Migration of naphthalene in a biochar-amended bioretention facility based on HYDRUS-1D analysis.

Biochar has been proved as a promising and efficient filler in bioretention facilities for enhancing the stormwater pollutants removal. However, the migration behaviors of stormwater pollutants in biochar filled bioretention facilities is unclear. In this study, as one of the most typical stormwater pollutants, naphthalene was selected as an example and a HYDRUS-1D model was first used to understand the migration behavior of naphthalene in a bioretention facility. In comparison with the conventional bioretention soil media (sandy loam), the amended biochar filled bioretention cell showed that the naphthalene removal rate was enhanced by up to 10.1%. Meanwhile, the experimental data was well-fitted by the "two-site sorption model" in HYDRUS-1D model. Another, the effect of rainfall intensity on the naphthalene migration in both bioretention columns was further investigated. The HYDRUS-1D model fitting indicated that the increase in rainfall intensity promoted naphthalene migration by increasing hydraulic conductivity and water flux. In addition, static batch experiments revealed that the biochar filled fillers achieved about 50% higher adsorption capacity than sandy loam. The sensitivity analysis from the HYDRUS-1D model data verified adsorption coefficient Kd and longitudinal dispersivity λ are the main factors affecting naphthalene migration. Finally, the model simulation displays that the proportion of naphthalene retained by the fillers was highest during high rainfall intensities, indicating that the fillers remain the most important fate for naphthalene. This study presents research on the behavior and mechanisms of stormwater pollutant transport through improved bioretention facilities.

Virally delivered CMYA5 enhances the assembly of cardiac dyads.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) lack nanoscale structures essential for efficient excitation-contraction coupling. Such nanostructures, known as dyads, are frequently disrupted in heart failure. Here we show that the reduced expression of cardiomyopathy-associated 5 (CMYA5), a master protein that establishes dyads, contributes to dyad disorganization in heart failure and to impaired dyad assembly in hiPSC-CMs, and that a miniaturized form of CMYA5 suitable for delivery via an adeno-associated virus substantially improved dyad architecture and normalized cardiac function under pressure overload. In hiPSC-CMs, the miniaturized form of CMYA5 increased contractile forces, improved Ca2+ handling and enhanced the alignment of sarcomere Z-lines with ryanodine receptor 2, a protein that mediates the sarcoplasmic release of stored Ca2+. Our findings clarify the mechanisms responsible for impaired dyad structure in diseased cardiomyocytes, and suggest strategies for promoting dyad assembly and stability in heart disease and during the derivation of hiPSC-CMs.

Revision Shoulder Arthroplasty: Predictors of Subsequent Revision Surgery and Economic Burden amongst Medicare Beneficiaries.

BACKGROUND: Revision shoulder arthroplasty continues to add an increasing burden on patients and the healthcare system. This study aimed to delineate long-term shoulder arthroplasty revision incidence, quantify associated Medicare spending, and identify relevant predictors of both revision and spending. METHODS: The complete 2016-2022(Q3) Medicare fee-for-service inpatient and outpatient claims data was analyzed. Patients receiving a primary total shoulder arthroplasty for osteoarthritis, rotator cuff pathology, or inflammatory arthropathy were included and subsequent ipsilateral revision surgeries were identified. The time to revision was modeled using the Prentice, Williams, and Peterson Gap Time Model. Medicare spending within 90 days post-discharge was modeled using a generalized linear model. The analysis was subdivided by index procedure type: anatomic total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA). RESULTS: A total of 82,949 primary TSAs and 172,524 RSAs were identified. Compared to index TSA cases, index RSA cases had a lower first revision rate in an observation window of nearly 7 years (1.9% vs. 3.5%, p<0.001), but a higher rate of second (11.4% vs. 4.9%, p<0.001) as well as third revision (13.8% vs. 13.8%, p=0.449). TSA spending was significantly lower than RSA spending for the index procedure ($21,531 vs. $23,267, p<0.001), first ($23,096 vs. $26,414, p<0.001), and second ($25,060 vs. $29,983, p<0.001) revision. There was no statistically significant difference in third revision between TSA and RSA groups ($31,313 vs. $30,829, p=0.860). Age, sex, race, and rheumatoid arthritis were among the top predictors of revisions. Top predictors of Medicare spending included having a non-osteoarthritis surgical indication, a hospital stay of three or more days, a discharge to a setting other than home, malnutrition, dementia, stroke, major kidney diseases, and being operated on in a teaching hospital. CONCLUSION: Compared with TSA, RSA was associated with a lower first revision rate, but a higher subsequent revision rate. An index RSA procedure was also associated with higher initial Medicare spending as well as subsequent revision surgery spending compared with an index TSA procedure. Demographics and comorbid medical conditions were among the top predictors of revisions, while procedure-related factors predicted Medicare spending.

