Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

BackgroundMonitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs.Hypothesis/objectiveAssessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location. Intraparenchymal transducer placement is associated with more adverse effects.AnimalsSeven adult, bred-for-research dogs.MethodsIn a prospective investigational study, microsensor ICP transducers were inserted into subdural and intraparenchymal locations at defined rostral or caudal locations within the rostrotentorial compartment under general anesthesia. Mean arterial pressure and ICP were measured continuously during physiological maneuvers, and for 20 hours after anesthesia.ResultsBaseline mean ± SD values for ICP and cerebral perfusion pressure were 7.2 ± 2.3 and 78.9 ± 7.6 mm Hg, respectively. Catheter position did not have a significant effect on ICP measurements. There was significant variation from baseline ICP accompanying physiological maneuvers (P < .001) and with normal activities, especially with changes in head position (P < .001). Pathological sequelae were more evident after intraparenchymal versus subdural placement.Conclusions and clinical importanceUse of a microsensor ICP transducer was technically straightforward and provided ICP measurements within previously reported reference ranges. Results support the use of an accessible dorsal location and subdural positioning. Transient fluctuations in ICP are normal events in conscious dogs and large variations associated with head position should be accounted for when evaluating animals with intracranial hypertension

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

BackgroundMonitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs.Hypothesis/objectiveAssessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location. Intraparenchymal transducer placement is associated with more adverse effects.AnimalsSeven adult, bred-for-research dogs.MethodsIn a prospective investigational study, microsensor ICP transducers were inserted into subdural and intraparenchymal locations at defined rostral or caudal locations within the rostrotentorial compartment under general anesthesia. Mean arterial pressure and ICP were measured continuously during physiological maneuvers, and for 20 hours after anesthesia.ResultsBaseline mean ± SD values for ICP and cerebral perfusion pressure were 7.2 ± 2.3 and 78.9 ± 7.6 mm Hg, respectively. Catheter position did not have a significant effect on ICP measurements. There was significant variation from baseline ICP accompanying physiological maneuvers (P < .001) and with normal activities, especially with changes in head position (P < .001). Pathological sequelae were more evident after intraparenchymal versus subdural placement.Conclusions and clinical importanceUse of a microsensor ICP transducer was technically straightforward and provided ICP measurements within previously reported reference ranges. Results support the use of an accessible dorsal location and subdural positioning. Transient fluctuations in ICP are normal events in conscious dogs and large variations associated with head position should be accounted for when evaluating animals with intracranial hypertension