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Introduction: Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus in vitro. We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunocompromised patients. Methods: First, we conducted a prospective, randomized, open-label, proof-of-concept study in 20 kidney transplant recipients (KTRs) on tacrolimus-based immunosuppression who contracted mild to moderate SARS-CoV-2 infection. Patients were randomized to continue tacrolimus or switch to voclosporin. Second, we performed a post hoc analysis on SARS-CoV-2 infections in 216 patients with lupus nephritis (LN) on standard immunosuppression who were randomly exposed to voclosporin or placebo as part of a clinical trial that was conducted during the worldwide COVID-19 pandemic. Results: The primary end point was clearance of SARS-CoV-2 viral load and that did not differ between voclosporin-treated KTRs (median 12 days, interquartile range [IQR] 8–28) and tacrolimus-treated KTRs (median 12 days, IQR 4–16) nor was there a difference in clinical recovery. Pharmacokinetic analyses demonstrated that, when voclosporin trough levels were on-target, SARS-CoV-2 viral load dropped significantly more (ΔCt 7.7 [3.4–10.7]) compared to tacrolimus-treated KTRs (ΔCt 2.7 [2.0-4.3]; P = 0.035). In voclosporin-exposed patients with LN, SARS-CoV-2 infection was detected in 6% (7/116) compared to 12% (12/100) in placebo-exposed patients (relative risk [RR] 1.4 [0.97–2.06]). Notably, no voclosporin-exposed patients with LN died from severe SARS-CoV-2 infection compared to 3% (3/100) in placebo-exposed patients (RR 2.2 [1.90–2.54]). Conclusion: This proof-of-concept study shows a potential positive risk-benefit profile for voclosporin in immunocompromised patients with SARS-CoV-2 infection. These results warrant further investigations on voclosporin to establish an equipoise between infection and maintenance immunosuppression.

Pathologists need to compare histopathological images of normal and diseased tissues between different samples, cases, and species. We have designed an interactive system, termed Comparative Pathology Workbench (CPW), which allows direct and dynamic comparison of images at a variety of magnifications, selected regions of interest, as well as the results of image analysis or other data analyses such as scRNA-seq. This allows pathologists to indicate key diagnostic features, with a mechanism to allow discussion threads amongst expert groups of pathologists and other disciplines. The data and associated discussions can be accessed online from anywhere in the world. The Comparative Pathology Workbench (CPW) is a web-browser-based visual analytics platform providing shared access to an interactive “spreadsheet” style presentation of image and associated analysis data. The CPW provides a grid layout of rows and columns so that images that correspond to matching data can be organised in the form of an image-enabled “spreadsheet”. An individual workbench can be shared with other users with read-only or full edit access as required. In addition, each workbench element or the whole bench itself has an associated discussion thread to allow collaborative analysis and consensual interpretation of the data.The CPW is a Django-based web-application that hosts the workbench data, manages users, and user-preferences. All image data are hosted by other resource applications such as OMERO or the Digital Slide Archive. Further resources can be added as required. The discussion threads are managed using WordPress and include additional graphical and image data. The CPW has been developed to allow integration of image analysis outputs from systems such as QuPath or ImageJ. All software is open-source and available from a GitHub repository.

Polarisation-dependent differential cross sections σT associated with the target asymmetry T have been measured for the reaction γp→→pπ0 with transverse target polarisation from π0 threshold to photon energies of 190 MeV. The data were obtained using a frozen-spin butanol target with the Crystal Ball / TAPS detector set-up and the Glasgow photon tagging system at the Mainz Microtron MAMI. Results for σT have been used in combination with our previous measurements of the unpolarised cross section σ0 and the beam asymmetry Σ for a model-independent determination of S- and P-wave multipoles in the π0 threshold region, which includes for the first time a direct determination of the imaginary part of the E0+ multipole.

