Circulating haematopoietic stem cells and long-term outcomes of COVID-19.

BACKGROUND AND AIMS: An acute depletion of circulating haematopoietic stem/progenitor cells (HSPCs) occurs during COVID-19, especially among patients with a poorer disease course. We herein examined whether HSPCs levels at hospital admission for COVID-19 predict 1-year mortality and the long-COVID syndrome. MATERIALS AND METHODS: Patients hospitalized for COVID-19 in an infectious disease ward were consecutively enrolled. Circulating HSPC levels were assessed by flow cytometry as cells expressing CD34 and/or CD133. Follow-up was performed for 12 months after hospitalization through the review of electronic medical records and demographic local registers. RESULTS: The study included 100 patients, 36 of whom reported symptoms of long-COVID and 20 died during follow-up. The reduction of 1-SD of HSPCs was associated with a 3- to 5-fold increase in the risk of 1-year mortality. Age, admission hyperglycaemia, C-reactive protein peak, liver enzymes, the need of high-flow oxygen and/or invasive ventilation were predictors of mortality at univariate analysis. Among pre-existing comorbidities, coronary heart disease and chronic kidney disease, but not diabetes, were associated with 1-year mortality. In multivariate analyses, HSPCs remained significantly associated with 1-year mortality independently of confounders. The development of pneumonia an in-hospital treatment with glucocorticoids and convalescent plasma were associated with long-COVID symptoms at follow-up. HSPCs, diabetes and other comorbidities were not predictors of long-COVID. CONCLUSIONS: In a cohort of patients hospitalized for COVID-19, lower HSPC levels at the time of admission were independent predictors of 1-year mortality. However, COVID-19 severity, but not HSPC level, was significantly associated with the development of long-COVID symptoms.

CCL18, CHI3L1, ANG2, IL-6 systemic levels are associated with the extent of lung damage and radiomic features in SARS-CoV-2 infection.

OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.

A computational study of the negative LiIn modified anode and its interaction with ß-Li3PS4 solid-electrolyte for battery applications.

All-solid-state lithium batteries (ASSLBs) have sparked interest due to their far superior energy density compared to current commercial material, but the heightened reactivity of the negative Li electrode can compromise the long-term cyclability of the cell, calling for the introduction of passivating layers or alloy anodes. In this article, we aim to explain the outstanding stability of LiIn alloy-based anodes over extended cycling by comparing its bulk and interface properties to Li-metal. Using density functional theory, we conducted an in-depth analysis of the LiIn surfaces' formation and subsequent structural stability in interfaces with the solid electrolyte ß-Li3PS4. Several LiIn facets are shown to possess sufficient structural stability, with the (110) surface being the most stable. The stable interfaces established with the ß-Li3PS4(100) surface featured favorable adhesion energy, low strain energy, and little reconstruction. By comparing these interface properties with the bulk properties of Li-metal and LiIn, we highlighted the influence of the cohesion energy, Fermi energy level, and band position of the two materials in the long-term stability of their anodes under battery conditions.

Integrated Approach of Life Cycle Assessment and Experimental Design in the Study of a Model Organic Reaction: New Perspectives in Renewable Vanillin-Derived Chemicals.

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization.

Risk of hospitalization and sequelae in patients with COVID-19 treated with 3-day early remdesivir vs. controls in the vaccine and Omicron era: A real-life cohort study.

