IL-1ß Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice.

BACKGROUND: Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions is the global leading cause of death. The most common and effective means to reduce these major adverse cardiovascular events, including myocardial infarction and stroke, is aggressive lipid lowering via a combination of drugs and dietary modifications. However, we know little regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering. METHODS: Smooth muscle cell lineage-tracing Apoe-/- mice were fed a high-cholesterol Western diet for 18 weeks and then a zero-cholesterol standard laboratory diet for 12 weeks before treating them with an IL (interleukin)-1ß or control antibody for 8 weeks. We assessed lesion size and remodeling indices, as well as the cellular composition of aortic and brachiocephalic artery lesions, indices of plaque stability, overall plaque burden, and phenotypic transitions of smooth muscle cell and other lesion cells by smooth muscle cell lineage tracing combined with single-cell RNA sequencing, cytometry by time-of-flight, and immunostaining plus high-resolution confocal microscopic z-stack analysis. RESULTS: Lipid lowering by switching Apoe-/- mice from a Western diet to a standard laboratory diet reduced LDL cholesterol levels by 70% and resulted in multiple beneficial effects including reduced overall aortic plaque burden, as well as reduced intraplaque hemorrhage and necrotic core area. However, contrary to expectations, IL-1ß antibody treatment after diet-induced reductions in lipids resulted in multiple detrimental changes including increased plaque burden and brachiocephalic artery lesion size, as well as increasedintraplaque hemorrhage, necrotic core area, and senescence as compared with IgG control antibody-treated mice. Furthermore, IL-1ß antibody treatment upregulated neutrophil degranulation pathways but downregulated smooth muscle cell extracellular matrix pathways likely important for the protective fibrous cap. CONCLUSIONS: Taken together, IL-1ß appears to be required for the maintenance of standard laboratory diet-induced reductions in plaque burden and increases in multiple indices of plaque stability.

Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency.

Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. In the formative state, genes important for pluripotency exit establish contacts with emerging enhancers within these multiway hubs, suggesting that the structural changes we have observed may play an important role in modulating transcription and establishing new cell identities.

IL-1ß inhibition partially negates the beneficial effects of diet-induced lipid lowering.

Background: Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions are the leading cause of death in the world. The most common and effective means to reduce these major adverse cardiovascular events (MACE), including myocardial infarction (MI) and stroke, is aggressive lipid lowering via a combination of drugs and dietary modifications. However, little is known regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering. Methods: Smooth muscle cell (SMC)-lineage tracing Apoe-/- mice were fed a Western diet (WD) for 18 weeks and then switched to a low-fat chow diet for 12 weeks. We assessed lesion size and remodeling indices, as well as the cellular composition of aortic and brachiocephalic artery (BCA) lesions, indices of plaque stability, overall plaque burden, and phenotypic transitions of SMC, and other lesion cells by SMC-lineage tracing combined with scRNA-seq, CyTOF, and immunostaining plus high resolution confocal microscopic z-stack analysis. In addition, to determine if treatment with a potent inhibitor of inflammation could augment the benefits of chow diet-induced reductions in LDL-cholesterol, SMC-lineage tracing Apoe-/- mice were fed a WD for 18 weeks and then chow diet for 12 weeks prior to treating them with an IL-1ß or control antibody (Ab) for 8-weeks. Results: Lipid-lowering by switching Apoe-/- mice from a WD to a chow diet reduced LDL-cholesterol levels by 70% and resulted in multiple beneficial effects including reduced overall aortic plaque burden as well as reduced intraplaque hemorrhage and necrotic core area. However, contrary to expectations, IL-1ß Ab treatment resulted in multiple detrimental changes including increased plaque burden, BCA lesion size, as well as increased cholesterol crystal accumulation, intra-plaque hemorrhage, necrotic core area, and senescence as compared to IgG control Ab treated mice. Furthermore, IL-1ß Ab treatment upregulated neutrophil degranulation pathways but down-regulated SMC extracellular matrix pathways likely important for the protective fibrous cap. Conclusions: Taken together, IL-1ß appears to be required for chow diet-induced reductions in plaque burden and increases in multiple indices of plaque stability.

Disturbance of eucalypt forests alters the composition, function, and assembly of soil microbial communities.

