"Living Well with Chronic Pain": Integrative Pain Management via Shared Medical Appointments.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary, nonpharmacological, integrative approach that uses shared medical appointments to improve health-related quality of life and reduce opioid medication use in patients with chronic pain. DESIGN: This is a retrospective, pre-post review of "Living Well with Chronic Pain" shared medical appointments (August 2016 through May 2018). SETTING: The appointments included eight 3-hour-long visits held once per week at an outpatient wellness facility. SUBJECTS: Patients with chronic, non-cancer-related pain. METHODS: Patients received evaluation and evidence-based therapies from a team of integrative and lifestyle medicine professionals, as well as education about nonpharmacological therapeutic approaches, the etiology of pain, and the relationship of pain to lifestyle factors. Experiential elements focused on the relaxation techniques of meditation, yoga, breathing, and hypnotherapy, while patients also received acupuncture, acupressure, massage, cognitive behavioral therapy, and chiropractic education. Patients self-reported data via the Patient-Reported Outcomes Measurement Information System (PROMIS-57) standardized questionnaire. Use of opioid medications was evaluated in morphine milligram equivalents. RESULTS: A total of 178 participants completed the PROMIS-57 questionnaire at the first and the last visits. Statistically significant improvements in all domains (Physical Functioning, Anxiety, Depression, Fatigue, Social Roles, Pain Interference, and Sleep Disturbance) were observed (P < 0.001) between the pre-intervention (visit 1) and post-intervention (visit 8) scores. Average opioid use decreased nonsignificantly over the 8-week intervention, but the lower rate of opioid use was not sustained at 6 and 12 months' follow-up. CONCLUSIONS: Patients suffering from chronic pain who participated in a multidisciplinary, nonpharmacological treatment approach delivered via shared medical appointments experienced reduced pain and improved measures of physical, mental, and social health without increased use of opioid pain medications.

Sleep, quality of life, and depression in endometrial cancer survivors with obesity seeking weight loss.

PURPOSE: Incidence and mortality rates of uterine cancer are increasing and, obesity, which is also rising, has been associated with uterine cancer development and mortality. A recent study found that poor sleep quality is common among endometrial cancer survivors and those with obesity had more sleep disturbances than those having normal weight. However, it is unclear if higher levels of obesity (Class III, BMI ≥ 40 kg/m2), which are rising rapidly, are differentially associated with sleep as well as depression and quality of life in endometrial cancer survivors. METHODS: We evaluated sleep, depression, and quality of life in 100 Stage I endometrial cancer survivors with obesity seeking weight loss enrolled in a lifestyle intervention (NCT01870947) at baseline. RESULTS: The average age was 60 years and mean BMI was 42.1 kg/m2 with 58% having a BMI ≥ 40 kg/m2. Most survivors (72.3%) had poor sleep quality and most (71.2%) reported sleeping < 7 h/night. Survivors with class III compared with class I obesity had significantly more sleep disturbances and daytime dysfunction; and, those with poor sleep had higher depression and lower quality of life. Survivors with a BMI ≥ 50 kg/m2 (~ 25%) had the highest levels of depression and lowest physical and emotional well-being. CONCLUSIONS: Our results reveal that endometrial cancer survivors with class III compared with class I obesity have poorer sleep quality, higher depression, and lower quality of life. Given the rising rates of obesity and uterine cancer mortality, interventions to combat both obesity and poor sleep are needed.

Plant-based, no-added-fat or American Heart Association diets: impact on cardiovascular risk in obese children with hypercholesterolemia and their parents.

OBJECTIVE: To perform a randomized trial to determine whether there is cardiovascular disease (CVD) risk reduction from a plant-based (PB), no-added-fat diet and the American Heart Association (AHA) diet in children. STUDY DESIGN: A 4-week (April 20, 2013 to May 18, 2013), prospective randomized trial was undertaken in a large, Midwestern hospital system's predominantly middle class outpatient pediatric practices. Thirty children (9-18 years of age) parent pairs with a last recorded child body mass index >95th percentile and child cholesterol >169 mg/dL were randomized to PB or AHA with weekly 2-hour classes of nutrition education. RESULTS: Children on PB had 9 and children on AHA had 4 statistically significant (P < .05) beneficial changes from baseline (mean decreases): body mass index z-score(PB) (-0.14), systolic blood pressure(PB) (-6.43 mm Hg), total cholesterol(PB) (-22.5 mg/dL), low-density lipoprotein(PB) (-13.14 mg/dL), high-sensitivity C-reactive protein(PB) (-2.09 mg/L), insulin(PB) (-5.42 uU/mL), myeloperoxidase(PB/AHA) (-75.34/69.23 pmol/L), mid-arm circumference(PB/AHA) (-2.02/-1.55 cm), weight(PB/AHA) (-3.05/-1.14 kg), and waist circumference(AHA) (-2.96 cm). Adults on PB and AHA had 7 and 2, respectively, statistically significant (P < .05) beneficial changes. The significant change favoring AHA was a 1% difference in children's waist circumference. Difficulty shopping for food for the PB was the only statistically significant acceptability barrier. CONCLUSIONS: PB and the AHA in both children and adults demonstrated potentially beneficial changes from baseline in risk factors for CVD. Future larger, long-term randomized trials with easily accessible PB foods will further define the role of the PB in preventing CVD.

Improving Outcomes in Allogeneic Transplantation and Chronic Graft-versus-Host Disease Patients through Lifestyle Medicine: Current Landscape and Future Directions.

Although lifestyle interventions have shown promise in oncology and for cancer survivorship, their potential to improve outcomes in allogeneic hematopoietic cell transplantation (allo-HCT) and chronic graft-versus-host disease (cGVHD) patients remains to be fully explored. Given the high rates of cardiovascular disease, metabolic syndrome, and secondary malignancy in this patient population, lifestyle modifications can serve as a vital frontline defense against chronic diseases. Current research has illuminated the potential supportive role of lifestyle interventions in the solid cancer patient population, which is encouraging future lifestyle medicine research for patients with hematologic malignancies and allo-HCT recipients. Recent studies have indicated the pernicious effects of poor lifestyle choices on the course of cGVHD development and survival. The intersection between certain pillars of lifestyle medicine (ie, nutrition and exercise) and allo-HCT patient outcomes has been more well documented than that of other pillars (ie, social relationships and spirituality). Ongoing randomized trials studying the effects of exercise and nutrition on clinical outcomes in cGVHD and allo-HCT patients may provide important future evidence of the role of lifestyle medicine in this patient population. In this review, we describe the current landscape of lifestyle medicine in allo-HCT and cGVHD, its potential, and propose ways to further develop this evolving field of medicine.

Lifestyle Medicine-Focused Shared Medical Appointments to Improve Risk Factors for Chronic Diseases and Quality of Life in Breast Cancer Survivors.

OBJECTIVES: Poor lifestyle choices play a significant role in the development and progression of preventable chronic diseases, including cancer. In this study, we evaluate the effectiveness of a comprehensive lifestyle medicine intervention on chronic disease risk factors and quality of life in breast cancer survivors. DESIGN: This is a retrospective review of a clinical program from January 2016 to July 2017. SETTINGS/LOCATION: It includes seven 2-h group medical visits held every other week at an outpatient wellness facility. SUBJECTS: Eligible participants are breast cancer survivors who have completed treatment, including those who remain on hormonal therapy. INTERVENTION: Patients receive education and experience in nutrition, culinary medicine, physical activity, and stress relief practices. OUTCOME MEASURES: Participants' weight, body mass index (BMI), body fat mass, lean body mass, and percent body fat were measured at visit 1 and visit 7. Standard validated questionnaires were used to measure perceived stress, depression, patient activation, physical and mental quality of life, dietary fat consumption, and dietary fruit, vegetable, and fiber consumption. RESULTS: A total of 31 patients participated in the group visits. Pre-post comparison data were not available for 10 patients. More than three-quarters of the 21 breast cancer survivors who attended 5 or more of the 7 group visits and provided data at the first and the last group visit decreased their body weight. On average, patients lost 4.9 pounds (-2.6%, p < 0.01), and their BMI decreased by 0.8 kg/m2 (-2.5%, p < 0.01). Changes in psychosocial variables of perceived stress, depression, patient activation, and quality of life trended in a positive direction, but did not reach statistical significance. Patients reported a significant decrease in average weekly fat consumption (-31.5%, p < 0.01). Most patients found the program educational and enjoyable, and nearly half of them described it as life changing. CONCLUSIONS: Breast cancer survivors could employ the prescribed lifestyle modifications to produce clinically relevant health benefits. Interdisciplinary teams of health care professionals may help breast cancer survivors with chronic diseases implement evidence-based, individualized, and effective lifestyle prescription through group medical visits.

