Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Factors influencing choice of medical vs. surgical treatment of pediatric appendicitis

PurposeTo examine what proportion of caregivers, if given a choice, would choose medical versus surgical treatment of appendicitis and what factors would be important in their decision.MethodsA survey was devised and given to the caregivers of children presenting to the pediatrician for a routine visit in community and academic pediatric clinics. The survey presented a summary of outcomes after medical (non-operative) and surgical treatment of uncomplicated appendicitis. Participants were then asked to choose medical versus surgical treatment if their child were to develop appendicitis. They were also asked to rate the importance of certain factors in their decision ? 1 being “not important” and 5 being “very important”.ResultsFour hundred surveys were distributed with an 86.2% (345/400) response rate. Six percent (21/342) of respondents reported a history of appendicitis and 49.4% (168/340) reported having known someone who had appendicitis. The majority of respondents, 85.3% (284/333), were mothers. A minority of respondents, 41.7% (95% CI: 36.7, 47.0), chose medical treatment over surgery for appendicitis. There was no statistical difference in the proportion of mothers (41.6%) versus fathers who chose medical treatment (41.3%). Caregivers who chose medical treatment were more likely to rate time in hospital (p = .008) and time out of school (p = 05) as important in decision making when compared with those who chose surgery. Those who chose surgical treatment were more likely to rate risk of recurrent appendicitis (p < .001) as important to decision making. In the multivariate analysis, those who rated time in hospital as very important had more than twice the odds of choosing medical therapy (OR 2.20, p = 0.02) when compared with those who rated it as less important. Not knowing someone who has had appendicitis was significantly associated with choosing medical therapy when compared with those who do know someone who has had appendicitis, OR 2.3, p = .002. Rating pain as very important was also significantly associated with choosing medical therapy, when compared to those rating pain 1–3, OR 3.38, p = .03.ConclusionsIn this survey of caregivers of children presenting for routine care, 41.7% would choose medical, or non-operative, therapy for their children with acute appendicitis. The risk of recurrence, time in hospital, and time out of school, pain, and knowing someone who has had appendicitis were all important factors that families may consider when making a decision. These data may be useful for surgeons counseling patients on which treatment to pursue.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.