Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Summary Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet–fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet–fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. Funding None.

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study.

Obstetrics and gynecology.

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.

Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain

A national survey of Italian physicians' attitudes towards end-of-life decisions following the death of Eluana Englaro: reply to M.Y. Rady.

Background Healthcare quality improvements are one of the most important goals to reach a better and safer healthcare system. Reviewing in-hospital mortality data is useful to identify areas for improvement, and to monitor the impact of actions taken to avoid preventable cases, such as those related to healthcare associated infections (HAI). Methods In this paper, we present the experience of the Mortality Committee of Bambino Gesu Children Hospital (OPBG). OPBG has instituted a process of systematic revision of all in-hospital deaths conducted by a multidisciplinary team. The goal is to identify system-wide issues that could be improved to reduce in-hospital preventable deaths. In this way, the mortality review goes alongside all the other risk management activities for the continuous quality improvement and patient safety. Results In years 2008-2017, we performed a systematic analysis of 1148 inpatient deaths. In this time period, the overall mortality rate was 0.4%. Forty-seven deaths were caused due to infections, 10 of which involved patients with HAI transferred to OPBG from other facilities or patients with community- acquired infections. Six deaths related to HAI were followed by claims compensations. All these cases were not followed by compensation because the onset of HAI was considered an inevitable consequence of the underlying disease. Conclusion Introduction of the mortality review committee has proved to be a valid instrument to improve the quality of the care provided in a hospital, allowing early identification of care gaps that could lead to an increase in mortality rates. Article Highlights Box: Reduction of preventable deaths is one of the most important goals to be achieved for any health-care system and to improve the quality of care. • Several studies have shown that analysis of morbidity and mortality rate helps to detect any factors that can lead to an increase in in-hospital mortality rates. • The review of in-hospital deaths allows to learn how to improve the quality and safety of care through identification of critical issues that lead to an increase in mortality ratio. • In some medical areas, such as intensive care units or surgery, the implementation of the conference on mortality and morbidity is more useful for assessing procedures at high risk of errors. • The implementation of existing databases with data deriving from the systematic review of medical records and in-hospital deaths appears to be desirable. • Mortality Review Committees can represent a very useful tool for all the health facilities for the reduction of preventable deaths, such as those related to HAI.

Improve Healthcare quality through Mortality Committee: Retrospective analysis of Bambino Gesù Children Hospital's ten years' experience 2008-2017

L'asbesto (o amianto) è un minerale appartenente al gruppo dei silicati fibrosi. Fino al 1991,per le caratteristiche dell’amianto,cioè la notevole resistenza alle elevate temperature, la sua conformazione in fibre e il costo molto basso è stato utilizzato per produrre materiali in grado di resistere alle alte temperature. I silicati di amianto a matrice solida avevano trovato largo uso in edilizia, nell’ impiantistica resistente al calore, nelle tubature per acquedotti e fognature, nei pannelli e fogli per controsoffittature, negli intonaci e come materiale fonoassorbente. Anche nell’industria manifatturiera è stato largamente impiegato per la produzione di manufatti ed oggetti di uso domestico, come isolante termico per alte e le basse temperature,condotte antifiamma, per la produzione di elettrodomestici con utilizzo di alte temperature (stufe, phon, etc.), nei freni nelle frizioni, negli schermi parafiamma nelle guarnizioni, nella produzione di tessuti per indumenti in grado di proteggere dal calore (guanti, tute ignifughe) e di tessuti da arredo resistenti a temperature elevate. L’esposizione ad atmosfere contenenti amianto può essere causa di numerose patologie come l’asbestosi polmonare, i mesoteliomi e il carcinoma polmonare. Le forme più nocive di amianto sono gli anfiboli, fra questi la crocidolite è quella con maggior potenziale neoplastico. Tuttavia, la diagnosi di malattia professionale correlata ad amianto non è semplice né automatica, occorre rispettare una serie di criteri, verificando markers immunoistochimici, monitoraggi biologici ed ambientali, anche personali, per accertare una correlazione effettiva. Inoltre, le conoscenze riguardo alle patologie asbesto-correlate ed i criteri diagnostici si sono evoluti nel tempo, e considerando il periodo di latenza delle malattie, in particolare delle neoplasie, è difficile verificare l’esposizione pregressa dei pazienti che hanno manifestato clinicamente la malattia solo in tempi recenti, magari 10-20 anni dopo l’ultima supposta esposizione. Riportiamo due case report di mesotelioma maligno, di supposta origine professionale amianto-correlata, discutendone l’eziologia alla luce di un Asbestos and onset of mesothelioma: Case Report www.preventionandresearch.com 136 Apr-Jun 2013|P&R Scientific|Volume 3|N°2 excursus della letteratura. Per censire, analizzandola, tutta la conoscenza scientifica circa la relazione tra salute umana e asbesto, prodotta dall’inizio della storia dell’utilizzo industriale ad oggi, abbiamo consultato la letteratura in rete tramite motori di ricerca con utilizzazione di parole chiave. Sono state interrogate con questo sistema le principali banche di dati scientifici mondiali (Pubmed, Cochrane, Embase, Tripdatabase), sono state censite un totale di 13551 pubblicazioni per ricostruire come e quando sono state pubblicate informazioni sui danni attribuibili ad asbesto. Gli argomenti fondamentali censiti sono stati: “Amianto e danni alla salute”, “Amianto e Mesotelioma Maligno”. In base ai risultati appresi tramite la nostra ricerca, una volta applicati ai due casi in esame, abbiamo appurato che non vi è certezza della diagnosi di mesotelioma maligno attribuito ai due pazienti, in quanto non sono stati applicati rigorosamente i criteri diagnostici suggeriti dalla letteratura internazionale sia sul piano clinico che su quello istopatologico ed immuno-chimico. Background Asbestos is a mineral belonging to the group of fibrous silicates. Asbestos fibers can be found free or weakly bound to each other (friable asbestos) or strongly bound to each other in the case of asbestos in compact matrix. Due to its remarkable resistance to high temperatures, its conformation in fibers and its very low cost, it was used until in Italy 1991 to produce materials able of withstanding high temperatures. The silicates of asbestos in the solid matrix were widely used in construction, in resistant to heat plant engineering, in plumbing for aqueducts and sewers, in panels and sheets for ceilings, in plaster and as sound-absorbing material. It was also widely used in the manufacturing industry for its sound-absorbing characteristics and for the production of manufactured articles and household equipment, such as thermal insulation for high and low temperatures, flame retardant ducts, for the production of appliances with use of high temperatures (stoves, hair dryer, etc.), in the clutches brakes, in the baffle plate display screens in the seals, in the production of clothing protecting from heat (gloves, fireproof suits) and in furnishing resistant to elevated temperatures. The exposure to atmospheres containing asbestos can be the cause of several diseases such as pulmonary asbestosis, mesothelioma and lung cancer. The amphiboles are the most dangerous forms of asbestos and the crocidolite is the one with the most neoplastic potential. The inhalation of even a single asbestos fiber may induce the onset of malignant mesothelioma or other forms of lung cancer. Differently from other substances and dangerous preparations, there is no risk threshold below which the concentration of asbestos fibers in inspired air may be considered safe. Obviously prolonged exposure to asbestos fibers, or inhalation of large amounts, increases exponentially the chances of developing asbestos-related malignancies. Before the eighties, the risk of exposure to asbestos was only considered work-related, but today asbestos is considered as an environmental pollutant. In 1992 legislative decree 257 banned in Italy the use and the processing of asbestos and it gave the standards for decontamination of the areas affected by asbestos pollution. Case report We report here two cases of pleural mesothelioma. Case 1: Male, born in 1956, worked for 18 years on several ships as non-commissioned officier. In 2004 he underwent surgery for right pneumonectomy with partial pericardial and right hemidiaphragm resection and subsequent reconstruction through Goretex implants, followed by successive cycles of radiotherapy. In 2005 the patient presented with \"anorexia, worsening dyspnea, and was operated again for mesothelioma, with laterocervical lymphadenopathy.\" The histopathological examination of biopsy material from laterocervical lymph node was so reported: \"localization of malignancy with morphological features consistent with mesothelioma\". Subsequently a right pleural effusion was found. After thoracentesis and cytologic evaluation of pleural fluid a pleural mesothelioma was once again confirmed. The definitive histological examination gives evidence of biphasic malignant mesothelioma infiltrating the lung, with lymph node micro metastasis pT3N1MX . Asbestos and onset of mesothelioma: Case Report www.preventionandresearch.com 137 Apr-Jun 2013|P&R Scientific|Volume 3|N°2 The patient's condition worsened, with the appearance of severe dyspnea and congestive cardio-circulatory followed by death on September 2005. From the autopsy: \"The right parietal pleura is in part thickened and in part replaced by implants. Absence of the right lung. On the left lung the presence of tenacious adhesions is found. The left pleura appears thickened because of the presence of a neoformation of lipidic consistency, that presents in section large necrotic areas; the above lesion expatiates infiltrating diffusely chest wall, left lung, pericardium, diaphragm, up to the falciform ligament and retroperitoneum and incorporating the mediastinal organs (esophagus and trachea). Multiple samples of the lipidic neoformation have been withdrawn in the pleura, the pericardium and the left lung”. From the medical report of the histopathological examination of pleuro-pulmonary biopsy material taken during autopsy: “Fairly cellular neoformation interesting massively visceral and parietal pleura with invasion by contiguity of the soft tissues of the chest wall and the lung parenchyma and interesting diffusely pericardium with infiltration by contiguity of the subepicardial myocardium and aspects of vascular invasion. The neoformation is mainly composed of atypical elements variously twisted and arranged in corrugated, swirling structures, and included in a fibrous stroma. We proceeded to set up preparations of neoplastic tissue treated with immunochemical techniques, in order to highlight the possible mesothelial origin of the tumor\". The following results have been achieved (Tab. 1): Table 1 Results of Case 1 neoplastic markers

Asbestos and onset of mesothelioma: case report

Background - Although cannabinoids consumption represents a current social and health problem, especially in a historical context characterized by an open orientation for recreational and therapeutic purposes, risks regarding neurotoxicity of such substances is a frequently overlooked issue. Objective - The present systematic review aims to summarize the available evidence regarding the mechanism of cannabinoids-induced brain damage as a substrate of neurological, psychiatric, and behavioral effects. Another objective is to provide support for future investigations and for legislative choices. Methods - The systematic literature search through PubMed and Scopus and a critical appraisal of the collected studies were conducted. Search terms were "(("Cannabinoids" OR "THC" OR "CBD") AND "Brain" AND ("Damage" OR "Toxicity"))" in title and abstracts. Studies examining toxic effects on the brain potentially induced by cannabinoids on human subjects were included. Results - At the end of the literature selection process, 30 papers were considered for the present review. The consumption of cannabinoids is associated with the development of psychiatric, neurocognitive, neurological disorders and, in some cases of acute consumption, even death. In this sense, the greatest risks have been related to the consumption of high-potency synthetic cannabinoids, although the consumption of phytocannabinoids is not devoid of risks. Conclusion - The research carried out has allowed to highlight some critical points to focus on, such as the need to reinforce the toxic-epidemiologic monitor of new substances market and the importance of information for both medical personnel and general population, with particular attention to the mostly involved age groups.

Paola Frati

Papers

A national survey of Italian physicians' attitudes towards end-of-life decisions following the death of Eluana Englaro: reply to M.Y. Rady.

Improve Healthcare quality through Mortality Committee: Retrospective analysis of Bambino Gesù Children Hospital's ten years' experience 2008-2017

Asbestos and onset of mesothelioma: case report

Cannabinoids and brain damage: A systematic review on a frequently overlooked issue.

How to fix democracy to fix health care