Comprehensive Lifestyle Modification Intervention to Improve Chronic Disease Risk Factors and Quality of Life in Cancer Survivors.

OBJECTIVES: Healthy lifestyle modifications, including weight management, regular physical activity, prudent diet, and stress relief, have been identified as key components of tertiary cancer prevention. In this study, we evaluate the effectiveness of a comprehensive, lifestyle medicine intervention, Lifestyle 180®, on chronic disease risk factors and quality of life in cancer survivors. DESIGN: Retrospective subgroup analysis of a clinical program. SETTINGS/LOCATION: An outpatient medical facility. SUBJECTS: Lifestyle 180 participants with a diagnosis of past cancer. INTERVENTION: Sixty-four hours of intensive nutrition, culinary medicine, physical activity, and stress relief practices over a 6-month period, with 9- and 12-month follow-up. OUTCOME MEASURES: Pre-postanalysis (baseline vs. 12 months) included biometrics: weight, body mass index (BMI), waist circumference, and blood pressure; standard laboratory tests: lipids, C-reactive protein, fasting insulin/glucose, and insulin resistance; and empirically validated questionnaires: perceived stress, depression, and quality of life. RESULTS: Fifty-eight cancer survivors participated in Lifestyle 180. Average age was 63 years, roughly 75% of participants were female, and the greatest majority had a diagnosis of breast, prostate, or skin cancer. Diagnosis of hyperlipidemia, hypertension, diabetes, and prediabetes presented in 47%, 57%, 22%, and 50% of patients, respectively. Forty-five percent of patients were obese, 24% were overweight, and 16% were depressed. At 12 months, participants lost an average of 14 pounds (-6.6%, p < 0.001) and 2.6 inches off their waist (-5.9%, p < 0.001). BMI decreased significantly by an average of 2.4 kg/m2 (-6.8%, p < 0.001). Significant decreases from well-managed baseline levels also occurred in most measured biomarkers (average change: high-density lipoprotein +3.3 mg/dL, p < 0.05; triglycerides -23.0 mg/dL, p < 0.01; C-reactive protein -1.3 mg/L, p < 0.01; fasting insulin -4.2 µU/mL, p < 0.05; and homeostasis model assessment-insulin resistance -1.5, p < 0.01; n = 40). Changes in psychosocial variables included significant improvements in perceived stress (-20%, p < 0.01) and quality of life (+54%, p < 0.001). We were unable to detect a difference in depressive symptoms. CONCLUSIONS: Cancer survivors participating in a comprehensive intervention could employ the prescribed lifestyle modifications to produce clinically relevant health and quality-of-life benefits. These data support the American Cancer Society (ACS) and American Society of Clinical Oncology (ASCO) recommendations to incorporate healthy lifestyle modifications into long-term cancer survivorship care.

Meningothelioma as the predominant histological subtype of midline skull base and spinal meningioma.

OBJECT: This study was undertaken to test a hypothesis that meningiomas of the midline skull base and spine are predominantly of the meningothelial histological subtype. METHODS: The cases of 794 consecutive patients who underwent resection for meningioma at the Cleveland Clinic between January 1991 and March 2004 were reviewed retrospectively. The authors analyzed the relationship between the tumors' histological subtypes and sites of origin in the 731 patients from this group who harbored tumors that were determined to be benign histologically (World Health Organization Grade I). Meningothelial meningiomas (MMs) accounted for 63.5% (464/731) of the Grade I tumors. The incidence of MM according to the site of origin was as follows: 84.9% (186/219) in the midline skull base, 58.3% (35/60) in the lateral skull base, 48.5% (183/377) in a non-skull base location, and 80% (60/75) in spinal locations. The incidence of MM in the midline skull base and spinal locations were significantly higher than in non-skull base or lateral skull base locations. CONCLUSIONS: Meningiomas of the midline neuraxis are predominantly meningotheliomas. Analysis of the increasingly available data on genetic and topographic characteristics of MMs suggests that they may represent a unique entity, contrary to the prevailing belief that all benign meningiomas are identical tumors.

