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1.
BMC Public Health ; 21(1): 766, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882884

RESUMO

BACKGROUND: The number of North Korean defectors (NKDs) escaping to South Korea has increased. The health status of NKDs is an essential factor for a successful settlement into South Korean society. However, no studies have been conducted on the health status of NKDs in terms of education and social support. The aim of this study was to determine the associations of education and social support with the self-rated health status among NKDs. METHODS: This study utilized data gained from face-to-face interviews with 126 NKDs. A multivariable logistic regression and path analysis were performed to assess the effects of education in South Korea and social support on their self-rated health status and to explore the complex relationships between direct and indirect effects of the variables. RESULTS: NKDs who did not experience regular education in South Korea responded that they were in poor health compared to their counterpart (OR = 5.78). Although a direct association between education in South Korea and self-rated health was not shown, there was an indirect path from education in South Korea to self-rated health through social support. CONCLUSIONS: Participation in regular education in South Korea is important for the health status of NKDs. Moreover, social support has an important role in the association between education and self-rated health. Social policies and NKD assistance programs should consider and reflect the combination of education and social support interventions relevant to the health status of NKDs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33866769

RESUMO

Ultrasonography facilitates arterial catheterization compared to traditional palpation techniques, especially in small arteries. For successful catheterization without complications, practitioners should be familiar with the anatomic characteristics of the artery and ultrasound-guided techniques. There are two approaches for ultrasound-guided arterial catheterization: the short-axis view out-of-plane approach and the long-axis view in-plane approach. There are several modified techniques and tips to facilitate ultrasound-guided arterial catheterization. This review deals with the anatomy relevant to arterial catheterization, several methods to improve success rates, and decrease complications associated with arterial catheterization.

3.
Toxins (Basel) ; 13(4)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918558

RESUMO

Breast reconstruction after mastectomy is commonly performed using transverse rectus abdominis myocutaneous (TRAM) flap. Previous studies have demonstrated that botulinum neurotoxin injections in TRAM flap surgeries lower the risk of necrosis and allow further expansion of arterial cross-sectional diameters. The study was designed to determine the ideal injection points for botulinum neurotoxin injection by exploring the arborization patterns of the intramuscular nerves of the rectus abdominis muscle. A modified Sihler's method was performed on 16 rectus abdominis muscle specimens. Arborization of the intramuscular nerves was determined based on the most prominent point of the xyphoid process to the pubic crest. All 16 rectus abdominis muscle specimens were divided into four muscle bellies by the tendinous portion. The arborized portions of the muscles were located on the 5-15%, 25-35%, 45-55%, and 70-80% sections of the 1st, 2nd, 3rd, and 4th muscle bellies, respectively. The tendinous portion was located at the 15-20%, 35-40%, 55-60%, and 90-100% sections. These results suggest that botulinum neurotoxin injections into the rectus abdominis muscles should be performed in specific sections.

4.
Molecules ; 26(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804361

RESUMO

When skin is exposed to UV radiation, melanocytes produce melanin. Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Therefore, the development of safe, natural therapeutics that inhibit the production of melanin is necessary. Elaeagnus umbellata (EU) has long been widely used as a folk medicinal plant because of pharmacological properties that include anti-ulcer, antioxidant, and anti-inflammatory properties. In this study, we investigated the antioxidant activity and melanogenesis inhibitory effects of EU fractions in B16-F10 melanoma cells. EU fractions showed a dose-dependent increase in antioxidant activity in radical scavenging activity. In addition, we evaluated the effect of EU fractions on tyrosinase activity and melanogenesis in α-melanocyte-stimulating hormone-induced B16-F10 melanoma cells. EU was noncytotoxic at 12.5-50 µg/mL. EU fractions effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of CREB and ERK involved in the melanogenesis pathway, and down-regulated expression of melanogenesis-related proteins. Interestingly, the anti-melanogenesis effect was most effective at a concentration of 50 µg/mL EU, and the effects of the fractions were superior to those of the extract. Therefore, our study suggests that EU has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

