Correlation of ACR TI-RADS and Patient Outcomes in a Real-World Cohort Presenting for Thyroid Ultrasonography.

Context: The American College of Radiology Thyroid Image Reporting and Data System (ACR TI-RADS) was developed to predict malignancy risk in thyroid nodules using ultrasound features. TI-RADS was derived from a database of patients already selected for fine-needle aspiration (FNA), raising uncertainty about applicability to unselected patients. Objective: We aimed to assess the effect of ACR TI-RADS reporting in unselected patients presenting for thyroid ultrasound in a real-world setting. Methods: Records for all patients presenting for thyroid ultrasonography in Canterbury, New Zealand, were reviewed across two 18-month periods, prior to and after implementation of TI-RADS reporting. Patient outcomes were compared between the 2 periods. Malignancy rates were calculated for nodules 10 mm or larger with a definitive FNA or histology result. Results: A total of 1210 nodules were identified in 582 patients prior to implementation of TI-RADS; 1253 nodules were identified in 625 patients after implementation of TI-RADS. TI-RADS category was associated with malignancy rate (0% in TR1 and TR2, 3% in TR3, 5% in TR4, 12% in TR5; P = .02); however, 63% of nodules were graded TR3 or TR4, for which malignancy rate did not meaningfully differ from baseline risk. After implementation of TI-RADS there was a small reduction in the proportion of patients proceeding to FNA (49% vs 60%; P < .01) or surgery (14% vs 18%; P < .05), with no difference in cancer diagnoses (3% vs 4%, not significant). Conclusion: TI-RADS category is associated with malignancy rate and may alter clinical decision-making in a minority of patients; however, it is nondiscriminatory in the majority of nodules. In this study of unselected patients, nodules classified as TR5 and thus considered "highly suspicious" for cancer had only a modest risk of malignancy.

Cyclic peptides target the aromatic cage of a PHD-finger reader domain to modulate epigenetic protein function.

Plant homeodomain fingers (PHD-fingers) are a family of reader domains that can recruit epigenetic proteins to specific histone modification sites. Many PHD-fingers recognise methylated lysines on histone tails and play crucial roles in transcriptional regulation, with their dysregulation linked to various human diseases. Despite their biological importance, chemical inhibitors for targeting PHD-fingers are very limited. Here we report a potent and selective de novo cyclic peptide inhibitor (OC9) targeting the Nε-trimethyllysine-binding PHD-fingers of the KDM7 histone demethylases, developed using mRNA display. OC9 disrupts PHD-finger interaction with histone H3K4me3 by engaging the Nε-methyllysine-binding aromatic cage through a valine, revealing a new non-lysine recognition motif for the PHD-fingers that does not require cation-π interaction. PHD-finger inhibition by OC9 impacted JmjC-domain mediated demethylase activity at H3K9me2, leading to inhibition of KDM7B (PHF8) but stimulation of KDM7A (KIAA1718), representing a new approach for selective allosteric modulation of demethylase activity. Chemoproteomic analysis showed selective engagement of OC9 with KDM7s in T cell lymphoblastic lymphoma SUP T1 cells. Our results highlight the utility of mRNA-display derived cyclic peptides for targeting challenging epigenetic reader proteins to probe their biology, and the broader potential of this approach for targeting protein-protein interactions.

The Effect of Universal Newborn Hearing Screening on Spoken Language after Cochlear Implantation.

BACKGROUND: The universal newborn hearing screening (UNHS) was fully implemented across New Zealand by 2010 to improve outcomes for children with prelingual deafness. A previous audit undertaken by our center, the Southern Cochlear Implant Programme (SCIP), demonstrated that UNHS has significantly reduced the time to referral and surgery for cochlear implants in these children. AIMS: This study aims to evaluate the relationship between earlier implantation and language development, the time taken to achieve age-appropriate language, and the effect of socioeconomic status on language skills. METHODS: This is a retrospective cohort study comparing prelingual children with severe to profound bilateral hearing loss who underwent cochlear implantation in SCIP before and after the introduction of the UNHS. The language outcomes were assessed using the Preschool Language Scale and/or the Peabody Picture Vocabulary Test. For the purpose of our study, the standard scores of these tests were expressed as global language scores (GLS). GLSs between 85 and 115 are considered within normal range for age. The socioeconomic status was categorized based on the New Zealand Index of Deprivation (NZDep). RESULTS: Children in the post-UNHS group (46/95 children) were referred to SCIP and received CI at a significantly earlier age (mean = 7 vs 20 mo, p = 8.95E-10, and mean = 13 vs. 24.7 mo, p = 1.43E-07). At 2 years postimplantation, the GLS was significantly higher in the post-UNHS group (mean scores = 93.3 vs. 79.1, p = 0.0213). The scores remained statistically higher in the post-UNHS group when assessed at 3 and 4 years postimplantation. At 2, 3, and 4 years postimplantation, there is a significant linear decrease in GLS with increasing age at cochlear implantation. We found no correlation between NZDep and GLS. CONCLUSION: Children identified through UNHS have the advantage of earlier diagnosis, earlier hearing intervention, and longer duration with the implants, and they can achieve age-appropriate spoken language after 2 years of implantation.