Forest disturbance has well-characterized effects on soil microbial communities in tropical and northern hemisphere ecosystems, but little is known regarding effects of disturbance in temperate forests of the southern hemisphere. To address this question, we collected soils from intact and degraded Eucalyptus forests along an east-west transect across Tasmania, Australia, and characterized prokaryotic and fungal communities using amplicon sequencing. Forest degradation altered soil microbial community composition and function, with consistent patterns across soil horizons and regions of Tasmania. Responses of prokaryotic communities included decreased relative abundance of Acidobacteriota, nitrifying archaea, and methane-oxidizing prokaryotes in the degraded forest sites, while fungal responses included decreased relative abundance of some saprotrophic taxa (e.g. litter saprotrophs). Forest degradation also reduced network connectivity in prokaryotic communities and increased the importance of dispersal limitation in assembling both prokaryotic and fungal communities, suggesting recolonization dynamics drive microbial composition following disturbance. Further, changes in microbial functional groups reflected changes in soil chemical properties-reductions in nitrifying microorganisms corresponded with reduced NO3-N pools in the degraded soils. Overall, our results show that soil microbiota are highly responsive to forest degradation in eucalypt forests and demonstrate that microbial responses to degradation will drive changes in key forest ecosystem functions.

Evaluating the role of bacterial diversity in supporting soil ecosystem functions under anthropogenic stress.

Ecosystem functions and services are under threat from anthropogenic global change at a planetary scale. Microorganisms are the dominant drivers of nearly all ecosystem functions and therefore ecosystem-scale responses are dependent on responses of resident microbial communities. However, the specific characteristics of microbial communities that contribute to ecosystem stability under anthropogenic stress are unknown. We evaluated bacterial drivers of ecosystem stability by generating wide experimental gradients of bacterial diversity in soils, applying stress to the soils, and measuring responses of several microbial-mediated ecosystem processes, including C and N cycling rates and soil enzyme activities. Some processes (e.g., C mineralization) exhibited positive correlations with bacterial diversity and losses of diversity resulted in reduced stability of nearly all processes. However, comprehensive evaluation of all potential bacterial drivers of the processes revealed that bacterial α diversity per se was never among the most important predictors of ecosystem functions. Instead, key predictors included total microbial biomass, 16S gene abundance, bacterial ASV membership, and abundances of specific prokaryotic taxa and functional groups (e.g., nitrifying taxa). These results suggest that bacterial α diversity may be a useful indicator of soil ecosystem function and stability, but that other characteristics of bacterial communities are stronger statistical predictors of ecosystem function and better reflect the biological mechanisms by which microbial communities influence ecosystems. Overall, our results provide insight into the role of microorganisms in supporting ecosystem function and stability by identifying specific characteristics of bacterial communities that are critical for understanding and predicting ecosystem responses to global change.

Machine-learning-derived heart and brain age are independently associated with cognition.

BACKGROUND AND PURPOSE: A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated. METHODS: Using 12-lead electrocardiograms, heart age was estimated for a population-based sample (N = 7779, age 40-85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis. RESULTS: Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3-36) of the HDA effect on the tapping test score was mediated through BDA. DISCUSSION: Heart delta age, representing the cumulative effects of life-long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA.

Volatile and Dissolved Organic Carbon Sources Have Distinct Effects on Microbial Activity, Nitrogen Content, and Bacterial Communities in Soil.

Variation in microbial use of soil carbon compounds is a major driver of biogeochemical processes and microbial community composition. Available carbon substrates in soil include both low molecular weight-dissolved organic carbon (LMW-DOC) and volatile organic compounds (VOCs). To compare the effects of LMW-DOC and VOCs on soil chemistry and microbial communities under different moisture regimes, we performed a microcosm experiment with five levels of soil water content (ranging from 25 to 70% water-holding capacity) and five levels of carbon amendment: a no carbon control, two dissolved compounds (glucose and oxalate), and two volatile compounds (methanol and α-pinene). Microbial activity was measured throughout as soil respiration; at the end of the experiment, we measured extractable soil organic carbon and total extractable nitrogen and characterized prokaryotic communities using amplicon sequencing. All C amendments increased microbial activity, and all except oxalate decreased total extractable nitrogen. Likewise, individual phyla responded to specific C amendments-e.g., Proteobacteria increased under addition of glucose, and both VOCs. Further, we observed an interaction between moisture and C amendment, where both VOC treatments had higher microbial activity than LMW-DOC treatments and controls at low moisture. Across moisture and C treatments, we identified that Chloroflexi, Nitrospirae, Proteobacteria, and Verrucomicrobia were strong predictors of microbial activity, while Actinobacteria, Bacteroidetes, and Thaumarcheota strongly predicted soil extractable nitrogen. These results indicate that the type of labile C source available to soil prokaryotes can influence both microbial diversity and ecosystem function and that VOCs may drive microbial functions and composition under low moisture conditions.

