On February 24, 2022, Russia launched a full-scale invasion of Ukraine that dominated headlines around the world. Millions of Ukrainians would flee the country, and a third of the population would be ...displaced. In the days following the invasion, Swedish migration expert Gregg Bucken-Knapp sent text messages to his Ukrainian colleagues, offering support and assistance. These were their responses. In a series of graphic vignettes, Messages from Ukraine takes the words of Ukrainian migration professionals and transforms them into snapshots of how war affects the lives of everyday people: those who are forced to flee home and seek safety elsewhere, those who choose to stay and volunteer or fight, those who witness events unfolding from afar, and those who find themselves trapped in cities under siege. Messages from Ukraine captures a moment in time to tell a timeless story about war, displacement, determination, and resilience. Proceeds from the sale of Messages from Ukraine will go to the Canada-Ukraine Foundation, a national charitable foundation that provides humanitarian aid to the people of Ukraine.
The war in Ukraine has altered the course of global history. These authors explore how.When Vladimir Putin's forces sought to conquer Ukraine in February 2022, they did more than threaten the ...survival of a vulnerable democracy. The invasion unleashed a crisis that has changed the course of world affairs. This conflict has reshaped alliances, deepened global cleavages, and caused economic disruptions that continue to reverberate around the globe. It has initiated the first great-power nuclear crisis in decades and raised fundamental questions about the sources of national power and military might in the modern age. The outcome of the conflict will profoundly influence the international balance of power, the relationship between democracies and autocracies, and the rules that govern global affairs. In War in Ukraine, Hal Brands brings together an all-star cast of analysts to assess the conflict's origins, course, and implications and to offer their appraisals of one of the most geopolitically consequential crises of the early twenty-first century. Essays cover topics including the twists and turns of the war itself, the successes and failures of US strategy, the impact of sanctions, the future of Russia and its partnership with China, and more.Contributors: Anne Applebaum, Joshua Baker, Alexander Bick, Hal Brands, Daniel Drezner, Peter Feaver, Lawrence Freedman, Francis Gavin, Brian Hart, William Inboden, Andrea Kendall-Taylor, Michael Kimmage, Michael Kofman, Stephen Kotkin, Mark Leonard, Bonny Lin, Thomas Mahnken, Dara Massicot, Michael McFaul, Robert Person, Kori Schake, and Ashley Tellis.
IntroductionSporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. ...We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.Methods501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.ResultsShort survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.ConclusionsThis study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.
Bickerstaff’s Brainstem Encephalitis (BBE) is a condition causing impairment of sensorium in association with ophthalmoplegia and ataxia. Here we present a case of BBE presenting with bilateral vocal ...cord paralysis.A 35-year-old female presented with a sore throat and shortness of breath in the context of a fall and ankle injury the previous day. She became confused and agitated in hospital. Several hours after pres- entation she was found cyanosed with stridulous breathing (with normal saturations). Fibre-optic nasola- ryngoscopy revealed bilateral vocal cord palsy. She was intubated and transferred to ICU. Investigations including a full infection screen, CSF analysis and MRI were normal and non-diagnostic. Examination during a sedation hold revealed a unilateral third, fourth, and bilateral sixth and seventh cranial nerve palsies. She had flaccid quadriparesis and was globally areflexic. Nerve conduction studies showed a motor predominant polyneuropathy. A diagnosis of BBE was made based on the clinical findings with acute confusion. She was treated with plasma exchange and immunoglobulins and was discharged with almost complete recovery.There are no previous case reports of vocal cord paralysis being the presenting feature of BBE. Neurologi- cal disease accounts for only 12% of cases of bilateral cord palsy. These causes may be systemic such as myasthenia gravis or diphtheria, or focal affecting the nucleus ambiguus in the medulla. However, clini- cians must recognise these cases promptly to ensure adequate investigation and treatment.
Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterised by reduced GCS/confusion, seizures and visual disturbance along with characteristic MRI findings. Autoimmune disorders ...have been identified in one third of patients with PRES.Here we discuss a 33-year-old female with SLE, who presented with reduced GCS and arm weakness. She had an AKI and metabolic acidosis and was admitted to ICU. Although the patients GCS improved, ongoing upper limb weakness remained. MRI imaging to rule out cerebral lupus, showed high T2 and FLAIR signal within the deep white matter of the occipital, frontal and parietal lobes. This was suggestive of PRES. Whilst in ICU the patient developed hypertension and was started on amlodipine. The patient also had a long history of immunosuppression with mycophenolate, hydroxychloroquine and rituximab. A neurology referral was sent for further advice.Although the name suggests, PRES is often not completely reversible and is not limited to the posterior cerebral cortex, as seen here. It still remains unclear whether it is the autoimmune condition or treatment of these conditions with immunosuppressant’s that is the primary association. Case reports linking PRES with immunosuppressant therapy have shown an early onset of symptoms following treatment, rather than years.
