Evaluating the 2023 Standardized Letter of Recommendation Form in Applications to Orthopaedic Surgery Residency.

BACKGROUND: Successfully matching into orthopaedic surgery residency is a challenging endeavor due to the limited number of available positions. Implementation of the Standard Letter of Recommendation (SLOR) in 2017 was intended to allow better comparisons between applicants; however, the form suffered from notable rank inflation ultimately requiring introduction of an updated SLOR for the 2023 to 2024 application cycle. The purpose of this study was to evaluate whether the 2023 SLOR improves on deficiencies of the 2017 SLOR. METHODS: Applications submitted to our institution during the 2023 to 2024 orthopaedic surgery residency application cycle were analyzed. Applicant objective metrics were collected, including US Medical Licensing Exam scores, clerkship grades, AΩA status, and research productivity. Scores for each domain of the 2023 SLOR forms were recorded. Mean scores were calculated for each question, and cumulative scores per SLOR were determined. Intraclass correlation coefficients were determined per applicant and evaluator. The Spearman rank correlation coefficient was calculated for comparison of SLOR cumulative scores and objective metrics. RESULTS: Three hundred sixty-eight applications were reviewed, and 743 2023 SLORs were submitted in conjunction with these applications. Most of the 2023 SLORs (n = 399, 53.70%) had cumulative scores placing applicants in at least the 90th percentile. Furthermore, 267 evaluators (72.36%) consistently gave scores of 99s and 10s for each question. Intraclass correlation coefficients were rated as fair to moderate agreement between evaluators for each applicant. Objective applicant metrics did not meaningfully correlate with SLOR cumulative scores. DISCUSSION: The 2023 SLOR demonstrated notable rank inflation with only 22.7% of applicants receiving a score of less than 7 on any domain. By contrast, 69.9% of applicants received a score of "rare, perfect gem" on at least one domain of the form. We encourage the American Orthopaedic Association Council of Orthopaedic Residency Director to continue to improve the form and provide guidance to residency program leadership on proper use of the grading system.

ClearScope: a fully integrated light sheet theta microscope for sub-cellular resolution imaging without lateral size constraints.

Three-dimensional (3D) ex vivo imaging of cleared intact brains of animal models and large human and non-human primate postmortem brain specimens is important for understanding the physiological neural network connectivity patterns and the pathological alterations underlying neuropsychiatric and neurological disorders. Light-sheet microscopy has emerged as a highly effective imaging modality for rapid high-resolution imaging of large cleared samples. However, the orthogonal arrangements of illumination and detection optics in light sheet microscopy limits the size of specimen that can be imaged. Recently developed light sheet theta microscopy (LSTM) technology addressed this by utilizing a unique arrangement of two illumination light paths oblique to the detection light path, while allowing perpendicular arrangement of the detection light path relative to the specimen surface. Here, we report development of a next-generation, fully integrated, and user-friendly LSTM system for rapid sub-cellular resolution imaging uniformly throughout a large specimen without constraining the lateral (XY) size. In addition, we provide a seamlessly integrated workflow for image acquisition, data storage, pre- and post-processing, enhancement, and quantitative analysis. We demonstrate the system performance by high-resolution 3D imaging of intact mouse brains and human brain samples, and complete data analysis including digital neuron tracing, vessel reconstruction and design-based stereological analysis in 3D. This technically enhanced and user-friendly LSTM implementation will enable rapid quantitative mapping of molecular and cellular features of interests in diverse types of very large samples.

The Pseudomonas aeruginosa sphBC genes are important for growth in the presence of sphingosine by promoting sphingosine metabolism.

Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing of susceptible bacteria. Pseudomonas aeruginosa is a common opportunistic pathogen that is less susceptible to sphingosine than many Gram-negative bacteria. Here, we determined that deletion of the sphBCD operon reduced growth in the presence of sphingosine. Using deletion mutants, complementation, and growth assays in P. aeruginosa PAO1, we determined that the sphC and sphB genes, encoding a periplasmic oxidase and periplasmic cytochrome c, respectively, were important for growth on sphingosine, while sphD was dispensable under these conditions. Deletion of sphBCD in P. aeruginosa PA14, P. protegens Pf-5, and P. fluorescens Pf01 also showed reduced growth in the presence of sphingosine. The P. aeruginosa sphBC genes were also important for growth in the presence of two other sphingoid bases, phytosphingosine and sphinganine. In wild-type P. aeruginosa, sphingosine is metabolized to an unknown non-inhibitory product, as sphingosine concentrations drop in the culture. However, in the absence of sphBC, sphingosine accumulates, pointing to SphC and SphB as having a role in sphingosine metabolism. Finally, metabolism of sphingosine by wild-type P. aeruginosa protected susceptible cells from full growth inhibition by sphingosine, pointing to a role for sphingosine metabolism as a public good. This work shows that metabolism of sphingosine by P. aeruginosa presents a novel pathway by which bacteria can alter host-derived sphingolipids, but it remains an open question whether SphB and SphC act directly on sphingosine.

Topology-Driven Discovery of Transmembrane Protein S-Palmitoylation.

Protein S-palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs), S-palmitoylation is implicated in conditions from inflammatory disorders to respiratory viral infections. Many small-scale experiments have observed S-palmitoylation at juxtamembrane Cys residues. However, most large-scale S-palmitoyl discovery efforts rely on trypsin-based proteomics within which hydrophobic juxtamembrane regions are likely underrepresented. Machine learning- by virtue of its freedom from experimental constraints - is particularly well suited to address this discovery gap surrounding TMP S-palmitoylation. Utilizing a UniProt-derived feature set, a gradient boosted machine learning tool (TopoPalmTree) was constructed and applied to a holdout dataset of viral S-palmitoylated proteins. Upon application to the mouse TMP proteome, 1591 putative S-palmitoyl sites (i.e. not listed in SwissPalm or UniProt) were identified. Two lung-expressed S-palmitoyl candidates (synaptobrevin Vamp5 and water channel Aquaporin-5) were experimentally assessed. Finally, TopoPalmTree was used for rational design of an S-palmitoyl site on KDEL-Receptor 2. This readily interpretable model aligns the innumerable small-scale experiments observing juxtamembrane S-palmitoylation into a proteomic tool for TMP S-palmitoyl discovery and design, thus facilitating future investigations of this important modification.

Mitonuclear effects on sex ratio persist across generations in interpopulation hybrids.

Eukaryotic energy production requires tight coordination between nuclear and mitochondrial gene products. Because males and females often have different energetic strategies, optimal mitonuclear coordination may be sex-specific. Previous work found evidence for sex-specific mitonuclear effects in the copepod Tigriopus californicus by comparing two parental lines and their reciprocal F1 crosses. However, an alternative hypothesis is that the patterns were driven by the parental source of nuclear alleles. Here we test this alternative hypothesis by extending the same cross to F2 hybrids, who receive both maternal and paternal nuclear alleles from F1 hybrids. Results confirm mitonuclear effects on sex ratio, with distorted ratios persisting from the F1 to F2 generations, despite reduced fitness in F2 hybrids. No sex by cross interactions were found for other phenotypic traits measured. Mitochondrial DNA content was higher in females. Both routine metabolic rate and oxidative DNA damage were lower in F2 hybrids than in parentals. The persistence of sex-specific mitonuclear effects, even in the face of F2 hybrid breakdown, attests to the magnitude of these effects, which contribute to the maintenance of within-population mitochondrial DNA polymorphisms.

Neurosurgical Residency Training at Veterans Affairs Medical Centers, the Resident Perspective.

