Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

Neurocritical Care - For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral...     

Quality of decision aids developed for women at average risk of breast cancer eligible for mammographic screening: Systematic review and assessment according to the International Patient Decision Aid Standards instrument

Mammographic screening contributes to a reduction in specific mortality, but it has disadvantages. Decision aids are tools designed to support people's decisions. Because these aids influence patient choice, their quality is crucial. The objective of the current study was to conduct a systematic review of decision aids developed for women eligible for mammographic screening who have an average breast cancer risk and to assess the quality of these aids. The systematic review included articles published between January 1, 1997, and August 1, 2019, in the PubMed, Embase, Cochrane, and PsycInfo databases. The studies were reviewed independently by 2 reviewers. Any study containing a decision aid for women eligible for mammographic screening with an average breast cancer risk was included. Two double-blind reviewers assessed the quality of the selected decision aids using the International Patient Decision Aid Standards instrument, version 3 (IPDASi). Twenty-three decision aids were extracted. Classification of decision aid quality using the IPDASi demonstrated large variations among the decision aids (maximum IPDASi score, 188; mean ± SD score, 132.6 ± 23.8; range, 85-172). Three decision aids had high overall scores. The 3 best-rated dimensions were disclosure (maximum score, 8; mean score, 6.8), focusing on transparency; information (maximum score, 32; mean score, 26.1), focusing on the provision of sufficient details; and probabilities (maximum score, 32; mean score 25), focusing on the presentation of probabilities. The 3 lowest-rated dimensions were decision support technology evaluation (maximum score, 8; mean score, 4.3), focusing on the effectiveness of the decision aid; development (maximum score, 24; mean score, 12.6), evaluating the development process; and plain language (maximum score, 4; mean score, 1.9), assessing appropriateness for patients with low literacy. The results of this review identified 3 high-quality decision aids for breast cancer screening.     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.     

Resection of hepatocellular carcinoma with tumor thrombus in the major vasculature. A European case-control series

Tumor thrombus in major vasculature is a frequent finding with a poor long-term prognosis in patients with hepatocellular carcinoma (HCC). The utility of surgical resection is still controversial. This study compared morbidity and survival after resection for HCC with and without tumor thrombus. Data of 108 patients who underwent major hepatic resection for HCC were prospectively recorded. Patients were divided into two groups. The venous thrombectomy (VT) group included 26 patients who had HCC with tumor thrombus in the portal or hepatic veins. The matched control group included 82 patients who had HCC without tumor thrombus. Surgical technique, early outcome, and late survival were analyzed in each group. Multivariate analysis was performed to assess the prognostic value of this feature. Surgical technique was comparable in the VT and control group with regard to extent of hepatectomy, procedure duration, and transfusion requirements. Early postoperative outcome was also comparable. Actuarial survival at 1, 3, and 5 years was 38%, 20%, and 13%, respectively, in the VT group (median: 9 months) versus 74%, 56%, and 33%, respectively, in the control group (median: 41 months). In the subgroup of patients with tumor thrombus limited to the portal vein, actuarial survival at 1, 3, and 5 years was 50%, 26%, and 17%, respectively, (median: 12 months) and two patients lived longer than 5 years. Multivariate analysis showed that incomplete resection, alphafetoprotein level greater than 100 N, more than two tumor nodules, and tumor thrombus in major vasculature were independent factors of poor prognosis. Survival after resection for HCC with tumor thrombus in the major vasculature is poorer than after resection for HCC without tumor thrombus. However, an aggressive surgical strategy can provide significant survival with comparable morbidity in selected cases, that is, tumor thrombus located in the portal vein only and expected complete resection of the lesions.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Breast milk donors in France: a portrait of the typical donor and the utility of milk banking in the French breastfeeding context.

Although information regarding attitudes and characteristics of human blood donors has been researched, little is known about the motivations and demographic and personality characteristics of women who choose to donate their breast milk. Eight milk banks in France participated in a study examining donor characteristics, providing data on 103 women. The results showed that the donors were women of average childbearing age with strong support at home. Almost half did not work outside of the home, compared to the national average of 80% of women in this age group; similarly, a large number (currently working or not) were from the health and social services fields. Reasons for donation were largely altruistic, and a general optimistic attitude prevailed within the participants. The results of this study provide useful information for the recruitment of potential donors as well as information on how to facilitate and provide optimal service through milk donation.