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Chronic inflammatory conditions, including inflammatory bowel diseases (IBD), psoriasis, and psoriatic arthritis, are prevalent among women of reproductive age; patients with active disease during pregnancy may be at an increased risk of adverse birth outcomes. For this reason, physicians are focused on approaches to controlling disease activity prior to and during pregnancy. The safety profile of many therapies used for these conditions has been relatively well established, though evidence on newer therapies is lacking. Ustekinumab is a relatively new interleukin-12/23 inhibitor approved for IBD, psoriasis, and psoriatic arthritis, whose safety in pregnancy is not yet fully understood. In this comprehensive review, we critically assess the available evidence on ustekinumab in pregnancy across animal studies and human case reports, case series, observational studies, and clinical practice guidelines. We show that, to date, studies have not identified an excess risk of adverse pregnancy outcomes among women exposed to ustekinumab in pregnancy, with few exposed pregnancies and potential for some bias. Clinical guidelines are conflicted regarding whether they recommend continuing or discontinuing ustekinumab, highlighting the paucity of data and need for more research on this issue.

OBJECTIVES/HYPOTHESIS Current methods of assessing rib cartilage dimensions for laryngotracheal reconstruction (LTR) are inexact, making surgical planning difficult. The purpose of this study was to determine the most appropriate rib for costal cartilage graft LTR to minimize the number of ribs harvested and improve surgical outcomes. STUDY DESIGN Retrospective review. METHODS Computed tomography imaging of chest scans in 25 children aged 1 to 18 years was evaluated. The lengths and widths of medial and lateral cartilaginous segments of ribs 4 to 7 were measured bilaterally. Right and left cartilaginous rib dimensions were compared using a two-sample t-test. Linear mixed-effect regression was performed to develop models quantifying the relationship between rib size and patient height, rib side, and rib number. RESULTS Regression analysis established strong models for medial rib length (R2 = 0.89) and for medial and lateral rib width (R2 = 0.71, 0.77, respectively). There was no difference in rib dimensions across chest sides. Rib length and width increased with child height. Total cartilaginous rib length increased from superiorly to inferiorly, primarily due to an increase in the dimensions of the medial portion of each rib. CONCLUSION Cartilaginous rib lengths and widths were associated with patient height, with taller children having longer ribs. Inferior ribs were longer than superior ribs, suggesting that inferior ribs may be preferred for LTR. There was no difference in cartilaginous rib length across chest side. Results may help surgeons with preoperative planning. LEVEL OF EVIDENCE Not applicable Laryngoscope, 2021.

This paper asked whether children fitted with bilateral hearing aids (BHA) develop normal perception of binaural cues which are the basis of spatial hearing. Data from children with BHA (n = 26, age = 12.6 ± 2.84 years) were compared to data from a control group (n = 12, age = 12.36 ± 2.83 years). Stimuli were 250 Hz click-trains of 36 ms and a 40 ms consonant-vowel /da/ at 1 Hz presented through ER3A insert-earphones unilaterally or bilaterally. Bilateral stimuli were presented at different interaural level difference (ILD) and interaural timing difference (ITD) conditions. Participants indicated whether the sound came from the left or right side (lateralization) or whether one sound or two could be heard (binaural fusion). BHA children lateralized ILDs similarly to the control group but had impaired lateralization of ITDs. Longer response times relative to controls suggest that lateralization of ITDs was challenging for children with BHA. Most, but not all, of the BHA group were able to fuse click and speech sounds similarly to controls. Those unable to fuse showed particularly poor ITD lateralization. Results suggest that ITD perception is abnormal in children using BHAs, suggesting persistent effects of hearing loss that are not remediated by present clinical rehabilitation protocols.

Background:Ustekinumab, an IL-12/23 inhibitor, is indicated in adult patients with inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) and vedolizumab, an α4β7 receptor antagonist is indicated in IBD only. Both are monoclonal antibodies harbouring an Fc portion, which are actively transported across the placenta, often reaching higher fetal than maternal levels. As fetuses could be exposed to therapeutic or supra-therapeutic levels of these drugs, there are concerns that these agents could cause immunosuppression after birth. However, evidence is lacking.Objectives:We compared the risk of serious infections in offspring exposed to ustekinumab, vedolizumab, tumour necrosis factor inhibitors (TNFi), and non-biologic immunosupressives versus offspring unexposed during pregnancy among women with IBD, PsO and/or PsA.Methods:We conducted a retrospective cohort study using the US MarketScan database, an employment insurance database. We included live births (01/2011-12/2018) among women with PsO, PsA, and/or IBD. Drug exposure was defined as ≥1 filled prescrip tion or infusion procedure code during pregnancy. In offspring, we evaluated serious infections within the first year of life as any single inpatient infection code. We performed multivariate analyses using logistic regression, adjusting for maternal age, co-morbidities, corticosteroid use, concomitant drug use, and preterm birth.Results:We included 16,115 offspring born to 7,612 women with PsO/PsA, 8,315 with IBD, and 188 with PsO/PsA and IBD. A total of 52 offspring were exposed to ustekinumab, 43 to vedolizumab (including 7 to both TNFi and vedolizumab),1,578 to TNFi, 1,857 to non-biologic immunosuppressives alone, and 12,585 unexposed to any drug. The percentage of serious infections in offspring exposed to ustekinumab was 3.9% (95% CI 0.5-13.9), versus 2.7% (95% CI 1.9-3.6) for TNFi, 2.3% (95% CI 0.06-13.0) for vedolizumab and 2.6 (95% CI 2.3-2.8) for those unexposed to any drug, though all estimates had wide, overlapping confidence intervals. Compared to children unexposed to any drug, there was a potential trend for increased risk with ustekinumab (OR 1.54, 0.37-6.45), but CIs were wide and included the null. For those exposed to vedolizumab (OR 0.82, 0.15-5.91) or TNFi (OR 0.98, 0.68-1.40) there was no clear excess risk.Conclusion:In a large cohort, we did not detect a clear excess risk for offspring exposed in-utero to, vedolizumab or anti-TNF’s, compared to unexposed patients; there was a signal for more events with ustekinumab, but confidence intervals were wide. Ongoing caution, as well as more research on short and long-term effects, is warranted for biologics actively transported across the placentaDisclosure of Interests:Jonah Gorodensky: None declared, Sasha Bernatsky: None declared, Waqqas Afif Consultant of: Abbvie, Amgen, Arena Pharmaceuticals, Dynacare, Janssen, Merck, Novartis, Pfizer, Sandoz, Takeda, Yvan St-Pierre: None declared, Kristian Filion: None declared, Evelyne Vinet: None declared