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Background: Nursing care plans document the nursing process, displaying actions, and illustrating expected outcomes. Their integration into electronic health records (EHRs) is critical for accurate documentation, enhanced by standardized nursing terminologies that promote communication, critical reasoning, and patient safety through consistent language for information., Objective: This study aimed to identify appropriate standardized nursing terminology tailored to the context of a Northern Italian Cancer Center and research facility for developing nursing care plans and starting their integration into institutional EHRs., Methods: Participatory action research was conducted to select proper terminology respecting the oncological setting, develop nursing care plans, and start their implementation in EHRs. The nursing team of a pilot ward collaborated closely with the researchers as coresearchers. Care plan samples were presented using the North American Nursing Diagnosis Association-International Nursing Intervention Classification, Nursing Outcomes Classification, and International Classification for Nursing Practice (ICNP) in the test section of the EHRs to gather nurses' preferences. Quantitative data collection, focus groups, and survey analyses were conducted., Results: Nurses chose the ICNP for its flexibility but sought better methods to define patient severity in assessments and outcomes. They suggested incorporating the Common Terminology Criteria for Adverse Events to enable context-sensitive care plans., Conclusions: End-user involvement is essential for developing EHRs, enhancing system usability, and reducing implementation resistance. Including nurses in management decisions empowers them, and improves care quality., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction . The experimental pre-clinical background and rationale are discussed as well.

Recent studies have emphasized the critical role of alteration in cellular plasticity in the development of fibrotic disorders, particularly pulmonary fibrosis, prompting further investigation into molecular mechanisms and therapeutic approaches. In this context, Precision Cut Lung Slices (PCLSs) emerge as a valuable ex vivo research tool. The process of PCLSs generation preserves most features of the naïve lung tissue, such as its architecture and complex cellular composition. We previously stimulated normal lung PCLSs with two different stimuli (fibrotic cocktail, composed by platelet lysate and TGFβ, or neutrophil extracellular traps) and we observed a significant elevation of Epithelial-Mesenchymal Transition (EMT) markers from 24 h to 72 h of culture. The aim of our work was to exploit this PCLSs based ex vivo model of EMT, to evaluate the effect of imatinib, an old tyrosine kinase inhibitor with reported anti-remodeling activities in vitro and in animal models. Imatinib treatment significantly decreased α-SMA and collagen expression already starting from 24 h on stimulated PCLS. Imatinib showed a significant toxicity on unstimulated cells (3-fold increase in ACTA2 expression levels at 24 h, 1.5-fold increase in COL1A1 expression levels at 24 h, 2-fold increase in COL3A1 expression levels at 72 h). Further evaluations on specific cell lines pointed out that drug effects were mainly directed towards A549 and LFs. In conclusion, our model confirms the anti-remodeling activity of imatinib but suggests that its direct delivery to alveolar epithelial cells as recently attempted by inhalatory preparation of the drug might be associated with a non-negligible epithelial cell toxicity.

Infections are a major cause of morbidity and mortality during neutropenia after hematopoietic stem cell transplantation (HSCT). The use of a low-microbial protective diet (PD) in the peritransplantation period is a standard of care, although its efficacy has never been tested prospectively. We conducted a multicenter, randomized, noninferiority trial, enrolling all consecutive adult patients undergoing high-dose induction chemotherapy or HSCT with the objective to compare nonrestrictive diet (NRD) vs PD. Overall, 222 patients were enrolled, randomly assigned, and analyzed. One hundred seventy-five subjects (79%) received autologous HSCT (auto-HSCT), 41 (18%) received allogeneic HSCT (allo-HSCT), and 6 (3%) patients received high-dose induction chemotherapy. There was no significant difference in terms of incidence of grade ≥2 infections and death during neutropenia in the 2 arms. In multivariable analysis, only multiple myeloma diagnosis, fluoroquinolone prophylaxis, and the absence of mucositis were associated with a lower incidence of grade ≥2 infections. We did not report any significant variation in terms of hospitalization length, incidence of mucositis and gastrointestinal infections, body weight, and serum albumin variations in the 2 arms. In allo-HSCT recipients, the incidence of acute graft-versus-host disease grade ≥3 was similar. NRD was associated with higher patient-reported satisfaction. In conclusion, NRD is not inferior to a traditional PD during neutropenia after HSCT, and our results demonstrated that implementing a restrictive diet unnecessary burdens patients' quality of life. The clinical trial was registered prospectively in the clinical trial registry of the Istituto Nazionale dei Tumori of Milan as INT54/16., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Rationale: Novel coronavirus-related disease (COVID-19) has profoundly influenced hospital organization and structures worldwide. In Italy, the Lombardy Region, with almost 17% of the Italian population, rapidly became the most severely affected area since the pandemic beginning. The first and the following COVID-19 surges significantly affected lung cancer diagnosis and subsequent management. Much data have been already published regarding the therapeutic repercussions whereas very few reports have focused on the consequences of the pandemic on diagnostic procedures., Methods: We, here, would like to analyze data of novel lung cancer diagnosis performed in our Institution in Norther Italy where we faced the earliest and largest outbreaks of COVID-19 in Italy., Results: We discuss, in detail, the strategies developed to perform biopsies and the safe pathways created in emergency settings to protect lung cancer patients in subsequent therapeutic phases. Quite unexpectedly, no significant differences emerged between cases enrolled during the pandemic and those before, and the two populations were homogeneous considering the composition and diagnostic and complication rates., Conclusions: By pointing out the role of multidisciplinarity in emergency contexts, these data will be of help in the future for designing tailored strategies to manage lung cancer in a real-life setting.

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9-191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis.

Surgery is part of a multimodal therapeutic approach to malignant pleural mesothelioma (MPM) although its real beneficial effect is still controversial. The optimal precise sequence of treatments within the trimodality is unclear, and should be decided upon a multidisciplinary consensus for each individual patient. Here, we analyzed the perioperative data of 19 MPM patients who underwent extended pleurectomy/decortication (EPD) with curative intent. The mean age at diagnosis was 67 years; 11 males and eight females. Ten patients were diagnosed with MPM via medical thoracoscopy (MT), and nine via video-assisted thoracoscopic surgery (VATS). The vast majority of cases harbored epitheliod forms. We compared neoadjuvant chemotherapy (NCT) followed by surgery (11 cases) versus surgery followed by adjuvant chemotherapy (ACT, 8 cases) within a 3-year period. All patients had extended pleurectomy/decortication and none had an extended pneumonectomy. Analysis of survival curves suggested that the short-term outcomes are better with upfront EDP followed by ACT if compared to EDP preceded by NCT. Although limited, the data highlighted the safety and feasibility of EPD, with manageable postoperative complications and no major burden for the patients., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background and Objective: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients. However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF., Methods: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer., Key Content and Findings: The data here presented mainly focus on gene mutations, epigenetics and novel therapeutic approaches. Moreover, epidemiology, prognostic variables and in new treatment strategies adopted in patients with IPF and lung cancer are discussed as well., Conclusions: Overall, the findings of this narrative review will be of help in defining the key molecular features that could applied in IPF setting with promising rationale to improve therapy and to better manage those cases carrying IPF and cancer concomitantly., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-880/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites., Competing Interests: Declaration of interests I.Z. reports compensation for consulting services with Implicit Biosciences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis., Methods: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance., Results: The median overall survival (OS) was 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine., Conclusion: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.

The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs that correlates with neutrophils count; moreover, the analysis of lung tissues of COVID-19 deceased patients showed a subset of alveolar reactive pneumocytes with a co-expression of epithelial marker and a mesenchymal marker, confirming the induction of EMT mechanism after severe SARS-CoV2 infection. By airway in vitro models, cultivating A549 or 16HBE at air-liquid interface, adding alveolar macrophages (AM), neutrophils and SARS-CoV2, we demonstrated that to trigger a complete EMT expression pattern are necessary the induction of NETosis by SARS-CoV2 and the secretion of AM factors (TGF-β, IL8 and IL1β). All our results highlight the possible mechanism that can induce lung fibrosis after SARS-CoV2 infection., 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 © 2021 Pandolfi, Bozzini, Frangipane, Percivalle, De Luigi, Violatto, Lopez, Gabanti, Carsana, D’Amato, Morosini, De Amici, Nebuloni, Fossali, Colombo, Saracino, Codullo, Gnecchi, Bigini, Baldanti, Lilleri and Meloni.)

Background: The reduced concentration of hyaluronic acid in the synovial fluid, leading to impairment of joint function and painful symptomatology during knee osteoarthritis (OA), can be restored by using injectable formulations of hyaluronic acid (HA) and chondroitin sulfate (CS), variable for relative composition, HA/CS molecular modifications, and injection protocols. The present study aims to assess the safety and performance of the intra-articular (IA) viscosupplementing agent HYALGO, a formulation combining 40 mg/mL HA (>1700 kDa) and 40 mg/mL CS, in the treatment of patients suffering from knee OA., Methods: 74 patients affected by knee lesions classified as grade II and III according to Kellgren and Lawrence classification were prospectively recruited and treated with three HYALGO injections (2 mL) given one week apart. Visual analogue scale (VAS) pain changes were monitored at each injection and over-time at 6, 14, and 26 weeks of follow-up. Secondary endpoints were: Western Ontario McMaster University Osteoarthritis index (WOMAC), Patient's Global Assessment (PGA) score, Clinical Observer Global Assessment (COGA) score, Outcome Measures in Rheumatology Committee (OMERACT) and Osteoarthritis Research Society International (OARSI) responders rates. Patients were also assessed for changes in their ultrasound joint scores according to the criteria of the OMERACT US Task Force Group., Results: Pain reduction was statistically significant starting from the first IA injection. Mean pain reduction from baseline to week 26 was -90.6%. At 26 weeks, WOMAC Pain was reduced by -62.7%, WOMAC Stiffness by -47.2%, WOMAC Physical Function by -54.1%; Total WOMAC by -53.8%. The VAS PGA change from baseline was -48.0 [mm] and VAS COGA -41.0 [mm]. Responders at week 26 were 78.4%. Ultrasound parameters (joint effusion, synovial thickness, and popliteal cysts) improved or remained stable from baseline to week 6., Conclusions: Three injections of HYALGO were safe and effective to manage symptomatic knee OA, with a beneficial effect that increased progressively over time, peaking 6 months after injection., (© 2021 Delhi Orthopedic Association. All rights reserved.)

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.

The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19., Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels., Results: ICU patients showed a marked increase in neutrophils (1.24 × 10 5  ml - 1 , 0.85-2.07), lower lymphocyte (0.97 × 10 5  ml - 1 , 0.024-0.34) and macrophages fractions (0.43 × 10 5  ml - 1 , 0.34-1.62) compared to IMW patients (0.095 × 10 5  ml - 1 , 0.05-0.73; 0.47 × 10 5  ml - 1 , 0.28-1.01 and 2.14 × 10 5  ml - 1 , 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05)., Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

From the end of 2019, the world population has been faced the spread of the novel coronavirus SARS-CoV-2 responsible for COVID-19 infection. In approximately 14% of the patients affected by the novel coronavirus, the infection progresses with the development of pneumonia that requires mechanical ventilation. At the moment, there is no specific antiviral treatment recommended for the COVID-19 pandemic and the therapeutic strategies to deal with the infection are only supportive. In our opinion, mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 pneumonia, due to the broad pharmacological effects it shows, including anti-inflammatory, immunomodulatory, regenerative, pro-angiogenic and anti-fibrotic properties., Competing Interests: M.L.T., S.P. and A.G.C. are co-founders and members of the advisory board of PharmaExceed S.r.l.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)