The role of stroke-induced immunosuppression as a predictor of functional outcome in the neurorehabilitation setting.

Stroke affects the interconnection between the nervous and immune systems, leading to a down-regulation of immunity called stroke-induced immunosuppression (SII). The primary aim of this study is to investigate SII role as a predictor of functional, neurological, and motor outcomes in the neurorehabilitation setting (NRB). We conducted a prospective observational study enrolling post-acute stroke patients hospitalized for neurorehabilitation. At NRB admission (T0) and discharge (T1), we assessed presence of SII (defined by a neutrophil-to-lymphocyte ratio ≥ 5) and we evaluated functional independence (Functional Independence Measure-FIM, Barthel Index-BI), motor performances (Tinetti Score, Hauser Ambulation Index) and neurological impairment (NIHSS). We enrolled 96 patients (45.8% females, 70.6 ± 13.9 years, 88.5% ischemic stroke). At T0, 15.6% of patients (15/96) had SII. When compared to immunocompetent patients (IC), the SII group was characterized by worse baseline functional independence, motor performances and neurological disability. The same was confirmed at T1 (FIM p = 0.012, BI p = 0.007, Tinetti p = 0.034, NIHSS p = 0.001). Neurological disability demonstrated a less pronounced improvement in SII (ΔNIHSS: SII: - 2.1 ± 2.3 vs. IC: - 3.1 ± 2.5, p = 0.035). SII group presented a higher percentage of infectious complications during the neurorehabilitation period (SII 80% vs. IC 25.9%; p = 0.001). SII may represent a negative prognostic factor in the neurorehabilitation setting. SII patients were characterized by poorer functional, motor, neurological performances and higher risk of infectious complications. ClinicaTrial registration: NCT05889169.

Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention.

This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care.

Effects of Chronic Hypertension on the Energy Metabolism of Cerebral Cortex Mitochondria in Normotensive and in Spontaneously Hypertensive Rats During Aging.

In this study the subcellular modifications undergone by cerebral cortex mitochondrial metabolism in chronic hypertension during aging were evaluated. The catalytic properties of regulatory energy-linked enzymes of Tricarboxylic Acid Cycle (TCA), Electron Transport Chain (ETC) and glutamate metabolism were assayed on non-synaptic mitochondria (FM, located in post-synaptic compartment) and on intra-synaptic mitochondria of pre-synaptic compartment, furtherly divided in "light" (LM) and "heavy" (HM) mitochondria, purified form cerebral cortex of normotensive Wistar Kyoto Rats (WKY) versus Spontaneously Hypertensive Rats (SHR) at 6, 12 and 18 months. During physiological aging, the metabolic machinery was differently expressed in pre- and post-synaptic compartments: LM and above all HM were more affected by aging, displaying lower ETC activities. In SHR at 6 months, FM and LM showed an uncoupling between TCA and ETC, likely as initial adaptive response to hypertension. During pathological aging, HM were particularly affected at 12 months in SHR, as if the adaptive modifications in FM and LM at 6 months granted a mitochondrial functional balance, while at 18 months all the neuronal mitochondria displayed decreased metabolic fluxes versus WKY. This study describes the effects of chronic hypertension on cerebral mitochondrial energy metabolism during aging through functional proteomics of enzymes at subcellular levels, i.e. in neuronal soma and synapses. In addition, this represents the starting point to envisage an experimental physiopathological model which could be useful also for pharmacological studies, to assess drug actions during the development of age-related pathologies that could coexist and/or are provoked by chronic hypertension.

A possible unexpected link: Could wheat elimination trigger food protein-induced enterocolitis syndrome in a celiac disease patient?

