Rexinoids Induce Differential Gene Expression in Human Glioblastoma Cells and Protein-Protein Interactions in a Yeast Two-Hybrid System.

Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize, and these protein-protein interactions and subsequent transactivating potential lead to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or downregulated. Expression analysis was performed in the U87 human glioblastoma cell line treated with a panel of rexinoids, and our analysis demonstrated that rexinoids with similar RXR EC50 values can have pronounced differences in differential gene expression. Rexinoid binding likely leads to distinctive RXR conformations that cause major downstream gene expression alterations via modulation of RXR interacting proteins. Yeast two-hybrid analysis of RXR bait with two RXR interacting partners demonstrates that rexinoids drive differential binding of RXR to distinctive protein partners. Physiochemical analysis of the rexinoids reveals that the molecules cluster similarly to their gene expression patterns. Thus, rexinoids with similar RXR binding affinities drive differential gene expression by stimulating additional binding patterns in RXR and its homo- and heteropartners, driven by the physicochemical characteristics of these molecules.

Lee Silverman voice treatment versus NHS speech and language therapy versus control for dysarthria in people with Parkinson's disease (PD COMM): pragmatic, UK based, multicentre, three arm, parallel group, unblinded, randomised controlled trial.

OBJECTIVES: To assess the clinical effectiveness of two speech and language therapy approaches versus no speech and language therapy for dysarthria in people with Parkinson's disease. DESIGN: Pragmatic, UK based, multicentre, three arm, parallel group, unblinded, randomised controlled trial. SETTING: The speech and language therapy interventions were delivered in outpatient or home settings between 26 September 2016 and 16 March 2020. PARTICIPANTS: 388 people with Parkinson's disease and dysarthria. INTERVENTIONS: Participants were randomly assigned to one of three groups (1:1:1): 130 to Lee Silverman voice treatment (LSVT LOUD), 129 to NHS speech and language therapy, and 129 to no speech and language therapy. LSVT LOUD consisted of four, face-to-face or remote, 50 min sessions each week delivered over four weeks. Home based practice activities were set for up to 5-10 mins daily on treatment days and 15 mins twice daily on non-treatment days. Dosage for the NHS speech and language therapy was determined by the local therapist in response to the participants' needs (estimated from prior research that NHS speech and language therapy participants would receive an average of one session per week over six to eight weeks). Local practices for NHS speech and language therapy were accepted, except for those within the LSVT LOUD protocol. Analyses were based on the intention to treat principle. MAIN OUTCOME MEASURES: The primary outcome was total score at three months of self-reported voice handicap index. RESULTS: People who received LSVT LOUD reported lower voice handicap index scores at three months after randomisation than those who did not receive speech and language therapy (-8.0 points (99% confidence interval -13.3 to -2.6); P<0.001). No evidence suggests a difference in voice handicap index scores between NHS speech and language therapy and no speech and language therapy (1.7 points (-3.8 to 7.1); P=0.43). Patients in the LSVT LOUD group also reported lower voice handicap index scores than did those randomised to NHS speech and language therapy (-9.6 points (-14.9 to -4.4); P<0.001). 93 adverse events (predominately vocal strain) were reported in the LSVT LOUD group, 46 in the NHS speech and language therapy group, and none in the no speech and language therapy group. No serious adverse events were recorded. CONCLUSIONS: LSVT LOUD was more effective at reducing the participant reported impact of voice problems than was no speech and language therapy and NHS speech and language therapy. NHS speech and language therapy showed no evidence of benefit compared with no speech and language therapy. TRIAL REGISTRATION: ISRCTN registry ISRCTN12421382.

A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome.

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE). METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 hours) from children with infantile epileptic spasms syndrome. RESULTS: For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/-EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements. CONCLUSIONS: These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Race, community, and doing sociology.

What further evidence is needed to effectively address the unsatisfactory schooling experiences and educational trajectory of Black youth to help shape their path toward more successful social outcomes? I return to this persistent question in my research to reflect on how I have used sociological research in prior observations, and to build on earlier studies. I show how following research participants over a period of time, and with attention to how they relate to and are nested in community, family and peers, has enabled me to more effectively document their experiences, imaginations, and ambitions from adolescence to adulthood. I contend that longitudinal studies, framed by a community referenced approach, best ensure that we attend to the complex, diverse, and transitional lives of Black youth, and the social, cultural, educational, economic, and political contexts they navigate. At this time of equity, diversity, and inclusion (EDI) initiatives, sociology could help to advance education about, and initiate action for, Black people so that the equity promised by Canadian multiculturalism might be realized.

Quelles sont les preuves supplémentaires nécessaires pour traiter efficacement les expériences scolaires insatisfaisantes et la trajectoire éducative des jeunes Noirs afin de les aider à s'orienter vers des résultats sociaux plus satisfaisants? Je reviens sur cette question persistante dans mes recherches pour réfléchir à la manière dont j'ai utilisé la recherche sociologique dans des observations antérieures et pour m'appuyer sur des études antérieures. Je montre comment le fait de suivre les participants à la recherche sur une certaine période, en prêtant attention à la manière dont ils sont liés et imbriqués dans la communauté, la famille et les pairs, m'a permis de documenter plus efficacement leurs expériences, leurs imaginations et leurs ambitions, de l'adolescence à l'âge adulte. Je soutiens que les études longitudinales, encadrées par une approche référencée par la communauté, sont le meilleur moyen de s'assurer que nous prenons en compte les vies complexes, diverses et transitoires des jeunes Noirs, ainsi que les contextes sociaux, culturels, éducatifs, économiques et politiques dans lesquels ils évoluent. À l'heure des initiatives d'EDI, la sociologie pourrait contribuer à faire progresser l'éducation sur les Noirs et à lancer des actions en leur faveur, afin que l'équité promise par le multiculturalisme canadien puisse se réaliser.

Rapid gene fusion testing using the NanoString nCounter platform to improve pediatric leukemia diagnoses in Sub-Saharan Africa.

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low cost, minimal technical and bioinformatics expertise required, ability to test sub-optimal RNA, and rapid turnaround time. Fusion results were analyzed blindly, then compared to morphology and flow cytometry results. Of 117 leukemia samples, 74 were fusion-positive, 30 were negative, 7 were not interpretable, and 6 failed RNA quality. Nine additional samples were negative for leukemia by flow cytometry and negative for gene fusions. All 74 gene fusions aligned with the immunophenotype determined by flow cytometry. Fourteen samples had additional information available to further confirm the accuracy of the gene fusion results. The testing provided a more precise diagnosis in >60% of cases, and 9 cases were identified that could be treated with an available tyrosine kinase inhibitor, if detected at diagnosis. As risk-stratified and targeted therapies become more available in SSA, implementing this testing in real-time will enable the treatment of pediatric cancer to move toward incorporating risk stratification for optimized therapy.

Quantifying soil accumulation of atmospheric mercury using fallout radionuclide chronometry.

Soils are a principal global reservoir of mercury (Hg), a neurotoxic pollutant that is accumulating through anthropogenic emissions to the atmosphere and subsequent deposition to terrestrial ecosystems. The fate of Hg in global soils remains uncertain, however, particularly to what degree Hg is re-emitted back to the atmosphere as gaseous elemental mercury (GEM). Here we use fallout radionuclide (FRN) chronometry to directly measure Hg accumulation rates in soils. By comparing these rates with measured atmospheric fluxes in a mass balance approach, we show that representative Arctic, boreal, temperate, and tropical soils are quantitatively efficient at retaining anthropogenic Hg. Potential for significant GEM re-emission appears limited to a minority of coniferous soils, calling into question global models that assume strong re-emission of legacy Hg from soils. FRN chronometry poses a powerful tool to reconstruct terrestrial Hg accumulation across larger spatial scales than previously possible, while offering insights into the susceptibility of Hg mobilization from different soil environments.

Overcoming barriers to implementation: Improving incidental coronary calcium reporting on non-EKG gated chest CT scans.

