Machine-learning-guided recognition of α and ß cells from label-free infrared micrographs of living human islets of Langerhans.

Human islets of Langerhans are composed mostly of glucagon-secreting α cells and insulin-secreting ß cells closely intermingled one another. Current methods for identifying α and ß cells involve either fixing islets and using immunostaining or disaggregating islets and employing flow cytometry for classifying α and ß cells based on their size and autofluorescence. Neither approach, however, allows investigating the dynamic behavior of α and ß cells in a living and intact islet. To tackle this issue, we present a machine-learning-based strategy for identification α and ß cells in label-free infrared micrographs of living human islets without immunostaining. Intrinsic autofluorescence is stimulated by infrared light and collected both in intensity and lifetime in the visible range, dominated by NAD(P)H and lipofuscin signals. Descriptive parameters are derived from micrographs for ~ 103 cells. These parameters are used as input for a boosted decision-tree model (XGBoost) pre-trained with immunofluorescence-derived cell-type information. The model displays an optimized-metrics performance of 0.86 (i.e. area under a ROC curve), with an associated precision of 0.94 for the recognition of ß cells and 0.75 for α cells. This tool promises to enable longitudinal studies on the dynamic behavior of individual cell types at single-cell resolution within the intact tissue.

Prehabilitation in patients with cirrhosis awaiting liver transplantation: protocol of a feasibility study.

INTRODUCTION: Patients with cirrhosis awaiting liver transplantation (LT) are often frail, and malnourished. The period of time on the waitlist provides an opportunity to improve their physical fitness. Prehabilitation appears to improve the physical fitness of patients before major surgery. Little is known about prehabilitation in patients with cirrhosis. The aim of this feasibility study will be to investigate the feasibility, safety, and effectiveness of a multimodal prehabilitation programme in this patient population. METHODS AND ANALYSIS: This is an open-label single-arm feasibility trial recruiting 25 consecutive adult patients with cirrhosis active on the LT waiting list of the McGill University Health Centre (MUHC). Individuals will be excluded based on criteria developed for the safe exercise training in patients with cirrhosis. Enrolled individuals will participate in a multimodal prehabilitation programme conducted at the PeriOperative Programme complex of the MUHC. It includes exercise training with a certified kinesiologist (aerobic and resistance training), nutritional optimisation with a registered dietician and psychological support with a nurse specialist. The exercise training programme is divided into an induction phase with three sessions per week for 4 weeks followed by a maintenance phase with one session every other week for 20 weeks. Aerobic training will be individualised based on result from cardiopulmonary exercise testing (CPET) and will include a high-intensity interval training on a cycle ergometer. Feasibility, adherence and acceptability of the intervention will be assessed. Adverse events will be reviewed before each visit. Changes in exercise capacity (6-minute walk test, CPET, liver frailty index), nutritional status and health-related quality of life will be assessed during the study. Post-transplantation outcomes will be recorded. ETHICS AND DISSEMINATION: The research ethics board of the MUHC has approved this study (2021-7646). Our findings will be submitted for presentation at national and international conferences, and for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT05237583.

The landscape of cancer-rewired GPCR signaling axes.

We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).

Towards a common definition of surgical prehabilitation: a scoping review of randomised trials.

BACKGROUND: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition. METHODS: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis. RESULTS: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.' CONCLUSIONS: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted.

Multimodal prehabilitation in elective oncological colorectal surgery enhances postoperative functional recovery: A secondary analysis of the PREHAB randomized clinical trial.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. The PREHAB trial revealed that prehabilitation in colorectal surgery leads to a reduction of severe complications and enhanced functional capacity. Nevertheless, risk selection for prehabilitation and the potential benefits for patients without postoperative complications remains unclear. This study aims to assess postoperative functional capacity, also in patients without postoperative complications. MATERIALS & METHODS: This study was a secondary analysis of the PREHAB trial. Functional capacity tests, including cardiopulmonary exercise testing (CPET), steep ramp test (SRT), 6-min walking test (6MWT), stair climb test (SCT), 30" sit-to-stand test (STS), timed-up-and-go test (TUG), and muscle strength assessments, were conducted at baseline (T0) and 4 weeks postoperatively (T3). The primary outcome was the relative change in functional capacity from baseline to postoperative (ΔT0-T3) per group (i.e., prehabilitation vs control). Secondary, identical analysis were performed for patients without postoperative complications in each group. RESULTS: Intention-to-treat analysis included 251 patients. For postoperative functional capacity, prehabilitation patients showed improvements in VO2peak (p = 0.024), VO2AT (p = 0.017), SRT (p = 0.001), 6MWT (p = 0.049), SCT (p = 0.012), and STS (p = 0.001) compared to the control group. Regarding muscle strength, prehabilitation patients showed improvements in estimated 1RM lateral pull down (p = 0.016), 1RM chest press (p = 0.001), 1RM leg press (p = 0.001) and HGS (p = 0.005) compared to controls. Additionally, prehabilitation patients more often reached baseline levels at T3 in VO2AT (p = 0.037), SRT (p = 0.008), 6MWT (p = 0.013), STS (p = 0.012), estimated 1RM lateral pull down (p = 0.002), 1RM chest press (p = 0.001) and 1RM leg press (p = 0.001) compared to controls. Moreover, even patients without postoperative complications in the prehabilitation group showed better postoperative functional capacity and more often reached baseline levels at T3, compared to controls. CONCLUSION: Multimodal prehabilitation in CRC surgery is associated with improved postoperative functional capacity, even in patients without postoperative complications.