Monocyte/Macrophage-Mediated Transport of Dual-Drug ZIF Nanoplatforms Synergized with Programmed Cell Death Protein-1 Inhibitor Against Microsatellite-Stable Colorectal Cancer.

Microsatellite-stable colorectal cancer (MSS-CRC) exhibits resistance to programmed cell death protein-1 (PD-1) therapy. Improving the infiltration and tumor recognition of cytotoxic T-lymphocytes (CTLs) is a promising strategy, but it encounters huge challenges from drug delivery and mechanisms aspects. Here, a zeolitic imidazolate framework (ZIF) coated with apoptotic body membranes derived from MSS-CRC cells is engineered for the co-delivery of ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) to MSS-CRC, named as Ab@Rg1/Att-ZIF. This system is selectively engulfed by Ly-6C+ monocytes during blood circulation and utilizes a "hitchhiking" mechanism to migrate toward the core of MSS-CRC. Ab@Rg1/Att-ZIF undergoes rapid disassembly in the tumor, released Rg1 promotes the processing and transportation of tumor antigens in dendritic cells (DCs), enhancing their maturation. Meanwhile, Att enhances the activity of the 26S proteasome complex in tumor cells, leading to increased expression of major histocompatibility complex class-I (MHC-I). These coordinated actions enhance the infiltration and recognition of CTLs in the center of MSS-CRC, significantly improving the tumor inhibition of PD-1 treatment from ≈5% to ≈69%. This innovative design, involving inflammation-guided precise drug co-delivery and a rational combination, achieves synergistic engineering of the tumor microenvironment, providing a novel strategy for successful PD-1 treatment of MSS-CRC.

Lower Visceral Fat is Related to Diabetic Peripheral Neuropathy.

Objective: Visceral fat area (VFA) levels have been found to exhibit a strong association with various conditions such as insulin resistance (IR), inflammation, oxidative stress, metabolic syndrome (MetS), hyperlipidemia, diabetes, and its vascular complications. These complications include hypertension, cardiovascular disease, diabetic retinopathy (DR), albuminuria, and cardiovascular autonomic dysfunction, which is considered one of the main types of diabetic neuropathy. This study aimed to investigate the correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes (T2DM). Methods: A retrospective analysis of clinical data of patients diagnosed with type 2 diabetes admitted to our hospital was conducted. After excluding 28 cases, a total of 488 patients were included, divided into the group with peripheral neuropathy (207 cases) and the control group without peripheral neuropathy (281 cases). The correlation between VFA and the presence of DPN was assessed using correlation and multiple logistic regression analyses. Results: In terms of general information, the group with peripheral neuropathy had lower BMI but longer duration of diabetes compared to the control group. Regarding biochemical indicators, VFA were lower in the group with peripheral neuropathy, while FPG and HbA1c levels were higher (all P<0.05). Spearman correlation analysis showed a negative correlation between VFA, and the presence of peripheral neuropathy in patients with type 2 diabetes (P<0.05). Logistic regression analysis indicated that VFA, duration of diabetes, and HbA1c level were influencing factors for the occurrence of peripheral neuropathy in patients with type 2 diabetes (P<0.05). Conclusion: This study revealed a correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes, highlighting the importance of monitoring visceral fat in such patients. In addition to lower levels of VFA, factors such as duration of diabetes and glycated hemoglobin (HbA1c) level were also associated with peripheral neuropathy in patients with T2DM.

