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Abstract Background Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. Methods Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24–51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. Results BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). Conclusion BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

The aim of this study was to investigate the influence of image resolution manipulation on the photogrammetric measurement of the rearfoot static angle. The study design was that of a reliability study. We evaluated 19 healthy young adults (11 females and 8 males). The photographs were taken at 1536 pixels in the greatest dimension, resized into four different resolutions (1200, 768, 600, 384 pixels) and analyzed by three equally trained examiners on a 96-pixels per inch (ppi) screen. An experienced physiotherapist marked the anatomic landmarks of rearfoot static angles on two occasions within a 1-week interval. Three different examiners had marked angles on digital pictures. The systematic error and the smallest detectable difference were calculated from the angle values between the image resolutions and times of evaluation. Different resolutions were compared by analysis of variance. Inter- and intra-examiner reliability was calculated by intra-class correlation coefficients (ICC). The rearfoot static angles obtained by the examiners in each resolution were not different (P > 0.05); however, the higher the image resolution the better the inter-examiner reliability. The intra-examiner reliability (within a 1-week interval) was considered to be unacceptable for all image resolutions (ICC range: 0.08-0.52). The whole body image of an adult with a minimum size of 768 pixels analyzed on a 96-ppi screen can provide very good inter-examiner reliability for photogrammetric measurements of rearfoot static angles (ICC range: 0.85-0.92), although the intra-examiner reliability within each resolution was not acceptable. Therefore, this method is not a proper tool for follow-up evaluations of patients within a therapeutic protocol.

Resumo: A doença infecciosa contribui para uma elevada morbilidade e mortalidade no doente oncológico, representando a pneumonia adquirida na comunidade a mais frequente.O desenvolvimento de PAC no doente neoplásico pa-rece advir da modificação de mecanismos de defesa imunitária resultante, quer da patologia maligna, quer do tratamento oncológico. O risco de infecção relacionada com o tipo de neoplasia pode associarse ao défice de imunidade humoral, celular ou do número de neutrófilos. As doenças hematológicas malignas podem predispor o doente à s infecções devido à substituição da medula por células neoplásicas. Consequentemente, estes doentes têm neutropenia funcional, apesar de apresentarem, muitas vezes, um número normal ou aumentado de neutrófilos. Por outro lado, estes doentes podem ter neutropenia como efeito secundário da quimioterapia e/ou radioterapia (neutropenia absoluta).A gravidade da neutropenia foi considerada como principal factor de risco isolado no doente neoplásico, com particular relevância se o número de neutrófilos â¤500cel/mm3.A mortalidade global atribuída à neutropenia febril no doente neoplásico é de 30-50%. Nas últimas décadas, o tratamento das infecções na população oncológica foi direccionado, primariamente, para o manuseamento da neutropenia febril, devido ao facto de o local da infecção não ser determinado em 50-80% dos casos. As guidelines da American Thoracic Society de 2001 utilizavam a neutropenia para identificar os quadros mais graves de PAC nos doentes oncológicos. Os doentes com patologia hematológica e neutropenia funcional ou indivíduos com qualquer tipo de neoplasia e neutropenia absoluta foram excluídos das referidas guidelines. A decisão de incluir doentes com tumores sólidos não neutropénicos foi baseada, apenas, na opinião de especialistas. Assim, os clínicos podiam sentir-se confiantes e tratar a PAC no doente oncológico não neutropénico como na população geral.No entanto, o papel da neutropenia no prognóstico de doentes neoplásicos hospitalizados com PAC não tinha, ainda, sido investigado O objectivo do presente estudo foi comparar o prognóstico de doentes neoplásicos e doentes imunocompetentes com PAC, bem como o prognóstico de indivíduos com patologia maligna e neutropenia absoluta ou funcional e sem neutropenia.Foi efectuada uma análise retrospectiva envolvendo 43 hospitais em 12 países no período compreendido entre Junho de 2001 e Janeiro de 2006. Foram incluídos os indivíduos com idadeâ¥18 anos com critérios de PAC, tendo sido eliminados os portadores de infecção VIH. A PAC foi definida pela presença de infiltrado pulmonar âde novoâ na radiografia do tórax na altura do internamento, associado a, pelo menos, um dos seguintes parâmetros: tosse ou aumento da intensidade desta; tax 37,8 ºC; número de leucócitos no sangue periférico (leucocitose, desvio esquerdo ou leucopenia).Neoplasia foi definida como qualquer tipo de malignidade diagnosticada nos 12 meses anteriores ou neoplasia activa. Considerou-se que esta estaria presente em doentes sob quimioterapia e/ou radioterapia nos 12 meses precedentes ou com sinais ou sintomas de neoplasia ao longo do último ano. Doentes com neoplasia de células escamosas ou basais da pele foram consideradas imunocompetentes.A neutropenia foi classificada como funcional ou absoluta. A primeira estava presente em doentes com doença hematológica maligna. A neutropenia absoluta correspondeu a um número de neutrófilos