Background: Establishing the effectiveness of high-protein supplementation in reducing cancer-related side effects is crucial., Objective: The study aimed to assess the effectiveness and safety of high-protein supplementation on clinical outcomes of patients undergoing cancer therapy., Methods: Systematic searches were conducted on Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane Central Register of Controlled Trials, and Scopus from inception until July 2023. Randomized controlled trials administering supplements with ≥10 g protein/serving, given to 20+ adult patients undergoing cancer therapy were included. Random-effects meta-analyses were used to estimate the effects of high-protein supplementation on the primary outcomes of body weight and health-related quality of life (HRQoL). We employed a vote-counting approach based on effect direction for secondary outcomes (that is, body composition, muscle function, hospitalization, response to cancer therapy/toxicity, survival, and systemic inflammation). Risk-of-bias (ROB) was assessed., Results: Thirty-five studies involving 3701 patients with diverse cancer types were included. Patients who received high-protein supplementation lost less body weight than controls (mean difference = 1.45 kg; 95% CI: 0.42, 2.48 kg; P = 0.006; I 2 = 80%). No differences in HRQoL were observed; all studies assessing HRQoL were rated as high ROB. A beneficial effect on muscle mass was found in 11 of 13 studies, although most had a high ROB due to assessment techniques. When considering higher quality studies, evidence of a beneficial effect was found in 5 of 5 studies for muscle strength, and 3 of 4 for hospitalization rate. Effects on other secondary outcomes were inconsistent or limited. No serious adverse effects were reported., Conclusions: High-protein supplementation mitigates weight loss, improves muscle strength, and lowers hospitalization rates in patients undergoing cancer therapy. These positive clinical outcomes, along with a favorable safety profile, suggest that high-protein supplementation may be a valuable addition to medical practice. However, given the need for more robust trials and the high ROB observed in the existing studies, these conclusions should be interpreted with caution. This review was prospectively registered with PROSPERO under the registration number CRD42021237372., Competing Interests: Conflict of interest CEO has received honoraria from Abbott Nutrition. JA reports receiving speaking and lecture fees from Baxter and Nutricia. AL reports receiving honoraria and/or paid consultancy from Abbott, Baxter, B. Braun, Fresenius Kabi, Nestlé Health Science, Nutricia, and Smartfish, and research grant from Fresenius Kabi. CMP has previously received honoraria and/or paid consultancy from Abbott Nutrition, Nutricia, Almased, Nestlé Health Science, Pfizer, and AMRA Medical. NK reports speaking and lecture fees and paid consultancy from Abbott Nutrition. The other authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer., Patients and Methods: Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test., Results: Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m 2 ; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (β = 0.37; 95% confidence interval 0.08-0.67; P = 0.014)., Conclusion: Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions., Competing Interests: Disclosure KF reports honoraria from Abbott Nutrition. MS reports grant/research support from AstraZeneca and Bristol Myers Squibb; consultancy for ISPEN; and honoraria from AstraZeneca, BMS, Merck, IPSEN, Viatris, and Novartis. KM reports grant/research support from Deciphera, Blueprint Medicines, AstraZeneca, and Actuate; advisory role with Pfizer Canada. KP reports grant/research support from U.S. Department of Veterans Affairs Rehabilitation Research and Development Service pRogram); speakers bureau of Abbott Nutrition Health Institute. JA reports honoraria from Danone. MS reports honoraria and/or paid consultancy from Life2Good. ND reports honoraria from Abbott Nutrition. CP reports honoraria and/or paid consultancy from Abbott Nutrition, Nutricia, Nestlé Health Science, Pfizer, and AMRA medical; and investigator-initiated funding from Almased. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cancer patients are at a high risk of malnutrition and disease-associated catabolic derangements. It is important to differentiate between 'simple' - voluntary or involuntary - caloric restriction with protein-sparing ketogenic metabolic adaptation and cachexia, characterized by the combination of weight loss and dysmetabolism, most prominently systemic inflammation. While both conditions result in the sacrifice of fat and protein stores and thus impact on treatment tolerance, complication rates and survival, the presence of metabolic derangements is especially dangerous by straining multiple organ functions. To avoid underdiagnosing and undertreating malnutrition, all cancer patients should be routinely screened for nutritional risk. At-risk patients require comprehensive assessment for contributing and treatable causes and, if available, multi-professional efforts to improve food intake, support anabolism, alleviate distress and antagonize pro-inflammatory processes. In curative settings, anabolic support should accompany or even precede anticancer treatments. Prehabilitation before major surgery, has been studied extensively, including muscle training as well as nutritional and/or psychological support. Recent meta-analyses report a consistent benefit on functional capacity and possible improvement in postoperative complications and length of hospital stay. In palliative settings, prevailing catabolic derangements require careful assessment of the individual constellation of disturbed functions and an empathic evaluation of benefits and risks of nutritional interventions. This is of special relevance in patients with an expected survival of less than a few months. Due to the complex interactions of mechanical, metabolic and psychological factors, multi-professional teams should be involved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jann Arends reports a relationship with Baxter that includes: speaking and lecture fees. Jann Arends reports a relationship with Danone Nutricia Research that includes: paid expert testimony and speaking and lecture fees., (© 2023 Published by Elsevier Ltd.)