BACKGROUND AND OBJECTIVE: Department of Veteran's Affairs (VA) Medical Centers play a crucial role in training neurosurgery residents. Although previous studies have examined the impact of VA rotations from the attending perspective, the resident experience remains unexplored. We present a national survey of neurosurgery residents to assess their perceptions of VA rotations, focusing on operative experience, call burden, longitudinal patient care experiences, and overall strengths and limitations. METHODS: A 33-question survey was distributed by email to all neurosurgery residents who had previously completed a VA rotation within the past 7 years. RESULTS: Responses were received from 77 residents, representing 36 out of 40 neurosurgical residency programs with an active VA rotation. Most residents (79.2%) found their VA rotations adequate in length, having spent a median of 5 months at the VA. Residents completed an average of 11.7 (SD 7.2) cases per month while at the VA, including 8.9 (SD 5.5) spine, 1.7 (SD 2.0) cranial, and 1.4 (SD 1.6) peripheral nerve cases. Many residents reported completing a greater proportion of spine and peripheral nerve cases at the VA compared with their primary clinical sites. Across all postgraduate years, residents felt that the VA offered increased operative autonomy (79.0% agreement) at the expense of total operative volume (98.7% agreement) and complexity (81.9% agreement). Importantly, 94.8% of residents participated in longitudinal patient care experiences, and 59.7% followed all patients longitudinally. CONCLUSION: The resident experience at the VA varies, presenting both strengths and limitations. Addressing these factors could enhance the overall effectiveness of VA rotations in neurosurgical training programs in the future.

Mammals show faster recovery from capture and tagging in human-disturbed landscapes.

Wildlife tagging provides critical insights into animal movement ecology, physiology, and behavior amid global ecosystem changes. However, the stress induced by capture, handling, and tagging can impact post-release locomotion and activity and, consequently, the interpretation of study results. Here, we analyze post-tagging effects on 1585 individuals of 42 terrestrial mammal species using collar-collected GPS and accelerometer data. Species-specific displacements and overall dynamic body acceleration, as a proxy for activity, were assessed over 20 days post-release to quantify disturbance intensity, recovery duration, and speed. Differences were evaluated, considering species-specific traits and the human footprint of the study region. Over 70% of the analyzed species exhibited significant behavioral changes following collaring events. Herbivores traveled farther with variable activity reactions, while omnivores and carnivores were initially less active and mobile. Recovery duration proved brief, with alterations diminishing within 4-7 tracking days for most species. Herbivores, particularly males, showed quicker displacement recovery (4 days) but slower activity recovery (7 days). Individuals in high human footprint areas displayed faster recovery, indicating adaptation to human disturbance. Our findings emphasize the necessity of extending tracking periods beyond 1 week and particular caution in remote study areas or herbivore-focused research, specifically in smaller mammals.

Risk Factors for Femoral Head Collapse in Osteonecrosis.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) affects at least 20,000 patients annually in the United States; however, the pathophysiology of disease progression is poorly understood. The purpose of this study was to determine the relative importance of three distinct elements and their relationship to the collapse of the femoral head: (1) identifiable risk factors; (2) femoral head anatomy; and (3) the extent of the necrotic lesion. METHODS: A single-center retrospective cohort study was performed on patients ≥ 18 years old who presented with ONFH. Ficat classification and femoral head anatomic parameters were measured on radiographs. Osteonecrotic lesion size was measured on magnetic resonance imaging using four validated methods. Multivariable regression analyses were performed to identify predictors of femoral head collapse. RESULTS: There were 105 patients and 137 hips included in the final cohort, of which 50 (36.5%) had collapse of the femoral head. Multivariable analyses demonstrated that medical risk factors (adjusted odds ratio (aOR): 1.15), alcohol exposure (aOR: 1.23), and increased alpha angle (aOR: 4.51) were predictive of femoral head collapse. Increased femoral head offset (aOR: 0.54) was protective against collapse. An increased size of the osteonecrotic lesion was significantly predictive of collapse with all four measure methods evaluated: three-dimensional (3D) volumetric (aOR: 3.73), modified Kerboul (aOR: 2.92), index of necrotic extent (aOR: 1.91), and modified index of necrotic extent (aOR: 2.05). CONCLUSIONS: In an analysis of patients who had ONFH, we identified risk factors such as alcohol exposure, high alpha angle, increased lesion size, and decreased femoral offset as increasing the risk of femoral head collapse. Given the challenges of studying this patient population, large prospective studies of patients who have ONFH should seek to identify whether these factors are reliable indicators of femoral head collapse.

Arbuscular mycorrhizal fungal spore communities and co-occurrence networks demonstrate host-specific variation throughout the growing season.