5.
Antioxidants (Basel) ; 10(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809444

RESUMO

The outer layer of purple sweet potato is removed during processing; however, this layer serves as a potential source of phenolics, especially anthocyanins. Herein, the phenolic composition and antioxidant activity were determined for the inner and outer layers of five purple sweet potato cultivars ('Sinjami', 'Jami', 'Danjami', 'Yeonjami', and 'Borami') harvested in Korea. Anthocyanins were identified using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometer (UHPLC-(ESI)-qTOF-MS) and ultra-high-performance liquid chromatography-linear ion trap mass spectrometer (UHPLC-Ion trap-MS), and their composition was quantified using HPLC-coupled with diode array detector (DAD). Non-anthocyanin phenolic compounds (phenolic acids and flavonols) were quantified using UHPLC-(ESI)-triple quadrupole (QqQ). A total of 20 anthocyanins, including non-acylated or acylated peonidin, cyanidin, and pelargonidin glycosides, were identified. Peonidin 3-caffeoyl-p-hydroxybenzoyl sophoroside-5-glucoside was the major anthocyanin, with the highest level in the 'Sinjami' cultivar (outer; 12,366 mg/kg DW, inner; 14,832 mg/kg DW). Additionally, 12 phenolic acids and 6 flavonols (quercetin derivatives) were identified, with the outer layers of all cultivars displaying higher total levels than the inner layers. 'Sinjami' and 'Jami' had higher phenolic acid and quercetin derivative content and antioxidant activities than the other three cultivars (p < 0.05). Thus, the outer layers of 'Sinjami' and 'Jami' cultivars could be potential sources of anthocyanins and other phenolics.

6.
Food Res Int ; 141: 110150, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33642016

RESUMO

In this study, we compared the volatile and sensory profiles of various black rice (Oryza sativa L.) cultivars varying in milling degree. In total, 51 volatiles were identified. 2-Acetyl-1-pyrroline (2-AP) was only detected in aromatic cultivars, and the amount varied depending on the cultivar. Additionally, a nonaromatic black rice cultivar (cv. Sinnongheukchal) contained high amounts of guaiacol. Descriptive analyses revealed significant differences in 13 sensory attributes between aromatic and nonaromatic black rice samples. After milling, the intensities of most volatile compound concentrations and sensory attributes decreased. However, the intensities of the "floral," "sweet aroma," and "sweet taste" sensory attributes increased, regardless of the cultivar. Partial least squares regression analysis showed that 2-AP correlated with the "popcorn" sensory attribute of aromatic black rice cultivars, whereas guaiacol was related to the "smoky" sensory attribute of cooked black rice. This information aids in the selection of black rice cultivars for various purposes in the food industry. For example, Heukhyangchal can be used as sources of food additives due to its smoky and popcorn-like aroma.

7.
J Dent Educ ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33682126

RESUMO

OBJECTIVE: To explore how video learning strategies influence students' Flipped learning (FL) achievement, deep approach to learning (DAL) and lifelong learning (LL) orientations and how DAL and LL can be promoted. METHODS: Data were collected from 65 dental students enrolled in a 21-week clinical periodontology course. Partial least squares structural equation modeling was conducted to investigate factors and pathways affecting FL achievement, DAL, and LL. RESULTS: FL achievement was predicted by repeated and in-advance video learning strategies. In-advance, meticulous, and expanded video learning strategies directly influenced DAL, and indirectly influenced LL via DAL. LL was not affected by any of the video learning strategies but by the DAL. CONCLUSION: This study implies that mere implementation of FL may not guarantee more developed DAL and enhanced LL. Redesigning a course with FL should entail revisiting and revising student assessment. LL is an inclusive approach that requires the long-term cultivation of meaning, experience, insight, learning, and practice.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33744984

