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Introduction: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. Methods: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. Results: Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p

I commenti ufficiali espressi dai Comitati olimpici e dagli organi di stampa di varie nazioni allo svolgimento delle Olimpiadi invernali di Cortina d’Ampezzo del 1956 furono unanimemente positivi, allineandosi con il Rapporto ufficiale di quasi 800 pagine pubblicato dall’organizzazione italiana. Studi successivi, sia italiani che internazionali, hanno confermato l’ottima riuscita dell’evento cortinese di marca italiana. Avvalendosi di fonti archivistiche primarie fino a ora inesplorate, questo elaborato si propone di evidenziare come tale acclamato successo fu veritiero, ma l’organizzazione italiana, nel caso specifico la Segreteria generale dei Giochi che dirigeva in Cortina la preparazione e lo svolgimento dell’evento riuscì a superare difficoltà importanti durante la preparazione e lo svolgimento dei Giochi. La gestione della territorialità, l’accoglienza e l’allestimento degli impianti si scontrò, almeno inizialmente, con difficoltà politiche e culturali, che avrebbero potuto creare un danno grave, se non risolti. Oltre alla possibile problematicità legata al funzionamento degli impianti e alla gestione dei Giochi, il Comitato organizzatore si confrontò con alcune controversie sul piano delle relazioni internazionali. Contestualmente, i Giochi si disputarono in un momento di tensione politica con la vicina Austria, a causa delle agitazioni in corso nel Sud Tirolo italiano. Sino al 1918, Cortina era stata tirolese e austriaca. La Segreteria del Comitato organizzatore si tenne scrupolosamente ai regolamenti olimpici e delle federazioni internazionali, riuscendo con mano sicura a risolvere situazioni critiche.

IntroductionAcute COVID-19 infection causes significant alterations in the innate and adaptive immune systems. While most individuals recover naturally, some develop long COVID (LC) syndrome, marked by persistent or new symptoms weeks to months after SARS-CoV-2 infection. Despite its prevalence, there are no clinical tests to distinguish LC patients from those fully recovered. Understanding the immunological basis of LC is essential for improving diagnostic and treatment approaches.MethodsWe performed deep immunophenotyping and functional assays to examine the immunological profiles of LC patients, individuals with active COVID-19, recovered patients, and healthy donors. This analysis assessed both innate and adaptive immune features, identifying potential biomarkers for LC syndrome. A Binomial Generalized Linear Model (BGLM) was used to pinpoint immune features characterizing LC.ResultsCOVID-19 patients exhibited depletion of innate immune cell subsets, including plasmacytoid and conventional dendritic cells, classical, non-classical, and intermediate monocytes, and monocyte-derived inflammatory dendritic cells. Elevated basal inflammation was observed in COVID-19 patients compared to LC patients, whose immune profiles were closer to those of healthy donors and recovered individuals. However, LC patients displayed persistent immune alterations, including reduced T cell subsets (CD4, CD8, Tregs) and switched memory B cells, similar to COVID-19 patients. Through BGLM, a unique adaptive immune signature for LC was identified, featuring memory CD8 and gd T cells with low proliferative capacity and diminished expression of activation and homing receptors.DiscussionThe findings highlight a unique immunological signature associated with LC syndrome, characterized by persistent adaptive immune dysregulation. While LC patients displayed recovery in innate immune profiles comparable to healthy and Recovered individuals, deficits in T cell and memory B cell populations were evident, differentiating LC from full recovery. These findings provide insights into LC pathogenesis and may support the development of diagnostic tools and targeted therapies.

The advancements of technological devices and software are putting mixed reality in the frontline of teaching medical personnel. The Microsoft ® HoloLens 2 ® offers a unique 3D visualization of a hologram in a physical, real environment and allows the urologists to interact with it. This review provides a state-of-the-art analysis of the applications of the HoloLens ® in a medical and healthcare context of teaching through simulation designed for medical students, nurses, residents especially in urology. Our objective has been to perform a comprehensively analysis of the studies in PubMed/Medline database from January 2016 to April 2023. The identified articles that researched Microsoft HoloLens, having description of feasibility and teaching outcomes in medicine with an emphasize in urological healthcare, have been included. The qualitative analysis performed identifies an increasing use of HoloLens in a teaching setting that covers a great area of expertise in medical sciences (anatomy, anatomic pathology, biochemistry, pharmacogenomics, clinical skills, emergency medicine and nurse education, imaging), and above these urology applications (urological procedures and technique, skill improvement, perception of complex renal tumors, accuracy of calyx puncture guidance in percutaneous nephrolithotomy and targeted biopsy of the prostate) can mostly benefit from it. The future potential of HoloLens technology in teaching is immense. So far, studies have focused on feasibility, applicability, perception, comparisons with traditional methods, and limitations. Moving forward, research should also prioritize the development of applications specifically for urology. This will require validation of needs and the creation of adequate protocols to standardize future research efforts.

