BACKGROUND: Despite research, there are still controversial areas in the management of Crohn\'s disease (CD).
OBJECTIVE: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.
METHODS: Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process.
RESULTS: Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator.
CONCLUSIONS: This document sought to pull together the best evidence, experts\' opinions, and treating physicians\' attitudes when using anti-TNF therapies in patients with CD.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, \"no-reflow\"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

Adult corals are among the most sensitive marine organisms to dissolved manganese and experience tissue sloughing without bleaching (i.e., no loss of Symbiodinium spp.) but there are no chronic toxicity data for this sensitive endpoint. We exposed adult Acropora millepora to manganese in 2-d acute and 14-d chronic experiments using tissue sloughing as the toxicity endpoint. The acute tissue sloughing median effect concentration (EC50) was 2560 μg Mn/L. There was no chronic toxicity to A. millepora at concentrations up to and including the highest concentration of 1090 μg Mn/L i.e., the chronic no observed effect concentration (NOEC). A coral-specific acute-to-chronic ratio (ACR) (EC50/NOEC) of 2.3 was derived. These data were combined with chronic toxicity data for other marine organisms in a species sensitivity distribution (SSD). Marine manganese guidelines were 190, 300, 390 and 570 μg Mn/L to provide long-term protection of 99, 95, 90, and 80 % of marine species, respectively.

OBJECTIVE: The Working Group for Neuro-Oncology of the German Society for Radiation Oncology in cooperation with members of the Neuro-Oncology Working Group of the German Cancer Society aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS).
METHODS: Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN including bevacizumab in clinical routine.
CONCLUSIONS: Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neuro-oncologist. A multistep approach as an opportunity to review as many characteristics as possible to improve diagnostic confidence is recommended. Additional information about radiotherapy (RT) techniques is crucial for the diagnosis of RN. Misdiagnosis of untreated and progressive RN can lead to severe neurological deficits. In this practice guideline, we propose a detailed nomenclature of treatment-related changes and a multistep approach for their diagnosis.

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients\' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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【中文题目：抗血管药物治疗放射性脑坏死专家共识】 【中文摘要：血管内皮生长因子（vascular endothelial growth factor, VEGF）的高水平表达是放射性脑坏死（cerebral radiation necrosis, CRN）发生的重要机制。抗血管生成药物（贝伐珠单抗）通过抑制VEGF，作用于脑坏死区域周围的血管组织，减轻CRN引起的脑水肿。许多研究证实贝伐珠单抗可有效缓解脑坏死症状，改善患者的体力状况评分以及减轻影像学上脑水肿范围。抗血管治疗的疗效主要与药物作用时长相关，低剂量抗血管药物即可达到较好的治疗效果。预防是最好的治疗，CRN的发生与肿瘤相关因素和治疗相关因素相关，通过控制两方面因素，可有效预防CRN。
】 【中文关键词：放射性脑坏死；抗血管生成药物；贝伐珠单抗；专家共识】.

Vascular occlusions can occur with injection of dermal fillers causing devastating outcomes for the patient. The occurrence, and subsequent management, of these negative outcomes is a source of significant stress to the aesthetic clinician. Complications management is an essential component of clinical practice and professionals must develop competence and confidence in the identification and effective treatment of a vascular occlusion. The relatively rare occurrence of a vascular occlusion mandates that learning must be largely through the study of theory in addition to the sharing of learning experiences within a collaborative clinical community. The delivery of optimal care begins with an understanding of the underlying pathophysiology and the ability to assess and elicit clinical signs. Establishing a clinical diagnosis, targeted therapy can commence in a timely fashion. This paper provides guidance on how to identify and manage a vascular occlusion caused by cross-linked hyaluronic acid. It provides a detailed description of the pathological process of tissue ischemia, and introduces identifiable stages which will help to determine the extent of ischemia and the time frame since ischemic onset. The stages are particularly important as they highlight when wound support may be needed.

As the use of injectable skin fillers increase in popularity, an increase in the reported adverse events is expected.
This systematic review supports the development of American Society for Dermatologic Surgery practice guideline on the management of adverse events of skin fillers.
Several databases for studies on risk factors or treatments of injection-related visual compromise (IRVC), skin necrosis, inflammatory events, and nodules were searched. Meta-analysis was conducted when feasible.
The review included 182 studies. However, IRVC was very rare (1-2/1,000,000 patients) but had poor prognosis with improvement in 19% of cases. Skin necrosis was more common (approximately 5/1,000) with better prognosis (up to 77% of cases showing improvement). Treatments of IRVC and skin necrosis primarily depend on hyaluronidase injections. Risk of skin necrosis, inflammatory events, and nodules may be lower with certain fillers, brands, injection techniques, and volume. Treatment of inflammatory events and nodules with antibiotics, corticosteroids, 5-FU, and hyaluronidase was associated with high response rate (75%-80%). Most of the studies were small and noncomparative, making the evidence certainty very low.
Practitioners must have adequate knowledge of anatomy, elicit history of skin filler use, and establish preemptive protocols that prepare the clinical practice to manage complications.

BACKGROUND: Necrotising otitis externa is a progressive infection of the external auditory canal which extends to affect the temporal bone and adjacent structures. Progression of the disease process can result in serious sequelae, including cranial nerve palsies and death. There is currently no formal published treatment guideline.
OBJECTIVE: This study aimed to integrate current evidence and data from our own retrospective case series in order to develop a guideline to optimise necrotising otitis externa patient management.
METHODS: A retrospective review of necrotising otitis externa cases within NHS Lothian, Scotland, between 2013 and 2018, was performed, along with a PubMed review.
RESULTS: Prevalent presenting signs, symptoms and patient demographic data were established. Furthermore, features of cases associated with adverse outcomes were defined. A key feature of the guideline is defining at-risk patients with initial intensive treatment. Investigations and outcomes are assessed and treatment adjusted appropriately.
CONCLUSIONS: This multi-departmental approach has facilitated the development of a succinct, systematic guideline for the management of necrotising otitis externa. Initial patient outcomes appear promising.

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