The Use of Multiplex Real-Time PCR for the Simultaneous Detection of Foodborne Bacterial Pathogens.

Foodborne pathogens continue to be a major health concern worldwide. Culture-dependent methodologies are still considered the gold standard to perform pathogen detection and quantification. These methods present several drawbacks, such as being time-consuming and labor intensive. The implementation of real-time PCR has allowed to overcome these limitations, and even reduce the cost associated with the analyses, due to the possibility of simultaneously and accurately detecting several pathogens in one single assay, with results comparable to those obtained by classical approaches. In this chapter, a protocol for the simultaneous detection of two of the most important foodborne pathogens, Salmonella spp. and Listeria monocytogenes, is described.

Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.

A major driver of neuronal hyperexcitability is dysfunction of K+ channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders. However, the impact of these variants on the molecular mechanisms underlying KCNQ3 channel function remains poorly understood and existing treatments have significant side effects. Here, we use voltage clamp fluorometry, molecular dynamic simulations, and electrophysiology to investigate NDD-associated variants in KCNQ3 channels. We identified two distinctive mechanisms by which loss- and gain-of function NDD-associated mutations in KCNQ3 affect channel gating: one directly affects S4 movement while the other changes S4-to-pore coupling. MD simulations and electrophysiology revealed that polyunsaturated fatty acids (PUFAs) primarily target the voltage-sensing domain in its activated conformation and form a weaker interaction with the channel's pore. Consistently, two such compounds yielded partial and complete functional restoration in R227Q- and R236C-containing channels, respectively. Our results reveal the potential of PUFAs to be developed into therapies for diverse KCNQ3-based channelopathies.

The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease.

PURPOSE: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. METHODS: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease. RESULTS: Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection. CONCLUSIONS: A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease.

Survival of infection with TEM ß-lactamase-producing Escherichia coli with Pan-ß-lactam resistance.

BACKGROUND: Antimicrobial resistance is a critical global health issue, significantly contributing to patient mortality. Recent antibiotic developments have aimed to counteract carbapenemase-producing Enterobacterales; however, the impact of their use on the emergence of antibiotic resistance is unknown. This study investigates the first case of a non-carbapenemase-producing, pan-ß-lactam-resistant Escherichia coli strain from a patient previously treated with ceftolozane-tazobactam and cefiderocol. METHODS: This study describes the clinical progression of a 39-year-old ICU patient who developed multiple infections, culminating in the isolation of a pan-ß-lactam-resistant E. coli strain (EC554). The resistance profile was characterised through MIC determination, whole-genome sequencing, the use of the ß-lactam inactivation method, RT-qPCR, efflux pump inhibition assays, outer membrane protein analysis, and blaTEM transformation. FINDINGS: The EC554 isolate displayed resistance to all tested ß-lactams and ß-lactam-ß-lactamase inhibitor combinations. Whole-genome sequencing revealed four plasmids in EC554, with the only ß-lactamase gene being blaTEM-252 on the pEC554-PBR-X1-X1 plasmid. We found that the extremely resistant phenotype was attributable to a combination of different mechanisms: a high expression of TEM-252, efflux pump activity, porin loss, and PBP3 mutations. INTERPRETATION: The findings illustrate the complex interplay of multiple resistance mechanisms in E. coli, highlighting the potential for high-level resistance even without carbapenemase production. This study underscores the importance of comprehensively characterising resistance mechanisms in order to inform effective treatment strategies and mitigate the spread of resistant strains.

Role of rectal colonization by third-generation cephalosporin-resistant Enterobacterales on the risk of surgical site infection after hepato-pancreato-biliary surgery.

