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.

Does a multimodal prehabilitation program improve sleep quality and duration in patients undergoing colorectal resection for cancer? Pilot randomized control trial.

Sleep difficulties are a common symptom in cancer patients at different stages of treatment trajectory and may lead to numerous negative consequences for which management is required. This pilot Randomized Controlled Trial (RCT) aims to assess the potential effectiveness of home-based prehabilitation intervention (prehab) on sleep quality and parameters compared to standard care (SOC) in colorectal cancer patients during the preoperative period and up to 8 weeks after the surgery. One hundred two participants (48.3% female, mean age 65 years) scheduled for elective resection of colorectal cancer were randomized to the prehab (n = 50) or the SOC (n = 52) groups. Recruitment and retention rates were 54% and 72%, respectively. Measures were completed at the baseline and preoperative, 4- and 8-week after-surgery follow-ups. Our mixed models' analyses revealed no significant differences between groups observed over time for all subjective and objective sleep parameters. A small positive change was observed in the perceived sleep quality only at the preoperative time point for the prehabilitation group compared to the SOC group, with an effect size d = 0.11 and a confidence interval (CI) between - 2.1 and - 0.1, p = .048. Prehab group patients with high anxiety showed a significant improvement in the rate of change of sleep duration over time compared to the SOC group, with a difference of 110 min between baseline and 8 weeks after surgery (d = 0.51, 95% CI: 92.3 to 127.7, p = .02). Multimodal prehabilitation intervention is feasible in colorectal cancer patients and may improve sleep duration for patients with high anxiety symptoms. Future large-scale RCTs are needed to confirm our results.

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.

Multimodal Prehabilitation for Peripheral Arterial Disease Patients with Intermittent Claudication-A Pilot Randomized Controlled Trial.

BACKGROUND: To establish the feasibility and safety of multimodal prehabilitation (MP), and to obtain pilot data on the change in quality of life, functional walking capacity, and the need for surgery for a full-scale trial. METHODS: Pilot randomized controlled trial that included patients older than 50 years old suffering from moderate to severe intermittent claudication and who were candidates for endovascular revascularization (ER). Participants were excluded if they presented with ischemic rest pain, gangrene or ulceration of the index leg, significant lesions in the iliac vessels, planned surgical bypass, comorbidities in which exercise was contraindicated or if they were unable to speak English or French. Participants were randomized in a 1:1 ratio to 12 weeks of MP or institutional standard of care (unsupervised walking advice). MP consisted of i)1 weekly supervised exercise session; ii) home-based exercise prescription; iii) nutritional counseling and supplementation; iv) smoking cessation therapy; and v) psychosocial support. Feasibility and safety were measured with recruitment and retention rates, as well as the occurrence of any adverse events. In addition, barriers to attend supervised sessions and compliance to each component were assessed. Change in functional walking capacity, health-related quality of life, and the rates of patients deciding not to undergo ER were collected and analyzed throughout the follow-up period of 12 months. RESULTS: Of the 37 patients referred for eligibility, 27 (73%) accepted to participate in the trial and were randomized. Of the 27 patients included, 24 completed the 12-week program. Adherence to each prehabilitation component was 83% interquartile range [72,93] for supervised exercise, 90% [83,96] for home-based exercise and 69% [45,93] for nutritional sessions. Fifty percent of patients were referred for and underwent psychosocial intervention and 40% of the active smokers enrolled in the smoking cessation program. No adverse events were observed during the program. The 2 main barriers for not fully adhering to the intervention were excessive pain while performing the exercises and the difficulty to keep up with the prescribed exercises. A statistically significant mean change (standard deviation (SD)) was seen in the MP group versus standard of care for functional capacity, mean (SD) 6 Min Walk Test 60 (74) vs. -11 (40) meters P < 0.05, and quality of life mean (SD) VascuQol 1.15 (0.54) vs. -0.3 (1.09) points P < 0.05. There was no statistically significant difference between groups in the rates of patients deciding to undergo ER during the 1-year follow-up period. CONCLUSIONS: The results of this pilot trial demonstrate that MP is safe and feasible. A 12-week MP program seems to improve quality of life and functional walking capacity to a greater extent than unsupervised walking advice. There is a need for a large-scale trial to investigate the effectiveness of MP at improving quality of life and assessing its impact on the rates of patients deciding not to undergo or delay ER. The long-term functional and quality of life outcomes of the patients deciding to undergo ER after prehabilitation also need to be assessed.

Preoperative optimization: Physical and cognitive pre-habilitation and management of chronic medication.