A survey of preoperative surgical nutrition practices, opinions, and barriers across Canada.

Malnutrition is prevalent among surgical candidates and associated with adverse outcomes. Despite being potentially modifiable, malnutrition risk screening is not a standard preoperative practice. We conducted a cross-sectional survey to understand healthcare professionals' (HCPs) opinions and barriers regarding screening and treatment of malnutrition. HCPs working with adult surgical patients in Canada were invited to complete an online survey. Barriers to preoperative malnutrition screening were assessed using the Capability Opportunity Motivation-Behaviour model. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using summative content analysis. Of the 225 HCPs surveyed (n = 111 dietitians, n = 72 physicians, n = 42 allied HCPs), 96%-100% agreed that preoperative malnutrition is a modifiable risk factor associated with worse surgical outcomes and is a treatment priority. Yet, 65% (n = 142/220; dietitians: 88% vs. physicians: 40%) reported screening for malnutrition, which mostly occured in the postoperative period (n = 117) by dietitians (n = 94). Just 42% (48/113) of non-dietitian respondents referred positively screened patients to a dietitian for further assessment and treatment. The most prevalent barriers for malnutrition screening were related to opportunity, including availability of resources (57%, n = 121/212), time (40%, n = 84/212) and support from others (38%, n = 80/212). In conclusion, there is a gap between opinion and practice among surgical HCPs pertaining to malnutrition. Although HCPs agreed malnutrition is a surgical priority, the opportunity to screen for nutrition risk was a great barrier.

Multimodal Prehabilitation for Patients Undergoing Endovascular Aortic Aneurysm Repair Surgery: A Feasibility Study.

BACKGROUND: Elective treatment options for aortic abdominal aneurysms include open repair or the less-invasive endovascular aortic aneurysm repair (EVAR). Recovery from EVAR is generally considered easier and faster than open repair. Despite this, EVAR remains a major procedure, and average return to preoperative quality of life is at least 3 months. The purpose of this study is to determine the safety and feasibility of multimodal prehabilitation, a multidisciplinary preoperative optimization intervention, in patients undergoing EVAR and its impact on perioperative functional capacity and quality of life. METHODS: Candidates for EVAR with an infra-renal abdominal aortic aneurysm <7.5cm were invited to participate in a 6-week multimodal prehabilitation program that included (1) supervised and home-based exercise, (2) nutritional support, (3) psychosocial support, and (4) smoking cessation. Functional capacity and quality of life were assessed at baseline, before surgery and 6 weeks postoperatively. Recruitment rate, safety, and compliance were also assessed. RESULTS: A total of 24 patients were included, 17 males (70%) and 7 females (30%). No adverse events occurred during the program. Compliance to each component of the program (median [Q1-Q3]) was 66% [67] for supervised training, 100% [67] for home-based training, and 100% [100] for nutrition. The multimodal prehabilitation program elicited a significant increase in functional capacity and quality of life preoperatively. CONCLUSION: Multimodal prehabilitation for patients awaiting EVAR is feasible and safe. Multimodal prehabilitation improves both functional capacity and quality of life preoperatively. Further research is needed to assess the impact of multimodal prehabilitation on postoperative quality of life and functional capacity. CLINICAL IMPACT: Multimodal prehabilitation is safe and feasible in patients awaiting endovascular aneurysm repair. The importance of this finding is that multimodal prehabilitation can be safely delivered preoperatively in patients awaiting EVAR. Although further research is needed, multimodal prehabilitation seems to improve preoperative functional capacity and quality of life. This could have an impact for the future implementation of prehabilitation interventions in order to increase functional reserve and quality of life preoperatively so that this high-risk population can cope better with the surgical stress and return to their normal life faster postoperatively.