Taste alteration and its relationship with nutritional status among cancer patients receiving chemotherapy, cross-sectional study.

The aim of this study is to determine the prevalence of taste alterations (TAs) during chemotherapy and their association with nutritional status and malnutrition. In addition to the associated factors with TA, including sociodemographic health-related factors and clinical status, and to investigate coping strategies to manage TA. A multicenter cross-sectional design study was conducted on 120 cancer patients aged at least 18 who had been undergoing at least one round of chemotherapy. TAs were evaluated using the chemotherapy-induced taste alteration scale (CiTAS), the malnutrition universal screening tool (MUST) was used for nutritional screening, the antineoplastic side effects scale (ASES) was used for subjective assessment of chemotherapy side effects, and the Charlson comorbidity index (CCI) was used for comorbidity assessment. SPSS21 software was used to analyze the data, and the independent T-test and one-way ANOVA test were used to determine the association between TAs and a variety of related variables. The prevalence of TAs was 98.3%. Among participants, 48.3% were at low risk of malnutrition, 20% at medium risk, and 31.7% at high risk. Malnutrition risk was associated with taste disorders (p<0.05). Patients' age, gender, educational level, and physical status were associated with TAs (p<0.05). Type of cancer, chemotherapy regimen, and number of chemotherapy cycles were also associated with TAs (p<0.05). A variety of antineoplastic side effects were associated with TAs (p<0.05), including nausea, vomiting, dry mouth, sore mouth and throat, excessive thirst, swallowing difficulty, appetite changes, weight loss, dizziness, lack of energy, disturbed sleep, anxiety, and difficulty concentrating. TAs were associated with an increased number of comorbidities, and individuals with diabetes, pulmonary diseases, and hypertension were associated with TAs (P<0.05). Patients in this study rarely practice self-management strategies to cope with TAs. A high prevalence (98.3%) of TAs in cancer patients receiving chemotherapy was found, and it was linked to a variety of negative outcomes. Chemotherapy-induced TAs are an underestimated side effect that requires more attention from patients and health care providers.

Fluoroscopy-Guided Salvage Photodynamic Therapy Combined with Nanoparticle Albumin-Bound Paclitaxel for Locally Advanced Esophageal Cancer after Chemoradiotherapy: A Case Report and Literature Review.

Background: Among total cancer deaths, esophageal cancer ranks sixth in mortality. Radiotherapy and chemotherapy remain the main treatments for unresectable, locally advanced esophageal cancer, but a relapse and drug resistance are still common. The optimized choice for therapeutic schemes with low toxicity and a high quality of life is unclear when local progression occurs after radiotherapy and chemotherapy. Fluoroscopy-guided photodynamic therapy (PDT) on patients with recurrent esophageal cancer in whom the endoscope cannot pass may be used as a salvage treatment, and nanoparticle albumin-bound paclitaxel (Nab-P) has been shown to be effective for advanced esophageal cancer. The combination of PDT and Nab-P might be an effective and tolerable option for advanced esophageal cancer. Case summary: The authors present a 65-year-old male patient diagnosed with esophageal squamous cell carcinoma (ESCC) confirmed to have developed local progression after receiving radiotherapy and chemotherapy. Severe esophageal stenosis, mild malnutrition and anemia, and radiation pneumonia were found when he was admitted to the authors' hospital. For rapid reduction of tumor burden and to restore normal diet, he received PDT by the X-ray fluoroscopy positioning method and Nab-P chemotherapy. The patient obtained clinical benefit from these treatments, and improved his quality of life. Conclusions: This case demonstrates potential advantages of fluoroscopy-guided PDT combined with Nab-P in reducing the tumor load, preserving organ function, and improving the quality of life, as well as the beneficial effect on locally advanced esophageal cancer after radiotherapy and chemotherapy. This combination therapy provides an alternative for the clinical treatment of locally advanced esophageal cancer and it has broad prospects in treatment of the disease. Core tip: Herein, the authors report a case of a patient with ESCC who suffered locally progressive disease after chemotherapy and radiotherapy as well as malnutrition and mild anemia because of feeding difficulties. The patient was treated with PDT, which was assisted by a new positioning technique of X-ray fluoroscopy and Nab-P chemotherapy, and finally achieved clinical benefits. In addition, a modified transnasal feeding tube was also applied in the process of fluoroscopy-guided PDT in this article.

Management of type 2 diabetes mellitus in older adults: eight case studies with focus SGLT-2 inhibitors and metformin.

