The Association between Race and Extended Length of Stay in Low-energy Proximal Humerus Fractures in Elderly Patients.

INTRODUCTION: Proximal humerus fractures (PHFs) are one of the most common fractures among patients aged 65 years and older, commonly due to low-energy mechanisms. It is essential to identify drivers of increased healthcare utilization in geriatric PHF patients and bring awareness to any disparities in care. Here, we identify factors associated with the likelihood of inpatient admission and prolonged hospital stay among patients aged 65 years and older who sustain PHF due to falls. METHODS: A national database was used to identify patients aged 65 years and older who suffered proximal humeral fractures due to a fall. Patient factors were analyzed for association with the likelihood of admission and odds of prolonged stay (≥5 days). RESULTS: In the study period, 75,385 PHF patients who met our inclusion criteria presented to the emergency department and 14,118 (18.7%) were admitted. Black race was significantly associated with decreased odds of admission (P < 0.001) and increased likelihood of prolonged stay (P = 0.007) compared with White patients. Patients aged 75 to 84 and 85+ were both more likely to be admitted (P < 0.001) and experienced a prolonged hospital stay (P = 0.015). Patients undergoing surgical intervention with reverse total shoulder arthroplasty were associated with admission and prolonged length of stay (P < 0.001). Hospitals in Midwestern (P < 0.001) and Western (P < 0.001) regions exhibited lower rates of admission and Northeastern hospitals were associated with prolonged stays (P = 0.001). Finally, trauma and nonmetropolitan (P < 0.001) centers were associated with admission. CONCLUSION: Our study highlights the notable influence of age and race on the likelihood of hospital admission and prolonged hospital stay. Specifically, Black patients exhibited prolonged hospital stay, which has been associated with lower-quality care, warranting additional exploration. Understanding these demographic and hospital-related factors is essential for optimizing resource allocation and reducing healthcare disparities in the care of PHF patients, especially as the population ages and the incidence of PHF continues to rise.

Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

Nuclear deformation regulates YAP dynamics in cancer associated fibroblasts.

Cells cultured on stiff 2D substrates exert high intracellular force, resulting in mechanical deformation of their nuclei. This nuclear deformation (ND) plays a crucial role in the transport of Yes Associated Protein (YAP) from the cytoplasm to the nucleus. However, cells in vivo are in soft 3D environment with potentially much lower intracellular forces. Whether and how cells may deform their nuclei in 3D for YAP localization remains unclear. Here, by culturing human colon cancer associated fibroblasts (CAFs) on 2D, 2.5D, and 3D substrates, we differentiated the effects of stiffness, force, and ND on YAP localization. We found that nuclear translocation of YAP depends on the degree of ND irrespective of dimensionality, stiffness and total force. ND induced by the perinuclear force, not the total force, and nuclear membrane curvature correlate strongly with YAP activation. Immunostained slices of human tumors further supported the association between ND and YAP nuclear localization, suggesting ND as a potential biomarker for YAP activation in tumors. Additionally, we conducted quantitative analysis of the force dynamics of CAFs on 2D substrates to construct a stochastic model of YAP kinetics. This model revealed that the probability of YAP nuclear translocation, as well as the residence time in the nucleus follow a power law. This study provides valuable insights into the regulatory mechanisms governing YAP dynamics and highlights the significance of threshold activation in YAP localization. STATEMENT OF SIGNIFICANCE: Yes Associated Protein (YAP), a transcription cofactor, has been identified as one of the drivers of cancer progression. High tumor stiffness is attributed to driving YAP to the nucleus, wherein it activates pro-metastatic genes. Here we show, using cancer associated fibroblasts, that YAP translocation to the nucleus depends on the degree of nuclear deformation, irrespective of stiffness. We also identified that perinuclear force induced membrane curvature correlates strongly with YAP nuclear transport. A novel stochastic model of YAP kinetics unveiled a power law relationship between the activation threshold and persistence time of YAP in the nucleus. Overall, this study provides novel insights into the regulatory mechanisms governing YAP dynamics and the probability of activation that is of immense clinical significance.

Publishing on Topical Subjects in Total Joint Arthroplasty Is Associated With Increased Social Media Attention.

