The Impact of a Multimodal Sport Science-Based Prehabilitation Program on Clinical Outcomes in Abdominal Cancer Patients: A Cohort Study.

BACKGROUND: The potential for prehabilitation programs to impact clinical outcomes is uncertain in abdominal cancer patients due to the short window of time to intervene and the weakened state of the patients. To improve the effectiveness of prehabilitation intervention, a multimodal sports science approach was implemented. METHODS: Prior to cancer-related surgery, 21 patients participated in a 4-week exercise and nutrition prehabilitation program comprised of blood flow restriction exercise (BFR) and a sports nutrition supplement. Retrospective data of 71 abdominal cancer patients who underwent usual preoperative care was used as a comparator control group (CON). At 90 days post-surgery, clinical outcomes were quantified. RESULTS: Prehabilitation was associated with a shorter length of hospital stay (P = .02) with 5.5 fewer days (4.7 ± 2.1 vs 10.2 ± 1.2 days in CON) and decreased incidence of any complications (P = .03). Prehabilitation was not related to incidence of serious complications (P = .17) or readmission rate (P = .59). The prehabilitation group recorded 58% more steps on day 5 after surgery (P = .043). DISCUSSION: A 4-week home-based prehabilitation program composed of BFR training and sports nutrition supplementation was effective in reducing postoperative complications and length of hospital stay in older patients with abdominal cancer.ClinicalTrials.gov Identifier: NCT04073381.

A Mobile App With Multimodality Prehabilitation Programs for Patients Awaiting Elective Surgery: Development and Usability Study.

BACKGROUND: Complying with a prehabilitation program is difficult for patients who will undergo surgery, owing to transportation challenges and a limited intervention time window. Mobile health (mHealth) using smartphone apps has the potential to remove barriers and improve the effectiveness of prehabilitation. OBJECTIVE: This study aimed to develop a mobile app as a tool for facilitating a multidisciplinary prehabilitation protocol involving blood flow restriction training and sport nutrition supplementation. METHODS: The app was developed using "Appy Pie," a noncoding app development platform. The development process included three stages: (1) determination of principles and requirements of the app through prehabilitation research team meetings; (2) app prototype design using the Appy Pie platform; and (3) app evaluation by clinicians and exercise and fitness specialists, technical professionals from Appy Pie, and non-team-member users. RESULTS: We developed a prototype of the app with the core focus on a multidisciplinary prehabilitation program with accessory features to improve engagement and adherence to the mHealth intervention as well as research-focused features to evaluate the effects of the program on frailty status, health-related quality of life, and anxiety level among patients awaiting elective surgery. Evaluations by research members and random users (n=8) were consistently positive. CONCLUSIONS: This mobile app has great potential for improving and evaluating the effectiveness of the multidisciplinary prehabilitation intervention in the format of mHealth in future.

Prehabilitation program composed of blood flow restriction training and sports nutrition improves physical functions in abdominal cancer patients awaiting surgery.

INTRODUCTION: The impact of prehabilitation remains controversial due to a short presurgical waiting period and the diminished capacity of the patient population. A strategy to augment and optimize the effectiveness of prehabilitations for abdominal cancer patients may be found in the unlikely field of sport science. We investigated the use of blood flow restriction training and sport nutrition supplementation to augment functional capacity and increase muscle strength in twenty-four abdominal cancer patients awaiting surgery. MATERIALS AND METHODS: The sport science-based program was comprised of blood flow restriction exercise 5 to 6 times per week and a daily sports nutrition supplement containing l-citrulline, creatine monohydrate, and whey protein. RESULTS: After 4 weeks of prehabilitation, 6-min walk test, timed up and go, short physical performance battery, 5-chair stand test and physical component score of quality of life were significantly improved (all p < 0.05). Total body and appendicular lean mass as assessed by dual energy X-ray absorptiometry increased by 0.73 ± 1.04 kg (p = 0.004) and 0.42 ± 0.64 kg (p = 0.006), respectively. Total body fat mass and trunk fat mass decreased (p = 0.004 and p = 0.021). There were no significant changes in hand grip strength, fear of falling, the mental component summary of quality of life, or fasting serum concentrations of myostatin, follistatin, and growth hormone. CONCLUSION: A multimodal prehabilitation program, which encompasses blood flow restriction training and sports nutrition supplements, is both feasible and effective in improving lean mass and physical function in abdominal cancer patients prior to surgery.

