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Nanotechnology for treatment of glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM), a grade IV astrocytoma as defined by the World Health Organization (WHO) criteria, is the most common primary central nervous system tumor in adults. After treatment with the current standard of care consisting of surgical resection, concurrent temozolomide (TMZ), and radiation, the median survival is only 15 months. The limited and less-effective treatment options for these highly aggressive GBMs call for the development of new techniques and the improvement of existing technologies. Nanotechnology has shown promise in treating this disease, and some nanomaterials have demonstrated the ability to cross the blood–brain barrier (BBB) and remain in GBM tissues. Although the retention of nanoparticles (NPs) in GBM tissue is necessary to elicit an antitumor response, the delivery of the NP needs to be enhanced. Current research in nanotechnology is directed at increasing the active targeting of GBM tissue not only for the aid of chemotherapeutic drug delivery but also for imaging studies. This review is aimed at describing advancements in increasing nanotechnology specificity to GBM tissue.

Open access
Non-invasive evaluation of fluid dynamic of aortoiliac atherosclerotic disease: Impact of bifurcation angle and different stent configurations

Abstract

Objectives

To non-invasively evaluate by computational fluid dynamic (CFD) analysis the physiology and rheology of aortoiliac bifurcation disease at different angles and different stent configurations.

Material and methods

For the analysis, we considered a physiologic model of abdominal aorta with an iliac bifurcation set at 30°, 45° and 70° without stenosis. Subsequently, a bilateral ostial common iliac stenosis of 80% was considered for each type of bifurcation. For the stent simulation, we reconstructed Zilver vascular self-expanding (Zilver; Cook, Bloomington, MN) and Palmaz Genesis Peripheral (Cordis, Miami, FL) stents.

Results

The physiologic model, across the different angles, static pressure, Reynolds number and stream function, were lower for the 30° bifurcation angle with a gradient from 70° to 30° angles, whereas all the other parameters were inversely higher. After stenting, all the fluid parameters decreased homogenously independent of the stent type, maintaining a gradient in favour of 30° compared to 45° and 70° angles. The absolute greater deviation from physiology was observed for low kissing when self-expandable stents were used across all angles; in particular, the wall shear stress was high at at 45° angle.

Conclusion

Bifurcation angle deeply impacts the physiology of aortoiliac bifurcations, which are used to predict the fluid dynamic profile after stenting. CFD, having the potential to be derived both from computed tomography scan or invasive angiography, appears to be an ideal tool to predict fluid dynamic profile before and after stenting in aortoiliac bifurcation.

Open access
Timing of transjugular intrahepatic portosystemic stent-shunt in Budd–Chiari syndrome: A UK hepatologist's perspective

Abstract

Budd–Chiari syndrome (BCS) is a rare but fatal disease caused by the obstruction in hepatic venous outflow tract (usually by thrombosis) and is further classified into two subtypes depending on the level of obstruction. Patients with BCS often have a combination of prothrombotic risk factors. Clinical presentation is diverse. Stepwise management strategy has been suggested with excellent 5-year survival rate. It includes anticoagulation, treatment of identified prothrombotic risk factor, percutaneous recanalization, and transjugular intrahepatic portosystemic shunt (TIPS) to reestablish hepatic venous outflow and liver transplantation in unresponsive patients. Owing to the rarity of BCS, there are no randomized controlled trials (RCTs) precisely identifying the timing for TIPS. TIPS should be considered in patients with refractory ascites, variceal bleed, and fulminant liver failure. Liver replacement is indicated in patients with progressive liver failure and in those in whom TIPS is not technically possible. The long-term outcome is usually influenced by the underlying hematologic condition and the development of hepatocellular carcinoma. This review focuses on the timing and the long-term efficacy of TIPS in patients with BCS.

Open access
Acute respiratory distress syndrome: An update and review

Abstract

Acute respiratory distress syndrome (ARDS) is a life threatening condition characterized by severe hypoxemia due to pulmonary gas exchange failure and was first recognized in 1960s.Since its first description, it has undergone intensive research in the past few decades to understand its pathogenesis and therapies. Despite this, the recommended therapies to decrease mortality in ARDS remain limited and include low-tidal volume mechanical ventilation, prone ventilation and recently, the ECMO rescue therapy in extreme cases. This review article will summarize the key features of ARDS with a brief overview of the therapeutic options in the management of ARDS.

Open access
Adenosquamous carcinoma of the esophagus: A literature review

Abstract

Adenosquamous carcinoma (ASC) of the esophagus is an uncommon type of esophageal cancer that contains both adenocarcinoma and squamous cell carcinoma elements. Data on this biologically unique type of cancer are limited and mainly stem from case reports and small case series. We performed an audit of the available literature and synthesized a review on the epidemiology, pathogenesis, histopathology, clinical manifestations, diagnosis, treatment and prognosis of ASCs. Adenosquamous carcinoma of the esophagus is a rare type of esophageal cancer. Histological examination is necessary to confirm the diagnosis of ASC and patients usually receive multimodal treatment. Patient outcomes are not well defined and further research could help us better understand the pathophysiology and unique needs of patients with this rare malignancy.

