Search

Benign paroxysmal positional vertigo (BPPV) represents the most frequent cause of peripheral vertigo. In most cases, it is successfully treated using the canalith repositioning procedure, but it is often followed by continuous lightheadedness in the absence of vertigo or nystagmus (residual dizziness, RD). Our aim is to describe the clinical effectiveness and the urine metabolomics profile of treating these patients with polyphenol compound supplementation. We enrolled 30 patients reporting RD after BPPV of the posterior semicircular canal (PSC) successfully treated using the Semont maneuver. Supplementation with a polyphenol compound was administered for 60 days, and patients were evaluated after 30 and 60 days of treatment using self-administered questionnaires (Visual Analog Scales for Dizziness and Nausea, Dizziness Handicap Inventory, DHI) and urine metabolomics analysis performed using 1H-NMR spectroscopy and multivariate followed by univariate analysis. Most patients reported excellent or good efficacy in the treatment of RD with a significant decrease in VAS and DHI values. The metabolomics analysis identified six significant metabolites related to the treatment, namely 1-methylnicotinamide, anserine, hippurate, lysine, methyl succinate and urea, indicating the inflammatory activities and antioxidant properties of the polyphenol compound. These preliminary data suggest that supplementation with a polyphenol compound could induce some metabolic changes that can help in recovery from RD. However, future steps will require confirmation with a more significant cohort of patients and an extension of the metabolomics evaluation to other problems concerning the different clinical aspects of BPPV, such as the high rate of relapse.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder evolving over the lifetime of individuals. The oral and gut microbial ecosystems are closely connected to each other and the brain and are potentially involved in neurodevelopmental diseases. This narrative review aims to identify all the available evidence emerging from observational studies focused on the role of the oral microbiome in ASD. A literature search was conducted using PubMed and the Cochrane Library for relevant studies published over the last ten years. Overall, in autistic children, the oral microbiota is marked by the abundance of several microbial species belonging to the Proteobacteria phylum and by the depletion of species belonging to the Bacteroidetes phylum. In mouse models, the oral microbiota is marked by the abundance of the Bacteroidetes phylum. Oral dysbiosis in ASD induces changes in the human metabolome, with the overexpression of metabolites closely related to the pathogenesis of ASD, such as acetate, propionate, and indoles, together with the underexpression of butyrate, confirming the central role of tryptophan metabolism. The analysis of the literature evidences the close relationship between oral dysbiosis and autistic core symptoms; the rebuilding of the oral and gut ecosystems by probiotics may significantly contribute to mitigating the severity of ASD symptoms.

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the “omics” sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all “omics.” Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere’s disease. In conclusion, metabolomics study indicates a “fil rouge” that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine.

The integrity of the gastrointestinal tract structure and function is seriously compromised by two pathological conditions sharing, at least in part, several pathogenetic mechanisms: inflammatory bowel diseases (IBD) and coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IBD and COVID-19 are marked by gut inflammation, intestinal barrier breakdown, resulting in mucosal hyperpermeability, gut bacterial overgrowth, and dysbiosis together with perturbations in microbial and human metabolic pathways originating changes in the blood and fecal metabolome. This review compared the most relevant metabolic and microbial alterations reported from the literature in patients with IBD with those in patients with COVID-19. In both diseases, gut dysbiosis is marked by the prevalence of pro-inflammatory bacterial species and the shortfall of anti-inflammatory species; most studies reported the decrease in Firmicutes, with a specific decrease in obligately anaerobic producers short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii. In addition, Escherichia coli overgrowth has been observed in IBD and COVID-19, while Akkermansia muciniphila is depleted in IBD and overexpressed in COVID-19. In patients with COVID-19, gut dysbiosis continues after the clearance of the viral RNA from the upper respiratory tract and the resolution of clinical symptoms. Finally, we presented and discussed the impact of gut dysbiosis, inflammation, oxidative stress, and increased energy demand on metabolic pathways involving key metabolites, such as tryptophan, phenylalanine, histidine, glutamine, succinate, citrate, and lipids.

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022.

The effectiveness of SARS-CoV-2 vaccines is currently undermined by the rapid spread of variants of concern affecting an increasing number of people worldwide. Thus, new vaccine candidates are required to limit new waves of infections. On the one hand, the development of personalized vaccines, both on a personal and population level, may overcome the inter-individual heterogeneity in vaccine-induced immune responses and in adverse side effects. On the other hand, the development of a universal coronaviruses vaccine broadly protective against all betacoronaviruses may overcome the coronaviruses genetic polymorphism due to the generation of new genomes and homologous genetic recombination in multiple species. The preparation of a tailored and universal vaccine, that is an “ideal” vaccine, could be realized with the contribution of the system biology approach and, in particular, of metabolomics, in conjunction with a global policy strategy and adequate public governance.

