Nutrition for the older adult - Current concepts. Report from an ESPEN symposium.

BACKGROUND & AIMS: In view of the global demographic shift, a scientific symposium was organised by the European Society for Clinical Nutrition and Metabolism (ESPEN) to address nutrition-related challenges of the older population and provide an overview of the current state of knowledge. METHODS: Eighteen nutrition-related issues of the ageing global society were presented by international experts during the symposium and summarised in this report. RESULTS: Anorexia of ageing, dysphagia, malnutrition, frailty, sarcopenia, sarcopenic obesity, and the metabolic syndrome were highlighted as major nutrition-related geriatric syndromes. Great progress has been made in recent years through standardised definitions of some but not all syndromes. Regarding malnutrition, the GLIM approach has shown to be suitable also in older adults, justifying its continuous implementation. For anorexia of ageing, a consensus definition is still required. Intervention approaches should be integrated and person-centered with the aim of optimizing intrinsic capacity and maintaining functional capacity. Landmark studies like EFFORT and FINGER have impressively documented the potential of individualised and multifactorial interventions for functional and health benefits. Combining nutritional intervention with physical training seems particularly important whereas restrictive diets and drug treatment should generally be used with caution because of undesirable risks. Obesity management in older adults should take into account the risk of promoting sarcopenia. CONCLUSIONS: In the future, even more individualised approaches like precision nutrition may enable better nutritional care. Meanwhile all stakeholders should focus on a better implementation of currently available strategies and work closely together to improve nutritional care for older adults.

Multimodal MRI Longitudinal Assessment of White and Gray Matter in Different SPG Types of Hereditary Spastic Paraparesis.

Hereditary spastic paraplegias (HSP) are a group of genetically and clinically heterogeneous neurologic disorders. Hereby we describe a relatively large group of patients (pts) affected by HSP studied at baseline (31 pts) and at follow-up (mean period 28.9 ± 8.4 months; 23 pts) with multimodal advanced MRI: high-resolution T1 images for voxel-based morphometry (VBM) analysis, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI). An age-matched healthy control (HC) group underwent the same neuroimaging protocol in a time schedule matched with the HSP patients. At baseline, VBM showed gray matter (GM) reduction in HSP in the right pre-frontal cortex and bilaterally in the thalami. MRS at baseline depicted in HSP patients compared to the HC group reduction of NAA/Cr ratio in the right pre-frontal region, increase of Cho/Cr ratio in the right pre-central regions, and increase of mI/Cr ratio on the left pre-central area. At cross-sectional follow-up analysis and longitudinal evaluation, no VBM and MRS statistically significant results were obtained. Tract-based spatial statistics (TBSS) analysis showed widespread DTI brain white matter (WM) alterations in patients compared to HC at baseline, which are characterized by reduction of fractional anisotropy (FA) and increase of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity, as confirmed on cross-analysis of the follow-up dataset. A longitudinal analysis with TBSS in HSP patients did not show significant variations, while upon applying region-based analysis we found increased FA and decreased MD and AD in specific brain WM fiber complex during follow-up. The changes were not correlated with the clinical presentation (pure vs complicated HSP), motor function, and motility indexes or history of specific treatments (botulinum toxin). In conclusion, the cross-sectional analysis of the multiparametric MRI data in our HSP patients confirmed the non-prominent involvement of the cortex in the primary motor regions but rather of other more associative areas. On the contrary, DTI demonstrated a widespread involvement of the brain WM, including the primary motor regions, which was confirmed at follow-up. The longitudinal analysis revealed an apparent inversion of tendency when considering the expected evolution of a neurodegenerative process: we detected an increase of FA and a decrease of MD and AD. These time-related modifications may suggest a repair attempt by the residual central WM fibers, which requires confirmation with a larger group of patients and with a longer time interval.

Formulation and Clinical Evaluation of Sodium Benzoate Oral Solution for the Treatment of Urea Cycle Disorders in Pediatric Patients.

