Failure to Diagnose Phaeochromocytoma Preoperatively: A Case Report and Review of Diagnostic Criteria

We present a case in which phaeochromocytoma was not diagnosed preoperatively despite extensive investigation. There was significant haemodynamic instability during surgery. We review current diagnostic criteria with a view to reducing such a risk in future

Case Report Failure to Diagnose Phaeochromocytoma Preoperatively: A Case Report and Review of Diagnostic Criteria

We present a case in which phaeochromocytoma was not diagnosed preoperatively despite extensive investigation. There was significant haemodynamic instability during surgery. We review current diagnostic criteria with a view to reducing such a risk in future

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group

Background: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. Methods: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. Results: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. Conclusions: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting

Alx4 and Msx2 play phenotypically similar and additive roles in skull vault differentiation

Alx4 and Msx2 encode homeodomain-containing transcription factors that show a clear functional overlap. In both mice and humans, loss of function of either gene is associated with ossification defects of the skull vault, although the major effect is on the frontal bones in mice and the parietal bones in humans. This study was undertaken to discover whether Alx4 and Msx2 show a genetic interaction in skull vault ossification, and to test the hypothesis that they interact with the pathway that includes the Fgfr genes, Twist1 and Runx2. We generated Alx4(+/–)/Msx2(+/–) double heterozygous mutant mice, interbred them to produce compound genotypes and analysed the genotype–phenotype relationships. Loss of an increasing number of alleles correlated with an incremental exacerbation of the skull vault defect; loss of Alx4 function had a marginally greater effect than loss of Msx2 and also affected skull thickness. In situ hybridization showed that Alx4 and Msx2 are expressed in the cranial skeletogenic mesenchyme and in the growing calvarial bones. Studies of the coronal suture region at embyonic day (E)16.5 revealed that Alx4 expression was decreased, but not abolished, in Msx2(−/–) mutants, and vice versa; expression of Fgfr2 and Fgfr1, but not Twist1, was reduced in both mutants at the same stage. Runx2 expression was unaffected in the coronal suture; in contrast, expression of the downstream ossification marker Spp1 was delayed. Double homozygous pups showed substantial reduction of alkaline phosphatase expression throughout the mineralized skull vault; they died at birth due to defects of the heart, lungs and diaphragm not previously associated with Alx4 or Msx2. Our observations suggest that Alx4 and Msx2 are partially functionally redundant, acting within a network of transcription factors and signalling events that regulate the rate of osteogenic proliferation and differentiation at a stage after the commitment of mesenchymal stem cells to osteogenesis

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group.

BACKGROUND: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care. METHODS: A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of ≥80% for consensus was set for all statements. RESULTS: Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0°C and 37.5°C using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable. CONCLUSIONS: Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.NIHR Cambridge Biomedical Research Centre (BRC-1215-20014