Microbial community assembly involves a series of ecological filtering mechanisms that determine the composition of microbial communities. While the importance of both broad and local level factors on microbial communities has been reasonably well studied, this work often is limited to single observations and neglects to consider how communities change over time (i.e., seasonal variation). Because seasonal variation is an important determinant of community assembly and determines the relative importance of community assembly filters, this represents a key knowledge gap. Due to their close associations with seasonal variation in plant growth and fitness, arbuscular mycorrhizal (AM) fungi are useful groups for assessing the importance of seasonal dynamics in microbial community assembly. We tested how seasonal variation (spring vs. summer), plant life history stage (vegetative vs. flowering), and host plant species (Baptisia bracteata var. leucophaea & Andropogon gerardii) influenced AM fungal spore community assembly. AM fungal spore community temporal dynamics were closely linked to plant host species and life history stage. While AM fungal spore communities demonstrated strong turnover between the spring (e.g., higher sporulation) and late summer (e.g., higher diversity), the strength and direction of these changes was modified by host plant species. Here we demonstrate the importance of considering temporal variation in microbial community assembly, and also show how plant-microbe interactions can modify seasonal trends in microbial community dynamics.

Changes in higher order cognitive function between four watch keeping schedules.

Maritime industries utilize many different watch keeping schedules to maintain vigilance and crew safety around the clock. These schedules can be fatiguing, negatively impacting vigilant attention. This has led to the consideration of schedules that might allow for more sleep time, but how these schedules impact higher order cognitive function remains unclear. These schedules require assessment with tasks that are relevant to real-world operations on maritime vessels. This study investigated the effect of four schedules on higher order cognitive function. N = 27 (16 female) participants were recruited to a 10-day laboratory study, comparing four schedules. The schedules investigated were eight-on/eight-off/four-on/four-off (8/8/4/4) with sleep from 09:30 to 16:00 (condition A); six-on/six-off (6/6) with sleep from 08:30 to 12:30 and 21:30 to 00:00 (condition B); four-on/four-off (4/4/4/4/4/4) with sleep from 18:00 to 00:30 (condition C); and four-on/four-off (4/4/4/4/4/4) with sleep from 01:30 to 08:00 (condition D). Higher order cognitive function was assessed 2-3× daily whilst "on watch" using tests of visual scanning, learning, working memory, mental flexibility, and visuomotor control. Conditions were ranked and stability of performance on watch was compared between conditions using Kruskal-Wallis tests. Cognitive function within condition B was ranked the worst for most of the tasks. However, the stability of higher order cognitive function was poorest across the waking day within condition A. These findings highlight the variability in cognitive capacities during different watch keeping schedules.

12-Lipoxygenase inhibition suppresses islet immune and inflammatory responses and delays autoimmune diabetes in human gene replacement mice.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing ß cells and involves an interplay between ß cells and cells of the innate and adaptive immune systems. We investigated the therapeutic potential of targeting 12-lipoxygenase (12-LOX), an enzyme implicated in inflammatory pathways in ß cells and macrophages, using a mouse model in which the endogenous mouse Alox15 gene is replaced by the human ALOX12 gene. Our findings demonstrate that VLX-1005, a potent 12-LOX inhibitor, effectively delays the onset of autoimmune diabetes in human gene replacement non-obese diabetic (NOD) mice. By spatial proteomics analysis, VLX-1005 treatment resulted in marked reductions in infiltrating T and B cells and macrophages with accompanying increases in immune checkpoint molecules PD-L1 and PD-1, suggesting a shift towards an immune-suppressive microenvironment. RNA sequencing analysis of isolated islets from inhibitor-treated mice revealed significant alteration of cytokine-responsive pathways. RNA sequencing of polarized proinflammatory macrophages showed that VLX-1005 significantly reduced the interferon response. Our studies demonstrate that the ALOX12 human replacement gene mouse provides a platform for the preclinical evaluation of LOX inhibitors and supports VLX-1005 as an inhibitor of human 12-LOX that engages the enzymatic target and alters the inflammatory phenotypes of islets and macrophages to promote the delay of autoimmune diabetes.

Stable transduction of the neonatal mouse liver using a hybrid rAAV/sleeping beauty transposon gene delivery system.

