Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Effect of high-dose intravenous ascorbic acid on cancer patients following ketogenic diet.

BACKGROUND: The role of ascorbic acid in cancer therapy is mainly due to its structural similarity with glucose. When supplemented intravenously in high dose, ascorbic acid can get into the cancer cells and induce apoptosis by causing mitochondrial damage. AIM: The aim was to study the efficacy of high-dose intravenous (IV) ascorbic acid as monotherapy in cancer patients following ketogenic diet and its role in improving the quality of life. RESULTS: C-reactive protein (CRP) and erythrocyte sedimentation rates (ESRs) were considered as parameters to determine the efficacy of the treatment, and substantial decrease in both the levels was observed within 1-week treatment. CRP levels declined from 3.1946 ± 3.2508 mg/L to 1.0606 ± 0.6706 mg/L (P = 2.27E-10), whereas ESR levels declined from 64.1333 ± 38.8253 mm/h to 31.6 ± 16.5520 mm/h (P = 0.0041). A decline in these parameters shows the association of ascorbic acid in reducing the inflammatory response in cancer. The renal effect of ascorbic acid was also studied by analyzing the creatinine level pre- and postascorbic acid treatment sessions, and it raised from 0.8526 ± 0.22904 to 1.1666 ± 0.2894 mg/dL (P = 1.18E-14). This showed the renal impact of ascorbic acid. CONCLUSION: The study highlighted the clinical benefit of IV ascorbic acid in the reduction of inflammatory response in cancer patients. The renal adverse events associated with ascorbic acid alarm the use with caution and therapeutic drug monitoring for ascorbic acid.

Potential of Vitamin D Food Fortification in Prevention of Cancer Deaths-A Modeling Study.

Meta-analyses of randomized controlled trials (RCTs) have estimated a 13% reduction of cancer mortality by vitamin D supplementation among older adults. We evaluated if and to what extent similar effects might be expected from vitamin D fortification of foods. We reviewed the literature on RCTs assessing the impact of vitamin D supplementation on cancer mortality, on increases of vitamin D levels by either supplementation or food fortification, and on costs of supplementation or fortification. Then, we derived expected effects on total cancer mortality and related costs and savings from potential implementation of vitamin D food fortification in Germany and compared the results to those for supplementation. In RCTs with vitamin D supplementation in average doses of 820-2000 IU per day, serum concentrations of 25-hydroxy-vitamin D increased by 15-30 nmol/L, respectively. Studies on food fortification found increases by 10-42 nmol/L, thus largely in the range of increases previously demonstrated by supplementation. Fortification is estimated to be considerably less expensive than supplementation. It might be similarly effective as supplementation in reducing cancer mortality and might even achieve such reduction at substantially larger net savings. Although vitamin D overdoses are unlikely in food fortification programs, implementation should be accompanied by a study monitoring the frequency of potentially occurring adverse effects by overdoses, such as hypercalcemia. Future studies on effectiveness of vitamin D supplementation and fortification are warranted.

The associations of circulating common and uncommon polyunsaturated fatty acids and modification effects on dietary quality with all-cause and disease-specific mortality in NHANES 2003-2004 and 2011-2012.

BACKGROUND: Associations of dietary or supplementary intake of several unsaturated fatty acids and mortality have been widely studied but the results were still hitherto inconsistent or limited. It is still need to explore the effects of these fatty acids by using the objective biomarkers. OBJECTIVE: We aimed to investigate the relevancy of several serum n-3 and n-6 fatty acids with all-cause and disease-specific mortality to confirm their health effects and effects on the associations between dietary quality and all-cause mortality. METHODS: A total of 4132 people from NHANES 2003-2004 and 2011-2012 and the mortality information was confirmed from the NDI. CPH models adjusted for known risk factors were conducted to explore the associations between circulating n-3 and n-6 fatty acids and all-cause or CVD or cancer mortality under complex sampling. We further evaluated their effects on association between dietary quality and all-cause mortality. RESULTS: A total of 437 deaths occurred during the mean follow-up of 83.34 months, including 157 CVD death and 100 cancer death. Serum LA, ALA, EPA and DHA were associated with all-cause mortality (HR in quintile5: LA:0.584, 95%CI: 0.387-0.882, Ptrend = 0.011; ALA:0.626, 95%CI: 0.432-0.907, Ptrend = 0.008; EPA:0.535, 95%CI: 0.375-0.764, Ptrend = 0.001; DHA:0.669, 95%CI: 0.468-0.955, Ptrend = 0.031). Additionally, serum EPA and ALA were respectively related to CVD and cancer mortality (Q5 HR: EPA:0.450, 95%CI: 0.23-0.854, Ptrend = 0.009; ALA:0.387, 95%CI: 0.167-0.900, Ptrend = 0.022). Serum AA, GLA, DGLA and SDA were not associated with any risk of mortality. The effect on all-cause mortality of the lower AHEI scores can be improved by adherence to a higher serum LA, EPA and DHA (in the lowest AHEI strata, LA in tertile3 compared to tertile1 HR:0.596, 95%CI: 0.366-0.970; EPA:0.660, 95%CI: 0.454-0.959; DHA:0.666, 95%CI; 0.444-1.000). CONCLUSIONS: Our results support the recent dietary recommendations to increase the intake of plant-derived and marine-derived n-6 and n-3 to improve the ability of primary and secondary prevention.

