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1.
Clin Oncol (R Coll Radiol) ; 35(9): e549-e560, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321887

RESUMO

AIMS: This study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. MATERIALS AND METHODS: The study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I-IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. RESULTS: Among 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3-77.3%), but varied less for the high-risk (range 77.1-91.6%) and low-risk groups (range 4.1-32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. CONCLUSIONS: Rates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.


Assuntos
Neoplasias da Mama , Fragilidade , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Estudos de Coortes , Inglaterra/epidemiologia , Mastectomia , Medicina Estatal , País de Gales/epidemiologia , Pessoa de Meia-Idade
2.
Rhinology ; 61(4): 338-347, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37083114

RESUMO

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. METHODOLOGY: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGFß1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGFß1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. RESULTS: TGFß1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGFß1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGFß1 increased ALP expression in sinus bone cells. Treatment with a TGFß inhibitor attenuated TGFß1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. CONCLUSIONS: Eosinophil-derived TGFß1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGFß1 may mediate aberrant bone remodeling in CRSwNP.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Eosinófilos , Rinite/complicações , Rinite/patologia , Fator de Crescimento Transformador beta , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Osteogênese , Sinusite/complicações , Sinusite/patologia , Inflamação/patologia , Doença Crônica
3.
Tech Coloproctol ; 27(7): 589-599, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36971849

RESUMO

PURPOSE: The da Vinci SP® (dVSP) surgical system (Intuitive Surgical, Sunnyvale, CA, USA), a robotic platform designed for single-incision surgery, overcame the need for multiple ports in traditional robotic surgery and issues including triangulation and retraction in single-incision laparoscopic surgery. However, previous studies only included case reports or series with small sample sizes. The aim of this study was to assess the safety and performance of the dVSP surgical system and its instruments and accessories for colorectal procedures. METHODS: The medical records of patients who had surgery with the dVSP from March 2019 to September 2021 at Ewha Womans University Seoul Hospital were investigated. The pathologic and follow-up data of patients who had malignant tumors were analyzed separately to evaluate oncological safety. RESULTS: Fifty patients (26 male and 24 female) with a median age of 59 years (interquartile range 52.5-63.0 years) were enrolled. The procedures included low anterior resection with total mesorectal excision (n = 16), sigmoid colectomy with complete mesocolic excision and central vessel ligation (CME + CVL) (n = 14), right colectomy with CME + CVL (n = 9), left colectomy with CME + CVL (n = 4), right colectomy (n = 6), and sigmoid colectomy (n = 1). Operative time significantly decreased after 25 cases (early phase vs. late phase; operative time 295.0 min vs. 250.0 min, p = 0.015; docking time 16.0 min vs. 12.0 min, p = 0.001; console time 212.0 min vs. 190.0 min, p = 0.019). Planned procedures were successfully completed in all patients. Postoperative outcomes were acceptable with only six cases of mild adverse events through a 3-month follow-up. No local recurrence and only one case of systemic recurrence occurred within 1 year postoperatively. CONCLUSIONS: This study demonstrated the surgical and oncological safety and feasibility of dVSP, which may be a novel surgical platform for colorectal surgery.


Assuntos
Cirurgia Colorretal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Robótica/métodos , Colectomia/métodos , Duração da Cirurgia , Estudos Retrospectivos
4.
Clin Oncol (R Coll Radiol) ; 35(4): e265-e277, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36764877

RESUMO

AIMS: Clinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age. MATERIALS AND METHODS: The study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms. RESULTS: Among 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival [adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64-0.87] and BCSS (aHR 0.78, 95% confidence interval 0.65-0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92-1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01-1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362). CONCLUSIONS: The association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Estudos de Coortes , Radioterapia Adjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos
5.
Hernia ; 27(1): 113-118, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35939245