Cases of association between celiac disease and wheat allergy have been described in the literature. However, to date, no reported cases have linked celiac disease with wheat food protein-induced enterocolitis syndrome (FPIES). We report a case of this association. A child diagnosed with celiac disease at the age of 2 years, following a gluten-free diet, experienced uncontrollable vomiting, and subsequent hypotension within 2 h of accidental ingestion of wheat flour. As a result, the child required hospitalization for fluid therapy. A similar episode occurred when the child turned 5 y, again resulting from accidental gluten ingestion. This time, the symptoms included vomiting, hypotension, and a loss of consciousness, leading to hospitalization for rehydration treatment. After this second episode, on suspicion of FPIES, the patient was referred to the pediatric allergists, who confirmed the diagnosis. To our knowledge, this is the first case of an association between celiac disease and FPIES. It has been hypothesized that exclusion diets in food-allergic children may lead to an increase in specific immunoglobulin E levels for those foods and, consequently, the risk of anaphylaxis. However, FPIES is not an immunoglobulin E-mediated condition. Hence, further investigations are warranted to elucidate the underlying mechanisms linking these 2 disorders.

Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.

PURPOSE: Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA. METHODS: A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool. RESULTS: A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding. CONCLUSION: The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico

El síndrome hemolítico urémico secundario a Streptococcus pneumoniae (SHU-Sp) es una complicación poco frecuente de las enfermedades invasoras por S. pneumoniae. Presenta una alta morbimortalidad, con requerimiento de transfusiones de glóbulos rojos y plaquetas, terapia de sustitución de la función renal de inicio precoz y más prolongada, así como mayores complicaciones a largo plazo, comparado con las formas secundarias a infección entérica por Escherichia coli productora de toxina Shiga. Presentamos el caso clínico de una preescolar de dos años, previamente sana, vacunada con tres dosis de PCV13, que desarrolló una insuficiencia renal aguda, anemia hemolítica y plaquetopenia, en el contexto de una neumonía con empiema y bacteriemia por S. pneumoniae.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is an uncommon complication of invasive pneumococcal infections. Patients with Sp-HUS have a higher mortality and long term morbidity than those due to HUS from Shiga toxin-producing Escherichia coli infections (STEC-HUS). They often require more red blood cells and platelet transfusions, and early initiation of renal substitution therapy, presenting a higher rate of arterial hypertension and chronic renal disease in the long term, compared to STEC-HUS. We report a healthy 2 year-old infant, vaccinated with three doses PCV13, that developed acute renal failure, hemolytic anemia and thrombocytopenia in the course of a complicated pneumococcal pneumonia with empyema and bacteremia.

Deep learning performance for detection and classification of microcalcifications on mammography.

BACKGROUND: Breast cancer screening through mammography is crucial for early detection, yet the demand for mammography services surpasses the capacity of radiologists. Artificial intelligence (AI) can assist in evaluating microcalcifications on mammography. We developed and tested an AI model for localizing and characterizing microcalcifications. METHODS: Three expert radiologists annotated a dataset of mammograms using histology-based ground truth. The dataset was partitioned for training, validation, and testing. Three neural networks (AlexNet, ResNet18, and ResNet34) were trained and evaluated using specific metrics including receiver operating characteristics area under the curve (AUC), sensitivity, and specificity. The reported metrics were computed on the test set (10% of the whole dataset). RESULTS: The dataset included 1,000 patients aged 21-73 years and 1,986 mammograms (180 density A, 220 density B, 380 density C, and 220 density D), with 389 malignant and 611 benign groups of microcalcifications. AlexNet achieved the best performance with 0.98 sensitivity, 0.89 specificity of, and 0.98 AUC for microcalcifications detection and 0.85 sensitivity, 0.89 specificity, and 0.94 AUC of for microcalcifications classification. For microcalcifications detection, ResNet18 and ResNet34 achieved 0.96 and 0.97 sensitivity, 0.91 and 0.90 specificity and 0.98 and 0.98 AUC, retrospectively. For microcalcifications classification, ResNet18 and ResNet34 exhibited 0.75 and 0.84 sensitivity, 0.85 and 0.84 specificity, and 0.88 and 0.92 AUC, respectively. CONCLUSIONS: The developed AI models accurately detect and characterize microcalcifications on mammography. RELEVANCE STATEMENT: AI-based systems have the potential to assist radiologists in interpreting microcalcifications on mammograms. The study highlights the importance of developing reliable deep learning models possibly applied to breast cancer screening. KEY POINTS: • A novel AI tool was developed and tested to aid radiologists in the interpretation of mammography by accurately detecting and characterizing microcalcifications. • Three neural networks (AlexNet, ResNet18, and ResNet34) were trained, validated, and tested using an annotated dataset of 1,000 patients and 1,986 mammograms. • The AI tool demonstrated high accuracy in detecting/localizing and characterizing microcalcifications on mammography, highlighting the potential of AI-based systems to assist radiologists in the interpretation of mammograms.