Recently, a benefit from administration of a 3-day course of early remdesivir (ER) in the outpatients' setting was reported. However, real-life data on its use is scarce. Therefore, we explored the ER clinical outcome in our outpatients' s cohort, compared to untreated controls. We included all patients who were prescribed ER from February to May 2022 and followed them up for 3 months and compared patients who received treatment with untreated controls. In the two groups the following outcomes were investigated: hospitalization and mortality rate, time of negativization and symptom's resolution, and postacute coronavirus disease 19 (COVID-19) syndrome prevalence. Overall, 681 patients were analyzed, mostly females (53.6%), and with a median age of 66 years (interquartile range: 54-77), 316 (46.4%) patients received ER, and 365 (53.6%) did not receive antiviral treatment (control group). Overall, 8.5% patients eventually required oxygen support, 8.7% were hospitalized for COVID-19, and 1.5% died. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and ER (adjusted odds ratio [aOR]: 0.049 [0.015; 0.16], p < 0.001) independently reduced hospitalization risk. ER was significantly associated with a shorter duration of SARS-CoV-2 positivity at nasopharyngeal swabs (aß -8.15 [-9.21; -7.09], p < 0.001) and of symptoms (aß -5.11 [-5.82; -4.39], p < 0.001), and with lower rate of COVID-19 sequelae compared to control group (aOR: 0.18 [0.10; 0.31], p < 0.001). Even in the SARS-CoV-2 vaccination and Omicron era, in patients at high risk of developing severe disease, ER demonstrated to have a good safety profile and to significantly reduce the risk of disease progression and COVID-19 sequelae compared to untreated controls.

Stability and Formation of the Li3PS4/Li, Li3PS4/Li2S, and Li2S/Li Interfaces: A Theoretical Study.

Solid electrolytes have shown superior behavior and many advantages over liquid electrolytes, including simplicity in battery design. However, some chemical and structural instability problems arise when solid electrolytes form a direct interface with the negative Li-metal electrode. In particular, it was recognized that the interface between the ß-Li3PS4 crystal and lithium anode is quite unstable and tends to promote structural defects that inhibit the correct functioning of the device. As a possible way out of this problem, we propose a material, Li2S, as a passivating coating for the Li/ß-Li3PS4 interface. We investigated the mutual affinity between Li/Li2S and Li2S/ß-Li3PS4 interfaces by DFT methods and investigated the structural stability through the adhesion energy and mechanical stress. Furthermore, a topological analysis of the electron density identified preferential paths for the migration of Li ions.

Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells.

Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B-/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair, and to control apoptosis. We evaluated the efficacy of a new drug schedule combining Dox and specific ATR (VE-821) or CHK1 (prexasertib, PX) inhibitors in the treatment of human B-/T cell precursor ALL cell lines and primary ALL leukemic cells. We found that ALL cell lines respond to Dox activating the G2/M cell cycle checkpoint. Exposure of Dox-pretreated ALL cell lines to VE-821 or PX enhanced Dox cytotoxic effect. This phenomenon was associated with the abrogation of the G2/M cell cycle checkpoint with changes in the expression pCDK1 and cyclin B1, and cell entry in mitosis, followed by the induction of apoptosis. Indeed, the inhibition of the G2/M checkpoint led to a significant increment of normal and aberrant mitotic cells, including those showing tripolar spindles, metaphases with lagging chromosomes, and massive chromosomes fragmentation. In conclusion, we found that the ATR-CHK1 pathway is involved in the response to Dox-induced DNA damages and we demonstrated that our new in vitro drug schedule that combines Dox followed by ATR/CHK1 inhibitors can increase Dox cytotoxicity against ALL cells, while using lower drug doses. • Doxorubicin activates the G2/M cell cycle checkpoint in acute lymphoblastic leukemia (ALL) cells. • ALL cells respond to doxorubicin-induced DNA damages by activating the ATR-CHK1 pathway. • The inhibition of the ATR-CHK1 pathway synergizes with doxorubicin in the induction of cytotoxicity in ALL cells. • The inhibition of ATR-CHK1 pathway induces aberrant chromosome segregation and mitotic spindle defects in doxorubicin-pretreated ALL cells.

Clinical Course May Be Independent from Neuroimaging in DEPDC-5-Related Epilepsy.

DEPDC5 is an upstream repressor of the mechanistic target of rapamycin pathway via the GATOR-1 complex. Pathogenic variants causing loss of function typically result in familial focal epilepsy with variable foci. Neuroimaging may either be normal or show brain malformations. Lesional and nonlesional cases may be present within the same family. Here, we describe a parent-child dyad affected by a truncating DEPDC5 pathogenic variant (c.727C > T; p.Arg243*), analyze the epilepsy clinical course, and describe neuroimaging characteristics from a 3T brain magnetic resonance imaging. Despite sharing the same variant, patients diverged both in terms of epilepsy severity and neuroimaging features. Surprisingly, the mother is still suffering from drug-resistant seizures and has normal neuroimaging, while the child has been experiencing prolonged seizure freedom notwithstanding a bottom-of-sulcus focal cortical dysplasia. An increasing gradient of severity has been proposed for families with GATOR1-related epilepsies. We confirm clinical and neuroradiological expressivities are variable and also suggest the prognostication of epilepsy outcome may be particularly difficult. The epilepsy outcome could partially be independent from brain structural abnormalities.

ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment.

ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3' region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment.

Drug-resistant epilepsy at the age extremes: Disentangling the underlying etiology.

The incidence of epilepsy is highest at the extreme age ranges: childhood and elderly age. The most common syndromes in these demographics - self-limited epilepsies of childhood and idiopathic generalized epilepsies in pediatric age, focal epilepsy with structural etiology in older people - are expected to be drug responsive. In this work, we focus on such epilepsy types, overviewing the complex clinical background of unexpected drug-resistance. For self-limited epilepsies of childhood and idiopathic generalized epilepsies, we illustrate drug-resistance resulting from syndrome misinterpretation, reason on possible unexpected courses of epilepsy, and explicate the influence of inappropriate treatments. For elderly-onset epilepsy, we show the challenges in differential diagnosis possibly leading to pseudoresistance and analyze how drug-resistant epilepsy can arise in stroke, neurocognitive disorders, brain tumors, and autoimmune encephalitis. In children and senior people, drug-resistance can be regarded as a hint to review the diagnosis or explore alternative therapeutic strategies. Refractory seizures are not only a therapeutic challenge, but also a cardinal sign not to be overlooked in syndromes commonly deemed to be drug-responsive.

From symmetry breaking in the bulk to phase transitions at the surface: a quantum-mechanical exploration of Li6PS5Cl argyrodite superionic conductor.

Lithium superionic conductor electrolytes may enable the safe use of metallic lithium anodes in all-solid-state batteries. The key to a successful application is a high Li conductivity in the electrolyte material, to be achieved through the maintenance of intimate contact with the electrodes and the knowledge of the chemical nature of that contact. In this manuscript, we tackle this issue by a theoretical ab initio approach. Focusing on the Li6PS5Cl, a thiophosphate with high ionic conductivity, we carry on thorough modeling of the surfaces together with the prediction of the thermal and elastic behaviour. Our investigation leads to some new findings: the bulk structure, as reported in the literature, appears to be metastable, with spontaneous symmetry breaking. Moreover, the relevant stoichiometric surfaces identified for stable and metastable crystal structures are not up-down symmetry related and they expose from one side Li2S and LiCl. Surface reconstructions can be interpreted as local phase transitions. We also predict entirely ab initio the morphology of crystallites, charge, and electrostatic potential at surfaces, together with the effect of temperature on structural properties and the elastic behaviour of this material. Such findings may constitute the relevant groundwork for a better understanding of ionic transport in Li-ion conductors at the electrolyte/anode and electrolyte/cathode interfaces.

Oral Cannabinoid Preparations for the Treatment of Chronic Migraine: A Retrospective Study.

OBJECTIVE: To explore the effectiveness and safety of three oral cannabinoid preparations (FM2®, Istituto farmaceutico militare, Firenze, Italy; Bedrocan®, Bedrocan International, Vandaam, Netherlands; and Bediol®, Bedrocan International, Vandaam, Netherlands) in the treatment of chronic migraine. DESIGN: Retrospective, cohort study. SUBJECTS: Patients with chronic migraine who received FM2, Bedrocan, or Bediol daily for the off-label treatment of their headache, for up to 6 months. METHODS: The number of migraine days per month, pain intensity, the number of acute medications taken per month, the number of days per month on which the patient took at least one acute medication, and adverse events were recorded at baseline and at 3 months and 6 months after the start of treatment with oral cannabinoid preparations. RESULTS: The number of migraine days did not change significantly after the third month or the sixth month when compared with baseline (P = 0.1182). The pain intensity (P = 0.0004), the acute medication consumption (P = 0.0006), and the number of days per month in which patients took at least one acute medication significantly decreased when compared with baseline (P = 0.0004). No significant differences were found between patients who were still taking a preventive treatment for chronic migraine and those who were not (all P > 0.05). Different oral cannabinoid preparations displayed similar levels of effectiveness (all P > 0.05). The adverse events were mostly mild and occurred in 43.75% of patients. CONCLUSIONS: Oral cannabinoid preparations may have a role in reducing pain intensity and acute medication intake in patients with chronic migraine, but the magnitude of the effect seems modest; further studies are needed.

