Prehabilitation in an Integrative Medicine Day Clinic for Patients Undergoing Neoadjuvant Treatment: Single-Center Feasibility Pilot Study.

BACKGROUND: Patients with cancer receiving neoadjuvant treatment prior to surgery are in a very stressful situation. Chemotherapy and radiation therapy put a strain on the quality of life and the pending surgery poses a relevant burden for many patients. Preparation of these patients for the intervention in terms of prehabilitation has great potential to reduce the burden of postoperative complications and may improve the clinical outcome. A prehabilitation approach also yields the possibility to address unmet patients' needs and to help them modify their lifestyle in a maintainable way. Therefore, a multimodal approach is mandatory during this critical period. OBJECTIVE: The aim of this study is to assess the feasibility of prehabilitation in an integrative medicine day clinic (PRIME-DC) prior to cancer surgery at a major university clinic. PRIME-DC is considered feasible if 80% of enrolled patients are willing and able to complete at least 6 out of the 8 weekly meetings, each lasting 6.5 hours, at such a clinic. Secondary end points aim to evaluate this multimodal program. METHODS: The PRIME-DC intervention combines mind-body medicine, exercise therapy, nutrition therapy, naturopathic counseling, and the application of a yarrow liver compress. Adult patients with cancer, with a primary tumor in the abdomen (including intraperitoneal cancer, stomach cancer, and extraperitoneal cancers such as pancreatic, bladder, rectal, esophageal, endometrial, ovarian, and cervical cancer) or the breast requiring a neoadjuvant oncological treatment setting are eligible to participate. The addressed cancer entities imply either an extensive surgical intervention with an expected need for prehabilitation (eg, abdominal surgery) or a neoadjuvant treatment of several months with a high burden of treatment-associated side effects (breast cancer). Adherence to the day clinic program is the primary end point being defined as presence during the day clinic session. Secondary end points are physical assessment and quality of life, together with a structured assessment of neoadjuvant treatment-associated side effects. Furthermore, to collect qualitative data voluntary participants of the day clinic will be interviewed in a semistructured way after completion of the day clinic program on each component of the study (mind-body intervention, exercise, nutrition, naturopathic counseling, and a yarrow liver compress). RESULTS: The procedures used in this study adhere to the tenets of the Declaration of Helsinki. As of February 2023, we enrolled 23 patients; the dominant cancer entity is breast cancer (18 enrolled patients). CONCLUSIONS: The presented protocol combines prehabilitation, lifestyle modification, naturopathic counseling, dietary assistance, and naturopathic treatment in an innovative and integrative way. TRIAL REGISTRATION: Deutsches Register Klinischer Studien German Clinical Trials Register DRKS00028126; https://drks.de/search/de/trial/DRKS00028126. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46765.

Design, development, and local production of lipid-based nutritional supplements to enhance the complementary feeding diet: A model for collaboration for a feeding trial in Bangladesh.

Background: Lipid-based nutrient supplements (LNS) are effective for treating childhood wasting and for preventing stunting, wasting, and anemia, but large-scale production and programmatic use are a barrier. Locally-developed and produced LNS may be more affordable and reduce logistical procurement and importation hurdles, while promoting private sector engagement and partnership. Methods: In northwestern Bangladesh, we conducted a community-based trial of complementary food supplementation to test its efficacy to reduce childhood stunting. Two locally-developed, small-quantity LNS (20g/day, rice-lentil and chick-pea based) were designed, developed first at small scale in the 'kitchen' laboratory under controlled conditions, followed by taking them to a local food manufacturer for larger production for the study. We describe here the partnership, required expertise and capacity, experiences, and lessons learned that made this uniquely complex undertaking possible Results: Key steps in the journey included addressing the dynamics of clear communication between partners, executing on carefully assigned tasks and roles, correcting course when needed, and maintaining timeliness and roadmaps. Knowledge of food science and technology was key in solving many food-production challenges that were encountered in taking the laboratory recipe to the factory. Factory production was established and had to meet quality and hygiene criteria set for young children. Conclusions: We provide documentation of this experience as a model to describe the various steps and considerations and what is entailed in local LNS production. We highlight the importance of a well-conceived collaboration with clear roles that created a 'win-win' situation for all partners for achieving common goals, establishing improved technology at the factory, and building new capacity to produce such products for children in a low resource setting. Key words: micronutrient, lipid-based nutrient supplements, maternal and child, malnutrition, multiagency collaboration.

Naturopathy, complementary and integrative medicine in medical education - position paper by the GMA Committee Integrative Medicine and Perspective Pluralism.

