A Change from a Spinal Immobilization to a Spinal Motion Restriction Protocol was Not Associated with an Increase in Disabling Spinal Cord Injuries.

BACKGROUND: Over the past decade, Emergency Medical Service (EMS) systems decreased backboard use as they transition from spinal immobilization (SI) protocols to spinal motion restriction (SMR) protocols. Since this change, no study has examined its effect on the neurologic outcomes of patients with spine injuries. OBJECTIVES: The object of this study is to determine if a state-wide protocol change from an SI to an SMR protocol had an effect on the incidence of disabling spinal cord injuries. METHODS: This was a retrospective review of patients in a single Level I trauma center before and after a change in spinal injury protocols. A two-step review of the record was used to classify spinal cord injuries as disabling or not disabling. A binary logistic regression was used to determine the effects of protocol, gender, age, level of injury, and mechanism of injury (MOI) on the incidence of significant disability from a spinal cord injury. RESULTS: A total of 549 patients in the SI period and 623 patients in the SMR period were included in the analysis. In the logistic regression, the change from an SI protocol to an SMR protocol did not demonstrate a significant effect on the incidence of disabling spinal injuries (OR: 0.78; 95% CI, 0.44 - 1.36). CONCLUSION: This study did not demonstrate an increase in disabling spinal cord injuries after a shift from an SI protocol to an SMR protocol. This finding, in addition to existing literature, supports the introduction of SMR protocols and the decreased use of the backboard.

Symptom Criteria for COVID-19 Testing of Heath Care Workers.

BACKGROUND: Symptom criteria for COVID-19 testing of heath care workers (HCWs) limitations on testing availability have been challenging during the COVID-19 pandemic. An evidence-based symptom criteria for identifying HCWs for testing, based on the probability of positive COVID-19 test results, would allow for a more appropriate use of testing resources. METHODS: This was an observational study of outpatient COVID-19 testing of HCWs. Prior to testing, HCWs were asked about the presence of 10 symptoms. Their responses were then compared to their subsequent pharyngeal swab COVID-19 polymerase chain reaction test results. These data were used to derive and evaluate a symptom-based testing criteria. RESULTS: A total of 961 HCWs were included in the analysis, of whom 225 (23%) had positive test results. Loss of taste or smell was the symptom with the largest positive likelihood ratio (3.33). Dry cough, regardless of the presence or absence of other symptoms, was the most sensitive (74%) and the least specific (32%) symptom. The existing testing criteria consisting of any combination of one or more of three symptoms (fever, shortness of breath, dry cough) was 93% sensitive and 9% specific (area unce the curve [AUC] = 0.63, 95% confidence interval [CI] = 0.59 to 0.67). The derived testing criteria consisting of any combination of one or more of two symptoms (fever, loss of taste or smell) was 89% sensitive and 48% specific (AUC = 0.75, 95% CI = 0.71 to 0.78). The hybrid testing criteria consisting of any combination of one or more of four symptoms (fever, shortness of breath, dry cough, loss of taste or smell) was 98% sensitive and 8% specific (AUC = 0.77, 95% CI = 0.73 to 0.80). CONCLUSION: An evidence-based approach to COVID-19 testing that at least includes fever and loss of taste or smell should be utilized when determining which HCWs should be tested.

Mosaic Tetrasomy 9p Associated With Inflammatory Bowel Disease.

The genetic basis of inflammatory bowel disease remains to be elucidated completely. Here we report on a patient with inflammatory bowel disease who has mosaic tetrasomy of the short arm of chromosome 9, a genomic region that harbours the type I interferon gene cluster. We show that increased interferon activation is present in peripheral blood and intestinal tissue from this patient, similar to previous reports of autoinflammatory organ damage driven by interferon activation in other patients with this chromosomal abnormality. To our knowledge, this is the first case of tetrasomy 9p-associated interferonopathy driving intestinal inflammation and highlights the role that type-I interferon pathways can play in the pathogenesis of intestinal inflammation.

A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity.

GPR55, an orphan G-protein coupled receptor, is activated by lysophosphatidylinositol (LPI) and the endocannabinoid anandamide, as well as by other compounds including THC. LPI is a potent endogenous ligand of GPR55 and neither GPR55 nor LPIs' functions in the brain are well understood. While endocannabinoids are well known to modulate brain synaptic plasticity, the potential role LPI could have on brain plasticity has never been demonstrated. Therefore, we examined not only GPR55 expression, but also the role its endogenous ligand could play in long-term potentiation, a common form of synaptic plasticity. Using quantitative RT-PCR, electrophysiology, and behavioral assays, we examined hippocampal GPR55 expression and function. qRT-PCR results indicate that GPR55 is expressed in hippocampi of both rats and mice. Immunohistochemistry and single cell PCR demonstrates GPR55 protein in pyramidal cells of CA1 and CA3 layers in the hippocampus. Application of the GPR55 endogenous agonist LPI to hippocampal slices of GPR55+/+ mice significantly enhanced CA1 LTP. This effect was absent in GPR55-/- mice, and blocked by the GPR55 antagonist CID 16020046. We also examined paired-pulse ratios of GPR55-/- and GPR55+/+ mice with or without LPI and noted significant enhancement in paired-pulse ratios by LPI in GPR55+/+ mice. Behaviorally, GPR55-/- and GPR55+/+ mice did not differ in memory tasks including novel object recognition, radial arm maze, or Morris water maze. However, performance on radial arm maze and elevated plus maze task suggests GPR55-/- mice have a higher frequency of immobile behavior. This is the first demonstration of LPI involvement in hippocampal synaptic plasticity.

FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance.

BACKGROUND: Irinotecan is a camptothecin analogue currently used in clinical practice to treat advanced colorectal cancer. However, acquired resistance mediated by the drug efflux pump ABCG2 is a recognized problem. We reported on a novel camptothecin analogue, FL118, which shows anticancer activity superior to irinotecan. In this study, we sought to investigate the potency of FL118 versus irinotecan or its active metabolite, SN-38, in both in vitro and in vivo models of human cancer with high ABCG2 activity. We also sought to assess the potency and ABCG2 affinity of several FL118 analogues with B-ring substitutions. METHODS: Colon and lung cancer cells with and without ABCG2 overexpression were treated with FL118 in the presence and absence of Ko143, an ABCG2-selective inhibitor, or alternatively by genetically modulating ABCG2 expression. Using two distinct in vivo human tumor animal models, we further assessed whether FL118 could extend time to progression in comparison with irinotecan. Lastly, we investigated a series of FL118 analogues with B-ring substitutions for ABCG2 sensitivity. RESULTS: Both pharmacological inhibition and genetic modulation of ABCG2 demonstrated that, in contrast to SN-38, FL118 was able to bypass ABCG2-mediated drug resistance. FL118 also extended time to progression in both in vivo models by more than 50% compared with irinotecan. Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance. CONCLUSIONS: Our results suggest that in contrast to SN-38 and topotecan, FL118 is a poor substrate for ABCG2 and can effectively overcome ABCG2-mediated drug resistance. Our findings expand the uniqueness of FL118 and support continued development of FL118 as an attractive therapeutic option for patients with drug-refractory cancers resulting from high expression of ABCG2.