The impact of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) rectal colonization in the development of subsequent infection after surgery is controversial. In particular, there is a lack of data in the context of hepato-pancreato-biliary (HPB) surgery. The objective of this study was to assess the prevalence of 3GCR-E intestinal carriage among patients undergoing elective HPB resection surgery and its impact on the incidence and etiology of surgical site infections (SSIs). This retrospective cohort study (January 2016-December 2022) was performed at Valme University Hospital (Seville, Spain). The inclusion criteria included (i) 18 years of age or older, (ii) undergoing elective HPB resection surgery, and (iii) availability of a periprocedural surveillance rectal swab culture to detect 3GCR-E. The prevalence of 3GCR-E intestinal carriage at elective HPB resection surgery was assessed, as well as SSI incidence at 30 days and possible associated factors. Two hundred nine patients were included. Eleven (5.3%) patients were colonized by 3GCR-E at baseline. According to 3GCR-E carriage status, 6 (55%) of the carriers developed SSI, whereas this occurred in 50 (25%) of non-carriers (P = 0.033). Likewise, the rates of SSI caused specifically by 3GCR-E were 83% (5 of 6) in 3GCR-E carriers and 6% (3 of 50) in non-carriers (P < 0.001). After multivariate analyses, 3GCR-E colonization at the time of surgery was identified as an independent predictor for developing SSI (adjusted odds ratio 4.63, 95% confidence interval: 1.177-18.232, P = 0.028). Despite a low prevalence of 3GCR-E intestinal carriage at surgery, 3GCR-E rectal colonization is associated with a higher risk of SSI among patients undergoing elective HPB resection surgery, with most SSIs being caused by the colonizing bacteria. IMPORTANCE: In this Spanish retrospective cohort study, previous 3GCR-E rectal colonization was associated with a higher risk of SSI after hepato-pancreato-biliary resection surgeries. Most of SSIs were caused by the colonizing bacteria, suggesting a rationale for adapted perioperative antibiotic prophylaxis in known 3GCR-E colonized patients.

Closing the value-based circle in shared decision-making: a digital framework for informing the shared decision-making process through patient reported outcome and experience measures.

Background: The spreading adoption of value-based models of healthcare delivery has incentivized the use of patient-reported outcomes and experience measures (PROMs and PREMs) in clinical practice, with the potential to enrich the decision-making process with patient-reported data. Methods: This perspective article explores PROs and the shared decision-making (SDM) process as components of value-based healthcare. We describe the potential of PROMs and PREMs within the decision-making process and present a digital framework for informing the shared decision-making process using aggregated data from a healthcare system PROMs and PREMs program, including early results from implementation in hospital network in Madrid, Spain. Results: The proposed digital framework incorporates aggregated data from a hospital network PROMs and PREMs program as part of a digital patient decision aid (PDA) for patients with lymphoma. After the first hematologist appointment, participating patients access the PDA to review relevant information about clinical and patient-reported outcomes for each of the possible options, assign a personal order of priority to different outcomes, and then select their preferred course of action. Patients' answers are automatically uploaded to the EHR and discussed with hematologists at the next appointment. After beginning treatment, patients are invited to participate in the network PROMs program; participants' PROMs data are fed back into the PDA, thus "closing the circle" between the decision-making process and patient-reported data collection.During the first 14 months after launching the decision aid in October 2022, of 25 patients diagnosed with follicular lymphoma at the four participating hospitals, 13 patients decided to participate. No significant differences in age or sex were observed between groups. Average SDM Q-9 score for patients filling in the questionnaire (n = 6) was 36.15 of 45 points. Conclusion: Various obstacles toward widespread implementation of SDM exist such as time constraints, lack of motivation, and resistance to change. Support and active engagement from policy makers and healthcare managers is key to overcome hurdles for capturing patient-reported data and carrying out shared decision-making at healthcare system level. Early results of a digital framework for PRO-enriched SDM seem to be beneficial to the decision-making process.

Phthalates and fatty acid markers in free-ranging cetaceans from an insular oceanic region: Ecological niches as drivers of contamination.

Plastic additives, such as phthalates, are ubiquitous contaminants that can have detrimental impacts on marine organisms and overall ecosystems' health. Valuable information about the status and resilience of marine ecosystems can be obtained through the monitoring of key indicator species, such as cetaceans. In this study, fatty acid profiles and phthalates were examined in blubber biopsies of free-ranging individuals from two delphinid species (short-finned pilot whale - Globicephala macrorhynchus, n = 45; common bottlenose dolphin - Tursiops truncatus, n = 39) off Madeira Island (NE Atlantic). This investigation aimed to explore the relations between trophic niches (epipelagic vs. mesopelagic), contamination levels, and the health status of individuals within different ecological and biological groups (defined by species, residency patterns and sex). Multivariate analysis of selected dietary fatty acids revealed a clear niche segregation between the two species. Di-n-butylphthalate (DBP), diethyl phthalate (DEP), and bis(2-ethylhexyl) phthalate (DEHP) were the most prevalent among the seven studied phthalates, with the highest concentration reached by DEHP in a bottlenose dolphin (4697.34 ± 113.45 ng/g). Phthalates esters (PAEs) concentration were higher in bottlenose dolphins (Mean ∑ PAEs: 947.56 ± 1558.34 ng/g) compared to pilot whales (Mean ∑ PAEs: 229.98 ± 158.86 ng/g). In bottlenose dolphins, DEHP was the predominant phthalate, whereas in pilot whales, DEP and DBP were more prevalent. Health markers suggested pilot whales might suffer from poorer physiological conditions than bottlenose dolphins, although high metabolic differences were seen between the two species. Phthalate levels showed no differences by ecological or biological groups, seasons, or years. This study is the first to assess the extent of plastic additive contamination in free-ranging cetaceans from a remote oceanic island system, underscoring the intricate relationship between ecological niches and contaminant exposure. Monitoring these chemicals and their potential impacts is vital to assess wild population health, inform conservation strategies, and protect critical species and habitats.