RESUMO

PURPOSE: Laparoscopic total extra-peritoneal (TEP) inguinal hernia repair is usually performed under general anesthesia (GA) for muscle relaxation. However, TEP hernia repair may be reluctant in high-risk patients of GA. The aim of this study was to compare the outcomes of the TEP under GA and local anesthesia (LA). METHODS: We retrospectively analyzed patients with inguinal hernia who underwent TEP under GA or LA in a single center from December 2016 to May 2018. The outcomes, such as demographics, duration of surgery, length of hospital stay, visual analog scale (VAS), and postoperative complications, were compared in each group. RESULTS: Seventy-six patients with inguinal hernia underwent TEP under GA (n = 52) or LA (n = 24). Total operation time (mean ± standard deviation; GA, 111.6 ± 23.0 min; LA, 76.3 ± 18.0 min; p < 0.001) and length of hospital stay (GA, 38.3 ± 11.6 min; LA, 30.3 ± 15.6 min; p < 0.014) were shorter in LA group compared to GA group. There were no significant differences in postoperative VAS (1 h, p = 0.247; 4 h, p = 0.086; 12 h, p = 0.469; 24 h, p = 0.411), postoperative adverse effects (vomiting, p = 0.570; urinary retention, p = 0.214; headache, p = 0.494), and postoperative complications (seroma, p = 0.348; scrotal edema, p = 0.178; recurrence, p = 0.822) between LA group and GA group. CONCLUSION: Compared with GA, there were no differences in postoperative pain and complications in patients who underwent TEP hernia repair under LA. Furthermore, in LA group, total operation time and length of hospital stay were shortened.


Assuntos
Hérnia Inguinal , Laparoscopia , Humanos , Hérnia Inguinal/cirurgia , Hérnia Inguinal/etiologia , Estudos Retrospectivos , Anestesia Local , Herniorrafia/efeitos adversos , Estudos Prospectivos , Laparoscopia/efeitos adversos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Lidocaína
6.
Rhinology ; 59(5): 451-459, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472546

RESUMO

BACKGROUND: Inconsistent results about the effect of air pollution on chronic rhinosinusitis (CRS) have been reported. This study aimed to evaluate the impact of meteorological conditions/air pollution on the prevalence of CRS in adult Koreans. METHODOLOGY: The data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 through 2015 were used. A CRS group (defined as ICD-10 codes J32, n=6159) was matched with a control group (n=24,636) in 1:4 ratios by age, sex, income, and region of residence. The meteorological conditions and air pollution data included the daily mean, highest, and lowest temperature (°C), daily temperature range (°C), relative humidity (%), ambient atmospheric pressure (hPa), sunshine duration (hr), and the rainfall (mm), SO2 (ppm), NO2 (ppm), O3 (ppm), CO (ppm), and PM10 (λg/m3) levels before the CRS diagnosis. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRS were analyzed using logistic regression analyses. RESULTS: When the NO2 level increased by 0.1 ppm, the odds for CRS increased 5.40 times, and when the CO level increased by 1 ppm and PM10 increased by 10 λg/m3, the odds for CRS decreased 0.75 times and 0.93 times, respectively. Other meteorological conditions, such as the mean/highest/lowest temperature, temperature range, rainfall and other air pollution, such as SO2 and O3, were not statistically significant. NO2 for 90 days before the index date increased the risk of CRS in all subgroups, except for the nasal polyp and older age subgroups. CONCLUSION: CRS is related to high concentrations of NO2.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Sinusite/epidemiologia
7.
ESMO Open ; 6(5): 100236, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34438242

RESUMO

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo , Feminino , Furanos , Humanos , Cetonas , Proteínas Nucleares/uso terapêutico , Paclitaxel/uso terapêutico , Testes Farmacogenômicos , Polimorfismo Genético , Estudos Prospectivos , Proteínas Repressoras/uso terapêutico , Gencitabina
8.
Br J Surg ; 108(11): 1341-1350, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34297818