BACKGROUND: Social media platforms are often used for research dissemination and collaboration. Given the increased prevalence of online-only publications, understanding what drives research dissemination is important. Here, we analyzed factors associated with increased social media attention among peer-reviewed publications in total knee arthroplasty, total hip arthroplasty, and unicompartmental knee arthroplasty. METHODS: We analyzed publications about total knee arthroplasty, total hip arthroplasty, or unicompartmental knee arthroplasty from 2010 to 2022 using a national database. We analyzed a weighted count of social media mentions, using negative binomial regressions adjusting for days since publication. Publications on "hot topics" in arthroplasty were examined including navigation/robotics, COVID-19, race/ethnicity, body mass index, and reimbursement. There were 9,542 publications included, 4,216 (44%) were open access (OA), 338 (3.5%) included navigation, 32 (0.34%) discussed race/ethnicity, 20 (0.2%) discussed COVID-19, 3,840 (40%) were randomized studies, 30 (0.3%) discussed reimbursement, and 2,867 (30%) were in top-10 orthopaedic journals. RESULTS: Factors associated with higher weighted score included studies about COVID-19 (50 versus 6.0, P < .001), race/ethnicity (15.8 versus 6.0, P < .001), OA status (6.3 versus 5.8, P = .001), and randomized studies (6.5 versus 5.7, P < .001). Studies from top-10 journals had a lower score (5.8 versus 6.2, P = .025), as did studies about body mass index (3.4 versus 6.1, P = .001). Studies about navigation and reimbursement did not have significantly different scores. CONCLUSIONS: Studies on COVID-19, race/ethnicity, randomized studies, and OA publication were associated with increased social media while those in top-10 orthopaedic journals had lower scores. LEVEL OF EVIDENCE: Level IV, Prognostic Study.

Effects of Spinal Deformities on Hiatal Hernia Occurrence and Recurrence.

BACKGROUND: Spinal deformities such as kyphosis, lordosis, and scoliosis have demonstrated a possible association between these deformities. Our hypothesis is that the presence of spinal deformities will increase the risk of hiatal hernia recurrence after repair. METHODS: The following data was retrospectively gleaned for patients undergoing hiatal hernia repair (1997-2022): age, sex, date of hiatal hernia repair, presence and type of spinal deformity, Cobb angle, type of hiatal hernia and size, type of hiatal hernia repair, recurrence and size, time to recurrence, reoperation, type of reoperation, and time to reoperation. RESULTS: Spinal deformities were present in 15.8% of 546 patients undergoing hiatal hernia repair, with a distribution of 21.8% kyphosis, 2.3% lordosis, 58.6% scoliosis, and 17.2% multiple. There was no difference in sex or age between groups. Spinal deformity patients were more likely to have types III and IV hiatal hernias (52.3% vs. 38.9%, p = 0.02) and larger hernias (median 5 [3-8] vs. 4 [2-6], p = 0.01). There was no difference in access, fundoplication use, or mesh use between groups. However, these patients had a higher recurrence rate (47.7% vs 30.0%, p = 0.001) and a shorter time to recurrence (months) (10.3 [5.6-25.1] vs 19.2 [9.8-51.0], p = 0.02). Cobb angle did not affect recurrence. CONCLUSIONS: Spinal deformity patients were more likely to have more complex and larger hiatal hernias. They were at higher risk of hiatal hernia recurrence after repair with shorter times to recurrence. This is a group that requires special attention with additional preoperative counseling and possibly use of surgical adjuncts in repair.

Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis.

OBJECTIVE: Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution. METHODS: Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal. Metabolic activity was interrogated by pathway scoring and gene set enrichment analysis. RESULTS: A total of 53 metabolic pathways were differentially regulated in at least one melanoma genomic subtype. Some notable findings include: BRAF/NRAS WT cells were enriched for fatty acid biosynthesis and depleted for metabolism of alanine, aspartate, and glutamate; BRAF(V600E) melanoma cells were enriched for beta-alanine metabolism and depleted for phenylalanine metabolism; NRAS(Q61L) melanoma cells were enriched for steroid biosynthesis and depleted for linoleic acid metabolism. CONCLUSION: Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.

Changes in Perioperative Outcomes after Robotic-Assisted Pulmonary Lobectomy during the COVID-19 Era.

Background: The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as "PreCOVID-19" and 83 patients as "COVID-19-Era" based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p ≤ 0.05 . Multivariable generalized linear regression was used to investigate predictors of postoperative complication. Results: COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. Conclusions: COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.

