Minor head injury in anticoagulated patients: performance of biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in the detection of intracranial injury. A prospective observational study.

OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.

Use of Exploratory Factor Analysis to Assess the Fitness Performance of Youth Football Players.

ABSTRACT: Perroni, F, Castagna, C, Amatori, S, Gobbi, E, Vetrano, M, Visco, V, Guidetti, L, Baldari, C, Luigi Rocchi, MB, and Sisti, D. Use of exploratory factor analysis to assess the fitness performance of youth football players. J Strength Cond Res 37(7): e430-e437, 2023-Football performance involves several physical abilities that range in aerobic, anaerobic, and neuromuscular domains; however, little is known about their interplay in profiling individual physical attributes. This study aimed to profile physical performance in youth football players according to their training status. One hundred seven young male soccer players (age 13.5 ± 1.4 years; height 168 ± 7 cm; body mass 57.4 ± 9.6 kg; and body mass index 20.2 ± 2.1 kg·m -2 ) volunteered for this study. Players' physical performance was assessed with football-relevant field tests for sprinting (10 m sprint), vertical jump (countermovement jump), intermittent high-intensity endurance (Yo-Yo Intermittent Recovery Test Level 1, YYIRT1), and repeated sprint ability (RSA). The training status was assumed as testosterone and cortisol saliva concentrations; biological maturation was estimated using the Pubertal Development Scale. Exploratory factor analysis (EFA) revealed 3 main variables depicting anthropometric (D1, 24.9%), physical performance (D2, 18.8%), and training status (D3, 13.3%), accounting for 57.0% of total variance altogether. The level of significance was set at p ≤ 0.05. The RSA and YYIRT1 performances were largely associated with D2, suggesting the relevance of endurance in youth football. This study revealed that for youth football players, a 3-component model should be considered to evaluate youth soccer players. The EFA approach may help to disclose interindividual differences useful to talent identification and selection.

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long-term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin-sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)-Akt, and p-ERK proteins in rat brain cortexes. PKCα increased in HI-injured rats and further increased with melatonin. p-Akt and p-ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.

Monocyte distribution width (MDW): a useful biomarker to improve sepsis management in Emergency Department.

OBJECTIVES: Sepsis is a time-dependent and life-threating condition. Despite several biomarkers are available, none of them is completely reliable for the diagnosis. This study aimed to evaluate the diagnostic utility of monocyte distribution width (MDW) to early detect sepsis in adult patients admitted in the Emergency Department (ED) with a five part differential analysis as part of the standard clinical practice. METHODS: A prospective cohort study was conducted on 985 patients aged from 18 to 96 and included in the study between November 2019 and December 2019. Enrolled subjects were classified into four groups based on sepsis-2 diagnostic criteria: control, Systemic Inflammatory Response Syndrome (SIRS), infection and sepsis. The hematology analyzer DxH 900 (Beckman Coulter Inc.) provides the new reportable parameter MDW, included in the leukocyte 5 part differential analysis, cleared by Food and Drug administration (FDA) and European Community In-Vitro-Diagnostic Medical Device (CE IVD) marked as early sepsis indicator (ESId). RESULTS: MDW was able to differentiate the sepsis group from all other groups with Area Under the Curve (AUC) of 0.849, sensitivity of 87.3% and specificity of 71.7% at cut-off of 20.1. MDW in combination with white blood cell (WBC) improves the performance for sepsis detection with a sensitivity increased up to 96.8% when at least one of the two biomarkers are abnormal, and a specificity increased up to 94.6% when both biomarkers are abnormal. CONCLUSIONS: MDW can predict sepsis increasing the clinical value of Leukocyte 5 Part Differential analysis and supporting the clinical decision making in sepsis management at the admission to the ED.

Relationship-based care model in paediatrics: A randomized controlled trial to implement the parents' perception of the quality of nursing care.