BACKGROUND: Sodium benzoate, a common food preservative, is used in the treatment of patients with urea cycle disorders (UCDs) as it stimulates ammonia removal by a non-urea cycle-based pathway. Despite its use in the clinical routine, no commercially available oral formulations currently exist. Liquid formulation is normally well accepted in pediatric age and allows precise dosage according to the children's needs. AIMS: (1) To prepare an oral sodium benzoate solution in different tastes and determine its stability, palatability, and tolerability and (2) to describe the long-term follow-up of two pediatric patients with UCDs treated with our formulation. METHODS: We prepared five oral solutions of sodium benzoate (200 mg/ml) by adding different flavoring agents. We measured drug concentration in the samples by high-performance liquid chromatography (HPLC). We evaluated palatability and tolerability with adult volunteers. Long-term drug compliance and metabolic control were appraised in two pediatric patients. RESULTS: All the oral solutions remained stable at room temperature along the 96-day test period, and they were well tolerated. The mint-flavored solution resulted the most palatable and preferred by adult volunteers. We report good drug compliance and good metabolic outcomes for both pediatric patients during the entire follow-up. CONCLUSIONS: Our study highlighted the stability and tolerability of flavored sodium benzoate oral solutions. These solutions were well accepted during a long-term follow-up and guaranteed a good metabolic control. Since taste attributes are critical to ensure acceptable medication adherence in the pediatric age, flavored liquid formulations of sodium benzoate may be an efficient strategy to achieve therapeutic outcomes in UCD pediatric patients.

What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women's kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

What we do and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease (CKD) affects approximately 10% of the world's adult population; it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, which not only offers an opportunity for diagnosis of kidney disease, but also states where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing, and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease and what we might learn in the future to improve outcomes worldwide.

What we do and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants.  In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

[What we do and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day].

On behalf of the World Kidney Day Steering Committee Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

The pathogenic LRRK2 R1441C mutation induces specific deficits modeling the prodromal phase of Parkinson's disease in the mouse.

The aim of the present study was to further explore the in vivo function of the Leucine-rich repeat kinase 2 (LRRK2)-gene, which is mutated in certain familial forms of Parkinson's disease (PD). We generated a mouse model harboring the disease-associated point mutation R1441C in the GTPase domain of the endogenous murine LRRK2 gene (LRRK2 R1441C line) and performed a comprehensive analysis of these animals throughout lifespan in comparison with an existing knockdown line of LRRK2 (LRRK2 knockdown line). Animals of both lines do not exhibit severe motor dysfunction or pathological signs of neurodegeneration neither at young nor old age. However, at old age the homozygous LRRK2 R1441C animals exhibit clear phenotypes related to the prodromal phase of PD such as impairments in fine motor tasks, gait, and olfaction. These phenotypes are only marginally observable in the LRRK2 knockdown animals, possibly due to activation of compensatory mechanisms as suggested by in vitro studies of synaptic transmission. Thus, at the organismal level the LRRK2 R1441C mutation does not emerge as a loss of function of the protein, but induces mutation specific deficits. Furthermore, judged by the phenotypes presented, the LRRK2-R1441C knock-in line is a valid preclinical model for the prodromal phase of PD.

Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review.

BACKGROUND: Although vegan-vegetarian diets are increasingly popular, no recent systematic reviews on vegan-vegetarian diets in pregnancy exist. OBJECTIVES: To review the literature on vegan-vegetarian diets and pregnancy outcomes. SEARCH STRATEGY: PubMed, Embase, and the Cochrane library were searched from inception to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms. SELECTION CRITERIA: Vegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan-vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate. DATA COLLECTION AND ANALYSIS: The high heterogeneity of the studies led to a narrative review. MAIN RESULTS: We obtained 262 full texts from 2329 references; 22 selected papers reporting maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan-vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitamin B12 and iron deficiencies. AUTHOR'S CONCLUSIONS: The evidence on vegan-vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.

