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Introduction: Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators., Methods: In this retrospective cohort study, conducted at Milan's Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes-non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death-in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM., Results: A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24-67%, PLR: 40-64%) were inferior to specificity values (NLR: 64-76%, PLR: 55-72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV., Conclusions: Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations., (© 2024. The Author(s).)

Several criteria exist to diagnose pulmonary aspergillosis with varying degrees of certainty in specific populations, including oncohaematological patients (EORTC/MSG), ICU patients (mAspICU) and COVID-19 patients (ECMM). At the beginning of the pandemic, however, the diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA) could not be performed easily, and the decision to treat (DTT) was empirical. In this cross-sectional retrospective study including patients with SARS-CoV-2 infection and suspicion of CAPA, we studied the concordance between the DTT and the three diagnostic criteria using Cohen's coefficient, and then we identified the factors associated with the DTT and corrected them by treatment to study the influence of the diagnostic criteria on survival. We showed good concordance of the DTT and mAspICU and ECMM criteria, with "compatible signs", "positive culture" and "positive galactomannan" influencing the DTT. Treatment also showed a positive effect on survival once corrected for a putative, possible or probable diagnosis of CAPA using mAspICU and ECMM criteria. We conclude that EORTC/MSGERC are not considered applicable in clinical practice due to the lack of inclusion of signs and symptoms and do not lead to improved survival. mAspICU and ECMM criteria showed a good degree of agreement with the DTT and a positive correlation with patient recovery.

Background and Objective: The standard non-invasive imaging technique used to assess the severity and extent of Coronary Artery Disease (CAD) is Coronary Computed Tomography Angiography (CCTA). However, manual grading of each patient's CCTA according to the CAD-Reporting and Data System (CAD-RADS) scoring is time-consuming and operator-dependent, especially in borderline cases. This work proposes a fully automated, and visually explainable, deep learning pipeline to be used as a decision support system for the CAD screening procedure. The pipeline performs two classification tasks: firstly, identifying patients who require further clinical investigations and secondly, classifying patients into subgroups based on the degree of stenosis, according to commonly used CAD-RADS thresholds., Methods: The pipeline pre-processes multiplanar projections of the coronary arteries, extracted from the original CCTAs, and classifies them using a fine-tuned Multi-Axis Vision Transformer architecture. With the aim of emulating the current clinical practice, the model is trained to assign a per-patient score by stacking the bi-dimensional longitudinal cross-sections of the three main coronary arteries along channel dimension. Furthermore, it generates visually interpretable maps to assess the reliability of the predictions., Results: When run on a database of 1873 three-channel images of 253 patients collected at the Monzino Cardiology Center in Milan, the pipeline obtained an AUC of 0.87 and 0.93 for the two classification tasks, respectively., Conclusion: According to our knowledge, this is the first model trained to assign CAD-RADS scores learning solely from patient scores and not requiring finer imaging annotation steps that are not part of the clinical routine., Competing Interests: Declaration of Competing Interest Riccardo Bellazzi is co-founder and shareholder of two spin-offs of the University of Pavia (Engenome s.r.l. and Biomeris s.r.l.) that operate in the field of data management, artificial intelligence and bioinformatics. All the other authors have nothing to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was Aspergillus (26.5%), followed by Candida (20.7%) and Mucor (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.

Introduction: The hyperinflammation phase of severe SARS-CoV-2 is characterised by complete blood count alterations. In this context, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) can be used as prognostic factors. We studied NLR and PLR trends at different timepoints and computed optimal cutoffs to predict four outcomes: use of continuous positive airways pressure (CPAP), intensive care unit (ICU) admission, invasive ventilation and death., Methods: We retrospectively included all adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia admitted from 23 January 2020 to 18 May 2021. Analyses included non-parametric tests to study the ability of NLR and PLR to distinguish the patients' outcomes at each timepoint. Receiver operating characteristic (ROC) curves were built for NLR and PLR at each timepoint (minus discharge) to identify cutoffs to distinguish severe and non-severe disease. Their statistical significance was assessed with the chi-square test. Collection of data under the SMACORE database was approved with protocol number 20200046877., Results: We included 2169 patients. NLR and PLR were higher in severe coronavirus disease 2019 (COVID-19). Both ratios were able to distinguish the outcomes at each timepoint. For NLR, the areas under the receiver operating characteristic curve (AUROC) ranged between 0.59 and 0.81, and for PLR between 0.53 and 0.67. From each ROC curve we computed an optimal cutoff value., Conclusion: NLR and PLR cutoffs are able to distinguish severity grades and mortality at different timepoints during the course of disease, and, as such, they allow a tailored approach. Future prospects include validating our cutoffs in a prospective cohort and comparing their performance against other COVID-19 scores., (© 2023. The Author(s).)