RESUMO

BACKGROUND: No well validated and contemporaneous tools for personalized prognostication of gastric adenocarcinoma exist. This study aimed to derive and validate a prognostic model for overall survival after surgery for gastric adenocarcinoma using a large national dataset. METHODS: National audit data from England and Wales were used to identify patients who underwent a potentially curative gastrectomy for adenocarcinoma of the stomach. A total of 2931 patients were included and 29 clinical and pathological variables were considered for their impact on survival. A non-linear random survival forest methodology was then trained and validated internally using bootstrapping with calibration and discrimination (time-dependent area under the receiver operator curve (tAUC)) assessed. RESULTS: The median survival of the cohort was 69 months, with a 5-year survival of 53.2 per cent. Ten variables were found to influence survival significantly and were included in the final model, with the most important being lymph node positivity, pT stage and achieving an R0 resection. Patient characteristics including ASA grade and age were also influential. On validation the model achieved excellent performance with a 5-year tAUC of 0.80 (95 per cent c.i. 0.78 to 0.82) and good agreement between observed and predicted survival probabilities. A wide spread of predictions for 3-year (14.8-98.3 (i.q.r. 43.2-84.4) per cent) and 5-year (9.4-96.1 (i.q.r. 31.7-73.8) per cent) survival were seen. CONCLUSIONS: A prognostic model for survival after a potentially curative resection for gastric adenocarcinoma was derived and exhibited excellent discrimination and calibration of predictions.


In this study the authors used a large nationwide dataset from England and Wales and tried to make a predictive model that estimated how long patients would survive after surgery for gastric cancer. They found that using a machine learning methodology provided excellent results and accuracy in predictions, significantly in excess of any other published model and traditional staging methods. The model will be useful to provide individualized prediction of survival to patients and in the future could be used to stratify treatments.


Assuntos
Adenocarcinoma/mortalidade , Gastrectomia , Neoplasias Gástricas/mortalidade , Adenocarcinoma/cirurgia , Inglaterra/epidemiologia , Seguimentos , Humanos , Período Pós-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida/tendências , Fatores de Tempo , País de Gales/epidemiologia
9.
Int J Oral Maxillofac Surg ; 50(10): 1280-1288, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33602646

RESUMO

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.


Assuntos
Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Neoplasias da Glândula Sublingual , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Mucoepidermoide/cirurgia , Humanos , Esvaziamento Cervical , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias da Glândula Sublingual/epidemiologia , Neoplasias da Glândula Sublingual/cirurgia
10.
Rhinology ; 59(3): 292-300, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315021

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.


Assuntos
Pólipos Nasais , Otite Média , Rinite , Sinusite , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Otite Média/complicações , Otite Média/epidemiologia , Rinite/epidemiologia , Sinusite/epidemiologia
11.
J Adolesc Health ; 67(3): 362-368, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32674964

RESUMO

PURPOSE: COVID-19 morbidity and mortality reports in the U.S. have not included findings specific to young adults. The Centers for Disease Control and Prevention provides a list of conditions and associated behaviors, including smoking, conferring vulnerability to severe COVID-19 illness regardless of age. This study examines young adults' medical vulnerability to severe COVID-19 illness, focusing on smoking-related behavior. METHODS: A young adult subsample (aged 18-25 years) was developed from the National Health Interview Survey, a nationally representative data set, pooling years 2016-2018. The medical vulnerability measure (yes vs. no) was developed, guided by the Centers for Disease Control and Prevention medical indicators. The estimates of medical vulnerability were developed for the full sample, the nonsmoking sample, and the individual risk indicators. Logistic regressions were conducted to examine differences by sex, race/ethnicity, income, and insurance. RESULTS: Medical vulnerability was 32% for the full sample and half that (16%) for the nonsmoking sample. Patterns and significance of some subgroup differences differed between the full and the nonsmoking sample. Male vulnerability was (33%) higher than female (30%; 95% CI: .7-.9) in the full sample, but lower in nonsmokers: male (14%) versus female (19%; 95% CI: 1.2-1.7). The white subgroup had higher vulnerability than Hispanic and Asian subgroups in both samples-full sample: white (31%) versus Hispanic (24%; 95% CI: .6-.9) and Asian (18%; 95% CI: .4-.5); nonsmokers: white (17%) versus Hispanic (13%; 95% CI: .06-.9) and Asian (10%; 95% CI: .3-.8). CONCLUSIONS: Notably, lower young adult medical vulnerability within nonsmokers versus the full sample underscores the importance of smoking prevention and mitigation.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Fumar/epidemiologia , Fumar/psicologia , Populações Vulneráveis , Adolescente , Adulto , COVID-19 , Infecções por Coronavirus/etnologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pandemias , Pneumonia Viral/etnologia , Índice de Gravidade de Doença , Fumar/etnologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
12.
Clin Exp Immunol ; 200(3): 260-271, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32056202