Introduction: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments., Material and Methods: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team., Results: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation., Conclusions: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-based (e.g., meat, fish, dairy) and plant-based (e.g., legumes) proteins in cancer are acknowledged and addressed. Although the optimal dietary amino acid composition to support muscle health in cancer is yet to be established, animal-based proteins have a composition that offers superior anabolic potential, compared to plant-derived proteins. Thus, animal-based foods should represent the majority (i.e., ≥65%) of protein intake during active cancer treatment. A diet rich in plant-derived proteins may support muscle anabolism in cancer, albeit requiring a larger quantity of protein to fulfill the optimal amino acid intake. We caution that translating dietary recommendations for cancer prevention to cancer treatment may be inadequate to support the pro-inflammatory and catabolic nature of the disease. We further caution against initiating an exclusively plant-based (i.e., vegan) diet upon a diagnosis of cancer, given the presence of elevated protein requirements and risk of inadequate protein intake to support muscle anabolism. Amino acid combination and the long-term sustainability of a dietary pattern void of animal-based foods requires careful and laborious management of protein intake for patients with cancer. Ultimately, a dietary amino acid composition that promotes muscle anabolism is optimally obtained through combination of animal- and plant-based protein sources., Competing Interests: Conflict of interest K.L.F has no conflicts to declare. J.A. reports receiving honoraria from Baxter, B. Braun, Berg-Apotheke, Falk, Fresenius-Kabi, Helsinn, Nestlè and Nutricia. P.J.A. reports consultancy fees and research income from Abbott Nutrition and Fresenius-Kabi. M.P.K.J.E has no conflicts to declare. T.J.M.G. reports receiving consulting fees for honoraria for lectures at industry-sponsored events; consulting fees from Nestlé Health Science and Nutricia. A.L. reports receiving consulting fees for honoraria for lectures at industry-sponsored events; consulting fees from Abbott, Baxter, BBraun, Fresenius Kabi, Nestlé Health Science, Nutricia, and Smartfish; and research grant from Freseni usKabi. D.N.L. has no conflicts to declare. S.M.P. reports grants from US National Dairy Council, during the conduct of the study; personal fees from the US National Dairy Council, non-financial support from Enhanced Recovery, outside the submitted work; In addition, Dr. Phillips has a patent Canadian 3052324 issued to Exerkine, and a patent US 20200230197 pending to Exerkine but reports no financial gains. P.R. has no conflicts to declare. N.E.P.D reports grants from Abbott Nutrition, Department of Defense, and National Institutes of Health, and honoraria from Abbott Nutrition. C.M.P. reports receiving honoraria and/or paid consultancy from Abbott Nutrition, Nutricia, Nestle Health Science, Fresenius Kabi, Pfizer, and Helsinn., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This practical guideline is based on the ESPEN Guidelines on Chronic Intestinal Failure in Adults., Methodology: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists, and nurses working with patients with chronic intestinal failure., Results: This practical guideline consists of 112 recommendations with short commentaries for the management and treatment of benign chronic intestinal failure, including home parenteral nutrition and its complications, intestinal rehabilitation, and intestinal transplantation., Conclusion: This practical guideline gives guidance to health care providers involved in the management of patients with chronic intestinal failure., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure FS reports receipt of unrestricted industry grants to institute for clinical research from Celgene, Fresenius and Helsinn, participation in company-led clinical cachexia trials for Novartis and participation in an advisory role for Helsinn, Mundipharma, Novartis, Fresenius and Kaiku Health (reimbursements to institute); TSS reports receipt of honoraria from Fresenius Kabi; MC reports receipt of payment from Tetra Biopharmaceuticals for helping to write research protocols; JA reports receipt of consultancy fees from Baxter and Danone and honoraria from Berg-Apotheke, Falk, Fresenius Kabi, Nutricia and Roche; CIR reports receipt of funding for independent educational events from Inpharm, Kyowa Kirin, Amgen Europe and Molteni SpA; MAEdvdS reports receipt of honoraria for independent lectures at educational and scientific events organised by Nutricia, Fresenius Kabi and Baxter; all other authors have declared no conflicts of interest.

