Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered ...to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels. Engineered T cells expanded, persisted, trafficked to marrow and exhibited a cytotoxic phenotype. Persistence of engineered T cells in blood was inversely associated with NY-ESO-1 levels in the marrow. Disease progression was associated with loss of T cell persistence or antigen escape, in accordance with the expected mechanism of action of the transferred T cells. Encouraging clinical responses were observed in 16 of 20 patients (80%) with advanced disease, with a median progression-free survival of 19.1 months. NY-ESO-1-LAGE-1 TCR-engineered T cells were safe, trafficked to marrow and showed extended persistence that correlated with clinical activity against antigen-positive myeloma.
Background: the European Working Group on Sarcopenia in Older People has developed a clinical definition of sarcopenia based on low muscle mass and reduced muscle function (strength or performance). ...Grip strength is recommended as a good simple measure of muscle strength when 'measured in standard conditions'. However, standard conditions remain to be defined.
Methods: a literature search was conducted to review articles describing the measurement of grip strength listed in Medline, Web of Science and Cochrane Library databases up to 31 December 2009.
Results: there is wide variability in the choice of equipment and protocol for measuring grip strength. The Jamar hand dynamometer is the most widely used instrument with established test-retest, inter-rater and intra-rater reliability. However, there is considerable variation in how it is used and studies often provide insufficient information on the protocol followed making comparisons difficult. There is evidence that variation in approach can affect the values recorded. Furthermore, reported summary measures of grip strength vary widely including maximum or mean value, from one, two or three attempts, with either hand or the dominant hand alone.
Conclusions: there is considerable variation in current methods of assessing grip strength which makes comparison between studies difficult. A standardised method would enable more consistent measurement of grip strength and better assessment of sarcopenia. Our approach is described.
An obstacle to cancer immunotherapy has been that the affinity of T-cell receptors (TCRs) for antigens expressed in tumors is generally low. We initiated clinical testing of engineered T cells ...expressing an affinity-enhanced TCR against HLA-A*01–restricted MAGE-A3. Open-label protocols to test the TCRs for patients with myeloma and melanoma were initiated. The first two treated patients developed cardiogenic shock and died within a few days of T-cell infusion, events not predicted by preclinical studies of the high-affinity TCRs. Gross findings at autopsy revealed severe myocardial damage, and histopathological analysis revealed T-cell infiltration. No MAGE-A3 expression was detected in heart autopsy tissues. Robust proliferation of the engineered T cells in vivo was documented in both patients. A beating cardiomyocyte culture generated from induced pluripotent stem cells triggered T-cell killing, which was due to recognition of an unrelated peptide derived from the striated muscle-specific protein titin. These patients demonstrate that TCR-engineered T cells can have serious and not readily predictable off-target and organ-specific toxicities and highlight the need for improved methods to define the specificity of engineered TCRs.
•Engineered T-cell receptors can have redundant recognition of alternative protein motifs, resulting in severe cardiac toxicity.•The use of induced pleuripotent stem cells (iPSCs) is a promising approach to identify potential off-target effects of engineered T cells.
Objective
To conduct a systematic review of the effectiveness of facial exercise therapy for facial palsy patients, updating an earlier broader Cochrane review; and to provide evidence to inform the ...development of telerehabilitation for these patients.
Data Sources
MEDLINE, EMBASE, CINAHL, Cochrane Library, PEDro and AMED for relevant studies published between 01 January 2011 and 30 September 2020.
Methods
Predetermined inclusion/exclusion criteria were utilised to shortlist abstracts. Two reviewers independently appraised articles, systematically extracted data and assessed the quality of individual studies and reviews (using GRADE and AMSTAR-2, respectively). Thematic analysis used for evidence synthesis; no quantitative meta-analysis conducted. The review was registered with PROSPERO (CRD42017073067).
Results
Seven new randomised controlled trials, nine observational studies, and three quasi-experimental or pilot studies were identified (n = 854 participants). 75% utilised validated measures to record changes in facial function and/or patient-rated outcomes. High-quality trials (4/7) all reported positive impacts; as did observational studies rated as high/moderate quality (3/9). The benefit of therapy at different time points post-onset and for cases of varying clinical severity is discussed. Differences in study design prevented data pooling to strengthen estimates of therapy effects. Six new review articles identified were all rated critically low quality.
Conclusion
The findings of this targeted review reinforce those of the earlier more general Cochrane review. New research studies strengthen previous conclusions about the benefits of facial exercise therapy early in recovery and add to evidence of the value in chronic cases. Further standardisation of study design/outcome measures and evaluation of cost-effectiveness are recommended.
Aims and objectives. The objective of this review was to locate and assess the evidence obtained from articles reporting empirical research that volunteers improve mealtime care of adults in ...institutional settings.
Background. Malnutrition in adult patients or residents in institutional care settings is common. Poor standards of mealtime care have been suggested to contribute to the development of malnutrition.
Design. A systematic review of the literature was undertaken.
Method. Key words were identified and used separately and in combination to search the electronic databases MEDLINE®, CINHAL®, BNI and EMBASE and the internet for relevant articles. Searches were undertaken in August 2008, April 2009 and July 1010.
Results. Ten studies fulfilled the criteria for inclusion. The methodologies of five of the 10 studies were unclear due to the brevity of the reports. The validity of the design of the other five studies varied. Generally the results suggested the use of volunteers in mealtime care increased satisfaction of patients, relatives, volunteers and staff concerning meal‐time assistance (assessed using methods such as questionnaires and focus groups) and three studies found increased nutritional intake in groups assisted by volunteers. However, few well designed and reported studies were identified.