BACKGROUND: Conventional adeno-associated viral (AAV) vectors, while highly effective in quiescent cells such as hepatocytes in the adult liver, confer less durable transgene expression in proliferating cells owing to episome loss. Sustained therapeutic success is therefore less likely in liver disorders requiring early intervention. We have previously developed a hybrid, dual virion approach, recombinant AAV (rAAV)/piggyBac transposon system capable of achieving stable gene transfer in proliferating hepatocytes at levels many fold above conventional AAV vectors. An alternative transposon system, Sleeping Beauty, has been widely used for ex vivo gene delivery; however liver-targeted delivery using a hybrid rAAV/Sleeping Beauty approach remains relatively unexplored. METHODS: We investigated the capacity of a Sleeping Beauty (SB)-based dual rAAV virion approach to achieve stable and efficient gene transfer to the newborn murine liver using transposable therapeutic cassettes encoding coagulation factor IX or ornithine transcarbamylase (OTC). RESULTS: At equivalent doses, rAAV/SB100X transduced hepatocytes with high efficiency, achieving stable expression into adulthood. Compared with conventional AAV, the proportion of hepatocytes transduced, and factor IX and OTC activity levels, were both markedly increased. The proportion of hepatocytes stably transduced increased 4- to 8-fold from <5%, and activity levels increased correspondingly, with markedly increased survival and stable urinary orotate levels in the OTC-deficient Spfash mouse following elimination of residual endogenous murine OTC. CONCLUSIONS: The present study demonstrates the first in vivo utility of a hybrid rAAV/SB100X transposon system to achieve stable long-term therapeutic gene expression following delivery to the highly proliferative newborn mouse liver. These results have relevance to the treatment of genetic metabolic liver diseases with neonatal onset.

Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial.

BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.

Longitudinal Improvement in Public Speaking Skills Through Participation in a Resident Public Speaking Curriculum.

OBJECTIVE: To promote public speaking skills, a pediatrics residency program developed a longitudinal public speaking curriculum grounded in deliberate practice and reflective practice. METHODS: Residents delivered annual presentations and received formal feedback. Audience evaluation forms from 2005-2017 were included for analysis. The form used 5-point scales (5= best) for specific presentation elements (clarity, eye contact/body language, pace, succinct text, minimally distracting delivery, clear conclusion, appropriate learning objectives, achieving learning objectives, and answering questions) and for overall quality. Longitudinal changes in scores were analyzed with paired t tests. RESULTS: Overall, 5,771 evaluations of 276 presentations given by 97 residents were analyzed. Between post-graduate year (PGY)-1 and PGY-3 presentations, mean overall rating increased from 4.38 to 4.59 (P<.001, d=0.51). The median percentage of 5-point scores increased from 50.0% (IQR, 24.3%-65.4%) to 72.5% (IQR, 53.3%-81.2%). Eight of 9 specific elements showed significant increases (median effect size 0.55). Residents whose initial presentations ranked in the bottom quartile had larger improvements than residents initially ranked in the top quartile. CONCLUSIONS: After pediatric residents participated in a public speaking curriculum with targeted objectives, formal feedback, and repeated practice, their public speaking skills improved. Public speaking curricula can and should be adopted more broadly in graduate medical education.

Active mutual conjoint estimation of multiple contrast sensitivity functions.

Recent advances in nonparametric contrast sensitivity function (CSF) estimation have yielded a new tradeoff between accuracy and efficiency not available to classical parametric estimators. An additional advantage of this new framework is the ability to independently tune multiple aspects of the estimator to seek further improvements. Machine learning CSF estimation with Gaussian processes allows for design optimization in the kernel, acquisition function, and underlying task representation, to name a few. This article describes a novel kernel for CSF estimation that is more flexible than a kernel based on strictly functional forms. Despite being more flexible, it can result in a more efficient estimator. Further, trial selection for data acquisition that is generalized beyond pure information gain can also improve estimator quality. Finally, introducing latent variable representations underlying general CSF shapes can enable simultaneous estimation of multiple CSFs, such as from different eyes, eccentricities, or luminances. The conditions under which the new procedures perform better than previous nonparametric estimation procedures are presented and quantified.