ABSTRACT Necrotizing enterocolitis (NEC) is among the most relevant gastrointestinal diseases affecting mostly prematurely born infants with low birth weight. While intestinal dysbiosis has been proposed as one of the possible factors involved in NEC pathogenesis, the role of the gut microbiota remains poorly understood. In this study, the gut microbiota of preterm infants was explored to highlight differences in the composition between infants affected by NEC and infants prior to NEC development. A large-scale gut microbiome analysis was performed, including 47 shotgun sequencing data sets generated in the framework of this study, along with 124 retrieved from publicly available repositories. Meta-analysis led to the identification of preterm community state types (PT-CSTs), which recur in healthy controls and NEC infants. Such analyses revealed an overgrowth of a range of opportunistic microbial species accompanying the loss of gut microbial biodiversity in NEC subjects. Moreover, longitudinal insights into preterm infants prior to NEC development indicated Clostridium neonatale and Clostridium perfringens species as potential biomarkers for predictive early diagnosis of this disease. Furthermore, functional investigation of the enzymatic reaction profiles associated with pre-NEC condition suggested DL-lactate as a putative metabolic biomarker for early detection of NEC onset. IMPORTANCE Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease occurring predominantly in premature infants whose etiology is still not fully understood. In this study, the analysis of infant fecal samples through shotgun metagenomics approaches revealed a marked reduction of the intestinal (bio)diversity and an overgrowth of (opportunistic) pathogens associated with the NEC development. In particular, dissection of the infant’s gut microbiome before NEC diagnosis highlighted the potential involvement of Clostridium genus members in the progression of NEC. Remarkably, our analyses highlighted a gastrointestinal DL-lactate accumulation among NEC patients that might represent a novel potential functional biomarker for the early diagnosis of NEC.

Objective: To investigate changes in the urine metabolome of very low birth weight preterm newborns with necrotizing enterocolitis (NEC) and feed intolerance, we conducted a longitudinal study over the first 2 months of life. The metabolome of NEC newborns was compared with two control groups that did not develop NEC: the first one included preterm babies with feed intolerance, while the second one preterm babies with good feed tolerance.Methods: Newborns developing NEC within the 3 weeks of life were identified as early onset NEC, while the remaining as late onset NEC. Case-control matching was done according to the gestational age (±1 week), birth weight (± 200 g), and postnatal age. A total of 96 urine samples were collected and analyzed. In newborns with NEC, samples were collected before, during and after the diagnosis over the first 2 months of life, while in controls samples were collected as close as possible to the postnatal age of newborns with NEC. Proton nuclear magnetic resonance (1H NMR) spectroscopy was used for metabolomic analysis. Data were analyzed by univariate and multivariate statistical analysis.Results: In all the preterm newborns, urine levels of betaine, glycine, succinate, and citrate positively correlated with postnatal age. Suberate and lactate correlated with postnatal age in preterms with NEC and in controls with food intolerance, while N,N-dimethylglycine (N,N-DMG) correlated only in controls with good digestive tolerance. Preterm controls with feed intolerance showed a progressive significant decrease of N-methylnicotinamide and carnitine. Lactate, betaine, myo-inositol, urea, creatinine, and N,N-dimethylglycine discriminated late-onset NEC from controls with good feed tolerance.Conclusion: Our findings are discussed in terms of contributions from nutritional and clinical managements of patients and gut microbiota.

The aim of this work is to investigate 7 secrets of COVID-19 (fever, ACE2 receptors, gut-lung axis, metabolomics, microbiomics, probiotics, diet), hoping to reveal a small part of some of these and to increase anyhow the knowledge on SARS-CoV-2 and its weaknesses to be able to defeat it. In particular, in the opinion of the authors, significant improvements in contrasting the Coronavirus, and the pandemics that will follow, could derive from the use of “omics” disciplines, namely metabolomics (the stethoscope of the future) and microbiomics (an unrecognized player). The discovery of new biomarkers using metabolomics could be used in clinical practice as predictive diagnostic tools or to evaluate the effectiveness and toxicity of a drug, in order to be able to provide the patient with a personalized, tailor-made medicine: precision medicine. Our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our understanding of viral infection, and create new ways in which we might treat and prevent it. We strongly believe that the 3 M’s (Metabolomics, Microbiomics and Machine learning [Artificial Intelligence]) will be the right route to the future for risk assessment, early diagnosis, patient management and decision-making. By now, probiotics could help, fighting face to face against the virus. Moreover, the diet may be a key driver in determining the severity of COVID-19 and further studies are needed to explore the secret language between diet, bacteria, viruses and metabolites in determining individualized susceptibility or resilience to COVID-19.