Effectiveness of virtual-walking intervention combined with exercise on improving pain and function in incomplete spinal cord injury: a feasibility study.

STUDY DESIGN: A feasibility pilot study. OBJECTIVE: To assess the feasibility a full-scale Randomized Controlled Trial aimed at assessing the beneficial effect of a Virtual Walking (VW)-based (Experimental intervention (EI)) on neuropathic pain and functionality in people with incomplete spinal cord injury (SCI). SETTING: A hospital service (Hospital Universitario y Politécnico La Fe) and disability associations (TetraSport, CODIFIVA and ASPAYM). METHODS: Twelve people with chronic incomplete SCI were randomized to EI (VW plus therapeutic exercise program (TE)) -or Control Intervention (CI (placebo VW and TE)) groups. A six-week intervention (3 sessions/week) was carried out. To assess feasibility, the following outcomes were used: level of restriction and validity of inclusion and exclusion criteria, participants' compliance, accessibility and acceptability of the intervention for participants, adequate pre-training time of physiotherapists. To explore therapy effectiveness, pain severity, and interference, mean and maximum isometric strength, walking speed, and walking ability were assessed before (Time 1, T1) and after (Time 2, T2) the intervention. RESULTS: 20% of the participants initially recruited did not meet inclusion criteria. In addition, all participants completed at least 80% of the intervention sessions and none of the participants dropped out before T2. No serious adverse event was found. Moreover, 91.67% of participants were willing to perform the intervention again and all therapists involved were adequately pre-trained. Finally, our preliminary results suggest that the proposed EI is effective. CONCLUSION: A full-scale RCT is feasible and preliminary results suggest that VW with TE could have a beneficial impact on pain and functionality in this population.

Multiple pathways for lanthanide sensitization in self-assembled aqueous complexes.

Lanthanide photoluminescence (PL) emission has attracted much attention for technological and bioimaging applications because of its particularly interesting features, such as narrow emission bands and very long PL lifetimes. However, this emission process necessitates a preceding step of energy transfer from suitable antennas. While biocompatible applications require luminophores that are stable in aqueous media, most lanthanide-based emitters are quenched by water molecules. Previously, we described a small luminophore, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid (PAnt), which is capable of dynamically coordinating with Tb(III) and Eu(III), and its exchangeable behavior improved their performance in PL lifetime imaging microscopy (PLIM) compared with conventional lanthanide cryptate imaging agents. Herein, we report an in-depth photophysical and time-dependent density functional theory (TD-DFT) computational study that reveals different sensitization mechanisms for Eu(III) and Tb(III) in stable complexes formed in water. Understanding this unique behavior in aqueous media enables the exploration of different applications in bioimaging or novel emitting materials.

Incidence and long-term outcomes of upper limb deep vein thrombosis associated with intracardiac devices: analysis of bleeding, recurrence, and sequelae.