Adhesive solid-state fermentation producing Aspergillus niger conidia on stainless-steel dixon ring supports.

An adhesive solid-state fermentation (adSSF) mode was developed to produce Aspergillus niger conidia, which used a stainless-steel Dixon ring as the support and water-retaining adhesive to load nutritional media on its surface. To obtain high conidia yields, the components of the water-retaining adhesive were screened, optimized by single-factor optimization and response surface methodology, and the optimal dosages of the main components were: wheat bran powder 0.023 g·cm-3bed, cassava starch 0.0022 g·cm-3bed, and xanthan gum 0.0083 g·cm-3bed. The experimentally tested conidia yield was 4.2-fold that without water-retaining adhesive but was 3.7% lower than the maximum yield predicted by the model. The observed double-side growth of A. niger on the Dixon ring supports improved space utilization of the fermentation bed, and the void fraction can increase with the shrinkage of the gel layer. In 1.6 L tray reactors with three-point online temperature monitoring, the inner-bed temperature of adSSF was at most 4 °C lower than the adsorbed carrier solid-state fermentation (ACSSF) mode, and the conidia yield was 1.68 × 108 conidia.cm-3bed, 61.5% higher than that of the ACSSF bed at the same time, but when the fermentation time was extended to 168 h, the conidia yield of the adSSF bed and ACSSF bed were close to each other. The results revealed that the high voidage of the adSSF bed was the main reason for low bed temperature, which can benefit the inner-bed natural convection and water evaporation.

Cerebrospinal Fluid Seeding Versus Inflammation in Setting of Ventriculoperitoneal Shunt as a Potential Cause for Distant Recurrence of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months, despite treatment, with most patients experiencing recurrence within 9 months of resection. The propensity of recurrence in GBM exemplifies the fatal course of the disease and remains an underlying area of study as novel instances of recurrence are encountered. The authors present a unique case of a 31-year-old male patient with a history of cerebellomedullary junction astrocytoma who later developed a supratentorial GBM followed by recurrence centered around a preexisting ventriculoperitoneal catheter and located in the hemisphere contralateral to his first GBM. Each of these lesions was initially thought to represent de novo glial neoplasms because of the absence of intervening T2 fluid-attenuated inversion recovery signal change between each lesion. However, next-generation sequencing using the GlioSeq™ platform revealed similar mutational profiles in both GBMs, suggesting an alternative method of migration of tumor cells to the shunt catheter site, and a local inflammatory environment likely triggering recurrence. This study concludes that in rare instances, in the presence of dormant glioma cells, intracranial foreign bodies may promote an inflammatory microenvironment that may activate tumorigenesis.

