Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation.

This study was designed to analyze cytokine levels in bronchoalveolar lavage (BAL) fluid of patients with pulmonary fibrosis (PF) and was performed at a University hospital. Nineteen veterans had mustard gas-induced PF, and 19 normal veterans were used as a control group. Chest roentgenograms, pulmonary function tests (PFTs), the percentage diffusing capacity of carbon monoxide (D(LCO)), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-12, and the growth factors transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) were performed in all cases. A transbronchial lung biopsy was done in all patients. There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-beta, EGF, and IGF-1 levels were also significantly increased in patients with PF compared with controls. A significant negative correlation was observed between the percentage of D(LCO) and IL-8 levels in BAL fluid in patients with PF (r = -0.47, p = 0.04). A significant negative correlation was also seen between the percentage of D(LCO) and TGF-beta (r = 0.53, p = 0.02) in these patients. Except for the percentage and the absolute number of the BAL fluid neutrophils (r = 0.70, p = 0.001 and r = -0.62, p = 0.005, respectively), no correlation was found between D(LCO)% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-beta showed a significant correlation with the degree of fibrosis (p = 0.004, p = 0.04). The increased levels of cytokines and growth factors in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced PF by recruitment of neutrophils and eosinophils into the lung.     

Development and implementation of an appropriateness guideline for use of CT in cases of suspected intraabdominal abscess

RATIONALE AND OBJECTIVES: The purpose of this study was to develop an evidence-based guideline for use of computed tomography (CT) in the evaluation of suspected abdominal abscess. The goal of the guidelines was to decrease the absolute number of CT examinations performed for suspected abdominal abscess and to increase the rate of positive CT examinations while not missing clinically relevant abscesses. MATERIALS AND METHODS: A multidisciplinary team developed an evidence-based guideline regarding use of CT to evaluate for suspected abscess. A control group consisted of patients scanned for suspected abscess during a 6-month period. The intervention group consisted of patients scanned in the 6 months after guideline implementation. Focal fluid collections depicted on CT scans were reviewed for both patient groups to determine if these collections were abscesses. The number and proportion of abscesses in each group were then compared. RESULTS: During the control period, 263 CT examinations for suspected abscess were performed, 75 of which (28.5%; 90% confidence interval [CI], 24%, 33%) depicted focal fluid and 25 of which (9.5%; 90% CI, 7%, 12%) depicted abscess. During the intervention period, 238 CT examinations were performed, 54 of which (22.7%; 90% CI, 18%, 27%) depicted fluid and 41 of which (17.2%; 90% CI, 13%, 21%) depicted abscess. CONCLUSION: A guideline was successful at decreasing the number of CT examinations and increasing the proportion of positive CT results for abdominal abscess. As with other inpatient utilization interventions, each practice must assess the cost-benefit trade-off of guideline implementation in complex clinical situations.     

Platelet-rich fibrin (PRF) gel modified by a carbodiimide crosslinker for tissue regeneration

Platelet-rich fibrin (PRF) as a rich source of effective growth factors has been used as a scaffold in tissue regeneration. It is known that PRF exhibits rapid degradability against enzymes, which should be decreased using crosslinking agents to reduce the release rate of growth factors and increase the effectiveness of tissue regeneration. In this study, a carbodiimide crosslinker with different concentrations (0.01%, 0.05%, 1%, and 2%) was used to modify and improve the properties of PRF gel. The crosslinked gels were evaluated with analyses such as SEM, swelling, degradability, mechanical strength, release test, cytotoxicity, and cell adhesion. The results showed that with increasing crosslinker concentration, the morphology of the fiber structure changes drastically, the swelling rate decreases from 300% (control) to 160% for the crosslinked gel, the degradation time for the control sample increases from 8 days to more than two weeks for the crosslinked gel, and the Young''s modulus increases from 0.15 MPa (control) to 0.61 MPa for the crosslinked samples. Growth factors also showed lower release with increasing crosslinking ratio. Cytotoxicity assays demonstrated that by increasing the crosslinker concentration to 1% w/v, no cytotoxicity was observed. Cellular studies with DAPI staining showed that the cells penetrated well into the gels and were well distributed, especially in gels with lower crosslinker concentrations. In addition, the modified PRF gel can be used as a scaffold for tissue regeneration.

1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) as a crosslinker can improve the physical and mechanical properties of PRF gel by forming covalent bonds.     

Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Introduction: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF^V600 mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.

Areas covered: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib, and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.

Expert opinion: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.     

Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine

Metabolic Brain Disease - Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine...