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Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

Background Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality. Methods Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included. Results Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43–1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01–3.23, p < 0.001). Conclusions VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.

Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis. MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit. From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study. Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide à la recherche sur la sclérose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).

Background During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with bla NDM-4 gene were investigated. Results The isolates exhibited the same PFGE profile and a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and β-lactams. The strains produced the NDM-4 carbapenemase and the bla NDM-4 gene was part of the variable region of a class 1 integron. MLST analysis revealed that all isolates belonged to sequence type 405 (ST405). Conclusions This is the first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL in Italy.

The surveillance of latent tuberculosis infection (LTBI) in both healthcare workers and healthcare students is considered fundamental for tuberculosis (TB) prevention. The aim of the present study was to estimate LTBI prevalence and evaluate potential risk-factors associated with this condition in a large cohort of medical students in Italy. In a cross-sectional study, performed between March and December 2012, 1511 eligible subjects attending the Medical School of the University of Genoa, trained at the IRCCS San Martino-IST Teaching Hospital of Genoa, were actively called to undergo the tuberculin skin test (TST). All the TST positive cases were confirmed with an interferon-gamma release assay (IGRA). A standardized questionnaire was collected for multivariate risk analysis. A total of 1302 (86.2%) students underwent TST testing and completed the questionnaire. Eleven subjects (0.8%) resulted TST positive and LTBI diagnosis was confirmed in 2 (0.1%) cases. Professional exposure to active TB patients (OR 21.7, 95% CI 2.9–160.2; P value 0.003) and previous BCG immunization (OR 28.3, 95% CI 3.0–265.1; P value 0.003) are independently associated with TST positivity. Despite the low prevalence of LTBI among Italian medical students, an occupational risk of TB infection still exists in countries with low circulation of Mycobacterium tuberculosis.

During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with bla.sub.NDM-4 gene were investigated. The isolates exhibited the same PFGE profile and a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and [beta]-lactams. The strains produced the NDM-4 carbapenemase and the bla.sub.NDM-4 gene was part of the variable region of a class 1 integron. MLST analysis revealed that all isolates belonged to sequence type 405 (ST405). This is the first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL in Italy.

During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with bla.sub.NDM-4 gene were investigated. The isolates exhibited the same PFGE profile and a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and [beta]-lactams. The strains produced the NDM-4 carbapenemase and the bla.sub.NDM-4 gene was part of the variable region of a class 1 integron. MLST analysis revealed that all isolates belonged to sequence type 405 (ST405). This is the first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL in Italy.

Resistive bend sensors have been increasingly used in different areas for their interesting property to change their resistance when bent. They can be employed in those systems where a joint rotation has to be measured, in particular biomedical systems, to measure human joint static and dynamic postures. In spite of their interesting properties, such as robustness, low price, and long life, the commercial bend sensors have a response which is not actually linear, as an electronic device to measure bend angles should be, to recover human posture without distortion. In this work, different interfaces for sensor device readout were analyzed and compared from the output response linearity point of view. In order to obtain a sensor characteristic as closer as possible to the ideal linear one, a way to calculate the sensor characteristic with a generalized resistive strip contour, starting from an empiric sheet resistance model, was developed, in order to find what is the more suitable nonuniform geometry.

The study defines the epidemiological characteristics of HIV-infection in the population of Genoa and estimates the entity of AIDS-cancer association. The cohort includes 317 subjects resident in the Municipality of Genoa, aged above 14 years and notified prior to 31 December 1991 and/or dead from AIDS in the period 1988-1991. From 1984 to 1991, 44 cases of tumour were recorded. The comparison between the rate ratios found in the AIDS patients' cohort and in the general population of Genoa strengthen the significant association highlighted in literature regarding overall cancer, 26.7 (p < 0.05), and in particular, Kaposi's sarcoma, 3239.4 (p < 0.05); non-Hodgkin's lymphomas, 84.8 (p < 0.05); Hodgkin's lymphomas, 20.6 (p < 0.05). Moreover, a significant increase in the risk of testicular seminoma, 61.5 (p < 0.05) and lung cancer, 18.0 (p < 0.05) is confirmed.

D'Angelo reviews \"Il salto dell'acciuga\" by Nico Orengo.