Pacemakers (PM) and implantable cardioverter-defibrillators are vital devices in contemporary clinical practice, but their growing adoption poses challenges. Complications, including lead migration, infections, and post-implantation venous thrombosis, underscore the importance of comprehensive investigation. This retrospective observational study enrolled patients diagnosed with upper limb deep vein thrombosis (DVT) secondary to intracardiac devices at a tertiary hospital from 2015 to 2022. The aim of the study was to determine the incidence and long-term outcomes (bleeding, DVT recurrence and sequelae) in these patients. Across the study period, 2681 intracardiac devices were implanted, with 12 cases of upper limb DVT documented. The majority of patients were male (91.7%), with a mean age of 63.92 years. DVT occurred in patients with PM (50%), implantable cardioverter-defibrillators (25%) and implantable cardioverter-defibrillators with Cardiac Resynchronization Therapy (25%). Treatment encompassed low-molecular-weight heparin (91.7%) during the acute episode and long-term anticoagulation with direct oral anticoagulants (75%) or vitamin K antagonists (25%). Over a mean follow-up period of 33.17 months, half of the patients exhibited long-term sequelae, notably collateral circulation (66.7%). Remarkably, no thrombosis recurrences were observed during follow-up. However, one patient (8.3%) experienced a major bleeding event during treatment, and one patient (8.3%) required device removal (PM) due to persistent symptoms. This study revealed upper limb DVT occurred in 0.45% of patients after intracardiac device implantation. Rate of thrombosis recurrence was low during follow-up. Although half of the patients developed long-term sequelae, the need for prolonged anticoagulant therapy in these cases remains uncertain.

Impact of the Choice of Diagnostic Criteria and Growth Reference on the Prevalence of Extrauterine Growth Restriction in Extremely-Low-Birthweight Infants.

BACKGROUND AND OBJECTIVES: Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. MATERIALS AND METHODS: An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. RESULTS: The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). CONCLUSIONS: The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.

Soluble urokinase type plasminogen activator receptor (suPAR) and mortality in acute pulmonary embolism.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated. MATERIAL AND METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality. RESULTS: Fifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48-0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63-61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69-40.99; p<0.01). CONCLUSION: suPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE.

Prenatal Screening for Chagas Disease in the Province of Guadalajara, Spain.

Introduction Chagas disease is caused by the protozoan Trypanosoma cruzi. It is endemic in 21 countries in Central and South America. Spain is the only nonendemic country with the highest number of Chagas disease cases outside the Americas. The only transmission mechanism in Spain is vertical transmission. Materials and methods We reviewed the records of pregnant women from endemic countries who underwent prenatal care at the Hospital Universitario de Guadalajara, from January 1, 2009, to December 31, 2022, to determine the rate of Chagas disease screening and vertical transmission. Results Out of a total of 1,681 pregnant women from endemic countries, prenatal screening was conducted on 316 (18.7%) of them. According to our study, the prevalence of the disease in the population of pregnant women from endemic countries is 0.95% with a 95% confidence interval (ranging from 0.32% to 2.75%), with three out of the 316 screened women testing positive for the disease. All positive cases were among Bolivian women. Vertical transmission was not observed in any of the cases. However, because of the small sample size, this study cannot conclusively determine the vertical transmission rate in the province of Guadalajara. Conclusions Implementing regulated prenatal screening protocols for Chagas disease at regional or national levels is necessary to increase the rate of prenatal screening. Additionally, increasing awareness of this condition among healthcare professionals and at-risk populations could further improve prenatal screening rates and treatment adherence.

Abdominal wall muscle weakness outcomes after split abdominal flap repair of large congenital diaphragmatic hernias in newborn.

PURPOSE: Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could be any associated abdominal muscle weakness. Our aim is to analyze the evolution of this abdominal muscle wall weakness. METHODS: Retrospective review of CDH repair by SAWMF (internal oblique muscle and transverse) from 2004 to 2023 focusing on the evolution of muscle wall weakness. RESULTS: Eighteen neonates of 148 CDH patients (12,1%) were repaired using SAWMF. Mean gestational age and birth weight were 35.7 ± 3.5 weeks and 2587 ± 816 g. Mean lung-to-head ratio was 1.49 ± 0.28 and 78% liver-up. Seven patients (38%) were prenatally treated by tracheal occlusion. Ninety-four percent of the flaps were used for primary repair and one to repair a recurrence. One patient (5.6%) experienced recurrence. Abdominal muscle wall weakness was present in the form of a bulge. Resolution of weakness at 1, 2 and 3 years was 67%, 89% and 94%, respectively. No patient required treatment for weakness or died. CONCLUSIONS: Abdominal muscular weakness after a split abdominal wall muscle flap repair is not a limitation for its realization since it is asymptomatic and presents a prompt spontaneous resolution. LEVEL OF EVIDENCE: IV.

Capabilities and limitations of Pb, Sr and Fe isotopic analysis of iron-rich slags: a case study on the medieval port at Hoeke (Belgium).

