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With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95 % CI 1.13–28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95 % CI 0.00–0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95 % CI 1.00–1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1 % decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Persistent metabolic uptake on PET/CT after first line chemotherapy (CT) for Large B cell lymphoma (LBCL) is associated with a poor prognosis. The fit patient (pt) will be considered for CAR-T therapy if refractory disease confirmed, but this is not without the risk of significant toxicity, both short and long term. For pts with localised refractory disease radiotherapy (RT) is an alternative salvage option and may spare some the need for CAR-T or other intensive systemic treatment. In this study we evaluate the outcome of pts receiving RT when not in complete metabolic response (CMR) and look at factors predicting response. This was a retrospective review of LBCL pts with residual FDG uptake on PET/CT after first line CT who received RT at our institution. Eligibility criteria included: treatment with curative intent, R-CHOP CT or similar, post CT PET/CT Deauville score (DS) 4 or 5, RT ≥30Gy within 8 weeks of CT. End points included: relapse rate, pattern of relapse, response to RT, PFS and OS. We identified 86 pts who received RT between Mar 2011 and Oct 2023. Pt and treatment characteristics are shown in table 1 below. 62 pts (72.1%) had DS4 and 24 (27.9%) DS5 pre RT. With a median FU of 42.4 months (1.1-164.1) from RT, 26/86 pts (30.2%) have relapsed. Relapses occurred early, at median 3.0 months (0.4-58.1) from RT. 3/26 (11.5%) relapses were in field, 17/26 (65.4%) out field and 6/26 (23.1%) in both. 11/24 (45.8%) pts with DS5 pre RT have relapsed compared to 15/62 (24.2%) with DS4. Relapses were less common in stage I/II disease, 7/42 pts (16.7%) vs 19/44 (43.2%) in advanced stage disease. There was no association between RT dose and relapse rate. 79 (91.9%) pts had a PET/CT after RT. 45/79 (57%) achieved CMR, 15 (19.0%) DS4 and 19 (24.1%) DS5.17/19 (89.5%) pts with DS5 post RT progressed vs 1 /15 (6.7%) with DS4 and 4/45 (8.9%) with CMR DS1-3. Median PFS and OS were not reached. Estimated 2 year PFS and OS were 72.9% and 80.2%, and 5 year PFS and OS, 64.2% and 74.8% for the whole cohort. For pts with DS4 pre RT, outcomes were excellent with 2 year PFS and OS of 82% and 84.7%, vs 49% and 68.1% in pts with DS5 pre RT. RT is an effective salvage treatment for many pts with LBCL not in CMR following initial CT and may avoid the need for further intensive systemic treatment including CAR-T. Outcomes were particularly good for patients with DS4 post CT, with the majority of this group achieving durable remissions after RT. [ABSTRACT FROM AUTHOR]

We modelled the evolution of virulence when co-infections were permitted and compared patterns generated by our modelling approach with those of other models. In support of current models, we found that strains with virulences above the maximum basic reproductive rate (Ro) were competitively superior, and that both high host density (as indexed by host encounter rate) and high parasite infectiousness favoured evolution of strains with high virulence. However, we found that co-existence typically did not continue indefinitely and that parasites with high virulences, and Ro values approaching unity, often did not persist. We examined the extent to which processes such as stochasticity and positive frequency dependence influenced patterns generated byour model. Also, we examined commonly used indices of parasite fitness [i.e. Ro and rate of spread (ROS)], and found that only ROS was positively related to competitive ability when co-infections were permitted. However, there was considerable variation in competitive ability that was not explained by variation in ROS. We conclude that our modelling approach can significantly influence patterns generated and that conclusions from single models or conclusions based on current indices of parasite fitness should be viewed with caution. We suggest empirical tests that distinguish our model from other models and further examine the impact of mechanisms such as positive frequency dependence on the evolution of virulence. [ABSTRACT FROM AUTHOR]

Legal wildlife trade creates opportunities for the sale of illegally procured animals and their derivatives, since it is difficult to differentiate legal from laundered items. This problem is common across many wildlife trade areas – exotic pets, ornaments, seafood – and involves a variety of taxa. Here, we tested the ability of bulk and compound‐specific stable isotope analysis to help monitor and regulate trade of the yellow‐crested cockatoo Cacatua sulphurea, a critically endangered species threatened by overexploitation for the pet trade. Global trade in wild‐caught yellow‐crested cockatoos was banned in 2002; sale of captive‐bred individuals, however, is still permitted. Our surveys in Hong Kong markets revealed more yellow‐crested cockatoos for sale in 2017–2018 than the total number recorded as legally imported over the previous 13 years, emphasizing the need for a forensic tool to identify the source of the individuals for sale in the markets. Stable isotope analysis was successful at distinguishing between captive and wild cockatoos; we found significant differences between wild and captive cockatoos in both stable carbon (P < 0.001) and stable nitrogen (P < 0.001) isotope values. Linear discriminant analysis allocated samples to the correct group with high reliability (Accuracy = 0.91, Kappa = 0.81), although reliability was lower for some individuals with values on the edge of the distribution. In cases where the bulk isotope analysis was ambiguous, compound‐specific stable isotope analysis, which provides carbon isotope values in specific amino acids, can be applied. We found six amino acids that differed significantly between captive and wild samples, with valine (P = 0.009) being the most informative. Together, stable and compound‐specific isotope analysis represents an important potential forensic tool to help combat illegal trade of cockatoos and could be expanded to other species threatened by wildlife trade. [ABSTRACT FROM AUTHOR]