AIM: To evaluate whether the application of the Relationship-based care model as a new treatment, called "Take 5 min", affects the level of anxiety, depression, and perceived quality of nursing care of parents of paediatric patients and the work satisfaction of the nursing staff. DESIGN: Single-blind randomized controlled trial. METHODS: The trial was performed from February-July 2016. The trial was conducted with one intervention (N = 101) and one control group (N = 90). Nurses applied the treatment named "Take 5 Minutes", which consisted of dedicating some short time (from 5 to 10 min) to the relationship with the parents using specifically designed communication strategies. The primary outcome was the evaluation of anxiety and depression of parents; the secondary was the parent perceived quality of nursing care. RESULTS: In the experimental group, participants had a lower level of anxiety and depression and highlighted that the effect of the "Take 5 Minutes" was proportional to the initial seriousness of parents' anxiety and depression. Higher scores for the perception of the quality of care were given from the parents of the experimental group. CONCLUSION: The "Take 5 Minutes" treatment offered to parents of paediatric patients demonstrated significant improvements in terms of their anxiety, depression, and perceived quality of nursing care. IMPACT: Caregivers of paediatric patients are subject to psychological disorders such as depression and anxiety. The communication by the nursing community is of fundamental importance in the management of anxiety and depression in the caregivers of hospitalized patients. Caregivers who received the "Take 5 Minutes" treatment demonstrated a significant decrease in anxiety and depression compared with the control group caregivers. The perceived level of quality of nursing care showed a significant increase in the group of caregivers who received the T5M treatment. The RBC model does not require extra costs for health organizations and can be applied during the usual practice of care. Practices such as T5M could become part of paediatric patient care guidelines and nurses should be trained to apply them. TRIAL REGISTRATION NUMBER: Padua Research: ID No. 10,034; ClinicalTrials.gov: ID No. NCT04199429.

Muscular viscoelastic characteristics of athletes participating in the European Master Indoor Athletics Championship.

PURPOSE: To investigate how the viscoelastic characteristics of muscles (non-neural tone, elasticity and stiffness) vary as a function of age and gender in a sample of track and field master athletes. To compare these findings with data on related sedentary subjects in literature. METHODS: A total of 390 athletes (aged 35-99) were assessed during the European Master Athletics Indoor Championship 2016. A non-invasive measurement device called MyotonPro was used to measure tone, stiffness, and elasticity in the biceps brachii and rectus femoris muscles at rest. Linear regression analysis was used to assess the correlation between age and the measured parameters. To compare our results with previously reported data, we stratified participants according to gender and age. RESULTS: Tone was found to not be dependent on age, whereas stiffness was found to be age dependent. Elasticity was found to be both physical activity and age dependent. Tone (only for men), elasticity, and stiffness were lower in master athletes than in sedentary subjects. CONCLUSIONS: Tone, elasticity, and stiffness change with aging; nevertheless, our findings suggest that physical activity can delay the effects of muscular aging, improving fitness in older people.

Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies.

BACKGROUND: Diets enriched with n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to exert a positive impact on muscle diseases. Flaxseed is one of the richest sources of n-3 PUFA acid α-linolenic acid (ALA). The aim of this study was to assess the effects of flaxseed and ALA in models of skeletal muscle degeneration characterized by high levels of Tumor Necrosis Factor-α (TNF). METHODS: The in vivo studies were carried out on dystrophic hamsters affected by muscle damage associated with high TNF plasma levels and fed with a long-term 30% flaxseed-supplemented diet. Differentiating C2C12 myoblasts treated with TNF and challenged with ALA represented the in vitro model. Skeletal muscle morphology was scrutinized by applying the Principal Component Analysis statistical method. Apoptosis, inflammation and myogenesis were analyzed by immunofluorescence. Finally, an in silico analysis was carried out to predict the possible pathways underlying the effects of n-3 PUFAs. RESULTS: The flaxseed-enriched diet protected the dystrophic muscle from apoptosis and preserved muscle myogenesis by increasing the myogenin and alpha myosin heavy chain. Moreover, it restored the normal expression pattern of caveolin-3 thereby allowing protein retention at the sarcolemma. ALA reduced TNF-induced apoptosis in differentiating myoblasts and prevented the TNF-induced inhibition of myogenesis, as demonstrated by the increased expression of myogenin, myosin heavy chain and caveolin-3, while promoting myotube fusion. The in silico investigation revealed that FAK pathways may play a central role in the protective effects of ALA on myogenesis. CONCLUSIONS: These findings indicate that flaxseed may exert potent beneficial effects by preserving skeletal muscle regeneration and homeostasis partly through an ALA-mediated action. Thus, dietary flaxseed and ALA may serve as a useful strategy for treating patients with muscle dystrophies.

