Chia‐Hui Chen

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

PURPOSE: Malnutrition is a frequent and serious problem in the elderly. Today there is no doubt that malnutrition contributes significantly to morbidity and mortality in the elderly. Unfortunately, the concept of malnutrition in the elderly is poorly defined. The purpose of this paper is to clarify the meaning of malnutrition in the elderly and to develop the theoretical underpinnings, thereby facilitating communication regarding the phenomenon and enhancing research efforts. SCOPE, SOURCES USED: Critical review of literature is the approach used to systematically build and develop the theoretical propositions. Conventional search engines such as Medline, PsyINFO, and CINAHL were used. The bibliography of obtained articles was also reviewed and additional articles identified. Key wards used for searching included malnutrition, geriatric nutrition, nutritional status, nutrition assessment, elderly, ageing, and weight loss. CONCLUSIONS: The definition of malnutrition in the elderly is defined as following: faulty or inadequate nutritional status; undernourishment characterized by insufficient dietary intake, poor appetite, muscle wasting and weight loss. In the elderly, malnutrition is an ominous sign. Without intervention, it presents as a downward trajectory leading to poor health and decreased quality of life. Malnutrition in the elderly is a multidimensional concept encompassing physical and psychological elements. It is precipitated by loss, dependency, loneliness and chronic illness and potentially impacts morbidity, mortality and quality of life.

IMPORTANCE: Older patients undergoing abdominal surgery commonly experience preventable delirium, which extends their hospital length of stay (LOS). OBJECTIVE: To examine whether a modified Hospital Elder Life Program (mHELP) reduces incident delirium and LOS in older patients undergoing abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial of 577 eligible patients enrolled 377 older patients (≥65 years of age) undergoing gastrectomy, pancreaticoduodenectomy, and colectomy at a 2000-bed urban medical center in Taipei, Taiwan, from August 1, 2009, through October 31, 2012. Consecutive older patients scheduled for elective abdominal surgery with expected LOS longer than 6 days were enrolled, with a recruitment rate of 65.3%. Participants were cluster randomized by room to receive the mHELP or usual care. INTERVENTIONS: The intervention (implemented by an mHELP nurse) consisted of 3 protocols administered daily: orienting communication, oral and nutritional assistance, and early mobilization. Intervention group participants received all 3 mHELP protocols postoperatively, in addition to usual care, as soon as they arrived in the inpatient ward and until hospital discharge. Adherence to protocols was tracked daily. MAIN OUTCOMES AND MEASURES: Presence of delirium was assessed daily by 2 trained nurses who were masked to intervention status by using the Confusion Assessment Method. Data on LOS were abstracted from the medical record. RESULTS: Of 577 eligible patients, 377 (65.3%) were enrolled and randomly assigned to the mHELP (n = 197; mean [SD] age, 74.3 [5.8] years; 111 [56.4%] male) or control (n = 180; mean [SD] age, 74.8 [6.0] years; 103 [57.2%] male) group. Postoperative delirium occurred in 13 of 196 (6.6%) mHELP participants vs 27 of 179 (15.1%) control individuals, representing a relative risk of 0.44 in the mHELP group (95% CI, 0.23-0.83; P = .008). Intervention group participants received the mHELP for a median of 7 days (interquartile range, 6-10 days) and had a shorter median LOS (12.0 days) than control participants (14.0 days) (P = .04). CONCLUSIONS AND RELEVANCE: For older patients undergoing abdominal surgery who received the mHELP, the odds of delirium were reduced by 56% and LOS was reduced by 2 days. Our findings support using the mHELP to advance postoperative care for older patients undergoing major abdominal surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01045330.

Abstract The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naïve T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function. Significance: To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy. This article is highlighted in the In This Issue feature, p. 2113

This study of mobile persuasion system explores the use of a mobile phone, when attached to an everyday object used by an everyday behavior, becomes a tool to sense and influence that behavior. This mobile persuasion system, called Playful Bottle system, makes use of a mobile phone attached to an everyday drinking mug and motivates office workers to drink healthy quantities of water. A camera and accelerometer sensors in the phone are used to build a vision/motion-based water intake tracker to detect the amount and regularity of water consumed by the user. Additionally, the phone includes hydration games in which natural drinking actions are used as game input. Two hydration games are developed: a single-user TreeGame with automated computer reminders and a multi-user ForestGame with computer-mediated social reminders from members of the group playing the game. Results from 7-week user study with 16 test subjects suggest that both hydration games are effective for encouraging adequate and regular water intake by users. Additionally, results of this study suggest that adding social reminders to the hydration game is more effective than system reminders alone.