Teprotumumab for thyroid eye disease: early response is not required for benefit

Purpose In recent trials, 50% of patients treated with teprotumumab for thyroid eye disease had significant improvements in proptosis at 6 weeks. However, a small subgroup of patients did not have a significant response by week 12. We examine the outcomes at week 24 in patients from both trials who had little or no proptosis response at week 12. Design In this post hoc analysis, data from teprotumumab-treated patients in the placebo-controlled randomized phases 2 and 3 trials were reviewed. Methods Patients treated with teprotumumab or placebo with a ≤2 mm reduction from baseline in proptosis at week 12 and completed assessments at both the weeks 12 and 24 visits were included. The main outcome measures were a change in proptosis, clinical activity score (CAS) and diplopia in response to teprotumumab therapy at baseline and weeks 6, 12, 18, and 24. Results From the phases 2 and 3 studies, 24 patients from the treated and placebo groups were included for analysis (48 total). In the teprotumumab group, of the 24 who had no improvement in proptosis (≥2 mm from baseline) at 12 weeks, 15 (63%) demonstrated a clinically significant improvement at week 24. No patients from the 24 placebo patients had a clinically significant improvement in proptosis at 12 weeks, and 24 weeks. At week 12, 22 patients (92%) in the teprotumumab group had a significant reduction in the CAS (≥2 points) and at 24 weeks all patients achieved this reduction. At week 12, 11 (46%) patients from the placebo group had a significant improvement, while 10 (42%) had a significant improvement at 24 weeks. 22 of the 24 patients (92%) in the teprotumumab group had a diplopia grade > 0 at baseline. At week 12, 12 of the 22 (55%) had improvement in diplopia ≥ 1 grade. By week 24, 16 patients (73%) had an improvement in diplopia ≥ 1 grade. In the placebo group, 15 (63%) had significant diplopia. At week 12, 3 (20%) from this group had improvement in diplopia ≥ 1 grade, while at 24 weeks this number rose to 4 (27%). Conclusions There is variability in the time taken to manifest a clinically significant response to teprotumumab, some patients my need a longer time to respond.

A Solitary Melanoma Metastasis Confined to the Submandibular Gland

Malignant melanoma is a type of cancer that most commonly originates from the skin, less frequently from mucosal surfaces, the eye, or meninges [<i>Annu Rev Pathol</i>. 2014;9(1):239–71]. In 2019, this type of malignancy was the third most frequent cancer to be diagnosed in males and the fifth most in females according to the American Cancer Society and the National Cancer Institute [<i>CA Cancer J Clin</i>. 2019;69(5):363–85]. The majority of the malignant melanomas in the head and neck region (85–90%) are cutaneous lesions, most often arising in the skin of the face [<i>Head Neck</i>. 2016;38:147–155]. In sharp contrast are the histological findings of metastatic melanoma with an unknown primary site: they are much more scarce and histologically difficult to diagnose. The literature is limited to case studies or small cohorts. In 2–6% of all patients suffering from metastatic melanoma, after clinical examination of the skin and mucosa, imaging, and other diagnostic examination, a primary tumor cannot be found [<i>Eur J Cancer</i>. 2004;40(9):1454–5]. A very small subgroup (0.5%) presents with a single focus of melanoma within the dermis or subcutaneous tissues [<i>Arch Dermatol</i>. 2000;136(11):1397–9]. We hereby report a case in this subgroup of a solitary melanoma metastasis found in the submandibular gland in a 59-year-old male. The tumor was discovered incidentally after surgical excision of this gland because of nodular enlargement.

Bribri media tantum verbs and the rise of labile syntax

In this article, we first show that the Bribri (Chibchan) middle voice suffix -r derives passive voice from active transitive and agentive intransitive verbs, as well as anticausative verbs from nominal and adjectival roots. Second, we focus on five media tantum verbs, i.e., forms that synchronically carry the -r suffix and have no counterpart without -r. Unlike most other verbs, these five forms are labile, i.e., they can occur in syntactically intransitive and transitive constructions with no (supra-)segmental change. After describing the valence patterns in which Bribri media tantum labile (MTL) verbs occur, we investigate whether: (i) their non-absolutive arguments behave like ergative phrases; and whether (ii) MTL verb forms in two-argument constructions behave like active voice transitive verb stems. Third, we outline a hitherto unnoticed diachronic path for the rise of lability in a small subgroup of Bribri media tantum verbs.