The dramatic and rapid widespread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is causing millions of infected subjects and thousand of deaths worldwide. The current global goal is to mitigate or suppress the burden of COronaVIrus Disease 2019 (COVID-19) and to adopt effective targeted therapies. Laboratory tests include molecular diagnostics and viral antigens recognition for the identification of SARS-CoV-2 in human biological materials, serologic methods for detecting serum antibodies against SARS-CoV-2 and routine blood and urine tests. Many molecular tests, mainly based on real-time polymerase chain reaction (RT-PCR), have been developed after the publication of the SARS-CoV-2 full-length genome sequence; several factors may affect their accuracy, including inadequate sample collection, thermal inactivation, viral load, and cross-reactivity. In-vitro diagnostic (IVD) companies have developed serologic methods optimized on high throughput analytical platforms; however very few methods currently detect IgM and the accurate quantitative measurement of antibodies are not still ready. Sensitivity and specificity require robust validation; point of care (POC) lateral flow immunochromatographic assays are far to be highly sensitive and specific and data obtained by these methods should be evaluated with caution. The effectiveness of serologic tests depends on the appropriateness of test request too. Routine biochemical data in adults with COVID-19 reveal alterations of various tests, including lymphopenia, thrombocytopenia, hypoalbuminemia, and serum elevation of several biomarkers, including D-dimer, ferritin, C-reative protein (CRP), cytokines. Cardiac troponins and N-terminal pro-brain natriuretic peptide (NT-pro BNP) are predictors of adverse outcome and death. Vertical transmission of SARS-CoV-2 has been not yet demonstrated exhaustively. Regrettably, in pregnant women, newborns and children with COVID-19, very limited and confusing data hamper a definitive conclusion on the value of routine laboratory tests. Emerging opportunities arise from the introduction of microbiomics, metabolomics, and pharmacometabolomics for improving patient’s care and outcome.

This Special Issue aimed to collect studies based on clinical applications of metabolomics in human disease [...]

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2–12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites—namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

The ability of metabolomics to provide a snapshot of an individual’s metabolic state makes it a very useful technique in neonatology for investigating the complex relationship between nutrition and the state of health of the newborn. Through an 1H-NMR metabolomics analysis, we aimed to investigate the metabolic profile of newborns by analyzing both urine and milk samples in relation to the birth weight of neonates classified as AGA (adequate for the gestational age, n = 51), IUGR (intrauterine growth restriction, n = 14), and LGA (large for gestational age, n = 15). Samples were collected at 7 ± 2 days after delivery. Of these infants, 42 were exclusively breastfed, while 38 received mixed feeding with a variable amount of commercial infant formula (less than 40%) in addition to breast milk. We observed a urinary spectral pattern for oligosaccharides very close to that of the corresponding mother’s milk in the case of exclusively breastfed infants, thus mirroring the maternal phenotype. The absence of this good match between the infant urine and human milk spectra in the case of mixed-fed infants could be reasonably ascribed to the use of a variable amount of commercial infant formulas (under 40%) added to breast milk. Furthermore, our findings did not evidence any significant differences in the spectral profiles in terms of the neonatal customize centile, i.e., AGA (adequate for gestational age), LGA (large for gestational age), or IGUR (intrauterine growth restriction). It is reasonable to assume that maternal human milk oligosaccharide (HMO) production is not or is only minimally influenced by the fetal growth conditions for unknown reasons. This hypothesis may be supported by our metabolomics-based results, confirming once again the importance of this approach in the neonatal field.

BackgroundOwing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer.MethodsSeventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate γ-globulin. A percentage of PEG-precipitable TSH ≥80% was considered suggestive of mTSH.ResultsNo correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%±1.9% in thyroid cancer patients and 44.1%±3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients.ConclusionThe presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia.

