Objective: Eosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitorrefractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated. Methods: Eleven adults with active EoO (.20 peak eosinophil number/high power field (hpf) and dysphagia) were randomised to 750 mg of mepolizumab (n = 5) or placebo (n = 6) and received two intravenous infusions, 1 week apart. Those not in complete remission (,5 peak eosinophil number/hpf) after 8 weeks received two further doses 4 weeks apart, 1500 mg of mepolizumab or placebo. The effect of mepolizumab was assessed clinically, endoscopically, histologically, and via blood and tissue biomarkers. Results: As assessed by immunofluorescence, a marked reduction of mean oesophageal eosinophilia (p = 0.03) was seen in the mepolizumab group (254%) compared with the placebo group (25%) 4 weeks after initiation of treatment. No further reduction of eosinophil numbers was observed in response to the two additional infusions in either group. Mepolizumab reduced tenascin C (p = 0.033) and transforming growth factor b1 (p = 0.05) expression in the oesophageal epithelial layer 13 weeks after initiation of treatment. Clinically, limited improvement of symptoms was seen, although a trend was seen between 4 and 13 weeks after initiation of mepolizumab treatment. Mepolizumab was well tolerated. Conclusions: Mepolizumab significantly reduced eosinophil numbers in oesophageal tissues in adult patients with active EoO, and changes in the expression of molecules associated with oesophageal remodelling were reversed. Minimal clinical improvement was achieved in a subgroup of patients with EoO. Mepolizumab had an acceptable safety profile, even at the high 1500 mg dose level. Trial registration number: NCT00274703Eosinophilic oesophagitis (EoO) is an emerging disease with a constantly increasing prevalence.

Objectives: To present a patient with acute hemorrhagic leukoencephalitis (AHLE) and a systematic review of the literature analyzing diagnostic procedures, treatment, and outcomes of AHLE. Methods: PubMed and Cochrane databases were screened. Papers published since 01/01/2000 describing adult patients are reported according to the PRISMA-guidelines. Results: A 59-year old male with rapidly developing coma and cerebral biopsy changes compatible with AHLE is presented followed by 43 case reports from the literature including males in 67% and a mean age of 38 years. Mortality was 47%. Infectious pathogens were reported in 35%, preexisting autoimmune diseases were identified in 12%. Neuroimaging revealed uni-or bihemispheric lesions in 65% and isolated lesions of the cerebellum, pons, medulla oblongata or the spinal cord without concomitant hemispheric involvement in 16%. Analysis of the cerebrospinal fluid showed an increased protein level in 87%, elevated white blood cells in 65%, and erythrocytes in 39%. Histology (reported in 58%) supported the diagnosis of AHLE in all cases. Glucocorticoids were used most commonly (97%), followed by plasmapheresis (26%), and intravenous immunoglobulins (12%), without a clear temporal relationship between treatment and the patients' clinical course. Conclusions: Although mortality was lower than previously reported, AHLE remains a life-threatening neurologic emergency with high mortality. Diagnosis is challenging as the level of evidence regarding the diagnostic yield of clinical, neuroimaging and laboratory characteristics remains low. Hence, clinicians are urged to heighten their awareness and to prompt cerebral biopsies in the context of rapidly progressive neurologic decline of unknown origin with the concurrence of the compiled characteristics. Future studies need to focus on treatment characteristics and their effects on course and outcome.

Objective We present a systematic review of the literature regarding types and anatomic distribution of fractures in association with generalized convulsive status epilepticus (GCSE) and convulsive seizures in adult patients accompanied by an illustrative case of a patient with GCSE and diffuse postictal pain from underlying bone fractures. Methods The library search engines PubMed and EMBASE were screened systematically using predefined search terms. All identified articles written in English were screened for eligibility by two reviewers. The preferred reporting items for systematic reviews and meta‐analyses guidelines were followed. Results The screening of 3145 articles revealed 39 articles meeting the inclusion criteria. Among all fractures, bilateral posterior fracture‐dislocations of the shoulders were reported most frequently (33%), followed by thoracic and lumbar vertebral compression fractures (29%), skull and jaw fractures (8%), and bilateral femoral neck fractures (6%). Risk factors for seizure‐related fractures are seizure severity, duration of epilepsy, the use of antiseizure drugs known to decrease bone density, and a family history of fractures. Based on these findings, a three‐step screening procedure is proposed to uncover fractures in the postictal state. All studies were retrospective without standardized screening methods for seizure‐associated fractures resulting in a very low level of evidence and a high risk of bias. Significance Posterior fracture‐dislocations of the shoulders, thoracic and lumbar vertebral compression, fractures of the skull and jaw, and bilateral femoral neck fractures are most frequently reported. Preventive measures including bone densitometry, calcium/vitamin D supplementation, and bisphosphonate therapy should be reinforced in epilepsy patients at risk of osteoporosis. As long as the effect of standardized screening of fractures is not investigated, it is too early to integrate such a screening into treatment guidelines. In the meantime, clinicians are urged to heighten awareness regarding seizure‐associated fractures, especially in patients with postictal pain, as symptoms can be unspecific and misinterpretation may impede rehabilitation.

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Respiratory infections following status epilepticus (SE) are frequent, and associated with higher mortality, prolonged ICU stay, and higher rates of refractory SE. Lack of airway protection may contribute to respiratory infectious complications. This study investigates the order and frequency of physicians treating a simulated SE following a systematic Airways-Breathing-Circulation-Disability-Exposure (ABCDE) approach, identifies risk factors for non-adherence, and analyzes the compliance of an ABCDE guided approach to SE with current guidelines. We conducted a prospective single-blinded high-fidelity trial at a Swiss academic simulator training center. Physicians of different affiliations were confronted with a simulated SE. Physicians (n = 74) recognized SE and performed a median of four of the five ABCDE checks (interquartile range 3–4). Thereof, 5% performed a complete assessment. Airways were checked within the recommended timeframe in 46%, breathing in 66%, circulation in 92%, and disability in 96%. Head-to-toe (exposure) examination was performed in 15%. Airways were protected in a timely manner in 14%, oxygen supplied in 69%, and antiseizure drugs (ASDs) administered in 99%. Participants’ neurologic affiliation was associated with performance of fewer checks (regression coefficient −0.49; p = 0.015). We conclude that adherence to the ABCDE approach in a simulated SE was infrequent, but, if followed, resulted in adherence to treatment steps and more frequent protection of airways.

Objective: This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE). Methods:Patients with anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended thirdline treatment, earlier (as first-or second-line treatment), and delayed (later as third-line treatment). Associations between timing of anesthesia and in-hospital outcomes were estimated by logistic regression.Results: Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio [OR] = .71, 95% confidence interval [CI] = .53-.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score

AIMS OF THE STUDY: To assess the frequency and variables associated with the need for ancillary tests to confirm suspected brain death in adult patients, and to assess the time from brain death to organ explantation in donors. We further sought to identify modifiable factors influencing the time between brain death and start of surgery. METHODS: Medical records and the Swiss organ allocation system registry were screened for all consecutive adult patients diagnosed with brain death at an intensive care unit of a Swiss tertiary medical centre from 2013 to 2020. The frequency and variables associated with the performance of ancillary tests (i.e., transcranial doppler, digital subtraction angiography, and computed tomography angiography) to confirm brain death were primary outcomes; the time from death to organ explantation as well as modifying factors were defined as secondary outcomes. RESULTS: Among 91 patients with a diagnosis of brain death, 15 were not explanted and did not undergo further ancillary tests. Of the remaining 76 patients, who became organ donors after brain death, ancillary tests were performed in 24%, most frequently in patients with hypoxic-ischaemic encephalopathy. The leading presumed causes of death (not mutually exclusive) were haemorrhagic strokes (49%), hypoxic-ischaemic encephalopathies (33%) and severe traumatic brain injuries (22%). Surgery for organ explantation was started within a median of 16 hours (interquartile range [IQR] 13–18) after death with delay increasing over time (nonparametric test for trend p = 0.05), mainly due to organ allocation procedures. Patients with brain death confirmed during night shifts were explanted earlier (during night shifts 14.3 hours, IQR 11.8–16.8 vs 16.3 hours, IQR 13.5–18.5 during day shifts; p = 0.05). CONCLUSIONS: Ancillary tests to confirm brain death are frequently performed, mainly in resuscitated patients. The delay to surgery for organ explantation after confirmed brain death was longer during day shifts, increased over time and was mainly determined by organ allocation procedures. The trial was registered on clinical trials.gov (identifier: NCT03984981)

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