Intratherapy or Posttherapy FDG PET or FDG PET/CT for Patients With Head and Neck Cancer: A Systematic Review and Meta-analysis of Prognostic Studies.

OBJECTIVE: The objective of this study was to determine the predictive value of intra-therapy or posttherapy FDG PET or FDG PET/CT with regard to overall survival (OS) and event-free survival (EFS) outcomes for patients with head and neck cancer (HNC). MATERIALS AND METHODS: A systematic search of the MEDLINE and EMBASE databases was performed. Studies in which PET/CT was performed during or after completion of primary therapy and for which survival outcomes were reported were included. OS and EFS were considered as outcomes. The pooled estimates of hazard ratios (HRs) and Mantel-Haenszel risk ratios (RRs) were generated for summary effects. RESULTS: Twenty-six studies were eligible for inclusion. The pooled HRs for OS (nine studies, 600 patients) and EFS (eight studies, 479 patients) were 3.55 (95% CI, 2.35-5.37) and 4.73 (95% CI, 2.61-8.56), respectively. Results from the RR analyses, including all 26 studies, showed that intratherapy or posttherapy PET/CT could significantly predict the 2-year and 3- to 5-year risk of death or disease progression. A positive PET result was associated with a more-than-sixfold increase in the risk of death within 2 years (2-year RR, 6.19 [95% CI, 3.04- 12.62]), which is attenuated--but remains significant--with longer follow-up (3- to 5-year RR, 2.42 [95% CI, 1.76-3.32]). The estimated pooled RRs for 2-year mortality were 8.31 (95% CI, 3.83-18.01) for posttherapy PET/CT versus 3.99 (95% CI, 1.43-11.10) for intratherapy PET/CT. CONCLUSION: Positive results of intratherapy or posttherapy PET/CT examinations strongly predict the risk of adverse events and death, particularly within 2 years but also up to 5 years, for patients with HNC.

Nutritional Screening, Initial Management and Referral for Older People with Sarcopenia or Frailty - Results from a UK-Wide Survey.

Objectives: We surveyed healthcare staff working with older people to understand current practice in nutrition screening, initial management and referral for older people with sarcopenia and frailty. Methods: We conducted a UK-wide web-based survey of staff working with older people in both hospital and community settings. Surveys were distributed through professional organisation e-mail lists and social media channels. Descriptive data were generated from categorical responses and inductive thematic analysis was applied to free-text responses. Results: Data were analysed from 169 respondents (110 hospital, 59 community), representing 99 healthcare organisations. 91 (83%) hospital respondents and 24 (41%) community respondents reported that nutrition screening was performed on all patients with sarcopenia or frailty. The Malnutrition Universal Screening Tool was most commonly used to trigger referral to dietetics teams, but there was considerable variation in management before referral, referral thresholds and referral pathways. Themes derived from free-text responses included the need for training, issues of responsibility and ownership, inadequate resources (time, staff and equipment) and ineffective or inefficient processes for referral and management. Conclusions: Current UK nutritional care for older people with sarcopenia and frailty is heterogeneous. There are opportunities for better tools, processes, training and resources to improve current practice and pathways.

Potential pitfalls in MALDI-TOF MS analysis of abiotically synthesized RNA oligonucleotides.

Demonstration of the abiotic polymerization of ribonucleotides under conditions consistent with conditions that may have existed on the prebiotic Earth is an important goal in "RNA world" research. Recent reports of abiotic RNA polymerization with and without catalysis rely on techniques such as HPLC, gel electrophoresis, and MALDI-TOF MS to analyze the reaction products. It is essential to understand the limitations of these techniques in order to accurately interpret the results of these analyses. In particular, techniques that rely on mass for peak identification may not be able to distinguish between a single, linear RNA oligomer and stable aggregates of smaller linear and/or cyclic RNA molecules. In the case of MALDI-TOF MS, additional complications may arise from formation of salt adducts and MALDI matrix complexes. This is especially true for abiotic RNA polymerization reactions because the concentration of longer RNA chains can be quite low and RNA, as a polyelectrolyte, is highly susceptible to adduct formation and aggregation. Here we focus on MALDI-TOF MS analysis of abiotic polymerization products of imidazole-activated AMP in the presence and absence of montmorillonite clay as a catalyst. A low molecular weight oligonucleotide standard designed for use in MALDI-TOF MS and a 3'-5' polyadenosine monophosphate reference standard were also run for comparison and calibration. Clay-catalyzed reaction products of activated GMP and UMP were also examined. The results illustrate the ambiguities associated with assignment of m/z values in MALDI mass spectra and the need for accurate calibration of mass spectra and careful sample preparation to minimize the formation of adducts and other complications arising from the MALDI process.

Guanine-centric self-assembly of nucleotides in water: an important consideration in prebiotic chemistry.

Investigations of plausible prebiotic chemistry on early Earth must consider not only chemical reactions to form more complex products such as proto-biopolymers but also reversible, molecular self-assembly that would influence the availability, organization, and sequestration of reactant molecules. The self-assembly of guanosine compounds into higher-order structures and lyotropic liquid crystalline "gel" phases through formation of hydrogen-bonded guanine tetrads (G-tetrads) is one such consideration that is particularly relevant to an RNA-world scenario. G-tetrad-based gelation has been well studied for individual guanosine compounds and was recently observed in mixtures of guanosine with 5'-guanosine monophosphate (GMP) as well. The present work investigates the self-assembly of GMP in the presence of the other RNA nucleotides. Effects of the total concentration and relative proportion of the nucleotides in the mixtures, the form (disodium salt vs. free acid) of the nucleotides, temperature, pH, and salt concentration were determined by visual observations and circular dichroism (CD) spectroscopy. The results show that formation of cholesteric G-tetrad phases is influenced by interactions with other nucleotides, likely through association (e.g., intercalation) of the nucleotides with the G-tetrad structures. These interactions affect the structure and stability of the G-tetrad gel phase, as well as the formation of alternate self-assembled GMP structures such as a continuous, hydrogen-bonded GMP helix or dimers and aggregates of GMP. These interactions and multiple equilibria are influenced by the presence of cations, especially in the presence of K(+). This work could have important implications for the emergence of an RNA or proto-RNA world, which would require mixtures of nucleotides at sufficiently high, local concentrations for abiotic polymerization to occur.