Patients who undergo lung transplantation are prone to develop lower respiratory tract infections, leading to severe acute respiratory failure (ARF). Endotracheal intubation may not be indicated in these patients in light of a higher rate of mortality due to infections. The application of non-invasive ventilation could play a role in bridging these patients through the episode of ARF waiting for medical treatment to have effect. We report the evidence of morphological and physiological effects of the application of non-invasive continuous positive airway pressure during ARF sustained by pneumonia in a patient who underwent left lung transplantation because of idiopathic pulmonary fibrosis (IPF). We studied the effects of the application of positive end-expiratory pressure on both the right native lung affected by IPF and the transplanted lung affected by pneumonia.

This review summarizes the present concepts regarding the biological processes that mediate intrinsic and innate host defense against microbial invasion of the lung. Innate immunity is the first line of defense of the higher organisms towards invading pathogens. It accomplishes a wide variety of activities including recognition and effector functions. The innate responses use phagocytic cells (macrophages, monocytes, and neutrophils), cells that release inflammatory mediators (basophils, mast cells, and eosinophils), and natural killer cells. The molecular component of innate responses includes complement, acute-phase proteins, and cytokines. Recognition of pathogen-associated molecular patterns is mediated by the pathogen receptors of the innate immune system, among these molecules toll-like receptors have emerged as fundamental components in the innate immune responses to infection, and a link between innate and adaptive immunity. Additional protection comes from polypeptide mediators of the innate host defense, such as the defensins and other antibiotic peptides. In view of the considerable burden in terms of mortality and morbidity that severe infections still pose worldwide, a better understanding of the biological basis of host-pathogen interactions opens stimulating future treatment perspectives.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rationale: In the WILLOW trial, the Dipeptidyl peptidase-1 inhibitor brensocatib reduced neutrophil serine protease (NSP) activity and prolonged time to first exacerbation in patients with bronchiectasis., Objectives: We hypothesized that, by reducing NSPs, brensocatib would affect antimicrobial peptides, mucins, and cytokines throughout the inflammatory cascade., Methods: The WILLOW trial was a phase 2 randomized trial of brensocatib (10mg and 25mg) versus placebo. Sputum was collected at baseline, week 4, week 24 (end of treatment) and week 28 (4 weeks post-treatment). The antimicrobial peptides secretory leukoproteinase inhibitor (SLPI) and α-defensin-3 were measured by ELISA, mucin-5AC (MUC5AC) by liquid chromatography mass spectrometry, myeloperoxidase by immunoassay and 45 inflammatory cytokines by Olink ® Target 48 assay. The relationship between these markers and sputum neutrophil elastase was validated using the EMBARC-BRIDGE bronchiectasis cohort., Measurements and Main Results: Of 82 patients randomized to 10mg brensocatib, 87 to 25mg brensocatib, and 87 to placebo, 71, 71 and 73 with sputum available for at least two time points were included. SLPI and α-defensin-3 increased significantly with brensocatib compared to placebo at both week 4 and week 24. MUC5AC reduced in response to treatment. Sub-analysis showed this was primarily among patients with high baseline neutrophil elastase. Myeloperoxidase did not change. 15 cytokines and chemokines increased significantly compared to placebo at week 4 or 28. CXCL10, CCL8, CCL7, CCL3 and IL-6 increased at both doses at both timepoints. In the EMBARC-BRIDGE cohort neutrophil elastase correlated inversely with SLPI, CCL13, IL7, CCL11, CXCL10, CCL8, CCL7, all markers increased by brensocatib., Conclusions: Brensocatib exerts broad anti-inflammatory effects beyond its known effects on serine proteases. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT03218917.