Predation-risk effects of predator identity on the foraging behaviors of frugivorous bats.

Predators directly and indirectly affect the density and the behavior of prey. These effects may potentially cascade down to lower trophic levels. In this study, we tested the effects of predator calls (playbacks of bird vocalizations: Tyto alba, Speotyto cunicularia, and Vanellus chilensis), predator visual stimuli (stuffed birds) and interactions of visual and auditory cues, on the behavior of frugivore phyllostomid bats in the field. In addition, we tested if the effects of predation risk cascade down to other trophic levels by measuring rates of seed dispersal of the tree Muntingia calabura. Using video recording, we found that bats significantly decreased the foraging frequency on trees when a visual cue of T. alba was present. However, no stimuli of potential predatory birds, including vocalization of T. alba, affected bat foraging frequency. There was a change in bat behavior during 7 min, but then their frequency of activity gradually increased. Consequently, the presence of T. alba decreased by up to ten times the rate of seed removal. These results indicate that risk sensitivity of frugivorous phyllostomid bats depends on predator identity and presence. Among the predators used in this study, only T. alba is an effective bat predator in the Neotropics. Sound stimuli of T. alba seem not to be a cue of predation risk, possibly because their vocalizations are used only for intraspecific communication. This study emphasizes the importance of evaluating different predator stimuli on the behavior of vertebrates, as well as the effects of these stimuli on trait-mediated trophic cascades.

BRAVISSIMO: 12-month results from a large scale prospective trial.

The BRAVISSIMO study is a prospective, non-randomized, multi-center, multi-national, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals in Italy. This manuscript reports the findings up to the 12-month follow-up time point for both the TASC A&B cohort and the TASC C&D cohort. The primary endpoint of the study is primary patency at 12 months, defined as a target lesion without a hemodynamically significant stenosis on Duplex ultrasound (>50%, systolic velocity ratio no greater than 2.0) and without target lesion revascularization (TLR) within 12 months. Between July 2009 and September 2010, 190 patients with TASC A or TASC B aortoiliac lesions and 135 patients with TASC C or TASC D aortoiliac lesions were included. The demographic data were comparable for the TASC A/B cohort and the TASC C/D cohort. The number of claudicants was significantly higher in the TASC A/B cohort, The TASC C/D cohort contains more CLI patients. The primary patency rate for the total patient population was 93.1%. The primary patency rates at 12 months for the TASC A, B, C and D lesions were 94.0%, 96.5%, 91.3% and 90.2% respectively. No statistical significant difference was shown when comparing these groups. Our findings confirm that endovascular therapy, and more specifically primary stenting, is the preferred treatment for patients with TASC A, B, C and D aortoiliac lesions. We notice similar endovascular results compared to surgery, however without the invasive character of surgery.

Kidney biopsy in pregnancy: evidence for counselling? A systematic narrative review.

