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Strahlentherapie Und Onkologie : Organ... Jun 2024Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to...
BACKGROUND
Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to evaluate the cost-effectiveness of bevacizumab for CRN treatment from the Chinese payers' perspective.
METHODS
A decision tree model was developed to compare the costs and health outcomes of bevacizumab and corticosteroids for CRN therapy. Efficacy and safety data were derived from the NCT01621880 trial, which compared the effectiveness and safety of bevacizumab monotherapy with corticosteroids for CRN in nasopharyngeal cancer patients, and demonstrated that bevacizumab invoked a significantly higher response than corticosteroids (65.5% vs. 31.5%, P < 0.001) with no significant differences in adverse events between two groups. The utility value of the "non-recurrence" status was derived from real-world data. Costs and other utility values were collected from an authoritative Chinese network database and published literature. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was evaluated via one-way and probabilistic sensitivity analyses.
RESULTS
Bevacizumab treatment added 0.12 (0.48 vs. 0.36) QALYs compared to corticosteroid therapy, along with incremental costs of $ 2010 ($ 4260 vs. $ 2160). The resultant ICER was $ 16,866/QALY, which was lower than the willingness-to-pay threshold of $ 38,223/QALY in China. The price of bevacizumab, body weight, and the utility value of recurrence status were the key influential parameters for ICER. Probabilistic sensitivity analysis revealed that the probability of bevacizumab being cost-effectiveness was 84.9%.
CONCLUSION
Compared with corticosteroids, bevacizumab is an economical option for CRN treatment in China.
PubMed: 38829437
DOI: 10.1007/s00066-024-02242-6 -
Archives of Razi Institute Dec 2023Pentoxifylline (PTXF) is a vasoactive agent that plays a significant role in the treatment of thin-layer endometrium cases. The PTXF, also identified as oxpentifylline,...
Pentoxifylline (PTXF) is a vasoactive agent that plays a significant role in the treatment of thin-layer endometrium cases. The PTXF, also identified as oxpentifylline, is a member of xanthine derivatives and a competitive nonselective phosphodiesterase inhibitor leading to the elevation of intracellular cAMP, inhibition of tumor necrosis factor and leukotriene synthesis, activation of protein kinase A, and reduction of inflammation and innate immunity. Moreover, it is used as an agent to relieve muscle pain in people with peripheral artery disease (vascular irregularities). It is also an acceptable choice for the treatment of radiation-induced fibrosis. Therefore, the present study aimed to determine the advantageous impact of PTXF and PTXF-loaded poly lactic-co-glycolic acid (PLGA) on female rats after being exposed to ethanol to create a thin layer of the endometrium. For this purpose, 50 female rats were selected and divided into five groups (G1: negative normal control, G2: positive control, G3: PLGA only, G4: preference PTXF, and G5: PLGA-PTXF groups) for a 20-day treatment period. In this study, the histopathological section revealed a perfect improvement in the tissues of the uterine horn of female rats that induced endometria and were treated with PLGA-PTXF. In this group of rats, clear healing was achieved and there was an increase in the thickness of endometrium and myometrium, compared to the ordinary PTXF-treated group which had the lowest recovery characteristics. However, the positive control group underwent a significant decrease in terms of endometrium and myometrium thickness as well as vascular and glandular density. This study showed that the PTXF-loaded PLGA had the capacity to heal the thin layer of the endometrium by improving the levels of histopathological changes, especially regarding the thickness of the endometrium and myometrium more than the ordinary PTXF.
Topics: Pentoxifylline; Animals; Female; Rats; Endometrium; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Wistar
PubMed: 38828173
DOI: 10.32592/ARI.2023.78.6.1762 -
Clinical Oncology (Royal College of... Apr 2024Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we...
AIMS
Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we present our preliminary data of RT dose escalation using Ga-Pentixafor PET scan. High Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain.
MATERIALS AND METHODS
This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range.
RESULTS
Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis.
CONCLUSIONS
The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of Ga-pentixafor PET scan for radiation dose escalation should be further explored.
CLINICAL TRIAL NUMBER
CTRI/2019/05/019146.
PubMed: 38821722
DOI: 10.1016/j.clon.2024.04.011 -
Journal of Neurosurgery May 2024Real-time MRI-guided focused laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment choice for challenging intracranial lesions that are...
OBJECTIVE
Real-time MRI-guided focused laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment choice for challenging intracranial lesions that are either resistant to conventional therapies or located in deep or critical areas of the brain. However, existing studies on LITT within surgical neuro-oncology are relatively small and have limited follow-up periods. The authors aimed to present a comprehensive analysis of their experiences with LITT in surgical neuro-oncology, with the intent to provide a clearer understanding of the safety and efficacy of this procedure.
METHODS
This study was an exploratory cohort analysis encompassing all patients who underwent LITT for brain tumors at a single center between 2013 and 2023. The primary focus was extent of ablation (EOA), time to recurrence (TTR), and overall survival (OS). Secondary outcomes, including the rate of complications, were also evaluated. Comparative analyses were conducted based on lesion subtypes, and factors predicting outcomes were identified.