Surgery is a significant stressor for older patient. Most are at higher risk of complications due to frailty and comorbidities. This article will review the impact of surgery on the older patient, perioperative risk assessment and stratification, prehabilitation, and specific screenings and interventions. Electronic searches of PubMed were conducted to identify relevant literature using the following search terms: prehabilitation, sarcopenia, osteosarcopenia, frailty, perioperative evaluation, and polypharmacy. Using the frailty phenotype allows for the early identification of geriatric syndromes and potential targets for interventions. However, it does not inform on potential cognitive impairment, which must be assessed separately. Prehabilitation, especially using multimodal interventions, aims to increase functional capacity during the preoperative period in anticipation of the upcoming stress of surgery and the metabolic cost of recovery. It comprises aerobic and resistance training, dietary interventions, psychological interventions, and cessation of adverse health behaviors. Addressing polypharmacy is also important during the perioperative period. Several frailty assessment tools exist, and special tests only take minutes to perform such as the gait speed and chair stand test. Early identification by surgeons leads to early referral to prehabilitation, which needs about four to six weeks to improve function. The decision to enroll patients in a prehabilitation program is based on the understanding of the needs to maintain a structured and personalized intervention taking into consideration the patient's health status, the type of surgery, and the state of the disease. Perioperative evaluation and prehabilitation for older adults are evolving fields, which are generating clinical and scientific interest. This article will review relevant topics to help clinicians adapt usual perioperative care to older patients' particular needs.

Association Between Physical Activity, Sedentary Behaviors, and Sleep-Related Outcomes Among Cancer Survivors: a Cross-Sectional Study.

BACKGROUND: Limited research has examined the association between moderate to vigorous physical activity (MVPA), sedentary behavior (SB), and sleep-related outcomes in cancer survivors. Therefore, this study aimed to examine these associations using a nationally representative sample of US adults. METHODS: Data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. A total of 3229 adults with cancer histories were included. Physical activity was measured through accelerometry, and questions on daily activities, sedentary time, and sleep were collected during the household interview. Weighted multivariable analyses were conducted after accounting for the complex sampling design of the NHANES dataset. RESULTS: After adjustments, physical activity and SB outcomes were associated with several self-reported sleep-related parameters. Increases in minutes of self-reported MVPA and SB were associated with a decreased likelihood of reporting ≥ 8 h of sleep (OR = 0.92, 95% CI = 0.86, 0.99 and OR = 0.88, 95% CI = 0.82, 0.95). Converse associations were found between device-measured MVPA and SB with the likelihood of reporting often/always feeling overly sleepy during the day (OR = 0.86, 95% CI = 0.75 and OR = 1.13, 95% CI = 1.05, respectively). However, an increased likelihood of waking up too early in the morning (OR = 1.22, 95% CI = 1.04) was observed with increases in minutes of device-measured MVPA. CONCLUSIONS: A sensible strategy to decrease the frequency of sedentary breaks and increase minutes of physical activity throughout the day may reduce sleep complaints reported in cancer survivors.

Reporting quality of randomized controlled trials in prehabilitation: a scoping review.

BACKGROUND: Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. METHODS: Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. SOURCES OF EVIDENCE: search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. CHARTING METHODS: identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). RESULTS: We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). CONCLUSION: Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions.

The landscape of cancer rewired GPCR signaling axes.

We explored the dysregulation of GPCR ligand signaling 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, which revealed that multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes. We showed that biosynthetic pathway enrichment from enzyme expression recapitulated pathway activity signatures from metabolomics datasets, providing valuable surrogate information for GPCRs responding to organic ligands. We found that several GPCRs signaling components were significantly associated with patient survival in a cancer type-specific fashion. 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 pairs 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. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).

Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

Socioeconomic status influences participation in cancer prehabilitation and preparation for surgical recovery: A pooled retrospective analysis using a validated area-level socioeconomic status metric.