BACKGROUND: Kidney diseases, which have a prevalence of 3% in women of childbearing age, are increasingly encountered in pregnancy. Glomerulonephritis may develop or flare up in pregnancy, and a differential diagnosis with pre-eclampsia may be impossible on clinical grounds. Use of kidney biopsy is controversial, but a systematic review has not been carried out to date. OBJECTIVES: To review the literature on kidney biopsy in pregnancy, with a focus on indications, risks and timing. SEARCH STRATEGY: Medline, Embase, CHINAL and the Cochrane Library were searched in September 2012, with 'pregnancy' and 'kidney biopsy' used as MESH and free terms, for the period 1980-2012. Results were filtered for 'human' if this option was available. SELECTION CRITERIA: Biopsies during pregnancy and within 2 months after delivery. Case reports (fewer than five cases) and kidney grafts were excluded. Paper selection was performed in duplicate. DATA COLLECTION AND ANALYSIS: Data were extracted in duplicate. The high heterogeneity in study design necessitated that the review be narrative, except for data on adverse events, which were analysed with regard to the timing of kidney biopsy. MAIN RESULTS: Of 949 references, 39 were selected, providing data on 243 biopsies in pregnancy and 1236 after delivery (timing was unclear in 106 women). The main aims of the studies were to define morphology in pre-eclampsia (23 studies), to carry out a risk-benefit analysis of kidney biopsy (11 studies), and to investigate pregnancy-related acute kidney injury (five studies). Four cases of major bleeding complications occurred at 23-26 weeks of gestation. Relevant complications were observed in 7% of women during pregnancy and 1% after delivery (P = 0.001). Kidney biopsy performed for the diagnosis of glomerulonephritis or pre-eclampsia led to therapeutic changes in 66% of cases. AUTHORS' CONCLUSIONS: The evidence on kidney biopsy in pregnancy is heterogeneous, but a significantly higher risk of complications (relative to postpartum biopsy) was found, with a possible peak at around 25 gestational weeks.

NEMO syndrome (incontinentia pigmenti) and systemic lupus erythematosus: a new disease association.

Congenital diseases are increasingly being recognised in adults because of clinical mimicry, variable clinical picture or rarity of the disease; pregnancy is a valuable diagnostic occasion. The present case is the first report of an association report between NEMO syndrome (an acronym of the mutated, non-functioning gene, NF-kB essential modulator), a rare X-linked disease, characterised by developmental anomalies, immunodepression and skin lesions, and systemic lupus erythematosus (SLE). A 35-year-old patient affected by SLE sought clinical advice in the 8th week of gestation. The diagnosis of SLE dated back to the age of 24, when multisystemic manifestations (pleuropericarditis, weight loss, alopecia, skin involvement, joint pain, kidney involvement) were observed. She had been treated with steroids since 1999; immunosuppressive drugs had been added for short periods. Developmental anomalies were present, including oligodontia, retinal problems, anomalies of the corpus callosum and pes planovalgus. Family history included multiple miscarriages, dental malformations and oligodontia and skin blistering in the first months of life. On these bases, incontinentia pigmenti (IP; or NEMO syndrome) was diagnosed and confirmed by genetic testing. The NEMO gene is implicated in immune deficiencies as well as in autoimmune diseases. This report may suggest a role for NF-kB essential modulator in the pathogenesis of SLE, in the context of the complex immunologic deficiencies increasingly associated with autoimmune diseases.

A ruptured right sinus of Valsalva diverticled aneurysm: echocardiographic diagnosis and surgical repair.

Aneurysms of sinus of Valsava (SV) are uncommon heart lesions resulting from either a congenital deficiency or an acquired degeneration of the aortic wall. Usually these lesions are asymptomatic and incidentally diagnosed by echocardiography. Therefore when rupture occurs, they might require a prompt surgical operation. We report the case of a 58-year-old man who suddenly developed chest pain. On physical examination a new finding of sistodyastolic murmur was detected. On two-dimensional echocardiography was evidenced an aneurysm of the right SV ruptured in the right atrium. The patient was submitted to urgent surgery. Surgical aneurysm exclusion was achieved through a double access either transaortic and trans-right atrium approach. The right SV was obliterated by suturing a dacron patch on the aortic site while complete exclusion of the aneurysm expanding in the right atrium, was acquired through the right atrium itself, by 5/0 continous prolene suture line. The postoperative course was uneventful and the patient was discharged on 6th postoperative day. Transesophageal echocardiography represent the gold standard technique to assess this disease and to plan the adequate surgical treatment. The management of an asymptomatic, non ruptured aneurysm is not clear, however surgery is advisable when the aneurysm is complicated by rupture with an acceptably low operative risk and good long-term outcome.