Background: A large part of the population in Germany makes use of naturopathic, complementary and integrative medical treatments. There are now numerous scientific studies that provide evidence of efficacy for certain indications. At German medical faculties, selected procedures and their application are taught within the cross-sectoral unit called QB 12 and some elective courses, with a focus on specific aspects are offered. So far, however, there has been no structured curriculum that longitudinally anchors teaching across medical studies and enables all students to consider naturopathic and complementary medical options for patient care later on and to integrate them effectively into the diagnostic and treatment process. Objective: The aim of this position paper is to show the relevance of this topic for medical education, to clarify terminology and to present core competencies and possible implementation options for training. Method: The Integrative Medicine and Perspective Pluralism Committee of the German Association for Medical Education developed this position paper in a multi-stage consensual process, in cooperation with the Forum of University Work Groups on Naturopathic Treatment and Complementary Medicine. Results: First, different umbrella terms were discussed and an existing definition of integrative medicine and health was chosen for subsequent use. Building on this step, the status of education and its scientific foundation in Germany was considered in an international context. In the next step, a competency profile for medical training, consisting of seven areas of competency, was developed and described in detail with regard to naturopathic, complementary and integrative medicine. Implementation options were identified using possible starting points in the curriculum and using established examples of best practice. Conclusion: Despite different priorities at each faculty, it was possible to find an agreement on the development of competencies and anchoring them in medical education on the basis of a common definition of terms. Currently, the implementation in the mandatory and elective areas is very heterogeneous. As part of the current revision of the Medical Licensure Act, there are many possible starting points for the integration of naturopathic and complementary medical teaching content, especially in interprofessional and general practice courses. The implementation and accompanying research of targeted teaching settings should lay the foundations for a long-term and binding integration into medical education. Overall, it is clear that medical education in the field of naturopathy and complementary and integrative medicine has the potential to develop comprehensive core medical competencies.

Interprofessional evidence-based counselling programme for complementary and integrative healthcare in patients with cancer: study protocol for the controlled implementation study CCC-Integrativ.

INTRODUCTION: According to international literature, patients with cancer wish to have information on complementary and integrative healthcare (CIH). Medical guidelines recommend actively approaching patients with cancer discussing potential benefits and risks of individual CIH methods. While some CIH methods, for example, acupuncture and yoga, have been proven effective in high-quality studies, other CIH methods lack studies or bear the risk of interactions with chemotherapeutics, for example, herbal drugs. Therefore, an evidence-based interprofessional counselling programme on CIH will be implemented at four Comprehensive Cancer Centres in the federal state of Baden-Wuerttemberg, Germany. METHODS AND ANALYSIS: A complex intervention consisting of elements on patient, provider and system levels will be developed and evaluated within a multilayer evaluation design with confirmatory evaluation on patient level. Patients with a cancer diagnosis within the last 6 months will receive three individual counselling sessions on CIH within 3 months (=intervention on patient level). The counselling will be provided by an interprofessional team of medical and nursing staff. For this purpose, an intensive online training programme, a CIH knowledge database and an interprofessional team-building process were developed and implemented (=intervention on provider level). Moreover, training events on the basics of CIH are offered in the outpatient setting (=intervention on system level). Primary outcome of the evaluation at the patient level is patient activation measured (PAM) with the PAM-13 after 3 months. Secondary outcomes, for example, quality of life, self-efficacy and clinical parameters, will be assessed at baseline, after 3 months and at 6 months follow-up. The intervention group (n=1000) will be compared with a control group (n=500, treatment as usual, no CIH counselling. The outcomes and follow-up times in the control group are the same as in the intervention group. Moreover, the use of health services will be analysed in both groups using routine data. A qualitative-quantitative process evaluation as well as a health economic evaluation will identify relevant barriers and enabling factors for later roll-out. ETHICS AND DISSEMINATION: The study has been approved by the appropriate Institutional Ethical Committee of the University of Tuebingen, No. 658/2019BO1. The results of these studies will be disseminated to academic audiences and in the community. TRIAL REGISTRATION NUMBER: DRKS00021779; Pre-results.

Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption.

Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n = 5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525.

Laparoscopic sleeve gastrectomy compared to a multidisciplinary weight loss program for obesity--effects on body composition and protein status.