RESUMO

PURPOSE: To analyze the evolution of type 3 neovascularization in eyes with age-related macular degeneration during anti-vascular endothelial growth factor (VEGF) treatment using optical coherence tomography angiography (OCTA) analysis. METHODS: Forty-one treatment-naïve eyes (37 patients) with type 3 neovascularization were retrospectively included in the study. The growth and morphological changes in the type 3 lesions, which were recorded using OCTA, were compared across time. RESULTS: The high-flow signal of the lesion on OCTA was significantly increased at the sub-retinal pigment epithelium (RPE) and the choriocapillaris during anti-VEGF treatment. The detection rate of the flow signal in the sub-RPE increased from 50.0% at baseline and 51.2% at 12 months to 65.9% at 24 months (P = 0.013). The flow signal extending into the choriocapillaris was detected in 0% of the eyes at baseline, 9.8% of the eyes at 12 months, and 17.1% of the eyes at 24 months (P = 0.018). The presence of subretinal drusenoid deposits (SDD) was significantly more frequent in the group with extension into the choriocapillaris (100%) than in the group without (61.8%, P = 0.036). For the four eyes with extension into the choroid, the morphological feature of the lesion on en face OCTA evolved into a tangled vascular network, similar to type 1 neovascularization. CONCLUSION: OCTA analysis revealed that type 3 neovascularization gradually extended downward toward the sub-RPE and choroid during anti-VEGF treatment. The extension of the lesion into the choriocapillaris, suggesting retinal-choroidal anastomosis, was significantly more frequent in eyes with SDD.

10.
Front Immunol ; 12: 650841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777049

RESUMO

Dendritic cells (DCs) have the ability to stimulate naïve T cells that coordinate subsequent adaptive response toward an inflammatory response or tolerance depending on the DC differentiation level. Inotodiol, a lanostane triterpenoid found in Inonotus obliquus (wild Chaga mushroom), is a natural compound with a wide range of biological activities. In this study, we investigated whether inotodiol promotes the maturation of bone marrow-derived DCs (BMDCs) and inotodiol-treated BMDCs induce T cell activation. Inotodiol increased the expression of surface maturation markers, including MHC-I, MHC-II, CD86, and CD40, on BMDCs without affecting the production of various cytokines, including TNF-α and IL-12p40 in these cells. T cells primed with inotodiol-treated BMDCs proliferated and produced IL-2, without producing other cytokines, including IL-12p40 and IFN-γ. Injection of inotodiol into mice induced maturation of splenic DCs and IL-2 production, and the administration of inotodiol and inotodiol-treated BMDCs induced the proliferation of adoptively transferred CD8+ T cells in vivo. The phosphatidylinositol-3-kinase inhibitor wortmannin abrogated the upregulation of Akt phosphorylation and CD86 and MHC-II expression induced by inotodiol. However, inotodiol failed to induce phosphorylation of the IκB kinase and degradation of IκB-α, and increased expression of CD86 induced by inotodiol was not blocked by an IκB kinase inhibitor. These results suggest that inotodiol induces a characteristic type of maturation in DCs through phosphatidylinositol-3-kinase activation independent of NF-κB, and inotodiol-treated DCs enhance T cell proliferation and IL-2 secretion.

