Implementing screening for social determinants of health using the Core 5 screening tool.

Social determinants of health (SDOH) have been documented to underpin 80% of overall health and are being increasingly recognised as key factors in addressing tertiary health outcomes. Yet, despite the widespread acceptance of the association of SDOH with health outcomes, more than two-thirds of hospitals do not screen for social risk factors that indicate individual-level adverse SDOH. Such screening for social risk factors represents the first step in connecting patients with resources and documents the prevalence of social needs. The aim of this project was to implement the Core 5 social risk screening tool and evaluate its efficacy and usability in identifying social risk factors in a presurgical spine population. Prior to this implementation, screening for social risk had not been performed. The Model for Improvement provided a framework for implementing and evaluating the Core 5 social risk screening tool. Methods included implementation of a patient self-report social risk screening tool, referral workflow to connect patients with needed resources and evaluation of staff feasibility in using the Core 5 tool. The results indicated that the screening tool identified patients with social risk factors and staff reported perceptions of efficacy and usability in clinical workflow. Overall, 52 of 88 (59%) of subjects in the presurgical spine population were effectively screened. Of these, five patients (10%) had identified social needs that needed to be addressed prior to surgery. The staff usability survey for the Core 5 tool demonstrated high acceptance and usability, with an average score of 4.4 (out of 5). Future work should evaluate the efficacy of the screening tool in other ambulatory and tertiary settings.

Effectiveness of standardised preoperative assessment and patient instructions on admission blood glucose for patients with diabetes undergoing orthopaedic surgery at a tertiary referral hospital.

Diabetes and hyperglycaemia affect a significant number of people and are associated with a variety of untoward effects, especially under physiological stress such as surgery. Due, in large part to limited evidence, clinical practice in monitoring blood glucose and treating hyperglycaemic conditions in the perioperative period is variable. We used Lean methodologies to implement a standardised approach to preoperative management of patients undergoing elective surgery in an effort to improve glycaemic control. Overall, we saw an appropriate increase in monitoring and a decrease in the rate of hyperglycaemia on presentation to the operating room. This approach may be useful in other care settings or patient populations, potentially contributing to improved glycaemic control and subsequent decrease in associated complications.

Scapholunate Interosseous Ligament Tears: Diagnostic Performance of 1.5 T, 3 T MRI, and MR Arthrography-A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: The study aimed to perform a systematic review and meta-analysis for evaluating the diagnostic accuracy of 1.5 Tesla and 3.0 Tesla magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA), in the detection of scapholunate interosseous ligament (SLIL) injury. MATERIALS AND METHODS: A literature search was performed (until July 2015) using the PubMed (MEDLINE), Embase, ISI Web of Science, Scopus, and conference proceedings. Original studies evaluating the diagnostic accuracy of MRI or MRA in the detection of SLIL injuries using arthroscopy or open surgery as the reference standard were included. RESULTS: Of the initial 930 published records and 103 conference proceedings, 24 studies (1902 MRI examinations) were included (median SLIL injury prevalence: 33% [interquartile range: 25-42]). Heterogeneity was detected for 1.5 T MRI (chi-square: 47.93, P < 0.001) but not for 3.0 T MRI (chi-square: 8.00, P value: 0.09) and MRA (chi-square: 14.54, P value: 0.34) studies. The sensitivities of 1.5 T MRI, 3.0 T MRI, and MRA for detection of SLIL injury were 45.7% (95% confidence interval: 40.1-51.4), 75.7% (66.8-83.2), and 82.1% (76.1-87.2), respectively. The specificities of 1.5 T MRI, 3.0 T MRI, and MRA for detection of SLIL injury were 80.5% (77.3-83.4), 97.1% (89.8-99.6), and 92.8% (90.2-94.9), respectively. The diagnostic odds ratios of 1.5 T MRI, 3.0 T MRI, and MRA for detection of SLIL injury were 5.56 (2.71-11.39), 23.23 (3.16-171.00), and 65.04 (32.89-128.62) (P value < 0.001), respectively. The results were consistent after addressing publication bias and sensitivity analyses. CONCLUSIONS: MRA is superior to 3.0 T MRI, and 3.0 T MRI is superior to 1.5 T MRI in terms of diagnostic performance. 3.0 T MRI has the highest specificity for the detection of SLIL injuries.

Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.

The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4-FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1 and FGF19 binding to FGFR4, 2) FGFR4-mediated signaling, colony formation, and proliferation in vitro, and 3) tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease.

Role of Marek's disease herpesvirus in the induction of tumours in Japanese quail (Coturnix coturnix japonica) by methylcholanthrene.

The QT35 cell line, established from 20-methylcholanthrene (MCA)-induced tumours in Japanese quail, is positive for Marek's disease virus (MDV), and therefore we examined whether MDV is important for the development of MCA-induced tumours. Japanese quail were inoculated with the JM16 strain of MDV at 1 or 3 days of age or left uninoculated. At 3 weeks of age, quail were injected in the breast muscle with 4 mg MCA in corn oil or corn oil alone. Quail were observed for tumours three times/week and at post mortem at 11 to 12 weeks of age. MDV DNA was detected by polymerase chain reaction (PCR) in spleens of 14/20 birds inoculated with JM16+corn oil and of 53/71 birds inoculated with JM16+MCA. Interestingly, 1/74 quail was positive in the MCA group alone for MDV DNA. Tumours were collected for histopathology, cell line development, and PCR and reverse transcriptase-PCR for the presence of MDV. Tumours developed in 38/83 MCA-treated and 32/85 JM16+MCA-treated quail. Fibrosarcomas without metastasis were the only tumours observed in the MCA-treated quail, while quail treated with JM16 and MCA developed undifferentiated tumours, fibrosarcomas, lymphosarcomas or combinations with or without metastasis. One out of 20 quail receiving JM16 alone developed a lymphosarcoma. Cell line development was not influenced by JM16. Tumours from MCA-treated quail were negative for MDV, while 19/29 were positive in the JM16+MCA group. MDV transcripts were present in 13/18 tumours examined in the JM16+MCA group. In conclusion, MDV did not affect tumour development but did influence tumour aggression and histological type.

BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken.

Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-B haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic BG1 locus. BG1 encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the BG1 3'-untranslated region (3'-UTR). The 3'-UTR of the BG1 allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that BG1 could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-B haplotype has been previously implicated. This work provides a mechanism by which MHC-B region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections.

Liver-specific activities of FGF19 require Klotho beta.

Hepatocyte function is regulated by members of the fibroblast growth factor (FGF) family of proteins, but little is known about the specific molecular mechanisms of this endocrine pathway. FGF19 regulates bile acid homeostasis and gall bladder filling; FGF19 binds only to FGF receptor 4 (FGFR4), but its liver-specific activity cannot be explained solely by the distribution of this receptor. Although it has been suggested that Klotho beta (KLB) may have a role in mediating FGF19 activity, we have provided for the first time definitive evidence that KLB is required for FGF19 binding to FGFR4, intracellular signaling, and downstream modulation of gene expression. We have shown that FGFR4 is widely distributed in mouse, whereas KLB distribution is more restricted. Liver was the only organ in which both genes were abundantly expressed. We show that in mice, FGF19 injection triggers liver-specific induction of c-Fos and repression of CYP7A1. The tissue-specific activity of FGF19 supports the unique intersection of KLB and FGFR4 distribution in liver. These studies define KLB as a novel FGFR4 coreceptor required for FGF19 liver specific functions.