Unorthodox PCNA Binding by Chromatin Assembly Factor 1.

The eukaryotic DNA replication fork is a hub of enzymes that continuously act to synthesize DNA, propagate DNA methylation and other epigenetic marks, perform quality control, repair nascent DNA, and package this DNA into chromatin. Many of the enzymes involved in these spatiotemporally correlated processes perform their functions by binding to proliferating cell nuclear antigen (PCNA). A long-standing question has been how the plethora of PCNA-binding enzymes exert their activities without interfering with each other. As a first step towards deciphering this complex regulation, we studied how Chromatin Assembly Factor 1 (CAF-1) binds to PCNA. We demonstrate that CAF-1 binds to PCNA in a heretofore uncharacterized manner that depends upon a cation-pi (π) interaction. An arginine residue, conserved among CAF-1 homologs but absent from other PCNA-binding proteins, inserts into the hydrophobic pocket normally occupied by proteins that contain canonical PCNA interaction peptides (PIPs). Mutation of this arginine disrupts the ability of CAF-1 to bind PCNA and to assemble chromatin. The PIP of the CAF-1 p150 subunit resides at the extreme C-terminus of an apparent long α-helix (119 amino acids) that has been reported to bind DNA. The length of that helix and the presence of a PIP at the C-terminus are evolutionarily conserved among numerous species, ranging from yeast to humans. This arrangement of a very long DNA-binding coiled-coil that terminates in PIPs may serve to coordinate DNA and PCNA binding by CAF-1.

Comparing outcomes of radial forearm free flaps and anterolateral thigh free flaps in oral cavity reconstruction: A systematic review and meta-analysis.

OBJECTIVES: To compare surgical morbidity, functional and aesthetic restoration, and health-related quality of life among patients receiving anterolateral thigh (ALT) or radial forearm (RFF) free flaps for intra-oral reconstruction. MATERIALS AND METHODS: PubMed, Medline, EMBASE, CINAHL, and CDSR databases were searched from 2000 to 2022. Primary outcomes included flap survival, recipient site complications, donor site morbidity, recovery of oral function, and quality of life among patients after oncologic resection and reconstruction of oral cavity defects with ALT or RFF. RESULTS: A total of 23 criteria-meeting studies with 685 ALT and 723 RFF patients were included. There were no differences between the two groups in flap survival or the likelihood of flap-related complications. There was a significantly lower likelihood of donor site morbidity among ALT patients, specifically hypertrophic scarring (OR 0.24, 95 % CI: 0.06-0.96), tendon exposure (OR 0.13, 95 % CI: 0.03-0.60), paresthesia (OR: 0.06, 95 % CI: 0.01-0.25), movement impairment (OR: 0.12, 95 % CI: 0.04-0.38), and social stigma (OR: 0.10, 95 % CI: 0.03-0.28). ALT patients were significantly more likely to be satisfied with the donor site appearance (OR: 8.75, 95 % CI: 1.11-68.73). There were no significant differences in recovery of regular diet and speech or quality of life. CONCLUSION: The findings suggest that the ALT achieves equivalent flap survival rates and oral function with less donor site morbidity compared to the RFF for intra-oral reconstruction. Nonetheless, choice of free flap should incorporate surgeon- and patient-specific factors that may not be reflected in the studies included in this meta-analysis.

Design of interactive augmented reality functions for robotic surgery and evaluation in dry-lab lymphadenectomy.

