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1.
J Evid Based Dent Pract ; 24(3): 101932, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39174167

RESUMO

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Pitman J, Christiaens V, Callens J, Glibert M, Seyssens L, Blanco J, Cosyn J. Immediate implant placement with flap or flapless surgery: A systematic review and meta-analysis. J Clin Periodontol. 2023 Jun;50(6):755-764. doi: 10.1111/jcpe.13795. Epub 2023 Mar 5. PMID: 36843361. SOURCE OF FUNDING: The study was funded by the authors and their affiliated institutions. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.


Assuntos
Carga Imediata em Implante Dentário , Humanos , Perda do Osso Alveolar , Implantação Dentária Endóssea/métodos , Implantes Dentários , Retalhos Cirúrgicos , Revisões Sistemáticas como Assunto , Metanálise como Assunto
2.
J Nutr Health Aging ; 26(7): 732-738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35842764

RESUMO

OBJECTIVES: The present study aimed to investigate the incidence of and risk factors for postoperative pneumonia and aspiration pneumonia after hip fracture surgery. DESIGN: Retrospective cohort study from 2005 to 2021. SETTING: Asan Medical Center in Seoul, Republic of Korea. PARTICIPANTS: A total 1,208 patients aged ≥ 65 years who underwent hip fracture surgery. MEASUREMENTS: Postoperative pneumonia was defined as cases with new infiltration on chest x-ray or chest computed tomography (CT) after surgery or confirmed by a pulmonologist's consultation and diagnosis. Aspiration pneumonia was defined as: 1) radiologic findings of hospital-acquired pneumonia on chest radiographs or CT, medical record of aspiration pneumonia confirmed by a pulmonologist's consultation, and history of vomiting or aspiration, or 2) gravity-dependent opacity on chest CT when the history of vomiting or aspiration is ambiguous. Patient demographics, past medical history, pre-injury Koval score, Charlson Comorbidity Index (CCI), blood test results, length of hospital stay, and in-hospital mortality were evaluated. A comparison analysis and binary logistic regression were performed to identify the incidence and risk factors for postoperative pneumonia and aspiration pneumonia. RESULTS: Postoperative pneumonia was diagnosed in 47 patients (3.9%), including 20 with aspiration pneumonia (1.7%). In the multivariate analysis, postoperative delirium (odds ratio [OR], 3.42; P < 0.001), American Society of Anesthesiologists (ASA) scores ≥ 3 (OR, 2.11; P = 0.021), and CCI (OR, 1.21; P = 0.013) were significant risk factors for postoperative pneumonia. Male sex (OR, 3.01; P = 0.017), postoperative delirium (OR, 3.16; P = 0.014), and preoperative serum albumin levels < 3.5 g/dL (OR, 7.00; P = 0.010) were significant risk factors for aspiration pneumonia. CONCLUSION: ASA classification ≥ 3, higher CCI, and postoperative delirium were the risk factors for postoperative pneumonia. Male sex, postoperative delirium, and lower preoperative serum albumin level were the risk factors for aspiration pneumonia. Thus, physicians should pay attention to patients with the risk factors.


Assuntos
Delírio , Fraturas do Quadril , Pneumonia Aspirativa , Pneumonia , Idoso , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia Aspirativa/complicações , Pneumonia Aspirativa/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica , Vômito/complicações
3.
Ann Oncol ; 33(10): 1021-1028, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35772665

RESUMO

BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Difosfato de Adenosina/uso terapêutico , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Progressão da Doença , Feminino , Humanos , Quimioterapia de Manutenção , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Ribose/uso terapêutico
5.
Ann Oncol ; 33(6): 593-601, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35219776

RESUMO

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.


