade , Útero/diagnóstico por imagem , Adulto Jovem , Dispositivos Intrauterinos de Cobre
2.
Diabet Med ; 37(8): 1316-1325, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32096571

RESUMO

AIMS: To examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate. METHODS: Data on 419 participants in tofogliflozin phase 2/3 trials were analysed. Changes in resting heart rate from baseline to week 24 were analysed using an analysis of covariance (ANCOVA) model with groups (tofogliflozin/placebo) as a fixed effect and baseline values as covariates. The antilipolytic effect was evaluated as adipose tissue insulin resistance (Adipo-IR) and was calculated as the product of fasting insulin and free fatty acid. Multivariate analysis evaluated independent factors for changes in resting heart rate from baseline to week 24. RESULTS: Of the participants, 58% were men, and mean age, HbA1c , BMI and resting heart rate were 57.6 years, 65 mmol/mol (8.1%), 25.5 kg/m2 and 66 bpm, respectively. At week 24, adjusted mean difference vs. placebo in the change from baseline was -2.3 bpm [95% confidence interval (CI) -4.6, -0.1] with tofogliflozin. Changes in resting heart rate were positively correlated with changes in Adipo-IR, whereas reductions in HbA1c , body weight and blood pressure were similar independent of changes in resting heart among quartiles of resting heart rate change. On multivariate analysis, higher baseline resting heart rates and Adipo-IR values were significantly associated with greater reductions in resting heart rate. CONCLUSIONS: Tofogliflozin corrected resting heart rate levels in accordance with baseline levels. Correction of high resting heart rates may be attributed to improved adipose tissue insulin resistance, leading to correction of hyperinsulinaemia.


Assuntos
Tecido Adiposo/metabolismo , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Frequência Cardíaca , Resistência à Insulina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Pressão Sanguínea , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Descanso , Redução de Peso
4.
J Infect Chemother ; 25(10): 743-749, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31257156

RESUMO

Candida auris is a multidrug-resistant and emergent pathogen that has caused healthcare-associated infection outbreaks. Recently, C. auris has spread worldwide; nevertheless, it was unexpectedly rare before 2009. Based on the molecular epidemiological analysis, C. auris may independently emerge at specific areas at first and recently may be transmitted to other continents. As C. auris cannot be detected using conventional methods, internally transcribed spacers, D1/D2 regions of the 26S rDNA sequencing, and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry method can be selected as comparatively accessible choices. Thus, detection of C. auris using the conventional method might be underestimated. In Japan, all C. auris strains were isolated from ear specimen and not from invasive mycoses. Japan strains were classified as an East Asian clade under a single clone. Although colonization, virulence, and infection pattern are almost the same as with other Candida species, its antifungal resistance is different. Fluconazole resistance is notably common, but resistance to all three classes of antifungals (azole, polyene, and echinocandin) rarely exists. Once C. auris is detected, screening, emphasis on hand hygiene adherence, use of single-patient room isolation, contact precaution, surveillance, and eradication from the environment and patients are appropriately required for infection control.


Assuntos
Antifúngicos/farmacologia , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Antifúngicos/uso terapêutico , Azóis/farmacologia , Azóis/uso terapêutico , Candida/efeitos dos fármacos , Candida/patogenicidade , Candidíase/epidemiologia , Candidíase/microbiologia , Farmacorresistência Fúngica Múltipla , Equinocandinas/farmacologia , Equinocandinas/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Polienos/farmacologia , Polienos/uso terapêutico , Prevalência
5.
Pharmazie ; 74(12): 760-762, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31907119

RESUMO

Cardiovascular surgery is a highly invasive intervention that is often performed in elderly patients at risks of complications because of malnutrition and reduced immunity. This study investigated nutritional factors that affected length of hospital stay in patients undergoing cardiovascular surgery. Among 68 patients who underwent surgery at the Department of Cardiovascular Surgery of Gifu Municipal Hospital between April 2013 and March 2015, 55 with complete data were included in the analysis. Data on serum albumin (ALB), transferrin (Tf), pre-albumin (PA) and retinol binding protein (RBP) levels were collected. The median length of hospital stay was 29 days (stays of ≥30 days were considered long-term hospitalization). Multivariate analysis (multiple logistic regression) included age (≥ 65 years), sex (female), and ALB (≤ 3.0 g/dL), Tf (≤ 150.0 mg/dL), PA (≤ 10.0 mg/dL) and RBP (≤ 1.5 mg/dL) levels. ALB [odds ratio (OR) 10.37, 95% CI (confidence interval): 1.185-90.80, P = 0.035] and Tf [OR 4.743, 95% CI: 1.375-16.36, P = 0.014] were significantly associated with length of hospital stay. Nutritional management of patients and careful monitoring of ALB and Tf levels can shorten length of hospital stay in patients undergoing cardiovascular surgery.