Quantification and prospective evaluation of serum NfL and GFAP as blood-derived biomarkers of outcome in acute ischemic stroke patients.

Identification of reliable and accessible biomarkers to characterize ischemic stroke patients' prognosis remains a clinical challenge. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are markers of brain injury, detectable in blood by high-sensitive technologies. Our aim was to measure serum NfL and GFAP after stroke, and to evaluate their correlation with functional outcome and the scores in rehabilitation scales at 3-month follow-up. Stroke patients were prospectively enrolled in a longitudinal observational study within 24 hours from symptom onset (D1) and monitored after 7 (D7), 30 ± 3 (M1) and 90 ± 5 (M3) days. At each time-point serum NfL and GFAP levels were measured by Single Molecule Array and correlated with National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Trunk Control Test (TCT), Functional Ambulation Classification (FAC) and Functional Independence Measure (FIM) scores. Serum NfL and GFAP showed different temporal profiles: NfL increased after stroke with a peak value at D7; GFAP showed an earlier peak at D1. NfL and GFAP concentrations correlated with clinical/rehabilitation outcomes both longitudinally and prospectively. Multivariate analysis revealed that NfL-D7 and GFAP-D1 were independent predictors of 3-month NIHSS, TCT, FAC and FIM scores, with NfL being the biomarker with the best predictive performance.

Psychological issues in breast cancer survivors confronted with motherhood: Literature review and a call to action.

Breast cancer is currently the most common cancer among women worldwide; in 15-25% of cases, patients are premenopausal at the time of diagnosis, and 50% of women desire pregnancy after cancer diagnosis. Motherhood after breast cancer involves complex psychological challenges with long-term consequences, though it is safely pursuable with adequate support. The purpose of this mini-review is to analyze the psychological implications surrounding pregnancy and motherhood after breast cancer and promote action in addressing the challenges that might affect women facing these life events.

How Radiomics Can Improve Breast Cancer Diagnosis and Treatment.

Recent technological advances in the field of artificial intelligence hold promise in addressing medical challenges in breast cancer care, such as early diagnosis, cancer subtype determination and molecular profiling, prediction of lymph node metastases, and prognostication of treatment response and probability of recurrence. Radiomics is a quantitative approach to medical imaging, which aims to enhance the existing data available to clinicians by means of advanced mathematical analysis using artificial intelligence. Various published studies from different fields in imaging have highlighted the potential of radiomics to enhance clinical decision making. In this review, we describe the evolution of AI in breast imaging and its frontiers, focusing on handcrafted and deep learning radiomics. We present a typical workflow of a radiomics analysis and a practical "how-to" guide. Finally, we summarize the methodology and implementation of radiomics in breast cancer, based on the most recent scientific literature to help researchers and clinicians gain fundamental knowledge of this emerging technology. Alongside this, we discuss the current limitations of radiomics and challenges of integration into clinical practice with conceptual consistency, data curation, technical reproducibility, adequate accuracy, and clinical translation. The incorporation of radiomics with clinical, histopathological, and genomic information will enable physicians to move forward to a higher level of personalized management of patients with breast cancer.

Prediction of the Malignancy of a Breast Lesion Detected on Breast Ultrasound: Radiomics Applied to Clinical Practice.

The study aimed to evaluate the performance of radiomics features and one ultrasound CAD (computer-aided diagnosis) in the prediction of the malignancy of a breast lesion detected with ultrasound and to develop a nomogram incorporating radiomic score and available information on CAD performance, conventional Breast Imaging Reporting and Data System evaluation (BI-RADS), and clinical information. Data on 365 breast lesions referred for breast US with subsequent histologic analysis between January 2020 and March 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 255) and a validation test group (n = 110). A radiomics score was generated from the US image. The CAD was performed in a subgroup of 209 cases. The radiomics score included seven radiomics features selected with the LASSO logistic regression model. The multivariable logistic model incorporating CAD performance, BI-RADS evaluation, clinical information, and radiomic score as covariates showed promising results in the prediction of the malignancy of breast lesions: Area under the receiver operating characteristic curve, [AUC]: 0.914; 95% Confidence Interval, [CI]: 0.876-0.951. A nomogram was developed based on these results for possible future applications in clinical practice.