RESUMO

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Antígenos CD20/imunologia , Membrana Celular/imunologia , Técnicas de Silenciamento de Genes , Proteínas de Neoplasias/imunologia , Molécula 1 de Interação Estromal/imunologia , Animais , Antígenos CD20/genética , Células CHO , Membrana Celular/genética , Cricetulus , Humanos , Proteínas de Neoplasias/genética , Octoxinol/química , Solubilidade , Molécula 1 de Interação Estromal/genética
13.
Sci Rep ; 10(1): 1510, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001732

RESUMO

Electrolytic ablation (EA) is a promising nonthermal tumor ablation technique that destroys malignant cells through induction of a locoregional pH change. EA is typically performed by inserting needle electrodes inside the tumor followed by application of direct current (DC), thus inducing electrolysis and creating localized pH changes around the electrodes. In this paper, we report an ultrasonically powered implantable EA microprobe that may increase the clinical relevance of EA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period). The wireless EA microprobe consists of a millimeter-sized piezoelectric ultrasonic receiver, a rectifier circuit, and a pair of platinum electrodes (overall size is 9 × 3 × 2 mm3). Once implanted through a minimally invasive procedure, the microprobe can stay within a solid tumor and be repeatedly used as needed. Ultrasonic power allows for efficient power delivery to mm-scale devices implanted deep within soft tissues of the body. The microprobe is capable of producing a direct current of 90 µA at a voltage of 5 V across the electrodes under low-intensity ultrasound (~200 mW/cm2). The DC power creates acidic (pH < 2) and alkaline (pH > 12.9) regions around the anode and the cathode, respectively. The pH change, measured using tissue-mimicking agarose gel, extends to 0.8 cm3 in volume within an hour at an expansion rate of 0.5 mm3/min. The microprobe-mediated EA ablative capability is demonstrated in vitro in cancer cells and ex vivo in mouse liver.

14.
Osteoporos Int ; 31(5): 983-993, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31863125

RESUMO

Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment. INTRODUCTION: Osteoclasts are responsible for bone resorption in bone-related disorders. Anti-cytokine therapeutic antibodies such as denosumab are effective for the treatment of osteoporosis. However, problems with antibody manufacturing and the immunogenicity caused by multiple antibody doses have led to the use of auto-cytokines as immunogens to induce anti-cytokine antibodies. METHODS: RANKL was point-mutated based on the crystal structure of the complex of RANKL and its receptor RANK. RESULTS: As a proof of concept, immunization with RANKL produced high levels of specific antibodies and blocked osteoclast development in vitro and inhibited osteoporosis in RANKL-treated or ovariectomized mouse models. CONCLUSIONS: The results demonstrate the successful use of mutated RANKL as an immunogen for the induction of anti-RANKL immune response. This strategy is useful in general anti-cytokine immunotherapy to avoid toxic side effects of osteoporosis treatment.


Assuntos
Reabsorção Óssea , Osteoporose , Animais , Sítios de Ligação , Imunoterapia , Camundongos , Osteoclastos , Osteoporose/tratamento farmacológico , Ligante RANK
15.
Int J Tuberc Lung Dis ; 23(11): 1142-1148, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31718749

RESUMO

SETTING: The Korea National Health and Nutrition Examination Survey is a national, population-based, cross-sectional surveillance programme.OBJECTIVE: 1) To investigate the prevalence of spontaneously healed pulmonary tuberculosis (SHPTB) on chest radiographs (CXRs) in South Korea, as well as its demographic and clinical associations, and 2) to determine the relationship between SHPTB and smoking.DESIGN: People with normal findings on CXRs (n = 24 190) and those with SHPTB (n = 1863) were compared in univariate, bivariate and multivariate analyses with respect to smoking and demographic and clinical factors.RESULTS: The prevalence of SHPTB was 7.2%. The proportion of patients with SHPTB tended to be higher in males, people of older age, ever smokers, as well as people with low body mass index and low education level. In bivariate analysis, after adjustments for age and sex, SHPTB was found more often among ex-smokers (P = 0.005) and current smokers (P = 0.024) than in non-smokers. Multivariate analyses revealed increased relative odds for SHPTB with increased age (P < 0.001), male sex (P < 0.001) and ex-smoker status (P = 0.016). Passive smoking was also significantly associated with SHPTB (P = 0.022).CONCLUSION: In addition to increasing the risk of active TB and negatively affecting the outcome of TB treatment, smoking is also associated with SHPTB, as detected on CXRs.