Purpose: Germ cell tumours are the most common cancer of male adolescents and young adults (AYA, age 18–39). Men in this age group have been healthy much of their lives, and a diagnosis of cancer can cause significant psychosocial distress. We therefore sought to examine the psychosocial needs of patients with germ cell tumour and determine whether needs vary based on age (AYA vs non-AYA). We hypothesized that AYA experience more anxiety and distress in emotional, practical and physical domains. Methods: We evaluated the responses of all patients referred to British Columbia (BC) Cancer who completed a pre-consultation health assessment form. This is a validated screening questionnaire for distress, subclinical/clinical symptoms of depression and anxiety and includes the Canadian Problem Checklist domains of emotional, informational, practical, spiritual, social/family and physical concerns. Results: Data were collected for 349 patients (2011–2015). Patient population was predominantly AYA (n = 227) with median age 33 (range 18–83). The top 3 AYA concerns were financial, work/school, frustration and anger. AYA patients more commonly scored positive for symptoms of subclinical/clinical anxiety than non-AYA (39.4% vs. 27.9%, p = 0.028). Those AYA patients with subclinical/clinical anxiety symptoms experienced more fears and worries, concerns regarding work/school, lack of understanding of their disease, finances and frustration and anger. Conclusions: The results of this study indicate that AYA with testicular cancer have unique needs and experience more self-reported anxiety symptoms with emotional, informational and practical concerns. This is valuable information to stakeholders for allocation of resources to address cancer survivorship amongst these patients. [ABSTRACT FROM AUTHOR]

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels ( r = 0·253, P < 0·03), and SLAM-R scores ( r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity ( r = -0·436, P < 0·01), levels of anti-dsDNA antibody ( r = -0·347, P < 0·02) and BAFF ( r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies. [ABSTRACT FROM AUTHOR]

OP02.06: Relationship between anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy To determine the presence of anti-SARS-CoV-2 antibodies in colostrum and mature milk in women who had SARS-CoV-2 infection during pregnancy or at delivery; to investigate the correlation between anti-SARS-CoV-2 antibodies in milk with antibody in maternal blood, severity of infection and time-interval from active illness; and to evaluate immunoglobulin evolution from colostrum to mature milk. IgA and IgG were present in 111/135 (82.2%) and 2/135 (1.5%) colostrum samples and 27/81 (33.3%) and 0/81 mature milk samples, respectively. [Extracted from the article]

Dung beetles impressively coordinate their 6 legs to effectively roll large dung balls. They can also roll dung balls varying in the weight on different terrains. The mechanisms underlying how their motor commands are adapted to walk and simultaneously roll balls (multitasking behavior) under different conditions remain unknown. This study unravels the mechanisms of how dung beetles roll dung balls and adapt their leg movements to stably roll balls over different terrains for multitasking robots. A modular neural-based loco-manipulation control inspired by and based on ethological observations of the ball-rolling behavior of dung beetles is synthesized. The proposed neural-based control contains a central pattern generator (CPG) module, a pattern formation network (PFN) module, and a robot orientation control (ROC) module. The integrated control mechanisms can control a dung beetle-like robot (ALPHA) with biomechanical feet to perform adaptive (multitasking) loco-manipulation (walking and ball-rolling) on various terrains (flat and uneven). It can deal with different ball weights (2.0 and 4.6 kg) and ball types (soft and rigid). The control mechanisms can serve as guiding principles for solving sensory-motor coordination for multitasking robots. Furthermore, this study contributes to biological research by enhancing the understanding of sensory-motor coordination for adaptive (multitasking) loco-manipulation behavior in animals., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The mammalian inner ear houses the vestibular and cochlear sensory organs dedicated to sensing balance and sound, respectively. These distinct sensory organs arise from a common prosensory region, but the mechanisms underlying their divergence remain elusive. Here, we showed that two evolutionarily conserved homeobox genes, Irx3 and Irx5 , are required for the patterning and segregation of the saccular and cochlear sensory domains, as well as for the formation of auditory sensory cells. Irx3/5 were highly expressed in the cochlea, their deletion resulted in a significantly shortened cochlea with a loss of the ductus reuniens that bridged the vestibule and cochlea. Remarkably, ectopic vestibular hair cells replaced the cochlear non-sensory structure, the Greater Epithelial Ridge. Moreover, most auditory sensory cells in the cochlea were transformed into hair cells of vestibular identity, with only a residual organ of Corti remaining in the mid-apical region of Irx3/5 double knockout mice. Conditional temporal knockouts further revealed that Irx3/5 are essential for controlling cochlear sensory domain formation before embryonic day 14. Our findings demonstrate that Irx3/5 regulate the patterning of vestibular and cochlear sensory cells, providing insights into the separation of vestibular and cochlear sensory organs during mammalian inner ear development.