Prevalence and dimensionality of hallucination-like experiences in young adults.

BACKGROUND: The study of hallucination-like experiences (HLEs) in non-clinical populations is increasingly used to corroborate etiological models of psychosis. This method capitalizes on the absence of confounding factors that typically affect the study of hallucinations in clinical subjects. AIM: To estimate the prevalence of HLEs in young adults; validate the mutidimensionality and explore the correlates of latent HLEs clusters. METHODS: Cross-sectional survey design. The extended 16-item Launay-Slade Hallucination Scale (LSHS-E) and the 12-item General Health Questionnaire (GHQ-12) were administered to 649 Italian college students (males: 47%). Confirmatory factorial analysis was used to test multidimensionality of the LSHS-E. Hierarchical nested, progressively constrained models were used to assess configural, metric and scalar invariance of the LSHS-E. Latent class analysis was used to test the existence of different profiles of responding across the identified hallucination-proneness dimensions. RESULTS: Factor analysis showed that the four-factor model had the best fit. Factors were invariant across demographic variables and levels of psychological distress. Three latent classes were found: a large class with no HLEs (70% of participants), a multisensory HLEs class (18.8%), and a high hallucination-proneness class (11%). Among those reporting high levels of HLEs, approximately half reported scores indicative of considerable psychological distress. CONCLUSIONS: Although HLEs have a relatively high prevalence in the general population, the majority of those experiences happen in isolation and are not associated to psychological distress. Approximately half of those individuals experiencing high levels of HLEs report significant psychological distress. This may be indicative of general risk for mental health conditions rather than specific risk for psychosis.

Facilitators and Barriers to Receiving Palliative Care in People with Kidney Disease: Predictive Factors from an International Nursing Perspective.

BACKGROUND: Palliative care (PC) focuses on relieving pain and difficult symptoms rather than treating disease or delaying its progress. Palliative care views death as a natural process and allows patients to live the last phase of their existence in the best possible way, encouraging them to express their opinions and wishes for a good death. Interventions are advocated to control symptoms and distress and promote wellbeing and social functioning. A multidisciplinary approach to support patients receiving palliative care is encouraged. OBJECTIVE: The aims of this study were to investigate the facilitators and barriers to PC in people with kidney disease from a nursing perspective and to explore predictive factors associated with nurse-perceived facilitators and barriers to PC in people with kidney disease. DESIGN: This study is a survey that adopted a questionnaire created in 2021 with Delphi methology, which included 73 statements divided into 37 facilitators and 36 barriers to PC in patients with kidney disease, to be scored using a Likert scale. PARTICIPANTS AND MEASUREMENTS: Participants were obtained through the membership database of the European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) of 2020. Inclusion criteria included being registered as a nurse, an EDTNA/ERCA member and understanding of the English language. The questionnaire was sent via email. RESULTS: Three profiles of respondents were found: the first group was characterized by the highest agreement percentages of facilitators and with an average value of 53.7% in barriers; the second was characterized by a lower endorsement of facilitators and similar agreement to the first group for barriers; the third group had a high probability (>80%) of items endorsing both barriers and facilitators. Predictive variables were significantly associated with "Years in nephrology" and "macro geographic area". CONCLUSIONS: This study demonstrates variation in PC practice across Europe. Some professionals identified fewer barriers to PC and appeared more confident when dealing with difficult situations in a patient's care pathway, while others identified more barriers as obstacles to the implementation of adequate treatment. The number of years of nephrology experience and the geographical area of origin predicted how nurses would respond. This study was not registered.

A home-based lifestyle intervention program reduces the tumorigenic potential of triple-negative breast cancer cells.

