Interstitial lung disease associated with combination therapy of dabrafenib and trametinib in metastatic BRAFV600E-mutated poorly differentiated thyroid cancer: A case report and review of the literature.

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system, accounting for ~ 5% of all thyroid nodules and 1% of all systemic malignancies. BRAF mutations, primarily p.V600E hot spot mutations, are found in 60 - 70% of papillary thyroid cancer cases (PTC) and in 33 - 40% of fatal anaplastic thyroid cancers (ATC), also called poorly differentiated thyroid cancer. Dabrafenib was approved by the United States Food and Drug Administration (FDA) in 2018 to be applied in combination with trametinib for unresectable advanced or metastatic anaplastic thyroid cancer harboring the BRAFV600E mutation. Unfortunately, there are few reports on the pathophysiology, molecular mechanism, and risk factors of interstitial lung disease induced by combined BRAF- and MEK-targeted therapy. CASE PRESENTATION: We treated a 73-year-old man with metastatic BRAFV600E-mutated poorly differentiated thyroid cancer using the combination of dabrafenib and trametinib. Although a significant morphologic tumor response was observed in our patient using combined BRAF- and MEK-targeted therapy, he presented with non-febrile respiratory failure, and his chest computed tomography (CT) revealed bilateral reticulation and pleural effusion. Withdrawal from dabrafenib-trametinib and administration of methylprednisolone rapidly improved his respiratory status and imaging features. CONCLUSION: The mechanisms of lung disease after the combined treatment with dabrafenib and trametinib are unclear. We hypothesized that dual-targeted therapy with a BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, might prevent the regeneration and proliferation of fibrotic epithelium in lung disease by blocking downstream proliferative signals.

Advanced treatment of dye wastewater using a novel integrative Fenton-like/MnO2-filled upward flow biological filter bed system equipped with modified ceramsite.

The deposal of residual hydrogen peroxide (H2O2) in Fenton-like system and the requirement of oxygen in bioreactor are essential parts for the treatment of integrative Fenton-like/bioreactor. A novel low-cost integrative Fenton-like and MnO2-filled upward flow biological filter bed (Fenton-like/MBFB) equipped with the modified ceramsite was constructed to evaluate the main properties and catalytic activity of modified ceramsite, and the optimal conditions of integrative system and compare integrative and traditional systems. In this study, the Fenton-like reactor with modified ceramsite had higher catalytic ability whose Acid Orange 7 (AO7) degradation efficiency reached to 79.3% due to large surface area and high porosity, compared with that with raw ceramsite (44.3%). Furthermore, total utilization efficiency of H2O2 in integrative system (from 32.41% to 53.51%) and removal efficiencies of COD and AO7 were remarkably improved, which would effectively decrease the waste of H2O2 and the setting of regulation pool and aeration tank. Thus, the integrative system can save 0.51 CNY/m3 in construction cost and 0.21 CNY/m3 in operating cost. The average COD removal efficiency, AO7 degradation efficiency and effluent DO concentration were achieved to 64.8%, 79.5% and 9.3 mg/L respectively in integrative system were achieved in integrative system during sixty successive runs. Also, the potential degradation pathway of contaminants was also proposed according to the OH-enhanced at Fenton-like reactor due to catalyst and adsorption of modified ceramsite and the removal of microorganisms and modified ceramsite for contaminants at MBFB. This study demonstrated the feasibility of integrative Fenton-like/MBFB filled with modified ceramsite for simultaneously decreasing operational cost and complexity and enhancing removal efficiency, thus provided a one-step alternative for refractory dye wastewater.

The Efficacy and Safety of DFN-15 for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies.

OBJECTIVES: The efficacy of DFN-15 for pain control of migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of DFN-15 versus placebo on pain control in migraine patients. PATIENTS AND METHODS: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through November 2019 for randomized controlled trials assessing the effect of DFN-15 versus placebo on pain control in migraine patients. This meta-analysis is performed using the random-effects model. RESULTS: Three randomized controlled trials are included in the meta-analysis. Overall, compared with the control group in migraine patients, lasmiditan treatment shows a positive impact on pain freedom at 2 hours (risk ratio [RR], 1.96; 95% confidence interval, 1.61-2.40; P < 0.00001), headache response at 2 hours (RR, 1.40; 95% CI, 1.25-1.57; P < 0.00001), and pain freedom at 24 hours (RR, 1.87; 95% CI, 1.33-2.62; P = 0.0003), but has no obvious influence or no substantial impact on no or mild disability level (RR, 1.21; 95% CI, 0.97-1.52; P = 0.09) or nausea (RR, 2.42; 95% CI, 0.53-11.01; P = 0.25). In addition, lasmiditan seems to result in the increase in dizziness (RR, 7.33; 95% CI, 1.83-29.30; P = 0.005) and paresthesia (RR, 5.17; 95% CI, 2.08-12.86; P = 0.0004). CONCLUSIONS: DFN-15 treatment may be effective and safe for pain control in migraine patients.

A study on the relationship between intrauterine device type and processing period and reproductive tract infections.

The intrauterine device (IUD) has corresponding side effects including reproductive tract infectious diseases, irregular vaginal bleeding, menoxenia, lower abdominal pain, pain in the lumbosacral region and ectopic gestation. A prior study conducted by Bhatia and Cleland reflected that contraceptive usage was one of the factors that influence the occurrence of RTIs in South India. Although many studies have been conducted in various parts of different countries with the aim to document the prevalence of RTIs and its risk factors, there remains a lack of sizable literature for Chinese women who use specific IUDs. Therefore, we conducted an analysis on the relationship of IUD type and processing period with the occurrence rate of RTI.

Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis.

Interleukins (ILs) are the most typical inflammatory and immunoregulatory cytokines. Evidences have shown that polymorphisms in ILs are associated with cerebral infarction risk. However, the results remain inconclusive. The present study was to evaluate the role of ILs polymorphisms in cerebral infarction susceptibility. Relevant case-control studies published between January 2000 and December 2015 were searched and retrieved from the electronic databases of Web of Science, PubMed, Embase and the Chinese Biomedical Database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. A total of 55 articles including 12619 cerebral infarction patients and 14436 controls were screened out. Four ILs (IL-1, IL-6, IL-10 and IL-18) contained nine single nucleotide polymorphisms (SNPs; IL-1α -899C/T, IL-1ß -511C/T and IL-1ß +3953C/T; IL-6 -174G/C and -572C/G; IL-10 -819C/T and -1082A/G; IL-18 -607C/A and -137G/C). Our result showed that IL-1α -899C/T and IL-18 -607C/A (under all the genetic models), and IL-6 -572C/G (under the allelic model, heterogeneity model and dominant model) were associated with increased the risk of cerebral infarction (P<0.05). Subgroup analysis by ethnicity showed that IL-6 -174G/C polymorphism (under all the five models) and IL-10 -1082A/G polymorphism (under the allelic model and heterologous model) were significantly associated with increased the cerebral infarction risk in Asians. Other genetic polymorphisms were not related with cerebral infarction susceptibility under any genetic models. In conclusion, IL-1α -899C/T, IL-6 -572C/G and IL-18 -607C/A might be risk factors for cerebral infarction development. Further studies with well-designed and large sample size are still required.