Case Report on a Multidisciplinary Approach to Address Malnutrition and Improve a Patient's Fitness for Treatment.

Approximately 5,700 people are diagnosed with myeloma each year in the UK. The standard of care is to receive an autologous stem cell transplant after completion of induction therapy. There are no specific dietary recommendations for people with myeloma, however they are at risk of malnutrition due to symptoms and side effects of treatments. This report describes the journey of a 73-year-old male diagnosed with immunoglobulin A (IgA) lambda myeloma in April 2021. The patient lost 23% of his body weight during 6 months of systemic anti-cancer treatment (SACT), resulting in postponing his transplant twice due to reduced fitness. This report describes an effective, although late, multidisciplinary intervention which was successful for the patient who managed to reestablish a healthy weight and good quality of life. The patient received his transplant in January 2023. This case highlights two important aspects of patient care that should not be underestimated in dietetic clinical practice: early screening and multidisciplinary collaboration. Monitoring the nutritional status of patients and providing early nutrition support can prevent hospital admissions, treatment delays and reduce the associated costs. Multidisciplinary teamwork can improve patient care and clinical outcomes, and it is fundamental to strengthen communication and collaboration among clinical disciplines.

Validity, reliability and acceptability of the Imperial Nutritional Screening System (INSYST): a tool that does not require the body mass index.

BACKGROUND: Nutritional screening tools are central to identifying malnourished patients, but their efficacy is often reduced as a result of difficulties in obtaining height for body mass index (BMI) calculations. The present study aimed to evaluate the validity, reliability and acceptability of the Imperial Nutritional Screening System (INSYST); a tool that does not require the BMI. METHODS: Patients were screened by the researcher within 72 h of admission using INSYST I & II, Malnutrition Universal Screening Tool (MUST) and Mini Nutritional Assessment (MNA), including taking height and weight. Routine INSYST data, completed by nursing staff, were subsequently collected. At risk and malnourished patients were combined for statistical analysis. Inter-tool and inter-rater agreement (kappa, kappa) was evaluated. Sensitivity and specificity were calculated. Nurses were timed using INSYST. Acceptability, including ease and speed of use, was evaluated. RESULTS: Kappa (agreement) scores (all P < 0.001) were substantial for INSYST I versus MUST and MNA (kappa = 0.73 and kappa = 0.76, respectively) and moderate for INSYST II (both kappa = 0.53). The sensitivity of INSYST I and II was high (95-100%), whereas specificity was lower (65-83%). The agreement between dietitian and nurse for INSYST I was substantial kappa = 0.77 and that for INSYST II was fair kappa = 0.39 (both P

Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia.

BACKGROUND AND PURPOSE: gamma-Secretase inhibitors (GSIs) block NOTCH receptor cleavage and pathway activation and have been under clinical evaluation for the treatment of malignancies such as T-cell acute lymphoblastic leukaemia (T-ALL). The ability of GSIs to decrease T-ALL cell viability in vitro is a slow process requiring >8 days, however, such treatment durations are not well tolerated in vivo. Here we study GSI's effect on tumour and normal cellular processes to optimize dosing regimens for anti-tumour efficacy. EXPERIMENTAL APPROACH: Inhibition of the Notch pathway in mouse intestinal epithelium was used to evaluate the effect of GSIs and guide the design of dosing regimens for xenograft models. Serum Abeta(40) and Notch target gene modulation in tumours were used to evaluate the degree and duration of target inhibition. Pharmacokinetic and pharmacodynamic correlations with biochemical, immunohistochemical and profiling data were used to demonstrate GSI mechanism of action in xenograft tumours. KEY RESULTS: Three days of >70% Notch pathway inhibition was sufficient to provide an anti-tumour effect and was well tolerated. GSI-induced conversion of mouse epithelial cells to a secretory lineage was time- and dose-dependent. Anti-tumour efficacy was associated with cell cycle arrest and apoptosis that was in part due to Notch-dependent regulation of mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Intermittent but potent inhibition of Notch signalling is sufficient for anti-tumour efficacy in these T-ALL models. These findings provide support for the use of GSI in Notch-dependent malignancies and that clinical benefits may be derived from transient but potent inhibition of Notch.

Membrane inlet mass spectrometric measurement of O2 and CO2 gradients in cultures of Lactobacillus paracasei and a developing Cheddar cheese ecosystem.

Membrane inlet mass spectrometry was used to measure O2 and CO2 as depth profiles in stab cultures of 0.1% agar Man Rogosa Sharpe medium inoculated with Lactobacillus paracasei CI3. Diffusion of CO2 from the central column of growth into the medium was observed to show lower concentrations where bacteria were absent. CO2 profiles developed in a manner similar to those in Cheddar cheese and O2 was undetectable at similar depths. Gases were analysed in Cheddar cheese over a maturation period of 200 d. O2 was detectable to depths of 13, 6 and 2.5 mm on days 2, 9 and 15, respectively, but then became undetectable at depths of 2.5-3 mm. CO2 concentrations measured within the cheese increased 10-fold from day 2 to day 200 to reach a value of around 15 mM. The progress of measured CO2 concentration over time at a given depth in cheese shows a hyperbolic type increase. Coefficient of regression values increase with depth to a maximum value of R2 = 0.93. In both systems, reductions and increases in CO2 were due to the absence or presence of bacterial growth, respectively. Confocal scanning laser and scanning electron microscopy was used to show spatial heterogeneity of microcolonies within the cheese ecosystem. This information can potentially be used as a non-sensory evaluation of cheese maturity status. Measurement of gases in a cheese ecosystem provides the first description of mass spectrometry being used to monitor the processes of microbial gaseous exchange with respect to O2 and CO2 in a cheese ecosystem.

Amino acid fermentation in non-starter Lactobacillus spp. isolated from cheddar cheese.

Amino acid fermentation profiles of nine strains of Lactobacillus spp., initially isolated from a 3-year-old Cheddar cheese, were determined using the Biolog MT microplatetrade mark method. Eight of the isolates were able to ferment amino acids, but only when incubated in the presence of exogenously supplied alpha-ketoglutaric acid that served as an acceptor in the initial transamination step in the fermentative degradation. The range of amino acids catabolized was strain dependent. Amino acid catabolites were detected by gas chromatography mass spectrometry (GCMS) in culture supernatant fluids of a representative non-starter lactic acid bacteria isolate Lactobacillus paracasei CI6.