Essential minerals are cofactors for synthesis of neurotransmitters supporting cognition and mood. An 8-week fully-blind randomised controlled trial of multinutrients for attention-deficit/hyperactivity disorder (ADHD) demonstrated three times as many children (age 6-12) had significantly improved behaviour ('treatment responders') on multinutrients (54 %) compared with placebo (18 %). The aim of this secondary study was to evaluate changes in fasted plasma and urinary mineral concentrations following the intervention and their role as mediators and moderators of treatment response. Fourteen essential or trace minerals were measured in plasma and/or urine at baseline and week eight from eighty-six participants (forty-nine multinutrients, thirty-seven placebos). Two-sample t tests/Mann-Whitney U tests compared 8-week change between treatment and placebo groups, which were also evaluated as potential mediators. Baseline levels were evaluated as potential moderators, using logistic regression models with clinical treatment response as the outcome. After 8 weeks, plasma boron, Cr (in females only), Li, Mo, Se and vanadium and urinary iodine, Li and Se increased more with multinutrients than placebo, while plasma phosphorus decreased. These changes did not mediate treatment response. However, baseline urinary Li trended towards moderation: participants with lower baseline urinary Li were more likely to respond to multinutrients ( P = 0·058). Additionally, participants with higher baseline Fe were more likely to be treatment responders regardless of the treatment group ( P = 0·036.) These results show that multinutrient treatment response among children with ADHD is independent of their baseline plasma mineral levels, while baseline urinary Li levels show potential as a non-invasive biomarker of treatment response requiring further study.

The migration of an electron-loss center (hole) in calf thymus DNA to bisbenzimidazole ligands bound in the minor groove is followed by pulse radiolysis combined with time-resolved spectrophotometry. The initially observed absorption spectrum upon oxidation of DNA by the selenite radical is consistent with spin on cytosine (C), as the GC • pair neutral radical, followed by the spectra of oxidized ligands. The rate of oxidation of bound ligands increased with an increase in the ratio ( r ) ligands per base pair from 0.005 to 0.04. Both the rate of ligand oxidation and the estimated range of hole transfer (up to 30 DNA base pairs) decrease with the decrease in one-electron reduction potential between the GC • pair neutral radical of ca. 1.54 V and that of the ligand radicals ( E 0 ', 0.90-0.99 V). Linear plots of log of the rate of hole transfer versus r give a common intercept at r = 0 and a free energy change of 12.2 ± 0.3 kcal mol -1 , ascribed to the GC • pair neutral radical undergoing a structural change, which is in competition to the observed hole transfer along DNA. The rate of hole transfer to the ligands at distance, R , from the GC • pair radical, k 2 , is described by the relationship k 2 = k 0 exp(constant/ R ), where k 0 includes the rate constant for surmounting a small barrier.