Acetyl-11-keto-beta-boswellic acid (AKBA) is cytotoxic for meningioma cells and inhibits phosphorylation of the extracellular-signal regulated kinase 1 and 2.

Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata (frankincense). AKBA has been recently identified as a novel, orally active, non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro. Because natural pentacyclic triterpenes have an antiproliferative effect against different tumor types, we investigated the effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas, common central nervous system tumors. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2-8 microM. At similar, physiologically achievable concentrations, AKBA rapidly (within minutes) and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk-1 and Erk-2) in meningioma cells stimulated with platelet-derived growth factor BB. High expression level of 5-LO was detected in primary meningioma cells and surgical specimens by immunoblotting analysis, suggesting the possible role of 5-LO in meningioma tumorigenesis. Considering the critical importance of the Erk-1/2 signal transduction pathway not only in meningiomas but in other human neoplasms, the interruption of signaling through this evolutionarily conserved pathway might be one of the mechanisms by which AKBA induces suppression of proliferation and apoptosis of different tumor types.

A way to reverse CAD?

PURPOSE: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. METHODS: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. RESULTS: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants­a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. CONCLUSION: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.

Docosahexaenoic acid, inflammation, and bacterial dysbiosis in relation to periodontal disease, inflammatory bowel disease, and the metabolic syndrome.

Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has been used to treat a range of different conditions, including periodontal disease (PD) and inflammatory bowel disease (IBD). That DHA helps with these oral and gastrointestinal diseases in which inflammation and bacterial dysbiosis play key roles, raises the question of whether DHA may assist in the prevention or treatment of other inflammatory conditions, such as the metabolic syndrome, which have also been linked with inflammation and alterations in normal host microbial populations. Here we review established and investigated associations between DHA, PD, and IBD. We conclude that by beneficially altering cytokine production and macrophage recruitment, the composition of intestinal microbiota and intestinal integrity, lipopolysaccharide- and adipose-induced inflammation, and insulin signaling, DHA may be a key tool in the prevention of metabolic syndrome.

Major cereal grain fibers and psyllium in relation to cardiovascular health.

Numerous studies reveal the cardiovascular benefits of consuming dietary fiber and, especially, cereal fiber. Cereal fiber is associated with cardiovascular risk reduction through multiple mechanisms and consuming a variety of cereal fiber sources offers health benefits specific to the source. Certain cereal fibers have been studied more extensively than others and provide greater support for their incorporation into a healthful diet. ß-glucan from oats or barley, or a combination of whole oats and barley, and soluble fiber from psyllium reduces the risk of coronary heart disease; inulin-type fructans added to foods and beverages may modestly decrease serum triacylglycerols; arabinoxylan and resistant starch may improve glycemic control. Individuals with low cereal fiber intake should increase their intake of whole grains in order to receive the benefits of whole grains in addition to fiber. For those adjusting to the texture and palatability of whole grains, turning to added-fiber products rich in ß-glucan and psyllium may allow them to reach their fiber goals without increasing caloric intake.

Mitigating preventable chronic disease: Progress report of the Cleveland Clinic's Lifestyle 180 program.