Introduction: The use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use., Methods: we present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis., Results: 14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated ( p  < 0.0001). Of interest, efficiency was also related to catheter location, being worse in those located in the femoral vein than in into the jugular or the subclavian veins ( p  < 0.05). In a multivariate analysis, the only variable significantly associated was catheter size (beta 0.238, p  < 0.01)., Discussion: Placing a CVC for PBPC collection in pediatric subjects is overall safe; CVC-related complications in pediatric healthy donors are very rare. Furthermore, we should try to place catheters of the largest caliber possible, since the efficiency of the collection is related to this variable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zubicaray, Martin-Consuegra, Nieto, Albi, Iriondo, Sebastian, Gálvez, Molina, González-Vincent, de Pablo, Castillo, Ramírez, Madero, Díaz and Sevilla.)

The incidence of long COVID in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting have to be elucidated. We prospectively enrolled all patients treated for a solid tumor at the department of Medical Oncology of the Fondazione IRCCS Policlinico San Matteo with a positive SARS-CoV-2 antigen or polymerase chain reaction test from January to September 2022 (Omicron surge). Ninety-seven patients answered the survey questions by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. Only twelve patients (12.4%) reported long COVID. No significant difference between early therapies anti-SARS-CoV-2 31 and long COVID ( p = 0.443) was seen. The female sex ( p = 0.024) and diabetes mellitus ( p = 0.014) are significantly associated with long COVID. No statistically significant difference between the two groups (Long COVID vs. No Long COVID) according to the time to nasal swab viral clearance ( p = 0.078). The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage.

Introduction: Few data about the safety of immune checkpoint inhibitors (ICIs) in the patients with solid tumor with Occult Hepatitis B Virus (OBI) are available. According to the Taormina Workshop on Occult HBV Infection Faculty Members we defined as potential-OBI (pOBI) the HBV DNA negativity with anti-hepatitis B core antibody (anti-HBc) positivity (pOBI seropositive), and the patients with HBsAg-negative and anti-HBc-negative and Hepatitis B surface antibody (anti-HBs)-negative are defined pOBI seronegative. The aim of this study is to investigate the prevalence of OBI in patients with solid tumors undergoing ICIs with or without chemotherapy and the incidence of reactivation (HBVr)., Methods: We retrospectively enrolled all HBsAg negative subjects who had received ICIs for at least three months. HBsAg and HBV DNA levels were repeated every 3 months until the end of the study and/or in case of ALT alterations. A univariate analysis was conducted in order to study for each variable available its ability to distinguish a potential OBI seropositive patient from a seronegative one., Results: 150 patients in our Oncology Unit were eligible. One hundred and seventeen patients (78%) received ICI as monotherapy, whereas 33 patients (22%) were treated with chemo-immunotherapy. The mainly used drugs for the ICI monotherapy were Pembrolizumab (47%), Nivolumab (33%) and Atezolizumab (11%). The prevalence of pOBI seropositive patients was 25.3%. We did not observe alterations of liver biochemistry nor HBVr., Discussion: This study highlights that about a quarter of our population had a potential occult hepatitis B. Immunotherapy might be considered as low risk of reactivation, regardless of the potential presence of episomal covalently closed circular DNA (cccDNA) in the liver, but the correct management still represents a challenge for oncologists and hepatologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lasagna, Albi, Maserati, Zuccarini, Quaccini, Baldanti, Sacchi, Bruno and Pedrazzoli.)

Background and Objectives: Extracorporeal photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD). However, information regarding lymphocyte collection for ECP in children is limited. The aim of this study was to analyse and compare lymphocyte collection for ECP in children using different devices and protocols. Moreover, we have studied both safety and variables of the infused product related to treatment efficacy., Patients and Methods: This was a retrospective study of 91 patients who underwent 1524 apheresis procedures with either the COBE Spectra or Spectra Optia system. The comparison study between the Optia protocols (MNC and CMNC) was prioritized. We analysed 578 procedures using the Optia blood cell separator: 204 and 374 using the MNC and the CMNC protocol, respectively., Results: The Optia CMNC protocol showed better collection efficiency, with increased lymphocyte collection per kg of body weight (p < 0.001). On multivariate analysis, the type of protocol showed no relationship with haematocrit or platelet loss. Most procedures were well-tolerated, with the most frequent adverse events related to venous access (21.7%). Seventy-one percent of patients had either partial or complete clinical GvHD response. In the multivariate model, only two variables were associated with a better response to ECP, younger age and a greater increase of B lymphocytes after treatment., Conclusion: Lymphocyte collection for ECP is well-tolerated in most children, achieving complete or partial response in more than half of GvHD patients. CMNC is the optimal software to perform lymphocyte collection in children., (© 2022 International Society of Blood Transfusion.)

