The Diet and Haemodialysis Dyad: Three Eras, Four Open Questions and Four Paradoxes. A Narrative Review, Towards a Personalized, Patient-Centered Approach

The history of dialysis and diet can be viewed as a series of battles waged against potential threats to patients’ lives. In the early years of dialysis, potassium was identified as “the killer”, and the lists patients were given of forbidden foods included most plant-derived nourishment. As soon as dialysis became more efficient and survival increased, hyperphosphatemia, was identified as the enemy, generating an even longer list of banned aliments. Conversely, the “third era” finds us combating protein-energy wasting. This review discusses four questions and four paradoxes, regarding the diet-dialysis dyad: are the “magic numbers” of nutritional requirements (calories: 30–35 kcal/kg; proteins > 1.2 g/kg) still valid? Are the guidelines based on the metabolic needs of patients on “conventional” thrice-weekly bicarbonate dialysis applicable to different dialysis schedules, including daily dialysis or haemodiafiltration? The quantity of phosphate and potassium contained in processed and preserved foods may be significantly different from those in untreated foods: what are we eating? Is malnutrition one condition or a combination of conditions? The paradoxes: obesity is associated with higher survival in dialysis, losing weight is associated with mortality, but high BMI is a contraindication for kidney transplantation; it is difficult to limit phosphate intake when a patient is on a high-protein diet, such as the ones usually prescribed on dialysis; low serum albumin is associated with low dialysis efficiency and reduced survival, but on haemodiafiltration, high efficiency is coupled with albumin losses; banning plant derived food may limit consumption of “vascular healthy” food in a vulnerable population. Tailored approaches and agreed practices are needed so that we can identify attainable goals and pursue them in our fragile haemodialysis populations

Future multimodal mobility scenarios within Europe

The European transport system faces multiple pressing challenges, including the need for significant emissions reduction in the sector and the provision of a seamless, multimodal journey to travellers. In order to address these challenges, a thorough understanding and assessment of different development pathways are required. This paper elaborates on four different scenarios developed within the scope of the Modus project. Based on these as well as additional insights from experts of the air and rail sector, initial implications for emissions reduction potential, travel times, or technological options are discussed

New intravenous calcimimetic agents: New options, new problems. an example on how clinical, economical and ethical considerations affect choice of treatment

Background. Dialysis treatment is improving, but several long-term problems remain unsolved, including metabolic bone disease linked to chronic kidney disease (CKD-MBD). The availability of new, efficacious but expensive drugs (intravenous calcimimetic agents) poses ethical problems, especially in the setting of budget limitations. Methods. Reasons of choice, side effects, biochemical trends were discussed in a cohort of 15 patients (13% of the dialysis population) who stared treatment with intravenous calcimimetics in a single center. All patients had previously been treated with oral calcimimetic agents; dialysis efficacy was at target in 14/15; hemodiafiltration was employed in 10/15. Median Charlson Comorbidity Index was 8. The indications were discussed according to the principlist ethics (beneficience, non maleficience, justice and autonomy). Biochemical results were analyzed to support the clinical-ethical choices. Results. In the context of a strict clinical and biochemical surveillance, the lack of side effects ensured “non-maleficence”; efficacy was at least similar to oral calcimimetic agents, but tolerance was better. Autonomy was respected through a shared decision-making model; all patients appreciated the reduction of the drug burden, and most acknowledged better control of their biochemical data. The ethical conflict resides in the balance between the clinical “beneficience, non-maleficience” advantage and “justice” (economic impact of treatment, potentially in attrition with other resources, since the drug is expensive and included in the dialysis bundle). The dilemma is more relevant when a patient’s life expectancy is short (economic impact without clear clinical advantages), or when non-compliance is an issue (unclear advantage if the whole treatment is not correctly taken). Conclusions. In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice. While ethical discussions are not aimed at finding “the right answer” but asking “the right questions”, this example can raise awareness of the importance of including an ethical analysis in the choice of “economically relevant” drugs

Intradialytic Nutrition and Hemodialysis Prescriptions: A Personalized Stepwise Approach