Background: Cancer-related cognitive impairment (CRCI) represents one of the most common and debilitating effects in patients surviving after cancer treatments. Neurocognitive deficits are important causes of disability and burden in cancer survivors. The true magnitude of CRCI is difficult to define due to significant heterogeneity of literature data. At present, there is no agreement on the gold standard for detection and grading of CRCI in clinical trials, and there is a lack of clear knowledge of its pathophysiology. Objectives: In this review, we aim to discuss some perspectives for future research to pursue in order to cover the gaps in knowledge in the CRCI field. Methods: We focused our literature research on the following relevant issues: neuroradiological correlates of CRCI; objective neuropsychological evaluation and subjective complaint assessment and their correlation with objective measures; timing of assessment; and possible treatments. Results: The correct methodology for evaluating cognitive deficits induced by anti-tumor treatments still requires a definition based on quality scientific evidence, and literature data are currently scarce. Conclusions: This review highlights the need for further research to understand the causes and consequences of cancer-related cognitive impairment using standardized and sensitive measures of cognitive functions and the long-term effects of chemotherapy on cognitive functions and to develop effective interventions.

Abstract Objective: This paper describes the first web-based self-completed 24-h recall designed to categorise food intake according to Nova groups – Nova24h – and its agreement with a reference tool in estimating the dietary relative contribution of the four Nova food groups (% of total energy intake). Design: Comparisons of estimates of dietary relative contributions of Nova groups obtained by Nova24h and one standard interviewer-led 24-h recall. Setting: Nationwide adult cohort study in Brazil. Participants: The subjects were 186 participants of the NutriNet Brasil Cohort Study (n 186). Results: No statistically significant differences were observed between the Nova24h and the reference tool mean contributions of unprocessed or minimally processed foods (52·3 % v. 52·6 %), processed culinary ingredients (11·6 % v. 11·9 %), processed foods (17·1 % v. 14·7 %) and ultra-processed foods (19·0 % v. 20·9 %). Intraclass correlation coefficients between individual estimates obtained for each Nova group showed moderate to good agreement (0·54–0·78). Substantial or almost perfect agreement between the tools was seen regarding the ability to rank participants according to quintiles of contribution of each Nova group (PABAK 0·69–0·81). Conclusions: Nova24h is a suitable tool for estimating the dietary relative energy contribution of Nova food groups in the NutriNet Brasil cohort. New studies are necessary to verify its adequacy in other populations.

Abstract Lipidomics studies have indicated an association between obesity and lipid metabolism dysfunction. This study aimed to evaluate and compare cardiometabolic risk factors, and the lipidomic profile in adults and older people. A cross-sectional study was conducted with 72 individuals, divided into two sex and age-matched groups: obese (body mass index—BMI ≥ 30 kg/m2; n = 36) and non-obese (BMI

Context: The resection technique used to excise tumor during robotic partial nephrectomy (RPN) is of paramount importance in achieving optimal clinical outcomes. Objective: To provide an overview of the different resection techniques used during RPN, and a pooled analysis of comparative studies. Evidence acquisition: The systematic review was conducted according to established principles (PROSPERO: CRD42022371640) on November 7, 2022. A population (P: adult patients undergoing RPN), intervention (I: enucleation), comparator (C: enucleoresection or wedge resection), outcome (O: outcome measurements of interest), and study design (S) framework was prespecified to assess study eligibility. Studies reporting a detailed description of resection techniques and/or evaluating the impact of resection technique on outcomes of surgery were included. Evidence synthesis: Resection techniques used during RPN can be broadly classified as resection (non-anatomic) or enucleation (anatomic). A standardized definition for these is lacking. Out of 20 studies retrieved, nine compared “standard” resection versus enucleation. A pooled analysis did not reveal significant differences in terms of operative time, ischemia time, blood loss, transfusions, or positive margins. Significant differences favoring enucleation were found for clamping management (odds ratio [OR] for renal artery clamping 3.51, 95% confidence interval [CI] 1.13–10.88; p = 0.03), overall complications (OR for occurrence 0.55, 95% CI 0.34–0.87; p = 0.01) major complications (OR for occurrence 0.39, 95% CI 0.19–0.79; p = 0.009), length of stay (weighted mean difference [WMD] −0.72 d, 95% CI −0.99 to −0.45; p

Simone Ferretti,1,* Chiara Mercinelli,2,* Laura Marandino,2 Giulio Litterio,1 Michele Marchioni,1 Luigi Schips1 1Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti, Urology Unit, Chieti, Italy; 2Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy*These authors contributed equally to this workCorrespondence: Michele Marchioni, Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti, Urology Unit, Chieti, Italy, Tel +393296544866, Fax +390871357756, Email mic.marchioni@gmail.comAbstract: The therapeutic landscape of metastatic hormone sensitive and metastatic castration-resistant prostate cancer (mCRPC) is rapidly changing. We reviewed the current treatment options for mCRPC, with insights on new available therapeutic strategies. Chemotherapy with docetaxel or cabazitaxel (for patients progressing on docetaxel), as well as treatment with androgen receptor axis targeted therapies, and Radium-223 are well-established treatment options for patients with mCRPC. The advent of theragnostic in prostate cancer established Lutetium-177 (177Lu)–PSMA-617 as a new standard of care for PSMA-positive mCRPC previously treated with ARAT and taxane-based chemotherapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, is approved for selected patients with mCRPC progressed on ARATs and in combination with abiraterone acetate as first-line treatment for mCRPC. Immunotherapy showed limited efficacy in unselected patients with mCRPC and novel immunotherapy strategies need to be explored. The search for biomarkers is a growing field of interest in mCRPC, and predictive biomarkers are needed to support the choice of treatment and the development of tailored strategies.Keywords: metastatic castration resistant prostate cancer, chemotherapy, androgen-receptors axis targeted therapies, PARP inhibitors, theragnostic, predictive biomarkers

Abstract Dispersion results from the variation of index of refraction as well as electric field confinement in sub-wavelength structures. It usually results in efficiency decrease in metasurface components leading to troublesome scattering into unwanted directions. In this letter, by dispersion engineering, we report a set of eight nanostructures whose dispersion properties are nearly identical to each other while being capable of providing 0 to 2π full-phase coverage. Our nanostructure set enables broadband and polarization-insensitive metasurface components reaching 90% relative diffraction efficiency (normalized to the power of transmitted light) from 450 nm to 700 nm in wavelength. Relative diffraction efficiency is important at a system level – in addition to diffraction efficiency (normalized to the power of incident light) – as it considers only the transmitted optical power that can affect the signal to noise ratio. We first illustrate our design principle by a chromatic dispersion-engineered metasurface grating, then show that other metasurface components such as chromatic metalenses can also be implemented by the same set of nanostructures with significantly improved relative diffraction efficiency.

Abstract This paper outlines the use of bidirectional reflectance measurements for the characterisation and evaluation of appearance changes in gilded surfaces caused by varnishing and cleaning. Oil and water gilding mock-ups representative of a 15th-century panel painting were varnished, and a selection of four varnish removal methods was applied. By measuring the bidirectional reflectance of the samples, their appearance was modelled and evaluated according to perceptual gloss attributes. Three main perceptual groups were found for each gilding type: unvarnished, varnished and cleaned surfaces. Finally, for the studied samples, the most appropriate method for removing dammar and colophony varnish from a gilded surface, in terms of appearance change, is solubilisation by applying an Evolon®CR compress.

Pietro Castellan,1 Simone Ferretti,2 Giulio Litterio,2 Michele Marchioni,1,2 Luigi Schips1,2 1Department of Urology, ASL02 Abruzzo, Chieti, Italy; 2Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti, Urology Unit, Chieti, ItalyCorrespondence: Simone Ferretti, Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti, Urology Unit, Chieti, Italy, Tel +393278733805, Fax +390871357756, Email ferretti.smn@gmail.comAbstract: Urinary incontinence is a common and debilitating problem in patients undergoing radical prostatectomy. Current methods developed to treat urinary incontinence include conservative treatments, such as lifestyle education, pelvic muscle floor training, pharmacotherapy, and surgical treatments, such as bulking agents use, artificial urinary sphincter implants, retrourethral transobturator slings, and adjustable male sling system. Pelvic floor muscle exercise is the most common management to improve the strength of striated muscles of the pelvic floor to try to recover the sphincter weakness. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and a-adrenergic drugs have been proposed as medical treatments for urinary incontinence after radical prostatectomy. Development of new surgical techniques, new surgical tools and materials, such as male slings, has provided an improvement of outcomes after UI surgery. Such improvement is still ongoing, and the uptake of new devices might lead to even better outcomes after UI surgery.Keywords: urinary incontinence, radical prostatectomy, pelvic muscle floor exercise, artificial urinary sphincter, male slings, anticholinergic agents, PDE5 inhibitors, duloxetine

Background: Cochlear implantation (CI) following endoscopic transcanal infrapromontorial vestibular schwannoma (VS) dissection is a feasible intervention in intracanalicular VS, with minimal extension into the cerebellopontine angle, but no audiologic results have ever been reported in the literature. Methods: From 2015 to 2021 in the Otorhynolaryngology Departments of Modena and Verona, three patients underwent this intervention. All were suffering from sporadic left-sided intracanalicular Koos I VS. Intraoperative electrically evoked auditory brainstem responses and electrophysiological measurements were performed before and after the placement of the electrode array, respectively. Since device activation one month after the surgery, each patient was followed up with audiometric tests, data logging, electrode impedance measurements and neural response telemetry performed at each scheduled fitting session at 15 days and 3, 6, 12 and 24 months. Results: Only in patient No. 3, an auditory benefit was observed and still evident even 36 months after activation. Impedances increased progressively in patient No. 1 and a benefit was never reported. Patient No. 2 left the follow-up for worsening comorbidities. Conclusions: CI following transcanal infrapromontorial VS resection is a beneficial intervention. The residual cochlear nerve after the tumour dissection and the course of electrophysiological measurements in the postoperative period were the main predictive factors for audiological outcomes.