Improving vitamin D testing and supplementation in children with newly diagnosed cancer: A quality improvement initiative at Rady Children's Hospital San Diego.

BACKGROUND: Vitamin D deficiency and insufficiency have been associated with poorer health outcomes. Children with cancer are at high risk for vitamin D deficiency and insufficiency. At our institution, we identified high variability in vitamin D testing and supplementation in this population. Of those tested, 65% were vitamin D deficient/insufficient. We conducted a quality improvement (QI) initiative with aim to improve vitamin D testing and supplementation among children aged 2-18 years with newly diagnosed cancer to ≥80% over 6 months. METHODS: An inter-professional team reviewed baseline data, then developed and implemented interventions using Plan-Do-Study-Act (PDSA) cycles. Barriers were identified using QI tools, including lack of automated triggers for testing and inconsistent supplementation criteria and follow-up testing post supplementation. Interventions included an institutional vitamin D guideline, clinical decision-making tree for vitamin D deficiency, insufficiency and sufficiency, electronic medical record triggers, and automated testing options. RESULTS: Baseline: N = 26 patients, four (15%) had baseline vitamin D testing; two (8%) received appropriate supplementation. Postintervention: N = 33 patients; 32 (97%) had baseline vitamin D testing; 33 (100%) received appropriate supplementation and completed follow-up testing timely (6-8 weeks post supplementation). Change was sustained over 24 months. CONCLUSIONS: We achieved and sustained our aim for vitamin D testing and supplementation in children with newly diagnosed cancer through inter-professional collaboration of hematology/oncology, endocrinology, hospital medicine, pharmacy, nursing, and information technology. Future PDSA cycles will address patient compliance with vitamin D supplementation and impact on patients' vitamin D levels.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases.

Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life.

Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations.

BACKGROUND: Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. METHODS: We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25-hydroxyvitamin D (25OHD) levels and BMD Z-scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. RESULTS: Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z-scores, while 25OHD as a continuous variable was not significantly associated with BMD Z-scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). CONCLUSION: There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year-long.

Body surface area-based omega-3 fatty acids supplementation strongly correlates to blood concentrations in children.

Omega-3 fatty acids have been suggested as a complement in cancer treatment, but doses are not established. We performed a dose-finding study in 33 children in remission from cancer. Participants were allocated to a body surface area (BSA) adjusted dose (mg/m2) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (40:60), ranging 233-3448 mg/m2 daily for 90 days. Fatty acid concentration in plasma phospholipids and red blood cells were determined by GC. Supplementation was well tolerated and correlated strongly with blood ω3-fatty acid concentrations and EPA showed the highest increase. Using the ω3-index disregards docosapentaenoic acid (DPA), which increased 30-43% in our study motivating an EDD-index (∑EPA,DPA,DHA). The ratio between arachidonic acid and EPA or DHA showed negative exponential trends. Dose per BSA enabled an individualized omega-3 supplementation decreasing the variation referred to interindividual differences. Based on our results, we suggest a dose of 1500 mg/m2 BSA for further studies.

Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan.