BACKGROUND: Prehabilitation employs exercise, nutrition, and psychological interventions to optimize physiological status in preparation for surgery. First, we described the extent to which material deprivation index score (MDIS) influenced prehabilitation participation. Second, we evaluated the extent to which prehabilitation influenced recovery as compared to control. METHODS: Pooled patient records from prospective multimodal prehabilitation studies in oncologic surgery were retrospectively examined. Patient postal codes were linked to their MDIS, a validated area-level socioeconomic status (SES) metric, as quintiles 1-5 (1 = highest SES). Functional capacity was evaluated with the 6-min walking test (6MWT) at baseline, before, and 8 weeks post-surgery. Influence of prehabilitation on length of hospital stay (LOS) was explored using generalized linear models with a negative binomial distribution adjusted for age, sex, surgical population, and MDIS. RESULTS: Recruitment records were available from 2014 onwards, yielding 1013 eligible patients for prehabilitation participation with MDIS data. Fewer patients with a low SES enrolled (Q1:62% vs. Q5:47%; P = 0.01) and remained in prehabilitation studies (Q1: 59% vs. Q5: 45%; P = 0.07). Prehabilitation study records were available from 2008 onward, yielding 886 enrolled patients with MDIS data (n = 510 prehabilitation, n = 376 control). Preoperative 6MWT similarly improved by > 20 m in response to prehabilitation across SES strata (P < 0.05). Postoperative 6MWT could not be evaluated due to substantial missing data. Prehabilitation had a significant protective influence on LOS, as compared to control, in unadjusted and adjusted models [adjusted IRR:0.77 (95% CI:0.68 to 0.87; P < 0.001]. CONCLUSION: Findings suggest that prehabilitation is effective across all SES; however, participation across SES quintiles was not equal. Barriers to participation must be identified and addressed. Once these barriers are addressed, prehabilitation may reduce surgical disparities among SES.

Neoadjuvant Prehabilitation Therapy for Locally Advanced Non-Small-Cell Lung Cancer: Optimizing Outcomes Throughout the Trajectory of Care.

BACKGROUND: Prehabilitation is well established for improving outcomes in cancer surgery. Combining prehabilitation with neoadjuvant treatments may provide an opportunity to rapidly initiate cancer-directed therapy while improving functional status in preparation for local consolidation. In this proof-of-concept study, we analyzed non-small-cell lung cancer patients who underwent simultaneous prehabilitation and neoadjuvant therapy. PATIENTS AND METHODS: We retrospectively analyzed all patients who underwent neoadjuvant treatment for non-small-cell lung cancer followed by curative intent surgery between 2015 and 2021. Patients who were screened for the prehabilitation program were identified. The screening included assessment of physical performance, nutritional status, and signs of anxiety and depression. RESULTS: We identified a total of 141 patients who underwent neoadjuvant therapy. Twenty patients were screened to undergo a prehabilitation program. Four patients did not complete the exercise program (1 surgical intervention too soon, 1 drop-out after the first session, and 2 patients were deemed fit without intervention). The postoperative median length of stay was 2 days (range 1-18). Patients improved their 6-minute-walk test despite undergoing neoadjuvant treatment by a mean of 33 meters (± 50, P = .1). Self-reported functional status (DASI) showed significant improvement by a mean of 10 points (± 11, P = .03), and HADS-anxiety-score was significantly reduced after the prehabilitation program by a mean of 1.5 points (± 1, P = .005). CONCLUSION: Neoadjuvant prehabilitation therapy is feasible and associated with encouraging results. The performance of all measures remains a logistic challenge. With multimodal strategies for lung cancer treatment becoming key to optimal outcomes, neoadjuvant prehabilitation therapy is a concept worthy of prospective multi-center evaluation.

PRECOGx: exploring GPCR signaling mechanisms with deep protein representations.

In this study we show that protein language models can encode structural and functional information of GPCR sequences that can be used to predict their signaling and functional repertoire. We used the ESM1b protein embeddings as features and the binding information known from publicly available studies to develop PRECOGx, a machine learning predictor to explore GPCR interactions with G protein and ß-arrestin, which we made available through a new webserver (https://precogx.bioinfolab.sns.it/). PRECOGx outperformed its predecessor (e.g. PRECOG) in predicting GPCR-transducer couplings, being also able to consider all GPCR classes. The webserver also provides new functionalities, such as the projection of input sequences on a low-dimensional space describing essential features of the human GPCRome, which is used as a reference to track GPCR variants. Additionally, it allows inspection of the sequence and structural determinants responsible for coupling via the analysis of the most important attention maps used by the models as well as through predicted intramolecular contacts. We demonstrate applications of PRECOGx by predicting the impact of disease variants (ClinVar) and alternative splice forms from healthy tissues (GTEX) of human GPCRs, revealing the power to dissect system biasing mechanisms in both health and disease.

Advocating for prehabilitation for patients undergoing gynecology-oncology surgery.

Implementation of Enhanced Recovery After Surgery (ERAS) protocols in gynecology-oncology has resulted in improved perioperative outcomes. However, ERAS does not include preoperative interventions to address the comorbidities, malnutrition, weight loss/obesity, decreased functional capacity and high degree of anxiety and depression that are present in the gynecology-oncology patients. The amalgamation of these risk factors with the surgical stress response and chemoradiotherapy-related toxicities is associated with worse postoperative functional capacity and impaired quality of life. Not surprisingly, surgical-related decline in physical fitness is one of the most distressing symptoms reported by cancer patients. Restoring pre-treatment physical status and accelerating recovery can be done through prehabilitation. Prehabilitation is a multimodal program combining exercise, nutrition and psychological interventions to strengthen patients physically and mentally before surgery by addressing modifiable risk factors during the preoperative period thereby filling this existing gap. It has shown promising results in the colorectal and thoracic surgery populations. This paper elaborates on risk factors specific to the gynecology-oncology population, highlights selection criteria that should prompt referral to a prehabilitation program and advocates for the implementation of these programs in this population.