PurposeOptic neuritis (ON) is a common feature of Multiple Sclerosis (MS). DARC is an intravenous fluo- rescent-tagged annexin V (ANX776) identifying cell stress and apoptosis with retinal imaging. ...We aimed to differentiate DARC spots in ON from healthy subjects using descriptive measures (DM) of DARC spots identified by a convolutional neural network-aided algorithm (CNN-AA).MethodsDARC spots were identified from anonymised DARC images obtained from ON (n=12; mean age=46) and healthy (n=68; mean age=48) participants after ANX776 administration using the CNN-AA (ISRCTN10751859). DM characteristics: mean, standard deviation (std), skew, kurtosis, coefficient of variation (cv), Euclidean distance from the nearest blood vessel (bvdist) and the 7Hu moments, were analysed on ON (n = 357) and healthy (n = 2457) eyes using two-tailed student t-tests. Distributions of spot metrics were analysed using two-sample Kolmogorov-Smirnov test.ResultsThe mean, cv and kurtosis (p £ 0.0001) and hu1 and std (p £ 0.001) were found to be significantly different between DARC spots in ON and healthy controls. Distributions of the individual DM metrics analysed, showed a significant difference (p £ 0.0001) between ON and healthy spots for the same variables (mean, cv, kurtosis, hu1 and std).ConclusionDM of DARC spots distinguish ON and healthy subjects. Further studies with larger ON groups are needed to replicate this finding.
ObjectiveTo calculate the efficiency index (EI), a recently described metric based on test accuracy and inaccuracy, for dementia diagnosis using the mini-Addenbrooke’s Cognitive Examination (MACE), ...and to compare this with balanced EI (BEI) and unbiased EI (UEI), based on balanced and unbiased accuracy and inaccuracy measures respectively. All efficiency indexes have boundary values of 0 and ∞; inflection point at 1; where value >1 indicates correct diagnostic classification and <1 indicates incorrect classification.ResultsUsing the dataset from a large (N = 755) prospective pragmatic study of MACE, in which 114 patients received criterion diagnosis of dementia, EI was 2.81 at the optimal MACE cut-off (≤20/30, deter- mined by maximal Youden index). BEI was 4.24 and UEI was 0.61 at this cut-off. Plotting values of EI, BEI, and UEI across the range of MACE cut-offs (≤11/30 to ≤29/30), UEI values were lowest, EI values were highest at lower cut-offs and BEI values were highest at higher cut-offs. Adjusting for dementia prevalence (fixed BEI), both EI and UEI values increased with dementia prevalence, with EI>UEI.ConclusionsEfficiency indexes are easily calculatedThese unitary metrics may have greater utility than others in communicating risk of correct diagnosis versus misdiagnosis of test outcomes.
Queen Elizabeth HospitalIntroductionCannabidiol (CBD) is approved for the treatment of refractory epilepsy associated with Dravet and Lennox-Gastaut syndromes. Affected individuals have co-morbid ...intellectual disability, making serum monitoring challenging. Those prescribed CBD at the Queen Elizabeth Hospital underwent at least one face to face appointment in the twelve months preceding treatment. Many were initiated on CBD remotely, in keeping with trust guidance to reduce the burden of face-to-face consultations during the Pandemic.NICE recommends liver function test (LFT) monitoring in those prescribed CBD at baseline, 1, 3 and 6 months, then periodically thereafter 2. All patients initiating CBD were offered LFT on site, with a recom- mendation to GPs to continue LFT monitoring in the community.Aim To assesses whether CBD patients undergo LFT monitoring in keeping with NICE guidance.ResultsOf thirty patients prescribed Cannabidiol for a minimum of six months, sixteen (53%) had LFTs undertaken at least once. Twelve (75%) were conducted by their GP. Three patients had abnormal LFT at some stage which normalised within six months of initiation of treatment.RecommendationsRegular liaison with community healthcare providers about LFT protocols and access to finger prick testing (both on site and community) would potentially facilitate regular serum monitoring.
A 31-year old male with a background of occasional Migraine without aura and mechanical lower back pain, presented with recurrent transient episodes of generalised headache, speech impairment, ...confusional state, and hemi-body sensory-motor symptoms. He had 9-10 episodes over a 2-week period. These were sudden, non-stereotypical, and lasted between 30-120 minutes. He was well in between and the very first episode happened just before his travel to the Canaries for holidays. He had 3 separate admissions with these episodes.Routine blood tests were normalContrast CT head and MRI brain showed transient generalised leptome- ningeal enhancement, CSF showed sequential WCC of 420 and 200 before returning to normal. Repeat EEG showed no epileptiform abnormality. Extensive tests for infectious agents including viral serology were all either negative or suggestive of previous exposure. Only HSV-7 PCR was positive. Inflammatory and paraneoplastic tests were negative. He fully recovered from these in 2 months with no sequelae.The clinical Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lympho- cytosis (HaNDL) is well described, rarely seen and poorly understood. Proposed mechanisms include migraine pathophysiology, post-infectious and immunological phenomenon. This is the first report of an active HSV-7 infection, causing HaNDL.
GNE myopathy is an adult-onset autosomal recessive distal myopathy uniquely characterised by quadri- ceps sparing. It was previously described in Japanese patients and a large ethnic cluster was ...identified in Jews originating from Iran. Since then, it is recognised to have a worldwide prevalence with multiple pathogenic variants. While compound heterozygous c.830G>A GNE myopathy has previously been reported, homozygous disease has only previously been reported in a non-Jewish Iranian cohort and the Indian subcontinent. Here we report a case of apparent homozygous c.830G>A GNE myopathy in a non-Jewish Iraqi patient.