Intracranial carotid artery calcification morphology differs in patients with lacunar and nonlacunar acute ischemic strokes.

BACKGROUND AND PURPOSE: Intracranial carotid artery calcifications (ICACs) are a common finding on noncontrast computed tomography (NCCT) and have been associated with an increased risk of ischemic stroke. However, no data are available about the association between ICAC patterns and stroke etiology. We investigated the association between ICAC patterns and etiological subtypes of ischemic stroke. METHODS: We retrospectively analyzed a single center cohort of patients admitted for ischemic stroke with known etiology. Each carotid artery was evaluated separately on NCCT scans to define the ICAC pattern (intimal, medial, mixed). The association between ICAC patterns and stroke etiology was investigated using logistic regression models adjusting for relevant confounders. RESULTS: A total of 485 patients were included (median age = 78 [interquartile range (IQR) = 70-85] years, 243 [50%] female, median National Institutes of Health Stroke Scale = 6 [IQR = 3-12]). Frequencies of ICAC patterns were: intimal, n = 96 (20%); medial, n = 273 (56%); mixed, n = 51 (11%), indistinct/absent, n = 65 (13%) patients. Intimal pattern was more frequent in lacunar compared with nonlacunar (33% vs. 16%, p < 0.001) stroke etiology, whereas medial pattern was less frequent in lacunar compared with nonlacunar stroke (36% vs. 62%, p < 0.001). After adjustment for confounders, intimal ICAC predominant pattern remained associated with lacunar stroke etiology in two multivariate models (Model 1: adjusted odds ratio [aOR] = 2.08, 95% confidence interval [CI] = 1.20-3.56; Model 2: aOR = 2.01, 95% CI = 1.16-3.46). CONCLUSIONS: Our study suggests that intimal ICAC pattern is associated with lacunar stroke and may serve as a marker for lacunar stroke etiology, possibly strengthening the relation between endothelial dysfunction and lacunar stroke.

Incretin-based drugs as potential therapy for neurodegenerative diseases: current status and perspectives.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent neurodegenerative disorders. Despite their pathophysiological and clinical differences, they share several mechanistic similarities at cellular and sub-cellular levels. The current treatments of AD and PD are only symptomatic, since many clinically-tested drugs failed to prevent or halt their progression. There is now evidence that type 2 diabetes mellitus is among the main risk factors for AD and PD and that the insulin resistance in the brain plays a crucial role in their neuropathological processes. Therefore, insulin nasal administration was suggested for the treatment of AD and PD, both in diabetic and non-diabetic patients. However, the adverse effects of chronic insulin prompted the research of alternative strategies, such as the novel antidiabetic drugs based on the incretin hormones glucagon-like protein-1 (GLP-1) and glucose-dependent insulinotropic Peptide (GIP). The rapid inactivation of these incretins by dipeptidyl-peptidase IV (DPP-IV) suggested the development of DPP-IV-resistant GLP-1 receptor agonists (GLP-1Ras), the recent dual GLP-1/GIP receptor agonists and the DPP-IV inhibitors (DPP-IVis). This review will first describe the experimental, pathophysiological and clinical approach for AD and PD treatment with insulin. Afterwards, the main pharmacologic properties of GLP-1Ras and of DPP-IVis will be discussed, detailing their ability to cross the BBB and get access to the brain for GLP-1Ras, and the novel strategies for BBB crossing as regards DPP-IVis. Emphasis will be placed on the main findings obtained from AD and PD experimental models about the neuroprotective effects of these drugs. For AD, the improvement of learning and memory exerted by incretin-based drugs correlated with reduction of chronic inflammation, brain Aß plaque, tau hyperphosphorylation, protection of mitochondria, enhancement of energy utilisation. For PD, both GLP-1Ras and of DPP-IVis reversed the nigrostriatal dopaminergic cell loss progression, restored dopamine synthesis, exerted anti-inflammatory activity and improved motor functions. Finally, the encouraging results of the first clinical trials on AD and PD patients and the adverse effects of GLP-1Ras and DPP-IVis will be discussed, highlighting how the above-mentioned neuroprotective effects have a great potential to be translated into clinical settings and that the incretin-based approach represents novel promising strategy for the treatment of AD and PD, although more convincing clinical pieces of evidence are required. In perspective, the new approaches that are being developed to allow GLP-1Ras and DPP-IVis rapid entering into the Central Nervous System may substantially contribute to their repurposing for neurodegenerative disease.

