Building new standards to prevent harm from medication errors in children with cancer

• Children with cancer receive many medications outside the hospital administered by their caregivers.
• The study by Walsh et al. shows the number and types of medication errors in these patients. The study includes data from three different centers.
• Importantly, the study shows the types of errors that cause harm. The authors describe how the harmful errors can be prevented.
• We suggest ways these results can be used to identify which patients and families will benefit from additional attention. Providing more help at clinic and in the home may help prevent harmful medication errors in children with cancer.

     

Physiological determinants of residual cerebral arterial pulsatility on best medical treatment after TIA or minor stroke

Cerebral arterial pulsatility is strongly associated with cerebral small vessel disease and lacunar stroke yet its dependence on central versus local haemodynamic processes is unclear. In a population-based study of patients on best medical managment, 4–6 weeks after a TIA or non-disabling stroke, arterial stiffness and aortic systolic, diastolic and pulse pressures were measured (Sphygmocor). Middle cerebral artery peak and trough flow velocities and Gosling’s pulsatility index were measured by transcranial ultrasound. In 981 participants, aortic and cerebral pulsatility rose strongly with age in both sexes, but aortic diastolic pressure fell more with age in men whilst cerebral trough velocity fell more in women. There was no significant association between aortic systolic or diastolic blood pressure with cerebral peak or trough flow velocity but aortic pulse pressure explained 37% of the variance in cerebral arterial pulsatility, before adjustment, whilst 49% of the variance was explained by aortic pulse pressure, arterial stiffness, age, gender and cardiovascular risk factors. Furthermore, arterial stiffness partially mediated the relationship between aortic and cerebral pulsatility. Overall, absolute aortic pressures and cerebral blood flow velocity were poorly correlated but aortic and cerebral pulsatility were strongly related, suggesting a key role for transmission of aortic pulsatility to the brain.     

Post-cardiac arrest intensive care in Sweden: A survey of current clinical practice

Background

European guidelines recommend targeted temperature management (TTM) in post-cardiac arrest care. A large multicentre clinical trial, however, showed no difference in mortality and neurological outcome when comparing hypothermia to normothermia with early treatment of fever. The study results were valid given a strict protocol for the assessment of prognosis using defined neurological examinations. With the current range of recommended TTM temperatures, and applicable neurological examinations, procedures may differ between hospitals and the variation of clinical practice in Sweden is not known.

Aim

The aim of this study was to investigate current practice in post-resuscitation care after cardiac arrest as to temperature targets and assessment of neurological prognosis in Swedish intensive care units (ICUs).

Methods

A structured survey was conducted by telephone or e-mail in all Levels 2 and 3 (= 53) Swedish ICUs during the spring of 2022 with a secondary survey in April 2023.

Results

Five units were not providing post-cardiac arrest care and were excluded. The response rate was 43/48 (90%) of the eligible units. Among the responding ICUs, normothermia (36–37.7°C) was applied in all centres (2023). There was a detailed routine for the assessment of neurological prognosis in 38/43 (88%) ICUs. Neurological assessment was applied 72–96 h after return of spontaneous circulation in 32/38 (84%) units. Electroencephalogram and computed tomography and/or magnetic resonance imaging were the most common technical methods available.

Conclusion

Swedish ICUs use normothermia including early treatment of fever in post-resuscitation care after cardiac arrest and almost all apply a detailed routine for the assessment of neurological prognosis. However, available methods for prognostic evaluation varies between hospitals.     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.