Utility of Machine Learning, Natural Language Processing, and Artificial Intelligence in Predicting Hospital Readmissions After Orthopaedic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Numerous applications and strategies have been utilized to help assess the trends and patterns of readmissions after orthopaedic surgery in an attempt to extrapolate possible risk factors and causative agents. The aim of this work is to systematically summarize the available literature on the extent to which natural language processing, machine learning, and artificial intelligence (AI) can help improve the predictability of hospital readmissions after orthopaedic and spine surgeries. METHODS: This is a systematic review and meta-analysis. PubMed, Embase and Google Scholar were searched, up until August 30, 2023, for studies that explore the use of AI, natural language processing, and machine learning tools for the prediction of readmission rates after orthopedic procedures. Data regarding surgery type, patient population, readmission outcomes, advanced models utilized, comparison methods, predictor sets, the inclusion of perioperative predictors, validation method, size of training and testing sample, accuracy, and receiver operating characteristics (C-statistic), among other factors, were extracted and assessed. RESULTS: A total of 26 studies were included in our final dataset. The overall summary C-statistic showed a mean of 0.71 across all models, indicating a reasonable level of predictiveness. A total of 15 articles (57%) were attributed to the spine, making it the most commonly explored orthopaedic field in our study. When comparing accuracy of prediction models between different fields, models predicting readmissions after hip/knee arthroplasty procedures had a higher prediction accuracy (mean C-statistic = 0.79) than spine (mean C-statistic = 0.7) and shoulder (mean C-statistic = 0.67). In addition, models that used single institution data, and those that included intraoperative and/or postoperative outcomes, had a higher mean C-statistic than those utilizing other data sources, and that include only preoperative predictors. According to the Prediction model Risk of Bias Assessment Tool, the majority of the articles in our study had a high risk of bias. CONCLUSION: AI tools perform reasonably well in predicting readmissions after orthopaedic procedures. Future work should focus on standardizing study methodologies and designs, and improving the data analysis process, in an attempt to produce more reliable and tangible results. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Development of Symptomatic Adjacent and Remote Level Compression Fractures Following Balloon-assisted Kyphoplasty in a Series of 1,318 Patients.

BACKGROUND: Balloon-assisted kyphoplasty (BAK) is a minimally invasive procedure to treat vertebral compression fractures (VCF). BAK not only restores vertebral height and corrects kyphotic deformity by cement augmentation, but it also may alter spinal biomechanics, leading to subsequent adjacent level VCFs. OBJECTIVES: This study aims to investigate the timing, location, and incidence of new VCFs following BAK and identify the risk factors associated with their occurrence. STUDY DESIGN: Single-institution observational study. METHODS: A prospectively collected cohort of 1,318 patients who underwent BAK by a single-surgeon from 2001 through 2022 was analyzed. The patients had pain that was unresponsive to nonsurgical management and a VCF secondary to osteoporosis, trauma, or neoplasm. The time between the index and subsequent fracture, fracture level, number of initial fractures, age, body mass index (BMI), tobacco use, and chronic corticosteroid use were recorded. RESULTS: Of 1,318 patients, 204 (15.5%) patients underwent a second BAK procedure an average of 373 days following BAK (range: 2-3,235 days). Third, fourth, and fifth procedures were less common (45, 12, and 6 patients, respectively). A total of 142 patients (69.6%) developed a subsequent fracture adjacent to the index level; adjacent and remote level fractures developed at different times (mean: 282 vs 581 days, P = 0.001). Patients treated for multiple VCFs in a single surgery were more likely to develop subsequent VCFs (P = 0.024) and at adjacent levels (P = 0.007). Subsequent VCFs were associated with older age (P < 0.001), women (P = 0.045), osteoporosis (P < 0.001), and chronic corticosteroid use (P < 0.001). A subgroup analysis of 812 (61.6%) patients who underwent BAK for degenerative indications revealed that osteoporosis (b = 0.09; 95% CI, 0.03-0.16; P = 0.005) and chronic corticosteroid use (b = 0.06; 95% CI, 0-0.11; P = 0.055) were associated with adjacent level fracture. For the entire cohort, almost every patient treated for both a thoracic and lumbar fracture (92.3%) developed an adjacent level second fracture (P = 0.005). LIMITATIONS: The true incidence of post-BAK fractures may be underestimated as surveillance is not routine in asymptomatic or osteoporotic patients. CONCLUSIONS: Symptomatic post-BAK VCFs are infrequent and may occur long after the initial procedure. Nearly two-thirds of subsequent fractures in our study occurred adjacent to the initially treated level; almost every patient who suffered thoracic and lumbar fractures at the same time developed an adjacent level second fracture. Additionally, osteoporosis and chronic corticosteroid use were associated with adjacent level fractures in patients who underwent surgery for degenerative indications.

Electron Deficiency is More Important than Conductivity in C-N Coupling for Electrocatalytic Urea Synthesis.