Objectives: Multiple myeloma (MM) is the second most common hematological malignancy. Progression free survival (PFS) and overall survival (OS) have substantially improved, nonetheless MM usually remains incurable. Patients with active disease may be affected by numerous comorbidities, including fatigue, depression and osteolytic lesions, which influence their quality of life (QoL). Albeit, it is known that exercising is beneficial for patients' QoL, few clinical trials are available in patients with MM. We therefore aimed to compare comorbidities and clinical outcome in physically active and inactive patients with MM., Material and Methods: We defined physical activity according to WHO criteria (150 min of moderate activity and two sessions of resistance training/week). We matched 53 physically active patients with 53 controls (for age, gender, cytogenetics, disease stage, and therapy) and compared the cohorts for incidence of comorbidities/MM symptoms (osteolytic lesions, anemia, infections, fatigue, depression, Revised-Myeloma Comorbidity Index [R-MCI]) and clinical outcome (treatment tolerance, responses to therapy, PFS and OS) in a retrospective audit. All patients were newly diagnosed with MM and received autologous stem cell transplantations (ASCT) between 2001 and 2017., Results: Physically active patients showed superior outcomes in R-MCI (p = 0.0005), fatigue (p = 0.0063), treatment tolerance (p = 0.0258) and hospital stays (p = 0.0072). Furthermore, they showed better treatment responses (p = 0.0366), especially complete remission (CR; p = 0.0018) as well as better OS and PFS., Conclusion: Physical activity in patients with MM undergoing ASCT seemed associated with better overall clinical outcome. Randomized clinical trials are required to understand the benefits and devise strategies for improving exercising among patients with MM., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients., Methods: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer., Results: A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients., Conclusion: This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care., Competing Interests: Conflicts of interest No conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period., Methods: To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018., Results: All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B 12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18)., Conclusion: The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT., Competing Interests: Conflict of interest R.T. received a research grant from Bayer AG, travel support from Falk-Pharma and serves as consultant for Bayer AG. D.W. received honoraria from Falk-Pharma. R.T., H.G., A.L., J.H., A.B., A.S., J.A., P.J., J.M., I.H., S.K., E.M. W-D., C.S., G.B. and D.W. did not receive payment or services from a third party for any aspect of the submitted work and have nothing further to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF)., Methods: In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions., Results: HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001)., Conclusions: This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Concurrent chemotherapy and radiotherapy (CCRT) followed by durvalumab immune therapy in appropriate patients is considered to be the standard of care in most fit stage III non-small-cell lung cancer (NSCLC) patients. However, CCRT is a toxic treatment that affects all organ systems and may cause acute and permanent side effects, some of which may be lethal. Supportive care is therefore of utmost importance in this clinical setting. A group of experts from the European Society for Therapeutic Radiology and Oncology (ESTRO) and the European Society of Medical Oncology (ESMO) identified the following items of importance for further improvement of supportive care: smoking cessation; nutrition before and during CCRT (including treatment and prevention of anorexia); physical exercise before and during CCRT; prevention and treatment of acute esophagitis and dysphagia; treatment of cough and dyspnea; treatment of skin reactions; treatment of fatigue; prophylaxis of nausea and emesis; prevention, diagnosis, and treatment of cardiac disease and damage; and optimization of radiotherapy techniques and chemotherapy adjustments to reduce toxicity in the era of immune therapy. The resulting recommendations are summarized in this manuscript and knowledge gaps identified, in which future investments are needed to improve supportive care and hence quality of life and survival for our stage III NSCLC patients., (Copyright © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

We recommend that intestinal failure associated liver disease (IFALD) should be diagnosed by the presence of abnormal liver function tests and/or evidence of radiological and/or histological liver abnormalities occurring in an individual with IF, in the absence of another primary parenchymal liver pathology (e.g. viral or autoimmune hepatitis), other hepatotoxic factors (e.g. alcohol/medication) or biliary obstruction. The presence or absence of sepsis should be noted, along with the duration of PN administration. Abnormal liver histology is not mandatory for a diagnosis of IFALD and the decision to perform a liver biopsy should be made on a case-by-case basis, but should be particularly considered in those with a persistent abnormal conjugated bilirubin in the absence of intra or extra-hepatic cholestasis on radiological imaging and/or persistent or worsening hyperbilirubinaemia despite resolution of any underlying sepsis and/or any clinical or radiological features of chronic liver disease. Nutritional approaches aimed at minimising PN overfeeding and optimising oral/enteral nutrition should be instituted to prevent and/or manage IFALD. We further recommend that the lipid administered is limited to less than 1 g/kg/day, and the prescribed omega-6/omega-3 PUFA ratio is reduced wherever possible. For patients with any evidence of progressive hepatic fibrosis or overt liver failure, combined intestinal and liver transplantation should be considered., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Driven by reduced nutritional intakes and metabolic alterations, malnutrition in cancer patients adversely affects quality of life, treatment tolerance and survival. We examined evidence for oral nutritional interventions during chemo(radio)therapy., Design: We carried out a systematic review of randomized controlled trials (RCT) with either dietary counseling (DC), high-energy oral nutritional supplements (ONS) aiming at improving intakes or ONS enriched with protein and n-3 polyunsaturated fatty acids (PUFA) additionally aiming for modulation of cancer-related metabolic alterations. Meta-analyses were carried out on body weight (BW) response to nutritional interventions, with subgroup analyses for DC and/or high-energy ONS or high-protein n-3 PUFA-enriched ONS., Results: Eleven studies were identified. Meta-analysis showed overall benefit of interventions on BW during chemo(radio)therapy (+1.31 kg, 95% CI 0.24-2.38, P = 0.02, heterogeneity Q = 21.1, P = 0.007). Subgroup analysis showed no effect of DC and/or high-energy ONS (+0.80 kg, 95% CI -1.14 to 2.74, P = 0.32; Q = 10.5, P = 0.03), possibly due to limited compliance and intakes falling short of intake goals. A significant effect was observed for high-protein n-3 PUFA-enriched intervention compared with isocaloric controls (+1.89 kg, 95% CI 0.51-3.27, P = 0.02; Q = 3.1 P = 0.37). High-protein, n-3 PUFA-enriched ONS studies showed attenuation of lean body mass loss (N = 2 studies) and improvement of some quality of life domains (N = 3 studies). Overall, studies were limited in number, heterogeneous, and inadequately powered to show effects on treatment toxicity or survival., Conclusion: This systematic review suggests an overall positive effect of nutritional interventions during chemo(radio)therapy on BW. Subgroup analyses showed effects were driven by high-protein n-3 PUFA-enriched ONS, suggesting the benefit of targeting metabolic alterations. DC and/or high-energy ONS were less effective, likely due to cumulative caloric deficits despite interventions. We highlight the need and provide recommendations for well-designed RCT to determine the effect of nutritional interventions on clinical outcomes, with specific focus on reaching nutritional goals and providing the right nutrients, as part of an integral supportive care approach.