Some vaccinated individuals still develop severe COVID-19, and the underlying causes are not entirely understood. We aimed at identifying demographic, clinical, and coinfection characteristics of vaccinated patients who were hospitalized. We also hypothesized that coinfections might play a role in disease severity and mortality. We retrospectively collected data from our COVID-19 registry for whom vaccination data were available. Patients were split into groups based on the number of administered doses (zero, one, two, or three). Data were assessed with Chi-square and Kruskal−Wallis tests and multiple logistic regression analysis. We collected data from 1686 patients and found that intra-hospital mortality was not associated to the vaccination status (e.g., p = 0.2 with three doses), while older age, sepsis, and non-viral pneumonia were (p < 0.001). Unvaccinated patients needed mechanical ventilation more often (8.5%) than vaccinated patients, in whom the probability of mechanical ventilation decreased with increasing doses (8.7%, 2.8%, 0%). We did not find more coinfections in vaccinated people. We concluded that there is a lack of real-life data to adequately characterize the pathophysiology and risk factors of patients who develop severe COVID-19, but coinfections do not appear to play a role in disease severity.

A mean-field selective optimal control problem of multipopulation dynamics via transient leadership is considered. The agents in the system are described by their spatial position and their probability of belonging to a certain population. The dynamics in the control problem is characterized by the presence of an activation function which tunes the control on each agent according to the membership to a population, which, in turn, evolves according to a Markov-type jump process. In this way, a hypothetical policy maker can select a restricted pool of agents to act upon based, for instance, on their time-dependent influence on the rest of the population. A finite-particle control problem is studied and its mean-field limit is identified via Γ -convergence, ensuring convergence of optimal controls. The dynamics of the mean-field optimal control is governed by a continuity-type equation without diffusion. Specific applications in the context of opinion dynamics are discussed with some numerical experiments., Competing Interests: Conflict of interestThe authors have not disclosed any competing interests., (© The Author(s) 2022.)

After the introduction of drastic containment measures aimed at stopping the epidemic contagion from SARS-CoV2, many governments have adopted a strategy based on a periodic relaxation of such measures in the face of a severe economic crisis caused by lockdowns. Assessing the impact of such openings in relation to the risk of a resumption of the spread of the disease is an extremely difficult problem due to the many unknowns concerning the actual number of people infected, the actual reproduction number and infection fatality rate of the disease. In this work, starting from a SEIRD compartmental model with a social structure based on the age of individuals and stochastic inputs that account for data uncertainty, the effects of containment measures are introduced via an optimal control problem dependent on specific social activities, such as home, work, school, etc. Through a short time horizon approximation, we derive models with multiple feedback controls depending on social activities that allow us to assess the impact of selective relaxation of containment measures in the presence of uncertain data. After analyzing the effects of the various controls, results from different scenarios concerning the first wave of the epidemic in some major countries, including Germany, France, Italy, Spain, the United Kingdom and the United States, are presented and discussed. Specific contact patterns in the home, work, school and other locations have been considered for each country. Numerical simulations show that a careful strategy of progressive relaxation of containment measures, such as that adopted by some governments, may be able to keep the epidemic under control by restarting various productive activities.

The adoption of containment measures to reduce the amplitude of the epidemic peak is a key aspect in tackling the rapid spread of an epidemic. Classical compartmental models must be modified and studied to correctly describe the effects of forced external actions to reduce the impact of the disease. The importance of social structure, such as the age dependence that proved essential in the recent COVID-19 pandemic, must be considered, and in addition, the available data are often incomplete and heterogeneous, so a high degree of uncertainty must be incorporated into the model from the beginning. In this work we address these aspects, through an optimal control formulation of a socially structured epidemic model in presence of uncertain data. After the introduction of the optimal control problem, we formulate an instantaneous approximation of the control that allows us to derive new feedback controlled compartmental models capable of describing the epidemic peak reduction. The need for long-term interventions shows that alternative actions based on the social structure of the system can be as effective as the more expensive global strategy. The timing and intensity of interventions, however, is particularly relevant in the case of uncertain parameters on the actual number of infected people. Simulations related to data from the first wave of the recent COVID-19 outbreak in Italy are presented and discussed.