Longitudinal Trajectories in Cortical Thickness and Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy in Older Adults

Background: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. Objective: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. Methods: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. Results: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. Conclusion: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

An Evaluation of Dual Systems Theories of Adolescent Delinquency in a Normative Longitudinal Cohort Study of Youth

Dual systems theories of adolescent risk-taking propose that the socioemotional and self-regulation systems develop at different rates, resulting in a peak in sensation-seeking in adolescence at a time when self-regulation abilities are not yet fully mature. This “developmental imbalance” between bottom-up drives for reward and top-down control is proposed to create a period of vulnerability for high-risk behaviors such as delinquency, substance use, unprotected sex, and reckless driving. In this study, data from the Swiss longitudinal normative z-proso study (n = 1522, n = 784 male; aged 11, 13, 15, 17, and 20) were used to test whether the presence of a developmental imbalance between sensation-seeking and self-regulation is associated with trajectories of engagement in delinquency across early adolescence to adulthood. Using a latent class growth analysis of sensation-seeking, self-regulation, and delinquency, it was found that a model with 3 classes was optimal in the whole sample and male sub-sample, including one class characterized by a developmental imbalance and corresponding adolescent peak in delinquency. In females, there was no evidence for a class that could be described according to the trajectories hypothesized in dual systems theory. This study’s results support the claim that a developmental imbalance may drive an adolescent increase in delinquency. However, this applies only to a small subgroup of individuals, particularly males.

Feasibility of an Outpatient Training Program after COVID-19

Long-term physical consequences of coronavirus disease 2019 (COVID-19) are currently being reported. As a result, the focus is turning towards interventions that support recovery after hospitalization. To date, the feasibility of an outpatient program for people recovering from COVID-19 has not been investigated. This study presents data for a physiotherapy-led, comprehensive outpatient pulmonary rehabilitation (PR) program. Patients were recruited after hospital discharge. Training consisted of twice weekly, interval-based aerobic cycle endurance (ACE) training, followed by resistance training (RT); 60–90 min per session at intensities of 50% peak work rate; education and physical activity coaching were also provided. Feasibility outcomes included: recruitment and dropout rates, number of training sessions undertaken, and tolerability for dose and training mode. Of the 65 patients discharged home during the study period, 12 were successfully enrolled onto the program. Three dropouts (25%) were reported after 11–19 sessions. Tolerability of interval-based training was 83% and 100% for exercise duration of ACE and RT, respectively; 92% for training intensity, 83% progressive increase of intensity, and 83% mode in ACE. We tentatively suggest from these preliminary findings that the PR protocol used may be both feasible, and confer benefits to a small subgroup of patients recovering from COVID-19.

O33 Baricitinib in the BSRBR-RA registry: characteristics and status of patients at first follow-up

