EGFR-Targeted Therapy for Non-Small Cell Lung Cancer: Focus on EGFR Oncogenic Mutation

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.     

Dentinal tubule penetration and root canal cleanliness following ultrasonic activation of intracanal‐heated sodium hypochlorite

This study investigated the effect of ultrasonic activation of intracanal‐heated sodium hypochlorite (NaOCl) on its dentinal tubular penetration and root canal cleanliness in vitro. In experiment 1, mandibular premolars were randomly allocated to three groups (n = 8): group A, ultrasonic activation; group B, ultrasonic activation of intracanal‐heated NaOCl and group C, syringe‐and‐needle irrigation. Penetration of the fluorescent‐labelled NaOCl was investigated using light microscopy. In experiment 2, mandibular premolars were randomly allocated to group B or C (n = 10), for histological analysis of the remaining pulp tissue and debris. Data were statistically analysed using Kruskal–Wallis and Mann–Whitney tests (P = 0.05). The highest penetration of NaOCl was observed in group B, followed by group A (P < 0.05). Group B showed significantly less amount of debris than group C (P < 0.05). Dentinal tubule penetration of NaOCl and root canal cleanliness were significantly improved by ultrasonic activation of intracanal‐heated NaOCl.     

Three-Dimensional Laparoscopic Sleeve Gastrectomy: Improved Patient Safety and Surgeon Convenience

One of the aims of laparoscopic surgery is to improve upon the results obtained by open surgery. This clearly appears to have been achieved in bariatric surgery. Two-dimensional (2-D) systems have been used to date, though new 3-dimensional (3-D) technologies have been introduced in an attempt to improve surgeon vision and thus increase the safety of the surgical techniques. Sixty obese patients underwent sleeve gastrectomy using a device equipped with 3-D optics allowing surgery to be viewed by the surgeon in 3 dimensions by using a specific monitor and wearing appropriate glasses. The mean patient age was 48.1 years. The mean weight was 114 kg (range, 92–172), with a mean body mass index (BMI) of 44 ± 5.21 kg/m². All surgeries were performed using the 3-D system, with a mean surgical time of 71 ± 49.6 minutes and a mean hospital stay of 3.0 ± 1.2 days. Only 1 intraoperative complication was recorded: retroperitoneal bleeding on insertion of the optical trocar. Over a mean follow-up period of 12 months, the mean body weight of the patients was 88 kg (range, 71–121), with a BMI of 30.56 ± 3.98 kg/m² and a percentage excess weight loss of 68.14% ± 7.89%. There was clear improvement of both the blood pressure and glucose levels. Three-dimensional sleeve gastrectomy is safe, viable, and fully reproducible compared with 2-D surgery, improving visualization of the surgical field, safety, and surgeon convenience. Randomized studies involving larger patient samples are needed for the comparison of results.Key words: 3-D laparoscopy, Bariatric surgery, Metabolic surgeryIn recent years, laparoscopic surgery has become clearly indicated in bariatric and metabolic surgery. This surgical technique has made it possible to reduce morbidity and mortality in comparison with conventional open surgery, and to shorten hospital stay. In addition to the usual 5-trocar technique, laparoscopic surgery has also produced satisfactory results with the single-port approach, which is regarded as less invasive and affords equivalent outcomes and improved aesthetic results.More recently, the possibility of using three-dimensional (3-D) surgery has been considered. The film Avatar (James Cameron, 2006) represented a starting point for a number of multinational medical engineering companies who launched projects that now allow us to use 3-D laparoscopic systems. This new technology offers the perception of depth, which was not previously available.Sleeve gastrectomy is one of the surgical techniques presently used to treat obesity. It was initially regarded as first-step surgery in patients with a high body mass index (BMI), before performing biliopancreatic diversion. Sleeve gastrectomy is currently considered to be a restrictive technique that can be used as a sole option in morbid obesity, even when accompanied by diabetes mellitus, as contemplated by the International Sleeve Gastrectomy Expert Panel Consensus of 2011.Three-dimensional laparoscopic sleeve gastrectomy requires 5 ports, like the two-dimensional (2-D) laparoscopic technique, and one of them must be enlarged to extract the sectioned stomach. However, 3-D visualization is very useful in all the surgical steps, as it improves spatial orientation and can increase the safety of the surgical technique.The present study analyzes the results of 3-D laparoscopic sleeve gastrectomy after a short 1-year follow-up period, with a view to evaluating its safety and feasibility in patients with severe or morbid obesity and type 2 diabetes.     

Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: series of six patients and review of literature

BACKGROUND:

Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation.

METHODS AND RESULTS:

The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2 g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7±7.5% at baseline to 50.3±8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53±6% (P not significant versus LVEF at discharge).

CONCLUSIONS:

Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population.     

Upper limb function evaluation scales for individuals with cerebral palsy: a systematic review

[Purpose] The aim of the present study was to perform a systematic review of the literature on the scales and methods most often used for the evaluation of upper limb function in individuals with cerebral palsy. [Materials and Methods] Searches were conducted in the Medline, PEDro, Lilacs, Scielo, and PubMed databases. The following inclusion criteria were used for the selection of articles: randomized controlled study, evaluation of upper limb function in individuals with cerebral palsy, and publication between 2006 and 2014. The methodological quality of the articles was evaluated using the PEDro evidence scale. [Results] Five articles met the inclusion criteria and achieved 6 points or higher on the PEDro scale of methodological quality. [Conclusion] The studies analyzed used different evaluation scales, but no consensus has been reached thus far on which scale is the most appropriate. Thus, further studies are needed to establish an adequate method for the evaluation of upper limb function in individuals with cerebral palsy.Key words: Cerebral palsy, Scale function, Upper limbs     

Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling

Recombinant adenoviral vectors (rAds) are lead vaccine candidates for protection against a variety of pathogens, including Ebola, HIV, tuberculosis, and malaria, due to their ability to potently induce T cell immunity in humans. However, the ability to induce protective cellular immunity varies among rAds. Here, we assessed the mechanisms that control the potency of CD8 T cell responses in murine models following vaccination with human-, chimpanzee-, and simian-derived rAds encoding SIV-Gag antigen (Ag). After rAd vaccination, we quantified Ag expression and performed expression profiling of innate immune response genes in the draining lymph node. Human-derived rAd5 and chimpanzee-derived chAd3 were the most potent rAds and induced high and persistent Ag expression with low innate gene activation, while less potent rAds induced less Ag expression and robustly induced innate immunity genes that were primarily associated with IFN signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics but did not alter memory responses or protection. These findings reveal that the magnitude of rAd-induced memory CD8 T cell immune responses correlates with Ag expression but is independent of IFN and STING and provide criteria for optimizing protective CD8 T cell immunity with rAd vaccines.