The Enhanced Recovery After Surgery (ERAS) Elements that Most Greatly Impact Length of Stay and Readmission.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to decrease length of stay (LOS) and improve patient outcomes in a wide variety of surgical fields; however, barriers exist preventing the implementation of all elements. We hypothesize that a subset of ERAS elements are most influential on LOS and readmission following colorectal surgery. STUDY DESIGN: A retrospective review of 840 patients was performed and their compliance with 24 ERAS components evaluated. Two independent machine-learning statistical algorithms were employed to determine which subset of ERAS elements was most impactful on LOS <3 days and hospital readmission. RESULTS: Increasing compliance with ERAS elements had an inverse linear relationship with LOS. Open (vs minimally invasive) surgery was associated with increased LOS. Early mobilization and multimodal pain management are the elements most protective against increased LOS. Readmissions increase with the number of morphine milligram equivalents (MME)/day. The subset of patients who underwent minimally invasive procedures, had multimodal pain control, and less than 16 MME per day were least likely (23%) to have >3-day LOS. Those patients who underwent an open procedure with less than 15 ERAS elements completed were most likely (84%) to have >3-day LOS. CONCLUSION: While increasing compliance with ERAS protocols and minimally invasive procedures decrease LOS and readmission overall, a subset of components-multimodal pain control, limited opioid use, and early mobilization-was most associated with decreased LOS and readmission. This study provides guidance on which ERAS elements should be emphasized.

Spatiotemporal Gradient and Instability of Wnt Induce Heterogeneous Growth and Differentiation of Human Intestinal Organoids.

In a conventional culture of three-dimensional human intestinal organoids, extracellular matrix hydrogel has been used to provide a physical space for the growth and morphogenesis of organoids in the presence of exogenous morphogens such as Wnt3a. We found that organoids embedded in a dome-shaped hydrogel show significant size heterogeneity in different locations inside the hydrogel. Computational simulations revealed that the instability and diffusion limitation of Wnt3a constitutively generate a concentration gradient inside the hydrogel. The location-dependent heterogeneity of organoids in a hydrogel dome substantially perturbed the transcriptome profile associated with epithelial functions, cytodifferentiation including mucin 2 expression, and morphological characteristics. This heterogeneous phenotype was significantly mitigated when the Wnt3a was frequently replenished in the culture medium. Our finding suggests that the morphological, transcriptional, translational, and functional heterogeneity in conventional organoid cultures may lead to a false interpretation of the experimental results in organoid-based studies.

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.

Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives.

Hyperphosphatemia and II(o) hyperparathyroidism are common and severe complications of chronic renal failure. Reduced dietary phosphorus has been shown to be an effective treatment in reducing serum phosphate and serum PTH. 2(')-Phosphophloretin inhibited small intestine apical membrane Na(+)/phosphate cotransport and reduced serum phosphate in adult rats. 2(')-PP and phosphoesters of phloretin were tested for inhibition of human small intestine brush border membrane alkaline phosphatase activity and for inhibition of Na(+)-dependent phosphate uptake. The IC(50)'s for inhibition of alkaline phosphatase suggested an order of inhibitory potency of 4-PP > phloretin > 4(')-PP > 2(')-PP. Inhibition of Na(+)-dependent phosphate uptake followed the sequence 2(')-PPz.Gt;4(')-PP > 4-PP > phloretin. These results are consistent with 2(')-PP being a specific inhibitor of human intestinal brush border membrane Na(+)/phosphate cotransport.

Inverse regulation of protein turnover and amino acid transport in skeletal muscle of hypercatabolic patients.

We have investigated the relationships between the rates of muscle protein synthesis and degradation and of transmembrane transport of selected amino acids in leg skeletal muscle of 19 severely burned patients and 18 normal controls in the postabsorptive state. Patients were studied on the 14 +/- 5 postburn day, and their mean burn size was 66% +/- 18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle and infusions of isotopic tracers of amino acids. Net muscle protein breakdown was greater in the patients because of an 83% increase in the rate of muscle protein degradation. The rate of muscle protein synthesis was also increased in the patients but to a lesser extent than protein degradation, i.e. by 50% with the arteriovenous phenylalanine balance technique and by 49% with the direct tracer incorporation method. The absolute values of inward transport of phenylalanine, leucine, and lysine were not significantly different in the two groups. However, the ability of transport systems to take up amino acids from the bloodstream, as assessed by dividing inward transport by amino acid delivery to leg muscle, were 50-63% lower in the patients. In contrast, outward phenylalanine and lysine transport were 40% and 67% greater in the patients than in the controls, respectively. We conclude the primary alteration in muscle protein metabolism is an acceleration of protein breakdown, and the increase in protein synthesis likely is due to increased intracellular amino acid availability as a result of accelerated breakdown. Transmembrane transport in the outward direction is accelerated, presumably to facilitate the export of amino acids from muscle to other tissues. In contrast, transmembrane transport in the inward direction is impaired relatively to the increased delivery of circulating amino acid to skeletal muscle secondary to accelerated blood flow.