Research Spotlight

Posted June 15th 2016

Il-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.

Yong-Jun Liu M.D.

Yong-Jun Liu M.D.

Ohne, Y., J. S. Silver, L. Thompson-Snipes, M. A. Collet, J. P. Blanck, B. L. Cantarel, A. M. Copenhaver, A. A. Humbles and Y. J. Liu (2016). “Il-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.” Nat Immunol 17(6): 646-655.

Full text of this article.

Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1beta was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1beta also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rbeta2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-gamma (IFN-gamma) and the loci encoding IL-5 and IL-13. Finally, IL-1beta potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1beta in facilitating ILC2 maturation and plasticity.


Posted June 15th 2016

Is it Fabry disease?

Raphael Schiffmann M.D.

Raphael Schiffmann M.D.

Schiffmann, R., M. Fuller, L. A. Clarke and J. M. Aerts (2016). “Is it fabry disease?” Genet Med: May 2016 [Epub ahead of print].

Full text of this article.

Fabry disease is caused by mutations in the GLA gene that lower alpha-galactosidase A activity to less than 25-30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual alpha-galactosidase A. The challenge is to determine which GLA variants can cause clinical manifestations related to Fabry disease. Here, we review the various types of GLA variants and recommend that pathogenicity be considered only when associated with elevated globotriaosylceramide in disease-relevant organs and tissues as analyzed by mass spectrometry. This criterion is necessary to ensure that very costly and specific therapy is provided only when appropriate.


Posted June 15th 2016

Outcomes after retroflexed gracilis muscle flap for vascular infections in the groin.

John F. Eidt M.D.

John F. Eidt M.D.

Ali, A. T., M. Rueda, S. Desikan, M. M. Moursi, R. An, H. Spencer, S. Rueda and J. F. Eidt (2016). “Outcomes after retroflexed gracilis muscle flap for vascular infections in the groin.” J Vasc Surg: May 2016 [Epub ahead of print].

Full text of this article.

OBJECTIVE: Multiple catheterizations and procedures on the femoral arteries can increase the risk of infection and eventual destruction of the overlying skin and subcutaneous tissue. Without adequate tissue coverage, vascular structures are exposed and, thus, vulnerable to disruption. This can lead to loss of limb and/or life and carries a significant mortality. We hypothesized that gracilis muscle flap (GMF) was a reliable adjunct in providing healthy tissue coverage for a complex surgical problem. METHODS: Retrospective review of charts was performed on all patients who had undergone GMF for groin infections at a tertiary care medical center. RESULTS: From 1997 to 2012, GMF was performed in 68 limbs (64 patients) by vascular surgeons for infectious etiology to cover the common femoral artery. At the time the GMF was placed, the femoral artery had synthetic graft/patch in 14 limbs, whereas 54 limbs had procedures with autologous conduit. Complete healing was achieved in 58 (85%) limbs. Treatment was deemed not successful in 10 limbs where patients continued to have persistent infection. Six out of 10 limbs had anastomosis disruption requiring emergent ligation of the common femoral artery. Nine patients died during the perioperative period (30-day). There were a total of 13 amputations in 12 patients. Limb salvage was achieved in 55 limbs (81%). Univariate analysis suggested that patients that had revascularization procedures with synthetic graft had a higher complication rate compared with autologous/vein reconstruction (24% vs 5%; P = .021). This group also has a higher rate of persistent infection compared with the autologous group (24% vs 2%; P = .006). Patients older than 75 years at the time of GMF had a higher incidence of GMF-related complications (57% vs 5%; P = .04). Multivariate analysis confirmed that presence of prosthesis led to higher incidence treatment failures and muscle flap complications at the surgical site (odds ratio, 6.6; P = .04; and odds ratio, 13.3; P = .03, respectively). CONCLUSIONS: GMF is technically simple to perform and provides durable soft tissue coverage with a high rate of healing for complex groin wounds even in the presence of synthetic conduit.


Posted June 15th 2016

Can children reduce delayed hospital arrival for ischemic stroke?: A systematic review of school-based stroke education.

Sonya A. Flanders M.S.N.

Sonya A. Flanders M.S.N.

Beal, C. C., S. A. Flanders and S. G. Bader (2016). “Can children reduce delayed hospital arrival for ischemic stroke?: A systematic review of school-based stroke education.” J Neurosci Nurs 48(3): E2-e13.

Full text of this article.

BACKGROUND: Delayed hospital arrival after onset of ischemic stroke reduces the number of patients eligible for tissue plasminogen activator, which must be given soon after stroke onset. There are conflicting results about the impact of mass media stroke education on timing of hospital arrival and tissue plasminogen activator administration rates. School-based programs are a new way to communicate stroke information. METHODS: A search of MEDLINE, CINAHL, PsycINFO, and ERIC databases from 1995 to 2014 identified school-based stroke education interventions. Twelve studies involving 3,312 children and 612 parents met criteria for review. RESULTS: School-based stroke education interventions were effective to improve knowledge of stroke symptoms among children in kindergarten through junior high. Improvement for stroke risk factors was less robust. Interventions were effective regardless of format, length, or who delivered the information. Despite low parental response rates in some studies, there was evidence that children transmitted stroke information to parents. CONCLUSIONS: School-based stroke education programs appear effective to improve knowledge of stroke symptoms. Research is needed to determine if children who participate are able to recognize stroke and respond appropriately by calling 911 in the real world. More study is needed about transfer of stroke knowledge from child to parent. Strategies to improve parent participation are needed.


Posted June 15th 2016

Effects of brief intervention on subgroups of injured patients who drink at risk levels.

Michael L. Foreman M.D.

Michael L. Foreman M.D.

Cochran, G., C. Field, M. Foreman, T. Ylioja and C. V. Brown (2016). “Effects of brief intervention on subgroups of injured patients who drink at risk levels.” Inj Prev 22(3): 221-225.

Full text of this article.

Alcohol-related injuries are a major source of admission for trauma care. Screening and brief intervention (SBI) for injured patients can result in decreased drinking and risk behaviors. It is not clear SBI is equally beneficial for all injured patients. A secondary data analysis of 553 patients admitted to two Level-1 trauma centers was conducted. Latent class analysis was used to identify patient subgroups based on injury-related risks and consequences of alcohol use. Intervention effects on drinking were examined among subgroups. Five subgroups were identified. Drinking improved in patients reporting multiple risks and injuries/accidents and drinking and driving. Patients that reported drinking and driving and taking foolish risks or fighting while drinking and taking foolish risks did not show improvements. Trauma centers may benefit from targeting interventions based on injury-related risks and consequences of alcohol use. Further research is needed to test bedside approaches for tailored interventions.