Assuntos
Procedimentos Cirúrgicos Cardiovasculares , Hospitalização , Tempo de Internação , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Albumina Sérica/análise , Transferrina/análise
6.
J Periodontal Res ; 53(1): 117-122, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29139559

RESUMO

BACKGROUND AND OBJECTIVE: It is well known that there is a strong relationship between periodontitis and cardiovascular disease (CVD). Tooth loss reflects an end-stage condition of oral diseases, such as periodontitis. Infection with specific periodontal pathogens is known as a possible factor that influences development of CVD. The aim of this study was to assess the relationship between the number of residual teeth and systemic inflammatory conditions in patients with CVD. MATERIAL AND METHODS: We divided 364 patients with CVD into four groups, according to the number of residual teeth: (i) ≥20 teeth; (ii) 10-19 teeth; (iii) 1-9 teeth; and (iv) edentulous. We recorded medical history, blood data and periodontal conditions. Serum samples were obtained and their IgG titers against three major periodontal pathogens were measured. RESULTS: Smoking rate and the prevalence of diabetes mellitus were higher in edentulous patients and in subjects with a few teeth compared with patients with many teeth. The levels of C-reactive protein were higher in patients with 1-9 teeth than in those with 10-19 teeth and with ≥20 teeth. The level of Porphyromonas gingivalis IgG in the group with 10-19 teeth was statistically higher than that in the group with ≥20 teeth. The level of P. gingivalis IgG in the edentulous group tended to be lower than that in the other groups. CONCLUSION: The patients with 1-9 teeth had the highest level of C-reactive protein among the four groups, and the patients with 10-19 teeth had the highest level of IgG to periodontal bacteria. We conclude that the number of remaining teeth may be used to estimate the severity of systemic inflammation in patients with CVD.


Assuntos
Anticorpos Antibacterianos/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/complicações , Porphyromonas gingivalis/imunologia , Perda de Dente/complicações , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Japão , Arcada Edêntula , Arcada Parcialmente Edêntula , Masculino
7.
Pharmazie ; 73(10): 598-604, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30223925

RESUMO

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.


Assuntos
Suplementos Nutricionais/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Medicamentos sem Prescrição/administração & dosagem , Idoso , Atenção à Saúde/estatística & dados numéricos , Dieta/estatística & dados numéricos , Feminino , Humanos , Estudos Retrospectivos , Automedicação/estatística & dados numéricos , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários
8.
Ultrasound Obstet Gynecol ; 49(6): 778-783, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27194129

RESUMO

OBJECTIVE: To evaluate the performance of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative discrimination between benign ovarian (including tubal and para-ovarian) tumors, borderline ovarian tumors (BOT), Stage I ovarian cancer (OC), Stage II-IV OC and ovarian metastasis in a gynecological oncology center in Brazil. METHODS: This was a diagnostic accuracy study including 131 women with an adnexal mass invited to participate between February 2014 and November 2015. Before surgery, pelvic ultrasound examination was performed and serum levels of tumor marker CA 125 were measured in all women. Adnexal masses were classified according to the IOTA ADNEX model. Histopathological diagnosis was the gold standard. Receiver-operating characteristics (ROC) curve analysis was used to determine the diagnostic accuracy of the model to classify tumors into different histological types. RESULTS: Of 131 women, 63 (48.1%) had a benign ovarian tumor, 16 (12.2%) had a BOT, 17 (13.0%) had Stage I OC, 24 (18.3%) had Stage II-IV OC and 11 (8.4%) had ovarian metastasis. The area under the ROC curve (AUC) was 0.92 (95% CI, 0.88-0.97) for the basic discrimination between benign vs malignant tumors using the IOTA ADNEX model. Performance was high for the discrimination between benign vs Stage II-IV OC, BOT vs Stage II-IV OC and Stage I OC vs Stage II-IV OC, with AUCs of 0.99, 0.97 and 0.94, respectively. Performance was poor for the differentiation between BOT vs Stage I OC and between Stage I OC vs ovarian metastasis with AUCs of 0.64. CONCLUSION: The majority of adnexal masses in our study were classified correctly using the IOTA ADNEX model. On the basis of our findings, we would expect the model to aid in the management of women with an adnexal mass presenting to a gynecological oncology center. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Doenças dos Anexos/diagnóstico por imagem , Estadiamento de Neoplasias , Doenças dos Anexos/patologia , Doenças dos Anexos/cirurgia , Adulto , Brasil , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
10.
Eur J Clin Microbiol Infect Dis ; 35(9): 1521-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27272122

RESUMO

Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well.