Importance: Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. Objective: To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. Design, Setting, and Participants: Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. Exposures: Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. Main Outcomes and Measures: Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. Results: A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled. In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: ß, -0.38; 95% CI, -0.55 to -0.21; P < .001; and S-IgG: ß, -0.39; 95% CI, -0.54 to -0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-IgG levels: 0.2 [IQR, 0.1-0.5] vs 0.1 [IQR, 0-0.3], P = .02; S-IgG levels: 0.15 [IQR, 0-0.3] vs 0.1[IQR, 0-0.2], P = .02). Conclusions and Relevance: In this cross-sectional study of Japanese patients with cancer and HCWs, the seroprevalence of SARS-CoV-2 antibodies did not differ between the 2 groups; however, findings suggest that comorbid cancer and treatment with systemic therapy, including chemotherapy and immune checkpoint inhibitors, may influence the immune response to SARS-CoV-2.

CRAFT for NMR lipidomics: Targeting lipid metabolism in leucine-supplemented tumor-bearing mice.

Lipid profiling by 1 H-NMR has gained increasing utility in many fields because of its intrinsically quantitative, nondestructive nature and the ability to differentiate small molecules based on their spectral location. Most nuclear magnetic resonance (NMR) techniques for metabolite quantification use frequency domain analysis that involves many user-dependent steps such as phase and baseline correction and quantification by either manual integration or peak fitting. Recently, Bayesian analysis of time-domain NMR data has been shown to reduce operator bias and increase automation in NMR spectroscopy. In this study, we demonstrate the use of CRAFT (complete reduction to amplitude-frequency table), a Bayesian-based approach to automate processing in NMR-based lipidomics using lipid standards and tissue samples of healthy and tumor-bearing mice supplemented with leucine. Complex mixtures of lipid standards were prepared and examined using CRAFT to validate it against conventional Fourier transform (FT)-NMR and derive a fingerprint to be used for analyzing lipid profiles of serum and liver samples. CRAFT and FT-NMR were comparable in accuracy, with CRAFT achieving higher correlation in quantifying several lipid species. Analysis of the serum lipidome of tumor-bearing mice revealed hyperlipidemia and no signs of hepatic triglyceride accumulation compared with that of the healthy group demonstrating that the tumor-bearing mice were in a state of precachexia. Leucine-supplementation was associated with minimal changes in the lipid profile in both tissues. In conclusion, our study demonstrates that the CRAFT method can accurately identify and quantify lipids in complex lipid mixtures and murine tissue samples and, hence, will increase automation and reproducibility in NMR-based lipidomics.

Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: a comprehensive systematic review with meta-analysis.

CONTEXT: Recent studies have outlined the potential role of dietary factors in patients who have survived cancer. OBJECTIVE: The aim of this study was to summarize the evidence of the relation between dietary intake of phytoestrogens and their blood biomarkers and, overall, cancer-specific mortality and recurrence in patients with cancer. DATA SOURCES: A systematic search of PubMed, EMBASE, and Web of Science databases of studies published up to September 2019 was performed. Databases were searched for prospective and retrospective cohort studies reporting on dietary phytoestrogen intake and/or blood biomarkers and the outcomes investigated. DATA EXTRACTION: Data were extracted from each identified study using a standardized form. DATA ANALYSIS: Twenty-eight articles on breast, lung, prostate, and colorectal cancer, and glioma were included for systematic review. Given the availability of studies, a quantitative meta-analysis was performed solely for breast cancer outcomes. A significant inverse association among higher dietary isoflavone intake, higher serum/plasma enterolactone concentrations, and overall mortality and cancer recurrence was found. Among other cancer types, 2 studies reported that higher serum enterolactone and higher intake of lignans were associated with cancer-specific survival for colorectal cancer and glioma, respectively. CONCLUSIONS: Dietary phytoestrogens may play a role in survival from breast cancer ; evidence regarding other cancers is too limited to draw any conclusions.

Systematic study of the selenium fractionation in human plasma from a cancer prevention trial using HPLC hyphenated to ICP-MS and ESI-MS/MS.