Background & Aims: The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements., Methods: ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need., Results: Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume., Conclusions: Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Patients with advanced cancer are at high risk of losing vital body resources resulting in malnutrition, immunodeficiency, impaired quality of life and worse clinical outcome. Prominent among the diverse factors contributing to this complex condition are metabolic derangements characterized by systemic inflammation, catabolism and accumulating changes in body composition. Because cure in advanced cancer still remains elusive, optimal supportive and integrated palliative care are required to allow patients to tolerate aggressive or long-term anticancer treatments, to maintain an adequate quality of life or to stay the course of advancing disease. Support needs to address and focus on all physical, psychological and social problems interfering with food intake, digestion and anabolism to maintaining adequate body resources and functions. Reliable screening for malnutrition, adequate assessment of the nutritional and metabolic status, and individualized multimodal care require the establishment of dedicated operating procedures involving experts and standardized pathways for communication among all participants involved in clinical cancer care. Therapeutic options include counseling, enriching foods, oral nutritional supplements, enteral and parenteral nutrition, metabolic modulation, exercise training, supportive care to enable and improve the intake of adequate amounts of food, as well as psycho-oncology and social support. Finally, to enable this new level of nutritional and metabolic patient care it appears necessary to establish common definitions and grading systems allowing not only for efficient treatment but allocating adequate medical resources to reach this goal.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Chronic Intestinal Failure (CIF) is the long-lasting reduction of gut function, below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. CIF is the rarest organ failure. Home parenteral nutrition (HPN) is the primary treatment for CIF. No guidelines (GLs) have been developed that address the global management of CIF. These GLs have been devised to generate comprehensive recommendations for safe and effective management of adult patients with CIF., Methods: The GLs were developed by the Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. The GRADE system was used for assigning strength of evidence. Recommendations were discussed, submitted to Delphi rounds, and accepted in an online survey of ESPEN members., Results: The following topics were addressed: management of HPN; parenteral nutrition formulation; intestinal rehabilitation, medical therapies, and non-transplant surgery, for short bowel syndrome, chronic intestinal pseudo-obstruction, and radiation enteritis; intestinal transplantation; prevention/treatment of CVC-related infection, CVC-related occlusion/thrombosis; intestinal failure-associated liver disease, gallbladder sludge and stones, renal failure and metabolic bone disease. Literature search provided 623 full papers. Only 12% were controlled studies or meta-analyses. A total of 112 recommendations are given: grade of evidence, very low for 51%, low for 39%, moderate for 8%, and high for 2%; strength of recommendation: strong for 63%, weak for 37%., Conclusions: CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for both the underlying gastrointestinal disease and to provide HPN support. The rarity of the condition impairs the development of RCTs. As a consequence, most of the recommendations have a low or very low grade of evidence. However, two-thirds of the recommendations are considered strong. Specialized management and organization underpin these recommendations., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Intestinal failure (IF) is not included in the list of PubMed Mesh terms, as failure is the term describing a state of non functioning of other organs, and as such is not well recognized. No scientific society has yet devised a formal definition and classification of IF. The European Society for Clinical Nutrition and Metabolism guideline committee endorsed its "home artificial nutrition and chronic IF" and "acute IF" special interest groups to write recommendations on these issues., Methods: After a Medline Search, in December 2013, for "intestinal failure" and "review"[Publication Type], the project was developed using the Delphi round methodology. The final consensus was reached on March 2014, after 5 Delphi rounds and two live meetings., Results: The recommendations comprise the definition of IF, a functional and a pathophysiological classification for both acute and chronic IF and a clinical classification of chronic IF. IF was defined as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth"., Conclusions: This formal definition and classification of IF, will facilitate communication and cooperation among professionals in clinical practice, organization and management, and research., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome., Methods: A group of experts met under the auspices of the European School of Oncology to review the literature and-on the basis of the limited evidence at present-make recommendations for malnutrition and cachexia management and future research., Conclusions: Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/altered metabolism (cachexia), a multi-modal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass and (if present) reducing systemic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: In cancer patients, metabolic alterations, reduced immune competence and anti-cancer treatment can increase the risk of infections. A rapid-acting nutritional intervention might reduce this risk and support overall treatment. The present study investigated whether one week of intervention with a specific medical food led to fatty acid incorporation and functional immunological changes., Methods: In a randomized, double-blind study, 38 cancer patients receiving radiotherapy consumed daily for one week 400 ml of specific medical food, which is high in protein and leucine, and enriched with fish oil and specific oligosaccharides (Active group), or iso-caloric/iso-nitrogenous product (Control group). Blood samples were taken at day 0 (baseline) and day 7., Results: After one week of intervention, the incorporation of EPA and DHA in white blood cells was significantly higher in the Active group (2.6% and 2.6% of total fatty acids) compared to the Control group (1.0% and 2.2% of total fatty acids) (p < 0.001 and p < 0.05). Serum PGE2 levels decreased in the Active group and increased in the Control group (p < 0.01). No differences were observed on cytokine production in LPS-stimulated whole blood cultures., Conclusions: In cancer patients receiving radiotherapy, nutritional intervention with a specific medical food rapidly increased the percentage EPA and DHA in white blood cell phospholipids and reduced serum levels of the inflammatory mediator PGE2 within one week. CLINICAL REGISTRATION NUMBER: NTR2121., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Clinical studies are emerging to support providing long chain n-3 fatty acids, found in fish oils, to prevent muscle loss, minimize side effects and improve chemotherapy response in patients with cancer. However, a recent report using experimental models made the concluding statement "..., the use of [fish oil] products during chemotherapy treatment should be avoided". This recommendation is not in line with current understanding of human nutrient requirements and needs to be carefully weighed against evidence supporting fish oil supplementation. The potential clinical detriment of consuming fish oil when undergoing platinum based therapies claimed by Roodhart et al. is not taken within the context of the collective work citing beneficial effects of fish oil in experimental models as well as in humans. Platinum-based therapies are standard of care for lung cancer in many regions of the world with no evidence that they are more or less effective than in countries where oily fish intake is minimal. Overall, the human nutrition recommendations made in the discussion of Roodhart et al. are not supported by the experimental evidence provided in the paper nor within the context of other work in this area., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: EndoTAG-1 (ET), a novel formulation of cationic liposomes carrying embedded paclitaxel (Taxol), shows antitumoral activity, targeting tumor endothelial cells in solid tumors. Patients with advanced metastatic cancer were evaluated investigating effects on pharmacokinetics and tumor vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and contrast-enhanced ultrasound (CEUS)., Patients and Methods: The pharmacokinetic (PK) profile of ET (22 mg/m(2) i.v.) was evaluated after single and repeated doses. DCE-MRI and CEUS explored hepatic metastases before, during and after the 4-week treatment cycle. Angiogenic biomarkers were assessed. Tumor response was evaluated by modified RECIST., Results: The PK profile demonstrated slight accumulation of paclitaxel after repeated doses. DCE-MRI parameters K(trans) and/or iAUC(60) showed a trend to decrease. Changes of blood flow-dependent parameters of DCE-MRI and CEUS were well correlated. Angiogenic biomarkers revealed no clear trend. ET was generally well tolerated; common toxic effects were fatigue and hypersensitivity reactions. Nine (9 of 18) patients had stable disease after the first treatment cycle. Four patients without disease progression continued treatment., Conclusions: This study including multiple pretreated patients with different metastatic cancer revealed individually distinctive hemodynamic alterations by DCE-MRI. The PK profiles of ET were similar as observed previously.