Membranome Similarity between Glioblastoma Multiforme Cell Lines and Primary Tumors.

Genes encoding for proteins associated with the plasma membrane, referred to as the membranome, have long been recognized to play an important role in the development and maintenance of glioblastoma multiforme (GBM). GBM cell lines are commonly used to mimic tumors for in vitro experiments, but the extent to which they resemble GBM tumors in relation to the membranome is unclear. The present study explores the resemblance of GBM cell lines to primary tumors regarding membranome expression. Gene expression data was retrieved from Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA). Membranomic genes were annotated and tumor purity was accounted for when correlating tumors and cell lines. The results suggest some commonly used cell lines, including AM38 and U87MG, display relatively little resemblance to tumors membranome. Differential gene expression analysis and subsequent gene set enrichment showed numerous genes related to neurexin/neuroligin, ion homeostasis, and synaptic signaling were downregulated in cell lines' membranomes compared to that of GBM tumors. The findings suggest that the membranome of GBM cell lines exhibit pronounced changes in gene expression compared to primary tumors and may not be completely representative of the disease process.

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data.

Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author's best knowledge, the present study represents a first-use case of the Interplanetary File Storage protocol for storing and retrieving spine imaging smart contracts. Methods: The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected. Results: It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records. Conclusions: The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Outcomes of surgical management and implant consideration for depressed skull fractures: A systematic review.

Background: Traumatic brain injuries (TBIs) are associated with high mortality and morbidity. Depressed skull fractures (DSFs) are a subset of fractures characterized by either direct or indirect brain damage, compressing brain tissue. Recent advances in implant use during primary reconstruction surgeries have shown to be effective. In this systematic review, we assess differences in titanium mesh, polyetheretherketone (PEEK) implants, autologous pericranial grafts, and methyl methacrylate (PMMA) implants for DSF treatment. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science from their inception to September 2022 to retrieve articles regarding the use of various implant materials for depressed skull fractures. Inclusion criteria included studies specifically describing implant type/material within treatment of depressed skull fractures, particularly during duraplasty. Exclusion criteria were studies reporting only non-primary data, those insufficiently disaggregated to extract implant type, those describing treatment of pathologies other than depressed skull fractures, and non-English or cadaveric studies. The Newcastle-Ottawa Scale was utilized to assess for presence of bias in included studies. Results: Following final study selection, 18 articles were included for quantitative and qualitative analysis. Of the 177 patients (152 males), mean age was 30.8 years with 82% implanted with autologous graft material, and 18% with non-autologous material. Data were pooled and analyzed with respect to the total patient set, and additionally stratified into those treated through autologous and non-autologous implant material.There were no differences between the two cohorts regarding mean time to encounter, pre-operative Glasgow coma scale (GCS), fracture location, length to cranioplasty, and complication rate. There were statistically significant differences in post-operative GCS (p < 0.0001), LOS (p = 0.0274), and minimum follow-up time (p = 0.000796). Conclusion: Differences in measurable post-operative outcomes between implant groups were largely minimal or none. Future research should aim to probe these basic results deeper with a larger, non-biased sample.

A High Preoperative Blood Urea Nitrogen to Serum Albumin Ratio Does Not Predict Worse Outcomes Following the Robotic-Assisted Pulmonary Lobectomy for Lung Cancer.

BACKGROUND:  The blood urea nitrogen to serum albumin ratio (BAR) is an emerging prognostic parameter of interest. The utility of BAR as a prognostic factor has not been analyzed in lung cancer patients undergoing pulmonary lobectomy. We evaluated the ability of High BAR to predict worse outcomes after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer. METHODS:  We retrospectively analyzed 400 patients who underwent RAPL from September 2010 to March 2022 by one surgeon. Patients were stratified by Low BAR (<6.25 mg/g) and High BAR (≥6.25 mg/g). Patients' demographics, tumor characteristics, comorbidities, surgical complications, outcomes, and survival were collected and compared by High and Low BAR groups. The primary outcome of interest was 30-day mortality. RESULTS:  Receiver operator curves (ROC) confirmed that 6.25 was an optimal threshold for estimating mortality based on Low and High BAR. There were no differences in surgical complications or outcomes between the Low and High BAR groups. The ability of BAR to predict 30-day mortality was evaluated with the area under the curve (AUC) analysis, which showed that higher BAR could not predict mortality (AUC=0.655; 95% CI, 0.435-0.875; p=0.166). Similarly, survival analysis revealed no difference in five-year overall survival between the Low and High BAR groups (p=0.079). CONCLUSION:  High BAR did not predict worse outcomes after RAPL for lung cancer in our study. Further studies are needed to better determine the prognostic ability of BAR in lower-risk populations.