Abstract Background This study aimed to assess the combined performance of serum (1,3)-β-d-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis between candidaemia and bacteraemia in three intensive care units (ICUs) in two large teaching hospitals in Italy. Methods From June 2014 to December 2015, all adult patients admitted to the ICU who had a culture-proven candidaemia or bacteraemia, as well as BDG and PCT measured closely to the time of the index culture, were included in the study. The diagnostic performance of BDG and PCT, used either separately or in combination, was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR+ and LR–). Changes from pre-test probabilities to post-test probabilities of candidaemia and bacteraemia were inferred from Fagan’s nomograms. Results One hundred and sixty-six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia (56%). When both markers indicated candidaemia (BDG ≥80 pg/ml and PCT

We reported data concerning the Gas Chromatography–Mass Spectrometry (GC–MS) based metabolomic analysis of amniotic fluid (AF) samples obtained from pregnant women infected with Human Cytomegalovirus (HCMV). These data support the publication “Primary HCMV Infection in Pregnancy from Classic Data towards Metabolomics: an Exploratory analysis” (C. Fattuoni, F. Palmas, A. Noto, L. Barberini, M. Mussap, et al., 2016) [2]. GC–MS and Multivariate analysis allow to recognize the molecular phenotype of HCMV infected fetuses (transmitters) and that of HCMV non-infected fetuses (non-transmitters); moreover, GC–MS and multivariate analysis allow to distinguish and to compare the molecular phenotype of these two groups with a control group consisting of AF samples obtained in HCMV non-infected pregnant women. The obtained data discriminate controls from transmitters as well as from non-transmitters; no statistically significant difference was found between transmitters and non-transmitters.

Autism diagnosis is moving from the identification of common inherited genetic variants to a systems biology approach. The aims of the study were to explore metabolic perturbations in autism, to investigate whether the severity of autism core symptoms may be associated with specific metabolic signatures; and to examine whether the urine metabolome discriminates severe from mild-to-moderate restricted, repetitive, and stereotyped behaviors. We enrolled 57 children aged 2–11 years; thirty-one with idiopathic autism and twenty-six neurotypical (NT), matched for age and ethnicity. The urine metabolome was investigated by gas chromatography-mass spectrometry (GC-MS). The urinary metabolome of autistic children was largely distinguishable from that of NT children; food selectivity induced further significant metabolic differences. Severe autism spectrum disorder core deficits were marked by high levels of metabolites resulting from diet, gut dysbiosis, oxidative stress, tryptophan metabolism, mitochondrial dysfunction. The hierarchical clustering algorithm generated two metabolic clusters in autistic children: 85–90% of children with mild-to-moderate abnormal behaviors fell in cluster II. Our results open up new perspectives for the more general understanding of the correlation between the clinical phenotype of autistic children and their urine metabolome. Adipic acid, palmitic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid can be proposed as candidate biomarkers of autism severity.

Metabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests.

In the United States, a very recent survey performed on children aged 8 years assessed an overall prevalence of 16.8 autistic children every 1,000 non-ASD children (equal to 1 child every 59), with a higher prevalence in boys (26.6 per 1,000) than in girls (6.6 per 1,000). Actually, very few human diseases like ASD can be considered the result of interplay between a multitude of factors: genetics, epigenetics, environment, socioeconomic status, maternal and neonatal infections, prenatal nutrients (i.e. folic acid), immune system, gut microbiota composition, maternal exposure to potentially toxic drugs (e.g. thalidomide) and environmental toxicants, and formula feeding (instead of breastfeeding). Taken individually, each of these factors may be considered a potential risk factor for developing ASD. However, the wide range of symptoms and disabilities depicting ASD as a “galaxy of social and communication difficulties” takes place through the combination of two or more factors cited above; notably, the role of each (e.g. genetics) cannot be dissociated from the context of epigenetic mechanisms and specific interactions. Today, we can accurately explore the metabolome and its variations over time in various perinatal conditions involved in ASD etiology, for example perturbations of the gut-brain axis, due to gut dysbiosis, and to the lack of the intestinal mucosal barrier, caused by inflammation. This means a great opportunity to establish an early diagnosis of ASD, to assess the risk of developing postnatal ASD and to search for new highly sensitive and specific biomarkers especially in urine. Most of the performed studies have found abnormalities in gut bacterial-derived compounds, tryptophan, vitamin B6, and purine metabolic pathways, phenylalanine and tyrosine biosynthesis, unbalanced concentration of intermediary compounds of the tricarboxylic acid cycle (TCA), also known as the citric-acid or Krebs cycle, and finally diet-derived metabolites. By using 1H NMR spectroscopy, our group found a combination of increased and decreased concentrations of: hippurate, glycine, creatine, tryptophan, D-threitol, and glutamate, creatinine, lactate, valine, betaine, and taurine, respectively. These findings strongly suggest a crucial role of oxidative stress and gut microflora in ASD development. In children with ASD, gut dysbiosis is characterized by the increase in Clostridium, Alistipes, Akkermansia, Caloramator, Sarcina spp., and by the reduction in Prevotella spp., E. siraeum, and Bifidobacterium spp. As a result, in these children the urine metabolome is marked by alterations in hippuric acid, p-hydroxyphenylacetic acid and 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid concentration. Moreover, propionic acid, related to Clostridium spp. is strongly involved. Metabolomics can lead to the discovery of dozens of biomarkers strongly implicated in the pathogenesis of ASD (i.e. mannitol, L-threonic acid, fucose, glycine, serine, and many others). Finally, the potential toxicity of acetaminophen (paracetamol), a very common analgesic and antipyretic drug widely used during pregnancy, after birth and in early childhood should be carefully considered in combination with the microbiome.