Parenteral nutrition offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. These guidelines are intended to provide evidence-based recommendations for the use of parenteral nutrition in cancer patients. They were developed by an interdisciplinary expert group in accordance with accepted standards, are based on the most relevant publications of the last 30 years and share many of the conclusions of the ESPEN guidelines on enteral nutrition in oncology. Under-nutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis and, per se, responsible for excess morbidity and mortality. Many indications for parenteral nutrition parallel those for enteral nutrition (weight loss or reduction in food intake for more than 7-10 days), but only those who, for whatever reason cannot be fed orally or enterally, are candidates to receive parenteral nutrition. A standard nutritional regimen may be recommended for short-term parenteral nutrition, while in cachectic patients receiving intravenous feeding for several weeks a high fat-to-glucose ratio may be advised because these patients maintain a high capacity to metabolize fats. The limited nutritional response to the parenteral nutrition reflects more the presence of metabolic derangements which are characteristic of the cachexia syndrome (or merely the short duration of the nutritional support) rather than the inadequacy of the nutritional regimen. Perioperative parenteral nutrition is only recommended in malnourished patients if enteral nutrition is not feasible. In non-surgical well-nourished oncologic patients routine parenteral nutrition is not recommended because it has proved to offer no advantage and is associated with increased morbidity. A benefit, however, is reported in patients undergoing hematopoietic stem cell transplantation. Short-term parenteral nutrition is however commonly accepted in patients with acute gastrointestinal complications from chemotherapy and radiotherapy, and long-term (home) parenteral nutrition will sometimes be a life-saving maneuver in patients with sub acute/chronic radiation enteropathy. In incurable cancer patients home parenteral nutrition may be recommended in hypophagic/(sub)obstructed patients (if there is an acceptable performance status) if they are expected to die from starvation/under nutrition prior to tumor spread.