Myeloid neoplasms are clonal disorders that arise via acquisition of genetic mutations leading to excessive proliferation and defective differentiation. Mutational profiling is vital as it has implications for diagnosis, prognosis, and therapeutic decision-making. Next-generation sequencing (NGS) has become a mainstay in the evaluation of myeloid malignancies, as it enables efficient characterization of multiple genetic changes. Herein, the analytical validation of the 37-gene Archer VariantPlex Core Myeloid panel is reported, using 58 DNA specimens with 87 single-nucleotide variants and 23 insertions/deletions. The panel achieved good depth of coverage, 100% analytical sensitivity and specificity for single-nucleotide variants and insertions/deletions ≤21 bp, and 100% reproducibility, with a reportable limit of detection determined as 5%. The Archer NGS panel can accurately and reproducibly detect variants of clinical significance in myeloid neoplasms. A retrospective analysis of 535 clinical specimens tested with the Archer NGS panel showed a frequency and pattern of mutations across myeloid malignancies that were similar to other published studies. A review of the diagnostic classification of patients with acute myeloid leukemia and myelodysplastic syndrome using the World Health Organization 2017/2022 and International Consensus Classification 2022 guidelines, in addition to European LeukemiaNet 2017/2022 risk stratification of patients with acute myeloid leukemia, was also performed to assess the utility of the molecular information provided by the Archer NGS panel., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Cutibacterium acnes ( C acnes ) is a commensal skin bacterium, primarily found in sebaceous glands and hair follicles, with a high prevalence in the shoulder region. It is the most common pathogenic organism in prosthetic joint infections after shoulder arthroplasty. Because of its low virulence, its diagnosis remains difficult., Purpose: To evaluate the relative effects of topical preparations in reducing C acnes in shoulder surgery., Study Design: Meta-analysis; Level of evidence, 1., Methods: We searched the MEDLINE, Embase, PsychINFO, and Cochrane Library databases in March 2022. Randomized controlled trials (RCTs) comparing any form of topical preparation in arthroscopic or open shoulder surgery were included. The primary outcome was a reduction in the number of positive C acnes cultures. Secondary outcomes were adverse events related to the application of topical preparations. We performed a network meta-analysis to facilitate simultaneous comparisons between multiple preparations across studies. We calculated differences between preparations using odds ratios and their 95% CIs. The risk of bias was assessed using the Cochrane risk-of-bias tool., Results: The search yielded 17 RCTs (1350 patients), of which 9 were suitable for the network meta-analysis (775 patients). Overall, 2 RCTs were deemed as having a low risk of bias, and 15 raised "some concerns" of bias. Preparations included benzoyl peroxide (BPO), BPO combined with clindamycin, chlorhexidine gluconate, hydrogen peroxide, povidone-iodine, and water with soap. Only BPO resulted in significantly lower odds of a positive C acnes culture compared with placebo or soap and water (odds ratio, 0.12 [95% CI, 0.04-0.36]). There was no statistically significant difference with all other topical preparations. The only adverse events were skin irritation from BPO and chlorhexidine gluconate in a small number of reported cases., Conclusion: BPO was the most effective topical agent in reducing the prevalence of C acnes in shoulder surgery. These results were limited by a combination of indirect and direct data. Future studies should focus on establishing the optimal frequency and duration of preoperative BPO to further reduce the burden of C acnes ., Registration: CRD42022310312 (PROSPERO)., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Patients with cancer often have unmet psychosocial needs. Early detection of who requires referral to a counsellor or psychiatrist may improve their care. This work used natural language processing to predict which patients will see a counsellor or psychiatrist from a patient's initial oncology consultation document. We believe this is the first use of artificial intelligence to predict psychiatric outcomes from non-psychiatric medical documents., Methods: This retrospective prognostic study used data from 47,625 patients at BC Cancer. We analyzed initial oncology consultation documents using traditional and neural language models to predict whether patients would see a counsellor or psychiatrist in the 12 months following their initial oncology consultation., Results: Here, we show our best models achieved a balanced accuracy (receiver-operating-characteristic area-under-curve) of 73.1% (0.824) for predicting seeing a psychiatrist, and 71.0% (0.784) for seeing a counsellor. Different words and phrases are important for predicting each outcome., Conclusion: These results suggest natural language processing can be used to predict psychosocial needs of patients with cancer from their initial oncology consultation document. Future research could extend this work to predict the psychosocial needs of medical patients in other settings., (© 2024. The Author(s).)

Dung beetles can effectively transport dung pallets of various sizes in any direction across uneven terrain. While this impressive ability can inspire new locomotion and object transportation solutions in multilegged (insect-like) robots, to date, most existing robots use their legs primarily to perform locomotion. Only a few robots can use their legs to achieve both locomotion and object transportation, although they are limited to specific object types/sizes (10%-65% of leg length) on flat terrain. Accordingly, we proposed a novel integrated neural control approach that, like dung beetles, pushes state-of-the-art insect-like robots beyond their current limits toward versatile locomotion and object transportation with different object types/sizes and terrains (flat and uneven). The control method is synthesized based on modular neural mechanisms, integrating central pattern generator (CPG)-based control, adaptive local leg control, descending modulation control, and object manipulation control. We also introduced an object transportation strategy combining walking and periodic hind leg lifting for soft object transportation. We validated our method on a dung beetle-like robot. Our results show that the robot can perform versatile locomotion and use its legs to transport hard and soft objects of various sizes (60%-70% of leg length) and weights (approximately 3%-115% of robot weight) on flat and uneven terrains. The study also suggests possible neural control mechanisms underlying the dung beetle Scarabaeus galenus' versatile locomotion and small dung pallet transportation.