BACKGROUND: Current guidelines recommend the reporting of incidental CAC on non-EKG-gated CT scans of the chest. The finding of incidental moderate or severe CAC on non-cardiac non-contrast chest CT correlates with a CAC score ≥ 100 Agatston units, a guideline-based indication for a clinician-patient discussion regarding the initiation of statin therapy. In contemporary practice, whether the presence and severity of incidental CAC are routinely reported on such CT scans of the chest is unknown. METHODS: At a major university hospital, we collected a one-month convenience sample of 297 patients who had chest CT imaging for indications other than lung cancer screening (OICT) and 42 patients who underwent lung cancer chest CT screening (LSCT). We evaluated reporting patterns of incidental CAC in the body and impression of the reports as compared to the overreading of such studies by a board-certified CT chest radiologist. We hypothesized and demonstrated that there was underreporting of incidental CAC on these scans. We then undertook an initiative to educate reporting radiologists on the importance of reporting CAC and implemented a reporting template change to encourage routine reporting. Then we repeated another one-month sample (n= 363 for the OICT and n= 63 for the LSCT groups) to evaluate reporting patterns following our intervention. RESULTS: The presence of incidental moderate and severe CAC was systematically underreported in the OICT group (0 and 4.8 %) and the severity was never mentioned in the impression of reports. In the LSCT group, the presence of incidental moderate and severe CAC was also underreported (66.7 % and 75 %) and the severity of CAC was mentioned 50 % of the time in the impression of the reports. Following the initiation of an educational program and radiology reporting template change, there was a significant increase in reporting of moderate or severe CAC in the OICT group (0 vs. 80.0 %, p < 0.001) and (4.8 vs. 93.5 %, p < 0.001) respectively and a significant increase in the reporting of the severity of incidental CAC for those with severe CAC in the LSCT group (50 vs. 94.1 %, p=0.006). CONCLUSION: Despite guideline recommendations, Incidental CAC was underreported at a large academic center. We implemented a system that significantly improved reporting patterns of incidental CAC. Failure to report incidental CAC represents a missed opportunity to initiate preventive therapies. Hospital systems interested in improving the quality of their radiology reporting procedures should examine their practices to assure that CAC quantification is routinely performed.

Genome size and chromosome number are critical metrics for accurate genome assembly assessment in Eukaryota.

The number of genome assemblies has rapidly increased in recent history, with NCBI databases reaching over 41,000 eukaryotic genome assemblies across about 2,300 species. Increases in read length and improvements in assembly algorithms have led to increased contiguity and larger genome assemblies. While this number of assemblies is impressive, only about a third of these assemblies have corresponding genome size estimations for their respective species on publicly available databases. In this paper, genome assemblies are assessed regarding their total size compared to their respective publicly available genome size estimations. These deviations in size are assessed related to genome size, kingdom, sequencing platform, and standard assembly metrics, such as N50 and BUSCO values. A large proportion of assemblies deviate from their estimated genome size by more than 10%, with increasing deviations in size with increased genome size, suggesting non-protein coding and structural DNA may be to blame. Modest differences in performance of sequencing platforms are noted as well. While standard metrics of genome assessment are more likely to indicate an assembly approaching the estimated genome size, much of the variation in this deviation in size is not explained with these raw metrics. A new, proportional N50 metric (PN50) is proposed, in which N50 values are made relative to the average chromosome size of each species. This new metric has a stronger relationship with complete genome assemblies and, due to its proportional nature, allows for a more direct comparison across assemblies for genomes with variation in sizes and architectures.

Olfactory investigation in the home cage.

We have developed a behavioral paradigm to study volitional olfactory investigation in mice over several months. We placed odor ports in the wall of a standard cage that administer a neutral odorant stimulus when a mouse pokes its nose inside. Even though animals were fed and watered ad libitum, and sampling from the port elicited no outcome other than the delivery of an odor, mice readily sampled these stimuli hundreds of times per day. This self-paced olfactory investigation persisted for weeks with only modest habituation following the first day of exposure to a given set of odorants. If an unexpected odorant stimulus was administered at the port, the sampling rate increased transiently (in the first 20 min) by an order of magnitude and remained higher than baseline throughout the subsequent day, indicating learned implicit knowledge. Thus, this system may be used to study naturalistic olfactory learning over extended time scales outside of conventional task structures.

From Operating Room to Courtroom: Analyzing Malpractice Trajectories in Cranial Neurosurgery.