BACKGROUND: Optimal obesity therapy is a matter of debate. Besides weight reduction, other criteria such as safety and nutritional status are of relevance. Therefore, we compared a favored surgical intervention with the most effective conservative treatment regarding anthropometry and nutritional status. METHODS: Fifty-four obese patients were included who underwent laparoscopic sleeve gastrectomy (LSG, n = 27) or a 52-week multidisciplinary intervention program (MIP, n = 27) for weight loss. Body weight, body composition assessed by bioelectrical impedance analysis, and serum protein levels were measured before and within 12 months after intervention. RESULTS: After 1 year of observation, excess weight loss was more pronounced following LSG (65 %) compared to MIP (38 %, p < 0.001). In both groups, body fat was clearly reduced, but a higher reduction occurred in the LSG group. However, protein status deteriorated particularly in the LSG group. Within 1 year, body cell mass declined from 37.1 to 26.9 kg in the LSG group, but only from 35.7 to 32.2 kg in the MIP group. This resulted in an increased mean extracellular mass/body cell mass ratio (1.42 versus 1.00, p < 0.001), in a decreased mean phase angle (4.4° versus 6.6°, p < 0.001), and in a lower prealbumin level in serum (p < 0.02) in the LSG group compared to the MIP group. CONCLUSIONS: LSG, compared to MIP, was more effective regarding excess weight loss and body fat loss within 1 year, however, induced more pronounced muscle mass and protein loss, possibly requiring particular interventions such as exercise or protein supplements.

Inpatient treatment of community-acquired pneumonias with integrative medicine.

Introduction. The aim of the presented observational case series was to evaluate the experience in treating patients with community-acquired pneumonia (CAP) within integrative medicine, particularly anthroposophic medicine in a well-experienced and specialized unit. Patients and Methods. Patients with proven CAP were evaluated (CAP-study group) based on a retrospective chart review. To estimate the severity of pneumonia, the pneumonia severity index (PSI) was applied. Treatment efficacy was evaluated regarding body temperature, CRP level, leukocytes blood count, the need to be treated on ICU, and mortality. Results were compared with the inpatient data of the Pneumonia PORT Validation Cohort. Results. 15/18 patients of the CAP-study group belonged to risk class groups I-III (low and moderate risk), 2 patients to risk class IV, and one patient to risk class V (severe pneumonia). 16/18 patients were treated with anthroposophic medicine only and 2/18 got additionally antibiotic therapy (both of risk class IV). A significant reduction of body temperature, CRP level, and leukocytes blood count has been obtained by applying anthroposophic medicine, while neither complications nor pneumonia-related death occurred. Compared with the control group there was no significant difference in mortality rate, whereby no patient had to be treated on the ICU, but the duration of hospital stay was significantly longer in the presented series. Conclusion. Inpatient treatment of CAP with anthroposophic medicine without the use of antibiotics may achieve reasonable results in selected cases. Additional larger sized prospective controlled trials should further clarify the role of AM in the treatment of CAP.

Pre- and postoperative nutritional deficiencies in obese patients undergoing laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been identified as an innovative surgical approach for the treatment of obesity and is increasingly applied worldwide. However, data on outcome of LSG regarding nutrient deficiencies, protein status, and body composition are scarce. METHODS: Obese subjects (54; f:m = 4:1) scheduled for LSG were included in this study. Micronutrient analysis, protein status assessment, and bioimpedance measures were performed before and 1, 3, 6, and 12 months after LSG. RESULTS: In 51% of the subjects, at least one micronutrient deficiency was found prior to surgery. Baseline concentrations were below normal for 25-OH vitamin D (27%), iron (29%), vitamin B6 (11%), vitamin B12 (9%), folate (6%), and potassium (7%). Frequencies of deficiencies for vitamin B12, folate, iron, and vitamin B6 tended to increase following LSG within the first year after intervention. Also, parameters of protein status (albumin, transferrin, cholinesterase, and total protein) decreased. After surgery, bioimpedance measures indicated a reduction of total body fat, but also of body cell mass. CONCLUSIONS: Preoperative micronutrient deficiencies were common in morbid obese individuals scheduled for LSG. LSG had a modest effect on micronutrient status by further reducing iron, vitamin B12, vitamin B6, and folate within the first year after intervention. Our data suggest that especially obese patients with preoperative deficits require control and supplementation of micronutrients and protein in the postoperative period.

Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice.

Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight (BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic tumor volume and plasma PSA concentrations were measured at regular intervals. Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and alpha- and gamma, delta-tocopherol concentrations. None of the single treatments significantly reduced tumor volume. In contrast, combined treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio) did not differ between experimental groups, indicating that PSA levels were not selectively affected. Lycopene was detected only in mice supplemented with lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing material. Liver alpha-tocopherol concentrations were increased in mice supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate alpha-tocopherol concentrations were increased only by the higher dose (83%, P < 0.05). Our data provide evidence that lycopene combined with vitamin E may inhibit the growth of prostate cancer and that PSA can serve as a biomarker of tumor response for this treatment regimen.

Noncompetitive plasma biokinetics of deuterium-labeled natural and synthetic alpha-tocopherol in healthy men with an apoE4 genotype.