Translational research for the evaluation of physical activity habits and lifestyle modifications based on nutrition and exercise has recently gained attention. In this study, we evaluated the effects of serum samples obtained before and after a 12-week home-based lifestyle intervention based on nutrition and exercise in breast cancer survivors in terms of modulation of the tumorigenic potential of breast cancer cells. The home-based lifestyle intervention proposed in this work consisted of educational counselling on exercise and nutritional behaviors and in 12 weeks of structured home-based exercise. Triple-negative breast cancer cell line MDA-MB-231 was cultured in semi-solid medium (3D culture) with sera collected before (PRE) and after (POST) the lifestyle intervention program. Spheroid formation was evaluated by counting cell colonies after 3 weeks of incubation. Results show a slight but significant reduction of spheroid formation induced by serum collected POST in comparison to those obtained PRE. Moreover, statistical analyses aimed to find physiologic and metabolic parameters associated with 3D cell proliferation revealed the proliferative inducer IGF-1 as the only predictor of cell tumorigenic potential. These results highlight the importance of lifestyle changes for cancer progression control in a tertiary prevention context. Translational research could offer a useful tool to identify metabolic and physiological changes induced by exercise and nutritional behaviors associated with cancer progression and recurrence risk.

Home-based lifestyle intervention for breast cancer survivors: A surprising improvement in the quality of life during the first year of COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic induced an extraordinary impact on public mental health to a degree not completely understood, especially in vulnerable populations such as breast cancer (BC) survivors. In this study, we described the short- (after 3-month) and long- (after 12-month) term effects of a multidisciplinary home-based lifestyle intervention in Italian women BC survivors during the first year of COVID-19 pandemic. MATERIALS AND METHODS: In total, 30 Italian BC survivors with risk factors for recurrence took part in the ongoing MoviS trial (protocol: NCT04818359). Between January 2020 and January 2021, a 3-month lifestyle intervention based on psychological counseling, nutrition, and exercise was carried out. Participants were asked to fill out psychological questionnaires for the assessment of quality of life (QoL) indicators (European Organization for Research and Treatment of Cancer QoL, EORTC-QLQ-C30) and psychological health measures such as fatigue (Brief Fatigue Inventory, BFI), distress (Distress Thermometer, DT and Psychological Distress Inventory, PDI), cancer-related fatigue (Verbal Rating Scale, VRS), and mood states (Profile of Mood States Questionnaire, POMS). IBM SPSS Statistical Software version 27.0 and R Project for Statistical Computing version 4.2.1 were used to process data. All participants were assessed at four time points: T0 (baseline), T1 (3-month), and follow-up at T2 and T3 (6- and 12-month, respectively) to measure primary (quality of life indicators) and secondary (psychological health) outcomes. Friedman non parametric test and Wilcoxon signed rank test (with Bonferroni correction) were conducted to investigate the statistically significant differences in psychometric scores and between assessment times. RESULTS: Compared to baseline (T0), at T1 most of the QoL indicators (i.e., symptoms of fatigue and general health) were improved (p < 0.017) with the exception of a worsening in participants' social functioning ability. Also, perception of severity of fatigue, distress, cancer-related fatigue, depression, and anger enhanced. Compared to baseline (T0), at T3 we mainly observed a stable condition with T0-T1 pairwise comparison, however other secondary outcomes (i.e., fatigue mood state, confusion, and anxiety) significantly improved. DISCUSSION: Our preliminary findings support the proposal of this lifestyle intervention for BC survivors. Despite the home-confinement due to the COVID-19 pandemic, the intervention surprisingly improved QoL indicators and psychological health of the participants.

Primum non Nocere: How to ensure continuity of care and prevent cancer patients from being overlooked during the COVID- 19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to all countries since December 2019, triggering a pandemic within weeks of the initial outbreak. Doctors were presented with the challenge of having to reimagine the traditional hospital organisation in order to effectively manage patients. PATIENTS AND METHODS: During the months of the COVID-19 pandemic our Institution was assisted by a call-center (CC) that triaged cancer patients planned for follow-up in our outpatient clinics: C1 (for female cancers), C2 (for gastrointestinal, urogenital, and thoracic tumours), and D1 (for melanoma and for patients with tumours in over 5 years follow up). Data refers to the period between 15 April and 3 July 2020. RESULTS: A total of 1054 patients have been included in our study and 1005 (95%) of the contacts were successful. The analysis showed a majority of female patients (74%) and patients affected by breast cancer (56%). Among the options provided 646 patients (92.4%) opted for online consultancy. CONCLUSION: This study has shown that cancer patients valued technology-mediated follow-up visits mainly during the beginning of the pandemic because patients themselves were afraid to come to the hospital. Although telemedicine has intrinsic limitations, it is important for providing assistance and preventing cancer patients from feeling isolated during an emergency.

