Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse ...events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.
•DC electrical injuries can occur when direct current (DC) passes through the body.•Medical consequences of DC electrical injuries were systematically analyzed.•The most common medical consequences ...are burns and skin lesions.•Awareness of DC electrical injuries may facilitate prevention and improve management.
Direct current (DC) powered equipment and devices, including photovoltaic systems, high-voltage direct current power lines and novel concepts in electromobility have become increasingly popular in recent years. However, under adverse circumstances by malfunction or mishandling of these applications electrical injuries may occur when electric current passes through the human body. This review aimed at systematically summarizing the medical consequences of DC electrical injuries described in case reports and case series.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guided the methodological conduct and reporting.
Sixteen case reports and 3 case series were eligible for this review and included 70 patients. The reviewed articles were very heterogeneous regarding sources of DC electrical injuries and the reported medical consequences, including burns and skin lesions (n=67), neurological consequences (n=11), unconsciousness (n=10), cardiac consequences (n=8) and bone fractures (n=6). Seventeen individuals did not survive the electrical injuries.
From the few available data and partly incomplete documentations of cases we could gather hints of DC medical consequences, however, it was not possible to identify well-defined medical consequences for various circumstances of DC electrical injuries in occupational and non-occupational settings. To achieve this goal, additional studies are required, each providing a comprehensive description of the medical consequences and the circumstances of the electrical injuries.
Summary
Interleukin (IL)‐17 is an emerging target for inflammatory skin disorders. Given the remarkable success of its therapeutic inhibition in psoriasis, the pathogenic role of this cytokine is ...being explored in other immune‐mediated diseases. Interestingly, IL‐17 is linked to particular skin conditions where its activation coincides with disease flares. The leading hypothesis for its contribution to proinflammatory signalling cascades is driving inflammasome activation. However, IL‐17 stimulation also releases a range of noninflammasome‐related cytokines from human skin. Furthermore, a role in cytotoxic responses and an important interplay with the microbiome is hypothesized. While treatment failure would be surprising in neutrophilic dermatoses, the picture might be more complex in lymphocyte‐mediated conditions. Nonetheless, increasing insights into the pathogenesis suggest that beneficial responses are also probable in the latter conditions. Study of this pathway in the skin reveals some intriguing aspects of the IL‐17‐related immunological network.
What's already known about this topic?
Anti‐interleukin (anti‐IL)‐17 treatment shows dramatic responses in patients with psoriasis.
The pathogenic involvement of IL‐17 also becomes clear in several other inflammatory skin disorders.
What does this study add?
In this review, we provide an overview of the current understanding of the IL‐17 pathway in immune‐regulated skin diseases.
This delineates the group of disorders that are likely to respond.
Linked Comment: Puig. Br J Dermatol 2016; 175:859–860.
AbstractObjectiveTo examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and ...heart failure in patients with migraine and in a general population comparison cohort.DesignNationwide, population based cohort study.SettingAll Danish hospitals and hospital outpatient clinics from 1995 to 2013.Participants51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year.Main outcome measuresComorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis.ResultsHigher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking.ConclusionsMigraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases.
Listeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternal–foetal and focal infections. Little is known about ...Lm-associated respiratory tract or lung infections.
We conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia reported to the French National Reference Centre for Listeria from January 1993 to August 2016.
Thirty-eight consecutive patients with pleural infection (n = 32), pneumonia (n = 5), or both (n = 1) were studied; 71% of these were men. Median age was 72 (range 29–90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0–5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1–33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up.
Lm is a rare but severe cause of pneumonia and pleural infection in older immunocompromised patients, requiring prompt diagnosis and adequate management and follow-up.
Given the poor results using hypofractionated radiotherapy for early breast cancer, a dose of 50 Gy in 25 fractions (fr) has been the standard regimen used by the Danish Breast Cancer Group (DBCG) ...since 1982. Results from more recent trials have stimulated a renewed interest in hypofractionation, and the noninferiority DBCG HYPO trial (ClincalTrials.gov identifier: NCT00909818) was designed to determine whether a dose of 40 Gy in 15 fr does not increase the occurrence of breast induration at 3 years compared with a dose of 50 Gy in 25 fr.