BACKGROUND: Augmented reality (AR) has been widely researched for use in healthcare. Prior AR for robot-assisted minimally invasive surgery has mainly focussed on superimposing preoperative three-dimensional (3D) images onto patient anatomy. This article presents alternative interactive AR tools for robotic surgery. METHODS: We designed, built and evaluated four voice-controlled functions: viewing a live video of the operating room, viewing two-dimensional preoperative images, measuring 3D distances and warning about out-of-view instruments. This low-cost system was developed on a da Vinci Si, and it can be integrated into surgical robots equipped with a stereo camera and a stereo viewer. RESULTS: Eight experienced surgeons performed dry-lab lymphadenectomies and reported that the functions improved the procedure. They particularly appreciated the possibility of accessing the patient's medical records on demand, measuring distances intraoperatively and interacting with the functions using voice commands. CONCLUSIONS: The positive evaluations garnered by these alternative AR functions and interaction methods provide support for further exploration.

Reflections on New Evidence on Crisis Standards of Care in the COVID-19 Pandemic.

Crisis standards of care have been widely developed by healthcare systems and states in the United States during the COVID-19 pandemic, and in some rare cases have actually been used to allocate medical resources. All publicly available U.S. crisis standards of care with a mechanism for allocating scarce resources make use of the Sequential Organ Failure Assessment (SOFA) score in hopes of assigning scarce resources to those patients who are more likely to survive. We reflect on the growing body of evidence suggesting that the SOFA score has limited accuracy in predicting mortality among patients hospitalized with COVID-19 and that the SOFA score systematically disfavors Black patients. Use of the SOFA score for allocating scarce resources may therefore result in Black patients with equal likelihood of survival being deprived of life-saving medical resources. There is also a risk of injustice for patients with non-COVID-19 diagnoses, for whom the SOFA score may be a more accurate prognostic score, but who might nevertheless be unfairly (de)prioritized when assessed alongside COVID-19 patients using the same scoring system. For these reasons we recommend that the SOFA score not be used for triage purposes during the COVID pandemic, and that a national effort be made to develop and empirically test crisis standards of care in advance of the next public health emergency.

Emergent properties of microbial communities drive accelerated biogeochemical cycling in disturbed temperate forests.

Despite ever-increasing availability of detailed information about microbial community structure, relationships of microbial diversity with ecosystem functioning remain unclear. We investigated these relationships at the Coweeta Hydrologic Laboratory, where past forest disturbances (e.g., clear-cut) have altered both ecosystem processes (e.g., increased N export) and microbial communities (e.g., increased bacterial diversity). We sampled soils from disturbed and adjacent reference forests, characterized resident microbial communities, and measured several microbial C-cycle and N-cycle process rates. Microbial communities from historically disturbed soils exhibited altered ecosystem functioning, including generally higher rates of C- and N-cycle processes. Disturbed soil microbial communities also exhibited altered ecosystem multifunctionality, a composite variable consisting of all measured process rates as well as extracellular enzyme activities. Although we found few relationships between ecosystem functions and microbial alpha diversity, all functions were correlated with microbial community composition metrics, particularly r:K strategist ratios of bacterial phyla. Additionally, for both ecosystem multifunctionality and specific processes (i.e., C- and N-mineralization), microbial metrics significantly improved models seeking to explain variation in process rates. Our work sheds light on the links between microbial communities and ecosystem functioning and identifies specific microbial metrics important for modeling ecosystem responses to environmental change.

Historical forest disturbance mediates soil microbial community responses to drought.

Despite the abundance of studies demonstrating the effects of drought on soil microbial communities, the role of land use legacies in mediating these drought effects is unclear. To assess historical land use influences on microbial drought responses, we conducted a drought-rewetting experiment in soils from two adjacent and currently forested watersheds with distinct land use histories: an undisturbed 'reference' site and a 'disturbed' site that was clear-cut and converted to agriculture ~60 years prior. We incubated intact soil cores at either constant moisture or under a drought-rewet treatment and characterized bacterial and fungal communities using amplicon sequencing throughout the experiment. Bacterial alpha diversity decreased following drought-rewetting while fungal diversity increased. Bacterial beta diversity also changed markedly following drought-rewetting, especially in historically disturbed soils, while fungal beta diversity exhibited little response. Additionally, bacterial beta diversity in disturbed soils recovered less from drought-rewetting compared with reference soils. Disturbed soil communities also exhibited notable reductions in nitrifying taxa, increases in putative r-selected bacteria, and reductions in network connectivity following drought-rewetting. Overall, our study reveals historical land use to be important in mediating responses of soil bacterial communities to drought, which will influence the ecosystem-scale trajectories of these environments under ongoing and future climate change.