Purpose: Comparisons of the surgical and anatomic results of rhegmatogenous retinal detachment surgery have been investigated previously. A systematic evaluation of the available evidence comparing quality of life outcomes of either pars plana vitrectomy, scleral buckling, or pneumatic retinopexy has not been evaluated to date. This article analyzes whether pars plana vitrectomy, scleral buckling, or pneumatic retinopexy for the treatment of rhegmatogenous retinal detachment results in differing quality of life outcomes., Methods: In February of 2022, a comprehensive search of MEDLINE, EMBASE, CINHAL, and Cochrane Library was conducted for studies on patients treated surgically for rhegmatogenous retinal detachment and included follow-up measurements of quality of life outcomes. Meta-analysis was completed using STATA v. 14.0. The main outcomes of interest were the mean vision-related quality of life score (VRQOL) and SD of VRQOL of each type of surgical procedure., Results: In this systematic review of 13 distinct trials including follow-up of patient quality of life after rhegmatogenous retinal detachment surgery ( n  = 1063), a better correlation was found between higher quality of life outcomes with scleral buckling than with pars plana vitrectomy (SMD = 0.62, CI: [0.31, 0.93]). There was also no signficant difference in quality of life outcomes between pneumatic retinopexy and pars plana vitrectomy (SMD = 0.08, CI: [-0.07, 0.22])., Conclusions: Scleral buckling results in better quality of life outcomes for patients when compared to pars plana vitrectomy. Pneumatic retinopexy did not show a difference in quality of life outcomes compared to pars plana vitrectomy.

Purpose: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors affect healing rate, functional outcomes, and patient satisfaction after rotator cuff repair., Methods: Medline, EMBASE, PsychINFO and the Cochrane Library were searched for randomized controlled trials (RCTs) investigating the use of NSAIDs and COX-2 inhibitors after arthroscopic rotator cuff repair. Primary outcomes included healing and retear rate, determined by radiological imaging. Secondary outcomes included shoulder-specific outcome measures and the visual analog scale (VAS). Risk of bias was graded using the Cochrane risk-of-bias v2.0 tool. The GRADE framework was used to assess certainty of findings., Results: Seven RCTs with a total of 507 patients were included (298 randomized to NSAID/COX-2 vs 209 randomized to control). NSAIDs use did not yield a difference in retear rate (P = .77). NSAIDs were shown to significantly reduce pain in the perioperative period (P = .01); however, no significant difference was present at a minimum of 6 months (P = .11). COX-2 inhibitors did not significantly reduce pain (P = .15). Quantitative analysis of ASES and UCLA scores showed NSAIDs significantly improved functional outcomes versus control (P = .004). COX-2 inhibitors did not significantly improve functional outcomes (P = .15). Two trials were deemed "low" risk of bias, four trials were graded to have "some concerns", and one trial was graded to have "high" risk of bias. Retear rate and functional PROMs were deemed to have "low" certainty. VAS pain scale was graded to have "moderate" certainty., Conclusions: This systematic review and meta-analysis indicates that NSAIDs do not affect healing rate after arthroscopic rotator cuff repair, but they do significantly improve postoperative pain and functional outcomes. No significant difference was seen in pain or functional outcomes with the use of COX-2 inhibitors., Level of Evidence: Level I, meta-analysis of randomized controlled trials., Competing Interests: Disclosure The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Global targets aim to reverse biodiversity declines by 2050 but require knowledge of current trends and future projections under policy intervention. First, given uncertainty in measurement of current trends, we propose a risk framework, considering probability and magnitude of decline. While only 11 of 198 systems analyzed (taxonomic groups by country from the Living Planet Database) showed declining abundance with high certainty, 20% of systems had a 70% chance of strong declines. Society needs to decide acceptable risks of biodiversity loss. Second, we calculated statistical power to detect trend change using ~12,000 populations from 62 systems currently showing strong declines. Current trend uncertainty hinders our ability to assess improvements. Trend change is detectable with high certainty in only 14 systems, even if thousands of populations are sampled, and conservation action reduces net declines to zero immediately, on average. We provide potential solutions to improve monitoring of progress toward biodiversity targets.