One thousand eight hundred eighty-two patients > 40 years of age who underwent breast-conserving surgery for node-negative breast cancer or ductal carcinoma in situ (DCIS) were randomly assigned to radiotherapy at a dose of either 50 Gy in 25 fr or 40 Gy in 15 fr. The primary end point was 3-year grade 2-3 breast induration assuming noninferiority regarding locoregional recurrence.
A total of 1,854 consenting patients (50 Gy, n = 937; 40 Gy, n = 917) were enrolled from 2009-2014 from eight centers. There were 1,608 patients with adenocarcinoma and 246 patients with DCIS. The 3-year rates of induration were 11.8% (95% CI, 9.7% to 14.1%) in the 50-Gy group and 9.0% (95% CI, 7.2% to 11.1%) in the 40-Gy group (risk difference, -2.7%; 95% CI, -5.6% to 0.2%;
= .07). Systemic therapies and radiotherapy boost did not increase the risk of induration. Telangiectasia, dyspigmentation, scar appearance, edema, and pain were detected at low rates, and cosmetic outcome and patient satisfaction with breast appearance were high with either no difference or better outcome in the 40-Gy cohort compared with the 50-Gy cohort. The 9-year risk of locoregional recurrence was 3.3% (95% CI, 2.0% to 5.0%) in the 50-Gy group and 3.0% (95% CI, 1.9% to 4.5%) in the 40-Gy group (risk difference, -0.3%; 95% CI, -2.3% to 1.7%). The 9-year overall survival was 93.4% (95% CI, 91.1% to 95.1%) in the 50-Gy group and 93.4% (95% CI, 91.0% to 95.2%) in the 40-Gy group. The occurrence of radiation-associated cardiac and lung disease was rare and not influenced by the fractionation regimen.
Moderately hypofractionated breast irradiation of node-negative breast cancer or DCIS did not result in more breast induration compared with standard fractionated therapy. Other normal tissue effects were minimal, with similar or less frequent rates in the 40-Gy group. The 9-year locoregional recurrence risk was low.
In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing ...31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.
Staff working in intensive care units (ICUs) have faced significant challenges during the COVID-19 pandemic which have the potential to adversely affect their mental health.
To identify the rates of ...probable mental health disorder in staff working in ICUs in nine English hospitals during June and July 2020.
An anonymized brief web-based survey comprising standardized questionnaires examining depression, anxiety symptoms, symptoms of post-traumatic stress disorder (PTSD), well-being and alcohol use was administered to staff.
Seven hundred and nine participants completed the surveys comprising 291 (41%) doctors, 344 (49%) nurses and 74 (10%) other healthcare staff. Over half (59%) reported good well-being; however, 45% met the threshold for probable clinical significance on at least one of the following measures: severe depression (6%), PTSD (40%), severe anxiety (11%) or problem drinking (7%). Thirteen per cent of respondents reported frequent thoughts of being better off dead, or of hurting themselves in the past 2 weeks. Within the sample used in this study, we found that doctors reported better mental health than nurses across a range of measures.
We found substantial rates of probable mental health disorders, and thoughts of self-harm, amongst ICU staff; these difficulties were especially prevalent in nurses. Whilst further work is needed to better understand the real level of clinical need amongst ICU staff, these results indicate the need for a national strategy to protect the mental health, and decrease the risk of functional impairment, of ICU staff whilst they carry out their essential work during COVID-19.
Background
The coronavirus disease 2019 (COVID‐19) outbreak is an unprecedented global public health challenge, leading to thousands of deaths every day worldwide. Despite the epidemiological ...importance, clinical patterns of children with COVID‐19 remain unclear. The aim of this study was to describe the clinical, laboratorial, and radiological characteristics of children with COVID‐19.
Methods
The Medline database was searched between December 1st 2019 and April 6th 2020. No language restrictions were applied. Inclusion criteria were (a) studied patients younger than 18 years old; (b) presented original data from cases of COVID‐19 confirmed by reverse‐transcription polymerase chain reaction; and (c) contained descriptions of clinical manifestations, laboratory tests, or radiological examinations.
Results
A total of 38 studies (1124 cases) were included. From all the cases, 1117 had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0% were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty‐five (36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper airway infections were reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities in computed tomography were reported in 63.0% of cases. The most prevalent abnormalities reported were ground‐glass opacities, patchy shadows, and consolidations. Only one death was reported.
Conclusions
Clinical manifestations of children with COVID‐19 differ widely from adult cases. Fever and respiratory symptoms should not be considered a hallmark of COVID‐19 in children.
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