Expression of bcl-2 oncoprotien in oral squamous cell carcinoma--an immunohistochemical study

Squamous cell carcinoma is the most common malignant neoplasm of the oral cavity. Number of mechanisms plays a role at the molecular level to transform normal cell into a neoplastic cell. There are a gamut of genes, which are expressed among which bcl-2, have gained a unique importance as inhibitor of apoptosis. In normal epithelial cells Bcl-2 is restricted to stem cells and cells which undergo mitosis. Bcl-2 blocks the post-mitotic phase from apoptosis. Reports of Bcl-2 protein expression in carcinomas are conflicting such as down regulation to elevated expression. In the present study 67 cases of squamous cell carcinomas of varying grades were studied and uniform cytoplasmic positivity were noted in 12 cases for Bcl-2 protein. Bcl-2 prolongs cell survival in epithelial cells and there by giving way to other external stimulus like action of carcinogens and viral agents and interaction with other genes and aids in progression to neoplasia. The possible roles of bcl-2 in the pathogenesis of oral squamous cell carcinoma are discussed.     

In-feed antibiotic effects on the swine intestinal microbiome

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1-11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.     

IL-13 receptor-directed cancer vaccines and immunotherapy

Many immunotherapy approaches including therapeutic cancer vaccines targeting specific tumor-associated antigens are at various stages of development. Although the significance of overexpression of (IL-13Rα2) in cancer is being actively investigated, we have reported that IL-13Rα2 is a novel tumor-associated antigen. The IL-13Rα2-directed cancer vaccine is one of the most promising approaches to tumor immunotherapy, because of the selective expression of IL-13Rα2 in various solid tumor types but not in normal tissues. In this article, we will summarize its present status and potential strategies to improve IL-13Rα2-directed cancer vaccines for an optimal therapy of cancer.     

Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations

BACKGROUND: Recurrence is frequent after piecemeal snare resection of large sessile colorectal polyps. The aim of this study was to evaluate the safety and efficacy of argon plasma coagulation (APC) in preventing recurrence when applied to the edge and base of the polypectomy site after apparently complete piecemeal resection. METHODS: Patients with large (>1.5 cm) sessile polyps removed by piecemeal snare cautery were placed into 2 groups. The first consisted of patients with polyps believed by the endoscopist to be completely excised. These patients were randomized to either no further therapy (control) or to APC of the rim and any residual mucosal or submucosal tissue in the base of the polypectomy site. The second group comprised patients in whom polyps, as judged by the endoscopist, were incompletely excised by snare polypectomy; APC was routinely applied without randomization to all visible remaining adenomatous tissue. Follow-up colonoscopy was performed within 3 months and 1 year; biopsy specimens were taken routinely from the resection site and further polypectomy was performed as indicated. RESULTS: There were fewer recurrences after APC in the randomized group (1/10 APC, 7/11 no APC; p = 0.02). In the group with initial incomplete snare polypectomy, recurrence was detected at 3 months in 6 of 13 despite APC. One patient was hospitalized with abdominal pain and minor rectal bleeding but required no intervention. There were no other episodes of significant late bleeding caused by piecemeal polypectomy. One patient was referred for surgery after unsuccessful endoscopic management. CONCLUSIONS: In patients with apparent complete endoscopic snare resection of large adenomas, postpolypectomy application of APC reduces adenomatous recurrence.     

Single-breath counting: a pilot study of a novel technique for measuring pulmonary function in children

Introduction

Although peak expiratory flow rate is the conventional way to measure asthma severity in adults, its use is problematic in children because it is effort dependent. Forced expiratory volume in 1 second (FEV₁) and the ratio of FEV₁ to forced vital capacity (FEV₁/FVC) are more accurate, but generally not available in the emergency department (ED). A better test is needed. Single-breath counting (SBC) is the measurement of how far an individual can count in a normal speaking voice after a maximal effort inhalation. The count is in cadence to a metronome set at 2 beats per second. Previous work has suggested that SBC correlates with standard measures of pulmonary function in adults. However, it has never been tested in children.

