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Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic.

Abstract Background Motor difficulties are common in many, but not all, autistic individuals. These difficulties can co-occur with other problems, such as delays in language, intellectual, and adaptive functioning. Biological mechanisms underpinning such difficulties are less well understood. Poor motor skills tend to be more common in individuals carrying highly penetrant rare genetic mutations. Such mechanisms may have downstream consequences of altering neurophysiological excitation-inhibition balance and lead to enhanced behavioral motor noise. Methods This study combined publicly available and in-house datasets of autistic (n = 156), typically-developing (TD, n = 149), and developmental coordination disorder (DCD, n = 23) children (age 3–16 years). Autism motor subtypes were identified based on patterns of motor abilities measured from the Movement Assessment Battery for Children 2nd edition. Stability-based relative clustering validation was used to identify autism motor subtypes and evaluate generalization accuracy in held-out data. Autism motor subtypes were tested for differences in motor noise, operationalized as the degree of dissimilarity between repeated motor kinematic trajectories recorded during a simple reach-to-drop task. Results Relatively ‘high’ (n = 87) versus ‘low’ (n = 69) autism motor subtypes could be detected and which generalize with 89% accuracy in held-out data. The relatively ‘low’ subtype was lower in general intellectual ability and older at age of independent walking, but did not differ in age at first words or autistic traits or symptomatology. Motor noise was considerably higher in the ‘low’ subtype compared to ‘high’ (Cohen’s d = 0.77) or TD children (Cohen’s d = 0.85), but similar between autism ‘high’ and TD children (Cohen’s d = 0.08). Enhanced motor noise in the ‘low’ subtype was also most pronounced during the feedforward phase of reaching actions. Limitations The sample size of this work is limited. Future work in larger samples along with independent replication is important. Motor noise was measured only on one specific motor task. Thus, a more comprehensive assessment of motor noise on many other motor tasks is needed. Conclusions Autism can be split into at least two discrete motor subtypes that are characterized by differing levels of motor noise. This suggests that autism motor subtypes may be underpinned by different biological mechanisms.

Abstract Background The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. Methods We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). Results 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008). Conclusions In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

BackgroundDiagnosis of child and adolescent psychopathologies involves a multifaceted approach, integrating clinical observations, behavioral assessments, medical history, cognitive testing, and familial context information. Digital technologies, especially internet-based platforms for administering caregiver-rated questionnaires, are increasingly used in this field, particularly during the screening phase. The ascent of digital platforms for data collection has propelled advanced psychopathology classification methods such as supervised machine learning (ML) into the forefront of both research and clinical environments. This shift, recently called psycho-informatics, has been facilitated by gradually incorporating computational devices into clinical workflows. However, an actual integration between telemedicine and the ML approach has yet to be fulfilled. ObjectiveUnder these premises, exploring the potential of ML applications for analyzing digitally collected data may have significant implications for supporting the clinical practice of diagnosing early psychopathology. The purpose of this study was, therefore, to exploit ML models for the classification of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) using internet-based parent-reported socio-anamnestic data, aiming at obtaining accurate predictive models for new help-seeking families. MethodsIn this retrospective, single-center observational study, socio-anamnestic data were collected from 1688 children and adolescents referred for suspected neurodevelopmental conditions. The data included sociodemographic, clinical, environmental, and developmental factors, collected remotely through the first Italian internet-based screening tool for neurodevelopmental disorders, the Medea Information and Clinical Assessment On-Line (MedicalBIT). Random forest (RF), decision tree, and logistic regression models were developed and evaluated using classification accuracy, sensitivity, specificity, and importance of independent variables. ResultsThe RF model demonstrated robust accuracy, achieving 84% (95% CI 82-85; P

Abstract Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Anemia is common in cancer patients and impacts on quality of life and prognosis. It is typically multifactorial, often involving different pathophysiological mechanisms, making treatment a difficult task. In patients undergoing active anticancer treatments like chemotherapy, decreased red blood cell (RBC) production due to myelosuppression generally predominates, but absolute or functional iron deficiency frequently coexists. Current treatments for chemotherapy-related anemia include blood transfusions, erythropoiesis-stimulating agents, and iron supplementation. Each option has limitations, and there is an urgent need for novel approaches. After decades of relative immobilism, several promising anti-anemic drugs are now entering the clinical scenario. Emerging novel classes of anti-anemic drugs recently introduced or in development for other types of anemia include activin receptor ligand traps, hypoxia-inducible factor-prolyl hydroxylase inhibitors, and hepcidin antagonists. Here, we discuss their possible role in the treatment of anemia observed in patients receiving anticancer therapies.