The development of disease screening methods using biomedical detection dogs relies on the collection and analysis of body odors, particularly volatile organic compounds (VOCs) present in body fluids. To capture and analyze odors produced by the human body, numerous protocols and materials are used in forensics or medical studies. This paper provides an overview of sampling devices used to collect VOCs from sweat and exhaled air, for medical diagnostic purposes using canine olfaction and/or Gas Chromatography-Mass spectrometry (GC-MS). Canine olfaction and GC-MS are regarded as complementary tools, holding immense promise for detecting cancers and infectious diseases. However, existing literature lacks guidelines for selecting materials suitable for both canine olfaction and GC-MS. Hence, this review aims to address this gap and pave the way for efficient body odor sampling materials. The first section of the paper describes the materials utilized in training sniffing dogs, while the second section delves into the details of sampling devices and extraction techniques employed for exhaled air and sweat analysis using GC-MS. Finally, the paper proposes the development of an ideal sampling device tailored for detection purposes in the field of odorology. By bridging the knowledge gap, this study seeks to advance disease detection methodologies, harnessing the unique abilities of both dogs and GC-MS analysis in biomedical research.

IntroductionRadiotherapy and esophageal stenting are usually employed to manage esophageal localization of distant cancer. However, they are also related to the occurrence of an increased risk of tracheoesophageal fistula. Tracheoesophageal fistula management in these patients involves dealing with poor general conditions and short-term prognosis. This paper presents the first case in literature of bronchoscopic fistula closure through an autologous fascia lata graft placement between two stents.Case report and aimA 67-years-old male patient was diagnosed with pulmonary squamous cell carcinoma in the inferior lobe of the left lung with mediastinal lymph node metastasis. After a multidisciplinary discussion, bronchoscopic repair of tracheoesophageal fistula with autologous fascia lata was decided without the removal of the esophageal stent due to the high risk on the esophagus possibly related to such a procedure. Oral feeding was progressively introduced without the development of aspiration symptoms. Videofluoroscopy and esophagogastroduodenoscopy were performed at 7 months showing no signs of tracheoesophageal fistula patency.ConclusionThis technique might represent a low risks viable option for patients unsuitable for open surgical approaches.

Background Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM).Objectives To assess the significance of DH/BS in patients with IM.Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1.Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p

Single-port (SP) robotic surgery is a novel technology and is at the beginning of its adoption curve in urology. The goal of this narrative review is to provide an overview of SP-robotic partial nephrectomy (PN) 4 years after the introduction of the da Vinci SP dedicated platform, focusing on perioperative outcomes, length of stay, and surgical technique. A nonsystematic review of the literature was conducted. The research included the most updated articles that referred to SP robotic PN. Since its commercial release in 2018, several institutions have reproduced robotic PN by using the SP platform, both via a transperitoneal and a retroperitoneal approach. The published SP-robotic PN series are generally based on preliminary experiences by surgeons who had previous experience with conventional multi-arms robotic platforms. The reported outcomes are encouraging. Overall, three studies reported that SP-robotic PN cases had nonsignificantly different operative time, estimated blood loss, overall complications rate, and length of stay compared to the conventional ‘multi-arms’ robotic PN. However, in all these series, renal masses treated by SP had overall lower complexity. Moreover, two studies underlined decreased postoperative pain as a major pro of adopting the SP system. This should reduce/avoid the need for opioids after surgery. No study compared SP-robotic versus multi-arms robotic PN in cost-effectiveness. Published experience with SP-robotic PN has reported the feasibility and safety of the approach. Preliminary results are encouraging and at least noninferior with respect to those from the multi-arms series. Prospective comparative studies with long-term oncologic and functional results are awaited to draw more definitive conclusions and better establish the more appropriate indications of SP robotics in the field of PN.

Resumo Desde o impeachment da presidenta Dilma Rousseff, uma série de mudanças estruturais foram implementadas no Brasil. No âmbito do direito do trabalho, ainda no Governo Temer, foram aprovadas as Leis n. 13.429/2017 e 13.467/2017. E, no primeiro ano do Governo Bolsonaro, essas reformas foram intensificadas com a edição das Medidas Provisórias (MPs) n. 870/2019, 873/2019, 881/2019 e 905/2019. À luz do objetivo declarado dessas alterações legislativas, qual seja a promoção de empregos, este artigo busca responder à seguinte pergunta: quais os impactos das mudanças na legislação trabalhista promovidas pelas MPs editadas pelo Governo Bolsonaro durante o primeiro ano de seu mandato? Para tanto, empregaram-se a avaliação legislativa, como método de abordagem, e a revisão bibliográfica, a análise documental e a sistematização de indicadores sobre emprego, condições de trabalho e economia, como técnicas de pesquisa. Dessa análise, extraiu-se que as modificações introduzidas pelas MPs, além de não se traduzirem em um melhor desempenho econômico, resultam na deterioração das condições de trabalho, sintetizadas em: I) desarticulação de estruturas para planejamento de políticas referentes ao direito do trabalho; II) desvalorização dos sindicatos; III) flexibilização de direitos trabalhistas; e IV) enfraquecimento de instâncias e normas de fiscalização.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design, setting, and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the “RNU-fecta.” A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a “tetrafecta” composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

Abstract Background COVID‑19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator‑associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). Methods Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. Results Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. Conclusions COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.

