World Health Organization Classification of Tumours

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

Pathology and genetics of tumors of soft tissue and bone

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Investigative Ophthalmology and Visual Science

Objective: We undertook a best-evidence synthesis on the incidence, risk factors and prevention of mild traumatic brain injury. Methods: Medline, Cinahl, PsycINFO and Embase were searched for relev ...

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Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

Corticosteroids, used prudently, are one of the most potent and effective modalities available in the treatment of ocular inflammation. However, they can produce a plethora of adverse ocular and systemic events. In order to optimise and target drug delivery, whilst minimising systemic adverse effects, a diverse range of local ophthalmic preparations and delivery techniques have been developed. Topical drops and ointments remain the primary methods for administration of ocular corticosteroids. However, ocular penetration of topical corticosteroid drops depends upon drug concentration, chemical formulation of corticosteroid, and composition of the vehicle, therefore, apparently small modifications in preparations can produce a more than 20-fold difference in intraocular drug concentration. Periocular injections of corticosteroids continue to have a useful, but limited, therapeutic role and longer acting, intraocular delayed-release devices are in early clinical studies. Although newer corticosteroids with lesser pressure elevating characteristics have been developed, corticosteroid-induced ocular hypertension and glaucoma continue to be significant risks of local and systemic administration. Posterior subcapsular cataract, observed following as little as 4 months topical corticosteroids use, is thought to be due to covalent binding of corticosteroid to lens protein with subsequent oxidation. Inappropriate use of topical corticosteroid in the presence of corneal infections also continues to be a cause of ocular morbidity. Other risks of locally administered ophthalmic corticosteroids include: tear-film instability, epithelial toxicity, crystalline keratopathy, decreased wound strength, orbital fat atrophy, ptosis, limitation of ocular movement, inadvertent intraocular injection, and reduction in endogenous cortisol. This extensive review assesses the therapeutic benefits of locally administered ocular corticosteroids in the context of the risks of adverse effects.

Locally administered ocular corticosteroids: benefits and risks.

Purpose To produce a two-dimensional reconstruction map of the living human sub-basal corneal nerve plexus using in vivo confocal microscopy. Methods Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. Results Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal nerve plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). Conclusions This is the first study to elucidate the overall distribution of sub-basal nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and nerves migrate centripetally in tandem.

Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy.

An extensive electronic search was undertaken in January 2004 to identify all relevant peer-reviewed publications on Orbscan slit-scanning/Placido computerized topography. Ninety-one publications were identified. These address elevation topography and best-fit sphere, accuracy and repeatability of anterior and posterior corneal elevation and keratometric maps, comparison of Orbscan-acquired data and Placido-based computerized videokeratography instruments, pachymetry measurement and correlation with ultrasound, screening eye-bank corneas, detection of keratoconus, identifying corneal ectasia after refractive surgery, and miscellaneous applications. Studies were analyzed and critically compared in relation to attributes, applications, and limitations of Orbscan corneal topography. The review highlights advantages of this technique in assessing the cornea in health and disease and after surgery and identifies specific aspects that require further investigation and clarification.

Orbscan computerized topography: attributes, applications, and limitations.

The exponential evolution of in vivo confocal microscopy (IVCM) has led to a significant enhancement in our knowledge of the living cornea in both its physiological and pathological states. Studies using white light and coherent light-based IVCM have enabled detailed quantitative analysis of sub-basal nerve parameters, and have also resulted in the elucidation of the two-dimensional architecture of the normal corneal sub-basal nerve plexus. However, accurate and repeatable methods for quantitative analysis of stromal nerves imaged by IVCM remain to be developed. The effect of corneal surgery on central corneal nerves has been well documented in many IVCM studies, and these studies provide an indication of the regenerative capacity of corneal nerves. IVCM has also clearly demonstrated the involvement of corneal nerves in diseases such as keratoconus, although it remains unclear whether these alterations are a cause of, or occur secondary to, the disease process. IVCM has also been proposed as non-invasive method of accurately diagnosing and assessing the progression of diabetic neuropathy, highlighting the potential application of this technique as an indicator of systemic disease. This review consolidates our knowledge of how IVCM has contributed significantly to our greater understanding of corneal nerves in the living human cornea in health and disease.

https://bjo.bmj.com/content/bjophthalmol/93/7/853.full.pdf

In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review.

Aims: To quantify and establish baseline normative data for age-related differences in cellular and innervation density in the normal, healthy, human cornea using laser scanning in vivo confocal microscopy. Methods: Cross-sectional study of 85 normal subjects assessed via corneal topography and laser scanning in vivo confocal microscopy. Results: Mean age was 38±16 years (range 18–87 years) and 60% of subjects were female. Anterior keratocyte density declined by 0.9% per year (r = −0.423, p 0.05). No association was observed between subject gender and corneal cell or innervation density. Conclusions: Using laser scanning in vivo confocal microscopy this study highlights a significant, and relatively linear, reduction in keratocyte and endothelial cell density with increasing subject age. Interestingly, corneal sub-basal nerve fibre density also significantly decreases with increasing age. In vivo laser scanning confocal microscopy provides a safe, non-invasive method for the establishment of normative data and assessment of alterations in human corneal microstructure following surgery or disease processes.

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Charles N J McGhee

Papers

Locally administered ocular corticosteroids: benefits and risks.

Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy.

Orbscan computerized topography: attributes, applications, and limitations.

In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review.

Age‐related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study