Abstract Introduction Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial Registration ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51. Graphical Abstract

Overcrowding in emergency departments (EDs) is a common and worldwide phenomenon, widely reported even by the non-specialist press. It contributes to a number of consequences that can affect both the number of resources available and the quality of care. Strategies to address this incriminating situation for patients, nurses, doctors, and hospital administrators are urgently needed. For this reason, and based on the input from the Ministry of Health, a series of projects and procedures have been developed in various Italian regions, aimed at reducing the waiting times and the diagnostic-therapeutic process of patients arriving in the ED. In this article, we will examine the main critical issues within EDs and discuss the most impactful strategies and solutions to manage these difficulties.

In this review, we discuss the management of burn patients in the emergency room. Burn injury is characterized by a hypermetabolic response with physiological, catabolic and immune effects. The treatment of burns requires a multidisciplinary approach and a proper management able to reduce both the damage and the risk of infections. The management of a burn patient begins with a primary evaluation: i) maintaining a high index of suspicion for the presence of airway compromise following smoke inhalation and secondary to burn edema; ii) identifying and managing associated mechanical injuries; maintaining hemodynamic normality with volume resuscitation; iii) controlling temperature; iv) removing the patient from the injurious environment. Secondary evaluation holds fundamental importance and is carried out through the head-to-foot objective examination and diagnostic investigations as well as the wound dressing. Clinicians also must take measures to prevent and treat the potential complications of specific burn injuries (e.g., compartment syndromes). The role of this article is to highlight some quick and effective guidelines for the management of burn patients in the early stages, within the emergency room, before the transfer to the burn unit.

Motor abnormalities are highly prevalent in children with autism spectrum disorder and are strongly predictive of adaptive functioning. Despite the documented sex bias in the prevalence of the disorder, the impact of sex differences on motor abnormalities has been overlooked. The goal of this study was to investigate differences in the motor profile of boys and girls with autism spectrum disorder aged 3-11 years using a multimethod approach. Ninety-eight children with autism spectrum disorder and 98 typically developing children were assessed using the Movement Assessment Battery for Children 2, the Developmental Coordination Disorder Questionnaire, and the kinematic analysis of a reach-to-drop task. Results from principal components analysis on reach-to-drop-dependent measures indicated four components, accounting for kinematic parameters of the motor task. Irrespective of sex, children with autism spectrum disorder showed worse scores on Movement Assessment Battery for Children 2 and Developmental Coordination Disorder Questionnaire subscales than typically developing children. Interestingly, a diagnosis-by-sex interaction was found on a kinematic feature measured in the last part of the movement, with girls with autism spectrum disorder presenting altered motor anticipation. Although preliminary, these findings suggested that sex-related nuances in motor functioning of children with autism spectrum disorder could be insufficiently captured by existing motor measures.

This paper proposes to apply a postharvest environmental stress to red apples, Malus domestica, variety Red Delicious in order to increase the polyphenols compounds (PP) content in their peels. The possibility of enhancing extractable PP provides a useful alternative for the use of discarded crops in the food industry. A great increase in PP was observed in response to light damage produced by the environmental stress applied in this work. Flavonols > anthocyanins > flavanols > dihydrochalcones > phenolic acids is the order in PP content. The interaction of the extracted PP from unstressed and stressed apple peels with beta-lactoglobulin (β-LG) was characterized. A PP/β-LG complex which was formed with one single binding site in the protein was determined. The interaction was spontaneous and enthalpy driven. PP extracted from unstressed samples had greater affinity for the protein than PP extracted from stressed samples, possibly due to the polar characteristic of anthocyanins. The results of this last study could provide a better understanding of the interaction between PP and β-LG to incorporate them into functional foods.

Background: this study aims to evaluate the efficacy of tixagevimab/cilgavimab (Evusheld™) against various SARS-CoV-2 variants, including newer Omicron sublineages, in an immunocompromised cohort and in vitro. Study design: Conducted in Italy, this research involves immunocompromised patients who received Evusheld. It evaluates serum neutralization activity against different SARS-CoV-2 strains (20A.EU1, BA.5, BQ.1, XBB.1.5, XBB.1.16, and EG.5) before (T0), after 14 (T1), and after 30 (T2) days from the tixagevimab/cilgavimab injection. Furthermore, the in vitro activity of Evusheld against SARS-CoV-2 VOCs was evaluated. Results: The cohort was composed of 72 immunocompromised patients. The serum neutralizing activity of tixagevimab/cilgavimab-treated patients was notably lower against newer variants such as BQ.1, XBB.1.5, XBB.1.16, and EG.5. Then, the in vitro study detailed specific EC50 values to quantify the activity of tixagevimab/cilgavimab against various SARS-CoV-2 VOCs. Newer variants like BQ.1 and XBB.1.5 exhibited notably lower neutralization, underscoring the challenges in effectively countering the evolving virus. Interestingly, tixagevimab/cilgavimab maintained reduced but still valid activity against EG.5 with an EC50 of 189 ng/mL and Cmax/EC90 of 110.7. Conclusions: Tixagevimab/cilgavimab efficacy wanes against novel subvariants. This underscores the critical need for ongoing adaptation and vigilance in prophylactic strategies to effectively counter the dynamic and unpredictable nature of the COVID-19 pandemic.