A Score to Predict the Malignancy of a Breast Lesion Based on Different Contrast Enhancement Patterns in Contrast-Enhanced Spectral Mammography.

Background: To create a predictive score of malignancy of a breast lesion based on the main contrast enhancement features ascertained by contrast-enhanced spectral mammography (CESM). Methods: In this single-centre prospective study, patients with suspicious breast lesions (BIRADS > 3) were enrolled between January 2013 and February 2022. All participants underwent CESM prior to breast biopsy, and eventually surgery. A radiologist with 20 years' experience in breast imaging evaluated the presence or absence of enhancement and the following enhancement descriptors: intensity, pattern, margin, and ground glass. A score of 0 or 1 was given for each descriptor, depending on whether the enhancement characteristic was predictive of benignity or malignancy (both in situ and invasive). Then, an overall enhancement score ranging from 0 to 4 was obtained. The histological results were considered the gold standard in the evaluation of the relationship between enhancement patterns and malignancy. Results: A total of 321 women (median age: 51 years; range: 22−83) with 377 suspicious breast lesions were evaluated. Two hundred forty-nine lesions (66%) have malignant histological results (217 invasive and 32 in situ). Considering an overall enhancement score ≥ 2 as predictive of malignancy, we obtain an overall sensitivity of 92.4%; specificity of 89.8%; positive predictive value of 94.7%; and negative predictive value of 85.8%. Conclusions: Our proposed predictive score on the enhancement descriptors of CESM to predict the malignancy of a breast lesion shows excellent results and can help in early breast cancer diagnosis and in avoiding unnecessary biopsies.

Brain bioenergetics in chronic hypertension: Risk factor for acute ischemic stroke.

Chronic hypertension is one of the key modifiable risk factors for acute ischemic stroke, also contributing to determine greater neurological deficits and worse functional outcome when an acute cerebrovascular event would occur. A tight relationship exists between cerebrovascular autoregulation, neuronal activity and brain bioenergetics. In chronic hypertension, progressive adaptations of these processes occur as an attempt to cope with the demanding necessity of brain functions, creating a new steady-state homeostatic condition. However, these adaptive modifications are insufficient to grant an adequate response to possible pathological perturbations of the established fragile hemodynamic and metabolic homeostasis. In this narrative review, we will discuss the main mechanisms by which alterations in brain bioenergetics and mitochondrial function in chronic hypertension could lead to increased risk of acute ischemic stroke, stressing the interconnections between hemodynamic factors (i.e. cerebral autoregulation and neurovascular coupling) and metabolic processes. Both experimental and clinical pieces of evidence will be discussed. Moreover, the potential role of mitochondrial dysfunction in determining, or at least sustaining, the pathogenesis and progression of chronic neurogenic hypertension will be considered. In the perspective of novel therapeutic strategies aiming at improving brain bioenergetics, we propose some determinant factors to consider in future studies focused on the cause-effect relationships between chronic hypertension and brain bioenergetic abnormalities (and vice versa), so to help translational research in this so-far unfilled gap.

Prediction of the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients With MRI-Radiomics: A Systematic Review and Meta-analysis.