Objectives: To compare the worsening of structural lung disease on high-resolution computed tomography (HRCT) with changes in spirometry results in cystic fibrosis (CF) patients, and analyse factors associated with the worsening of structural lung disease over time., Methods: A total of 31 CF subjects (mean age 11.03 ± 3.67 years old) were prospectively evaluated by two HRCT and spirometry tests performed 4 years apart. HRCT abnormalities were scored using the Bhalla scoring system. Comparisons between changes on HRCT and spirometry were made for all patients, and also for groups categorized by age, sex, genotypic alterations and lung obstruction., Results: The mean HRCT Bhalla scoring, forced expiratory volume in 1 s (FEV1 %pred.) and forced vital capacity (FVC %pred.) were 7.92 ± 3.59, 87.76 ± 20.52 and 96.54 ± 15.12, respectively. There was a significant deterioration in the Bhalla score (p < 0.01) and in certain categories: severity of bronchiectasis, peribronchial thickening, mucous plugging and bronchial divisions. Females had a more pronounced worsening of the Bhalla score than males (p = 0.048). No change over time was found in FEV1 and FVC. Only sex was associated with a deterioration in HRCT., Conclusions: HRCT Bhalla scoring changes statistically significantly over 4 years, but spirometry results do not. Worsening on HRCT is more evident in females., Key Points: • HRCT Bhalla scoring changes significantly over 4 years, spirometry results do not. • Females experience faster respiratory deterioration than males. • Spirometry results are not associated with deterioration in HRCT.

The study of formations and dynamics of opinions leading to the so-called opinion consensus is one of the most important areas in mathematical modelling of social sciences. Following the Boltzmann-type control approach recently introduced by the first two authors, we consider a group of opinion leaders who modify their strategy accordingly to an objective functional with the aim of achieving opinion consensus. The main feature of the Boltzmann-type control is that, owing to an instantaneous binary control formulation, it permits the minimization of the cost functional to be embedded into the microscopic leaders' interactions of the corresponding Boltzmann equation. The related Fokker-Planck asymptotic limits are also derived, which allow one to give explicit expressions of stationary solutions. The results demonstrate the validity of the Boltzmann-type control approach and the capability of the leaders' control to strategically lead the followers' opinion., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)

To monitor the course of lung damage in patients with cystic fibrosis (CF) using the different chest X-ray and high resolution computed tomography (HRCT) scoring systems that have been developed. The HRCT technique is more sensitive than chest radiography to evaluate the anatomy. However, in paediatric patients, the use of CT should be kept to a minimum, and guidelines for radiation protection and dose reduction should be applied. One of the most used classification systems for HRCT is the one proposed by Bhalla in 1991, which helps in the assessment of the severity and course of the disease in these patients depending on the different imaging findings. We present various examples of these criteria for HRCT, observed while reviewing a group of 48 paediatric patients., (Copyright © 2010 SERAM. Published by Elsevier Espana. All rights reserved.)

Background: Pleuropulmonary blastoma (PPB) is the most common lung neoplasms in childhood. Usually presents as recurrent respiratory infections and in some cases as pneumothorax., Case Report: We report the case of a 2-year-old patient that was diagnosed with PPB, that first manifested as recurrent pneumothorax. Three chest computed tomography were necessary for the diagnosis. The first 2 tomographies showed no abnormalities suggestive of malignancy. The patient had a family history of both PPB and leukemia. Three years and a half after completion of treatment, the patient is in complete remission., Conclusions: PPB is an uncommon disease but is the most common pulmonary neoplasms in childhood. We must suspect it in patients with a suggestive family history and recurrent pneumothorax in the same location.

Introduction: Enlarged vestibular aqueduct (EVA) is the commonest congenital anomaly found with imaging techniques in paediatric sensorineural hearing loss (SNHL). Our aim was to describe clinical and audiological findings in paediatric hearing loss associated to EVA., Methods: Retrospective review of 55 children with imaging-technique EVA findings from 2000 to 2009. Subjective and/or objective audiological tests were analysed and audiological findings related to clinical features were described., Results: Thirty-seven patients (67.27%) showed bilateral EVA and 18 (32.72%) were unilateral. Hearing loss was bilateral in 46 (83.63%) patients and unilateral in 9 (16.36%). Mean age at diagnosis was 3.78 years. Fifty-three (96.36%) children showed SNHL (28 bilateral and profound), while 2 (3.63%) patients had mixed hearing loss. There were 3 cases of hearing loss progression, 2 fluctuations, 2 of them were asymmetric and 2 patients suffered from vestibular symptoms. Concomitant image findings were 6 cochlear hypoplasia, 2 enlarged internal auditory canals, 1 enlarged vestibule and 1 hypoplastic lateral semicircular canal. Six clinical syndromes were found (2 cases of Down's, and 1 each of Jacobsen, Pendred, Waardenburg and branchio-oto-renal). One child was positive for GJB2 mutation. Familial hearing loss was demonstrated on 12 (21.8%) cases., Conclusion: The clinical picture of hearing loss associated to EVA is characterised by great variability. It should be included in the differential diagnosis of unexplained mixed hearing loss. Familial and syndromic findings have to be taken into consideration in the diagnostic evaluations of such patients. Knowledge about the natural history of this illness is needed so as to give parents prognostic information., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)