Assuntos
Redução da Medicação , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Mutação , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas , Piperazinas , Poli(ADP-Ribose) Polimerases , Resultado do Tratamento
6.
Clin Exp Dermatol ; 47(2): 335-342, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34431555

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a devastating chronic inflammatory skin disease with frequent recurrences. Various systemic treatments and procedures have been used but the efficacy of fractional microneedling radiofrequency (FMR) has not been reported. AIM: To evaluate the clinical and histological efficacy of FMR in the treatment of HS lesions. METHODS: An 8-week, prospective, split-body, unblinded study was conducted, which enrolled 10 adult patients with mild to moderate HS to receive 3 sessions of FMR treatment biweekly. HS severity was assessed using the number and type of lesions, HS Physician Global Assessment (HS-PGA) and the modified Sartorius score (mSS). Skin biopsies were performed on participants to assess change in inflammation before and after FMR. RESULTS: Severity of HS was significantly reduced on the FMR-treated side of the body, but not on the control side. Inflammatory HS lesions were significantly reduced after 4 weeks, while HS-PGA and mSS were significantly decreased after 6 weeks. Immunohistochemistry staining showed decreased expression of inflammatory markers including neutrophil elastases, interleukin (IL)-8 and IL-17, tumour necrosis factor-α, transforming growth factor-ß1 and matrix metalloproteinases. CONCLUSION: FMR may be a viable treatment option for mild to moderate HS.


Assuntos
Hidradenite Supurativa/terapia , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idade de Início , Feminino , Hidradenite Supurativa/imunologia , Hidradenite Supurativa/patologia , Humanos , Interleucinas/análise , Masculino , Metaloproteinases da Matriz/análise , Agulhas , Projetos Piloto , Estudos Prospectivos , Terapia por Radiofrequência/instrumentação , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
7.
Respir Med Res ; 80: 100792, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34091200

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. METHODS: Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. RESULTS: Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted. CONCLUSION: There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO REGISTRATION NUMBER: CRD42019122745.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Fibrose Pulmonar Idiopática , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Estudos Prospectivos
8.
ESMO Open ; 6(3): 100149, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33984680

RESUMO

Ovarian cancer is one of the deadliest gynaecological malignancies and tends to be diagnosed at an advanced stage. Similar to many malignancies, surgery plays a critical role in many aspects of ovarian cancer management. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the induction of hyperthermia and delivery of intraperitoneal chemotherapy directly into the peritoneal cavity. Combined with cytoreductive surgery, HIPEC is an emerging treatment modality for ovarian cancer. Ovarian cancer survival outcomes can be improved by treatment with surgery and HIPEC in selected patients. Thus, this study aimed to review the current role of surgery and HIPEC in epithelial ovarian cancer. Evidence from the monumental and recent literature will be introduced.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia
9.
ESMO Open ; 6(2): 100049, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33578192

RESUMO

BACKGROUND: There is no clear consensus on the recommended second-line treatment for patients with metastatic pancreatic cancer who have disease progression following gemcitabine-based therapy. We retrospectively evaluated the clinical outcomes of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (FL) and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in patients who had failed on the first-line gemcitabine-based therapy. PATIENTS AND METHODS: From January 2015 to August 2019, 378 patients with MPC who had received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as second-line treatment across 11 institutions were included in this retrospective study. RESULTS: There were no significant differences in baseline characteristics between groups, except age and first-line regimens. With a median follow-up of 6 months, the median progression-free survival (PFS) was 3.7 months with nal-IRI/FL versus 4.6 months with FOLFIRINOX (P = 0.44). Median overall survival (OS) was 7.7 months with nal-IRI/FL versus 9.7 months with FOLFRINOX (P = 0.13). There was no significant difference in PFS and OS between the two regimens in the univariate and multivariate analyses. The subgroup analysis revealed that younger age (<70 years) was associated with better OS with FOLFIRINOX. In contrast, older age (≥70 years) was associated with better survival outcomes with nal-IRI/FL. Adverse events were manageable with both regimens; however, the incidence of grade 3 or higher neutropenia and peripheral neuropathy was higher in patients treated with FOLFIRINOX than with nal-IRI/FL. CONCLUSIONS: Second-line nal-IRI/FL and FOLFIRINOX showed similar effectiveness outcomes after progression following first-line gemcitabine-based therapy. Age could be the determining factor for choosing the appropriate second-line therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , República da Coreia , Estudos Retrospectivos
10.
HIV Med ; 22(2): 92-101, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33022830

RESUMO

OBJECTIVES: The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. METHODS: We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint-years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. RESULTS: In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non-smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint-years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. CONCLUSIONS: In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.