Objectives

The aims of this study are to determine if SBC can be easily performed by children and to assess the correlation between SBC and standard measures of pulmonary function in a pediatric population.

Methods

This was a prospective observational study of a convenience sample of children presenting to the pulmonary clinic for scheduled pulmonary function testing (PFT). Peak expiratory flow rate, FEV₁, FVC, forced expiratory flow 25% to 75%, and FEV₁/FVC were measured and recorded. After PFT, subjects were asked to perform SBC. Three attempts were allowed, and the average was recorded. Correlation was determined by the Pearson coefficient.

Results

Sixty-seven children (ages 5-18 years, 64% male) were enrolled. All were able to understand and complete the testing. Indications for PFT included asthma and/or allergies (n = 44), cystic fibrosis (n = 9), and other chronic diseases (n = 14). The correlations (r) of SBC to peak expiratory flow rate, FEV₁, FVC, forced expiratory flow 25% to 75%, and FEV₁/FVC were 0.55, 0.66, 0.71, 0.44, and −0.29, respectively (P < .05 for all results).

Conclusion

Single-breath counting is easy to perform in children, seems to correlate well with standard measures of pulmonary function, and shows promise for measuring asthma severity in children. Further work to define the range of reference SBC values (as a function of age and/or body size) and an evaluation of the utility of SBC in an ED population of acute asthmatics is indicated.     

Therapeutic apheresis: a review of complications and recommendations for prevention and management

Therapeutic apheresis procedures are a form of extracorporeal therapy that use different techniques to separate blood into the different components out of which the part containing the etiological agent in a disease process is discarded and the rest of the components of blood are re-infused into the patient, frequently with the addition of a replacement fluid or volume. These complex procedures have inherent risks of adverse events and factors that may impact on the incidence these events include the underlying disease state, anticoagulation techniques, replacement fluid type including the volume, issues related to the vascular access used, and the therapeutic apheresis procedure type and technique. We present a representative case based review of common complications of therapeutic apheresis and suggestions about how to prevent or manage these as presented at the 2010 Therapeutic Apheresis Academy.     

Non-medical Switching from Originator Tumor Necrosis Factor Inhibitors to Their Biosimilars: Systematic Review of Randomized Controlled Trials and Real-World Studies

Tumor necrosis factor (TNF) inhibitors are widely used biologics for the treatment of several chronic inflammatory diseases. The launch of anti-TNF biosimilars has introduced the possibility of non-medical switching between originator biologics and their biosimilars. However, the potential clinical and patient-reported consequences of non-medical switching remain largely unknown, as much of the evidence comes from poorly or uncontrolled real-world evidence (RWE) studies that often have an element of bias and nonstandardized outcome measures. To appropriately evaluate the safety, efficacy, and immunogenicity of non-medical switching from an originator to its biosimilar, we propose that seven key study design elements should be considered when assessing the existing evidence: studies should be (1) randomized and double-blind, (2) adequately controlled, and (3) adequately powered; include (4) multiple switching, (5) an assessment of immunogenicity, and (6) adequate follow-up duration; and (7) report individual patient-level outcomes. This systematic review assessed the robustness and consistency of the current non-medical switching evidence, with a focus on TNF inhibitors. A comprehensive literature search (January 2012–February 2018) identified 98 publications corresponding to 91 studies (17 randomized controlled trials and 74 RWE studies) describing non-medical switching from a TNF inhibitor originator to its biosimilar. When assessing the totality of this evidence, none of the non-medical switching studies conducted to date were found to use all seven of the key design elements, and the absence of these elements dilutes the robustness of the data. Furthermore, discontinuation rates varied widely among studies (0–87%), suggesting heterogeneity and inconclusiveness of the current efficacy, safety, and immunogenicity evidence, particularly at an individual patient level. Therefore, patients should not be indiscriminately switched from an originator TNF inhibitor to its biosimilar for non-medical reasons. Switching decisions should remain between the treating physicians and their patients and be made on a case-by-case basis, relying upon robust scientific evidence.Funding: AbbVie.Plain Language Summary: Plain language summary available for this article.