A Novel Cough Simulation Device for Education of Risk Mitigation Techniques During Aerosol-Generating Medical Procedures.

The COVID-19 pandemic has drawn attention to aerosol-generating medical procedures (AGMPs) in health care environments as a potential mode of transmission. Many organizations and institutions have published AGMP safety guidelines, and several mention the use of simulation in informing their recommendations; however, current methods used to simulate aerosol generation are heterogenous. Creation of a high-fidelity, easily producible aerosol-generating cough simulator would meet a high-priority educational need across all medical specialties. In this communication, we describe the design, construction, and user study of a novel cough simulator, which demonstrates the utility of simulation in raising AGMP safety awareness for providers of all roles, specialties, and training levels.

Fit for Purpose Assessment: A New Direction for IACUCs.

The organization and function of the institutional animal care and use committee (IACUC) is the key component of government regulation and oversight of necessary scientific research using live animals and of AAALAC - International accreditation of animal care and use programs in the United States. The regulations, roles, and responsibilities of IACUCs have evolved since their inception 35 years ago from a limited focus on animal welfare and specific animal procedures to embracing scientific quality, data reproducibility and translation, and animal welfare as inextricably interdependent and critical components of generation of new scientific knowledge and medical treatments. A current challenge for IACUCs is in evaluating whether benefits to be derived (eg, new knowledge or treatments) justify any unavoidable pain, stress, or injury associated with proposed research protocols, because the former are long-term and at best speculative outcomes, whereas the latter are immediate and tangible for the study animals. Scientific consensus is that research most likely to generate significant new knowledge and medical treatments is that conducted to high scientific, technical, and quality standards and reported with full transparency to facilitate reproducibility. As an alternative to current benefits evaluations included in risk benefit and harm benefit constructs, the authors propose that IACUCs assess the proposed research for scientific quality and alignment of study elements with the study purpose (e.g., Fit for Purpose [FfP]), including justifications for study design components, selection of primary endpoints and technologies, rationale for data and statistical analyses, and research communication plans. Fit for Purpose endpoints are objective, immediate, and impactful as are the potential risks for study animals, and at the same time they are the best predictors for achievement of longer-term benefits. We propose that IACUCs and any revision of The ILAR Guide consider FfP concepts in place of traditional benefits assessment to accelerate the generation of new knowledge and treatments benefiting medical and veterinary patients and the environment through better science and animal welfare rather than to continue to rely on speculative future outcomes.

Historical land use has long-term effects on microbial community assembly processes in forest soils.

Land use change has long-term effects on the structure of soil microbial communities, but the specific community assembly processes underlying these effects have not been identified. To investigate effects of historical land use on microbial community assembly, we sampled soils from several currently forested watersheds representing different historical land management regimes (e.g., undisturbed reference, logged, converted to agriculture). We characterized bacterial and fungal communities using amplicon sequencing and used a null model approach to quantify the relative importance of selection, dispersal, and drift processes on bacterial and fungal community assembly. We found that bacterial communities were structured by both selection and neutral (i.e., dispersal and drift) processes, while fungal communities were structured primarily by neutral processes. For both bacterial and fungal communities, selection was more important in historically disturbed soils compared with adjacent undisturbed sites, while dispersal processes were more important in undisturbed soils. Variation partitioning identified the drivers of selection to be changes in vegetation communities and soil properties (i.e., soil N availability) that occur following forest disturbance. Overall, this study casts new light on the effects of historical land use on soil microbial communities by identifying specific environmental factors that drive changes in community assembly.

A Review of Otolaryngology Malpractice Cases with Associated Court Proceedings from 2010 to 2019.