Background/Aims Baricitinib is a once-daily orally administered Janus kinase (JAK)-inhibitor approved for the treatment of moderate-to-severe active rheumatoid arthritis (RA). The British Society for Rheumatology Biologics Registry-RA (BSRBR-RA) captures real-world data on biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), including baricitinib, in the UK. Patients are followed up 6-monthly for the first 3 years and annually thereafter. Objectives of this study were to describe baseline characteristics and status (continuation with baricitinib and disease activity) at first follow-up after initiating baricitinib. Analysis was performed independently of the register study team at BSRBR-RA. Methods The study included patients initiating baricitinib and registered in the BSRBR-RA baricitinib cohort between 1 January 2018 and 31 March 2019. Continuation with baricitinib and disease activity score for 28-joint count with erythrocyte sedimentation rate (DAS28-ESR) were assessed in those completing first follow-up at 6 months in the overall population and in the following subgroups: without prior b/tsDMARD experience; with prior b/tsDMARD experience; and receiving baricitinib monotherapy. Continuation was summarised as N (%) remaining on baricitinib at first follow-up (interruptions ≤28 days were permitted). Results During the study period, 409 patients enrolled in the baricitinib cohort. Most were female (76%), the mean disease duration was 13 years (standard deviation [SD] 10) and most had received a prior biologic (63%). Mean and median DAS28-ESR were 5.6 (SD 1.2) and 5.7 (interquartile range 5.1-6.4), respectively. Thirty-nine percent were on baricitinib monotherapy. Overall, 16% were on baricitinib 2mg, 84% on 4mg and 30% were receiving concomitant corticosteroids. First follow-up data were available for 163 patients, of whom 122 (75%) remained on baricitinib. DAS28-ESR was lower at first follow-up than at baseline both overall and in all subgroups (Table 1). Conclusion In an RA study population with severe longstanding disease, in which almost two thirds had received biologics, baricitinib showed good effectiveness and tolerability (continuation) in patients completing first follow-up. Although sample sizes were small, subgroup results suggested good baricitinib effectiveness in all subgroups studied. Further analyses are needed to assess longitudinal outcomes in larger sample sizes at follow-ups beyond 6 months. Disclosure C.J. Edwards: Honoraria; Abbvie, BMS, Biogen, Celgene, Fresenius, Gilead, GSK, Janssen, Lilly, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB. Member of speakers’ bureau; Abbvie, BMS, Biogen, Celgene, Fresenius, Gilead, GSK, Janssen, Lilly, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB. Grants/research support; Abbvie, Biogen. J. Mount: Other; Employee at Eli Lilly and Company. A. Meeks: Other; Contractor at Eli Lilly and Company. L. Zaremba-Pechmann: Other; Contractor at Eli Lilly and Company. A. Mian: Other; Employee at Eli Lilly and Company. E. Larsson: Other; Employee at Eli Lilly and Company. E. Dennision: Other; Lilly, Pfizer and UCB.

The Role of Sleep in the Transition from Acute to Chronic Musculoskeletal Pain in Youth—A Narrative Review

Musculoskeletal pain is common in the general pediatric population and is a challenge to youth, their parents, and society. The majority of children experiencing musculoskeletal pain will recover; however, a small subgroup of youth develops chronic pain. There is limited understanding of the factors that affect the transition from acute to chronic pain in youth. This review introduces sleep deficiency in the acute to chronic pain transition, exploring the potential mediational or mechanistic role and pathways of sleep in this process, including the interaction with sensory, psychological, and social components of pain and highlighting new avenues for treatment. Biological mechanisms include the increased production of inflammatory mediators and the effect on the hypothalamus-pituitary-adrenal (HPA) axis and on the dopaminergic signaling. Psychological and social components include the effect of sleep on the emotional-affective and behavioral components of pain, the negative impact on daily and social activities and coping strategies and on the reward system, increased pain catastrophizing, fear of pain, pain-related anxiety, hypervigilance, and social isolation. Future longitudinal studies are needed to elucidate these mechanistic pathways of the effect of sleep on the transition from acute to chronic pain, which may lead to the development of new treatment targets to prevent this transition.