An algorithm for the management of traumatic abdominal wall hernia based on a 9-year review.

BACKGROUND: Traumatic abdominal wall hernia (TAWH) is a rare consequence of blunt abdominal trauma, usually in the setting of multitrauma, with little consensus or guidelines for management. We present a case series of patients with traumatic herniae over a 9-year period and a suggested management algorithm. METHOD: Retrospective review of all patients with TAWH from 1st January 2011 to 31st December 2019 at a Level 1 adult Major Trauma Centre. Clinical presentation, surgical intervention and complications and recurrence were analysed. RESULTS: Forty-seven patients were found to have TAWH, 0.5% of all major trauma admissions. Thirty (63.8%) were repaired, 12 acutely, 11 semi-acute and 7 delayed. All but 1 (fall>3 m) were transport associated, with a median Injury Severity Score (ISS) of 29. Follow-up data for operative cases were available for all but one (97%). Seven (23.3%) cases had a recurrence, more common in the acute repair group (33.3%) compared to semi-acute (18.2%), and elective group (14.3%). CONCLUSION: TAWH is a rare but potentially serious consequence of blunt abdominal trauma. This series has favoured earlier repair for anterior TAWH, or all those undergoing a laparotomy for other reasons, and elective repair for lumbar or lateral TAWH that do not require a laparotomy for other conditions. We present our preferred algorithm for management, accepting that there are many available strategies in this heterogeneous group of injuries. Loss of follow up and recurrence are a concern, and clinicians are encouraged to develop processes to ensure that TAWH are not a 'forgotten hernia'.

A scoping review of social determinants of health curricula in post-graduate medical education.

Social determinants of health are responsible for 50% of ill health. The Royal College of Physicians and Surgeons of Canada CanMEDS role of "physician advocate" requires physicians to attain competency in this particular domain, but physician trainees feel this is not well covered in their training programs. This study performed a scoping review of social determinants of health curricula that had been described, implemented and evaluated in post-graduate medical education. A search using MEDLINE(OvidSP) database, with search terms "residency," "curriculum," and "social determinants" with no age, language, and publication date restrictions was done. Researchers identified a total of 12 studies, all from the United States, in internal medicine (n=4), pediatrics (n=4), family medicine (n=2), or multiple (n=2) residency programs. Most curricula (n=8, 67%), were longitudinal, and most contained both patient or community exposure (n=11, 92%) and/or classroom-based components (n=10, 83%). Most (78%) curricula improved participant related outcomes, including exam performance, awareness regarding personal practice, confidence, improved screening for social determinants of health and referral to support services. Program specific outcomes were frequently positive (50%) and included resident satisfaction and high course evaluation scores, high representation of resident and faculty from minority groups, applicability of training to underserviced populations, and improved engagement of marginalized community members. When evaluated, academic outcomes were always positive, and included acceptance of scholarly projects to national conferences, publication of research work, grants earned to support health projects, local or national awards for leadership and community engagement, and curriculum graduates later pursuing related Masters degrees and/or establishing medical practices in underserved areas. Only one study reported a patient-related outcome, with advice provided by health care providers considered by patients to be helpful. Researchers used these results to design recommendations for creation of a post-graduate curriculum to address social determinants of health were provided.

Dietary lipids alter the effect of steroids on transport of glucose after intestinal resection: Part II. Signalling of the response.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. Budesonide (Bud) increases the jejunal D-glucose uptake, and this effect is prevented through a polyunsaturated fatty acid (PUFA) diet. This study was undertaken to assess the possible signalling effect of budesonide, prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids. METHODS: Northern blots were performed. RESULTS: Steroids reduced the jejunal but not the ileal expression of proglucagon. Ornithine decarboxylase (ODC) expression was reduced in the jejunum. CONCLUSIONS: c-jun, ODC, and proglucagon may be involved in the adaptive response that occurs with steroids and variations in dietary lipids after intestinal resection.

Dietary lipids alter the effect of steroids on the transport of glucose after intestinal resection: Part I. Phenotypic changes and expression of transporters.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the effect on D-glucose uptake of budesonide (Bud), prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids (PUFA). METHODS: In vitro ring uptake technique, Western blots, and Northern blots were performed. RESULTS: Bud increased the jejunal D-glucose uptake, and this effect was prevented by feeding PUFA. SGLT1 and Na+/K+ ATPase protein and mRNA abundance did not correlate with the change in the rate of uptake of glucose. CONCLUSIONS: (1) Bud increased the jejunal glucose uptake, (2) the activity of the sugar transporter does not correlate with the abundance of protein or their respective mRNAs, (3) th Bud effect on glucose uptake is prevented by feeding PUFA. Thus, the desired intestinal adaptive response after intestinal resection may be enhanced further by the administration of the locally acting steroid budesonide and by feeding a saturated compared with a polyunsaturated fatty acid diet.