Background: Cancer is common and disproportionately impacts older adults. Moreover, cancer care of older adults is complex, and the current Canadian cancer care system struggles to address all of the dimensions. In this project, our goal was to understand the barriers and facilitators to caring for older adults with cancer from perspectives of healthcare professionals and cancer care allies, which included community groups, seniors' centers, and other community-based supports., Methods: In collaboration with a patient advisory board, we conducted focus groups and interviews with multiple local healthcare professionals and cancer care allies in British Columbia, Canada. We used a descriptive qualitative approach and conducted a thematic analysis using NVivo software., Results: A total of 71 participants of various disciplines and cancer care allies participated. They identified both individual and system-level barriers. Priority system-level barriers for older adults included space and staffing constraints and disconnections within healthcare systems, and between healthcare practitioners and cancer care allies. Individual-level barriers relate to the complex health states of older adults, caregiver/support person needs, and the needs of an increasingly diverse population where English may not be a first or preferable language., Conclusions: This study identified key barriers and facilitators that demonstrate aligned priorities among a diverse group of healthcare practitioners and cancer care allies. In conjunction with perspectives from patients and caregivers, these findings will inform future improvements in cancer care. Namely, we emphasize the importance of connections among health systems and community networks, given the outpatient nature of cancer care and the needs of older adults., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8-10 week old NSG mice. Once leukemic engraftment was confirmed by HLA-DR expression in the peripheral blood, human peripheral blood mononuclear cells (hPBMCs) were injected into the mice. One week post-hPBMCs injection, Nivolumab (PD-1 inhibitor) or PBS vehicle control was administered to the mice bi-weekly. In our Nivolumab treated mice, FA-AML1, but not Kasumi-1-engrafted mice, had significantly prolonged overall survival. Both FA-AML1 and Kasumi-1 engrafted mice had decreased spleen weights. Higher leukemic infiltration into vital organs was observed in FA-AML1 engrafted mice compared to Kasumi-1 engrafted mice. In conclusion, our novel humanized murine model of FA-mutated AML is an attractive tool for supporting further studies and clinical trials using PD-1 inhibitors to treat FA-mutated AML., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many plant traits covary with environmental gradients, reflecting shifts in adaptive strategies and thus informing about potential consequences of future environmental change for vegetation and ecosystem functioning. Yet, the evidence of trait-environment relationships (TERs) remains too heterogeneous for reliable predictions, partially due to insufficient consideration of trait syndromes specific to certain growth forms and habitats. Moreover, it is still unclear whether non-native and native plants' traits align similarly along environmental gradients, limiting our ability to assess the impacts of future plant invasions. Using a Bayesian multilevel modelling framework, we assess TERs for native and non-native woody and herbaceous plants across six broad habitat types in Central Europe at a resolution of c. 130 km 2 and use them to project trait change under future environmental change scenarios until 2081-2100. We model TERs between three key plant traits (maximum height, H max ; specific leaf area, SLA; seed mass, SM) and individual environmental factors (7 climate variables and % urban land cover) and estimate trait change summed across all environmental effects. We also quantify the change in the average trait difference between native and non-native plants. Our models depict multiple TERs, with important differences attributed to biogeographical status and woodiness within and across habitat types. The overall magnitude of trait change is projected to be greater for non-native than native taxa and to increase under more extreme scenarios. Native woody plant assemblages may generally experience a future increase across all three traits, whereas woody non-natives may decline in H max and increase in SLA and SM. Herbaceous H max is estimated to increase and SLA to decrease in most habitats. The obtained trait projections highlight conditions of competitive advantage of non-native plants over natives and vice versa and can serve as starting points for projecting future changes in ecosystem functions and services., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed., Objectives: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals., Methods: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained., Results: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients., Conclusions: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A growing body of evidence suggests de novo lipogenesis as a key metabolic pathway adopted by cancers to fuel tumorigenic processes. While increased de novo lipogenesis has also been reported in hepatocellular carcinoma (HCC), understanding on molecular mechanisms driving de novo lipogenesis remains limited. In the present study, the functional role of sortilin, a member of the vacuolar protein sorting 10 protein receptor family, in HCC was investigated. Sortilin was overexpressed in HCC and was associated with poorer survival outcome. In functional studies, sortilin-overexpressing cells conferred tumorigenic phenotypes, namely, self-renewal and metastatic potential, of HCC cells via the cancer secretome. Proteomic profiling highlighted fatty acid metabolism as a potential molecular pathway associated with sortilin-driven cancer secretome. This finding was validated by the increased lipid content and expression of fatty acid synthase (FASN) in HCC cells treated with conditioned medium collected from sortilin-overexpressing cells. The enhanced tumorigenic properties endowed by sortilin-driven cancer secretome were partly abrogated by co-administration of FASN inhibitor C75. Further mechanistic dissection suggested protein stabilization by post-translational modification with O-GlcNAcylation as a major mechanism leading to augmented FASN expression. In conclusion, the present study uncovered the role of sortilin in hepatocarcinogenesis via modulation of the cancer secretome and deregulated lipid metabolism., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Millipedes can avoid obstacle while navigating complex environments with their multi-segmented body. Biological evidence indicates that when the millipede navigates around an obstacle, it first bends the anterior segments of its corresponding anterior segment of its body, and then gradually propagates this body bending mechanism from anterior to posterior segments. Simultaneously, the stride length between pairs of legs inside the bending curve decreases to coordinate the leg motions with the bending mechanism of the body segments. In robotics, coordination between multiple legs and body segments during turning for navigating in complex environments, e.g., narrow spaces, has not been fully realized in multi-segmented, multi-legged robots with more than six legs., Method: To generate the efficient obstacle avoidance turning behavior in a multi-segmented, multi-legged (millipede-like) robot, this study explored three possible strategies of leg and body coordination during turning: including the local leg and body coordination at the segment level in a manner similar to millipedes, global leg amplitude change in response to different turning directions (like insects), and the phase reversal of legs inside of turning curve during obstacle avoidance (typical engineering approach)., Results: Using sensory inputs obtained from the antennae located at the robot head and recurrent neural control, different turning strategies were generated, with gradual body bending propagation from the anterior to posterior body segments., Discussion: We discovered differences in the performance of each turning strategy, which could guide the future control development of multi-segmented, legged robots., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mingchinda, Jaiton, Leung and Manoonpong.)