Assuntos
Ascaris/isolamento & purificação , Larva Migrans/epidemiologia , Larva Migrans/patologia , Toxocara/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Japão/epidemiologia , Larva Migrans/parasitologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Am J Transplant ; 15(6): 1644-53, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25649117

RESUMO

Tofacitinib fixed-dose regimens attained better kidney function and comparable efficacy to cyclosporine (CsA) in kidney transplant patients, albeit with increased risks of certain adverse events. This post-hoc analysis evaluated whether a patient subgroup with an acceptable risk-benefit profile could be identified. Tofacitinib exposure was a statistically significant predictor of serious infection rate. One-hundred and eighty six kidney transplant patients were re-categorized to above-median (AME) or below-median (BME) exposure groups. The 6-month biopsy-proven acute rejection rates in AME, BME and CsA groups were 7.8%, 15.7% and 17.7%, respectively. Measured glomerular filtration rate was higher in AME and BME groups versus CsA (61.2 and 67.9 vs. 53.9 mL/min) at Month 12. Fewer patients developed interstitial fibrosis and tubular atrophy (IF/TA) at Month 12 in AME (20.5%) and BME (27.8%) groups versus CsA (48.3%). Serious infections occurred more frequently in the AME group (53.0%) than in BME (28.4%) or CsA (25.5%) groups. Posttransplant lymphoproliferative disorder (PTLD) only occurred in the AME group. In kidney transplant patients, the BME group preserved the clinical advantage of comparable acute rejection rates, improved renal function and a lower incidence of IF/TA versus CsA, and with similar rates of serious infection and no PTLD.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Rim , Rim/fisiopatologia , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Adulto , Biópsia , Ciclosporina/efeitos adversos , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Transtornos Linfoproliferativos/epidemiologia , Masculino , Pessoa de Meia-Idade , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco
12.
Parasite Immunol ; 37(4): 204-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25711956

RESUMO

One of the most common zoonotic helminth infections is caused by species in the genus Toxocara, particularly Toxocara canis and T. cati (Syn. T. mystax). However, their relative contribution to toxocarosis in humans remains largely unknown because causative larvae are seldom recovered and uncertainties regarding the validity of existing serological assays. In this study, we used sera from a pig model experimentally infected with T. canis and T. cati to evaluate whether a Western blot could discriminate between the two species. No proteins were observed that could be used as a diagnostic tool. In addition, a heterogenic protein pattern between individual hosts was found, which was most pronounced in the T. cati-infected pigs. There is therefore an urgent need to optimize and validate current methods or develop new species-specific serological methods in order to implement appropriate control measures.


Assuntos
Western Blotting/métodos , Toxocara canis/isolamento & purificação , Toxocara/isolamento & purificação , Toxocaríase/diagnóstico , Toxocaríase/parasitologia , Animais , Antígenos de Helmintos , Reações Cruzadas , Diagnóstico Diferencial , Modelos Animais de Doenças , Humanos , Especificidade da Espécie , Organismos Livres de Patógenos Específicos , Sus scrofa , Toxocara/classificação , Toxocara canis/imunologia , Toxocaríase/imunologia , Zoonoses/diagnóstico , Zoonoses/imunologia , Zoonoses/parasitologia
14.
Br J Cancer ; 110(6): 1571-8, 2014 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-24504365

RESUMO

BACKGROUND: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. METHODS: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) were performed to detect RET gene rearrangement. RESULTS: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B-RET fusion genes, whereas 3 possessed CCDC6-RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). CONCLUSIONS: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Adulto Jovem
15.
Ann Oncol ; 25(1): 138-42, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24297085

RESUMO

BACKGROUND: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. MATERIALS AND METHODS: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. RESULTS: BRAF mutations were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%), and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P = 0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75% of V600E-mutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. CONCLUSION: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Receptores Proteína Tirosina Quinases/genética , Análise de Sequência de DNA , Proteínas ras/genética
16.
Dis Esophagus ; 27(7): 617-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23980646