11.
J Gen Intern Med ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523343

RESUMO

BACKGROUND: Recent clinical trials suggest that e-cigarettes may be more effective for smoking cessation than traditional cessation aids, yet primary care physician (PCP) practices regarding e-cigarette recommendations for smokers have not been studied in-depth. OBJECTIVE: To identify factors influencing PCP recommendation of e-cigarettes for smoking cessation. DESIGN: Discrete choice experiment and survey. PARTICIPANTS: Florida PCPs. MEASURES: The survey included a discrete choice experiment in which PCPs indicated whether they would recommend e-cigarettes for each of 8 hypothetical patient profiles with the following contrasting characteristics: e-cigarette use, interest in approved cessation methods, smoking intensity, prior experience with approved cessation medications, quit intention, age, and comorbidity. Responses were summarized using descriptive statistics and standardized scores (SS). KEY RESULTS: The sample (n = 216) was predominately male (76%), white (66%), and non-Hispanic (78%), and most respondents had held their medical degree for 20+ years (77%). The response rate was 28.7%. Most PCPs thought e-cigarettes were at least somewhat effective for smoking cessation (66%) and lowering disease risk (65%); 31% perceived e-cigarettes to be equally/more effective than traditional cessation aids. PCPs were split regarding whether e-cigarettes were less (50%) or equally harmful (38%) as cigarettes. Yet, few were very confident in their ability to counsel patients on e-cigarettes risks (27%) or benefits (15%). PCPs recommended e-cigarettes in 27% of patient profiles they evaluated. The most important factors influencing the decision to recommend or not recommend e-cigarette were patients' prior use of nicotine replacement therapy with (SS = 0.22, 95% CI = 0.17-0.27) and without use of other medications for cessation (SS = 0.18, 95% CI = 0.13-0.23), and being middle age (50 years old) with chronic obstructive pulmonary disease (SS = 0.16, 95% CI = 0.10-0.23). CONCLUSIONS: Considering the increased patient use of e-cigarettes and increasing use for cessation, this study highlights the need for guidelines and education to aid PCPs' counseling of patients about e-cigarette use.

12.
A A Pract ; 15(2): e01369, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33560646

RESUMO

Point-of-care ultrasound has been integrated into airway management because it allows for rapid and noninvasive assessments. We present 2 cases of unexpected subglottic stenosis in infants during induction of anesthesia. Intubation failed even with endotracheal tubes that were small for patients' age. Airway ultrasound was used to measure the subglottic airway diameters, which were 2.0 and 3.0 mm in first and second cases, respectively. The severity of subglottic stenosis in the first case was grade III, requiring emergent tracheostomy. In conclusion, airway ultrasound helps to assess possibility of intubation and plan further airway management in children with unexpected difficult airway.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33541038

RESUMO

background: We review our institutional experience with pediatric laryngomalacia (LM) cases and report our experience in patients undergoing supraglottoplasty using the spontaneous respiration using intravenous anesthesia and high-flow nasal oxygen (STRIVE Hi) technique. Methods: The medical records of 29 children with LM who visited XX Hospital between January 2017 and March 2019 were retrospectively reviewed. Surgical management was performed using the STRIVE Hi technique. Intraoperative findings and postoperative surgical outcomes, including complications and changes in symptoms and weight, were analyzed. Results: Of the total study population of 29 subjects, 20 (68.9%) were female. The patients were divided according to the Onley's classification as follows: type I (n = 13, 44.8%), II (n = 10, 34.5%), and III (n = 6, 20.7%). Twenty-five patients (86.2%) had comorbidities. Seventeen patients (58.6%) underwent microlaryngobronchoscopy under STRIVE Hi anesthesia. Four patients with several desaturation events required rescue oxygenation by intermittent intubation and mask bagging during the STRIVE Hi technique. However, the procedure was completed in all patients without any severe adverse effects. Overall, 15 children (51.7%) underwent supraglottoplasty. Among the subjects who underwent supraglottoplasty, 14 (93.3%) showed improvement of symptoms, and their postoperative weight percentile was significantly increased (p = 0.026). One patient required tracheostomy immediately after supraglottoplasty due to associated neurological disease. Conclusion: The STRIVE Hi technique is feasible for supraglottoplasty in LM patients, while type III LM patients with micrognathia or glossoptosis may have a higher risk of requiring rescue oxygenation during the STRIVE Hi technique.

14.
BMC Bioinformatics ; 22(1): 96, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639834

RESUMO

BACKGROUND: microRNAs (miRNAs) have been shown to play essential roles in a wide range of biological processes. Many computational methods have been developed to identify targets of miRNAs. However, the majority of these methods depend on pre-defined features that require considerable efforts and resources to compute and often prove suboptimal at predicting miRNA targets. RESULTS: We developed a novel hybrid deep learning-based (DL-based) approach that is capable of predicting miRNA targets at a higher accuracy. This approach integrates convolutional neural networks (CNNs) that excel in learning spatial features and recurrent neural networks (RNNs) that discern sequential features. Therefore, our approach has the advantages of learning both the intrinsic spatial and sequential features of miRNA:target. The inputs for our approach are raw sequences of miRNAs and genes that can be obtained effortlessly. We applied our approach on two human datasets from recently miRNA target prediction studies and trained two models. We demonstrated that the two models consistently outperform the previous methods according to evaluation metrics on test datasets. Comparing our approach with currently available alternatives on independent datasets shows that our approach delivers substantial improvements in performance. We also show with multiple evidences that our approach is more robust than other methods on small datasets. Our study is the first study to perform comparisons across multiple existing DL-based approaches on miRNA target prediction. Furthermore, we examined the contribution of a Max pooling layer in between the CNN and RNN and demonstrated that it improves the performance of all our models. Finally, a unified model was developed that is robust on fitting different input datasets. CONCLUSIONS: We present a new DL-based approach for predicting miRNA targets and demonstrate that our approach outperforms the current alternatives. We supplied an easy-to-use tool, miTAR, at https://github.com/tjgu/miTAR . Furthermore, our analysis results support that Max Pooling generally benefits the hybrid models and potentially prevents overfitting for hybrid models.


Assuntos
Aprendizado Profundo , MicroRNAs , Humanos , MicroRNAs/genética , Redes Neurais de Computação
15.
Endocrinology ; 162(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33570110

RESUMO

Pancreatic islet beta cells (ß-cells) synthesize and secrete insulin in response to rising glucose levels and thus are a prime target in both major forms of diabetes. Type 1 diabetes ensues due to autoimmune destruction of ß-cells. On the other hand, the prevailing insulin resistance and hyperglycemia in type 2 diabetes (T2D) elicits a compensatory response from ß-cells that involves increases in ß-cell mass and function. However, the sustained metabolic stress results in ß-cell failure, characterized by severe ß-cell dysfunction and loss of ß-cell mass. Dynamic changes to ß-cell mass also occur during pancreatic development that involves extensive growth and morphogenesis. These orchestrated events are triggered by multiple signaling pathways, including those representing the transforming growth factor ß (TGF-ß) superfamily. TGF-ß pathway ligands play important roles during endocrine pancreas development, ß-cell proliferation, differentiation, and apoptosis. Furthermore, new findings are suggestive of TGF-ß's role in regulation of adult ß-cell mass and function. Collectively, these findings support the therapeutic utility of targeting TGF-ß in diabetes. Summarizing the role of the various TGF-ß pathway ligands in ß-cell development, growth and function in normal physiology, and during diabetes pathogenesis is the topic of this mini-review.

16.
Tuberculosis (Edinb) ; 127: 102052, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548864

RESUMO

A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow (SA), fourteen intermediate (IA) and six rapid acetylators (RA). As expected, isoniazid exposure was higher (mean AUC, 28.4 versus 7.6 mg*h/L) and systemic clearance lower (mean apparent clearance, 14.8 versus 50.6 L/h) in SAs than RAs. The formulas to estimate isoniazid exposure were constructed using one or more concentration-time points that correlate with the area under the concentration-time curve (AUC). The LSS using a formula of single concentration-time point at 4 h post dose (C4) is applicable for all acetylators to the therapeutic drug monitoring (TDM) of isoniazid in patients with tuberculosis when evaluated using the Deming regression and Bland-Altman plot (AUC = 1.53 + 10.03*C4, adjusted r2 = 0.95, p < 0.001). Considering that SAs are more prone to adverse effects, pre-dose NAT2 genotyping would be valuable for optimal isoniazid dosing in conjunction with TDM.