RESULTS
Three hundred thirteen patients underwent LITT procedures. During a mean follow-up of 10.4 months, 66.8% of patients remained alive and 26.2% of the ablated lesions recurred. The mean age of the cohort was 60.4 ± 13.3 years (58.5% female). The lesion subtypes that were treated comprised metastases (30%), glioblastoma (GBM; 41.6%), low-grade glioma (9.1%), radiation necrosis (11.4%), and meningioma (2.2%). The permanent neurological deficit rate was 14% (n = 44), with 25 (8%) of them new-onset deficits and 19 deficits (6.1%) that were present preoperatively and did not resolve after LITT. The mean TTR and OS were 12.2 and 38.1 months, respectively. TTR and OS varied significantly by lesion subtype (p < 0.001, log-rank analysis). A high-grade lesion was identified as the single factor linked to tumor recurrence. Age, high-grade lesion, preoperative lesion volume, and readmission within 30 days were identified as factors significantly associated with OS in the multivariable Cox regression analysis. EOA > 100% predicted longer OS in metastases and GBM by log-rank analysis.
CONCLUSIONS
LITT stands as a secure and feasible ablative treatment choice for intracranial lesions, potentially suitable for specific patient cases otherwise not amenable to surgical intervention. These findings further corroborate the safety of the procedure and its favorable outcomes, underscoring its potential significance in clinical practice.
PubMed: 38820611
DOI: 10.3171/2024.3.JNS245 -
Plastic and Reconstructive Surgery.... May 2024Incision healing after mastectomy and immediate reconstruction can be supported with closed-incision negative pressure therapy (ciNPT). Studies have reported patients...
BACKGROUND
Incision healing after mastectomy and immediate reconstruction can be supported with closed-incision negative pressure therapy (ciNPT). Studies have reported patients receiving postoperative care with ciNPT after breast surgery exhibited lower rates of dehiscence, infection, necrosis, and seroma, compared with standard dressings. A recent approach to ciNPT involves the application of negative pressure to the incision and a wider area of surrounding tissue. In this retrospective review, we investigated the outcomes of ciNPT using full-coverage dressings over the entire breast after mastectomy and reconstruction.
METHODS
Patients underwent mastectomies and immediate prepectoral breast reconstruction with an implant or tissue expander. After surgery, patients received oral antibiotics and ciNPT with full-coverage foam dressings at -125 mm Hg.
RESULTS
All 54 patients (N = 105 incisions) were women, with a mean age of 53.5 years and 29.1 kg per m body mass index. Common comorbidities included prior chemotherapy (31.3%) or radiation (21.6%), hypertension (14.8%), and diabetes (5.6%). Procedures included skin-reducing (34.3%), skin-sparing (7.6%), and nipple-sparing (58.1%) mastectomies. Lymph nodes were removed in 38 (36.2%) incisions. All patients were discharged home with ciNPT on postoperative day (POD) 1, and ciNPT was discontinued on POD 5-7. At POD 30, three patients developed seromas, requiring revision. Of these, one required removal of the left tissue expander. The remaining 102 incisions (97.1%) healed without complication.
CONCLUSIONS
Among this cohort, the use of ciNPT with full-dressing coverage of the breast incisions and surrounding soft tissue was effective in supporting incisional healing after mastectomy and immediate reconstruction.
PubMed: 38818231
DOI: 10.1097/GOX.0000000000005809 -
World Journal of Stem Cells May 2024Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of...
BACKGROUND
Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.
AIM
To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE) mouse model and an cellular model.
METHODS
ApoE mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways.
RESULTS
DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.
CONCLUSION
This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE mice on a HFD, and could be of greater value in stem cell-based treatments for AS.
PubMed: 38817328
DOI: 10.4252/wjsc.v16.i5.575 -
International Journal of Nanomedicine 2024Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in...
INTRODUCTION
Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy.
METHODS
Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections.
RESULTS
The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments.
CONCLUSION
MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.
Topics: Animals; Cisplatin; Lung Neoplasms; Mice; Imiquimod; Mice, Inbred C57BL; Hydrogels; Apoptosis; Nanostructures; Photothermal Therapy; Antineoplastic Agents; Cell Line, Tumor; Drug Delivery Systems; Humans; Temperature; Dendritic Cells; Drug Carriers; Carcinoma, Lewis Lung
PubMed: 38813391
DOI: 10.2147/IJN.S449541 -
European Journal of Ophthalmology May 2024Radiation-induced scleral necrosis (RISN) is a less frequent complication of brachytherapy for uveal melanoma, and may require surgical treatment in selected cases. We...
PURPOSE
Radiation-induced scleral necrosis (RISN) is a less frequent complication of brachytherapy for uveal melanoma, and may require surgical treatment in selected cases. We aimed to identify the prognostic factors for RISN treatment.