Assuntos
Pulmão/diagnóstico por imagem , Radiografia Torácica , Fumar/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Tuberculose Pulmonar/diagnóstico por imagem
16.
Curr Oncol ; 26(4): e558-e570, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31548825

RESUMO

Background: In the early developmental phase of a postmortem rapid tissue donation (rtd) program for patients with metastatic cancer, we surveyed health care professionals (hcps) and oncology patients at the McGill University Health Centre (muhc) to assess their knowledge and attitudes pertaining to rtd from metastatic cancer patients for research purposes. Methods: A 23-item survey was developed and distributed to hcps at tumour board meetings, and a related 26-item survey was developed and distributed to oncology patients at the muhc Cedars Cancer Centre. Results: The survey attracted participation from 73 hcps, including 37 attending physicians, and 102 oncology patients. Despite the fact that 88% of hcps rated their knowledge of rtd as none or limited, 42% indicated that they would feel comfortable discussing rtd with their cancer patients. Of the responding hcps, 67% indicated that their current knowledge of rtd would affect their decision to discuss such a program with patients, which implies the importance of education for hcps to facilitate enrolment of patients into a rtd program. Of responding patients, 78% indicated that they would not be uncomfortable if their doctor discussed rtd with them, and 61% indicated that they would like it if their doctor were to discuss rtd with them. The hcps and patients felt that the best time for patients to be approached about consenting to a rtd program would be at the transition to palliative care when no treatment options remain. Conclusions: At the muhc, hcps and patients are generally enthusiastic about adopting a rtd program for patients with metastatic cancer. Education of hcps and patients will be an important determinant of the program's success.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias/psicologia , Obtenção de Tecidos e Órgãos/métodos , Cadáver , Tomada de Decisão Clínica , Conhecimentos, Atitudes e Prática em Saúde , Hospitais Universitários , Humanos , Masculino , Metástase Neoplásica , Cuidados Paliativos , Inquéritos e Questionários
17.
Int J Tuberc Lung Dis ; 23(6): 678-684, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31315699

RESUMO

BACKGROUND Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) share common risk factors. They could therefore be expressed in a single patient. However, the prevalence, clinical characteristics and prognosis of individuals with comorbid IPF and COPD are not known. METHOD From 2003 to 2007, the Korean Interstitial Lung Disease Study Group created a register for idiopathic interstitial pneumonia using 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) criteria. Of the 1546 IPF patients assessed, 143 had decreased lung function consistent with COPD (IPF-COPD). COPD was diagnosed based on age (≥40 years) and pulmonary function (forced expiratory volume in 1 sec [FEV1]/forced vital capacity [FVC] ratio < 0.7). RESULTS The median age of the IPF-COPD group was 71.0 years (interquartile range 66.0-76.0); most patients were male (88.1%). FVC (%) was significantly higher in the IPF-COPD group; however, FEV1 (%) was significantly lower in the IPF-COPD group (P < 0.001). Diffusing capacity of the lung for carbon monoxide (DLCO) was not significantly different between the two groups. In survival analysis, age and FVC (%), but not COPD, were significantly associated with prognosis (respectively P = 0.003, 0.001 and 0.401). COPD severity was also not related to prognosis (P = 0.935). CONCLUSION The prevalence of IPF-COPD was estimated to be ∼9.2% among all IPF patients; prognosis of patients with IPF-COPD was not worse than those with IPF alone. .


Assuntos
Fibrose Pulmonar Idiopática/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/patologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/patologia , Sistema de Registros , República da Coreia/epidemiologia , Capacidade Vital
18.
Clin Oncol (R Coll Radiol) ; 31(7): e87-e93, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30982667

RESUMO

Dysphagia in people with advanced oesophageal cancer can be treated by oesophageal stents, external beam radiotherapy (EBRT) and intraluminal brachytherapy. Despite guidelines recommending brachytherapy for patients with a predicted life expectancy exceeding 3 months, its uptake in the UK has been limited. Here we examine the strength of the evidence supporting the use of brachytherapy compared with oesophageal stents and EBRT and possible reasons for its limited uptake. Trials and observational studies suggest brachytherapy alone confers a benefit to patients, but its impact is less immediate than oesophageal stents; the evidence on effectiveness and value-for-money is limited. Moreover, stronger evidence will probably be insufficient to increase uptake, due to the extra complexity of delivery compared with stents and EBRT and a lack of experience among specialists.