Metabolomics, the latest of the “omics” sciences, has a non-selective approach and can thus lead to the identification of all the metabolites (molecules < 1 kDa) in a biological system. The metabolomic profile can be considered the most predictive phenotype capable of evaluating epigenetic modifications determined by external factors. It is so close to the phenotype as to be considered the phenotype itself in its unique individuality (fingerprinting), both in health (phenome), and disease (diseasome). Urine, compared to other biological liquids, has the advantage of being a complex fluid with many components, including intermediate metabolites. Metabolomics may thus play a role in the study of different kidney diseases and overcome diagnostic difficulties. We shall present the studies that to our knowledge have been published on Nephrology and Pediatric Nephrology. Some are experimental while others are clinical. We have not considered carcinomas and transplantations. Although scarce, the data on adults and the very few ones in pediatrics are quite interesting. Further studies on kidneys are needed to determine the practical clinical impact of metabolomics in kidney renal pathologies. The “multiplatform” “omic” study of urine and namely metabolomics can contribute to improving early diagnosis and the outcome of kidney diseases.

Serum IgE assay is a mainstay step in the allergy work up. Allergenic extracts and molecular components are available at present. This real life study compared the serum specific IgE levels against allergenic extracts with allergenic molecules in patients allergic to Parietaria, Betulaceae, and mites. This retrospective real life study included 489 subjects with respiratory allergy. Inclusion criteria were 1) documented diagnosis of allergic rhinitis (AR) and/or allergic asthma, and 2) documented allergy to Parietaria judaica (Par j) 2 (216 patients: 112 females, mean age 42 years), or to Betula verrucosa (Bet v) 1 (62 patients: 35 females, mean age 3 years), or Dermatophagoides pteronyssinus (Der p) 1 (211 patients: 107 females, mean age 34 years); and mono-allergy. Serum IgE, specific both for total/crude allergen extracts and individual purified/recombinant allergens, were assessed by ImmunoCap system. The serum IgE levels to birch extract were very strongly (R2=0.96) related to IgE to Bet v 1. There was a strong (R2=0.71) correlation between Dermatophagoides pteronyssinus IgE and Der p 1. A very strong (R2=0.87) correlation also existed between Parietaria extract IgE and Par j 2 IgE levels. However, there was discrepancy between percentages of positivity between allergenic extracts and molecules. Therefore, allergen molecular diagnostics may represent a useful way in allergy work up, but deserves caution in particular circumstances.

This paper is a prelude to proceedings of the 10th International Workshop on Neonatology to be held in Cagliari, Italy from October 21st to 25th, 2014. These proceedings will be a significant milestone, highlighting the new frontiers of perinatal and neonatal research. Over the five days of this meeting, we aim to (1) examine the roots of the new directions in perinatal and neonatal research; (2) predict the trajectories of advancement in medical technologies, research, clinical care and teaching that will be the future of perinatology and neonatology. The discussion will be in four sections: • back to the future: the placenta and perinatal programming; • paradigm shift: the revolution of metabolomics in perinatalogy and neonatology; • brave new world: the microbiome and microbiomics from perinatal to adult life; • new inhabitants on the planet earth: adults who were born with extremely low birth weight. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy) · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