OBJECTIVES: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been recently introduced for type 2 diabetes treatment with significant cardiovascular, renal benefits. Yet, they have frequently been refrained in older adults. Metformin is regarded the first-line diabetes therapy for all ages; still it is associated with weight loss and frailty in older adults. We aimed to outline our experience with three oldest-old patients with high cardiovascular risk managed with SGLT-2 inhibitors, and five patients with anorexia/weight loss managed by metformin cessation. METHODS: We outlined demographics, comorbidities, geriatric syndromes, functional status, and diabetes duration, and presented the changes in frailty by noting pre-intervention and post-intervention frailty scores. We outlined benefits and side effects related to SGLT-2 inhibitors, and the deprescription reasons and represcription practices of metformin therapy. We gave details on baseline and current diabetes treatment, overall medication regimen, and current status of the patients. RESULTS: Among the case studies with SGLT-2 inhibitors, two patients were frail and reversed to pre-frailty status after SGLT-2 intervention, while the third patient was and remained robust. All patients had clinical improvements with better blood pressure and glucose control. Among the case studies treated with metformin, all were frail before the cessation of metformin. Four reversed to pre-frailty and one became robust after intervention. CONCLUSION: The findings of our case studies suggest considering SGLT-2 inhibitors in patients with accompanying heart failure/high cardiovascular risk factors and cessation of metformin in those with malnutrition/malnutrition risk. These approaches have potential to improve frailty and inappropriate medication use in diabetic older adults.

[Impact of antineoplastic drugs on the nutritional status of older patients with cancer. Can the medical oncologist minimize the impact of these drugs on the nutrirional status of these patients?] / Repercusión de los fármacos antineoplásicos sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo médico minimizar el impacto de estos fármacos sobre el estado nutricional del enfermo mayor?

INTRODUCTION: Aging is associated, per se, with the loss of functional reserve of different organs and systems, a greater risk of vulnerability and frailty, sarcopenia and malnutrition, a reality that is extended to cancer patients. There are several factors that are associated with malnutrition in the elderly individual, such as the difficulty in regulating food intake, loss of appetite and anorexia associated with age, alteration of the senses of taste and smell, dysgeusia or economic problems. In the case of the cancer patient, other factors are added to these factors, such as: type of tumor; tumor stage; evolutionary moment of the disease; and baseline situation. Many therapeutic strategies used against the tumor, such as surgery, treatment with radiotherapy (concomitant or not with chemotherapy) and treatment with antitumor drugs influence also the risk of malnutrition. Thus, for example, concomitant chemo-radiation therapy in head and neck tumors, in lung cancer or in pelvic tumors represents a high nutritional risk antitumor therapy. Some of the repercussions of malnutrition in the oncological elderly are severe. Thus, for example, malnutrition in these individuals is associated with: worse survival; increased risk of early discontinuation of chemotherapy treatment; increased risk of chemotherapy toxicity; increased toxicity from other antitumor drugs; and increased risk of mortality during chemotherapy treatment. Taking this information into account, it is essential: to optimize the nutritional status in older patients with cancer prior to starting a systemic antitumor treatment; to carry out a nutritional follow-up throughout the treatment; and to offer early and intense management of malnutrition once it appears, with the purpose of minimizing the impact of antitumor drugs in older patients with cancer. Early management of malnutrition could improve drugs tolerance and increase the health-related quality of life in these patients.

INTRODUCCIÓN: El envejecimiento se asocia a la pérdida de reserva funcional de distintos órganos y sistemas, a un mayor riesgo de vulnerabilidad y de fragilidad, a la sarcopenia y a la malnutrición, realidad que se hace extensible a los pacientes oncológicos. Varios factores se asocian a la malnutrición en el individuo de edad avanzada: dificultad para regular la ingesta de alimentos, pérdida de apetito y anorexia asociadas a la edad, alteración de los sentidos del gusto y olfato, disgeusia o problemas económicos. En el caso del paciente oncológico, a estos factores se añaden otros como: tipo de tumor; estadio tumoral; momento evolutivo de la enfermedad; y situación basal. También las distintas estrategias terapéuticas utilizadas frente al tumor, como cirugía, tratamiento con radioterapia (concomitante o no a quimioterapia) y tratamiento con fármacos antitumorales influyen en el riesgo de malnutrición. Así, por ejemplo, la quimio-radioterapia concomitante en tumores de cabeza y cuello, en cáncer de pulmón o en tumores de localización pélvica, representa una terapia antitumoral de alto riesgo nutricional. Algunas de las repercusiones de la malnutrición en el anciano oncológico son severas. La malnutrición en estos individuos se asocia a: peor supervivencia; mayor riesgo de interrupción precoz del tratamiento con quimioterapia; aumento en el riesgo de toxicidad de la quimioterapia; mayor toxicidad por otros fármacos antitumorales; y riesgo incrementado de mortalidad durante el tratamiento con quimioterapia. Teniendo en cuenta esta información, resulta fundamental optimizar el estado nutricional en el anciano oncológico previo al inicio de un tratamiento antitumoral sistémico, hacer un seguimiento a lo largo del tratamiento y ofrecer un manejo precoz e intenso de la malnutrición una vez aparezca, con la finalidad de minimizar el impacto de los fármacos antitumorales en el anciano, de mejorar la tolerancia de tales fármacos y aumentar la calidad de vida relacionada con la salud en estos pacientes.