In this work, an analytical approach was developed for Pb, Sr, and Fe isotopic analysis of archaeological samples recovered from an iron work site by using multi-collector inductively coupled plasma - mass spectrometry (MC-ICP-MS). The sample types include slag, coal, clay and hammer scales, all obtained from an archaeological site at Hoeke (Belgium). Despite the wide concentration range of the target elements present in the samples and some sample manipulations necessarily performed outside of a clean laboratory facility, the analytical procedure yielded accurate and precise results for QA/QC standards while blank levels were negligible. Preliminary results concerning Pb, Sr and Fe isotope ratio variations in archaeological materials associated with iron working processes are provided. The samples revealed high variability in metal isotopic compositions, with the 208Pb/207Pb ratio ranging from 2.4261 to 2.4824, the 87Sr/86Sr ratio from 0.7100 to 0.7220, and δ 56Fe values from -0.34 to +0.08‰, which was tentatively attributed to the mixing of materials during the iron production process or variability within the source material. Also, contamination introduced by coal and furnace/hearth lining material could have contributed to the wide range of isotopic compositions observed. Because of the absence of information and data for primary ore samples to compare with, the provenance of the materials could not be established. The present study highlights the challenges in interpreting archaeological data, particularly in terms of the isotopic variability observed. It underscores the necessity of integrating analysis data with historical and archaeological knowledge. Further research, involving detailed analysis of these source materials combined with robust historical evidence, is essential to validate hypotheses concerning the origin of iron.

Extrauterine growth restriction in very-low-birthweight infants: prevalence and concordance according to Fenton, Olsen, and INTERGROWTH-21st growth charts in a multicenter Spanish cohort.

Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, "true" cross-sectional, and "true" longitudinal definitions. Concordance was assessed with Fleiss' kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and "true") was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and "true" cross-sectional) and INTERGROWTH-21st (longitudinal and "true" longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, "true" cross-sectional, and "true" longitudinal. Concordance was good or very good for EUGR by length and head circumference.Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR. What is known: • EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and "true" definition) • Different growth charts have been used for EUGR diagnosis What is new: • Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants • For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length.

Neurolipid systems: A new target for the treatment of dementia.

Neurolipids comprise a diverse class of bioactive lipids that include molecules capable of activating G protein­coupled receptors, thereby inducing systemic effects that contribute to the maintenance of homeostasis. Dementia, a non­specific brain disorder characterized by a common set of signs and symptoms, usually arises subsequent to brain injuries or diseases and is often associated with the aging process. Individuals affected by dementia suffer from the disruption of several neurotransmitter and neuromodulatory systems, among which neurolipids play an important role, including the endocannabinoid, lysophosphatidic acid and sphingosine 1­phosphate systems. In this review, we present an overview of the most recent and pertinent findings regarding the involvement of these neurolipidic systems in dementia, including data from a wide range of both in vitro and in vivo experiments as well as clinical trials.

Determinants of Metastatic Colorectal Cancer With Permanent Liver- Limited Disease.

Colorectal cancer (CRC) is a complex and genetically heterogeneous disease presenting a specific metastatic pattern, with the liver being the most common site of metastasis. Around 20%-25% of patients with CRC will develop exclusively hepatic metastatic disease throughout their disease history. With its specific characteristics and therapeutic options, liver-limited disease (LLD) should be considered as a specific entity. The identification of these patients is particularly relevant in view of the growing interest in liver transplantation in selected patients with advanced CRC. Identifying why some patients will develop only LLD remains a challenge, mainly because of a lack of a systemic understanding of this complex and interlinked phenomenon given that cancer has traditionally been investigated according to distinct physiological compartments. Recently, multidisciplinary efforts and new diagnostic tools have made it possible to study some of these complex issues in greater depth and may help identify targets and specific treatment strategies to benefit these patients. In this review we analyze the underlying biology and available tools to help clinicians better understand this increasingly common and specific disease.

Bowel-associated dermatosis-arthritis syndrome, a diagnostic challenge in a young child with very early-onset inflammatory bowel disease.

A 14-month-old girl with very early-onset inflammatory bowel disease (VEO-IBD) was admitted with a flare of her bowel disease and subsequently developed high fevers, joint pain, and skin lesions during her hospitalization. Workup demonstrated bowel-associated dermatosis-arthritis syndrome in the setting of VEO-IBD, a neutrophilic dermatosis rarely reported in children that can be challenging to diagnose and treat, with limited literature for patients under 2 years of age.