Dialysis and nutrition are two sides of the same coin—dialysis depurates metabolic waste that is typically produced by food intake. Hence, dietetic restrictions are commonly imposed in order to limit potassium and phosphate and avoid fluid overload. Conversely, malnutrition is a major challenge and, albeit to differing degrees, all nutritional markers are associated with survival. Dialysis-related malnutrition has a multifactorial origin related to uremic syndrome and comorbidities but also to dialysis treatment. Both an insufficient dialysis dose and excessive removal are contributing factors. It is thus not surprising that dialysis alone, without proper nutritional management, often fails to be effective in combatting malnutrition. While composite indexes can be used to identify patients with poor prognosis, none is fully satisfactory, and the definitions of malnutrition and protein energy wasting are still controversial. Furthermore, most nutritional markers and interventions were assessed in hemodialysis patients, while hemodiafiltration and peritoneal dialysis have been less extensively studied. The significant loss of albumin in these two dialysis modalities makes it extremely difficult to interpret common markers and scores. Despite these problems, hemodialysis sessions represent a valuable opportunity to monitor nutritional status and prescribe nutritional interventions, and several approaches have been tried. In this concept paper, we review the current evidence on intradialytic nutrition and propose an algorithm for adapting nutritional interventions to individual patients

Imaging the early development of seeds

Imaging the early development of seeds

Itraconazole associated quadriparesis and edema: a case report

<p>Abstract</p> <p>Introduction</p> <p>Itraconazole is an anti-fungal agent widely used to treat various forms of mycosis. It is particularly useful in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Side effects are uncommon and usually mild. Mild neuropathy is noted to occur very rarely. We present an unusual and, to the best of our knowledge, as yet unreported case of severe neuropathy and peripheral edema due to itraconazole in the absence of a concomitant risk factor.</p> <p>Case presentation</p> <p>A 72-year-old Caucasian man was started on itraconazole following diagnosis of severe asthma with fungal sensitization. One month later he presented with severe bilateral ankle edema with an elevated serum itraconazole level. The itraconazole dose was reduced but his ankle edema persisted and he developed weakness of all four limbs. Itraconazole was completely stopped leading to improvement in his leg edema but he became bed bound due to weakness. He gradually improved with supportive care and neurorehabilitation. On review at six months, our patient was able to mobilize with the aid of two elbow crutches and power had returned to 5/5 in distal extremities and 4+/5 in proximal extremities. The diagnosis was established based on the classical presentation of drug-induced neuropathy and negative investigatory findings for any alternative diagnoses.</p> <p>Conclusion</p> <p>We report the case of a patient presenting with an unusual complication of severe neuropathy and peripheral edema due to itraconazole. Clinicians should be alert to this association when encountered with neuropathy and/or edema in an itraconazole therapy recipient.</p

Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. This syndrome is infrequent and corresponds to a peculiar small subgroup of patients with symptomatic gallstone disease. The patients with the LPAC syndrome present typically with the following main features: age less than 40 years at onset of symptoms, recurrence of biliary symptoms after cholecystectomy, intrahepatic hyperechoic foci or sludge or microlithiasis along the biliary tree. Defect in ABCB4 function causes the production of bile with low phospholipid content, increased lithogenicity and high detergent properties leading to bile duct luminal membrane injuries and resulting in cholestasis with increased serum gamma-glutamyltransferase (GGT) activity. Intrahepatic gallstones may be evidenced by ultrasonography (US), computing tomography (CT) abdominal scan or magnetic resonance cholangiopancreatography, intrahepatic hyperechogenic foci along the biliary tree may be evidenced by US, and hepatic bile composition (phospholipids) may be determined by duodenoscopy. In all cases where the ABCB4 genotyping confirms the diagnosis of LPAC syndrome in young adults, long-term curative or prophylactic therapy with ursodeoxycholic acid (UDCA) should be initiated early to prevent the occurrence or recurrence of the syndrome and its complications. Cholecystectomy is indicated in the case of symptomatic gallstones. Biliary drainage or partial hepatectomy may be indicated in the case of symptomatic intrahepatic bile duct dilatations filled with gallstones. Patients with end-stage liver disease may be candidates for liver transplantation

A High Throughput Genetic Screen Identifies New Early Meiotic Recombination Functions in Arabidopsis thaliana

Meiotic recombination is initiated by the formation of numerous DNA double-strand breaks (DSBs) catalysed by the widely conserved Spo11 protein. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation; however, unlike Spo11, few of these are conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we took advantage of a high-throughput meiotic mutant screen carried out in the model plant Arabidopsis thaliana. A collection of 55,000 mutant lines was screened, and spo11-like mutations, characterised by a drastic decrease in chiasma formation at metaphase I associated with an absence of synapsis at prophase, were selected. This screen led to the identification of two populations of mutants classified according to their recombination defects: mutants that repair meiotic DSBs using the sister chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1. We found that in Arabidopsis thaliana at least four proteins are necessary for driving meiotic DSB repair via the homologous chromosomes. These include the previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2. Analysing the mutants defective in DSB formation, we identified the previously characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2 and AtPRD3. Our data thus increase the number of proteins necessary for DSB formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent) PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes