admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

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

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

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Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

Risk factors for severe and critically ill COVID-19 patients: A review.

South Australia is presently in the throes of major changes to its regulatory system governing land use, development of land and the development of planning policy against which development assessment decisions are to be made. Eventually the planning and development control system established under the Development Act 1993 (SA) will be replaced by a new system implemented by the Planning, Development and Infrastructure Act 2016 (SA) (the new Act).

COVID-19 Generated Changes to Planning and Development Controls in South Australia (preprint)

Hepatic angiosarcoma (HAS) is a malignant mesenchymal neoplasm composed of highly atypical, pleomorphic endothelial cells, which diffusely grow along liver sinusoids and other preformed vascular channels, especially at the periphery of the tumor, replacing normal endothelial cells. More solid areas, resembling sarcomas, can be found [1]. Far less common than hepatocarcinoma, representing less than the 2% of all the primary malignant hepatic tumors, HAS is still the most frequent primary malignant mesenchymal neoplasm of the liver. Although most of HAS do not carry a specific etiology, several chemical carcinogens, including vinyl chloride monomer (VCM), Thorotrast (thorium dioxide), and arsenic, have been listed as being responsible for occupational cases. VCM is a colorless, sweet-smelling gas primary used in the production of polyvinyl chloride (PVC), whose resins are almost ubiquitously present in building materials, construction, and home furnishings. VCM is now classified as an International Agency for Research on Cancer (IARC) Group 1 carcinogen, due to the correlation between HAS and its occupational exposure [2]: initially described in three workers at a VCM polymerization plant in Kentucky in 1974 [3], several other HAS occupational cases have been reported worldwide in the following decades, all linked to workers’ exposure to VCM [4, 5]. Because HAS is an extremely rare tumor, both radiological and histological diagnosis could be really challenging and their integration with clinical data and history has a key role in reaching the correct diagnosis. Herein the case of a primary multifocal HAS is described, with initially misleading unspecific radiological findings. Suggesting the biopsy a malignant vascular lesion of the liver, an autopsy was performed, which confirmed the diagnosis of HAS.

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Multifocal Hepatic Angiosarcoma with Atypical Presentation: Case Report and Literature Review.

Late radiation-induced cardiac conduction system abnormalities.

Objective This prospective study was designed to analyze the incidence and the factors associated with impairment in left ventricular systolic function (LVSF) overtime in patients with rheumatoid arthritis (RA) without overt cardiac disease. In particular, we verified the hypothesis that a relationship between worsening of LVSF and markers of RA disease activity exists. Methods One hundred forty outpatients with RA without overt heart disease underwent clinical, laboratory, and echocardiographic evaluation at baseline and after 35 (interquartile range [IQR] 23-47) months of follow-up. A clinical Disease Activity Index (CDAI) score greater than 10 indicated the presence of moderate-high RA disease activity; data on anticitrullinated peptide antibody (ACPA) positivity were recorded at baseline. Stress-corrected midwall fractional shortening (sc-MFS) was used as a measure of LVSF and was considered impaired if less than 86.5%. Results At 36 (IQR 23-47) months follow-up, impaired sc-MFS was detected in 60 of 140 (43%) patients, compared with 80 patients with normal sc-MFS. Disease duration and activity, ACPA positivity, inflammatory markers, cardiovascular and antirheumatic therapies, and sc-MFS were similar between the two groups at baseline. A multiple logistic regression analysis showed ACPA positivity, moderate-high disease activity (CDAI greater than 10), and disease duration as independent predictors of impaired sc-MFS at follow-up. Finally, a simple clinical score to predict worsening of LVSF at midterm was built (area under the curve of 0.80, with a sensibility and specificity of 78% and 82%, respectively). Conclusion Disease duration, ACPA positivity, and moderate-high disease activity are independent prognosticators of LVSF impairment in RA. Adverse changes in heart function could be prevented by good control of inflammation and modulation of autoimmunity.

Disease Activity and Anticitrullinated Peptide Antibody Positivity Predict the Worsening of Ventricular Function in Rheumatoid Arthritis.

Objectives: Clinical expression of rheumatoid arthritis (RA) varies by gender, but whether cardiovascular disease (CVD) is gender related in RA is unknown. Left ventricular (LV) hypertrophy (LVH) is a hallmark of CVD in RA patients. We investigated whether the association of LVH with RA is gender driven. Methods: Consecutive outpatients with established RA underwent echocardiography with measurement of LVH at baseline and one follow-up. All participants had no prior history of CVD or diabetes mellitus. We assessed CVD risk factors associated with LVH at follow-up, including sex, age, arterial blood pressure, and body mass index (BMI). We also evaluated inflammatory markers, autoimmunity, disease activity, and the use of RA medications as predictors of LVH. Results: We recruited 145 RA patients (121 females, 83%) and reassessed them after a median (interquartile range) of 36 months (24-50). At baseline, women were more dyslipidemic but otherwise had fewer CVD risk factors than men, including less prevalent smoking habit and hypertension, and smaller waist circumference. At follow-up, we detected LVH in 42/145 (44%) RA patients. LV mass significantly increased only in women. In multiple Cox regression analysis, women with RA had the strongest association with LVH, independently from the presence of CVD risk factors (OR, 6.56; 95% CI, 1.34-30.96) or RA-specific characteristics (OR, 5.14; 95% CI, 1.24-21.34). BMI was also significantly and independently associated with LVH. Conclusion: Among established RA patients, women carry the highest predisposition for LVH.

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Sex-Specific Association of Left Ventricular Hypertrophy With Rheumatoid Arthritis.

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Haemodynamic instability in a critically ill patient with covid-19 pneumonia: searching over the chest - report of a clinical case and mini-review of the literature

Andrea Dalbeni

Papers

Multifocal Hepatic Angiosarcoma with Atypical Presentation: Case Report and Literature Review.

Late radiation-induced cardiac conduction system abnormalities.

Disease Activity and Anticitrullinated Peptide Antibody Positivity Predict the Worsening of Ventricular Function in Rheumatoid Arthritis.

Sex-Specific Association of Left Ventricular Hypertrophy With Rheumatoid Arthritis.

Haemodynamic instability in a critically ill patient with covid-19 pneumonia: searching over the chest - report of a clinical case and mini-review of the literature