Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Abstract. Employing whole-genome analysis we have characterized a large family of genes coding for calpain-related proteins in three kinetoplastid parasites. We have defined a total of 18 calpain-like sequences in Trypanosoma brucei, 27 in Leishmania major, and 24 in Trypanosoma cruzi. Sequence characterization revealed a well-conserved protease domain in most proteins, although residues critical for catalytic activity were frequently altered. Many of the proteins contain a novel N-terminal sequence motif unique to kinetoplastids. Furthermore, 24 of the sequences contain N-terminal fatty acid acylation motifs indicating association of these proteins with intracellular membranes. This extended family of proteins also includes a group of sequences that completely lack a protease domain but is specifically related to other kinetoplastid calpain-related proteins by a highly conserved N-terminal domain and by genomic organization. All sequences lack the C-terminal calmodulin-related calcium-binding domain typical of most mammalian calpains. Our analysis emphasizes the highly modular structure of calpains and calpain-like proteins, suggesting that they are involved in diverse cellular functions. The discovery of this surprisingly large family of calpain-like proteins in lower eukaryotes that combines novel and conserved sequence modules contributes to our understanding of the evolution of this abundant protein family.

The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced, nonsquamous non-small cell lung cancer.

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Large randomized phase III prospective studies continue to redefine the standard of therapy in medical practice. Often when studies do not meet the primary endpoint, it is common to explore possible benefits in specific subgroups of patients. In addition, these analyses may also be done, even in the case of a positive trial to find subsets of patients where the therapy is especially effective or ineffective. These unplanned subgroup analyses are justified to maximize the information that can be obtained from a study and to generate new hypotheses. Unfortunately, however, they are too often overinterpreted or misused in the hope of resurrecting a failed study. It is important to distinguish these overinterpreted, misused, and unplanned subgroup analyses from those prespecified and well-designed subgroup analyses. This overview provides a practical guide to the interpretation of subgroup analyses.

AIMTo systematically review the literature on women with both diabetes in pregnancy (DIP) and depression during or after pregnancy.METHODSIn this systematic literature review, PubMed/MEDLINE and EMBASE were searched (13 November 2015) using terms for diabetes (type 1, type 2, or gestational), depression, and pregnancy (no language or date restrictions). Publications that reported on women who had both DIP (any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion. All study types were eligible for inclusion; conference abstracts, narrative reviews, nonclinical letters, editorials, and commentaries were excluded, unless they provided treatment guidance.RESULTSOf 1189 articles identified, 48 articles describing women with both DIP and depression were included (sample sizes 36 to > 32 million). Overall study quality was poor; most studies were observational, and only 12 studies (mostly retrospective database studies) required clinical depression diagnosis. The prevalence of concurrent DIP (any type) and depression in general populations of pregnant women ranged from 0% to 1.6% (median 0.61%; 12 studies). The prevalence of depression among women with gestational diabetes ranged from 4.1% to 80% (median 14.7%; 16 studies). Many studies examined whether DIP was a risk factor for depression or depression was a risk factor for DIP. However, there was no clear consensus for either relationship. Importantly, we found limited guidance on the management of women with both DIP and depression.CONCLUSIONGiven the increasing prevalence of diabetes and depression, high-quality research and specific guidance for management of pregnant women with both conditions are warranted.

Hazard ratios (HRs) are used commonly to report results from randomized clinical trials in oncology. However, they remain one of the most perplexing concepts for clinicians. A good understanding of HRs is needed to effectively interpret the medical literature to make important treatment decisions. This article provides clear guidelines to clinicians about how to appropriately interpret HRs. While this article focuses on the commonly used methods, the authors acknowledge that other statistical methods exist for analyzing survival data.

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