Conclusions. There is some evidence that volunteers can improve mealtime care of adult patients or residents in institutional settings, however few well designed studies are reported.
Relevance to clinical practice. This review demonstrates that there is limited evidence that the use of volunteers improves mealtime care of adult patients or relatives in institutional settings.
OBJECTIVES: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships.
DESIGN: Cross‐sectional and ...retrospective cohort study.
SETTING: Hertfordshire, United Kingdom.
PARTICIPANTS: Two thousand nine hundred eighty‐three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom.
MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer.
RESULTS: Grip strength was positively associated with height and weight at birth and inversely related to age (all P<.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43 kg (95% confidence interval (CI)=0.13–0.74) in men (P=.005) and 0.48 kg (95% CI=0.24–0.72) in women (P<.001) was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age, and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength.
CONCLUSION: These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the antiinflammatory actions of omega‐3 fatty acids may play a role in the prevention of sarcopenia.
Objective: to investigate the relationship between grip strength and health-related quality of life (HRQoL). Design: cross-sectional survey within a cohort study design. Setting: the county of ...Hertfordshire in the UK. Participants: a total of 2,987 community-dwelling men and women aged 59–73 years of age. Measurements: grip strength was used as a marker of sarcopaenia and measured using a Jamar dynamometer. HRQoL was assessed using the eight domain scores of the Short Form-36 (SF-36) questionnaire, and subjects in the lowest sex-specific fifth of the distribution were classified as having ‘poor’ status for each domain. Results: men and women with lower grip strength were significantly more likely to report a poor as opposed to excellent to fair overall opinion of their general health (GH) odds ratio (OR) per kilogram decrease in grip strength = 1.13, 95% CI = 1.06–1.19, P<0.001 in men, 1.13, 95% CI = 1.07–1.20, P<0.001 in women. Among men, after adjustment for age, size, physical activity and known co-morbidity, decreased grip strength was associated with increased prevalence of poor SF-36 scores for the physical functioning (PF) (OR per kilogram decrease in grip strength = 1.03, 95% CI = 1.01–1.06, P = 0.007) and GH domains (OR = 1.03, 95% CI = 1.01–1.05, P = 0.01). Similar associations were seen in women. Conclusions: our findings suggest that lower grip strength is associated with reduced HRQoL in older men and women. This does not appear to be explained by age, size, physical activity or co-morbidity and may reflect the link between sarcopaenia and generalised frailty. Individuals with sarcopaenia may benefit from interventions to improve muscle mass and strength before the onset of chronic disorders usually associated with impaired HRQoL.
Background & Aims:
Altered mucosal glycosylation in inflammatory bowel disease and colon cancer could affect mucosal bacterial adherence. This study aimed to quantify and characterize ...mucosa-associated and intramucosal bacteria, particularly
Escherichia coli, in these conditions.
Methods:
Mucosa-associated bacteria were isolated, after dithiothreitol mucolysis, from biopsy samples obtained at colonoscopy (Crohn’s disease, n = 14 patients; ulcerative colitis, n = 21; noninflamed controls, n = 24) and at surgical resection (colon cancer, n = 21). Intramucosal bacteria were grown after gentamicin treatment followed by hypotonic lysis.
Results:
Mucosa-associated and intramucosal bacteria were cultured more commonly in Crohn’s disease (79%,
P = 0.03; and 71%,
P < 0.01, respectively), but not ulcerative colitis (38% and 48%), than in noninflamed controls (42% and 29%) and were commonly cultured from colon cancers (71% and 57%). Mucosa-associated
E. coli, which accounted for 53% of isolates, were more common in Crohn’s disease (6/14; 43%) than in noninflamed controls (4/24, 17%), as also were intramucosal
E. coli: Crohn’s disease, 29%; controls, 9%.
E. coli expressed hemagglutinins in 39% of Crohn’s cases and 38% of cancers but only 4% of controls, and this correlated (
P = 0.01) with adherence to the I407 and HT29 cell lines. Invasion was cell-line dependent.
E. coli, including nonadherent isolates, induced interleukin-8 release from the cell lines.
E. coli adhesins showed no blood group specificity, excepting 1 cancer isolate (HM44) with specificity for the Thomsen-Friedenreich antigen, but they could be blocked by soluble plantain fiber.
Conclusions:
These studies support a central role for mucosally adherent bacteria in the pathogenesis of Crohn’s disease and colon cancer. Soluble plant fibers that inhibit their adherence have therapeutic potential.
Unhealthy diets are typical of university students and are often thought to be unrepresentative of the general population. The main aim was to determine the energy and nutrient intakes of a large ...cohort of undergraduate university students; and to compare to gender-specific dietary reference values (DRVs) and nutrient data from the general population.
Data was collected from 639 university students aged 18-24 years who completed 4-day diet diaries. The energy and nutrient intake was determined and percentage energy values calculated and compared with dietary reference values (DRVs) and the National Diet and Nutrition Survey (NDNS) and Family Food Statistics. Logistic regression methods were used to identify micronutrients functioning as predictors of exceeding DRVs.
Energy intakes were lower than the DRV. The percentage total energy values for protein, fat, saturated fat and carbohydrate exceeded DRVs but the percentage energy from alcohol was below the maximum 5%. The DRVs were met for vitamin C, thiamin, and sodium/salt. Iron and calcium intakes were met in males but not in females. Intakes for fibre and vitamin A were below the DRV. Student data was comparable to the NDNS, with the exception of alcohol, fibre, vitamin A, calcium and sodium/salt, which were all lower than the NDNS.
This study contradicts the stereotypical assumption that students are following a high energy, fat, saturated fat, total sugars, salt and alcohol diet compared with the general population.
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