Mechanisms of checkpoint inhibition-induced adverse events

Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.     

Biomethane generation from biogas upgrading by means of thin-film composite membrane comprising Linde T and fluorinated polyimide: optimization of fabrication parameters

Generation of biogas from organic substances is an attractive evolution of energy generation from fossil-based energy supply to renewable resources. In order to exhibit viability in terms of technical execution while being economically feasible, successful purification strategies for biomethane formation must be applicable to industrial gas streams at realistic pressures and temperatures. Membrane-based upgrading technologies have great potential to promote biogas processes because they involve less energy and low maintenance. However, the development of membranes with good polymer-filler contact and minimum defects remains a great challenge. Hitherto, researchers have been making many attempts at developing an established route to fabricate thin-film composite membranes. In the present work, an innovative coupling between Linde T and fluorinated polyimide was employed for biogas upgrading. A facile technique for membrane fabrication was proposed via optimization of the fabrication parameters. The results indicated that composite membrane fabricated with 2 hours of total dispersion duration demonstrated a homogeneous distribution of Linde T particles in the fluorinated polyimide matrix and improved the separation characteristics by up to 172% in upgrading biomethane quality. Thus, the fabricated membrane is feasible to be employed for large-scale and lucrative production with enhanced performance in biogas purification via the feasible fabrication method employed in this work.

Generation of biogas from organic substances is an attractive evolution of energy generation from fossil-based energy supply to renewable resources.     

Breast Conservation After Neoadjuvant Chemotherapy

Background Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients.Methods The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics.Results Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography.Conclusions The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.     

Gastrointestinal stromal tumours: a broad spectrum of clinical presentations

Gastrointestinal stromal tumours, though rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. The most frequent sites of origin are the stomach and the small bowel, but they can occur anywhere in the gastrointestinal tract. Mesenteric and retroperitoneal forms have been described. The Authors present their personal experience with the treatment of gastrointestinal stromal tumours, with particular reference to the broad spectrum of clinical presentations and to the consequent therapeutic implications. We report on a retrospective analysis of the clinical presentations and courses, surgical management and pathological features of 27 patients with such tumours treated in our institution from 1993 to 2005. The variables analysed were the morphological and clinical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephonic follow-up in all patients. One tumour was located in the oesophagus, 14 in the gastric area, 7 in the small bowel, 2 in the colon-rectum, and 3 in the peritoneum. All patients studied received radical surgical treatment. In 7 patients surgical resection was extended to other organs. No postoperative mortality or major postoperative complications were observed. Twenty-two patients are still alive at follow-up. Three patients died as a result of neoplastic relapse and 2 of other causes. The median survival was 36 months. The actuarial 3- and 5-year survival rates were 89.7% and 67.8%, respectively. Our experience indicates that the site of origin of gastrointestinal stromal tumours with their broad spectrum of clinical presentations may influence both the therapeutic choice (neoadjuvant utilisation of imatinib mesylate) and the surgical treatment (wedge resection vs enlarged operations).     

Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort

Background  

Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings.