Predictors of Clavien-Dindo Grade III-IV or Grade V Complications after Metastatic Spinal Tumor Surgery: An Analysis of Sociodemographic, Socioeconomic, Clinical, Oncologic, and Operative Parameters.

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such as sociodemographic or socioeconomic data on outcomes. We retrospectively analyzed data from 165 patients who underwent surgery for spinal metastases between 2012-2023. The primary outcome was development of major complications (i.e., Clavien-Dindo Grade III-IV complications), and the secondary outcome was 30-day mortality (i.e., Clavien-Dindo Grade V complications). An exploratory data analysis that included sociodemographic, socioeconomic, clinical, oncologic, and operative parameters was performed. Following multivariable analysis, independent predictors of Clavien-Dindo Grade III-IV complications were Frankel Grade A-C, lower modified Bauer score, and lower Prognostic Nutritional Index. Independent predictors of Clavien-Dindo Grade V complications) were lung primary cancer, lower modified Bauer score, lower Prognostic Nutritional Index, and use of internal fixation. No sociodemographic or socioeconomic factor was associated with either outcome. Sociodemographic and socioeconomic factors did not impact short-term surgical outcomes for metastatic spinal tumor patients in this study. Optimization of modifiable factors like nutritional status may be more important in improving outcomes in this complex patient population.

Physical Compatibility of Intravenous Ondansetron Hydrochloride and Nafcillin Sodium.

Information on the physical compatibility of intravenous (IV) medications is vital for patient care and safety in acute care settings. Drug information resources list ondansetron and nafcillin as IV compatible, however, bolus concentrations of ondansetron are not reported. This study investigated the in vitro physical compatibility of bolus and infusion concentrations of ondansetron hydrochloride with nafcillin sodium. Two admixtures were prepared: 1) ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL, and 2) ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL. The admixtures were prepared in triplicate using aseptic technique according to manufacturer guidance and stored at room temperature (22-23 °C) for up to 24 hours. Admixtures were examined for visual precipitation, turbidity, and pH at baseline and at 1, 5, 8, and 24 hours. Admixture 1 developed a haze immediately after mixing, which was sustained over 24 hours. There was a demonstrative change in absorbance after 1 hour, but pH remained stable until hour 24. Admixture 2 developed a haze at 5 hours, but the absorbance and pH remained stable until hour 24; a decrease in the pH was observed in all samples at hour 24. This in vitro study revealed that ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL are not physically compatible when administered through the same IV line. No demonstrative change was observed with ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL; however, concurrent administration of these medications is questionable when delivered through an IV line for periods of five hours or longer.

Reprint of: Determining the association between grocery nutrition scores and number of medications taken for metabolic syndrome: A pilot study.

BACKGROUND: Metabolic syndrome is a cluster of disease states that increases an individual's risk of developing diabetes or cardiovascular disease. When treating metabolic syndrome, lifestyle and diet are primary areas for interventions. A dietician-led grocery nutrition system scoring patients' purchases may correlate to better control of metabolic health. OBJECTIVE: To compare the number of medications taken for metabolic syndrome for patients with grocery nutrition scores at goal versus those below goal as pre-defined by the dietician team. PRACTICE DESCRIPTION: This exploratory, retrospective cohort pilot study took place in a single pharmacy within a large community pharmacy chain in Northwest Ohio. PRACTICE INNOVATION: This retrospective cohort study compared the number of medications taken for metabolic syndrome between two groups: patients with a grocery nutrition score at a dietician-set goal and patients not at goal. EVALUATION METHODS: Data were collected from May 2022 to March 2023, with patients completing a questionnaire collecting information on demographics. In addition, the questionnaire, grocery nutrition scores, and patient medication records were collected. Descriptive statistics were calculated for demographic items. A number of medications taken for metabolic syndrome by patients at dietician-set grocery nutrition score goal and not at goal were compared using a Mann-Whitney U test. RESULTS: A total of 40 patients were enrolled in this study. There was not a significant difference in a number of medications taken for metabolic syndrome between groups, with patients who had a grocery nutrition score at goal taking an average of 1.20 medications compared to 1.96 for those with grocery nutrition scores below goal. CONCLUSIONS: While no statistical difference in mean medication use was identified, grocery nutrition scores may help understand patients' dietary habits. Larger studies are required to test the relationship between grocery nutrition scores, patient-specific factors, and medications taken for metabolic syndrome.

International Initiatives of the American Heart Association: Original Concepts, Present Programs, and Future Focus: A Science Advisory From the American Heart Association.

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings. Although the AHA's and American Stroke Association's international efforts have expanded substantially since those early days, global knowledge exchange remains the bedrock of its international endeavors. As the AHA turns 100, we reflect on the successful global efforts in prevention, resuscitation, global advocacy, quality improvement, and health equity that have guided the organization to a place of readiness for "advancing health and hope, for everyone, everywhere." Motivated by the enormous potential for population health gains in an aging world, the AHA is entering its second century with redoubled commitment to improving global cardiovascular and cerebrovascular health for all.

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial.

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Indications and Outcomes of Laser Retinopexy in Eyes With High-Risk Lattice Degeneration.

Purpose: To examine the characteristics of eyes with high-risk lattice degeneration treated with laser retinopexy and determine the indications, safety, and outcomes of the treatment. Methods: This interventional single-surgeon consecutive retrospective study was conducted at Wills Eye Hospital between 2014 and 2021. The series included eyes with lattice degeneration with high-risk lesions. Documented characteristics and outcomes of these eyes and fellow eyes were documented. Results: The study comprised 167 eyes of 143 patients (53.3% women; mean age [±SD], 50 ± 17 years). Complications after laser treatment included new posterior vitreous detachment (PVD) (n = 21), epiretinal membrane (ERM) (n = 13), retinal detachment (RD) (n = 5), and additional laser required (n = 22). Eyes that developed ERMs were more likely to develop PVDs (odds ratio, 5.39; 95% CI, 1.57-18.47). Patents who developed ERMs were older (mean, 60 ± 7 years vs 49 ± 17 years; P = .016), as were those developing PVDs (mean, 59 ± 8 years vs 48 ± 17; P = .005). No eye with a new ERM required surgery (n = 13). Four eyes with a new RD required laser retinopexy alone; 1 eye was treated surgically. No eye had an RD at the most recent evaluation. Conclusions: Despite high-risk lesions in areas of lattice degeneration, few eyes developed RDs after prophylactic laser retinopexy. Older patients may have a higher risk for ERM or PVD after laser treatment. Eyes with post-laser PVD were more likely to develop an ERM.

Uncovering molecular mechanisms for amelanotic/hypopigmented primary cutaneous melanoma.

BACKGROUND: A portion of approximately 2-20% of cutaneous melanoma (CM) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. OBJECTIVES: Since the degree to which somatic mutations and copy number aberrations (CNA) in genes associated with skin-lightening or albinism may contribute to the loss of tumour pigmentation in AHM samples has not yet been addressed, we have investigated loss of function mutations of key pigmentation genes in matched germline and AHM as well as pigmented melanoma (PM) tumour DNA samples. METHODS: An analysis of clinical and histopathological characteristics together with whole exome sequencing data of 34 fresh frozen primary CM, graded according to the amount of pigmentation present was performed. Together with germline and somatic variant analysis, 30 samples were previously analysed for CNA changes. This study focussed on germline and somatic variants in the coding region of 16 genes known to be associated with albinism/hypopigmentation or variation in human pigmentation in all samples. Chromosomal regions encompassing these 16 genes were examined for DNA copy loss or gain. RESULTS: The finding that red hair related MC1R and TYR R402Q loss of activity gene variant alleles and genotypes are associated with AHM was validated in this study. Germline AHM-related gene variants were enriched in 70% (n=7 of 10) of AHM patients vs 8.3% (n=2 of 24) of PM patients. This surprisingly high frequency of rare germline variants in AHM patients constitutes the "first hit" and confirms that AHM patients are more likely to be albinism allele carriers than patients with PM. Next, in CNA analysis of each tumour sample, 50% (n=4 of 8) AHM samples with a pigmentation gene variant had LOH in the region containing the corresponding gene, and 25% (=2 of 8) had loss-of-heterozygosity (LOH) in chromosomal regions of two AHM-related genes. CONCLUSIONS: This study proposes that the likely molecular mechanism for development of amelanogenesis in AHM is carriage of an albinism/hypopigmentation allele followed by LOH of the corresponding gene in the tumour.

Higher modified frailty index score is associated with 30-day postoperative complications following simultaneous bilateral total knee arthroplasty.

BACKGROUND: There is no clear consensus regarding patient populations at highest risk for complications from simultaneous bilateral total knee arthroplasty (TKA). The purpose of this study was to determine whether the comorbidities comprising the modified Frailty Index (mFI) were correlated with poor outcomes following simultaneous bilateral TKA. METHODS: From 2006 to 2019, patients undergoing bilateral TKA aged 50 years or older were identified in a national database. The 5-item mFI was calculated based on the presence of five comorbidities: diabetes, congestive heart failure, hypertension, chronic obstructive pulmonary disease, and dependent functional status. Chi-squared and multivariable regression analyses were used to evaluate the association of mFI scores with postoperative complications. RESULTS: The study analyzed 8,776 patients with an average age of 65 years. After adjustment on multivariable regression analysis, compared to patients with a mFI score of 0, those with a score of 1 had an increased risk of pulmonary complication (OR 3.14; p = 0.011), renal problem (OR 12.86; p = 0.022), sepsis complication (OR 2.82; p = 0.024), postoperative transfusion (OR 1.19; p = 0.012), and non-home discharge (OR 1.17; p = 0.002).Patients with a score of 2 compared to 0 had similar complications when compared. These patients had an increased risk of cardiac complication (OR 4.84; p = 0.009) and prolonged hospital stay (OR 4.06; p < 0.001). CONCLUSION: Increased mFI scores were associated with significantly higher complication rates in patients undergoing simultaneous bilateral TKA compared to unilateral TKA. Our results can be used to identify which patients may need a staged bilateral TKA or preoperative optimization to safely undergo a simultaneous bilateral TKA. LEVEL OF EVIDENCE: III.

Seasonal variability in the feeding ecology of an oceanic predator.

Complementary approaches (stomach contents, DNA barcoding, and stable isotopes) were used to examine seasonal shifts in the feeding ecology of an oceanic predator, yellowfin tuna (Thunnus albacares, n = 577), in the northern Gulf of Mexico. DNA barcoding greatly enhanced dietary resolution and seasonally distinct prey assemblages were observed for both sub-adults and adults. In general, diet was characterized by ommastrephid squids and exocoetids in spring, juvenile fishes (i.e., carangids and scombrids) in summer, migratory coastal fishes during fall, and an increased consumption of planktonic prey (e.g., amphipods) in winter. Seasonal variability in bulk stable isotope values (δ13C, δ15N, and δ34S) was also observed, with low δ15N values and high δ34S values during late summer/early fall and high δ15N values (low δ34S) during late winter/early spring. Bayesian stable isotope mixing models corroborated seasonal diet shifts, highlighting the importance of oceanic nekton in spring/summer, coastal nekton during fall, and oceanic plankton during winter. Seasonal shifts in diet appeared to be influenced by prey reproductive cycles, habitat associations, and environmental conditions. Findings highlight the complex food web dynamics supporting an opportunistic oceanic predator and the importance of seasonal cycles in prey availability to predator resource utilization in open-ocean ecosystems.

Estimated Investment Need to Increase England's Capacity to Diagnose Eligibility for an Alzheimer's Treatment to G7 Average Capacity Levels.

BACKGROUND: As disease-modifying Alzheimer's (AD) treatments are becoming available, concerns have been raised that even high-income countries lack the diagnostic capacity to accurately identify eligible patients in a timely manner. OBJECTIVES: We analyze how much NHS England would have to invest in capacity for AD specialists, biomarker testing with PET scans or CSF testing and MRI scans to reach G7 average levels and estimate the effect on wait times in the diagnostic process. DESIGN: Desk research and expert interviews for cost and capacity data. Markov model to estimate wait times. SETTING: NHS England. MEASUREMENTS: AD specialists, and PET and MRI scanners per capita in G7 countries and wait times in England under different investment scenarios. RESULTS: England has the lowest number of PET and MRI scanners and the second-lowest of AD specialists per capita among the G7 countries. An investment of GBP 14 billion over ten years would be needed to reach G7 average levels, of which 31%, 22%, 10%, 37% would be devoted to capacity for memory assessment services, PET scanning, CSF analysis, and MRI scanning, respectively. This investment would reduce estimated average wait times by around 87% between 2023 and 2032. CONCLUSIONS: The NHS England has large gaps in diagnostic capacity for AD. Without substantial investments, AD patients in England would experience substantial wait times and avoidable disease progression.

Corrigendum: Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

[This corrects the article DOI: 10.3389/fimmu.2024.1384623.].

Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.

Acknowledging and addressing real-world challenges to treating immune-related adverse events.

Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatment. However, their success is mitigated by the recognition that ICI-induced immune-related adverse events (irAEs) pose considerable challenges to patients and clinicians. These autoimmune toxicities are heterogeneous, unpredictable, and reflect a disease state resulting from a change in the immune system of patients. This contrasts with the typical acute nature of toxicities from chemotherapy and molecularly targeted oncology therapies. Management is further complicated by the extended bioavailability of these agents in patients as well as the persistence of autoimmune pathology. Currently, irAE treatment remains suboptimal in many areas, as many expert guidelines remain vague on the optimal selection, dosing, and duration of steroids and the use of other immunosuppressive agents. This coupled with delays in diagnosis and difficulties for patients accessing effective irAE treatment results in barriers to effective irAE care. The latter is complicated by the lack of US Food and Drug Administration-approved irAE treatments that lead to insurance denials, as well as the high cost of biological immunosuppressant therapies. Fortunately, rheumatologists and other subspecialists with expertize in the management of chronic autoimmune conditions have become more involved in irAE diagnosis and management and may help navigate treatment. In this commentary, we discuss these issues and propose potential solutions to advance the field.

Estimated Pulse-Wave Velocity and Magnetic Resonance Imaging Markers of Cerebral Small-Vessel Disease in the NOMAS.

BACKGROUND: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging. METHODS AND RESULTS: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (ß=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment. CONCLUSIONS: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.

Cmai: Predicting Antigen-Antibody Interactions from Massive Sequencing Data.

The interaction between antigens and antibodies (B cell receptors, BCRs) is the key step underlying the function of the humoral immune system in various biological contexts. The capability to profile the landscape of antigen-binding affinity of a vast number of BCRs will provide a powerful tool to reveal novel insights at unprecedented levels and will yield powerful tools for translational development. However, current experimental approaches for profiling antibody-antigen interactions are costly and time-consuming, and can only achieve low-to-mid throughput. On the other hand, bioinformatics tools in the field of antibody informatics mostly focus on optimization of antibodies given known binding antigens, which is a very different research question and of limited scope. In this work, we developed an innovative Artificial Intelligence tool, Cmai, to address the prediction of the binding between antibodies and antigens that can be scaled to high-throughput sequencing data. Cmai achieved an AUROC of 0.91 in our validation cohort. We devised a biomarker metric based on the output from Cmai applied to high-throughput BCR sequencing data. We found that, during immune-related adverse events (irAEs) caused by immune-checkpoint inhibitor (ICI) treatment, the humoral immunity is preferentially responsive to intracellular antigens from the organs affected by the irAEs. In contrast, extracellular antigens on malignant tumor cells are inducing B cell infiltrations, and the infiltrating B cells have a greater tendency to co-localize with tumor cells expressing these antigens. We further found that the abundance of tumor antigen-targeting antibodies is predictive of ICI treatment response. Overall, Cmai and our biomarker approach filled in a gap that is not addressed by current antibody optimization works nor works such as AlphaFold3 that predict the structures of complexes of proteins that are known to bind.

Combinatorial macrophage induced innate immunotherapy against Ewing sarcoma: Turning "Two Keys" simultaneously.