This work represents the first systematic speciation study of selenium (Se) in plasma from subjects participating in a pilot study for a cancer prevention trial (PRECISE). This involved supplementation of elderly British and Danish individuals with selenised yeast for 6 months and 5 years, respectively, at 100, 200, and 300 µg Se/day or placebo. Speciation data was obtained for male plasma using HPLC-ICP-MS and HPLC-ESI-MS/MS. With the proposed strategy, approximately 1.5 mL of plasma was needed to determine total Se concentration and the fractionation of Se in high molecular weight (HMW) and low molecular weight (LMW) pools, and for quantification and identification of small Se species. For the first time, Se-methyl-selenocysteine (MSC) and methyl-2-acetamido-2deoxy1-seleno-ß-D-galactopyranoside (Selenosugar-1) were structurally confirmed in plasma after supplementation with selenised yeast within the studied range. Determination of selenomethionine (SeMet) incorporated non-specifically into albumin (SeALB) was achieved by HPLC-ICP-MS after hydrolysis. By subtracting this SeMet concentration from the total Se in the HMW pool, the concentration of Se incorporated into selenoproteins was calculated. Results from the speciation analysis of the free Se metabolite fraction (5% of total plasma Se) suggest a significant increase in the percentage of Se (as SeMet plus Selenosugar-1) of up to 80% of the total Se in the LMW fraction after 6 months of supplementation. The Se distribution in the HMW fraction reflects a significant increase in SeALB with Se depletion from selenoproteins, which occurs most significantly at doses of over 100 µg Se/day after 5 years. The results of this work will inform future trial design. Graphical abstract.

Low Vitamin D Status in a Cancer Patient Population from Franconia, Germany.

BACKGROUND: Vitamin D has been shown to be associated with reduced risk and severity of COVID-19 and exerts regulating effects on all hallmarks of cancer. The goal of this study was to analyze the vitamin D status of a cancer patient cohort from our clinic in the Franconian region, Germany. METHODS: 25-hydroxyvitamin D concentrations were available for 116 patients included in prospective trials in our clinic. Associations of vitamin D with anthropometric and blood parameters were investigated using Kendall's τ correlation coefficients and linear regression. RESULTS: A total of 57 patients (49.1%) were vitamin D deficient (<20 ng/mL), and 92.2% did not meet the recommended vitamin D level of 40 ng/mL. There was a strong negative association between vitamin D and leukocyte count (τ = -0.173, p = 0.007) and C-reactive protein concentration (τ = -0.172, p = 0.007). In linear regression, the most important variables for predicting vitamin D levels were (in order of decreasing importance) season, fat mass index, platelet, and leukocyte count. CONCLUSIONS: Despite appeals towards medical societies to target widespread vitamin D deficiency in Germany more than 10 years ago, our data indicate that these have been without avail. Low vitamin D levels in cancer patients should be corrected using reasonable sun exposure and supplements.

Ameliorative effects of ginsenosides on myelosuppression induced by chemotherapy or radiotherapy.

BACKGROUND: and ethnopharmacological relevance: As the major side effect of radiotherapy or chemotherapy, myelosuppression usually leads to anemia, hemorrhage, immunosuppression, and even fatal infections, which may discontinue the process of cancer treatment. As a result, more and more attention is paid to the treatment of myelosuppression. Ginseng, root of Panax ginseng Meyer (Panax ginseng C. A. Mey), is considered as the king of herbs in the Orient, particularly in China, Korea and Japan. Ginsenosides, the most important active ingredients of ginseng, have been shown to have a variety of therapeutic effects, such as neuroprotective, anti-cancer and anti-diabetic properties. Considering that ginsenosides are closely associated with the pathogenesis of myelosuppression, researchers have carried out a few experiments on ginsenosides to attenuate myelosuppression induced by chemotherapy or radiotherapy in recent years. AIM OF THE STUDY: To summarize previous studies about the effects of ginsenosides on alleviating myelosuppression and the mechanisms of action. METHODS: Literatures in this review were searched in PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, and ScienceDirect. RESULTS: Ginsenosides play an important role in relieving myelosuppression predominantly by restoring hematopoiesis and immunity. CONCLUSION: Ginsenosides might be potential candidates for the treatment of myelosuppression induced by chemotherapy or radiotherapy.

Non-classical effects of vitamin D: Non-bone effects of vitamin D.

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of "vitamin-hormone D", and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO) are also summarised.

Effect of Papaya Leaves (Carica papaya L.) Extract on Immune Response (TLR-7, TLR-9) and Inflammation (COX-2) in Rats Induces DMBA (7,12-Dimethylbenz[a]antrasen).