Previous studies comparing the biokinetics of deuterated natural (RRR) and synthetic (all-rac) alpha-tocopherol (vitamin E) used a simultaneous ingestion or competitive uptake approach and reported relative bioavailability ratios close to 2:1, higher than the accepted biopotency ratio of 1.36:1. The aim of the current study was to compare the biokinetics of deuterated natural and synthetic vitamin E using a noncompetitive uptake model both before and after vitamin E supplementation in a distinct population. Healthy men (n = 10) carrying the apolipoprotein (apo)E4 genotype completed a randomized crossover study, comprised of two 4-wk treatments with 400 mg/d (RRR-alpha-tocopheryl and all-rac-alpha-tocopheryl acetate) with a 12-wk washout period between treatments. Before and after each treatment period, the subjects consumed a capsule containing 150 mg deuterated alpha-tocopheryl acetate in either the RRR or all-rac form depending on their treatment regimen. Blood was obtained up to 48 h after ingestion, and tocopherols analyzed by LC/MS. After deuterated all-rac administration, plasma deuterated tocopherol maximum concentrations and area under the concentration vs. time curves (AUC) were lower than those following RRR administration. The RRR:all-rac ratios determined from the deuterated biokinetic profiles (maximum concentration; C(max)) and AUCs were 1.35:1 +/- 0.17 and 1.33:1 +/- 0.18, respectively. The 4-wk supplementation with either RRR or all-rac significantly increased plasma alpha-tocopherol concentrations (P < 0.001), but decreased the plasma response to newly absorbed deuterated RRR or all-rac alpha-tocopherol. Using a noncompetitive uptake approach, the relative bioavailability of natural to synthetic vitamin E in apoE4 males was close to the currently accepted biopotency ratio of 1.36:1.

The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men.

The natural folate derivative, 5-methyltetrahydrofolate ([6S]-5-MTHF), could be an option for supplementation and fortification but its bioavailability remains unclear. This study compared the bioavailability of [6S]-5-MTHF with that of folic acid (FA) by measuring plasma folate responses after a single ingestion of equivalent doses of the two folate forms. In a double-blind, crossover study, 13 men (presaturated with FA) received in random order each of the following treatments administered orally at 1-wk intervals: 1) placebo capsule; 2) 500 micro g FA capsule; and 3) 500 micro g [6S]-5-MTHF capsule. Plasma total folate concentrations were measured before and up to 10 h after each treatment (n = 10 samples per treatment). Plasma folate concentrations increased significantly (compared with baseline) from 0.5 to 5 h after both folate treatments. The maximum plasma folate response did not differ between the two treatments (mean +/- SEM, 33.4 +/- 3.9 vs. 31.8 +/- 3.9 nmol/L, P = 0.7, for FA and [6S]-5-MTHF, respectively) and typically occurred in individuals between 0.5 and 3 h postprandially. The area under the plasma folate response curve was significantly greater after both folate treatments compared with placebo, and the response did not differ between the treatments. These results indicate that the short-term bioavailabilities of [6S]-5-MTHF and FA are equivalent. Supplementation with the natural folate derivative could have all the beneficial effects associated with FA, but without the potential disadvantage of masking the anemia of vitamin B-12 deficiency.

Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts.

The photoprotective potential of the dietary antioxidants vitamin C, vitamin E, lycopene, beta-carotene, and the rosemary polyphenol, carnosic acid, was tested in human dermal fibroblasts exposed to ultraviolet-A (UVA) light. The carotenoids were prepared in special nanoparticle formulations together with vitamin C and/or vitamin E. Nanoparticle formulations, in contrast to dimethylsulphoxide, stablized lycopene in the cell culture medium and allowed efficient cellular uptake. The presence of vitamin E in the formulation further increased the stability and cellular uptake of lycopene. UVA irradiation of the human skin fibroblasts led to a 10-15-fold rise in metalloproteinase 1 (MMP-1) mRNA. This rise was suppressed in the presence of low microM concentrations of vitamin E, vitamin C, or carnosic acid but not with beta-carotene or lycopene. Indeed, in the presence of 0.5-1.0 microM beta-carotene or lycopene, the UVA-induced MMP-1 mRNA was further increased by 1.5-2-fold. This increase was totally suppressed when vitamin E was included in the nanoparticle formulation. Heme-oxygenase 1 (HO-1) mRNA expression was strongly induced by UVA irradiation but none of the antioxidants inhibited this effect at the concentrations used in this study. Indeed, beta-carotene or lycopene (0.5-1.0 microM) led to a further 1.5-fold rise in the UVA-induced HO-1 mRNA levels. In conclusion, vitamin C, vitamin E, and carnosic acid showed photoprotective potential. Lycopene and beta-carotene did not protect on their own but in the presence of vitamin E, their stability in culture was improved and the rise in MMP-1 mRNA expression was suppressed, suggesting a requirement for antioxidant protection of the carotenoids against formation of oxidative derivatives that can influence the cellular and molecular responses.