The electrocatalytic C-N coupling from CO2 and nitrate emerges as one of the solutions for waste upgrading and urea synthesis. In this work, we constructed electron-deficient Cu sites by the strong metal-polymer semiconductor interaction, to boost efficient and durable urea synthesis. In situ Raman spectroscopy identified the existence of electron-deficient Cu sites and was able to withstand electrochemical reduction conditions. Operando synchrotron-radiation Fourier transform infrared spectroscopy and theoretical calculations disclosed the vital role of electron-deficient Cu in adsorption and C-N coupling of oxygen-containing species. The electron-deficient Cu displayed a high urea yield rate of 255.0 mmol h-1 g-1 at -1.4 V versus the reversible hydrogen electrode and excellent electrochemical durability, superior than that of non-electron-deficient counterpart with conductive carbon material as the support. It can be concluded that the regulation of site electronic structure is more important than the optimization of catalyst conductive properties in the C-N coupling reactions.

Multifunctional surface of the nano-morphic PEEK implant with enhanced angiogenic, osteogenic and antibacterial properties.

Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co2+ notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co2+ and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.

Fasting-Induced Molting Impacts the Intestinal Health by Altering the Gut Microbiota.

Fasting-induced molting (FIM) is a common method used to improve the laying performance of aged laying hens. Nevertheless, this approach may impose various stresses on chickens, such as disruptions in intestinal flora and inflammation issues within the intestines. However, the impact of an imbalance in intestinal flora on intestinal health during the FIM process remains elusive. Therefore, intestinal injury, the microbiome, and the metabolome were analyzed individually and integrated to elucidate the impact of the intestinal flora on intestinal health during the FIM process. The findings indicated that fasting resulted in a notable reduction in villus height and villus/crypt ratio, coupled with elevated levels of intestinal inflammation and permeability. During the fasting period, microbiota compositions changed. The abundance of Escherichia_Shigella increased, while the abundance of Ruminococcaceae_UCG-013 and Lactobacillus decreased. Escherichia_Shigella was positively correlated with Citrinin and Sterobilin, which lead to intestinal inflammation. Ruminococcaceae_UCG-013 and Lactobacillus exhibited positive correlations with Lanthionine and reduced Glutathione, thereby reducing intestinal inflammation. This study screened the intestinal probiotics, Ruminococcaceae UCG-013 and Lactobacillus, that influence gut health during the fasting period, providing an experimental basis for improving gut microbiota and reducing intestinal inflammation during the FIM process.

Improvements in technology and the expanding role of time-driven, activity-based costing to increase value in healthcare provider organizations: a literature review.

Objective: This study evaluated the influence of technology on accurately measuring costs using time-driven activity-based costing (TDABC) in healthcare provider organizations by identifying the most recent scientific evidence of how it contributed to increasing the value of surgical care. Methods: This is a literature-based analysis that mainly used two data sources: first, the most recent systematic reviews that specifically evaluated TDABC studies in the surgical field and, second, all articles that mentioned the use of CareMeasurement (CM) software to implement TDABC, which started to be published after the publication of the systematic review. The articles from the systematic review were grouped as manually performed TDABC, while those using CM were grouped as technology-based studies of TDABC implementations. The analyses focused on evaluating the impact of using technology to apply TDABC. A general description was followed by three levels of information extraction: the number of cases included, the number of articles published per year, and the contributions of TDABC to achieve cost savings and other improvements. Results: Fourteen studies using real-world patient-level data to evaluate costs comprised the manual group of studies. Thirteen studies that reported the use of CM comprised the technology-based group of articles. In the manual studies, the average number of cases included per study was 160, while in the technology-based studies, the average number of cases included was 4,767. Technology-based studies, on average, have a more comprehensive impact than manual ones in providing accurate cost information from larger samples. Conclusion: TDABC studies supported by technologies such as CM register more cases, identify cost-saving opportunities, and are frequently used to support reimbursement strategies based on value. The findings suggest that using TDABC with the support of technology can increase healthcare value.