An increase in the number of outbreaks of Acinetobacter infection was notified in The Netherlands during 1999-2001. The present study compared the outbreaks at the species and strain levels, and analysed the epidemiology and control measures at the different locations. For each institute, three representative isolates from three patients were identified to the species and strain levels by genotyping methods. A questionnaire investigated the impact of the outbreak, the control measures that were taken, and the possible effects of the measures. Seven outbreaks were associated with Acinetobacter baumannii (three outbreaks with a strain designated strain A, two outbreaks with a strain designated strain B, and one outbreak each with strains designated C and D). An additional outbreak was caused by genomic species 13TU, which is related closely to A. baumannii. Strains B and D were identified as European clones III and II, respectively. Except for two hospitals with outbreaks caused by strain A, there was no known epidemiological link between the participating hospitals. In all hospitals the outbreak occurred on one or several intensive care units, and spread to other departments was noted in two hospitals. The number of patients affected ranged from six to 66 over a period of 2-22 months. In most outbreaks, patients were the likely reservoir from which spread occurred. In all hospitals, a large panel of measures was required to bring the outbreak to an end. Extensive environmental sampling yielded numerous positive samples in most but not all hospitals.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

Background: We have demonstrated that a single T-cell epitope pCol(28-40) (SQTTANPSCPEGT) alone, which is derived from NC1 domain of alpha3 chain of type IV collagen (Col4alpha3 NC1), can induce severe glomerulonephritis in Wistar Kyoto rats. This study further characterized this T-cell epitope., Methods: A series of synthetic peptides derived from pCol (28-40) were tested in vivo and in vitro for their T-cell epitope activity and nephritogenicity. Major histocompatability complex (MHC) class II molecules in Wistar Kyoto rats were cloned, and MHC restriction of pCol(28-40) was determined., Results: The T-cell epitope pCol(28-40) was restricted by rat MHC class II RT.1Bl. Ten amino acid residues (29 to 38) were mapped to be the minimum core of the T-cell epitope, which was capable of inducing the T-cell response and severe glomerulonephritis. Only three residues were identified as absolutely critical for the T-cell epitope: position 31 (T) was an anchor residue to the class II molecule, and positions 33 (N) and 34 (P) contributed to the specificity of the T-cell epitope. Thus, only substitution at those positions completely abrogated nephritogenicity of the T-cell epitope. Interestingly, pCol (28-40) also bound to human MHC class II human MHC class II molecule HLA-DRB*1501, which has been linked to human anti-glomerular basement membrane (GBM) disease, suggesting that human homologue of pCol(28-40) could be a potential human T-cell epitope., Conclusion: Our study demonstrated that only few residues in the nephritogenic T-cell epitope pCol(28-40) were critical. Our finding also revealed that pCol(28-40) is a potential nephritogenic T-cell epitope in Goodpasture's syndrome.

Objectives: To investigate the influence of different electrolyte concentrations on the electrical resistance of sound human enamel-dentine cylinders in vitro., Methods: Forty cylinders of 3-mm diameter and 2-mm length were drilled from 40 extracted caries-free third molar teeth. For ease of handling the samples were fixed in Perspex discs by means of a cyanoacrylate-adhesive. An a.c. source (frequency 500 Hz, amplitude 1 microA) with a high internal resistance was applied. Only Ohm's resistance was measured. The resistance measurements on the samples were made after storage in distilled water, 0.16 mM NaCl, 1.6 mM NaCl and 16 mM NaCl and 160 mM NaCl for 24 h., Results: The mean resistance values were 2026 +/- 152, 1835 +/- 178, 1605 +/- 364, 483 +/- 265 and 60 +/- 33 k omega, respectively. All values were statistically significantly different (Wilcoxon test; P < 0.0001)., Conclusion: It is concluded that the choice of electrolyte solution influences the resistance values of the enamel-dentine samples. This effect should be taken into account when measuring electrical resistances in vivo and in vitro.

The fluoride level in saliva is considered an important parameter in caries prevention. Elevation of the salivary fluoride level by a fluoride-releasing orthodontic bonding adhesive would most likely be beneficial in the prevention of enamel caries. In this study, the fluoride level in saliva was measured after bonding brackets with a visible light-curing adhesive containing fluoride (12.4 wt% total F). The fluoride released from the adhesive has been shown in a previous study to inhibit demineralization adjacent to orthodontic brackets in vivo. Twenty-four patients each had 20 brackets bonded and saliva samples taken before bonding (t = 0) and after 1, 3, and 6 months. The participants were requested to brush daily with a fluoride toothpaste during the study period. The saliva fluoride analysis was done with the microdiffusion method. The analysis of the saliva showed fluoride levels (+/- SD) of 0.011 +/- 0.007, 0.011 +/- 0.009, 0.0011 +/- 0.007, and 0.012 +/- 0.008 ppm at t = 0, 1, 3, and 6 months, respectively. There was no significant difference at the 5% level. The study indicated indirectly that the caries inhibiting effect of the orthodontic adhesive shown previously was most likely due to a localized fluoridation of the cariogenic environment rather than to an elevation of the fluoride level in saliva.

