Protocol for multi-site randomized trial of inpatient palliative care for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation.

BACKGROUND: Patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) commonly experience debilitating physical and psychological symptoms during a 3-4-week-hospitalization. During hospitalization, caregivers (i.e., family and friends) also endure immense emotional stress as they witness their loved one struggle with HSCT toxicities. Yet interventions to improve quality of life (QOL) and reduce psychological distress during HSCT are limited. METHODS: We are conducting a multi-site randomized controlled trial of inpatient integrated palliative and transplant care versus usual care in 360 patients hospitalized for HSCT and their caregivers at three academic centers. Intervention participants meet with a palliative care clinician at least twice weekly during the HSCT hospitalization to address their physical and psychological symptoms. Patients assigned to usual care receive all supportive care measures provided by the HSCT team and could be seen by palliative care upon request. We assess patient QOL (Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), post-traumatic stress (PTSD) symptoms (PTSD checklist), symptom burden (Edmonton Symptom Assessment Scale), and fatigue (FACT-Fatigue) as well as caregiver-reported outcomes at baseline, 2 weeks, 3-months, 6-months, and 12-months post-HSCT. The primary endpoint is to compare QOL at week-2 during HSCT hospitalization between the two groups when patients typically experience their QOL nadir during HSCT. CONCLUSIONS: This multi-site trial will define the role of palliative care for improving QOL and care for patients with hematologic malignancies undergoing HSCT and their caregivers.

Is soy protein effective in reducing cholesterol and improving bone health?

Hyperlipidemia associated with cardiovascular health, and bone loss with regard to osteoporosis contribute to increased morbidity and mortality and are influenced by diet. Soy protein has been shown to reduce cholesterol levels, and its isoflavones may improve bone health. The objective of this study was to determine the effects of soy protein on lipid profiles and biomarkers of bone metabolism and inflammation. Ninety men and women (aged 27-87) were randomly assigned to consume 40 g of soy or casein protein daily for three months. Both soy and casein consumption significantly reduced bone alkaline phosphatase (P = 0.011) and body fat % (P < 0.001), tended to decrease tartrate-resistant acid phosphatase (P = 0.066), and significantly increased serum insulin-like growth factor-I (IGF-1) (P < 0.001), yet soy increased IGF-1 to a greater extent (P = 0.01) than casein. Neither treatment affected total cholesterol, HDL cholesterol, LDL cholesterol, or C-reactive protein. These results demonstrate that daily supplementation of soy and casein protein may have positive effects on indices of bone metabolism and body composition, with soy protein being more effective at increasing IGF-1, an anabolic factor, which may be due to soy isoflavones' role in upregulating Runx2 gene expression, while having little effect on lipid profiles and markers of inflammation.

The effects of supplemental vitamin E on hematological parameters in a rat model of ovarian hormone deficiency.

OBJECTIVE: Menopause is associated with adverse changes in hematological parameters. Although the antioxidative and anti-inflammatory properties of vitamin E have been previously demonstrated, the effects of vitamin E on hematopoietic parameters are not well-documented. This study investigated the effects of supplemental vitamin E on hematological parameters in a rat model of ovarian hormone deficiency. METHODS: Twelve-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx). Animals were randomly divided among five treatment groups (n = 12/group) as follows: Sham; Ovx; Ovx + 300, Ovx + 525, or Ovx + 750 mg/kg diet of vitamin E for 100 days. RESULTS: Compared with Sham, ovariectomy increased leukocyte subpopulation counts including lymphocytes (2.01 × 10/mm; 95% confidence interval [CI] 0.11, 4.03; P = 0.03), monocytes (0.35 × 10/mm; 95% CI 0.60, 0.11; P = 0.01), neutrophils (0.72 × 10/mm; 95% CI 0.26, 1.19; P = 0.01), eosinophils (0.07 × 10/mm; 95% CI 0.12, 0.30; P = 0.00), and basophils (0.13 × 10/mm; 95% CI 0.04, 0.21; P = 0.02). Medium dose (MD) (-0.26 × 10/mm; 95% CI -0.47, -0.05; P = 0.007) and high dose (HD) (-0.22 × 10/mm; 95% CI -0.43, -0.01; P = 0.037) supplemental vitamin E attenuated Ovx-induced increases in monocyte counts. Low dose (LD) (-0.55 × 10/mm; 95% CI -0.95, -0.15; P = 0.003), MD (-0.61 × 10/mm; P = 0.001), and HD (-0.54 × 10/mm; 95% CI -0.95, -0.14; P = 0.004) supplemental vitamin E attenuated Ovx-induced increases in neutrophil counts. LD (-0.05 × 10/mm; 95% CI -0.08, -0.11; P = 0.006), MD (-0.05 × 10/mm; 95% CI -0.08, -0.11; P = 0.005), and HD (-0.05 × 10/mm; 95% CI -0.09, -0.01; P = 0.004) supplemental vitamin E also attenuated the Ovx-induced increase in eosinophil counts. Only LD (-0.09 × 10/mm; 95% CI -0.17, -0.02; P = 0.009) supplemental vitamin E attenuated the Ovx-induced increase in basophil counts. The remaining hematological parameters assessed were not significantly affected by ovariectomy or supplemental vitamin E. CONCLUSION: These findings suggest that vitamin E in the form of α-tocopherol acetate may provide protection against ovarian hormone deficiency-associated adverse changes in hematological parameters.

Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel.

BACKGROUND: Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease. METHODS: To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated. RESULTS: In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort. CONCLUSIONS: In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians.

Soy protein with or without isoflavones failed to preserve bone density in gonadal hormone-deficient male rat model of osteoporosis.

Soy with its isoflavones has been shown to positively influence bone mineral density in female ovariectomized rats; hence, we hypothesized a similar effect in orchidectomized (ORX) male rats. Forty male Sprague-Dawley rats, aged 95 days, were divided into 4 groups and were either sham operated (Sham) or ORX. The ORX groups were fed a soy protein-based diet (SOY), an isoflavone-depleted soy protein diet (SOY-), or a casein based diet for 65 days after surgery. Orchidectomy increased the rate of bone turnover, resulting in reduced bone mineral density and bone mineral content by 3.5% and 14%, respectively, and compromised biomechanical properties. The mean femoral length of ORX animals was also significantly shorter than Sham animals, but ORX rats that were fed SOY diet did not experience this reduction in bone length, implicating a role for soy protein in bone growth (4.02 ± 0.02, 3.93 ± 0.01, 3.99 ± 0.02, 3.91 ± 0.01 for Sham, ORX, SOY, SOY-, respectively). The SOY and SOY- positively influenced the biomechanical properties of bone such as yield and ultimate force, the measures of bone elasticity, and plasticity. In terms of bone histomorphometry, the data indicate that SOY- tends to reduce ORX-induced increase in bone turnover as evidenced by suppressed bone formation rate/mineralized surface by about 9%. Overall, our results indicated that soy protein, regardless of its isoflavone content, was unable to prevent the ORX-induced femoral decrease in bone density and mineral content. However, soy may enhance the quality of bone as indicated by increased yield force.

A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia.

Autosomal recessive ataxias are heterogeneous group of disorders characterized by cerebellar atrophy and peripheral sensorimotor neuropathy. Molecular characterization of this group of disorders identified a number of genes contributing to these overlapping phenotypes. Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive form of ataxia caused by mutations in the SETX gene. We report on a consanguineous family with autosomal recessive inheritance and clinical characteristics of AOA2, and no mutations in the SETX gene. We mapped the AOA locus in this family to chromosome 17p12-p13. Sequencing of all genes in the refined region identified a homozygous missense mutation in PIK3R5 that was absent in 477 normal controls. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis.

One-year soy protein supplementation does not improve lipid profile in postmenopausal women.

OBJECTIVE: The risk of heart disease increases significantly in women after menopause mostly because of estrogen deficiency. Soy protein, a good source of isoflavones that are known to bind estrogen receptors, has also been promoted as a dietary means for reducing the risk of heart disease. The aim of this study was to examine the effects of soy protein consumption on heart disease risk in postmenopausal women. METHODS: Moderately hypercholesterolemic postmenopausal women were randomly assigned to consume soy or control foods daily for 1 year. Serum samples were analyzed for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (Apo) A, and Apo B. Sixty-two women completed the study. RESULTS: There was a trend for total cholesterol and high-density lipoprotein cholesterol levels to increase after 1 year of soy protein supplementation (230.04 +/- 6.1 vs 242.57 +/- 6.2 mg/dL, P < 0.1, and 56.87 +/- 2.5 vs 60.33 +/- 2.5 mg/dL, P < 0.1, respectively). There were no significant differences in low-density lipoprotein cholesterol or triglyceride levels; however, a significant increase in Apo B levels (105.5 +/- 5.9 vs 120.21 +/- 5.9 mg/dL; P = 0.002) and a significant decrease in Apo A levels (189.36 +/- 10 vs 173.21 +/- 10 mg/dL; P = 0.009) were seen. CONCLUSIONS: Our data indicate that 1-year soy protein supplementation did not confer cardiovascular benefits, in terms of favorable alterations in the lipid profile, in this cohort of postmenopausal women. These findings, as well as those from other studies, lend credence to the decision of the Food and Drug Administration to reevaluate the soy protein health claim issued a decade ago.

The combination of genistin and ipriflavone prevents mammary tumorigenesis and modulates lipid profile.