O presente artigo apresentará a formação histórica da dívida pública brasileira e a sua concepção enquanto mecanismo de dominação e reprodução da estrutura colonial. Para isso, será analisada a atuação dos seus mecanismos formais de produção e reprodução, realizando um recorte temporal acerca desse contexto pandêmico que é utilizado pelo Estado brasileiro como pretexto para perpetuar e intensificar o endividamento. Assim, a dívida pública será abordada como uma ferramenta de alinhamento do país ao Sistema-Mundo e, em vista disso, essa concepção será relacionada aos estudos decoloniais, abordando criticamente o endividamento público como uma moderna sujeição dos países periféricos perante as “nações centrais”. Destarte, buscar-se-á elucidar essas questões através da análise dos aparelhos estatais de controle social e ideológico que constroem a figura do “homem endividado”. Para tal, o presente artigo utilizará a metodologia descritiva e a revisão bibliográfica.

Objective: The role of lymph node dissection (LND) is still controversial in patients with renal cell carcinoma undergoing surgery. We aimed to provide a comprehensive review of the literature about the effect of LND on survival, prognosis, surgical outcomes, as well as patient selection and available LND templates. Methods: Recent literature (from January 2011 to December 2021) was assessed through PubMed and MEDLINE databases. A narrative review of most relevant articles was provided. Results: The frequencies in which LNDs are being carried out are decreasing due to an increase in minimally invasive and nephron sparing surgery. Moreover, randomized clinical trials and meta-analyses failed to show any survival advantage of LND versus no LND. However, retrospective studies suggest a survival benefit of LND in high-risk patients (bulky tumors, T3-4 stage, and cN1 patients). Moreover, extended LND might provide important staging information, which could be of interest for adjuvant treatment planning. Conclusion: No level 1 evidence of any survival advantage deriving from LND is currently available in literature. Thus, the role of LND is limited to staging purposes. However, low grade evidence suggests a possible role of LND in high-risk patients. Randomized clinical trials are warranted to corroborate these findings.

Objective: No standard strategy for diagnosis and management of positive surgical margin (PSM) and local recurrence after partial nephrectomy (PN) are reported in literature. This review aims to provide an overview of the current strategies and further perspectives on this patient setting. Methods: A non-systematic review of the literature was completed. The research included the most updated articles (about the last 10 years). Results: Techniques for diagnosing PSMs during PN include intraoperative frozen section, imprinting cytology, and other specific tools. No clear evidence is reported about these methods. Regarding PSM management, active surveillance with a combination of imaging and laboratory evaluation is the first option line followed by surgery. Regarding local recurrence management, surgery is the primary curative approach when possible but it may be technically difficult due to anatomy resultant from previous PN. In this scenario, thermal ablation (TA) may have the potential to circumvent these limitations representing a less invasive alternative. Salvage surgery represents a valid option; six studies analyzed the outcomes of nephrectomy on local recurrence after PN with three of these focused on robotic approach. Overall, complication rates of salvage surgery are higher compared to TA but ablation presents a higher recurrence rate up to 25% of cases that can often be managed with repeat ablation. Conclusion: Controversy still exists surrounding the best strategy for management and diagnosis of patients with PSMs or local recurrence after PN. Active surveillance is likely to be the optimal first-line management option for most patients with PSMs. Ablation and salvage surgery both represent valid options in patients with local recurrence after PN. Conversely, salvage PN and radical nephrectomy have fewer recurrences but are associated with a higher complication rate compared to TA. In this scenario, robotic surgery plays an important role in improving salvage PN and radical nephrectomy outcomes.

Abstract Background The optimal prophylactic dose of heparin in patients with coronavirus-associated disease 2019 (COVID-19) in the emergency department (ED) is debated. This study aimed to analyze different thromboprophylaxis approaches in unvaccinated COVID-19 patients admitted to ED without initial venous thromboembolism. Methods Retrospectively, the effect of intermediate/high versus low dose heparin treatment was evaluated from December 2020 to July 2021 in a tertiary Academic Hospital in northeast Italy. The primary outcome comprised arterial or venous thromboembolism or all-cause death within 30 days. Secondary outcomes comprised each single primary outcome component or major hemorrhagic event. Cox regression was used to determine predictors of the primary outcome and propensity score weights to balance the effect of heparin treatment on all outcomes. Results Data of 144 consecutive patients (age 70 ± 13, 33% females) were included in the study. High-dose prophylactic heparin was used in 69%, intermediate in 15%, and low in 17% of patients. The primary outcome occurred in 48 patients. Independent predictors of the primary outcome were COVID-19 severity (hazards ratio (HR) 1.96, 95% confidence interval (CI) 1.05–3.65, p = 0.035) and D-dimer levels (HR each log ng/dl 1.38, 95% CI 1.04–1.84, p = 0.026). Intermediate/high dose heparin did not affect the risk of the primary outcome compared with the low dose (weighted HR 1.39, 95% CI 0.75–2.56, p = 0.292). Intermediate/high heparin increased the risk of major hemorrhagic events (weighted HR 5.92, 95% CI 1.09–32, p = 0.039). Conclusions In unvaccinated COVID-19 patients admitted to ED, prophylaxis with heparin at the intermediate/high dose did not reduce primary outcome compared with the low dose but increased the risk of major hemorrhagic events.

Context: Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity as primary minimally invasive surgical treatment for localized renal tumors, and it has preferably been performed with a transperitoneal approach. However, the retroperitoneal approach represents an alternative approach given potential advantages. Objective: To provide an updated analysis of the comparative outcomes of retroperitoneal RAPN (R-RAPN) versus transperitoneal RAPN (T-RAPN). Evidence acquisition: A systematic review of the literature was performed up to September 2021 using MEDLINE, EMBASE, and Web of Science databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. A sensitivity analysis was performed considering only matched-pair studies. Evidence synthesis: Seventeen studies, which were published between 2013 and 2021, were retrieved. None of them was a randomized clinical trial. Among the 6,266 patients included in the meta-analysis, 2261 (36.1%) and 4,005 (63.9%) underwent R-RAPN and T-RAPN, respectively. No significant difference was found in terms of baseline features. The T-RAPN group presented a higher rate of male patients (odds ratio [OR]: 0.86, p = 0.03) and larger tumor size (weighted mean difference [WMD]: 0.2 cm; p = 0.003). The R-RAPN group reported more frequent posterior renal masses (OR: 0.23; p

The cyanobacterium Arthrospira platensis, spirulina, is a source of pigments such as phycobiliprotein and phycocyanin. Phycocyanin is used in the food, cosmetics, and pharmaceutical industries because of its antioxidant, anti-inflammatory, and anticancer properties. The different steps involved in extraction and purification of this protein can alter the final properties. In this review, the stability of phycocyanin (pH, temperature, and light) is discussed, considering the physicochemical parameters of kinetic modeling. The optimal working pH range for phycocyanin is between 5.5 and 6.0 and it remains stable up to 45 °C; however, exposure to relatively high temperatures or acidic pH decreases its half-life and increases the degradation kinetic constant. Phycobiliproteins are sensitive to light; preservatives such as mono- and di-saccharides, citric acid, or sodium chloride appear to be effective stabilizing agents. Encapsulation within nano- or micro-structured materials such as nanofibers, microparticles, or nanoparticles, can also preserve or enhance its stability.

We report detecting infectious Toscana virus in the seminal fluid of a 25-year-old man from Italy returning from Elba Island. The presence of infectious virus in human semen adds Toscana virus to the long list of viruses detected in this genital fluid and indicates a potential for sexual transmission.

Abstract Background It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long‐term (2 years) following the endoscopic procedure. Results Sixty‐six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01). Conclusions Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.

Abstract Background Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. Methods This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. Results The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients’ survival was found for SIM (10-year OS = 53.2% for SIM

Abstract Background Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔP es) and nasal (ΔP nos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔP es and ΔP nos served as primary outcome. The effect of ΔP nos measurements on respiratory rate and ΔP es was also assessed. Results ΔP es and ΔP nos were strongly correlated at admission (R 2 = 0.88, p

A partir de reflexões sobre os desafios do uso da linguagem como forma de comunicação no âmbito do Direito, e das dificuldades enfrentadas por um indivíduo que responde a processo judicial em idioma que não domina, o presente texto discorre sobre o intérprete judicial e a razão da assistência por tradutor, como uma garantia judicial inerente ao Estado democrático de direito. Construídas as premissas sobre a garantia ao intérprete judicial, debate-se a hipótese de dispensar tal profissional substituindo-o pela aplicação de programas digitais (software) de tradução que converta o idioma das decisões e atos processuais, trazendo relato de ocasiões registradas na jurisprudência do emprego desta tecnologia. Confrontase, então, a efetividade dos softwares de tradução frente a relevância da garantia de que o acusado possa compreender os atos judiciais, em consonância com direitos fundamentais, resguardados na Constituição Federal, e direitos humanos, assinalados na Convenção Americana sobre Direitos Humanos. A metodologia empregada corresponde a pesquisa bibliográfica, análise de legislação e revisão de jurisprudência, resultando, ao final, na percepção de que há relevante disparidade entre a amplitude necessária à concretização da garantia judicial examinada e a questionável efetividade dos métodos automatizados de tradução de atos processuais.

Renal medullary carcinoma (RMC) is a rare form of renal cell carcinoma that has a poor prognosis. It is known to be associated with sickle cell trait or disease, although the exact underlying mechanisms are still unclear. The diagnosis is made through immunochemical staining for SMARCB1 (INI1). In this report, we present a case of a 31-year-old male patient with sickle cell trait who was diagnosed with stage III right RMC. Despite the poor prognosis, the patient survived for a remarkable duration of 37 months. Radiological assessment and follow-up were primarily performed using 18F-FDG PET/MRI. The patient underwent upfront cisplatin-based cytotoxic chemotherapy before surgical removal of the right kidney and retroperitoneal lymph node dissection. Identical adjuvant chemotherapy was administered post-surgery. Disease relapses were detected in the retroperitoneal lymph nodes; these were managed with chemotherapy and surgical rechallenges. We also discuss the oncological and surgical management of RMC, which currently relies on perioperative cytotoxic chemotherapy strategies, as there are no known alternative therapies that have been shown to be superior to date.

BackgroundDiet quality is associated with psychobiological, psychological, biological, and physiological factors of individuals, and in the context of prolonged stress, such as the COVID-19 pandemic, it can lead to a worsening of the quality of food for undergraduates. This study aimed to analyze diet quality and associated factors in Brazilian undergraduates.MethodsData were collected from 4,799 undergraduate students from all Brazilian regions, from August 2020 to February 2021. The online questionnaire contained socioeconomic variables, the ESQUADA scale to assess diet quality, self-referred changes in weight, the Brazilian food insecurity scale (EBIA), sleep assessment and the perceived stress scale. Unconditional multiple logistic regression analysis was performed to study variables associated with poor and very poor diet quality.ResultsMost of participants presented a good diet quality (51.7%), while 9.8% had a poor or very poor diet quality and only 1.1% had an excellent diet quality. 58.2% of undergraduates reported to have an increase in weight during the pandemic and 74.3% of the students presented elevated stress during the pandemic. Logistic regressions showed students who gained weight during the pandemic presented the highest AOR = 1.56 (95% CI = 1.12–2.20) for poor or very poor diet quality. The elevated perceived stress was also associated with a higher AOR = 2.85 (95% CI = 1.71–4.74) for poor or very poor diet quality.ConclusionMost of the studied undergraduates presented a good diet quality. Nevertheless, poor/very poor diet quality was associated with higher perceived stress and weight gain. Our study indicated that policies should beaimed at the socioeconomically most vulnerable undergraduates, those in a situation of food and nutritional insecurity, high perceived stress, and who gained weight during the pandemic.

Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions.

Behaviour is the response of living things to their environment and external stimulation, and is one of the parameters to be observed when assessing animal welfare. Any alteration from the conditions found in nature can lead to the occurrence of some specific behaviours, called stereotypies which are characterised as repetitive, consistent patterns of behaviour usually defined as having no apparent ultimate or proximal functions. It has been reported that once stabled or subjected to stressful activities, horses have more susceptibility of developing behavioural disturbances; therefore, behavioural disorders in horses are a strong indicator of poor welfare. Cannabis spp.-derived molecules have been studied under different medical conditions; the therapeutic potentials of phytocannabinoids are related to the effects of delta-9-tetrahydrocannabinol, cannabidiol (CBD), and other compounds. Cannabidiol has many activities within the central nervous system, such as anxiolytic, antidepressant, antipsychotic, anticonvulsant, and anti-inflammatory activities. Some studies have recently shown the potential and successful therapeutic use of phytocannabinoids in veterinary medicine. This clinical case report described a 22-year-old mare suffering from chronic crib-biting and wind-sucking, and the successful outcome of four weeks-therapy with CBD. This is the first report of the successful therapeutic use of phytocannabinoids in equine behavioural disorders.

PurposeWe hypothesized that two-tier re-classification of the “M” (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).MethodsMulticenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, “Oligometastatic”) and M2 (>3, “Polymetastatic”). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current “M” staging.Results429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p

Mechanisms regulating flower senescence are not fully understood in any species and are particularly complex in composite flowers. Dahlia (Dahlia pinnata Cav.) florets develop sequentially, hence each composite flower head includes florets of different developmental stages as the whole flower head ages. Moreover, the wide range of available cultivars enables assessment of intraspecific variation. Transcriptomes were compared amongst inner (younger) and outer (older) florets of two flower head ages to assess the effect of floret vs. flower head ageing. More gene expression, including ethylene and cytokinin pathway expression changed between inner and outer florets of older flower heads than between inner florets of younger and older flower heads. Additionally, based on Arabidopsis network analysis, different patterns of co-expressed ethylene response genes were elicited. This suggests that changes occur in young inner florets as the whole flower head ages that are different to ageing florets within a flower head. In some species floral senescence is orchestrated by the plant growth regulator ethylene. However, there is both inter and intra-species variation in its importance. There is a lack of conclusive data regarding ethylene sensitivity in dahlia. Speed of senescence progression, effects of ethylene signalling perturbation, and patterns of ethylene biosynthesis gene expression differed across three dahlia cultivars (‘Sylvia’, ‘Karma Prospero’ and ‘Onesta’) suggesting differences in the role of ethylene in their floral senescence, while effects of exogenous cytokinin were less cultivar-specific.

Edible flowers are appreciated due to their aesthetic features, nutritional value and antioxidant properties. Tulbaghia simmleri Beauv. (Amaryllidaceae family) flowers are characterized by a pleasant garlic taste and are consumed both as fresh and dried products. The aim of this work was to assess the effect of chilling temperature (+4°C) on the visual quality, nutritional content, and aroma profile of T. simmleri flowers after two (T2) and six (T6) days of storage. Colorimetric analysis highlighted a reduction in petal brightness at T6 and hence their darkening, due to a significant increase in a* coordinate and decrease in the b* one. Total polyphenols and flavonoids content remained unchanged until the end of the experiment, while total anthocyanins increased at T2. Flowers antioxidant activity (DPPH assay) decreased progressively during cold storage, while catalase (CAT) and ascorbate peroxidase (APX) activities increased. The aroma profile was analyzed by HS-SPME associated with GC-MS, underlining that fresh flowers were dominated by high content in monoterpenes (around 80%), with 1,8-cineol as main compound (53.1%). Cold storage reduced this class of volatiles while sesquiterpenes and non-terpenes increased; between them, benzyl benzoate reached 12%.

Background and aimCOVID-19, the infectious disease caused by SARS-CoV-2 virus that has been causing a severe pandemic worldwide for more than 2 years, is characterized by a high heterogeneity of clinical presentations and evolution and, particularly, by a varying severity of respiratory involvement. This study aimed to analyze the diversity and taxonomic composition of the gut microbiota at hospital admission, in order to evaluate its association with COVID-19 outcome. In particular, the association between gut microbiota and a combination of several clinical covariates was analyzed in order to characterize the bacterial signature associate to mild or severe symptoms during the SARS-CoV-2 infection.Materials and methodsV3–V4 hypervariable region of 16S rRNA gene sequencing of 97 rectal swabs from a retrospective cohort of COVID-19 hospitalized patients was employed to study the gut microbiota composition. Patients were divided in two groups according to their outcome considering the respiratory supports they needed during hospital stay: (i) group “mild,” including 47 patients with a good prognosis and (ii) group “severe,” including 50 patients who experienced a more severe disease due to severe respiratory distress that required non-invasive or invasive ventilation. Identification of the clusters of bacterial population between patients with mild or severe outcome was assessed by PEnalized LOgistic Regression Analysis (PELORA).ResultsAlthough no changes for Chao1 and Shannon index were observed between the two groups a significant greater proportion of Campylobacterota and Actinobacteriota at phylum level was found in patients affected by SARS-CoV-2 infection who developed a more severe disease characterized by respiratory distress requiring invasive or non-invasive ventilation. Clusters have been identified with a useful early potential prognostic marker of the disease evolution.DiscussionMicroorganisms residing within the gut of the patients at hospital admission, were able to significantly discriminate the clinical evolution of COVID-19 patients, in particular who will develop mild or severe respiratory involvement. Our data show that patients affected by SARS-CoV-2 with mild or severe symptoms display different gut microbiota profiles which can be exploited as potential prognostic biomarkers paving also the way to new integrative therapeutic approaches.

This study aimed to investigate a miniaturized extraction methodology with analysis by GC-MS for simultaneous detection and quantification of cocaine (COC), benzoylecgonine (BZE) and cocaethylene (CE) in hair to monitor drug addicts. The process was done following the international guide of the Scientific Task Force on Forensic Toxicology. After sample extraction, derivatizing solution was added, clean-up was done by the Hollow Fiber Liquid Phase Microextraction (HF-LPME) and adapted to use the ultrasonic bath, a simple and easy-to-handle device. Isobutylchloroformate was first used as derivatization reagent to convert benzoylecgonine to isobutylbenzoylecgonine. Analytes quantification occurred within a linear range of 0.1 to 20 ng mg-1 for COC and 0.05 to 5 ng mg-1 for BZE and CE, with a correlation coefficient of r > 0.99. Limits of detection were 0.05; 0.03 and 0.03 ng mg-1, whereas limits of quantification were 0.1; 0.05 and 0.05 ng mg-1 for COC; BZE and CE, respectively. There was no matrix effect interference. Intra and inter-day precision and accuracy were acceptable according to international guidelines. The analytical method HF-LPME-GC-MS was successfully applied to 14 hair samples from patients admitted in drugs detoxification programs. All samples resulted positive for cocaine (0.80-> 20 ng mg-1) and benzoylecgonine (0.20-> 5 ng mg-1), 11 samples were positive for cocaethylene (0.10-> 0.60 ng mg-1).

Abstract Background The main clinical consequences of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection are pneumonia and respiratory failure even requiring mechanical ventilation. In this context, the lung parenchyma is highly prone to ventilator-related injury, with pneumothorax and persistent air leak as the most serious adverse events. So far, endobronchial valve (EBV) positioning has proved efficacious in treating air leaks with a high success rate. Case presentation We report, for the first time, two cases of patients affected by SARS-CoV-2-related pneumonia complicated with bacterial super-infection, experiencing pneumothorax and persistent air leaks after invasive mechanical ventilation. Despite the severity of respiratory failure both patients underwent rigid interventional bronchoscopy and were successfully treated through EBV positioning. Conclusions Persistent air leaks may result from lung tissue damage due to a complex interaction between inflammation and ventilator-related injury (VILI), especially in the advanced stages of ARDS. EBV positioning seems to be a feasible and effective minimally invasive therapeutic option for treating this subset of patients.

Abstract Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.