Symptomatic isolated axillary lymph node sarcoidosis: an unusual presentation.

An 82-year-old woman admitted following a 4-week history of feeling unwell, abdominal pain and constipation. Initial investigations revealed severe hypercalcaemia with suppressed parathyroid hormone and elevated 1,25-dihydroxycholecalciferol. ACE was also raised. CT scans of the head, chest, abdomen and pelvis were normal. Fluorodeoxyglucose-positron emission tomography scan showed metabolically active right axillary lymphadenopathy which when biopsied under ultrasound guidance confirmed sarcoidosis. The patient was started on high-dose prednisolone with resolution of symptoms within 2 weeks. Isolated lymph node sarcoidosis is uncommon, and the reported usual sites are lymph nodes in the head and neck. Rarely has it been reported in the axillary lymph nodes.

Excluding subarachnoid haemorrhage within 24 hours: to LP or not to LP?

BACKGROUND AND PURPOSE: Subarachnoid haemorrhage (SAH) is a potentially life-threatening cause of acute headache. Current conventional practice in the United Kingdom (UK) is for head computed tomography (CT) followed by cerebrospinal fluid (CSF) xanthochromia analysis if the head CT is normal. However, with increasing radiological accuracy, head CT alone may be sufficient to exclude SAH without requiring CSF xanthochromia for confirmation. This study aims to determine whether CSF xanthochromia is still required to confirm exclusion of SAH after normal head CT within a tertiary referral centre. METHODS: Data was obtained from Nottingham University Hospitals (NUH) NHS Trust databases on 999 patients presenting with symptoms suspicious of SAH from 2012 to 2015. All patients had CSF xanthochromia analysis when head CT was normal or inconclusive for suspected SAH. RESULTS: A total of 179 patients were diagnosed with SAH (17.9%). 176 patients were diagnosed radiologically and 3 patients required further investigations. The 3 of the 802 patients who underwent lumbar puncture (LP) and were identified as having had SAH presented more than 24 hours after ictus. When stratified according to the time of presentation, a normal CT head was observed in those who presented within 24 hours from ictus (sensitivity of 100% [95% CI 92.5-100] and negative predictive value of 100% [97.2-100]). CONCLUSION: Within a tertiary referral centre for SAH, a normal head CT has a very high negative predictive value to exclude SAH when carried out within 24 hours from ictus provided a 3rd generation CT scanner is utilised, and the scan is reported by a neuroradiologist. CSF xanthochromia analysis in this cohort may still be indicated in those presenting with a high clinical suspicion of SAH and in hospital settings where neuroradiologists or 3rd generation CT scanners are not easily accessible.

Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess potential biomarkers to predict outcomes for people with IPF. METHODS: PROFILE is a large prospective longitudinal cohort of treatment-naive patients with IPF. We adopted a two-stage discovery and validation design using patients from the PROFILE cohort. For the discovery analysis, we examined 106 patients and 50 age and sex matched healthy controls from Nottingham University Hospitals NHS Trust and the Royal Brompton Hospital. We did an unbiased, multiplex immunoassay assessment of 123 biomarkers. We further investigated promising novel markers by immunohistochemical assessment of IPF lung tissue. In the validation analysis, we examined samples from 206 people with IPF from among the remaining 212 patients recruited to PROFILE Central England. We used the samples to attempt to replicate the biomarkers identified from the discovery analysis by use of independent immunoassays for each biomarker. We investigated the predictive power of the selected biomarkers to identify individuals with IPF who were at risk of progression or death. The PROFILE studies are registered on ClinicalTrials.gov, numbers NCT01134822 (PROFILE Central England) and NCT01110694 (PROFILE Royal Brompton Hospital). FINDINGS: In the discovery analysis, we identified four serum biomarkers (surfactant protein D, matrix metalloproteinase 7, CA19-9, and CA-125) that were suitable for replication. Histological assessment of CA19-9 and CA-125 suggested that these proteins were markers of epithelial damage. Replication analysis showed that baseline values of surfactant protein D (46·6 ng/mL vs 34·6 ng/mL, p=0·0018) and CA19-9 (53·7 U/mL vs 22·2 U/mL; p<0·0001) were significantly higher in patients with progressive disease than in patients with stable disease, and rising concentrations of CA-125 over 3 months were associated with increased risk of mortality (HR 2·542, 95% CI 1·493-4·328, p=0·00059). INTERPRETATION: We have identified serum proteins secreted from metaplastic epithelium that can be used to predict disease progression and death in IPF. FUNDING: GlaxoSmithKline R&D and the UK Medical Research Council.

Lipoprotein X in a patient with cholestasis and hypertriglyceridaemia.

Hypertriglyceridaemia is an established cause of acute pancreatitis and responds to insulin therapy in addition to lipid lowering medication. We report a case of severe hypertriglycaeridemia of 149 mmol/L in a 36-year-old man with type 2 diabetes who presented to the surgical ward with abdominal pain due to pancreatitis and developed acute cholestasis, jaundice and eruptive xanthomata. His triglycerides improved to 3.8 mmol/L with sliding scale insulin within two weeks of in-hospital stay. However, his total cholesterol remained raised at 23.7 mmol/L. The lipoprotein electrophoresis confirmed the presence of lipoprotein X associated with bile obstruction, which contributed to an increase in total cholesterol. The total cholesterol normalized on improvement of his cholestasis.