Virtual Prehabilitation in Patients With Cancer Undergoing Surgery During the COVID-19 Pandemic: Protocol for a Prospective Feasibility Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, preoperative care, also termed prehabilitation, has become increasingly relevant due to the decreasing functional and psychosocial health of patients with cancer, which is a result of the pandemic restrictions. Concurrently, access to telehealth has improved; telehealth comprises all remote care delivery facilitated by information technologies (ie, virtually). OBJECTIVE: The aim of this protocol is to describe the rationale and methodology for a major trial investigating the feasibility and safety of multimodal virtual prehabilitation services (ie, teleprehabilitation). METHODS: This single-arm feasibility trial aims to recruit 100 patients with cancer to receive teleprehabilitation throughout their preoperative period. The inclusion criteria are as follows: (1) 18 years of age or older, (2) scheduled for elective cancer surgery and referred by a surgeon, (3) medically cleared by the referring physician to engage in physical activity, and (4) have a good comprehension of the English or French language. Feasibility will be assessed by documenting recruitment, adherence, and retention rates, in addition to patients' motives for not participating in the trial, low participation, or discontinuation. The secondary outcome of safety will be assessed by reporting program-related adverse events. RESULTS: The Montreal General Hospital Foundation funded the project in August 2020. The protocol was then approved by the Research Ethics Board of the McGill University Health Centre in January 2021 (ID No. 2021-6730). The first patient was recruited in March 2021, and recruitment is expected to end in September 2022. As of March 2022, 36 patients have been recruited, including 24 who have completed their participation. No adverse events have been reported. Data collection is expected to conclude in November 2022. Data analysis will be performed, and the results will be published by the beginning of 2023. CONCLUSIONS: This trial will provide guidance on the use of telehealth in the administration of prehabilitation services. The trial will provide a large amount of information that will respond to gaps in the literature, as there are minimal reports on the use of telehealth rehabilitation and prehabilitation services among elderly populations and in acute contexts, such as the preoperative period. TRIAL REGISTRATION: ClinicalTrials.gov NCT0479956; https://clinicaltrials.gov/ct2/show/NCT04799561. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29936.

Successes and challenges of implementing teleprehabilitation for onco-surgical candidates and patients' experience: a retrospective pilot-cohort study.

This study documents the implementation of a multimodal teleprehabilitation program (e.g., completion rate, exercise metrics, and program successes and challenges) for cancer patients undergoing surgery. It also documents the patients' experience of the program. This pilot-cohort study included adults scheduled for elective thoracic and abdominal cancer resection surgery, referred to the prehabilitation clinic to engage in physical activity, and received a teleprehabilitation program between August 1st, 2020, and February 28th, 2021. The technology platform provided to the patients included a tablet and a wearable device to facilitate communication and data collection. Data collected for this article were acquired through virtual physical activity monitoring in addition to patient charts. Qualitative data collected comprised of successes and challenges of implanting a teleprehabilitation program, in addition to patients' perspectives of the program. Quantitative data collected comprised of the exercise metrics, perioperative functional outcomes, in addition to the surgical and postoperative outcomes. Ten patients (8 males and 2 females; mean age: 68.3 years, SD 11.96) diagnosed with various thoracoabdominal malignancies were included in the current descriptive study. The successes identified were related to recruitment and assessment, improvement in functional capacity, clinic scheduling and interventions, and optimal medical follow-up. The challenges identified were related to the adoption of the technologies by patients and the multidisciplinary team, the accurate acquisition of patient physical activity data, and the initial costs to acquire the new technologies. Patients were satisfied with the teleprehabilitation program (i.e., services delivered; average appreciation: 96%), and they perceived the technologies provided to be 90% user-friendly. The findings of the current study highlight important concepts in view of the current international health paradigm changes prioritizing remote interventions facilitated through digital communication technologies. It provides important insight into the clinical application of telehealth in elderly populations, notably in the context of acute preoperative cancer care. This article may provide guidance for other cancer care facilities aiming to implement teleprehabilitation programs.

BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA-based vaccine-encoding SARS-CoV-2 full-length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS-CoV-2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease-susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS-CoV-2-naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.