The Determinants of Complementary Feeding Introduction Vary According to the Type of Food and Infants' Ages: A Cohort Study-ClaB, Brazil.

INTRODUCTION: Food inadequacies in the first 6 months of life are considered a global problem, with an emphasis on early complementary feeding introduction (CFI). This study aimed to identify the determinants of CFI. METHODS: A birth cohort study (N = 641). Data on infant feeding was collected before 30 days, and at 2, 4, and 6 months of age and, at baseline, data regarding socioeconomic status, demographics, maternal and infant health, obstetric history, and infant care. The hypothesis was that the risk determinants for early CFI vary according to the type of food and the age range of this introduction. Twelve Cox regression models were fit with four outcomes (formula; other types of milk; other beverages; and solid/semi-solid foods) considering three different age ranges of the infant at their introduction (< 2 months, 2-4 months, and 4-6 months). RESULTS: The introduction of the four food groups analyzed was early (median ages of introduction: formulas = 45 days; other milks = 135 days; other beverages = 120 days; solids and semi-solids = 135 days). The determinants that increased the risk of introducing formulas before 2 months were: primiparity, employed without maternity leave, mothers with unsatisfactory prenatal counseling and those who had cesarean sections. Not living with a partner, infant pacifier use at 2 months of age had a higher risk of introducing formula between 2 and 4 months of age. Non-white skin color, more than 35 years old, low maternal education, and lower family income increased the risk of introducing other types of milk between 2 and 4 months of age. Between 4 and 6 months of age, adolescent and low education level mothers had a higher risk of introducing other types of milk, unemployed was a protective factor against the introduction of other foods and beverages in this age group. CONCLUSIONS: The determinants of early CFI varied according to the type of food and the age of introduction.

A Review of Mechanical and Chemical Sensors for Automotive Li-Ion Battery Systems.

The electrification of passenger cars is one of the most effective approaches to reduce noxious emissions in urban areas and, if the electricity is produced using renewable sources, to mitigate the global warming. This profound change of paradigm in the transport sector requires the use of Li-ion battery packages as energy storage systems to substitute conventional fossil fuels. An automotive battery package is a complex system that has to respect several constraints: high energy and power densities, long calendar and cycle lives, electrical and thermal safety, crash-worthiness, and recyclability. To comply with all these requirements, battery systems integrate a battery management system (BMS) connected to an complex network of electric and thermal sensors. On the other hand, since Li-ion cells can suffer from degradation phenomena with consequent generation of gaseous emissions or determine dimensional changes of the cell packaging, chemical and mechanical sensors should be integrated in modern automotive battery packages to guarantee the safe operation of the system. Mechanical and chemical sensors for automotive batteries require further developments to reach the requested robustness and reliability; in this review, an overview of the current state of art on such sensors will be proposed.

The value of computed tomography in assessing the risk of death in COVID-19 patients presenting to the emergency room.

OBJECTIVE: The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. METHODS: Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20-39%, 40-59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). RESULTS: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899-0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912-0.953) when adding CT extension. CONCLUSIONS: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. KEY POINTS: • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy.

Management of Asbestos Containing Materials: A Detailed LCA Comparison of Different Scenarios Comprising First Time Asbestos Characterization Factor Proposal.