We performed a systematic review and a meta-analysis of studies using MRI-radiomics for predicting the pathological complete response in breast cancer patients undergoing neoadjuvant therapy , and we evaluated their methodological quality using the radiomics-quality-score (RQS). Random effects meta-analysis was performed pooling area under the receiver operating characteristics curves. Publication-bias was assessed using the Egger's test and visually inspecting the funnel plot. Forty-three studies were included in the qualitative review and 34 in the meta-analysis. Summary area under the receiver operating characteristics curve was 0,78 (95%CI:0,74-0,81). Heterogeneity according to the I2 statistic was substantial (71%) and there was no evidence of publication bias (P-value = 0,2). The average RQS was 12,7 (range:-1-26), with an intra-class correlation coefficient of 0.93 (95%CI:0.61-0.97). Year of publication, field intensity and synthetic RQS score do not appear to be moderators of the effect (P-value = 0.36, P-value = 0.28 and P-value = 0.92, respectively). MRI-radiomics may predict response to neoadjuvant therapy in breast cancer patients but the heterogeneity of the current studies is still substantial.

Acrocyanosis in a large italian pediatric series during the Covid-19 pandemic.

BACKGROUND: SARS-CoV2 infection may present at onset with cutaneous manifestations as chilblains, pernio-like lesions characterized by rapid onset, itching, pain and tenderness and quick improvement with re-warming as similarly observed in primary acrocyanosis. The purpose of the present study was to detect in a single institution series of pediatric patients, during COVID-19 pandemic, the prevalence of acrocyanosis compared to previous period and an eventual correlation with SARS-Cov2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection or other secondary etiologies of this disorder. METHODS: We retrospectively analyzed the prevalence of pediatric patients with acrocyanosis between January 2020 and July 2021, compared to the same period of previous year. All patients were investigated with capillaroscopies, clinical and laboratory texts. Those patients referred to our Institution, during the Covid-19 pandemic were also examined for SARS-CoV2 serologies to find out an eventual specific correlation with this secondary potential etiology. RESULTS: During the first wave of Covid-19 pandemic we observed an increased prevalence of this manifestation. The analysis showed that the higher prevalence of patients with acrocyanosis, in this period, was not related to SARS-Cov2 infection. CONCLUSIONS: The acrocyanosis in pediatric patients is rarely associated with rheumatological diseases, being more frequently a primary disorder and strictly related to a sedentary lifestyle.

Clonidine and Brain Mitochondrial Energy Metabolism: Pharmacodynamic Insights Beyond Receptorial Effects.

Clonidine is an anti-hypertensive drug that inhibits the release of norepinephrine from pre-synaptic terminals binding to pre-synaptic α2-adrenoreceptors. Some studies suggest that this drug decreases brain energy expenditure, particularly in hypoxic-ischemic injury. However, data about clonidine effects on the functional parameters regulating brain energy metabolism are lacking. In this study, the effects of acute clonidine treatment (5 µg×kg-1 i.p., 30 min) were evaluated on the catalytic activity of regulatory energy-linked enzymes of Krebs' cycle, Electron Transport Chain and glutamate metabolism of temporal cerebral cortex of 3-month-old male Sprague-Dawley rats. Enzyme activities were assayed on non-synaptic "free" mitochondria (FM) of neuronal perikaryon and partly of glial cells, and on intra-synaptic "light" (LM) and "heavy" mitochondria (HM), localized within synaptic terminals. This subcellular analysis differentiates clonidine effects on post-synaptic and pre-synaptic neuronal compartments. The results showed that clonidine increased citrate synthase, cytochrome oxidase and glutamate-oxaloacetate transaminase activities of FM. In LM, citrate synthase activity was decreased, while cytochrome oxidase and glutamate-oxaloacetate transaminase activities were increased; on the contrary, citrate synthase, cytochrome oxidase and glutamate dehydrogenase were all decreased in HM. Therefore, clonidine exerted different effects with respect to brain mitochondria, coherently with the in vivo energy requirements of each synaptic compartment: the drug increased energy-linked enzyme activities in post-synaptic compartment, while the metabolic variations were complex in the pre-synaptic one, being enzyme activities heterogeneously modified in LM and decreased in HM. This study highlights the relationships existing between the clonidine-induced neuroreceptorial effects and the energy metabolism in pre- and post- synaptic bioenergetics.