OBJECTIVES/HYPOTHESIS: To report key characteristics of the landscape of malpractice litigation with associated court proceedings in otolaryngology over the previous decade. STUDY DESIGN: Retrospective database review. METHODS: The LexisNexis database was queried to identify otolaryngology-related malpractices cases that yielded court opinions, jury verdicts, and settlements from federal and state courts across the United States from 2010 to 2019. Cases settled outside of court were not identifiable. Provider subspecialty, procedures, error type, legal allegations, and case outcomes were recorded. Frequency of error type was compared between otolaryngology subspecialties using Fisher exact tests. RESULTS: Ninety-four medical malpractice cases related to otolaryngology with evidence of court proceedings were identified for the period between 2010 and 2019. An otolaryngologist was named as the sole defendant in 39 cases (41%). Rhinology was the most frequently implicated subspecialty (28% of all cases), followed by head and neck surgery (17%) and facial plastics (7%). Improper surgical performance was cited in nearly half of the identified cases (49%), followed by failure to diagnose/refer/treat (32%). Outcome and liability data were available for 56 cases (60%). Of these 56 cases, 50 (89%) were ruled in favor of the defendant otolaryngologist. Of the cases ruled in favor of the plaintiff, the average indemnity was $4.24 M (range, $150,000 M-$10.25 M). Fisher exact tests demonstrated statistically significant differences in consent issues (P = .040), failure to diagnose/refer/treat (P = .024), and improper surgical performance (P = .026) between subspecialties. CONCLUSIONS: In a limited, database-derived sample of medical malpractice cases involving otolaryngologists, trends in error type by subspecialty may warrant further investigation to identify specialty-wide and subspecialty-specific areas of practice improvement and education. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:E1081-E1085, 2021.

National Database Research in Head and Neck Reconstructive Surgery: A Call for Increased Transparency and Reproducibility.

OBJECTIVE: To reproduce a published study comparing outcomes of patients who underwent microvascular reconstruction by plastic surgeons and otolaryngologists and to examine how case selection and methodology using the National Surgical Quality Improvement Program (NSQIP) data set can affect results and conclusions. STUDY DESIGN: Cross-sectional analysis of US national database. SETTING: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2005 to 2017. SUBJECTS AND METHODS: A recently published study that used the NSQIP database to compare outcomes after head and neck free tissue transfer between plastic surgeons and otolaryngologists was reproduced. Different approaches to case selection and statistical analysis were evaluated and their effects on statistical significance and study conclusions were compared. RESULTS: When all cases of free tissue transfer, captured in NSQIP between 2005 and 2017, were compared between plastic surgery and otolaryngology, plastic surgery patients appeared to have lower rates of complications and length of stay. However, a more in-depth analysis demonstrated that these results were confounded by older and sicker otolaryngology patients. A second analysis of the same NSQIP data, limited to only head and neck oncologic reconstructions, demonstrated that otolaryngology patients had fewer complications on univariate and multivariable analysis. CONCLUSION: We demonstrated how case selection and analysis can significantly affect results. It is incumbent upon researchers who use NSQIP and other publicly available data sets to fully detail their methodology to allow other researchers to reproduce and evaluate their work and for the journal editorial process to carefully evaluate the methodology and conclusions of their contributing authors.

Impact of Lymph Node Yield on Survival in Surgically Treated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: (1) To estimate the association between neck dissection lymph node yield (LNY) and survival among patients with surgically treated human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). (2) To identify a clinically relevant quality metric for surgical treatment of HPV-related OPSCC. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. SUBJECTS AND METHODS: From the National Cancer Database, 4130 patients were identified with HPV-associated OPSCC treated with primary surgery from 2010 to 2016. Based on prior literature, an adequate neck dissection LNY was defined as ≥18 lymph nodes. To determine whether LNY is associated with survival, univariable and multivariable Cox proportional hazards regression was performed. Analysis was stratified by adjuvant therapy regimen. RESULTS: A total of 2113 patients (51.2%) underwent surgery with or without adjuvant radiation (S ± RT), and 2017 patients (48.8%) underwent surgery with adjuvant chemoradiation. LNY ≥18 was associated with a 5-year survival benefit of 7.15% (91.7% for LNY ≥18, 84.5% for LNY <18, P = .004) for the S ± RT cohort on unadjusted survival analysis. For the S ± RT group, LNY ≥18 was associated with decreased hazard of death (hazard ratio, 0.45; 95% CI, 0.29-0.70; P < .001) after adjustment for patient characteristics, TNM staging, surgical margins, extranodal extension, and treating facility characteristics. For surgery with adjuvant chemoradiation, the adjusted hazard ratio estimate for LNY ≥18 was 0.64 (95% CI, 0.41-1.00), but the result was not statistically significant (P = .052). CONCLUSION: An adequate LNY from a neck dissection may affect survival when HPV-related OPSCC is treated with up-front surgery.