The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.

BACKGROUND: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model. METHODS: Male Sprague-Dawley rats were randomly divided into two groups (n = 8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40 mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism. RESULTS: 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-α in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats. CONCLUSIONS: Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition? / Bør beregning av cellegiftdose ved tarmkreft baseres på kroppssammensetning?

BACKGROUND: Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. MATERIAL AND METHOD: We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. RESULTS: Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. INTERPRETATION: The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

The effects of chemotherapy on energy metabolic aspects in cancer patients: A systematic review.

BACKGROUND & AIMS: Cancer survival rates have increased significantly creating more awareness for comorbidities affecting the Quality of Life. Chemotherapy may induce serious metabolic alterations. These complications can create an energy imbalance, worsening prognosis. The effect of chemotherapy on energy metabolism remains largely unknown. The purpose of this systematic review is to determine the impact of chemotherapy on energy metabolism, creating more insight in a patients' energy requirements. METHODS: We identified relevant studies up to May 2nd, 2019 using PubMed and Web of Science. Studies including all types of cancer and stages were selected. Only patients that underwent chemotherapy whether or not followed by surgery or radiotherapy were selected. Maximum follow-up was set at 6 months. Resting energy expenditure (REE), measured by indirect calorimetry (IC) or predicted by the Harris-Benedict equation (HBEq), was our primary outcome. Results regarding body composition were considered as secondary outcome parameter. RESULTS: 16 studies were selected, including 267 patients. Overall, a significant decrease in REE [-1.5% to -24.91%] 1-month post-chemotherapy was reported. Two studies on breast cancer conducted a 3 and 6-month follow-up and found an increase in REE of 4.01% and 5.72% (p < .05), revealing a U-shaped curve in the expression of REE. Changes are accompanied by (non)significant variations in body composition (Fatmass (FM) and Fatfree Mass (FFM)). HBEq tends to underestimate REE by 4.03%-27.1%. CONCLUSION: Alterations in REE, accompanied by changes in body composition, are found during and after chemotherapy in all cancer types and stages, revealing a U-shaped curve. Changes in FFM are suggested to induce variations in REE concomitant to catabolic effects of the disease and administered drug. HBEq tends to underestimate REE, stressing the need for adequate assessment to meet patients' energy requirements and support dietary needs.

Oligomeric Enteral Nutrition in Undernutrition, due to Oncology Treatment-Related Diarrhea. Systematic Review and Proposal of An Algorithm of Action.

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient's intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition.

Malnutrition Risk in Kidney Recipients Treated With Mycophenolate Mofetil Is Associated With IMPDH1 rs2278294 Polymorphism.

BACKGROUND: Malnutrition is known to increase morbidity and mortality in renal transplant recipients, whereas little is known about genetic predisposition to low body mass index (BMI) in the transplant setting. Inosine monophosphate dehydrogenase (IMPDH) regulates intracellular fat accumulation, pre-adipicytes maturation, and is a target of mycophenolic acid (MPA) used as a standard immunosuppressant. We hypothesized that MPA may interfere with fat tissue formation and weight gain in kidney transplant recipients and this process may be modified by IMPDH1 or IMPDH2 (genes encoding constitutive and inducible IMPDH) small nucleotide polymorphism variants. STUDY DESIGN: In an observational longitudinal study of kidney transplant recipients treated with mycophenolate mofetil, genetic factors were IMPDH1 (rs2278294, rs2278293) and IMPDH2 (rs11706052) allelic variants, the main outcome was the time-dependent change in BMI, and secondary outcomes were occurrence of BMI below 18.5 or 20 kg/m2. RESULTS: In a study group of 190 patients, no association was found between BMI changes and rs11706052 and rs2278293 variants. In terms of rs2278294, we found that allele G was associated with significantly slower BMI gain in a dominant model of inheritance. Concerning secondary endpoints, none of the AA carriers were underweight at 6 months post-implantation, while at least 2% of G allele carriers were underweight. From the first post-transplant year, all AA carriers had BMI above 20 kg/m2, while among G allele carriers at least 10% had BMI < 20 kg/m2 by generalized estimating equations. CONCLUSION: Based on our results, we postulate that MPA derivates influence post-transplant BMI and potentially also body fat content. In consequence, genotyping rs2278294 would potentially allow clinicians to personalize MPA treatment.

Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting Chemicals and Mycotoxins through Stable Isotope Techniques.

Multiple drivers of the double burden of malnutrition (DBM) include a rapid shift from predominantly plant-based diets to energy-dense foods based on meats, milk, animal fats and vegetable oils. The shift to overweight and obesity is driven by increased exposure to mass media, urbanization, technological advances in food processing, rising income and increased population density associated with increased access to cheap foods. At the same time, undernutrition persists mainly due to food insecurity and lack of access to safe water, sanitation and adequate health care. All known nutrition interventions result in only one third reduction in stunting. Little consideration has been given to hazardous exposure to endocrine disrupting chemicals (EDCs) and microbial toxins as major components of the malnutrition-causal framework. These hazards include microbial toxins, for example, mycotoxins, and environmental pollutants such as persistent organic pollutants (POPs), some of which are known to disrupt the endocrine system. These hazards sit at the cross road of undernutrition and overweight and obesity since the exposure cuts across the critical window of opportunity (the first 1000 days). In this review, we update on the role of food and environmental contaminants, especially EDCs and aflatoxins, in child growth and on the implications for metabolic dysfunction and disease risk in later life, and discuss potential applications of nuclear and isotopic techniques to elucidate the underlying biological mechanisms, outcome indicators, as well as occurrence levels.

Updates in nutrition and polypharmacy.

PURPOSE OF REVIEW: Medications have the potential to affect nutritional status in negative ways, especially as the number of medications increase. The inter-relation between polypharmacy and malnutrition is complex and not fully delineated in previous studies. More research has been done and compiled in the last year, which helps to clarify this relationship. This review brings together the most recent literature with the previous research to help healthcare providers to better assess and manage medication therapy in older adults. RECENT FINDINGS: Recent evidence confirms a synergistic negative effect of polypharmacy and malnutrition on outcomes of older adults. In addition, several drug classes, including common antihypertensive agents, acetylcholinesterase inhibitors, multivitamins, proton pump inhibitors, HMG-CoA reductase inhibitors (statins), antiplatelet agents and metformin, have been implicated in important drug-nutrient interactions. These are reviewed in detail here. Ongoing research endeavors are described. SUMMARY: Healthcare practitioners can use this review to identify potentially inappropriate medications and patients at highest risk of experiencing a medication-related adverse reaction in order to systematically deprescribe these high-risk medications.

Apremilast induced chronic diarrhea and malnutrition.

Apremilast is used as a systemic therapy for the treatment of psoriasis and psoriatic arthritis. This drug is considered relatively safe with a very low incidence of serious side effects. Common side effects are diarrhea, nausea, headache, nasopharyngitis, upper respiratory tract infections which are mild to moderate in severity. Diarrhea tends to occur within 2 weeks of starting treatment and resolve spontaneously within 4 weeks without dose adjustment or discontinuation of therapy. Chronic diarrhea and malnutrition due to apremilast have not been reported yet. We report a case of apremilast induced chronic diarrhea leading to malnutrition, necessitating discontinuation of therapy.

Screening for malnutrition in patients with gastro-entero-pancreatic neuroendocrine tumours: a cross-sectional study.

OBJECTIVES: To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET). DESIGN: Cross-sectional study. SETTING: University Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence. PARTICIPANTS: Patients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities. MAIN OUTCOME MEASURE: To identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment. RESULTS: MUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients. CONCLUSIONS: Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.

Serum diamine oxidase activity as a predictor of gastrointestinal toxicity and malnutrition due to anticancer drugs.

