SummaryBackgroundPublic objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths.MethodsThis study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed.FindingsWe assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26–40) for CT, 43% (36–50) for MRI, and 30% (24–37) for the consensus radiology report; 10% (3–17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28–41) of 182 cases for CT reports, 76 (42%; 35–49) of 182 cases for MRI reports, and 88 (48%; 41–56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9–27), 21% (13–32), and 16% (10–25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16).InterpretationWe found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy.FundingPolicy Research Programme, Department of Health, UK.

Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples we characterized CD8 + T cell gene expression across a cohort of MM patients receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8 + transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over four-fold greater, with preferential induction of mitosis and interferon related genes. Early samples from patients with durable clinical benefit demonstrated over-expression of T cell receptor (TCR) encoding genes. By mapping TCR clonality we find responding patients have more large clones (those occupying >0.5% of repertoire) post-treatment than non-responding patients or controls, and this correlates with effector memory T cell percentage. Single-cell RNA-sequencing of eight post-treatment samples demonstrates large clones over-express genes implicated in cytotoxicity and characteristic of effector memory T cells including CCL4, GNLY, and NKG7 . The six-month clinical response to ICB in MM patients is associated with the large CD8 + T cell clone count 21 days after treatment and agnostic to clonal specificity, suggesting that post-ICB peripheral CD8 + clonality can provide information regarding long-term treatment response and potentially facilitate treatment stratification.

Secondary pleural infection is an important complication of pneumonia. Over 40% of Background -Standard treatment for pleural infection includes catheter drainage patients with community acquired pneumonia develop an associated pleural effusion 1 2 and and antibiotics. Tube drainage often fails if the fluid is loculated by fibrinous adhesions about 15% of these become secondarily infected. 1 2 In the UK pleural infection has a when surgical drainage is needed. Streptokinase may aid the process of pleural drain-mortality of about 20%.3 The transition of a simple effusion to the infected state is heralded age, but there have been no controlled trials to assess its efficacy.by fibrin deposition in the pleural cavity 4 and by indicators of white cell and bacterial metaMethods -Twenty four patients with infected community acquired parapneu-bolism within the effusion fluid (falling pH and glucose levels and rising levels of lactate monic effusions were studied. All had either frankly purulent/culture or Gram dehydrogenase).1 5-8 Once secondary infection of the pleural space has occurred, the mainstay stain positive pleural fluid (13 cases; 54%) or fluid which fulfilled the biochemical of management is effective drainage of the pleural collection.9 10 criteria for pleural infection. Fluid was drained with a 14 F catheter. The antiTraditionally, drainage of the pleural space has been achieved by simple aspiration, biotics used were cefuroxime and metronidazole or were guided by culture. catheter drainage, or thoracotomy with decortication or rib resection. 9 Of these approaches, Subjects were randomly assigned to receive intrapleural streptokinase, surgical procedures achieve the best drainage but carry an obvious morbidity. Less invasive 250 000 IU daily, or control saline flushes for three days. The primary end points drainage techniques are often limited by the loculation of pleural fluid by fibrinous septae, related to the efficacy of pleural drainage -namely, the volume of pleural fluid the presence of fibrinous clots within the empyema fluid which may block chest drains, and drained and the chest radiographic response to treatment. Other end points the development of an infected fibrinous pleural "rind". 9were the number of pleural procedures needed and blood indices of inflammation. Uncontrolled studies have suggested that intrapleural streptokinase may improve the drainResults -The streptokinase group drained more pleural fluid both during the days age of infected pleural effusions by lysis of the intrapleural fibrinous adhesions. [11][12][13][14][15][16][17][18][19] None of of streptokinase/control treatment (mean (SD) 391 (200) ml versus 124 (44) ml; these series includes a control group which makes interpretation of their results difficult. difference 267 ml, 95% confidence interval (CI) 144 to 390; p<0.001) and overall (2564 The weaknesses of these series means that this form of treatment is still controversial 20 and the (1663) ml versus 1059 (502) ml; difference 1505 ml, 95% CI 465 to 2545; p<0.01)...

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