There are currently approximately one hundred biomarkers used in clinical practice, very few (a drop in the ocean) in comparison with the large numbers acclaimed in more than 150,000 scientific papers; intriguingly, most of these promising biomarkers will never become part of routine clinical practice. The ability of high throughput proteomics, metabolomics and other 'omics' platforms to profile a large number of analytes in a single array is increasing the complexity of biomarker validation. This innovation calls for global re-thinking of the role of clinical pathologists in transforming experimental data into clinically available tests. It has become more and more clear that health and disease can only be studied in an outstanding way by using complex systems such as integrative systems biology, systems medicine, and network medicine. In particular metabolomics will contribute to guiding the medicine of the past, towards the medicine of the present and the medicine of the future and perhaps will actually contribute to unveil many mysteries of medicine. The dynamic range of the metabolome is revealed by subjecting the organism to physiological and pathological changes in the state of health: this means that we are quite different from each other and these differences are accentuated when faced with changes, especially if very significant and/or extreme, for example, in cases of fasting or asphyxia. Indeed, in the next few years we will witness a profound change in medicine and healthcare as a result of progresses in technology and the ability to analyze large amounts of data from single patients (Big Data). Only by being aware of complexity and biological variability, by improving our knowledge, by feeding and treating different individuals in different ways, and most of all by better defining the state of health of each individual and his/her resilience, will medicine be in a position to respond in a personalized and customized way (and not approximately and epidemiologically) to the problems of human health. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

Our times are characterized by the dichotomy between the increasing need for health care and the global decrease in economic resources. Neonatology is at the centre of this scenario for several reasons. Firstly, the availability of molecular and genetic tests has made possible the accurate prenatal diagnosis of a series of diseases caused by transmissible and non-transmissible genetic defects, thus leading to the development of large-scale screening programmes and the consequent proper medical and surgical treatments. Secondly, thanks to improvements in assistance in intensive therapy in the last fifteen years, there has been a substantial increase in low, very low and extremely low weight premature births (LBW, VLBW and ELBW respectively). The survival rate of these premature neonates is good and their quality of life following the neonatal period has also improved. How can we combine the need to count on excellent laboratory diagnoses with the need to reduce the cost of healthcare and, more in particular, the costs of purchasing advanced systems of diagnosis? Three considerations can be formulated: 1) it is essential to eliminate waste, but it is just as essential to ensure the quality of the products (instrumentation and diagnostic kits); 2) we should change the objective of issuing tenders for the supplying of health equipment and services from the present scenario, which provides for supply contracts, often in-service, of diagnostic systems, we should change to contracts that call for a policy of savings through the providing of products of excellence. Although at first sight this may appear paradoxical, in reality it masks a vaster matter that involves different stakeholders: health professionals, suppliers and the public administration; 3) the use of sophisticated techniques and the study of molecular profiles are capable of generating far-reaching prospects for healthcare, investments and savings. An example of this is represented by metabolomics, one of the emerging “omics” disciplines, applicable in numerous fields such as that of infections of neonates and children. If, by means of experimental studies properly validated in clinical trials, metabolomics were found to be capable of recognizing eight to ten metabolites, thus making early identification of a clinical picture of systemic infection possible, an industrial investment could lead to the production of a dipstick containing these freeze-dried metabolites, like the dipstick commonly used in the chemical and physical analysis of urine. Such a disposable item would be extremely easy to use, economical and available to all mothers for testing the risk of sepsis of their babies simply by immersing the stick in the urine at a cost estimated at less than half a US dollar.

Candida is an important cause of bloodstream infections (BSI), causing significant mortality and morbidity in health care settings. From January 2008 to December 2010 all consecutive patients who developed candidemia at San Martino University Hospital, Italy were enrolled in the study. A total of 348 episodes of candidaemia were identified during the study period (January 2008-December 2010), with an incidence of 1,73 episodes/1000 admissions. Globally, albicans and non-albicans species caused around 50% of the cases each. Non-albicans included Candida parapsilosis (28.4%), Candida glabrata (9.5%), Candida tropicalis (6.6%), and Candida krusei (2.6%). Out of 324 evaluable patients, 141 (43.5%) died within 30 days from the onset of candidemia. C. parapsilosis candidemia was associated with the lowest mortality rate (36.2%). In contrast, patients with C. krusei BSI had the highest mortality rate (55.5%) in this cohort. Regarding the crude mortality in the different units, patients in Internal Medicine wards had the highest mortality rate (54.1%), followed by patients in ICU and Hemato-Oncology wards (47.6%).This report shows that candidemia is a significant source of morbidity in Italy, with a substantial burden of disease, mortality, and likely high associated costs. Although our high rates of candidemia may be related to high rates of BSI in general in Italian public hospitals, reasons for these high rates are not clear and warrant further study. Determining factors associated with these high rates may lead to identifying measures that can help to prevent disease.