BACKGROUND: Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo. METHODS: Macrophages were derived from human peripheral blood monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Flow cytometry- and microscopy-based in-vitro phagocytosis assays were performed to evaluate macrophage phagocytosis of ES cells. Annexin-V assay was performed to evaluate apoptosis. CD47 was knocked out by CRISPR/Cas9 approach. ES cell-based and patient-derived-xenograft (PDX)-based mouse models were utilized to assess the effects of MAG and/or DOX on ES tumor development and animal survival. RNA-Seq combined with CIBERSORTx analysis was utilized to identify changes in tumor cell transcriptome and tumor infiltrating immune cell profiling in MAG and/or DOX treated xenograft tumors. RESULTS: We found that MAG significantly increased macrophage phagocytosis of ES cells in vitro (p < 0.01) and had significant effect on reducing tumor burden (p < 0.01) and increasing survival in NSG mouse model (p < 0.001). The csCRT level on ES cells was significantly enhanced by DOX in a dose- and time-dependent manner (p < 0.01). Importantly, DOX combined with MAG significantly enhanced macrophage phagocytosis of ES cells in vitro (p < 0.01) and significantly decreased tumor burden (p < 0.01) and lung metastasis (p < 0.0001) and extended animal survival in vivo in two different mouse models of ES (p < 0.0001). Furthermore, we identified CD38, CD209, CD163 and CD206 as potential markers for ES-phagocytic macrophages. Moreover, we found increased M2 macrophage infiltration and decreased expression of Cd209 in the tumor microenvironment of MAG and DOX combinatorial therapy treated tumors. CONCLUSIONS: By turning "two keys" simultaneously to reactivate macrophage phagocytic activity, our data demonstrated an effective and highly translatable alternative therapeutic approach utilizing innate (tumor associated macrophages) immunotherapy against high-risk metastatic ES.

Psoriasis and Sleep Disturbance: A US Population-Based Study Using the NHANES Database.

INTRODUCTION: Psoriasis, a chronic inflammatory skin condition, affects approximately 3.0% of the US population, with patients often experiencing significant sleep disturbances. These disturbances include a higher prevalence of conditions such as obstructive sleep apnea, restless leg syndrome, and insomnia. Given the additional risks for cardiovascular disease, metabolic disorders, and depression linked to both poor sleep and psoriasis, addressing sleep issues in this patient group is critical. METHODS: The study utilized National Health and Nutrition Examination Survey (NHANES) data, focusing on individuals aged ≥ 20 years who provided information on psoriasis status and sleep. Multistage stratified survey methodology was applied, with multivariable logistic regression models used to examine the association between psoriasis and sleep issues, adjusting for factors such as age, gender, and health history. RESULTS: Psoriasis diagnosis was significantly associated with trouble sleeping (adjusted odds ratio [aOR] 1.88; 95% confidence interval [CI] 1.44-2.45). There was no significant association between psoriasis and sleep quantity. Older age, female gender, and a history of sleep disorders were predictors of trouble sleeping among psoriasis patients. CONCLUSIONS: Psoriasis is significantly associated with sleep disturbances, independent of sleep duration. This underscores the need for clinical screening focusing on sleep quality rather than quantity in psoriasis patients to effectively identify and treat sleep-related comorbidities. Further research using objective sleep measures is warranted to guide clinical management and improve patient quality of life.

Total Shoulder Arthroplasty is associated With Less Pain and Better Functional Outcomes, but Humeral Head Resurfacing may be Preferred in Younger, Higher Demand Patients: A Short-Term Outcomes Study in Patients with Glenohumeral Osteoarthritis.

Objectives: This study aimed to compare short-term outcomes following Total Shoulder Arthroplasty (TSA) and Humeral Head Resurfacing (HHR) in patients with glenohumeral osteoarthritis (GHOA). Methods: A retrospective analysis included patients who had undergone either TSA or HHR for GHOA at a single institution. Baseline demographics, complications, range of motion (active forward flexion, FF and active external rotation, ER), visual analog scores (VAS), and Subjective Shoulder Values (SSV) were collected. Results: A total of 69 TSA and 56 HHR patients were analyzed. More HHR patients were laborers (44% versus 21%, P=0.01). There were more smokers in the TSA group (25% versus 11%, P=0.04) and more cardiovascular disease in the HHR cohort (64% versus. 6%, p<0.0001). Postoperative FF was similar, but ER was greater in the HHR (47° ± 15°) vs. TSA group (40° ± 12°, P = 0.01). VAS was lower after TSA vs. HHR (median 0, IQR 1 versus median 3.7, IQR 6.9, p<0.0001), and SSV was higher after TSA (89% ± 13% vs. 75% ± 20% after HHR; p<0.0001). Post-operative impingement was more common after HHR (32% vs. 3% for TSA, p<0.0001). All other complications were equivalent. Conclusion: While younger patients and heavy laborers had improved ER following HHR, their pain relief was greater after TSA. Decisions on surgical technique should be based on patient-specific demographic and anatomic factors.