Effect of a lifestyle intervention program's on breast cancer survivors' cardiometabolic health: Two-year follow-up.

The purpose of this study is to assess the cardiometabolic responses of a lifestyle intervention (LI) conducted at home among breast cancer (BC) survivors during the two years of COVID-19 pandemic. A 3-month LI focused on diet and exercise was performed on thirty BC survivors (women; stages 0-II; non-metastatic; aged 53.6 ± 7.6 years; non-physically active) with a risk factor related to metabolic/endocrine diseases. Anthropometrics, cardiorespiratory fitness (V˙O2max), physical activity level (PAL), adherence to the Mediterranean diet (MeDiet modified questionnaire), and several biomarkers (i.e., glycemia, insulin, insulin resistance [HOMA-IR] index, triglycerides, high- [HDL] and low- [LDL] density lipoproteins, total cholesterol, progesterone, testosterone, and hs-troponin) were evaluated before and 3-, 6-, 12-, and 24-month after the LI. Beneficial effects of the LI were observed on several variables (i.e., body mass index, waist circumference, MeDiet, PAL, V˙ O2max, glycemia, insulin, HOMA-IR index, LDL, total cholesterol, triglycerides, testosterone) after 3-month. The significant effect on Mediterranean diet adherence and V˙ O2max persisted up to the 24-month follow-up. Decreases in HOMA-IR index and triglycerides were observed up to 12-month, however did not persist afterward. This study provides evidence on the positive association between LI and cardiometabolic health in BC survivors.

Movement and health beyond care, MoviS: study protocol for a randomized clinical trial on nutrition and exercise educational programs for breast cancer survivors.

BACKGROUND: Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. METHODS: One hundred seventy-two BC survivor women, aged 30-70 years, non-metastatic, stage 0-III, non-physically active, 6-12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40-70% of heart rate reserve) and duration (20-60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). DISCUSSION: This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. TRIAL REGISTRATION: ClinicalTrials.gov  NCT04818359 . Retrospectively registered on March 26, 2021.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.

Anti-TNFα Drugs and Interleukin Inhibitors: Epidemiological and Pharmacovigilance Investigation in COVID-19 Positive Patients.

Cytokine patterns and immune activation in patients with Coronavirus 2019 (COVID-19) seem to resemble the case of rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Biological drugs, such as anti-tumor necrosis factor α (TNFα) and interleukin (IL) inhibitors, appear to be protective against adverse outcomes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, these treatments are associated with an increased risk of secondary infections. The aim of the study was to examine the association between the use of immunomodulatory drugs and the risk of SARS-CoV-2-associated positivity, hospitalization and death compared to other commonly prescribed treatment regimens among patients with immune-mediated inflammatory diseases. METHODS: All patients with RA, Psoriasis and IBD were included in this observational analysis and treated with anti-TNFα, IL-inhibitors, Methotrexate (MTX) and Sulfasalazine drugs during the year 2020-2021. The population consisted of 932 patients and demographic, clinical and pharmacological data were analyzed. RESULTS: Although no significant differences were observed between patients treated with biological and synthetic drugs in terms of hospitalization and death, the multivariate logistic model showed that the type of drug influences the possibility of COVID-19 positivity. CONCLUSIONS: The results of this analysis support the use of biological drugs and justify further research investigating the association of these biological therapies with COVID-19 outcomes.

Evaluation of Two-Month Antibody Levels after Heterologous ChAdOx1-S/BNT162b2 Vaccination Compared to Homologous ChAdOx1-S or BNT162b2 Vaccination.

We evaluated the post-vaccination humoral response of three real-world cohorts. Vaccinated subjects primed with ChAdOx1-S and boosted with BNT162b2 mRNA vaccine were compared to homologous dosing (BNT162b2/BNT162b2 and ChAdOx1-S/ChAdOx1-S). Serum samples were collected two months after vaccination from a total of 1248 subjects. The results showed that the heterologous vaccine schedule induced a significantly higher humoral response followed by homologous BNT162b2/BNT162b2 and ChAdOx1-S/ChAdOx1-S vaccines (p < 0.0001). Moreover, analyzing factors (i.e., vaccine schedule, sex, age, BMI, smoking, diabetes, cardiovascular diseases, respiratory tract diseases, COVID-19 diagnosis, vaccine side effects) influencing the IgG anti-S response, we found that only the type of vaccine affected the antibody titer (p < 0.0001). Only mild vaccine reactions resolved within few days (40% of subjects) and no severe side effects for either homologous groups or the heterologous group were reported. Our data support the use of heterologous vaccination as an effective and safe alternative to increase humoral immunity against COVID-19.