Assuntos
Cannabis , Infecções por HIV , Pneumopatias , Estudos Transversais , Infecções por HIV/complicações , Humanos , Pneumopatias/diagnóstico por imagem , Capacidade Vital
11.
Neurochirurgie ; 67(2): 189-192, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33049286

RESUMO

Pneumorrhachis (PR) is a rare radiological condition characterized by the presence of intraspinal air. PR is commonly classified as spontaneous (nontraumatic), traumatic, or iatrogenic, and iatrogenic PR is the most common and often occurs secondary to invasive procedures such as epidural anesthesia, lumbar puncture, or spinal surgery. PR is usually asymptomatic, but it can produce symptoms associated with its underlying pathology. Here, we report a rare case of intramedullary cervical PR following a cervical epidural steroid injection (ESI) and include pertinent discussion.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Espaço Epidural/diagnóstico por imagem , Pneumorraque/diagnóstico por imagem , Esteroides/administração & dosagem , Analgésicos/uso terapêutico , Feminino , Humanos , Injeções Epidurais/efeitos adversos , Pessoa de Meia-Idade , Pneumorraque/tratamento farmacológico , Pregabalina/uso terapêutico
12.
J Dent Res ; 99(3): 249-256, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31977286

RESUMO

Lateral cephalometry has been widely used for skeletal classification in orthodontic diagnosis and treatment planning. However, this conventional system, requiring manual tracing of individual landmarks, contains possible errors of inter- and intravariability and is highly time-consuming. This study aims to provide an accurate and robust skeletal diagnostic system by incorporating a convolutional neural network (CNN) into a 1-step, end-to-end diagnostic system with lateral cephalograms. A multimodal CNN model was constructed on the basis of 5,890 lateral cephalograms and demographic data as an input. The model was optimized with transfer learning and data augmentation techniques. Diagnostic performance was evaluated with statistical analysis. The proposed system exhibited >90% sensitivity, specificity, and accuracy for vertical and sagittal skeletal diagnosis. Clinical performance of the vertical classification showed the highest accuracy at 96.40 (95% CI, 93.06 to 98.39; model III). The receiver operating characteristic curve and the area under the curve both demonstrated the excellent performance of the system, with a mean area under the curve >95%. The heat maps of cephalograms were also provided for deeper understanding of the quality of the learned model by visually representing the region of the cephalogram that is most informative in distinguishing skeletal classes. In addition, we present broad applicability of this system through subtasks. The proposed CNN-incorporated system showed potential for skeletal orthodontic diagnosis without the need for intermediary steps requiring complicated diagnostic procedures.


Assuntos
Inteligência Artificial , Cefalometria , Redes Neurais de Computação , Curva ROC
13.
Clin Radiol ; 75(1): 57-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445764

RESUMO

AIM: To investigate the incidence and clinical characteristics of acute pancreatitis following percutaneous insertion of metallic biliary stents in patients with unresectable pancreatic cancer. The clinical efficacy of metallic stent insertion was also evaluated. MATERIALS AND METHODS: Data from 143 patients (75 men, 68 women; mean age, 65.8 years; range, 35-88 years) with unresectable pancreatic cancer who underwent percutaneous metallic biliary stent insertion between March 2007 and December 2017 were evaluated retrospectively. The incidence and clinical characteristics of acute pancreatitis were analysed. Stent patency and patient survival rates were calculated by Kaplan-Meier analysis. RESULTS: Technical success was achieved in all patients. Among 31 patients with serum amylase levels above normal values (30-110 U/l), only nine had symptoms of acute pancreatitis (incidence, 6.4%). No statistically significant risk factors were identified. Pancreatitis was successfully managed with conservative treatment at a mean of 2.9 days (range, 1-4 days). The median stent patency and patient survival times were 117 days (95% confidence interval [CI], 87-148 days) and 150 days (95% CI, 125-174.9 days), respectively. CONCLUSIONS: Acute pancreatitis was a relatively rare complication after percutaneous insertion of metallic biliary stents in patients with unresectable pancreatic cancer, and no significant risk factors were identified. Therefore, insertion of metallic biliary stents was seen to be a feasible and effective treatment approach in this patient group.


Assuntos
Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia , Pancreatite/prevenção & controle , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Neoplasias Pancreáticas/mortalidade , Pancreatite/epidemiologia , Pancreatite/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
14.
Cancers (Basel) ; 13(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33561073

RESUMO

Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7-31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5-28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6-41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5-50.2) vs. low-exposure (15.1%, 95% CI 7.3-28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9-41.5) vs. low (Africa) (13.1, 95% CI 6.5-24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.