Open access
Does hepatic impairment influence renal function parameters in liver cirrhosis?
Open access
Dyspepsia amongst end stage renal disease undergoing hemodialysis: Views from a large tertiary care center

Abstract

Background and Objectives

Gastrointestinal symptoms are common in patients with end stage renal disease (ESRD) among which dyspepsia is frequently observed. The aim of the study was to determine the frequency and associations of dyspepsia in ESRD patients using the Leeds questionnaire.

Methods

All ESRD patients on maintenance hemodialysis were consecutively enrolled in the study. Leeds questionnaire was used to interrogate the patients for the assessment of dyspepsia. Mean and standard deviation were calculated for age, body mass index (BMI), disease duration and number of hemodialysis sessions. Independent t-test and Chi square tests were used for statistical analysis.

Results

Total number of patients was 200, out which 118 (59.3%) were male. The mean age was of 41.4 years. According to the Leeds questionnaire, dyspepsia was present in 62 (63.9%) patients. Younger patients (age 20–40 years) more frequently had dyspeptic symptoms (61.5% patients), retrosternal pain (156 patients, 78.0%), regurgitation (127 patients, 63.5%), dysphagia (67 patients, 33.5%), and nausea (142 patients, 71.0%). Patients presented with intermittent pattern of symptoms in 179 (89.5%) cases, while continuous symptoms in 6 (3.0%). Dyspepsia was associated with aspartate aminotransferase (AST) levels > 25 U/L (P = 0.001), alanine aminotransferase (ALT) levels > 28U/L (P = 0.000) and gamma glutamyl transferase (GGT) levels > 34 U/L (P = 0.002). On multivariate analysis, urea, creatinine, and presenting symptoms of dysphagia and belching showed significant statistical association with dyspepsia.

Conclusion

Dyspepsia is a common problem affecting patients with end stage renal disease and is associated with raised serum AST, ALT and GGT in such patients.

Open access
Hepatitis C screening in commercially insured U.S. birth-cohort patients: Factors associated with testing and effect of an EMR-based screening alert

Abstract

Background and Objectives

Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates.

Methods

All birth-cohort outpatients between 2010 and 2015 were identified. HCV-Ab test results, clinical, and demographic variables were extracted from the EMR, and factors associated with testing were analyzed by logistic regression. True birth-cohort HCV screening rates were determined by detailed chart review for all outpatient visits during one calendar month. An automated Best Practice Alert was used to identify unscreened patients at the point of care, and to prompt HCV testing. Screening rates before and after system-wide implementation of the BPA were compared.

Results

The historic HCV-Ab testing rate was 11.2% (11,976/106,753). Younger age, female gender, and African American, Asian, or Hispanic ethnicity, and medical comorbidities such as chronic hemodialysis, HIV infection, and rheumatologic and psychiatric comorbidities were associated with higher testing rates. However, during the one-month sampling period, true age cohort-based testing was performed in only 69/10,089 patients (0.68%). Following the system-wide implementation of the HCV BPA, testing rates increased from 0.68% to 10.76% (P<0.0001).

Conclusions

We documented low HCV-Ab testing rates in our baby boomers population. HCV testing was typically performed in the presence of known risk factors or established liver disease. The implementation of an EMR-based HCV BPA resulted in a marked increase in testing rates. Our study highlights current HCV screening gaps, and the utility of the EMR to improve screening rates and population health.

Open access
Hypoxia-inducible factor may induce the development of liver fibrosis in Budd–Chiari syndrome by regulating CD248/endosialin expression: A hypothesis

Abstract

Budd-Chiari syndrome (BCS) leads to the development of liver fibrosis in most of the cases. However, the mechanism of BCS-related liver fibrosis is unclear, and it may be largely different from that induced by chronic viral hepatitis. Hepatic stellate cell (HSC) and its specific marker CD248/endosialin are known to play an important regulatory role in the development of liver fibrosis. Additionally, hypoxia microenvironment and hypoxia-inducible factor (HIF) are involved in the regulation of CD248/endosialin. Therefore, we hypothesize that hypoxia microenvironment which develops due to BCS can regulate the expression of CD248/endosialin in HSC via HIF signaling pathway, which then affects the function of HSC and development of liver fibrosis. To confirm the hypothesis, two major investigations are necessary: (1) in the BCS animal model and clinical studies, the relationship between the severity of liver fibrosis and the expression of HIF and CD248/endosialin in HSC will be explored; and (2) in the in vitro cell system, the effect of hypoxic microenvironment, HIF-1α or HIF-2α, on the expression of CD248/endosialin in HSC will be explored. It will be important to elucidate whether HIF signaling pathway regulates the expression of CD248/endosialin, thereby inducing the development of BCS-related liver fibrosis.

Open access