EPSC 2020 Planetary Science Wiki Edit-a-thon

&lt;p&gt;&lt;strong&gt;Background&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Wikipedia is an open source, web-based encyclopedia, allowing anonymous and registered users to create, edit and improve articles. A survey in 2018 showed that as many as 90% of Wikipedia's editors were male and as many as 81% of contributors were from the Global North [1]. &amp;#160;&lt;/p&gt;&lt;p&gt;In addition, there are fewer contributions about women, especially in STEM fields, and they are usually less developed [2]. In October 2014, only 15.53% of English Wikipedia's biographies were about women [3]. The WikiProject &lt;strong&gt;Women in Red&lt;/strong&gt; was founded in July 2015 with the objective to address this gender bias in Wikipedia content. They succeeded in increasing the above-mentioned percentage to &lt;strong&gt;18.71%&lt;/strong&gt; as of 11 January 2021 [2].&lt;/p&gt;&lt;p&gt;Today, Wikipedia is within the 20 most popular websites [4] and every month it attracts more than 1 billion unique visitors [5]. Wikipedia therefore has a huge potential to change publics perception of who is doing science and what a scientist &amp;#8216;looks&amp;#8217; like.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;(Women) planetary scientists on Wikipedia?&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;In June 2020, there were only 189 planetary scientist biographies on the English Wikipedia, including 48 biographies of female planetary scientists (25%). This percentage is in agreement with the percentage of women in the International Astronomical Union from all ESA&amp;#8217;s Member States (24%) [6], but planetary scientists are clearly underrepresented on Wikipedia. Many of them either do not have a Wikipedia biography yet, or if they do, they are often misclassified under the category of &amp;#8220;astronomers&amp;#8221; or &amp;#8220;astrophysicists&amp;#8221;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;A Planetary Sciences&lt;/strong&gt;&lt;strong&gt; Edit-a-thon&lt;/strong&gt;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&lt;/p&gt;&lt;p&gt;The Diversity Committee of the Europlanet Society aims to highlight diversity within the planetary science community. Therefore, they organised, in collaboration with Women in Red and WikiDonne, the first &lt;strong&gt;Planetary Science Wiki Edit-a-thon&lt;/strong&gt; during the Europlanet Science Congress (EPSC) 2020 [7]. An Edit-a-thon (&amp;#8216;edit marathon&amp;#8217;) is an organized event where editors from an online community (such as Wikipedia in this case) write, translate and improve articles on a specific topic [2]. Thirty persons received a basic editing training, resulting in 1 new article and 5 translated ones. A small subgroup still meets every month to continue the project.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;References&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;[1] https://meta.wikimedia.org/wiki/Community_Insights/2018_Report&lt;/p&gt;&lt;p&gt;[2] https://en.wikipedia.org/wiki/Wikipedia:WikiProject_Women_in_Red &amp;#160;&lt;/p&gt;&lt;p&gt;[3] Eduardo Graells-Garrido, Mounia Lalmas, Filippo Menczer, &quot;First Women, Second Sex: Gender Bias in Wikipedia&quot;, arXiv, 9 February 2015, p. 3.&lt;/p&gt;&lt;p&gt;[4] &quot;Wikipedia.org Traffic, Demographics and Competitors&quot;.&amp;#160;www.alexa.com. Retrieved&amp;#160;October 1,&amp;#160;2019.&lt;/p&gt;&lt;p&gt;[5] https://stats.wikimedia.org/#/all-wikipedia-projects&lt;/p&gt;&lt;p&gt;[6] Piccialli A., et al., Participation of women scientists in ESA Solar System missions: a historical trend, Adv. Geosci., 53, 169&amp;#8211;182, https://doi.org/10.5194/adgeo-53-169-2020, 2020.&lt;/p&gt;&lt;p&gt;[7] https://www.europlanet-society.org/epsc-2020-planetary-science-wiki-edit-a-thon/&amp;#160;&amp;#160;&amp;#160;&amp;#160;&lt;/p&gt;

Incremental role of CT coronary angiography in the assessment of left ventricular diastolic function

ObjectiveTo determine whether Computed Tomography (CT) coronary angiography (CTCA) has clinical value for the assessment of left ventricular (LV) diastolic dysfunction (DD) beyond traditional information on coronary artery anatomy.MethodIn this retrospective study, a consecutive group of 72 patients (mean age 59±13 years)—who met the eligibility criteria of sinus rhythm, no significant valvular abnormalities, and who had transthoracic echocardiogram (TTE)—were analysed. The CTCA was prospectively triggered during diastole. Outcomes of interest were CTCA derived LV and left atrial (LA) volumes, diastolic expansion (DE) index: LV volume÷LA volume and DE fraction (DEF): [(LV volume–LA volume)÷LV volume]×100. TTE-LA volume was measured as maximum, minimum and pre-A. Studied patients were divided according to the current classification of LVDD as a reference standard. A small subgroup of nine patients underwent further invasive cardiac catheterisation.ResultsCTCA-LV and LA volumes were larger compared with TTE, 37%±20% and 11%±21%, respectively. CTCA-LA volume correlated well with all TTE-LA volumes (maximum: R2=0.58; pre-A wave: R2=0.39; minimum: R2=0.26; p<0.0001) with the smallest differences in maximum LA volume (9±32 mL; mean±2 SD). The DE and DEF correlated with both LA function and LVDD. DE >1.65 and DE <1.40 have good specificity (85% and 88%, respectively), and positive predictive value to differentiate LVDD. DE and DEF were dependent on the patients’ age but independent of other variables.ConclusionsCTCA derived diastasis volume indices can provide additional quantifiable information on LVDD.