RESUMO

Esophageal perforation occurring during or after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is a rare, but serious complication. However, reports of its characteristics, including endoscopic imaging and management, have not been fully detailed. To analyze and report the clinical presentation and management of esophageal perforations occurred during or after EMR/ESD. Four hundred seventy-two esophageal neoplasms in 368 patients were treated (171 EMR; ESD 306) at Northern Yokohama Hospital from 2003 to 2012. Esophageal perforation occurred in a total of seven (1.9%) patients, all of whom were male and had undergone ESD. The etiology of perforation was: three (42.9%) intraoperative; three (42.9%) balloon dilatation for stricture prevention; one (14.2%) due to food bolus impaction. All cases were managed non-operatively based on the comprehensive assessment of clinical severity, extent of the injury, and the time interval from perforation to treatment onset. Conservative management included (i) bed rest and continuous monitoring to determine the need for operative intervention; (ii) fasting and intravenous fluid infusion/ tube feeding; and (iii) intravenous antibiotics. All defects closed spontaneously, save one case where closure was achieved by endoscopic clipping. Surgery was not required. Conservative management for esophageal perforation during advanced endoscopic resection is may be possible when there is no delay in diagnosis or treatment. Decision-making should be governed purely by multidisciplinary discussion.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Dissecação/métodos , Neoplasias Esofágicas/cirurgia , Perfuração Esofágica/diagnóstico , Mucosa/cirurgia , Complicações Pós-Operatórias/diagnóstico , Idoso , Dilatação/efeitos adversos , Dilatação/métodos , Dissecação/efeitos adversos , Endoscopia do Sistema Digestório/efeitos adversos , Endoscopia do Sistema Digestório/métodos , Perfuração Esofágica/etiologia , Perfuração Esofágica/terapia , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos
17.
ESMO Open ; 9(4): 102981, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38613908

RESUMO

BACKGROUND: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP. MATERIALS AND METHODS: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response. RESULTS: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively). CONCLUSION: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Feminino , Medicina de Precisão/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Adulto Jovem , Doenças Raras/genética , Doenças Raras/tratamento farmacológico , Genômica/métodos
18.
Gene Ther ; 20(1): 112-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22241176

RESUMO

Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy. Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR). Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells. There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry. Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401. OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection. OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells. OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods. OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples. These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.


Assuntos
Adenoviridae/genética , Telomerase/genética , Replicação Viral/genética , Linhagem Celular Tumoral , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Humanos , Vírus Oncolíticos/genética , Telomerase/metabolismo , Transcrição Gênica , Transformação Genética
19.
Osteoarthritis Cartilage ; 21(1): 165-74, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23017871

RESUMO

OBJECTIVE: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and adisintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. METHODS: Human chondrocytes were seeded in stretch chambers at a concentration of 5 × 10(4)cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12h, followed by uniaxial cyclic tensile strain (CTS) (0.5Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. RESULTS: HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) MAPKs was downregulated by both HDAC inhibitors. CONCLUSION: The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.


Assuntos
Proteínas ADAM/metabolismo , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas ADAM/genética , Proteína ADAMTS5 , Western Blotting , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estresse Mecânico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Endoscopy ; 45(7): 585-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23801316

RESUMO

BACKGROUND AND STUDY AIM: Intrapapillary capillary loops (IPCLs) show distinct pattern changes corresponding to tumor progression and depth of invasion, important for in vivo characterization of superficial squamous cell carcinoma (SCC). We examined the relation between invasion depth and histopathologic IPCL diameter. PATIENTS AND METHODS: Prospectively, before lesion resection, magnification endoscopy and narrow band imaging were used to identify IPCL patterns of type V1 (corresponding to tumors limited to the mucosa; 10 patients) and type Vn (submucosally invading tumors; 10 patients). Post-resection, IPCL samples (type I [normal mucosa], n = 103; V1, n = 113; Vn, n = 100) were stained with hematoxylin & eosin, CD34, and desmin, and vessel diameter measured using light microscopy. RESULTS: Mean (standard deviation [SD]) histopathologic calibers of IPCLs of types I, V1, and Vn were significantly different, being 7.7 (2.8) µm, 21.9 (7.4) µm, and 65.2 (22.9) µm; type 1 vs. V1, P < 0.001; V1 vs. Vn, P < 0.001. CONCLUSIONS: Magnification endoscopy observation of IPCLs allows in vivo discrimination between intramucosal and submucosally invasive cancer.


Assuntos
Capilares/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Esôfago/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esôfago/irrigação sanguínea , Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Mucosa/cirurgia , Invasividade Neoplásica , Estudos Prospectivos
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