BACKGROUND: Poor lifestyle choices are key in development and progression of preventable chronic diseases. The purpose of the study was to design and test a program to mitigate the physical and fiscal consequences of chronic diseases. METHODS: Here we report the outcomes for 429 participants with one or more chronic conditions, including obesity, hypertension, hyperlipidemia and diabetes mellitus, many of whom had failed traditional disease management programs, who enrolled into a comprehensive lifestyle intervention. The Lifestyle 180 program integrates nutrition, physical activity and stress management interventions and was conducted at the Wellness Institute of the Cleveland Clinic, United States. An intensive 6 week immersion course, with 8 hours of group instruction per week, was followed by 3 follow-up, 4 hour-long sessions over the course of 6 months. RESULTS: Changes in biometric (weight, height, waist circumference, resting heart rate and blood pressure) and laboratory variables (fasting lipid panel, blood glucose, insulin, hemoglobin A1c, ultra sensitive C-reactive protein) at 6 months were compared with baseline (pre-post analysis). At week 30, biometric and laboratory data were available for 244 (57%) and 299 (70%) participants, respectively. These had a mean ± SD reduction in weight (6.8 ± 6.9 kg, P < 0.001), waist circumference (6.1 ± 7.3 cm, P < 0.001), glucose (4.5 ± 29.6 mg/dL or 0.25 ± 1.64 mmol/L, P = 0.009), triglycerides (26.4 ± 58.5 mg/dL or 0.30 ± 0.66 mmol/L, P < 0.001), low-density lipoprotein cholesterol (LDL) (7.9 ± 25.1 mg/dL or 0.2 ± 0.65 mmol/L, P < 0.001), hemoglobin A1c (HgbA1c) (0.20 ± 0.64%, P = 0.001), insulin (3.8 ± 11 microU/ml or 26.6 ± 76.4 ρmol, P < 0.001) and ultra sensitive C-reactive protein (US - CRP) (0.9 ± 4.8 mg/dL or 7.3 ± 40.2 nmol/L, P = 0.012), an increase in mean high-density lipoprotein cholesterol (HDL) (3.7 ± 8.4 mg/dL or 0.1 ± 0.22, P < 0.001), and decreased use of medications. CONCLUSION: Implementation of a comprehensive lifestyle modification program among adults with common chronic conditions results in significant and clinically meaningful improvements in biometric and laboratory outcomes after 6 months.

Increased expression of 5-lipoxygenase in high-grade astrocytomas.

OBJECTIVE: 5-Lipoxygenase (5-LO) oxidizes arachidonic acid into proinflammatory eicosanoids that may promote tumorigenesis. In this study, we investigated whether 5-LO is expressed in human astrocytomas and what effect its expression may have on patient outcome. METHODS: Increased 5-LO messenger ribonucleic acid and protein expression was detected by the polymerase chain reaction and antibody-based approaches, respectively, in surgical astrocytoma specimens and established glioblastoma multiforme cell lines compared with primary cell culture from the human white matter. RESULTS: Immunohistochemical analysis revealed predominantly nuclear 5-LO staining in 44 of 49 glioblastoma multiforme samples (90%), 8 of 10 (80%) anaplastic astrocytomas samples, and 3 of 13 (23%) low-grade astrocytoma samples analyzed. Double-staining experiments with anti-CD-68 (macrophage/microglial marker) and anti-5-LO antibodies suggest that both CD-68-positive and CD-68-negative tumor cells express 5-LO protein. Staining of 5-LO was significantly more frequent in high-grade than in low-grade tumors (P = 0.001). Patients whose tumors expressed 5-LO were significantly older, had lower preoperative Karnofsky performance scores and shorter survival than patients whose tumors did not express 5-LO. After adjusting for pathological diagnosis and age, respectively, neither Karnofsky performance score nor survival were significantly associated with 5-LO staining. CONCLUSION: These data indicate that 5-LO is overexpressed in high-grade astrocytomas and supports the idea that eicosanoids may play a role in tumorigenesis of these brain tumors.

Cytotoxic action of acetyl-11-keto-beta-boswellic acid (AKBA) on meningioma cells.

Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate of the tree Boswellia serrata (frankincense). Because pentacyclic triterpenes have antiproliferative and cytotoxic effects against different tumor types, we investigated whether AKBA would act in a similar fashion on primary human meningioma cell cultures. Primary cell cultures were established from surgically removed meningioma specimens. The number of viable cells in the absence/presence of AKBA was determined by the non-radioactive cell proliferation assay. The activation status of the proliferative cell marker, extracellular signal-regulated kinase-1 and -2 (Erk-1 and Erk-2) was determined by immunoblotting with the antibody that recognizes the activated form of these proteins. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 - 8 microM. At low micromolar concentrations, AKBA rapidly and potently inhibited the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB. The cytotoxic action of AKBA on meningioma cells may be mediated, at least in part, by the inhibition of the Erk signal transduction pathway. Because of the central role the Erk pathway plays in signal transduction and tumorigenesis, further investigation into the potential clinical use for AKBA and related boswellic acids is warranted.