Purpose: Non-tuberculous mycobacteria (NTM) account for high clinical burden, and treatment can be challenging. Moreover, accessibility of NTM medications varies across centers. These challenges may lead to unplanned therapeutic changes, discontinuations, potentially affecting patient outcomes. Aim of this survey was to evaluate the accessibility of NTM-targeting drugs in Italy (with a particular focus on clofazimine) in centers associated with the IRENE Registry, a collaborative network of healthcare professionals., Methods: A cross-sectional, internet-based, questionnaire-survey on the use and availability of clofazimineand other NTM-targeting drugs was sent to 88 principal investigators of the IRENE network in Italyin 2020. The questionnaires were designed with closed-ended and open-ended questions and distributed using the SurveyMonkey® platform., Results: The surveys underscore the more frequent involvement of pulmonologists (42%) and infectious disease specialists (34%) in NTM treating strategies. Respondents were distributed across 18 out of20 Italian regions, with a significant concentration in the north, encompassing university hospitalsand outpatient clinics. Molecular testing is available in 40% of the involved centers, while phenotypic in 30% of the centers. Centers have a multidisciplinary team and an appointed pharmacy service for NTM drugs distribution in 10 and 75% of the cases, respectively. Substantial variability was observed in drug availability and accessibility, drug regimen composition, and drug dosage, particularly for medications like clofazimine., Conclusions: This study shows the high heterogeneity of anti-NTM drug availability in Italy and prompts toward a harmonization in antibiotic prescription and access; it also emphasizes the challenges in determining the optimal therapeutic strategies for treating NTM-infections., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

Football is one of the most widely practiced sports in the world, and competition significantly influences athletic performance, especially in adolescents who experience emotional pressure that impacts their performance through the management of performance-related stress. Physical education is integrated within the school curriculum, but it is also typically delivered in sports associations engaged in competitive activities, which become informal learning environments as they pursue the same educational goals as schools. However, few studies have focused on this aspect, particularly the role of emotions and their relationship with performance anxiety in adolescent football players. The aim of this study was to analyze the relationship between pre-competitive anxiety and emotional regulation in adolescents regarding competitive performance. The study design was exploratory. A sample of 79 Under-19 football players, with a mean age of 14.6 (±1.89) years, was recruited through convenience sampling. A battery of pre-competition questionnaires was administered, including the Sport Anxiety Scale-2 (SAS-2) to measure anxiety levels and the Trait Emotional Intelligence Questionnaire (TEIQue-SF) to assess pre-competition emotional levels. Spearman's correlation was used to evaluate the strength and direction of the relationship between emotional levels and anxiety, while Chi-square test was employed to examine differences in anxiety levels across different player roles. The results showed that 70% of the football players displayed normal anxiety levels, with no significant differences across player positions. No significant correlation was found between emotional levels and anxiety. The primary causes of anxiety were cognitive concerns and bodily sensations, which negatively affected concentration. Although emotions were generally high, they did not appear to directly influence performance anxiety, suggesting that other factors may contribute to pre-competitive emotional regulation. In conclusion, contrary to common belief, performance anxiety in adolescent football competitions does not have a direct impact on emotional levels., 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., (© 2025 Aliberti, D'Elia, Giardullo and Raiola.)

Background : Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods : This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results : A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28-6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13-3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06-5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions : The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach.

Objective: This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED)., Methods: Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 h of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analysed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility., Results: Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, P < 0.001) and associated with ESBL production (OR = 2.202, P = 0.031) and urosepsis (OR = 1.688, P = 0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, P < 0.001) and methicillin resistance (7.9% vs. 3.6%, P = 0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, P < 0.001)., Conclusions: Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED., Competing Interests: Declaration of competing interests None declared., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ophthalmic surgical procedures are widely acknowledged for their safety and efficacy. Undoubtedly, advances in ophthalmic surgery, along with the improvement of anaesthetic techniques, have contributed to the reduction in the occurrence of these events. However, although uncommon, systemic severe and life-threatening adverse events can still occur and it is imperative for an ophthalmologic surgeon to have a comprehensive understanding of them to act in terms of proactive prevention, prompt recognition, and optimal treatment, thus maximizing patients' outcomes. Among life-threatening complication following ophthalmic surgery, cardiovascular events represent the most common ones, including a range of different clinical entities: the oculocardiac reflex, potentially leading to haemodynamic instability and asystole; iatrogenic vascular air embolism, in form of venous air embolism or "pefluorocarbon syndrome", which can lead to obstruction of the pulmonary circulation, respiratory distress and cardiovascular collapse; postoperative venous thromboembolism, in the context of which the management of perioperative antiplatelet and anticoagulant therapy has a crucial role. Furthermore, among infectious complications, that are more commonly limited to the ocular tissues, necrotizing fasciitis represents a potentially lethal infection. This review aims to provide an up-to-date, evidence-based overview of potential life-threatening complications associated with ophthalmic surgery, exploring pathogenesis, risk factors, signs, symptoms, and, briefly, management strategies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)