Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters

To assess the efficacy of an antibiofilm/antimicrobial agent combination, we incubated catheter segments colonized with one of six studied bacterial organisms in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecycline, or saline. Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline significantly decreased all viable biofilm-associated bacteria and was synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.     

Predictors of aneurysm occlusion following treatment with the WEB device: systematic review and case series

The Woven EndoBridge (WEB) device is becoming increasingly popular for treatment of wide-neck aneurysms. As experience with this device grows, it is important to identify factors associated with occlusion following WEB treatment to guide decision making and screen patients at high risk for recurrence. The aim of this study was to identify factors associated with adequate aneurysm occlusion following WEB device treatment in the neurosurgical literature and in our case series. A systematic review of the present literature was conducted to identify studies related to the prediction of WEB device occlusion. In addition, a retrospective review of our institutional data for patients treated with the WEB device was performed. Demographics, aneurysm characteristics, procedural variables, and 6-month follow-up angiographic outcomes were recorded. Seven articles totaling 450 patients with 456 aneurysms fit our criteria. Factors in the literature associated with inadequate occlusion included larger size, increased neck width, partial intrasaccular thrombosis, irregular shape, and tobacco use. Our retrospective review identified 43 patients with 45 aneurysms. A total of 91.1% of our patients achieved adequate occlusion at a mean follow-up time of 7.32 months. Increasing degree of contrast stasis after WEB placement on the post-deployment angiogram was significantly associated with adequate occlusion on follow-up angiogram (p?=?0.005) and with Raymond-Roy classification (p?=?0.048), but not with retreatment (p?=?0.617). In our systematic review and case series totaling 450 patients with 456 aneurysms, contrast stasis on post-deployment angiogram was identified as a predictor of adequate aneurysm occlusion, while morphological characteristics such as larger size and wide neck negatively impact occlusion.

     

“Turn the tail,not the head”: a simple,quick and inexpensive technique for the safe removal of jammed/stripped locking screws

European Journal of Orthopaedic Surgery & Traumatology - A jammed screw is a well-known complication of locking plates. Noncompliance to the standard techniques, nonusage of torque limiting...     

Synthesis of novel pyrazolobenzothiazine 5,5-dioxide derivatives as potent anti-HIV-1 agents

A new series of pyrazolobenzothiazine-based carbohydrazides was prepared in a facile way, starting with commercially available sodium saccharine. The final products were sufficiently characterized by spectroscopic techniques. In addition, compound 5k was confirmed with X-ray crystallography as well. All the compounds were screened for anti-HIV-1 and cytotoxicity activities. Overall, out of 15 compounds, seven exhibited good activity with EC₅₀ values <20 μM. Compounds 5c, 5d, 5g, 5j and 5k appeared as the potent anti-HIV-1 agents with EC₅₀ values <5.0 μM. The structure–activity relationship would facilitate the discovery of new molecules with better profile of HIV inhibition activity.     

A molecular connection of Pterocarpus marsupium,Eugenia jambolana and Gymnema sylvestre with dipeptidyl peptidase-4 in the treatment of diabetes

Context: Pterocarpus marsupium (PM) (Leguminosae), Eugenia jambolana (EJ) (Myrtaceae) and Gymnema sylvestre (GS) (Asclepiadaceae) are the most important medicinal plants in the Indian system of traditional medicine for the treatment of hyperglycemia.

Objectives: Dipeptidyl peptidase-4 (DPP-4) inhibitors are the emerging class of anti-diabetic agents. However, only few compounds are commercially available. Therefore, in the present study we tried to explore the naturally occurring PM, EJ and GS semi-standardized extracts for their potential DPP-4 inhibition in vitro and in vivo.

Materials and methods: DPP-4 inhibition was evaluated by in vitro inhibitory assay, and enzyme kinetics were calculated using one-phase exponential decay equation. Glucose load (2?g/kg) was administered to control and diabetic rats 30?min following extract administration (100, 200 and 400?mg/kg) orally once, and blood samples were withdrawn at 0, 0.5, 1, 1.5, 2 and 3?h to measure plasma active glucagon-like peptide-1 (GLP-1) levels.

Results: PM and EJ inhibit DPP-4 potently with IC₅₀ values of 273.73?±?2.96 and 278.94?±?6.73?µg/mL, respectively, compared to GS (773.22?±?9.21?µg/mL). PM, EJ and GS exhibit long duration of action with enzyme inhibitory half-lives of 462.3, 317.2 and 153.8?min, respectively. Extracts significantly increase GLP-1 levels compared to negative control groups and peak GLP-1 level was observed at 2?h for PM and EJ, whereas for GS it was at 1.5?h

Discussion and conclusion: Taken together, results suggest the extracts may have potent DPP-4 inhibitory action, and their hypoglycemic action attributed through an increase in plasma active GLP-1 levels.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

Tumor Size Predicts Vascular Invasion and Histologic Grade Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3–5 cm, 24.7 %; 5–7 cm, 38.3 %; 7–15 cm, 32.9 %, ≥15 cm, 55.6 %; (p?<?0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3–5 cm, 19.8 %; 5–7 cm, 24.2 %; 7–15 cm, 21.1 %; >15 cm, 31.6 % (p?=?0.04). The presence of perineural invasion (odds ratio [OR]?=?2.98) and regional lymph node metastasis (OR?=?4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p?<?0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC.