This is the first Italian translation of the address delivered by Wilfred Trotter at the opening of the Session 1932-33 at the University College Hospital medical school. Besides its indubious interest for the history of Medical Education, it still presen

Questa è la traduzione in italiano del discorso tenuto dal celebre chirurgo inglese Wilfred Trotter all’apertura dei corsi dell’ University College Hospital dell’anno 1932. Oltre ad avere interesse per la storia della Medical Education, presenta tuttora aspetti di grande attualità, specie per l’affermazione della “facoltà umana” come elemento essenziale della medicina.This is the first Italian translation of the address delivered by Wilfred Trotter at the opening of the Session 1932-33 at the University College Hospital medical school. Besides its indubious interest for the history of Medical Education, it still presents considerations of great actuality even today, particularly on the transition from pre-clinical to clinical studies, the role of science in clinical medicine, the need to maintain a critical mind and to cultivate the “human faculty” as an essential element of clinical medicine and of the good doctor. Some similarities with the Greek text from the 4th century BC, On Ancient Medicine, are underscored

Democratic evaluation of clinical clerkship in a medical school. A case study

We report a case study of democratic evaluation of a clinical clerkship for medical students. We used a mixed model combining interviews and questionnaires to students, teachers and nurses involved in 9 weekly clerkship rotations in 7 hospital wards. The main outcome variable in quantitative analysis was the score of perceived usefulness for professional development of 42 Observable Practice Activities (OPAs) that each student should perform during clerkship. Scores were higher when the OPA was performed more consistently, was performed in small groups, and when the teaching and the evaluation methods were perceived as valid. The overall satisfaction for the program of teacher was high and did not correlate with students’ perceptions. The burden for patients was perceived as slightly higher in nurses, and did not correlate with teachers’ perceptions. When returned to students, teachers and nurses, these data could contribute to improve the program. Contrariamente ai tipi di valutazione basati su standard normativi pre-determinati dalla istituzione stessa (valutazione burocratica) o da un corpo professionale esterno (autocratica), la valutazione democratica è un tentativo aperto, indipendente, non normativo (in quanto non vincolante per gli organizzatori né i partecipanti) di dare voce a tutti gli attori coinvolti nel programma valutato. Per questo è più probabile che fornisca una descrizione del programma più dal punto di vista dei partecipanti che da quello delle aspettative degli organizzatori, fornendo così ad entrambi i gruppi suggerimenti utili per svilupparlo e migliorarlo. Abbiamo utilizzato questo approccio per valutare l’impatto della introduzione in un tirocinio clinico del CdL in Medicina di una lista di attività cliniche che gli studenti dovevano effettuare, documentandole su un apposito libretto. Si è costituito un gruppo di valutazione indipendente autorizzato dal Comitato Didattico, costituito da un docente, una specializzanda, ed un gruppo di studenti. Abbiamo utilizzato una metodologia mista, basata su questionari, domande aperte e interviste. Quale principale variabile quantitativa abbiamo scelto la percezione dell’utilità di ognuna delle attività svolte per il proprio sviluppo professionale. Alcune attività non venivano svolte regolarmente. Sono risultate effettuate il 75%, con un massimo di 100% in due reparti ad un minimo del 44%. Limitando l’analisi a queste, la maggior parte delle attività è stata valutata positivamente. Fattori che sono risultati influenzare positivamente i punteggi delle singole attività sono la divisione in piccoli gruppi (6 o meno), la validità delle modalità di presentazione e di valutazione (se previsto), la consistenza di effettuazione fra le varie rotazioni. Questi dati, restituiti ai docenti e agli studenti, possono essere utili per migliorare il programma.

Democratic evaluation of clinical clerkship in a medical school. A case study

We report a case study of democratic evaluation of a clinical clerkship for medical students. We used a mixed model combining interviews and questionnaires to students, teachers and nurses involved in 9 weekly clerkship rotations in 7 hospital wards. The main outcome variable in quantitative analysis was the score of perceived usefulness for professional development of 42 Observable Practice Activities (OPAs) that each student should perform during clerkship. Scores were higher when the OPA was performed more consistently, was performed in small groups, and when the teaching and the evaluation methods were perceived as valid. The overall satisfaction for the program of teacher was high and did not correlate with students’ perceptions. The burden for patients was perceived as slightly higher in nurses, and did not correlate with teachers’ perceptions. When returned to students, teachers and nurses, these data could contribute to improve the program.

Oxygen Therapy during Exercise in Patients with Interstitial Lung Diseases

Introduction: ILDs are a varied group of diffuse parenchymal lung diseases associated with high morbidity and mortality. Current treatments can only slow their progression but not cure the disease. Other treatments such as oxygen therapy can also be used as support. We know very little about the effects of oxygen therapy on patients with ILDs. The aim of this study was to collect data from the literature in order to determine whether oxygen therapy can actually decrease the mortality rate or whether it is only suitable for supportive therapy for patients with ILDs. Methods: We reviewed the literature since 2010 on oxygen therapy during exercise in patients with ILDs. Studies that used cardio-pulmonary tests were excluded. We only reviewed those that used the 6 min walking test (6MWT) or the free walking test. We located 11 relevant articles. Results: All the articles except a Japanese study showed an augmentation in oxyhaemoglobin saturation during exercise when oxygen was supplied. A 2018 study called AmbOx provided important data on the effects of oxygen therapy during daily activities, showing significant improvements in quality of life. Conclusions: This review showed that the literature on the benefits of oxygen therapy in patients with ILDs does not provide sufficient evidence to draft specific guidelines. It was not possible to conclude whether oxygen therapy has an effect on mortality or can only play a supportive role. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Prognostic Biomarkers of Sarcoidosis: A Comparative Study of Serum Chitotriosidase, ACE, Lysozyme, and KL-6

Purpose. Sarcoidosis is a systemic granulomatous disease with unknown etiology. Many clinical presentations have been reported, and acute disease needs to be distinguished from subacute and chronic disease. The unpredictable clinical course of the disease prompted us to evaluate the clinical utility of biomarker serum detection in sarcoidosis follow-up. Methods. Serum concentrations of chitotriosidase, ACE, KL-6, and lysozyme were analyzed by different methods in a population of 74 sarcoidosis patients (46 on steroid therapy at sampling) regularly monitored at Siena Sarcoidosis Regional Referral Centre and in a group of controls with the aim of comparing their contribution to clinical management of sarcoidosis patients. Results. KL-6 concentrations were significantly elevated in sarcoidosis patients with lung fibrosis and were significantly correlated with DLco and CPI score, while chitotriosidase was significantly higher in patients with extrapulmonary localizations. With a cut-off value of 303.5 IU/ml, KL-6 showed the best sensitivity (78%), while chitotriosidase reported the best specificity (85%) among the biomarkers. Conclusions. KL-6 is a reliable biomarker of fibrotic lung involvement in sarcoidosis patients. Among biomarkers, KL-6 showed the best sensitivity and serum chitotriosidase the best specificity, even in patients on chronic steroid therapy, and seemed to correlate with extrapulmonary localizations

Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series

Background: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and describe the trend of routine oncomarkers in IPF patients over the longest follow-up yet reported. Materials and methods: A systematic search of the literature in PubMed was performed to find relevant studies published up to 24 September 2020. The most common oncomarkers were chosen to select papers related to pulmonary fibrosis. Then, 24 IPF patients and 25 non-IPF patients, followed at Careggi ILD Referral Centre and Siena Regional Referral Centre for ILD, were enrolled consecutively. Results: A few studies reported an association between serum oncomarkers and severity of IPF. NSE, CEA, Ca19.9, and Ca125 were higher in the IPF, than in the non-IPF, group at every follow-up (p < 0.05). Ca15.3 concentrations were higher in the IPF, than the non-IPF, group at t3 (p = 0.0080) and t4 (p = 0.0168). To improve the specificity and sensitivity of Ca15.3, a panel of biomarkers was analyzed, with the IPF group as dependent variable, and chitotriosidase, Cyfra 21.1, Ca15.3, Ca125, and Ca19.9 as independent variables. Conclusions: This study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more “personalized” medical approach to patients affected by IPF

Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction

Background Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD).Methods This single-centre retrospective study enrolled 87 LTX patients (median age 55.81 years; 41 females, 23 single LTX, 64 bilateral LTX). All patients were managed with a pre-emptive anti-CMV approach. The incidences of the first episode of CMV infection, 1, 3, 6 and 12 months after LTX, were 12.64%, 44.26%, 50.77% and 56.14%. A median interval of 41 days elapsed between LTX and the first episode of CMV infection. The median blood load of CMV-DNA at diagnosis was 20,385 cp/ml; in 67.64% of cases, it was also the peak value. Patients who had at least one episode had shorter CLAD-free survival. Patients who had three or more episodes of CMV infection had the worst outcome.Results CMV infection was confirmed to be a common event in lung transplant patients, particularly in the first three months after transplant. It had a negative impact on transplant outcome, being a major risk factor for CLAD. The hypothesis that lower viral replication thresholds may increase the risk of CLAD is interesting and deserves further investigation. © 2022, The Author(s)

Characterization of NKG2-A/-C, Kir and CD57 on NK Cells Stimulated with pp65 and IE-1 Antigens in Patients Awaiting Lung Transplant

Introduction: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present study aimed to investigate NK and T cell subsets of patients awaiting LTx. We analyzed the cellular populations between reactive and non-reactive QuantiFERON (QF) CMV patients for the prediction of immunological response to infection. Methods: Seventeen pre-LTx patients and 15 healthy controls (HC) have been enrolled. QF and IFN-gamma ELISA assay detections were applied. NK cell subsets and T cell and proliferation assay were detected before and after stimulation with pp-65 and IE-1 CMV antigens after stratification as QF+ and QF-. Furthermore, we quantified the serum concentrations of NK- and T-related cytokines by bead-based multiplex analysis. Results: CD56(br)CD16(low)NKG2A(+)KIR(+) resulted in the best discriminatory cellular subsets between pre-LTx and HC. Discrepancies emerged between serology and QF assay. Better proliferative capability emerged from patients who were QF+, in particular in CD8 and CD25-activated cells. CD56(br)CD16(low), adaptive/memory-like NK and CD8Teff were highly increased only in QF+ patients. Conclusions: QF more than serology is useful in the detection of patients able to respond to viral infection. This study provides new insights in terms of immunological responses to CMV in pre-LTX patients, particularly in NK and T cells biology

Morphometric analysis of lymphatics vessels in fibrotic human lung

In pulmonary fibrosis, the usual interstitial pneumonia (UIP) pattern is characterised by heterogeneous, patchy fibrosis, with areas of normal lung adjacent to areas of complete destruction (honeycombing) and by fibroblastic foci (FF). The NSIP pattern which is characteristic of systemic sclerosis, is characterised by a more homogeneous involvement of the lung without honeycombing and FF. Little is known on lymphatic vessels in lung fibrosis. Defective lymphatic clearance could lead to prolonged exposure to pathogenic antigens and/or pro-inflammatory/pro-fibrotic mediators. We evaluated the distribution and morphology of lymphatic vessels in lung biopsies of 6 patients with UIP, 6 NSIP and 5 controls. Consecutive sections were stained with Movat’s pentachrome and with double immunostaining for von Willebrand factor and podoplanin (D2-40). Area, perimeter and position were recorded for vessels with a diameter > 5µm. We investigated separately in lintralobular, sub-pleural, and interlobular spaces. Lymphatics were consistently larger in subpleural spaces and in interlobular septa than in intralobular tissue. In the latter, the density of lymphatic vessels was significantly reduced in NSIP and in UIP (both 21±1 mm-2) compared to controls (35±4 mm-2) . In controls, 85±6% of the intralobular lymphatics were close (< 100 µm) to a blood vessel, and only 5±4% were in the proximity of bronchoalveolar spaces, while in the disease groups they were less frequently perivascular (NSIP 55 ±3%, UIP 56 ±2%) and more frequently associated with the bronchoalveolar lumen (NSIP 85 ±3%, UIP 69 ±2%). By contrast, in interlobular septa, lymphatic density was significantly increased in NSIP (303±28 mm-2) and in UIP (286±124 mm-2) compared to controls (96±69 mm-2). No differences in lymphatic density was seen in subpleural spaces. Thus, our data show a marked redistribution of lymphatic vessels within the lung in pulmonary fibrosis, without noticeable differences between the NSIP and UIP patterns