Innovative scanning electron microscopic investigation in blood samples of patients affected by leukaemia: A physical-chemical-biological approach.

The study proposes an innovative, interdisciplinary observation on blood samples of patients coming from the region Marche (Italy) suffering from acute myeloid leukaemia (AML) by means of a scanning electron microscope coupled with an X-ray microprobe of an Energy Dispersive Spectroscope. A novel protocol of blood preparation was studied and prepared to identify exogenous, potentially toxic foreign bodies coming from an environmental contamination. The results on the four different blood fractions of 38 blood samples (erythrocytes, leukocytes, platelets, and plasma) indicate that the circulating blood of leukaemic patients shows the systematic presence of physical contaminants, with a frequency and concentration which are statistically meaningful as compared to the healthy controls. The chemical compositions of the particles were identified as well as the frequency of the elements they were composed of. The analysis of these chemical compositions demonstrated that these patients had undergone a remarkable environmental, occupational, industrial exposure at some time. A possible pathological mechanism based on a nano-bio-interaction between the internalized environmental particulate matter and the blood components is hypothesized and discussed.

Cortisol, chronotype, and coping styles as determinants of tolerance of nursing staff to rotating shift work.

Hypothalamo-pituitary-adrenal axis activity and cortisol patterns are likely to play a role in shift work tolerance, i.e., ability to adapt to shift work without suffering stress-related consequences. Yet, the evidence is scanty. Here, salivary cortisol output during night shifts and leisure days was assessed in fast-forward rotating shift work nursing staff (N = 30), and possible links with a series of variables - gender (30% male), age (M = 39.6, SEM = 1.57 y), years of service (M = 12.43, SEM = 1.48 y), BMI (M = 23.29, SEM = 0.66 Kg/m2), self-rated chronotype, sleep quality, and psycho-behavioral factors - were investigated. Main results show that cortisol output during night shifts: i) is larger in morning-oriented chronotypes, thus affected by the circadian misalignment between biological and working rhythms; ii) associates with dysfunctional coping styles at work; iii) positively correlates with diurnal cortisol secretion on leisure days, i.e., individuals with larger cortisol output during shifts display higher cortisol secretion on non-working days. Chronotype and psycho-behavioral factors explain most of the correlational weight linking cortisol output during the night shift and off-days. In conclusion, we confirm salivary cortisol testing as a suitable objective marker of occupational stress and propose it as a valuable index for monitoring shift work tolerance, in combination with chronotype. Moreover, we emphasize the importance of evaluating psycho-behavioral factors in professional settings, because these modifiable variables can be addressed with tailored psychological interventions to ameliorate poor job satisfaction, reduce work-related distress, and avoid chronic cortisol excess experienced by shift workers.

Real-Life Analysis with Erenumab: First Target Therapy in the Episodic and Chronic Migraine's Prophylaxis.

BACKGROUND: to research retrospectively the efficacy of Erenumab's treatment, thus allowing to describe a summary more in line with the reality observed every day in clinical practice, relative to a sample of patients widely heterogeneous. The study aims to confirm the efficacy of Erenumab, in terms of reduction of migraine days per month, from baseline to month 12 of treatment. Additional objectives included a reduction in the number of days of symptomatic drug use and change from baseline in the Migraine Disability Assessment Score Questionnaire (MIDAS); Methods: the analysis included all patients treated for 12 months with Erenumab during the year 2019-2020. The population analyzed consists of twenty-six patients from the Neurology outpatient clinic in Fossombrone. Several quantitative and qualitative variables were recorded by reading the medical records of the patients. The MIDAS was administered to patients to assess the disability related to migraine; Results: at the end of treatment, a statistically significant reduction in the mean number of monthly migraine days, acute medication use per month, and MIDAS questionnaire score was observed; Conclusions: as a preventive treatment of episodic and chronic migraine, our analysis data confirm the efficacy of Erenumab for the prevention of the migraine. The success is achieved in 96% of cases.