Assuntos
Braquiterapia/métodos , Transtornos de Deglutição/radioterapia , Neoplasias Esofágicas/radioterapia , Cuidados Paliativos/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Bone Joint J ; 101-B(1): 75-82, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30601053

RESUMO

AIMS: The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation. PATIENTS AND METHODS: A total of 134 haemodialyzed patients aged more than 50 years who underwent surgical treatment for pyogenic spondylodiscitis were included in the study. Their mean age was 66.4 years (50 to 83); 66 were male (49.3%) and 68 were female (50.7%). They were divided into two groups according to whether spinal instrumentation was used or not. Propensity score matching was used to attenuate the potential selection bias. The outcome of treatment was compared between these two groups. RESULTS: A total of 89 patients (66.4%) underwent non-instrumented surgery and 45 (33.5%) underwent instrumented surgery. There were no significant differences in the rates of postoperative complications, except for an increased rate of wound problems in the instrumented group, which was found in the unmatched cohorts (p = 0.034). There were no significant differences in the rate of recurrent infections (p = 0.328 for the unmatched cohort; p = 0.269 for the matched cohort) and mortality rate, including in-hospital (p = 0.713 for the unmatched cohort; p = 0.738 for the matched cohort) and one-year rates (p = 0.363 for the unmatched cohort; p = 0.787 for the matched cohort), between the groups. However, the interval between the initial diagnosis and the first recurrence was significantly longer in the instrumented group (p = 0.008 for the unmatched cohort; p = 0.032 for the matched cohort). CONCLUSION: Instrumented surgery for haemodialyzed patients with pyogenic spondylodiscitis showed similar outcomes, including recurrence and mortality, to non-instrumented surgery, despite the instrumented group having more severe neurological deficit, a larger number of involved levels, and increased kyphotic angle.


Assuntos
Discite/cirurgia , Procedimentos Ortopédicos/instrumentação , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Vértebras Cervicais/cirurgia , Discite/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Tempo de Internação/estatística & dados numéricos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Parafusos Pediculares , Complicações Pós-Operatórias/etiologia , Infecções Relacionadas à Prótese/microbiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Resultado do Tratamento
20.
Anaesthesia ; 73(10): 1260-1264, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30120832

RESUMO

We evaluated the effect of pre-operative serratus anterior plane block on postoperative pain and opioid consumption after thoracoscopic surgery. We randomly allocated 89 participants to block with 30 ml ropivacaine 0.375% (n = 44), or no block without placebo or sham procedure (n = 45). We analysed results from 42 participants in each group. Serratus anterior plane block reduced mean (SD) remifentanil dose during surgery, 0.12 (0.06) mg.h-1 vs. 0.16 (0.06) mg.h-1 , p = 0.016, and reduced mean (SD) fentanyl consumption in the first 24 postoperative hours, 3.8 (1.9) µg.kg-1 vs. 5.7 (1.6) µg.kg-1 , p = 0.000004. Block also reduced the worst median (IQR [range]) pain scores reported in the first 24 postoperative hours: 6 (5-7 [3-10]) vs. 7 (6-7 [3-10]), p = 0.027. Block decreased dissatisfaction with pain management, categorised as 'highly unsatisfactory', 'unsatisfactory', 'neutral', 'satisfactory' or 'highly satisfactory': 1/2/21/18/0 vs. 1/14/15/11/1, p = 0.0038. There were no differences in the rates of nausea, vomiting, dizziness or length of hospital stay. Serratus anterior plane block may be used to reduce pain and opioid use after thoracoscopic lung surgery.


Assuntos
Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Toracoscopia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Esquema de Medicação , Feminino , Fentanila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Remifentanil/administração & dosagem , Adulto Jovem
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