A peculiar pattern of expression of the transferrin receptor (CD71) by reticulocytes in patients given recombinant human erythropoietin (rHuEPO): a novel marker for abuse in sport?

To overcome the limitation of the currently adopted direct method to detect recombinant Human Erythropoietin (rHuEpo) abuse in sport, indirect analysis of blood parameters are increasingly used as part of the anti-doping strategies. The aim of the present work is to identify whether immunophenotype modifications on erythroid cells may be indicative of previous rHuEPO administration. The study was conducted on dialyzed patients under treatment with rHuEPO (DPT). Dialyzed patients without rHuEPO therapy (DP) and volunteer donors (H) were used as controls. The analysis of erythroid cells immunophenotype, performed using a multiparametric flow cytometry technique, showed a peculiar pattern of CD71 expression following rHuEPO treatment. In particular CD71 showed an increased expression in mature and intermediate reticulocytes and a surprisingly decreased expression in immature reticulocytes. In conclusion, the analysis of reticulocyte maturation stages with TO/CD71 double staining may be considered as a valid alternative indirect method for the detection of rHuEPO abuse.

Characterization and biological activity of the main flavonoids from Swiss Chard (Beta vulgaris subspecies cycla).

The molecular components of a phenolic fraction (P2), obtained from liquid chromatography of a Swiss Chard (Beta vulgaris subsp. cycla) extract, were identified using HPLC-ESI-MS/MS. The primary P2 components were: vitexin-2''O-rhamnoside, its demethylated form 2''-xylosylvitexin, isorhamnetin 3-gentiobioside, and rutin. P2 "in toto" and the single components were characterized for antioxidant capacity, antimitotic activity on MCF-7 human breast cancer cells and for toxicity to human lymphocytes and macrophages. P2 inhibited MCF-7 cell proliferation (IC(50) value = 9 microg/ml) without inducing apoptosis, showed no toxicity to human lymphocytes and slight toxicity to macrophages. Vitexin-2''O-rhamnoside strongly inhibited DNA synthesis in MCF-7 cells, whereas 2''-xylosylvitexin and isorhamnetin 3-gentiobioside were activators; combinations of activators and inhibitors maintained the over-all inhibitory effect.

Antibiotic treatment for acute 'uncomplicated' or 'primary' pyelonephritis: a systematic, 'semantic revision'.

The definition of acute pyelonephritis is controversial. There are two contrasting approaches: (1) acute pyelonephritis is a severe infectious disease involving the kidney parenchyma, and specific imaging techniques are required for diagnosis; (2) acute pyelonephritis is a urinary tract infection, and diagnosis and therapy follow simplified clinical and laboratory pathways. In this study, recent randomized controlled trials (RCTs) were systematically reviewed and the diagnostic and therapeutic approaches to acute 'uncomplicated' pyelonephritis were analysed. Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) and Chinal were searched employing Mesh, Emtree and free terms on 'pyelonephritis'. Limits included human, period (1995-2004), and trials-reviews (where available). In total, 904 references and 175 full-text were retrieved; 29 were pertinent RCTs. Seven RCTs were added from reference lists (indexed on urinary tract infections). Imaging examinations were performed in 11 of 14 studies on children (diagnostic requisite in two) and in two studies on adults; scarring was not analysed in adults. Clinical definitions varied widely (fever >37.8 to >39 degrees C, culture titres 10(4) >10(5)). Studies on adults were limited to short-term end-points (microbiological sterilization, clinical improvement). Duration of therapy was 4-20 days. The trend was towards shorter periods of therapy, mainly on an outpatient basis; intravenous therapy, if performed, was usually limited to the first 1-3 days. For acute uncomplicated pyelonephritis, the tendency is towards 2 weeks of mainly oral antibiotic therapy. However, the recent literature on adults does not discriminate among different upper urinary tract infections nor does it provide data on renal scarring. While cost constraints point towards short-term therapies, further studies are needed to assess the prevalence and long-term effect of kidney scars.