Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.
Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.
Results: Significant difference was found in the superotemporal and temporal areas.
Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer. 相似文献
Area covered: This review discusses the development of BRAF inhibitor-based combination therapies for BRAF-mutant advanced melanoma.
Expert opinion: Future strategies for the treatment of advanced melanoma include novel combination therapies using BRAF/MEK inhibitors and immune checkpoints inhibitors or histone deacetylase inhibitors. These combination therapies might enhance antitumor responses against melanoma, prolonging survival in advanced melanoma patients. Further clinical studies are needed to optimize these novel combination therapies. 相似文献
Commonly used cytotoxics in these patients include paclitaxel, dacarbazine, platins, and temozolomide. The overall response rates of these agents are usually disappointing and short-lived.
Areas covered: Herein, the author provides a literature review of the role of nab-paclitaxel in metastatic melanoma including coverage of its pharmacokinetics, pharmacodynamics and efficacy.
Expert opinion: The role of chemotherapy in the treatment of metastatic melanoma is limited to patients who failed checkpoint inhibitors and, when applicable, targeted agents, and those not appropriate for clinical trials. nab-Paclitaxel has single agent activity in chemotherapy-naïve untreated metastatic melanoma which compares favorably to the activity of weekly paclitaxel or single agent dacarbazine. However, the activity in chemotherapy-pretreated patients is modest. Data on nab-paclitaxel in patients pretreated with targeted agents or check point inhibitors are lacking. Further advances are expected from new checkpoint inhibitors and targeted agents for the treatment of metastatic melanoma in addition to the optimal combination and sequencing of these agents. 相似文献
Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.
Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.
Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).
Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend. 相似文献
Area covered: In this review, the authors discuss the representative research of c-Met inhibitors published in recent years. Furthermore, it provides background research of c-Met kinase inhibitors, the introduction of drugs on the market and in clinical research, and the research progress of novel small molecule inhibitors. In particular, this review emphasizes the important role of ‘5-atoms linker’ in the design of some novel c-Met enzyme inhibitors.
Expert opinion: Discovering novel c-Met kinase inhibitors via natural product chemistry may become a new research field. Though it is difficult, the key to developing better c-Met kinase inhibitors is structural optimization. 相似文献
Areas covered: In this review, the authors discuss the evidence for currently approved therapies for cutaneous melanoma, including adjuvant therapy, potential new biomarkers, and emerging treatments with early phase clinical trial data. The authors have searched both the PubMed and clinicaltrials.gov databases for published clinical trials and discuss selected landmark trials of current therapies and of investigational treatment strategies with early evidence for the treatment of melanoma.
Expert opinion: Significant efficacy has been demonstrated with both immune checkpoint inhibitors and targeted therapies in treating advanced melanoma. A multitude of novel therapies are in development and there is need for instructive biomarker assessment to identify patients likely to respond or be refractory to current therapies, to identify mechanisms of resistance and to direct further treatment options to patients based on individual disease biology. 相似文献
Methods: Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms “randomized controlled trials”, “dexketoprofen”, “celecoxib”, “etoricoxib”, “parecoxib” and “acute pain”.
Results: Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30?minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting.
Conclusion: In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting. 相似文献
Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.
Expert opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance. 相似文献
The kynurenine pathway (KP) is the main metabolic route of tryptophan degradation, in the course of which several neuroactive compounds are generated. The imbalance of the neurotoxic and neuroprotectant metabolites can lead to excitotoxicity and overproduction of reactive oxygen species, which both contribute to the progression of HD. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme of the KP that has various immune modulatory roles.
Areas covered: Current knowledge of the involvement of KP in HD pathogenesis with a particular focus on IDO1. By reviewing the diverse roles of the enzyme in kynurenine production, immune modulation, and serotonin metabolism, we elucidate the factors that make this enzyme a therapeutic target.
Expert opinion: Due to the complexity of HD and the various effects that IDO1 exerts, targeting this enzyme, while highly profitable, may be a great challenge. Through IDO1 activity, neurodegeneration, inflammatory processes and depressive symptoms, often related to HD, can be modulated. Ongoing trials of IDO1 inhibitors in other areas of medicine offer advantages for initiating approaches toward this enzyme as a therapeutic target. 相似文献
Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.
Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1+ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment. 相似文献
Areas covered: The efficacy of DPP-4 inhibitors in the treatment of diabetic kidney disease and possible adjunct with insulin in the treatment of T1DM to preserve beta-cell function. Pertinent literature was identified through Medline, PubMed and ClinicalTrials.gov (1997-November 2018) using the search terms T1DM, sitagliptin, vildagliptin, linagliptin, beta-cell function, diabetic nephropathy. Only articles are written in the English language, and clinical trials evaluating human subjects were used.
Expert opinion: DPP-4 inhibitors can be used safely in patients with diabetic kidney disease and do not appear to exacerbate existing diabetic nephropathy. Linagliptin reduces albuminuria and protects renal endothelium from the deleterious effects of hyperglycemia. The effects of DPP-4 inhibitors on preserving beta-cell function in certain subtypes of T1DM [e.g. Latent Autoimmune Diabetes in Adult (LADA) and Slowly Progressive Type 1 Diabetes (SPIDDM)] are encouraging and show promise. 相似文献
Areas covered: This review focuses on the use of histone deacetylase inhibitors as pharmacological tools to prevent or delay cachexia, with reference to muscle wasting.