This work addresses the complex issue of asbestos containing materials (ACMs) management, by focusing on the scenario of six municipalities comprised in the Reggio Emilia province of Emilia Romagna Italian region. Particularly, the life cycle assessment (LCA) methodology was applied in order to assess in a quantitative and reliable manner the human toxicity as well as the ecotoxicity impacts associated with all of the different phases of ACMs management. The latter comprises mapping of ACMs, creation of a risk map for defining priority of intervention, encapsulation and removal of ACMs, as well as the as obtained asbestos containing waste (ACW) end of life. Particularly, a thermal inertisation treatment performed in a continuous industrial furnace was considered as the innovative end of life scenario to be compared with what actually was provided by the legislation of many countries worldwide, that is, the disposal of ACW in a controlled landfill for hazardous wastes. A characterization factor for asbestos fibers released both in outdoor air and in occupational setting was proposed for the first time and included in the USEtox 2.0 impact assessment method. This allowed us to reliably and quantitatively highlight that inertisation treatments should be the preferred solutions to be adopted by local and national authorities, especially if the obtained inert material finds application as secondary raw materials, thus contributing to a decrease in the environmental damage (limited to its toxicological contributions) to be associated with asbestos management.

The NV-N+ charged pair in diamond: a quantum-mechanical investigation.

The NV-N+ charged pair in diamond has been investigated by using a Gaussian-type basis set, the B3LYP functional, the supercell scheme and the CRYSTAL code. It turns out that: (i) when the distance between the two defects is larger than 6-7 Å, the properties of the double defect are the superposition of the properties of the individual defects. (ii) The energy required for the reaction NV0 + Ns→ NV- + N+ is roughly -1.3 eV at about 12 Å, irrespective of the basis set and functional adopted, and remains negative at any larger distance. (iii) These results support the observation of a charge transfer mechanism through a Ns→ NV0 donation occurring in the ground state, through a tunnelling process, without irradiation. (iv) The IR spectrum of the two subunits is characterized by specific peaks, that might be used as fingerprints. (v) Calculation of electrostatic interaction permitted an estimate of the effective charge of the defects.

Erenumab for the preventive treatment of chronic migraine complicated with medication overuse headache: an observational, retrospective, 12-month real-life study.

BACKGROUND: Erenumab is a monoclonal antibody blocking the calcitonin gene-related peptide receptor, which has been approved for the preventive treatment of chronic migraine (CM). The aim of this study was to explore the safety and effectiveness of erenumab in patients suffering from CM and medication overuse headache (MOH) in a real-life setting, up to 1 year. METHODS: Data regarding 81 patients treated with erenumab were retrospectively analyzed. Every 3 months, the following variables were collected: the mean number of headache days per month (headache index (HI)), the average number of painkillers taken per month (analgesic consumption (AC)), the mean number of days with painkiller consumption (number of days on medication (NDM)), the headache intensity (numeric rating scale (NRS) score), the 6-item Headache Impact Test (HIT-6), and the Self-Reported Instrument to Assess Work-Related Difficulties in Patients With Migraine (HEADWORK) scores. RESULTS: The HI, AC, and NDM and the NRS, HIT-6, and HEADWORK scores were significantly lower at every time point from the 3rd month onward compared to baseline (all P < 0.0001). No significant differences were found between patients who underwent painkiller detoxification before starting erenumab and those who did not (all P > 0.05). No significant differences were found between patients taking erenumab in combination with other preventive treatments and the ones taking it alone (all P ≥ 0.05). Five patients dropped out because of adverse events, which resolved after stopping erenumab. CONCLUSION: Erenumab was safe and effective for CM complicated with MOH. Painkiller withdrawal and the association with other preventive treatment(s) seem useless.

Is COVID-19 lockdown associated with vitamin D deficiency?

All vitamin D tests carried out for outpatients aged 18 years or older during the last 3 years at an Italian University Hospital was reviewed. The serum vitamin D concentrations measured since the Italian coronavirus diseases 2019 (COVID-19) lockdown to present did not significantly differ from the previous 2 years (78 vs. 77 nmol/l; P = 0.277), whilst the prevalence of vitamin D deficiency was found to be even marginally lower in 2020 (16.0% vs. 17.9%; P = 0.003). These results suggest that vitamin D deficiency in our province has not increased during the Italian COVID-19 outbreak or in correspondence with the nationwide lockdown.

Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas.

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.