Abstract
BACKGROUND
Glioblastoma (GB) is the most common primary malignant brain tumor in adults. It remains uncertain the potential effects of health disparities in this patient population.
METHODS
...We conducted a retrospective chart review of newly diagnosed GB patients from 2000–2015 at a free standing dedicated cancer center (MD Anderson Cancer Center - MDACC) and a safety net county hospital (Ben Taub General Hospital - BT) located in Houston, Texas. We obtained demographics, insurance status, clinical variables, extent of resection, treatment, and other known prognostic variables (Karnofsky Score – KPS) to evaluate their role on overall GB survival (OS).
RESULTS
We identified 1,073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, primary language, insurance status, marital status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) consisting of concurrent chemoradiation followed by adjuvant temozolomide between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p<0.0176). Of the 177 BT patients, 40 (23%) had KPS KPS <70 at diagnosis, compared to 6 (0.01%) of the 896 MDACC patients. Only 81 (45.8%) of BT patients received SOC compared to 577 (64%) of MDACC patients (p<0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p<0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had a KPS less than 70 at time of diagnosis and 77 (80%) did not have insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance potentially affecting their ability to receive SOC.
Background
Examine the potential effects of health disparities in survival of glioblastoma (GB) patients.
Methods
We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to ...2015 at a free standing dedicated cancer center (MD Anderson Cancer Center—MDACC) and a safety net county hospital (Ben Taub General Hospital—BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score—KPS) to evaluate their role on overall GB survival (OS).
Results
We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance.
Conclusions
GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.
Abstract
BACKGROUND
Standard of care (SOC) and patient survival in glioblastoma have changed little in the past 17 years. We evaluated in a phase 3 trial whether adding an autologous tumor ...lysate-loaded dendritic cell vaccine (murcidencel) to SOC extends survival. Patients and
METHODS
Newly diagnosed glioblastoma patients were randomized 2:1 to either murcidencel or placebo. Under a crossover design, all patients could receive murcidencel following tumor recurrence. All parties remained blinded regarding treatments before recurrence. Patients thus received murcidencel at new diagnosis (nGBM) or at recurrence (rGBM) following crossover from placebo. The primary and secondary endpoints compare overall survival (OS) with contemporaneous, matched external controls. Four sets of analyses were conducted to ensure rigorous matching of the controls, reduce biases, and confirm the robustness of the results.
RESULTS
331 patients were enrolled. With the crossover, 89% received murcidencel. Median OS (mOS) for nGBM patients (n = 232) was 19.3 months from randomization (22.4 months from surgery) with murcidencel vs. 16.5 months from randomization in the controls (HR = 0.80, p = 0.002). Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%. For rGBM (n = 64), mOS was 13.2 months from relapse vs. 7.8 months in the controls (HR = 0.58, p < 0.001). Survival at 24 months post-recurrence was 20.7% vs. 9.6%, and at 30 months post-recurrence was 11.1% vs 5.1%. In nGBM patients with methylated MGMT (n = 90), mOS was 30.2 months from randomization (33 months from surgery) with murcidencel vs. 21.3 months from randomization in the controls (HR = 0.74, p = 0.027). The treatment was well tolerated, with only 5 serious adverse events deemed at least possibly related to the vaccine.
CONCLUSION
Clinically meaningful and statistically significant survival extension was seen in both nGBM and rGBM patients treated with murcidencel and SOC compared with contemporaneous, matched external controls who received SOC alone.
Despite a clear association of patient's age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of ...viral load dynamics with patient's age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients' plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.
Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated ...with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.
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•Critical COVID-19 is associated with enhanced eosinophil-mediated inflammation•FcγR signal and complement activation are elevated in critical COVID-19•Immune complexes and MAC are consistently detected in lung tissues from fatal cases•Th2-biased humoral responses are associated with critical COVID-19
Kim et al. find that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. Increased Th2-biased immune responses, accompanying overt complement activation, are seen in the critical group. These findings suggest that enhanced eosinophil-mediated inflammation and dysregulated humoral responses might be drivers of severe COVID-19.
We analyzed the relationship between actual and perceived body, the effect of body shape on this relationship, and age and gender differences within it. Descriptive statistics were analyzed using ...body measurement data of 6,172 Koreans aged 15–69 years, in addition to a survey about perceived body types. We determined the body perception type according to the congruence between perceived and actual body. Using the body proportion index, we identified whether there were physical features depending on perception type. Women perceived their bodies more objectively than did men and eased their physical evaluation standards in their 50s. On the other hand, men tended to underestimate their obesity levels since their youth. In addition, participants underestimating their bodies had a high body mass index. These results provide an overall understanding of the tendency to perceive the body differently by age and gender and may be used as a reference in clothing design.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality. High-mobility group ...box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.
Glioblastoma (GBM) is the most lethal primary brain tumor with few treatment options. The survival of glioma-initiating cells (GICs) is one of the major factors contributing to treatment failure. ...GICs frequently produce and respond to their own growth factors that support cell proliferation and survival. In this study, we aimed to identify critical autocrine factors mediating GIC survival and to evaluate the anti-GBM effect of antagonizing these factors. Proteomic analysis was performed using conditioned media from two different patient-derived GBM tumor spheres under a growth factor-depleted status. Then, the antitumor effects of inhibiting an identified autocrine factor were evaluated by bioinformatic analysis and molecular validation. Proteins secreted by sphere-forming GICs promote cell proliferation/survival and detoxify reactive oxygen species (ROS). Among these proteins, we focused on midkine (MDK) as a clinically significant and pathologically relevant autocrine factor. Antagonizing MDK reduced the survival of GBM tumor spheres through the promotion of cell cycle arrest and the consequent apoptotic cell death caused by oxidative stress-induced DNA damage. We also identified PCBP4, a novel molecular predictor of resistance to anti-MDK treatment. Collectively, our results indicate that MDK inhibition is an important therapeutic option by suppressing GIC survival through the induction of ROS-mediated cell cycle arrest and apoptosis.
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