METHODS
All patients with brachytherapy for uveal melanoma treated at our institution between 01/1999 and 12/2016 who developed RISN were followed until 02/2021. Various parameters were evaluated through univariable and multivariable Cox regression analysis. The surgical intervention due to RISN was the principal outcome event of this study.
RESULTS
Of 115 patients in the final cohort, 51 individuals (44%) underwent RISN treatment (conjunctival revision [n = 2], patching [n = 46] or enucleation [n = 3]) at median 1.80 months after RISN occurrence. Significant RISN characteristics were summarized into a novel RISN severity scale - Grade I: largest diameter ≤ 5 mm and no progression; Grade II: largest diameter > 5 mm or any progression during the follow-up; Grade III: presence of uveal prolapse; and Grade IV: leakage through open eyewall perforation. In the multivariable analysis, the RISN severity scale (aHR = 2.37 per grade increase, p = 0.01) and the time between brachytherapy and RISN occurrence (<15 months, aHR = 6.33, p < 0.0001) were independently associated with the study endpoint. The RISN severity scale showed high diagnostic accuracy for prediction of RISN treatment (AUC = 0.869).
CONCLUSIONS
In our series, about the half of RISN cases underwent surgical treatment. The presented novel severity scale for RISN might become a helpful tool for clinical management of individuals with RISN. We recommend external validation of the diagnostic accuracy of the presented scale.
PubMed: 38807558
DOI: 10.1177/11206721241257979 -
Analytical Chemistry Jun 2024Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome...
Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: ∼19 nm; length: ∼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: ∼35 nm; width: ∼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.
Topics: Immunotherapy; Animals; Mice; DNA; Cytokines; Spectrum Analysis, Raman; Gold; Biosensing Techniques; Metal Nanoparticles; Humans; Silver; Nanotubes; Neoplasms; Interferon-gamma; Tumor Necrosis Factor-alpha
PubMed: 38804540
DOI: 10.1021/acs.analchem.4c01626 -
Cardiovascular Diabetology May 2024Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio...
Association of stress hyperglycemia ratio with left ventricular function and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a 3.0 T cardiac magnetic resonance study.
BACKGROUND
Stress hyperglycemia, which is associated with poor prognosis in patients with acute myocardial infarction (AMI), can be determined using the stress hyperglycemia ratio (SHR). Impaired left ventricular function and microvascular obstruction (MVO) diagnosed using cardiac magnetic resonance (CMR) have also been proven to be linked to poor prognosis in patients with AMI and aid in risk stratification. However, there have been no studies on the correlation between fasting SHR and left ventricular function and MVO in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Therefore, this study aimed to investigate the additive effect of fasting SHR on left ventricular function and global deformation in patients with ASTEMI and to explore the association between fasting SHR and MVO.
METHODS
Consecutive patients who underwent CMR at index admission (3-7 days) after primary percutaneous coronary intervention (PPCI) were enrolled in this study. Basic clinical, biochemical, and CMR data were obtained and compared among all patients grouped by fasting SHR tertiles: SHR1: SHR < 0.85; SHR2: 0.85 ≤ SHR < 1.01; and SHR3: SHR ≥ 1.01. Spearman's rho (r) was used to assess the relationship between fasting SHR and left ventricular function, myocardial strain, and the extent of MVO. Multivariable linear regression analysis was performed to evaluate the determinants of left ventricular function and myocardial strain impairment in all patients with AMI. Univariable and multivariable regression analyses were performed to investigate the correlation between fasting SHR and the presence and extent of MVO in patients with AMI and those with AMI and diabetes mellitus (DM).
RESULTS
A total of 357 patients with ASTEMI were enrolled in this study. Left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI) were significantly lower in SHR2 and SHR3 than in SHR1. Compared with SHR1 and SHR2 groups, left ventricular strain was lower in SHR3, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strains. Fasting SHR were negatively correlated with LVEF, LVGFI, and GRS (r = - 0.252; r = - 0.261; and r = - 0.245; all P<0.001) and positively correlated with GCS (r = 0.221) and GLS (r = 0.249; all P <0.001). Multivariable linear regression analysis showed that fasting SHR was an independent determinant of impaired LVEF, LVGFI, GRS, and GLS. Furthermore, multivariable regression analysis after adjusting for covariates signified that fasting SHR was associated with the presence and extent of MVO in patients with AMI and those with AMI and DM.
CONCLUSION
Fasting SHR in patients with ASTEMI successfully treated using PPCI is independently associated with impaired cardiac function and MVO. In patients with AMI and DM, fasting SHR is an independent determinant of the presence and extent of MVO.
Topics: Humans; Male; ST Elevation Myocardial Infarction; Middle Aged; Female; Ventricular Function, Left; Aged; Coronary Circulation; Blood Glucose; Hyperglycemia; Microcirculation; Predictive Value of Tests; Risk Factors; Ventricular Dysfunction, Left; Percutaneous Coronary Intervention; Biomarkers; Fasting; Magnetic Resonance Imaging, Cine; Prognosis; Magnetic Resonance Imaging; Time Factors
PubMed: 38802898
DOI: 10.1186/s12933-024-02271-6