Omics analysis of uveal melanoma: Leukocyte gene signatures reveal novel survival distinctions and indicate a prognostic role for cytolytic activity scoring.

Objective: The significant metastatic potential of uveal melanoma (UVM) lends to high mortality. Even with successful local tumor treatment, many patients will develop metastatic disease. The present study aims to elucidate the relationship between tumor-infiltrating immune cell (TIIC) diversity and survival to identify potential therapeutic targets and improve UVM prognosis. Methods: Bulk deconvolution was used to determine the relative proportions of 22 hematopoietic TIIC from 80 UVM tumor samples. Cytolytic activity (CYT) was determined, and associated survival probabilities were mined using time-to-event data. Nominal P-values were subjected to FDR correction. Results: High relative abundance of tumor-infiltrating naïve B cells, resting memory CD4+ T cells, and monocytes correlated with better overall and disease-free survival probability. Low relative abundance of CD8+ T cells correlated with better overall survival and disease-free survival probability. CYT correlated positively with relative abundance of naïve B cells, resting memory CD4+ T cells, and monocytes. CYT correlated negatively with relative abundance of CD8+ T cells. Conclusion: Infiltrating naïve B cells, resting memory CD4+ T cells, monocytes, and CD8+ T cells are potential therapeutic targets in UVM that warrant further investigation. High CYT estimates associate with worse UVM survival outcomes.

Current Approaches to Craniopharyngioma Management.

Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location and invasive potential, with profound adverse effects for the patient if left to grow. Indeed, gross total resection may also be accompanied by unwelcome sequalae, underscoring the need for continued investigation. In the present work, we provide a scoping review of current CP management, with emphasis on our knowledge of their genesis, available treatment options, post-intervention clinical outcomes. Leading theories of CP development are (1) the embryonic theory, explaining the development of adamantinomatous CP from epithelial remnants of Rathke's pouch and (2) the metaplastic theory, which describes papillary CP development as a result of adenohypophyseal cell metaplasia. Treatment may include surgery, intracystic therapy, or irradiation depending on tumor size, history and location. However, whether a single ideal approach and timing for CP intervention exists remains debated. We appraise and critique these areas with priority for emerging basic results and innovation.

Dose-independent threshold illumination for non-invasive time-lapse fluorescence imaging of live cells.

Fluorescent microscopy employs monochromatic light for excitation, which can adversely affect the cells being observed. We reported earlier that fibroblasts relax their contractile force in response to green light of typical intensity. Here we show that such effects are independent of extracellular matrix and cell lines. In addition, we establish a threshold intensity that elicits minimal or no adverse effect on cell contractility even for long-time exposure. This threshold intensity is wavelength dependent. We cultured fibroblasts on soft 2D elastic hydrogels embedded with fluorescent beads to trace substrate deformation and cell forces. The beads move towards cell center when cells contract, but they move away when cells relax. We use relaxation/contraction ratio (λ r), in addition to traction force, as measures of cell response to red (wavelength, λ=635-650 nm), green (λ=545-580 nm) and blue (λ=455-490 nm) lights with varying intensities. Our results suggest that intensities below 57, 31 and 3.5 W/m2 for red, green and blue lights, respectively, do not perturb force homeostasis. To our knowledge, these intensities are the lowest reported safe thresholds, implying that cell traction is a highly sensitive readout of the effect of light on cells. Most importantly, we find these threshold intensities to be dose-independent; i.e., safe regardless of the energy dosage or time of exposure. Conversely, higher intensities result in widespread force-relaxation in cells with λ r > 1. Furthermore, we present a photo-reaction based model that simulates photo-toxicity and predicts threshold intensity for different wavelengths within the visible spectra. In conclusion, we recommend employing illumination intensities below aforementioned wavelength-specific thresholds for time-lapse imaging of cells and tissues in order to avoid light-induced artifacts in experimental observations.