15.
Gynecol Oncol ; 155(2): 186-191, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31519320

RESUMO

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Intervalo Livre de Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Indazóis , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
18.
Clin Exp Dermatol ; 43(6): 708-712, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29744907

RESUMO

Sugar is a well-known cosmetic ingredient for moisturizing skin with minimal side-effects. Several reports have demonstrated an antimelanogenic effect of sugar in melanocytes. We evaluated the whitening efficacy of galacturonic acid (GA), the main component of pectin, as an anti-melanogenic agent. GA significantly suppressed melanin synthesis and secretion in a concentration-dependent manner in α-melanocyte stimulating hormone-treated B16 melanoma cells, and inhibited tyrosinase activity and expression at a dose of 10 mmol/L. In a three-dimensional human skin equivalent (MelanoDerm), GA clearly brightened tissue colour. Haematoxylin and eosin and Fontana-Masson (F&M) staining of tissue sections revealed decreased melanin production without skin tissue collapse in the presence of GA. Interestingly, GA dramatically suppressed gene expression of the melanogenic proteins tyrosinase, tyrosinase-related protein (TYRP)-1 and microphthalmia-associated transcription factor, but not TYRP-2. The results support the utility of GA as an effective candidate antimelanogenic agent.


Assuntos
Ácidos Hexurônicos/farmacologia , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Transtornos da Pigmentação/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Expressão Gênica , Ácidos Hexurônicos/uso terapêutico , Humanos , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Camundongos , Pele/efeitos dos fármacos , Pele/metabolismo
19.
Ann Oncol ; 29(5): 1220-1226, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29438463

RESUMO

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
20.
Orthop Traumatol Surg Res ; 104(3): 341-346, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29458202

RESUMO

BACKGROUND: Intra-operative estimation of stem anteversion in total hip arthroplasty (THA) using postero-lateral approach is made by the surgeon's visual assessment, using the tibia as a guide, with the assumption that tibial axis is vertical to the trans-epicondylar axis. However, the accuracy of the intra-operative estimation has rarely been verified with postoperative CT-scans, with controversies regarding these measurements particularly in case of knee osteoarthritis. Therefore we performed a prospective study to: (1) determine the accuracy of the intra-operative measurement and (2) investigate factors affecting the discrepancy between the surgeon's estimation and the real stem anteversion. HYPOTHESIS: Intra-operative estimation of stem anteversion correlated with the real stem anteversion on CT-scan. PATIENTS AND METHODS: Sixty-seven THAs using cementless straight stems (65 patients) without ipsilateral total knee arthroplasty were prospectively evaluated to compare the intra-operative measurement of stem anteversion with the real stem anteversion on computed tomography (CT) scans. There were 33 men and 34 women with a mean age of 59.7years (range, 27-84years) at the time of surgery. Age, tibia plateau angle, native femoral anteversion, femoro-tibial angle, body mass index, operative site, gender, coronal and sagittal tilt of the stem, stem type, ipsilateral knee osteoarthritis, and preoperative diagnosis were analyzed to evaluate the factors affecting the discrepancy between the intra-operative and CT measurements. RESULTS: The intra-operative estimation (mean, 21.5°±8.5°; range, 5.0°-39.0°) was greater than the CT measurement (mean, 19.5°±8.7°; range, 4.5°-38.5°) by 2.0°. The mean absolute value of discrepancy was 4.5°. The correlation coefficient between intra-operative and CT measurements was 0.837. The femoro-tibial angle was associated with the discrepancy between the two measurements. In the presence of genu varum deformity, the intra-operative measurement underestimated the stem anteversion. DISCUSSION: Although intra-operative estimation of stem anteversion was slightly greater than the real stem anteversion, there was an excellent correlation between the two. The femoro-tibial angle should be considered to optimize the stem anteversion during cementless THA using postero-lateral approach. LEVEL OF EVIDENCE: Level III, prospective case control study.


Assuntos
Artroplastia de Quadril/métodos , Articulação do Quadril/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Condução Óssea , Estudos de Casos e Controles , Feminino , Fêmur/diagnóstico por imagem , Prótese de Quadril , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Tíbia/diagnóstico por imagem
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