Ultrasound measurement of the optic nerve sheath diameter (US ONSD) has been proposed as a method to diagnose elevated intracranial pressure (EICP), but the optimal threshold is unclear. The aim of this study was to assess the accuracy of US ONSD, as compared to head computed tomography (CT), in detecting EICP of both traumatic and non-traumatic origin. We conducted a prospective, cross-sectional, multicenter study. Patients presenting to the emergency department with a suspect of traumatic or non-traumatic brain injury, referred for an urgent head CT, underwent US ONSD measurement. A US ONSD ≥5.5 mm was considered positive. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for three ONSD cut-offs: 5.5 (primary outcome), 5.0, and 6.0 mm. A receiver operating characteristic (ROC) curve was also generated and the area under the ROC curve calculated. Ninetynine patients were enrolled. The CT was positive in 15% of cases and the US ONSD was positive in all of these, achieving a sensitivity of 100% [95% confidence interval (CI) 78; 100] and a negative predictive value of 100% (95% CI 79; 100). The CT was negative in 85% of cases, while the US ONSD was positive in 69% of these, achieving a specificity of 19% (95% CI 11; 29) and a positive predictive value of 18% (95% CI 11; 28). The US ONSD, with a 5.5 mm cut-off, might safely be used to rule out EICP in patients with traumatic and non-traumatic brain injury in the ED. In limited-resources contexts, a negative US ONSD could allow emergency physicians to rule out EICP in low-risk patients, deferring the head CT.

Background and Purpose—Systemic thrombolysis represents the main proven therapy for acute ischemic stroke, but safe treatment is reported only in well-established stroke units. To extend the use of tissue plasminogen activator (tPA) treatment in primary care hospitals on isolated areas through telemedic was the purpose of specific initiatives in southern Umbria, Italy. Methods—The stroke center of Foligno established a telestroke network to provide consultations for three local hospitals in southern Umbria. The telemedic system consists of a digital network that includes a two-way video conference system and imaging sharing. The main network hospital established specialized stroke wards/teams in which qualified teams treat acute stroke patients. Physicians in these hospitals are able to contact the stroke centers 24 h per day. Quality data are available to support the safe implementation of the stroke procedures. Those available from governmental authorities and local datasets are volume of hospitalization, in-hospital mortality, 30-days mortality, and discharge setting. Objective of the study was to assess the annual hospitalization volume in both the hub and spoke hospitals for ischemic stroke and appraise the performance of the network after the introduction of the telestroke system. Results—A total of 225 systemic thrombolyses were performed in time period indicated above all hospitals. In the main spoke hospital, 41 procedures were performed after teleconsultations were made available. The thrombolysis rate in the hub hospital ranged between 10% in 2016 and 20% in 2019, while in the spoke hospital was below 5% in 2016 and raised to 15% in 2019. The statistically significant difference, in the number of procedures, between hub and spoke in the beginning of the observation time disappeared after introduction of the telestroke network. No increase of the mortality was found. Conclusions—The present data suggest that systemic thrombolysis indicated via stroke experts in the setting of teleconsultation shows similar complication rates to those reported in the National Institute of Neurological Disorders and Stroke trial. Therefore, tPA treatment is also safe in this context and can be extended to primary hospitals.

We describe the first public data release of the Dark Energy Survey, DES DR1, consisting of reduced single-epoch images, co-added images, co-added source catalogs, and associated products and services assembled over the first 3 yr of DES science operations. DES DR1 is based on optical/near-infrared imaging from 345 distinct nights (2013 August to 2016 February) by the Dark Energy Camera mounted on the 4 m Blanco telescope at the Cerro Tololo Inter-American Observatory in Chile. We release data from the DES wide-area survey covering ∼5000 deg2 of the southern Galactic cap in five broad photometric bands, grizY. DES DR1 has a median delivered point-spread function of g = 1.12, r = 0.96, i = 0.88, z = 0.84, and Y = 0.″90 FWHM, a photometric precision of