BACKGROUND AND OBJECTIVES: Nearly all neurosurgeons in the United States will be named defendants in a malpractice claim before retirement. We perform an assessment of national malpractice trends in cranial neurosurgery to inform neurosurgeons on current outcomes, trends over time, benchmarks for malpractice coverage needs, and ways to mitigate lawsuits. METHODS: The Westlaw Edge and LexisNexis databases were searched to identify medical malpractice cases relating to open cranial surgery between 1987 and 2023. Extracted data included date of verdict, jurisdiction, outcome, details of sustained injuries, and any associated award/settlement figures. RESULTS: Of 1550 cases analyzed, 252 were identified as malpractice claims arising from open cranial surgery. The median settlement amount was $950 000 and the average plaintiff ruling was $2 750 000. The highest plaintiff ruling resulted in an award of $28.1 million. Linear regression revealed no significant relationship between year and defendant win (P-value = .43). After adjusting for inflation, award value increased with time (P-value = .01). The most common cranial subspecialties were tumor (67 cases, 26.6%), vascular (54 cases, 21.4%), infection (23 cases, 9.1%), and trauma (23 cases, 9.1%). Perioperative complications was the most common litigation category (96 cases, 38.1%), followed by delayed treatment (40 cases, 15.9%), failure to diagnose (38 cases, 15.1%), and incorrect choice of procedure (29 cases, 11.5%). The states with most claims were New York (40 cases, 15.9%), California (24 cases, 9.5%), Florida (21 cases, 8.3%), and Pennsylvania (20 cases, 7.9%). CONCLUSION: Although a stable number of cases were won by neurosurgeons, an increase in award sizes was observed in the 37-year period assessed. Perioperative complications and delayed treatment/diagnosis were key drivers of malpractice claims.

Reducing NICU Unplanned Extubations From Tube Dislodgement.

OBJECTIVES: Unplanned extubations (UEs) can be a frequent problem and are associated with adverse outcomes. This quality improvement initiative sought to reduce UEs from tube dislodgement in a level IV NICU utilizing methods applicable to other ICUs and performed with minimal monetary funds. METHODS: From January 2019 to July 2023, an interdisciplinary quality improvement team used the Model for Improvement and performed sequential interventions to improve the outcome measure of UEs per 100 ventilator days. Process measures included adherence to a modified, site-specific UE care bundle derived from the Solutions for Patient Safety network, whereas the number of endotracheal tube-related pressure injuries was used as a balancing measure. Statistical process control charts and established rules for special cause variation were applied to analyze data. RESULTS: Sequential interventions reduced the rate of UEs from a baseline of 2.3 to 0.6 UEs per 100 ventilator days. Greater than 90% adherence with the UE care bundle and apparent cause analysis form completion occurred since December 2020. There were no endotracheal tube-related pressure injuries. CONCLUSIONS: A sustained reduction in UEs was demonstrated. Leveraging a multidisciplinary team allowed for continuous UE analysis, which promoted tailored consecutive interventions. UE care bundle audits and the creation of a postevent debrief guide, which helped providers share a common language, were the most impactful interventions. Next steps include disseminating these interventions to other ICUs across our hospital enterprise. These low-cost interventions can be scalable to other NICUs and PICUs.

Genome assembly of the southern pine beetle (Dendroctonus frontalis Zimmerman) reveals the origins of gene content reduction in Dendroctonus.

Dendroctonus frontalis, also known as southern pine beetle (SPB), represents the most damaging forest pest in the southeastern United States. Strategies to predict, monitor and suppress SPB outbreaks have had limited success. Genomic data are critical to inform on pest biology and to identify molecular targets to develop improved management approaches. Here, we produced a chromosome-level genome assembly of SPB using long-read sequencing data. Synteny analyses confirmed the conservation of the core coleopteran Stevens elements and validated the bona fide SPB X chromosome. Transcriptomic data were used to obtain 39,588 transcripts corresponding to 13,354 putative protein-coding loci. Comparative analyses of gene content across 14 beetle and 3 other insects revealed several losses of conserved genes in the Dendroctonus clade and gene gains in SPB and Dendroctonus that were enriched for loci encoding membrane proteins and extracellular matrix proteins. While lineage-specific gene losses contributed to the gene content reduction observed in Dendroctonus, we also showed that widespread misannotation of transposable elements represents a major cause of the apparent gene expansion in several non-Dendroctonus species. Our findings uncovered distinctive features of the SPB gene complement and disentangled the role of biological and annotation-related factors contributing to gene content variation across beetles.

Ethnic minorities treated with new-generation drug-eluting coronary stents in two European randomised clinical trials.