Return to Play After Arthroscopic Management of Rotator Cuff Tears in Professional Athletes of Contact Sports.

Background: Rotator cuff tears are rare injuries in professional athletes who participate in contact sports, and limited data exist to guide players and team physicians regarding outcomes after surgical management. Purpose: To report the outcomes and return-to-play rates of professional contact sport athletes who underwent arthroscopic management of rotator cuff tears. Study Design: Case series; Level of evidence, 4. Methods: All professional athletes of contact sports who underwent arthroscopic management of a rotator cuff tear between 2002 and 2019 at the institution were identified. Patient information collected were age, sport, position, date of injury, date of surgery, and time to return to play; surgical data included tear size, acuity, pattern, and procedure performed. The primary outcome measure was the ability to return to play and the number of games played after surgery. Results: Overall, 10 rotator cuff tears in 9 professional athletes (8 tears in football players and 2 tears in hockey players) were identified; 9 of the tears were full-thickness tears that underwent arthroscopic single-row repair, while 1 was a partial tear that was debrided. Of the 9 athletes, 8 were able to return to play at the same level, at a mean time of 9.5 ± 4.3 months. The mean playing time after surgery was 32 ± 25 games (2.7 ± 2 seasons) for the football players and 22 games (1 season) for the hockey player who returned. Postoperative imaging was available in 8 of the 10 tears, and 7 of 8 (88%) demonstrated a healed repair. One football player and 1 hockey player with large (>3 cm) full-thickness tears did not return to play. The mean age of these players was 34.5 years and both had >10 years of professional playing experience.≥. Conclusion: The study findings demonstrated that the majority (80%; n = 8) of the professional athletes in contact sports in this series were able to return to play at the same level after arthroscopic management of a symptomatic rotator cuff tear.

Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease. METHODS: English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements. RESULTS: Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030). CONCLUSIONS: CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

Relative Value Unit (RVU) and Medicare Severity Diagnosis-related Group (MS-DRG) Reimbursement in Cervical Spinal Fusion: A 2011-2023 Trends Report.

STUDY DESIGN: Level 3 retrospective database study. OBJECTIVE: This study aims to compare work RVU (wRVU), practice expense RVU (peRVU), malpractice RVU (mpRVU), and inflation-adjusted facility price alongside MS-DRG relative weight length of stay (LOS) for cervical spine fusions between 2011 and 2023. SUMMARY OF BACKGROUND DATA: Both RVU and MS-DRG reimbursement have been studied in various surgical subspecialties; however, little investigation has centered on cervical spine fusions. To the best of our knowledge, this is the first study to investigate trends in RVU and MS-DRG reimbursement in cervical spine fusion throughout the COVID-19 pandemic. METHODS: Center for Medicaid and Medicare Services (CMS) physician fee schedule was queried between 2011 and 2023 for RVU and facility reimbursement using common single and multilevel anterior and posterior cervical fusion codes. RVU facility prices were inflation adjusted to 2023. MS-DRG reimbursement data from 2011 to 2022 were compiled for cervical spinal fusion procedures with major complication or comorbidity (MCC) 471, complication or comorbidity (CC) 472, and without CC/MCC 473. Compound annual growth rates (CAGRs), Mean Annual Change, and yearly percent changes were calculated. RESULTS: No changes in wRVU were seen for all cervical CPT codes; however, the CAGR of peRVU (-0.51%±0.60%) and mpRVU (0.69%±0.41%) demonstrated marginal fluctuations. Every CPT code displayed an inflation-adjusted facility price decrease (-2.18%±0.24%). When assessing MS-DRG, there were marginal changes in geometric mean LOS (0.17%±0.45%), arithmetic mean LOS (-0.15%±0.84%), and relative weight (1.09%±0.68%). Unlike RVU reimbursement, the yearly percent change differs between each MS-DRG code. CONCLUSIONS: Inflation-adjusted RVU reimbursement facility prices demonstrated a consistent decrease, while DRG code reimbursement stayed relatively consistent over the study period. This data may help surgeons and hospitals become cognizant of temporal variations in reimbursement patterns as it may affect their personal practice. LEVEL OF EVIDENCE: Level III retrospective study.