Introduction: Countries with large economies are observing a growing number of culturally and linguistically diverse (CALD) older adults, many of whom will be affected by cancer. Little is known about the experiences and factors that influence cancer treatment decision-making in this population. The purposes of this scoping review are: (1) to summarize the published literature on cancer treatment-related decision-making with this population; and (2) to identify potential differences in how cancer treatment decisions are made compared to non-CALD older adults with cancer., Materials and Methods: We conducted a scoping review following Arksey and O'Malley and Levac methods, Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review Guidelines. We conducted a comprehensive multidatabase search, screening 1,139 titles/abstracts. Following data abstraction, we analyzed the data using tabular and narrative summary., Results: We extracted data from six studies that met the inclusion criteria: four quantitative and two qualitative; five from the United States and one from Canada. Three themes were identified: (1) barriers to decision-making, (2) the influence of family and friends on decisionmaking, and (3) differences in uptake and types of treatment received between CALD and non-CALD older adults., Discussion: This comprehensive review of treatment decision-making among CALD older adults with cancer highlights the paucity of research in this area. The findings are limited to North American populations and may not represent experiences in other regions of the world. Future research should focus on studying their treatment-related decision-making experiences to improve the quality of care for this vulnerable population., Competing Interests: Declaration of Competing Interest BL has received honoraria from AstraZeneca outside of the submitted work. LAC has received payment for expert testimony, for travel to attend a meeting, and is an elected board of directors for the Advanced Practitioner Society for Hematology and Oncology (unpaid). LN and RJ are elected members of the board of directors for the Canadian Association of Nurses in Oncology (unpaid). CME, SP, KK, RJ, KK, PSB, JL, YZ, MP, CB, FK, JLK, TR, EB, CK, LK, and KRH have no disclosures., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: There are significant implications for both patients and providers when patients do not attend outpatient specialist appointments. Nonattendance has an impact on the efficiency of health care, provider resources and patient health outcomes., Aims: In this qualitative study we aimed to gather insights on how Dunedin Hospital notifies patients about their appointments, the implications for the hospital and for patients and how the system could be improved., Methods: We interviewed 13 hospital staff members and nine patients who volunteered to participate because they had missed appointments as a result of communication problems. Interviews were transcribed and analysed thematically using NVivo software., Results: Dunedin Hospital relies heavily on posted letters to inform people about their appointments, with some also receiving reminder texts closer to the time of the appointment. Frustration with the current system was a common theme among both patients and staff. Almost all patients had missed an appointment because of a letter not arriving. While most patients found that the text reminders were helpful, most said they were sent too late and did not allow enough time for arrangements to be made for their appointments. Almost all patients experienced treatment delays, which caused distress. Most patients believed a self-booking system would improve the ability to attend their appointments, and most of them wanted to be notified of appointments via email., Conclusions: We recommend that a patient-oriented approach to communication should be implemented, and alternative methods of communication should be explored., (© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Competing Interests: Conflicts of interest: Nicole R. LeBoeuf is a consultant and has received honoraria from Bayer, Seattle Genetics, Sanofi, Silverback and Synox Therapeutics outside the scope of the submitted work. The other authors declare they have no conflicts of interest.

Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.

Estimating biodiversity change across the planet in the context of widespread human modification is a critical challenge. Here, we review how biodiversity has changed in recent decades across scales and taxonomic groups, focusing on four diversity metrics: species richness, temporal turnover, spatial beta-diversity and abundance. At local scales, change across all metrics includes many examples of both increases and declines and tends to be centred around zero, but with higher prevalence of declining trends in beta-diversity (increasing similarity in composition across space or biotic homogenization) and abundance. The exception to this pattern is temporal turnover, with changes in species composition through time observed in most local assemblages. Less is known about change at regional scales, although several studies suggest that increases in richness are more prevalent than declines. Change at the global scale is the hardest to estimate accurately, but most studies suggest extinction rates are probably outpacing speciation rates, although both are elevated. Recognizing this variability is essential to accurately portray how biodiversity change is unfolding, and highlights how much remains unknown about the magnitude and direction of multiple biodiversity metrics at different scales. Reducing these blind spots is essential to allow appropriate management actions to be deployed. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.