Analysis of injected cement volume and clinical outcomes following balloon-assisted kyphoplasty in a series of 368 patients.

OBJECTIVE: Balloon-assisted kyphoplasty (BAK) is a modified vertebroplasty technique developed to treat vertebral compression fractures (VCFs) secondary to osteoporosis. This study investigates the association between injected cement volume and the development of subsequent VCFs after BAK. METHODS: A retrospective analysis of 368 patients who underwent BAK at a single institution was performed from 2001 to 2021. Inclusion was defined by at least 2 years of follow-up. Clinical characteristics and outcomes following BAK, including subsequent fractures at adjacent and remote levels, were identified. Patients that underwent a thoracic BAK were stratified by injected cement volume: below or equal to the median (≤ 6.0 mL, 265 vertebrae) or above the median (> 6.0 mL, 144 vertebrae). Patients that underwent a lumbar BAK were similarly stratified: below or equal to the median (≤ 8.0 mL, 233 vertebrae) or above the median (>8.0 mL, 160 vertebrae). RESULTS: A total of 802 vertebrae were treated. The average volume of cement was recorded in the thoracic (6.2 ± 1.9 mL) and lumbar (7.8 ± 1.8 mL) vertebrae. In the thoracic spine, vertebrae that were injected with > 6.0 mL of cement underwent a greater change in local kyphotic angle (P = 0.0001) and were more likely to develop adjacent-level VCFs (P = 0.032) after kyphoplasty. Univariate analysis did not elucidate any additional risk factors. There were no statistical differences in clinical outcomes between the three groups of lumbar vertebrae. CONCLUSIONS: Larger volumes of injected cement were associated with a greater change in local kyphosis and subsequent adjacent-level fractures after BAK in the thoracic spine. This association was not found in the lumbar spine. Close attention to injected cement volumes must be made in the thoracic spine and patients who undergo significant kyphotic correction should be carefully observed postoperatively.

A preoperative risk assessment tool for predicting adverse outcomes among total shoulder arthroplasty patients.

BACKGROUND: With the increased utilization of Total Shoulder Arthroplasty (TSA) in the outpatient setting, understanding the risk factors associated with complications and hospital readmissions becomes a more significant consideration. Prior developed assessment metrics in the literature either consisted of hard-to-implement tools or relied on postoperative data to guide decision-making. This study aimed to develop a preoperative risk assessment tool to help predict the risk of hospital readmission and other postoperative adverse outcomes. METHODS: We retrospectively evaluated the 2019-2022(Q2) Medicare fee-for-service inpatient and outpatient claims data to identify primary anatomic or reserve TSAs and to predict postoperative adverse outcomes within 90 days postdischarge, including all-cause hospital readmissions, postoperative complications, emergency room visits, and mortality. We screened 108 candidate predictors, including demographics, social determinants of health, TSA indications, prior 12-month hospital, and skilled nursing home admissions, comorbidities measured by hierarchical conditional categories, and prior orthopedic device-related complications. We used two approaches to reduce the number of predictors based on 80% of the data: 1) the Least Absolute Shrinkage and Selection Operator logistic regression and 2) the machine-learning-based cross-validation approach, with the resulting predictor sets being assessed in the remaining 20% of the data. A scoring system was created based on the final regression models' coefficients, and score cutoff points were determined for low, medium, and high-risk patients. RESULTS: A total of 208,634 TSA cases were included. There was a 6.8% hospital readmission rate with 11.2% of cases having at least one postoperative adverse outcome. Fifteen covariates were identified for predicting hospital readmission with the area under the curve of 0.70, and 16 were selected to predict any adverse postoperative outcome (area under the curve = 0.75). The Least Absolute Shrinkage and Selection Operator and machine learning approaches had similar performance. Advanced age and a history of fracture due to orthopedic devices are among the top predictors of hospital readmissions and other adverse outcomes. The score range for hospital readmission and an adverse postoperative outcome was 0 to 48 and 0 to 79, respectively. The cutoff points for the low, medium, and high-risk categories are 0-9, 10-14, ≥15 for hospital readmissions, and 0-11, 12-16, ≥17 for the composite outcome. CONCLUSION: Based on Medicare fee-for-service claims data, this study presents a preoperative risk stratification tool to assess hospital readmission or adverse surgical outcomes following TSA. Further investigation is warranted to validate these tools in a variety of diverse demographic settings and improve their predictive performance.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

Racial and gender disparities in utilization of outpatient total shoulder arthroplasties.