BACKGROUND & AIMS: Recent reports have indicated that soy isoflavones may be protective against breast cancer. However, the effects of the synthetic isoflavone, ipriflavone, on mammary tumorigenisis, alone or in combination with genistin, a soy isoflavone, have not been investigated. METHODS: Eighty-eight 36-day-old female Sprague-Dawley rats were divided as follows: Gen (20 mg genistin/kg body weight), Ipr (200 mg ipriflavone/kg body weight), Gen+Ipr (20/200 mg per kg body weight, respectively), and control (solvent vehicle). A week later, animals were injected with a single dose of methylnitrosourea. The isoflavones and solvent vehicle were administered daily via gastric gavage for 84 days post methylnitrosurea injection. RESULTS: The Gen+Ipr group had the lowest number of palpable tumors and adenocarcinomas per group, the least palpable tumors per rat, and the highest serum total and non-HDL cholesterol levels. No changes in circulating levels of indicators of oxidative stress were detected due to treatment. CONCLUSIONS: The findings of this study imply that the combination of genistin and ipriflavone is effective in suppressing mammary methylnitrosurea-induced tumorigenesis and also the lipid environment of the tumor cells that impact tumor growth or proliferation. Further studies are needed to establish the optimal dose of genistin and ipriflavone, individually or in combination, for the prevention of mammary tumorigenesis.

WITHDRAWN: The combination of genistin and ipriflavone prevents mammary tumorigenesis and modulates lipid profile.

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.

Flaxseed reduces plasma cholesterol and atherosclerotic lesion formation in ovariectomized Golden Syrian hamsters.

BACKGROUND: Dietary modification contributes significantly in reducing cardiovascular disease (CVD) risk factors including lowering cholesterol and atherosclerosis. The purpose of this study was to investigate the effects of flaxseed, a rich source of lignans, alpha-linolenic acid and soluble fiber mucilage, on the prevention of ovariectomy-induced rise in total cholesterol and atherosclerotic lesions. METHODS: Seventy-two 6-month-old female Golden Syrian hamsters were either ovariectomized (ovx) or sham-operated (sham) and randomly assigned to six groups (n = 12): sham, ovx, or ovx plus either 17beta-estradiol (E(2), 10 microg/kg body weight) or semi-purified diet adjusted for macronutrients and fiber to contain one of the three doses of flaxseed (7.5, 15, or 22.5%) for 120 days. RESULTS: Ovariectomy significantly elevated plasma total-, HDL-, and free-cholesterol concentrations. Similar to estrogen, all doses of flaxseed were effective in preventing the ovx-induced rise in plasma total cholesterol. Triglyceride concentrations were significantly higher in the flax-fed hamsters. There were no significant differences in plasma non-HDL- and esterified-cholesterol among the treatment groups. Ovariectomy also increased the number of hamsters with lesions and the aortic fatty streak area. All three doses of flaxseed reduced the fatty streak area and the incidence of lesions to levels similar to the sham group. CONCLUSION: The findings of this study show that flaxseed is beneficial in reducing plasma cholesterol and plaque formation induced by ovarian hormone deficiency.

Soy isoflavones prevent ovariectomy-induced atherosclerotic lesions in Golden Syrian hamster model of postmenopausal hyperlipidemia.

OBJECTIVE: Soy isoflavones, as dietary supplements, may reduce the formation of atherosclerotic lesions that increase in women after menopause. The objectives of this study were to determine whether (1) ovariectomized (ovx) hamsters will develop atherosclerotic lesions and (2) soy isoflavones can dose-dependently prevent the ovariectomy-induced rise in plasma cholesterol and atherosclerotic lesions in hamsters. DESIGN: Seventy-two 6-month-old female Golden Syrian hamsters were randomly assigned to six groups: sham-operated; ovx control; ovx + 17beta-estradiol (E(2); 10 microg E(2) per kilogram of body weight); and ovx + 9.5 (low-dose), 19 (medium-dose), or 38 (high-dose) mg isoflavones per kilogram diet. Treatments were initiated immediately after surgery and continued for 120 days. Blood was drawn via abdominal aorta for assessment of circulating lipids, and tissues were collected, including the aortic arch for assessment of atherosclerotic lesions. RESULTS: All three doses of isoflavones prevented the rise in plasma total cholesterol from ovx; and, as the isoflavone dose increases, the cholesterol-lowering effects of isoflavones become more pronounced (7.8%, 11.8%, and 19.6% reductions in total cholesterol for low-dose, medium-dose, and high-dose, respectively). Ovx hamsters developed atherosclerotic lesions without being on an atherogenic diet. Ninety-two percent of hamsters in the ovx control group had atherosclerotic lesions compared with only 8% in sham, 62% in the E(2) group, 29% in the low-dose group, 38% in the medium-dose group, and 58% in the high-dose group. The aortic fatty streak area was approximately 20 times higher in ovx hamsters compared with the sham animals. All doses of isoflavones were able to significantly reduce fatty streak area to that of the sham group. CONCLUSIONS: Soy isoflavones, independent of the protein source, prevent hypercholesterolemia and the formation of atherosclerotic lesions induced by ovarian hormone deficiency in hamsters. The antiatherogenic mechanisms of isoflavones need further investigation.