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As the COVID-19 pandemic progresses neurological complications are increasingly being reported. Posterior reversible encephalopathic syndrome (PRES) is a clinico-radiological syndrome characterised by headache, visual loss, encephalopathy and seizures, and the development of vasogenic white matter lesions in a classically parieto-occipital distribution. The pathophysiology of PRES is incompletely understood, but both hyperperfusion secondary to hypertension, and endothelial dysfunction leading to vasogenic oedema have been implicated. Here we present a case series of 2 hospitalised COVID-19 patients with markedly different disease severity, both of whom developed PRES. Patient 1 presented with confusion and headache without significant systemic features, on a background of known hypertension. Patient 1 had a single generalised seizure and was managed with levetiracetam and antihypertensives, and showed complete clinical recovery. In contrast, patient 2 presented with respiratory distress, metabolic disturbance and encephalopathy requiring critical care admission. Patient 2 had a protracted admission, developing marked visual disturbance and generalised seizures requiring multiple agents. In both cases initial CT/MRI showed characteristic posterior PRES-like leukoencephalopathy with resolution on follow-up imaging, and CSF biochemistry, cytology and virology were normal. This case series highlights the potential for neurological complications in COVID-19 patients across the spectrum of disease severity.Philip.hayton@nhs.net

The emergence of Japanese encephalitis virus (JEV) in eastern Australia in 2022 caused extensive reproductive disease in pigs and is a threat to public health. Groups of weaned piglets were experimentally infected with the Australian outbreak strain of JEV (genotype 4). All pigs challenged at 5 weeks of age were infected after an intradermal injection of 1 × 105.5 (n = 4) or 1 × 104.5 TCID50/pig (n = 5). Intranasal instillation was less effective at this age, infecting 3/4 pigs with the same higher dose and 1/5 with the lower dose. Intradermal injection using 1 × 105.0 TCID50/pig also infected 9/9 pigs at 11 weeks of age. Infection in all cases was confirmed by qRT-PCR of blood samples, which identified a viremia peak at 3–4 days and detected JEV-specific antibodies as early as 5 days after the challenge. The detection of JEV in oral and nasal swabs and in saliva from chew ropes was less consistent. JEV was detected in the tonsils of 21/22 infected pigs and was isolated from the tonsils of 9/9 pigs sampled 19 days after the challenge at 11 weeks of age. The infected pigs showed no clinical signs other than pyrexia on Days 4–6. Histopathology consistent with JEV infection was evident in the nervous tissues of all but two pigs sampled 28 days after the challenge and was characterized by meningitis, encephalitis and gliosis throughout the brain. Serological studies showed extensive cross-reactivity between JEV and Murray Valley encephalitis virus using blocking ELISAs. However, the determination of limiting-dilution titres allowed for the identification of the infecting virus. This in vivo infection model will be useful in evaluating JEV vaccines and for comparative pathogenesis studies with other JEV genotypes.

The presence of a wildlife reservoir for Mycobacterium bovis complicates the eradication of bovine tuberculosis (BTB) from domestic cattle populations. For the BTB eradication program in Fiji, there is concern about the small Indian mongoose (Herpestes auropunctatus), which is overabundant and in direct contact with cattle. Consequently, a survey of mongooses trapped on three BTB affected dairy farms led to necropsy of 85 mongooses during January–February 2017. Thirty (35%) mongooses had gross pathological changes including possible granulomas detected at necropsy, and tissues from these animals were taken for histopathological examination. Granulomatous lesions were present in 53% of animals examined histopathologically but acid-fast bacilli were not observed and the majority of lesions in lung and kidney were associated with the nematodes Pulmostrongylus herpestis and Capillaria sp., respectively. Nevertheless, assuming test sensitivity of 35% for the current study, from this sample of 85 mongooses it can be concluded with 95% confidence that if present in the mongoose population susceptible to trapping, M. bovis prevalence was ≤10%. The prevalence of intercurrent lesions raised concerns about gross pathology as a screening test for M. bovis infection in mongooses in Fiji, and therefore pathogen detection methods such as bacterial culture and direct tissue PCR are recommended for future surveys. These are needed to completely rule out the mongoose as a reservoir host for M. bovis in Fiji.

IntroductionCONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC).MethodsThe treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic (‘COVID’ cohort, 16/03/2020-10/05/2020), with 12-month follow-up.ResultsAmong 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8–4.1) vs. 4.4 (IQR 3.6–5.2) months, p = 0.093).ConclusionPathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

Idiopathic intracranial hypertension (IIH) is a condition of raised CSF pressure without any apparent structural lesion or problem with venous drainage. We present a lady who was initially diagnosed with IIH, but was later found to have an unusual brain tumour.A 30 year old lady presented in 2012 with a three month history of headaches, nausea and vomiting, two weeks of blurred vision and one week of double vision on looking left. Visual acuity was 6/6 on the right and 6/9 on the left with a left relative afferent pupillary defect, bilateral papilloedema and left lateral rectus palsy. MRI showed ventriculomegaly. Lumbar puncture revealed normal constituents with an opening pressure of 60 cm H2O. In the absence of a space occupying lesion or venous occlusion a diagnosis of IIH was made. A ventriculoperitoneal shunt was inserted and she was discharged but didn't attend follow-up. She re-presented in May 2014 with headaches and intermittent left arm and leg numbness. An MRI revealed widespread CSF pathway infiltration, leptomeningeal enhancement, tonsillar descent and an extensive cervical syrinx. She underwent posterior fossa decompression and biopsy, which was histologically confirmed as pilocytic astrocytoma.Ventriculomegaly is not a feature of IIH. This case illustrates the wide differential of raised CSF pressure and that careful assessment of brain imaging and CSF constituents is required prior to making what is, in effect, a diagnosis of exclusion.

Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.Competing Interest StatementThe authors have declared no competing interest.