Purpose: About one-fifth of newly diagnosed cancer patients are parents to young children. These patients are at higher risk of psychosocial stress and inability to attend treatment due to having to balance their own healthcare needs with childcare duties. This study aims to explore the impact of childcare on cancer parents and elicit their perspectives on potential supports. The results could help inform the implementation of suitable childcare programs to remove this barrier in accessing care., Methods: Patients at a large Canadian cancer treatment center were screened by oncologists for having minor children at home. Secure electronic surveys were then distributed to consenting participants. Domains surveyed included patient demographics, childcare burden, impact on treatment, and preference for childcare supports., Results: The mean age of correspondents was 43.9 (range 33-54), 46 patients (92%) were female, and breast cancer was the most common primary tumor. The median number of children per correspondent was two, and their mean age was 8.4. Balancing childcare with cancer treatment had a significant impact on self-reported stress levels for most correspondents. Twenty (40%) participants had to reschedule and 7 (14%) participants missed at least one appointment due to childcare conflicts. During the COVID-19 pandemic, access to childcare resources decreased while childcare responsibilities increased. Three-quarters of correspondents reported that a flexible childcare would make it easier for them to adhere to appointment schedules., Conclusion: Childcare is a significant psychosocial barrier for patients accessing cancer care. Our results indicate that most parents undergoing treatment may benefit from hospital-based childcare services., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes., Objective: Examine the impact of melanoma subtypes on cirAE onset and survival among ICI recipients., Methods: Retrospective multi-institutional cohort study. Multivariate time-series regressions were utilized to assess relationships between melanoma subtype, cirAE development, and survival., Results: Among 747 ICI recipients, 236 (31.6%) patients developed a cirAE. Patients with acral melanoma were less likely to develop a cirAE (hazard ratio [HR] = 0.41, P = .016) compared to patients with nonacral cutaneous melanoma. Across all melanoma subtypes, cirAEs were associated with reduced mortality (HR = 0.76, P = .042). Patients with acral (HR = 2.04, P = .005), mucosal (HR = 2.30, P < .001), and uveal (HR = 4.09, P < .001) primaries exhibited the worst survival., Limitations: Retrospective cohort study., Conclusion: This is the first study to demonstrate differences in cirAE development among melanoma subtypes. The presence of cirAEs was associated with better survival. Further, the lower incidence of cirAEs may be a marker of immunotherapy response, which is reflected in the association between acral melanoma and mortality., Competing Interests: Conflicts of interest YRS is an advisory board member/consultant and has received honoraria from Incyte Corporation, Castle Biosciences, Galderma, and Sanofi outside of the submitted work. SGK is an advisory board member/consultant for AbbVie, Celldex Therapeutics, Galderma, Incyte Corporation, Johnson & Johnson, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Kiniksa Pharmaceuticals and has served as an investigator for Galderma, Kiniksa Pharmaceuticals, Pfizer Inc, and Sanofi. NRL is a consultant and has received honoraria from Bayer, Seattle Genetics, Sanofi, Silverback and Synox Therapeutics outside the submitted work., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab., Methods: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan-Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy., Results: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis., Conclusion: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients.

Purpose: We assessed the accuracy of quotations in the published literature of the Wound Management of Open Lower Limb Fractures (WOLLF) Randomized Clinical Trial., Methods: A literature search was performed to identify all citations of WOLLF from 2018 to 2021. Duplicate papers, non-English language papers, textbooks, technical tip videos, Ph.D. theses, and other grey literature were excluded from analysis. Eligible publications had their full text assessed by 2 independent reviewers who used a validated framework of error classification., Results: We identified 62 original papers that met our eligibility criteria and referenced WOLLF. Of the 62 papers, 12 contained a quotation error (12/62, 19%). Errors were classified into major and minor. There were 7 major errors and 5 minor errors. The majority of quotation errors (7/12, 58%) occurred due to multi-referencing, where groups of references were used to support single assertions. There was substantial agreement between the two independent reviewers as determined by a Kappa coefficient of 0.761., Conclusion: Our study demonstrated a 19% quotation error rate in the literature regarding WOLLF. The majority were due to multi-referencing. We suggest that both authors and reviewers carefully check the source literature of key references., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC., Methods: All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher's exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test., Results: 3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m., Conclusions: There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST., (© 2023. The Author(s).)

Competing Interests: Conflicts of interest Dr Mostaghimi has received consulting fees from Pfizer, hims, Digital Diagnostics, Concert, Lilly, Abbvie, Equillium, Boehringer Ingelheim; equity: hims, Acom, Seebe; licensing/royalties: Pfizer, Concert, Lilly; medical advisory board: hims, digital diagnostics; clinical trials: Lilly, Concert; and editorial: Associate editor, JAMA Dermatology. Dr Semenov is an advisory board member/consultant and has received honoraria from Incyte Corporation, Castle Biosciences, Galderma, and Sanofi outside of the submitted work. Dr Theodosakis, authors Young, Pagan, Yoon, Getachaw, Leung, and Nguyen have no conflicts of interest to declare.