BACKGROUND AND OBJECTIVE: TLR is known to regulate the immune system in cancer. TLR-7 and TLR-9 can enhance the antitumor immune system in many types of solid tumors. Cyclooxygenase-2 (COX-2) is a biomarker of inflammation. This study aimed to investigate the effect of papaya leaves extract on immune response (TLR 7, TLR 9) and inflammation (COX-2) in rats induced DMBA. MATERIALS AND METHODS: This experimental study used Sprague dawley female rats of age more less 50 days. Rats were divided into 4 groups: Negative Control (NC), Positive Control (PC), Cancer Drug Doxorubicin (DOXO) and Papaya Leaves Extract (PLE). The study was conducted for 13 weeks. DMBA induction performed for 5 weeks with administration of 2 times per week. RESULTS: the expression of TLR-7 of PLE and DOXO was higher than PC groups significantly different (p<0.05). The expression of TLR-9 of PLE was higher than NC, PC and DOXO groups but not significantly different (p>0.05) while the expression of COX-2 of PLE and DOXO groups was lower than NC and PC groups but not significantly different (p>0.05). CONCLUSION: It can be concluded that papaya leaves extract can improve the immune system and reduce inflammation. It shows that papaya leaves extract has potent as anti-cancer.

Use of plasma-free amino acids as biomarkers for detecting and predicting disease risk.

This paper reviews developments regarding the use of plasma-free amino acid (PFAA) profiles as biomarkers for detecting and predicting disease risk. This work was initiated and first published in 2006 and was subsequently developed by Ajinomoto Co., Inc. After commercialization in 2011, PFAA-based tests were adopted in over 1500 clinics and hospitals in Japan, and numerous clinician-led studies have been performed to validate these tests. Evidence is accumulating that PFAA profiles can be used for diabetes prediction and evaluation of frailty; in particular, decreased plasma essential amino acids could contribute to the pathophysiology of severe frailty. Integration of PFAA evaluation as a biomarker and effective essential amino acid supplementation, which improves physical and mental functions in the elderly, could facilitate the development of precision nutrition, including personalized solutions. This present review provides the background for the technology as well as more recent clinical findings, and offers future possibilities regarding the implementation of precision nutrition.

Electrolytes supplementation can decrease the risk of nephrotoxicity in patients with solid tumors undergoing chemotherapy with cisplatin.

BACKGROUND: Cisplatin is an important drug in the treatment of various Cancers. However, this drug causes nephrotoxicity that is linked to electrolyte derangement. The aim of this study was to evaluate the effect of electrolyte supplementation in reducing kidney injury in patients receiving cisplatin-based regimen. METHODS: This was non-randomized interventional study conducted at Ocean Road Cancer Institute (ORCI) among patients with confirmed solid tumors. Patients who received cisplatin-based chemotherapy at a dose of ≥50 mg with intravenous normal saline supplemented with Magnesium, Calcium and Potassium (triple electrolyte supplementation) were compared with those who received cisplatin-based chemotherapy with normal saline alone. The patients were followed up for 4 weeks and serum creatinine was measured at every visit. Nephrotoxicity was defined as serum creatinine elevation > 1.5 times that at baseline. RESULTS: A total of 99 patients were recruited, whereby 49 patients (49.5%) received electrolyte supplementation (treatment group) and 50 patients (51.5%) did not receive electrolyte supplementation (control group). The incidence risk of nephrotoxicity was 20.41% (n = 10) in the treatment group and 54% (n = 27) in the control group. Patients in the control group were 2.6 times more likely to experience nephrotoxicity as compared to treatment group [Relative Risks (RR); 2.6, 95%CI; 1.5-4.9, P < 0.0001]. The most common malignancy was cervical cancer, n = 43 (87.8%) in treatment group and n = 45 (90.0%) in the control group (P = 0.590). The Kaplan-Meier analysis and the log-rank test revealed that electrolytes supplementation was associated with extended survival with less nephrotoxicity incidences [P = 0.0004; Hazard ratio (HR) 0.3149; 95% CI 0.165 to 0.6011]. CONCLUSIONS: Electrolytes supplementation decreases the risk of nephrotoxicity after chemotherapy with cisplatin. A randomized controlled trial with a larger sample size is recommended to evaluate the robustness of these findings.