In the present in vivo study, the cariostatic potential of a titanium tetrafluoride (TiF4) solution applied topically around orthodontic brackets was investigated with quantitative microradiography. Also characteristics of the TiF4-treated enamel surface were examined with scanning electron microscopy (SEM). Ten pairs of premolars to be extracted for orthodontic treatment were used in the first part of this study. Brackets were bonded on all teeth with an orthodontic adhesive, and 10 randomly selected premolars served as controls, whereas a similar number were treated with 1% TiF4 around brackets for 60 seconds. After 4 weeks with no topical fluoride supplementation, all teeth were extracted and stored for analysis. Results indicated the 1% TIF4 solution reduced lesion depths and total mineral loss, at the bracket periphery, significantly during the 4-week period. The presence of a surface coating was demonstrated by SEM micrographs. It was concluded that TiF4 may provide a high level performance as a prophylactic agent for orthodontic purposes.

This study was designed to investigate the cariostatic potential in vivo of a visible light-curing adhesive for the bonding of orthodontic brackets. The fluoride release of the adhesive in water and saliva was also measured. Ten orthodontic patients with premolars to be extracted participated. One bracket with Heliosit-Orthodontic (no fluoride) was positioned on the buccal surface of one premolar (control), and another bracket with Orthodontic cement VP 862 (containing fluoride) was positioned on the experimental contralateral premolar. The adhesives were cured with a Heliolux II lamp, and the teeth were extracted after 4 weeks. The patients used a fluoride toothpaste during the experiment. The mineral content of the enamel adjacent to the brackets was determined by quantitative microradiography. The fluoride release from disk-shaped plates of the fluoride adhesive was measured in water for a 6-month period and in human saliva for 24 hours. The fluoride adhesive reduced lesion depths by about 48% than the nonfluoride adhesive (P less than 0.05, t test). The largest release of fluoride from the plates in water was observable within the first week. However, a significant amount of fluoride was still released after 6 months. The fluoride release in saliva was significantly lower in human saliva at pH 7 than in water (P less than 0.01, t test). When salivary pH was lowered to 4, to mimic a cariogenic challenge, the amount of fluoride released increased up to the value measured in water. It was concluded that the regular use of fluoride toothpastes is insufficient to inhibit lesion development around orthodontic brackets.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to investigate the cariostatic effect of two glass ionomer cements on in vivo demineralization of partly uncovered enamel beneath orthodontic bands. A 4-week clinical trial was conducted on a group of five patients with nine pairs of premolars to be extracted for orthodontic purposes. Specially designed orthodontic bands were cemented with either Ketac-Cem (K-C) or Aqua-Cem (A-C). A local cariogenic milieu was created between the buccal surface of the premolars and the inner surface of the bands to secure plaque accumulation. The mineral content of the teeth was quantified by microradiography. The data were compared with data from a previous study of patients in the same age group with bands that had been cemented with a non-F cement. After comparison with the non-F group, the lesion depth (ld) was reduced by 63% for K-C and by 55% for A-C. This reduction was statistically significant at the 2.5% level (t test). The total mineral loss in teeth cemented with glass ionomer cements (delta Z) was reduced, in comparison with the loss in teeth cemented with non-F cement, by 49% with K-C and by 27% with A-C. The differences were statistically significant only for the K-C group (t test, p less than 0.025). There were no significant differences between the two glass ionomer cements with respect to either lesion depth or total mineral loss values (paired t test; p greater than 0.05). This investigation shows that fluoride released from glass ionomer cements contributes substantially to demineralization "reduction." However, these cements do not provide complete caries protection in sites where access is difficult.

To allow in vivo determination of synthetic rates for individual proteins, physiological incorporation of infused [15N]glycine into urinary hippuric acid has been used as an indicator of intrahepatic tracer dilution. Although the kidneys might contribute to hippurate production, the relationship between hepatic, plasma, and urinary hippurate has not yet been established in humans. To further investigate these issues we developed a fast, sensitive, and reliable method for measuring simultaneously hippurate concentrations and in vivo tracer incorporation into hippurate in plasma and urine using stable isotopes and gas chromatography-mass spectrometry. We then tested this assay under several experimental conditions. Reference compounds [( 15N]- and [ring-2H5]hippurate) were synthesized and gave linear standard curves. Postabsorptive hippurate plasma levels in healthy subjects ranged from 1.2 to 10.5 microM and protein binding was 79 +/- 6% (mean +/- SD). Following a bolus dose of [15N]glycine tracer appeared in plasma hippurate; enrichment in hippurate was indistinguishable from that in glycine after an equilibration period of 20 min, indicating a close relationship between intracellular glycine and plasma hippurate. A 16-h infusion of [15N]glycine resulted in identical enrichment levels in urinary and plasma hippurate; glycine enrichment in a hepatic export protein (VLDL-ApoB) was approaching plasma hippurate but not plasma free glycine enrichment. The ability to monitor plasma hippurate is of practical advantage compared to the sampling of urine. Furthermore it allows the monitoring of rapid events in the intrahepatic dilution of an infused glycine tracer. This assay may, therefore, become an important tool in the study of hepatic protein metabolism.