17.
Alcohol Alcohol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33550367

RESUMO

OBJECTIVES: In this tutorial, we examine methods for exploring missingness in a dataset in ways that can help to identify the sources and extent of missingness, as well as clarify gaps in evidence. METHODS: Using raw data from a meta-analysis of substance abuse interventions, we demonstrate the use of exploratory missingness analysis (EMA) including techniques for numerical summaries and visual displays of missing data. RESULTS: These techniques examine the patterns of missing covariates in meta-analysis data and the relationships among variables with missing data and observed variables including the effect size. The case study shows complex relationships among missingness and other potential covariates in meta-regression, highlighting gaps in the evidence base. CONCLUSION: Meta-analysts could often benefit by employing some form of EMA as they encounter missing data.

18.
Sci Rep ; 11(1): 856, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441685

RESUMO

Adequate viral replication in tumor cells is the key to improving the anti-cancer effects of oncolytic adenovirus therapy. In this study, we introduced short hairpin RNAs against death-domain associated protein (Daxx), a repressor of adenoviral replication, and precursor terminal protein (pTP), an initiator of adenoviral genome replication, into adenoviral constructs to determine their contributions to viral replication. Both Daxx downregulation and pTP overexpression increased viral production in variety of human cancer cell lines, and the enhanced production of virus progeny resulted in more cell lysis in vitro, and tumor regression in vivo. We confirmed that increased virus production by Daxx silencing, or pTP overexpression, occurred using different mechanisms by analyzing levels of adenoviral protein expression and virus production. Specifically, Daxx downregulation promoted both virus replication and oncolysis in a consecutive manner by optimizing IVa2-based packaging efficiency, while pTP overexpression by increasing both infectious and total virus particles but their contribution to increased viral production may have been damaged to some extent by their another contribution to apoptosis and autophagy. Therefore, introducing both Daxx shRNA and pTP in virotherapy may be a suitable strategy to increase apoptotic tumor-cell death and to overcome poor viral replication, leading to meaningful reductions in tumor growth in vivo.

19.
J Pharmacokinet Pharmacodyn ; 48(2): 253-259, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33387166

RESUMO

PURPOSE: High concentrations of sevoflurane causes respiratory depression, mainly due to the decrease in tidal volume (TV) during spontaneous ventilation. The purpose of this study was to identify clinical variables that affect the relationship between TV and sevoflurane concentration, and to establish a population pharmacodynamic modelling approach to TV and sevoflurane concentration in children. A prospective observational study involving 48 patients (≤ 6 years of age) scheduled to undergo general anesthesia using laryngeal mask airway was performed. When the inspiratory sevoflurane concentration reached 2 vol%, the vaporizer was increased to 4 vol% for 5 min, then sevoflurane was decreased to 2 vol% for 5 min. During the study period, TV, end-tidal carbon dioxide, and sevoflurane concentration were recorded every 30 s. Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the TV-sevoflurane concentration relationship. To collapse hysteresis of the pharmacokinetic and pharmacodynamic relationship, the semicompartmental model was applied which does not require a structural model for equilibration delay causing the hysteresis. TV decreased with increasing inspiratory sevoflurane concentrations. Hysteresis between the TV and sevoflurane concentration was observed and was accounted for when the model was developed. Initial TV and maximal reduction in TV were related to body weight. The γ (a steepness of the concentration-response relation curve) was 8.78 and the keo, (a first-order rate constant determining the equilibrium between the end-tidal sevoflurane concentration and effect site sevoflurane concentration) was 2.27 min-1. Changes in TV were correlated with sevoflurane concentration with spontaneous breathing during sevoflurane anesthesia. The initial and maximal TV were related to body weight, in a pediatric population.

20.
Oncologist ; 26(5): 362-e724, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33512054

RESUMO

LESSONS LEARNED: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC. BACKGROUND: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer. METHODS: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m2 p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls. RESULTS: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment. CONCLUSION: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.

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