BACKGROUND: Utilization in outpatient total shoulder arthroplasties (TSAs) has increased significantly in recent years. It remains largely unknown whether utilization of outpatient TSA differs across gender and racial groups. This study aimed to quantify racial and gender disparities both nationally and by geographic regions. METHODS: 168,504 TSAs were identified using Medicare fee-for-service inpatient and outpatient claims data and beneficiary enrollment data from 2020 to 2022Q4. The percentage of outpatient cases, defined as cases discharged on the same day of surgery, was evaluated by racial and gender groups and by different census divisions. A multivariate logistics regression model controlling for patient sociodemographic information (White vs. non-White race, age, gender, and dual eligibility for both Medicare and Medicaid), hierarchical condition category (HCC) score, hospital characteristics, year fixed effects, and patient residency state fixed effects was performed. RESULTS: The TSA volume per 1000 beneficiaries was 2.3 for the White population compared with 0.8, 0.6, and 0.3 for the Black, Hispanic, and Asian population, respectively. A higher percentage of outpatient TSAs were in White patients (25.6%) compared with Black patients (20.4%) (P < .001). The Black TSA patients were also younger, more likely to be female, more likely to be dually eligible for Medicaid, and had higher HCC risk scores. After controlling for patient sociodemographic characteristics and hospital characteristics, the odds of receiving outpatient TSAs were 30% less for Black than the White group (odds ratio 0.70). Variations were observed across different census divisions, with South Atlantic (0.67, P < .01), East North Central (0.56, P < .001), and Middle Atlantic (0.36, P < .01) being the 4 regions observed with significant racial disparities. Statistically significant gender disparities were also found nationally and across regions, with an overall odds ratio of 0.75 (P < .001). DISCUSSION: Statistically significant racial and gender disparities were found nationally in outpatient TSAs, with Black patients having 30% (P < .001) fewer odds of receiving outpatient TSAs than White patients, and female patients with 25% (P < .001) fewer odds than male patients. Racial and gender disparities continue to be an issue for shoulder arthroplasties after the adoption of outpatient TSAs.

Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency.

OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions. METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched. RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02). CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

The compensatory role of T cells from lymph nodes in mice with splenectomy.

The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well-established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes.

Association between neck circumference and bone mineral loss: A cross-sectional study in Sichuan province in China.

BACKGROUND: The associations of fat distribution with bone health are debatable. We aimed to investigate the associations between neck circumference (NC) and bone mineral loss among the adult Chinese population in Sichuan province. METHODS: We examined overall NC size and NC stratums (≤35 cm, 3538 cm) with bone mineral density (BMD) at the femoral neck, lumbar spine, total hip skeletal sites in 135 men and 479 women respectively, and assessed whether adiposity, lipids, and calcium and phosphorus levels, might have a biased role in the relationship of NC and bone mineral loss with linear regression, logistic regression, and restricted cubic spline models. RESULTS: The overall NC size is not independently associated with BMD at all sites. However, stratification for NC revealed that the positive correlation between NC and BMD at all sites were significant in the NC stratum 1 (≤35 cm) in women (all p<0.05) and NC stratum 2 (3538 cm) compared with NC stratum 1 using logistic regression. However, in women, no statistically significant association was observed between NC stratum 1 and BMD values after adjustment for the same confounders. CONCLUSIONS: Our findings suggest a NC stratum-specific association between NC size and bone mineral loss in men in Sichuan province in China, but not in women.