Expert opinion: Novel histone deacetylase inhibitors could be considered as exercise mimetics and this supports their use as a treatment for muscle-wasting associated diseases, such as cachexia. The ability of some of these inhibitors to modulate the release of extracellular vesicles from tumor cells is a potential tool for restricting the development of cancer-induced muscle protein depletion. There are few clinical trials that are testing histone deacetylase inhibitors as a treatment for cachexia; this reflects the lack of robust experimental evidence of effectiveness. The determination of the pathogenic mechanisms of muscle wasting and the identification of suitable histone deacetylase inhibitors that target such mechanisms are necessary. 相似文献
Areas covered: The purpose of this review is to discuss the chemical treatment options for pediatric atopic dermatitis, including immunomodulators and small molecule inhibitors. A systematic literature search was conducted, and publications were reviewed for applicable treatment guidelines.
Expert opinion: Topical therapy is first-line for pediatric atopic dermatitis. Providers should work closely with patients and caregivers to promote the success of topical treatments. In disease refractory to topical treatments, systemic agents may be considered. Clinical trials are ongoing for the use of biologics in the treatment of pediatric AD. When choosing the most appropriate treatment, physicians should consider the drug efficacy, potential adverse effects, patient adherence, and quality of life for both patients and caregivers. Additional studies are required to determine the safest and most effective doses for systemic therapy in childhood AD. 相似文献
Materials and methods: The study was developed in an installed additive manufacturing machine, having controlled temperature and humidity in an industrial unit where metal parts were being produced using stainless steel powders of granulometry of 10 to 35?μm.
Results and discussion: Monitoring of airborne nanoparticles emission was made using adequate equipment, which showed considerable number of nanoparticles over the baseline, having the same composition as the steel powder used.
Conclusion: It is concluded that the values of professional exposure to nanoparticles are high in these workstations and that the nanoparticles to which the workers are exposed are small in size (around 15?nm), thus having a strong capacity for alveolar penetration and, consequently, with a strong possibility of passing to the bloodstream, accumulating in the body. 相似文献
Method: Three hundred and seventy-five patients were assessed. Socio-demographic characteristics, addiction severity, lifetime abuse, suicidal ideation and attempts, and psychopathological symptoms were explored.
Results: Eighty-two patients (21.9%) presented with a history of lifetime abuse and were included in the study (37 men and 45 women). Sixty-two per cent of them presented with lifetime suicidal ideation (12.2% in the last month), and 30.5% with suicide attempts (1.2% in the last month). Patients with suicidal ideation or attempts showed a more severe addiction profile (assessed by the EuropASI) and more psychopathological symptoms (assessed by the SCL-90-R).
Conclusion: This study highlights the relationship between previous traumatic experiences and suicidal behaviours. According to these results, systematic screening of suicidal risk in patients seeking treatment in addiction centres with histories of abuse is recommended. 相似文献
Areas covered: This review covers investigational EC therapeutics acting on the PI3K/AKT/mTOR pathway. The authors review the results of clinical studies and highlight ongoing trials.
Expert opinion: Several new agents are under evaluation for treating patients with metastatic, recurrent, and persistent EC. Clinical trials investigating PI3K/AKT/mTOR inhibitors have yielded controversial results. In the near future, new studies with dual inhibitors or multi-pathways inhibitors as mono or combination therapies with conventional chemotherapy (CT) or other targeted drugs may provide more promising data. Moreover, the evaluation of new serum and histological biomarkers is an attractive strategy for patient selection. 相似文献
Methods: A Markov model was developed to measure economic and health outcomes of novel regimens for genotype 1b, 2, 3, and 6 HCV infections compared with PR treatment. Clinical, cost, and utility inputs were gathered from published sources. Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) are shown. The uncertainty was facilitated by one-way and probabilistic sensitivity analyses.
Results: For genotype 1b HCV infection, the combination of paritaprevir, ritonavir, ombitasvir and dasabuvir was cost-saving compared with four competing alternatives. The ICERs of sofosbuvir plus ribavirin for genotypes 2 and 3 were lower than the threshold ($18,234/QALY). Among available strategies for patients with genotype 6, sofosbuvir in combination with ribavirin was the cost-saving alternative compared with PR. The results were robust to sensitivity analyses.
Conclusions: For both genotype 1b and 6 HCV infections in the context of Chinese patients, there were combinations of DAAs that were cost-saving compared with the usual PR treatment, and cost-effective for genotypes 2 and 3. 相似文献
Areas covered: The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon.
Expert opinion: Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future. 相似文献
Methods: Twelve in-depth interviews were conducted with several actors: visitors, staff members, volunteers, and persons involved from outside the meeting place.
Results: First, Villa Voortman was experienced as ‘a place to be’, providing visitors a possibility to feel safe and accepted, and belong to a peer group. Voluntary participation to activities is crucial to install such feeling. In time, the meeting place also becomes ‘the place to be’, as visitors start to feel at home. Secondly, it functions as ‘a place to be me’, helping participants to (re-)build their identity and become visible citizens.
Conclusions: The findings are highly consistent with recovery literature and Lacanian ideas on the treatment of psychosis. Some ‘contours’ that shape the daily practice of Villa Voortman could be identified: particularizing to personal needs, having a focus on personal, social, and structural aspects of recovery and the coexistence of different discourses. 相似文献