BACKGROUND AND AIM: Objective evaluation of intestinal mucosal damage due to anticancer drugs is generally difficult. Serum diamine oxidase (DAO) activity is reported to reflect the integrity and maturity of the small intestinal mucosa. Therefore, we investigated whether serum DAO activity is an indicator of gastrointestinal toxicity or nutritional status in patients receiving chemotherapy. METHODS: We prospectively enrolled 20 patients with unresectable metastatic gastric cancer who received oral S-1 (80 mg/m(2) ) on days 1-14, and intravenous cisplatin (60 mg/m(2) ) and docetaxel (50 mg/m(2) ) on day 8 every 3 weeks. Serum DAO activity was measured by colorimetry. Gastrointestinal toxicity was evaluated by Common Toxicity Criteria for Adverse Events version 4.0. Endoscopic examination and biopsy of duodenal mucosa assessed mucosal damage. Malnutrition was evaluated by measuring serum total protein and albumin levels. RESULTS: Serum DAO activity decreased step-by-step significantly during anticancer drug treatment and recovered after drug holidays. In all 14 patients who experienced diarrhea, serum DAO activity significantly decreased prior to diarrhea onset. Percent decrease in DAO activity was significantly correlated with severity of diarrhea. Significant correlation was observed between percent decrease in DAO activity and percent decrease in duodenal villus height or surface area from baseline. There were also significant correlations between percent decrease in serum DAO activity at day 14 and percent decrease in serum total protein or albumin levels at day 21 from baseline. CONCLUSION: Serum DAO activity sensitively indicates gastrointestinal damage prior to symptom onset and can be a useful predictor of intestinal mucosal damage and nutritional status in patients receiving chemotherapy.

Nutritional status in children with cancer: Before, during and after therapy.

CONTEXT: Malnutrition is prevalent in children with cancer at diagnosis, especially in low- and middle-income countries (LMIC) where the great majority of children live. It is associated with an added burden of morbidity and mortality. AIMS: Answers were sought to the best measure of nutritional status in LMIC, the impact of anti-neoplastic therapy, effective interventions to achieve normal nutritional status and the impact of these on clinical outcomes. RESULTS: Arm anthropometry offers reasonable estimates of fat mass and lean body mass that are both impacted adversely by treatment. Nutritional supplementation, including the use of simple local resources, is beneficial and can improve survival. Long-term survivors may continue to exhibit perturbed nutritional status. CONCLUSIONS: The prevalence and severity of malnutrition in children with cancer in LMIC demand attention. Opportunities exist to conduct studies in India to examine the effects of nutritional interventions, including on the overall well-being of survivors.

Dopaminergic agents and nutritional status in Parkinson's disease.

BACKGROUND: Malnutrition has been found in up to 24% of patients with Parkinson's disease; dopaminergic drugs might impair nutritional status. We evaluated the association of nutritional status with the use of dopaminergic agents. METHODS: We analyzed data from 75 elderly patients with Parkinson's disease attending a geriatric day hospital. Nutritional status was assessed by the Mini Nutritional Assessment (MNA). Dopaminergic drugs were normalized for weight. RESULTS: In linear regression, total levodopa (l-dopa) equivalent daily dose (LEDD) was associated with worse MNA (B = -0.14, 95% CI = -0.26--0.02; P = 0.019). This association remained significant only for l-dopa (B = -0.19, 95% CI = -0.32--0.52; P = 0.007), but not dopaminergic agent dosages. Increasing l-dopa dosages were associated with increasing probability of risk of malnutrition (P for trend = 0.049). CONCLUSIONS: In our population, LEDD was associated with worse nutritional status and risk of malnutrition; this association was limited to use of l-dopa.

Genotoxicity testing of peptides: folate deprivation as a marker of exaggerated pharmacology.

The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level.

Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia.

Hyperphosphatemia contributes to increased cardiovascular mortality through vascular calcification (VC) in patients with chronic kidney disease (CKD). Malnutrition and inflammation are also closely linked to an increased risk of cardiovascular death in CKD. However, the effects of Pi overload on inflammation and malnutrition remain to be elucidated. The aim of the present study was to investigate the effects of dietary Pi loading on the interactions among inflammation, malnutrition, and VC in CKD. We used control rats fed normal diets and adenine-induced CKD rats fed diets with different Pi concentrations ranging from 0.3% to 1.2% for 8 wk. CKD rats showed dietary Pi concentration-dependent increases in serum and tissue levels of TNF-α and urinary and tissue levels of oxidative stress markers and developed malnutrition (decrease in body weight, serum albumin, and urinary creatinine excretion), VC, and premature death without affecting kidney function. Treatment with 6% lanthanum carbonate blunted almost all changes induced by Pi overload. Regression analysis showed that serum Pi levels closely correlated with the extent of inflammation, malnutrition, and VC. Also, in cultured human vascular smooth muscle cells, high-Pi medium directly increased the expression of TNF-α in advance of the increase in osteochondrogenic markers. Our data suggest that dietary Pi overload induces systemic inflammation and malnutrition, accompanied by VC and premature death in CKD, and that inhibition of Pi loading through dietary or pharmacological interventions or anti-inflammatory therapy may be a promising treatment for the prevention of malnutrition-inflammation-atherosclerosis syndrome.