BACKGROUND: Several ethnic minorities have an increased risk of cardiovascular events, but previous European trials that investigated clinical outcome after coronary stenting did not assess the patients' ethnic background. AIMS: To compare ethnic minority and Western European trial participants in terms of both cardiovascular risk profile and 1­year clinical outcome after percutaneous coronary intervention. METHODS: In the BIO-RESORT and BIONYX randomised trials, which assessed new-generation drug-eluting stents, information on patients' self-reported ethnic background was prospectively collected. Pooled patient-level data of 5803 patients, enrolled in the Netherlands and Belgium, were analysed in this prespecified analysis. The main endpoint was target vessel failure after 1 year. RESULTS: Patients were classified as belonging to an ethnic minority (n = 293, 5%) or of Western European origin (n = 5510, 95%). Follow-up data were available in 5772 of 5803 (99.5%) patients. Ethnic minority patients were younger, less often female, more often current smokers, more often medically treated for diabetes, and more often had a positive family history of coronary artery disease. The main endpoint target vessel failure did not differ between ethnic minority and Western European patients (3.5% vs 4.9%, hazard ratio 0.71, 95% confidence interval 0.38-1.33; p = 0.28). There was also no difference in mortality, myocardial infarction, and repeat revascularisation rates. CONCLUSIONS: Despite the unfavourable cardiovascular risk profile of ethnic minority patients, short-term clinical outcome after treatment with contemporary drug-eluting stents was highly similar to that in Western European patients. Further efforts should be made to ensure the enrolment of more ethnic minority patients in future coronary stent trials.

Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccine.

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with SCD and 63 controls. The median proportion of UMBCs was lower in children with SCD compared with controls (4.7% vs. 6.6%, p < .001). Naïve B cells were higher in SCD compared with controls (80.6 vs. 76.3%, respectively, p = .02). UMBC frequency declined by 3.4% per year increase in age in SCD (95% CI: 2%, 4.7%, p < .001), but not in controls. A majority of children in all cohorts had an IgM concentration in the normal range for age and there were no differences between groups (p = .13). Subjects developed titers adequate for long-term protection to fewer serotypes in the polysaccharide vaccine than controls (14.7 vs. 19.4, p < .001). In this cohort, bacteremia was rare and specific clinical complications were not associated with UMBC proportion. In summary, UMBC deficiency occurs in SCD and is associated with age. Future studies should investigate B cell subsets prospectively and identify the mechanism of B cell loss in the spleen.

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Final 5-year report of BIONYX comparing the thin-composite wire-strut zotarolimus-eluting stent versus ultrathin-strut sirolimus-eluting stent.

BACKGROUND: The BIONYX randomized trial is the first study to evaluate the Resolute Onyx durable polymer-coated zotarolimus-eluting stent (ZES) in all-comers. Furthermore, it is the first trial to assess safety and efficacy of this stent versus the Orsiro biodegradable-polymer sirolimus-eluting stent (SES) in all-comers, paying particular attention to patients with diabetes. It has previously shown promising results until 3 years of follow-up. AIMS: We aimed to assess long-term clinical outcome after percutaneous coronary intervention (PCI) with Onyx ZES versus Orsiro SES at 5-year follow-up. METHODS: The main composite endpoint was target vessel failure (TVF): cardiac death, target vessel myocardial infarction, or target vessel revascularization. Time to primary and secondary endpoints was assessed using Kaplan-Meier methods, applying the log-rank test for between-group comparison. RESULTS: Follow-up was available in 2414/2488 (97.0%) patients. After 5 years, TVF showed no significant difference between Onyx ZES and Orsiro SES (12.7% vs. 13.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] [0.75-1.17], plog-rank = 0.55). Landmark analysis between 3- and 5-year follow-up found a lower target lesion revascularization rate for Onyx ZES (1.1% vs. 2.4%, HR 0.47, 95% CI [0.24-0.93], plog-rank = 0.026). A prespecified subgroup analysis showed no significant between-stent difference in clinical outcome among patients with diabetes. After treatment with Onyx ZES, patients aged ≥75 years had significantly lower rates of TVF (13.8% vs. 21.9%, HR 0.60, 95% CI [0.39-0.93], plog-rank = 0.023). CONCLUSIONS: The final 5-year analysis of the randomized BIONYX trial showed favorable and similar long-term outcomes of safety and efficacy for Onyx ZES and Orsiro SES in both all-comers and patients with diabetes.