Search Results (13)

Immunotherapy is a promising treatment option for many cancers but is associated with the development of peripheral neuropathy in some patients. This retrospective cross-sectional EMR-based prevalence study was performed at MD Anderson Cancer Center with an aim to define the prevalence and epidemiology of Programmed Cell Death Protein 1 (PD-1) inhibitor-associated polyneuropathy. A total of 12,092 patients treated with a PD-1 inhibitor between 4 March 2016 and 18 June 2023 were identified and those on immunotherapy monotherapy were isolated. A total of 817 patients had documented neuropathy-associated with PD-1 inhibitor exposure, corresponding to a prevalence of 6.76% (6.76%, 95% CI 6.31–7.22). Data was stratified to assess for association between peripheral neuropathy and agent, sex, race, ethnicity, smoking and diabetes status. Patients identifying as “Other” race had higher prevalence of neuropathy compared to White or Caucasian patients (OR 1.514, p = 0.0189) and non-Hispanic or Latino patients had higher prevalence of neuropathy compared to Hispanic or Latino patients (OR 1.502, p = 0.0078). Current-smokers had significantly lower prevalence of neuropathy compared to never-smokers (OR 0.716, p = 0.0368). These disparities underscore the importance of further investigation in genetics and mechanisms to identify therapeutic interventions for PD-1 inhibitor-associated peripheral neuropathy. Full article

To investigate the sintering shrinkage behavior of multigeneration, multilayer zirconia materials using geometrical measurements. Seven zirconia CAD/CAM materials were analyzed, comprising two mono-generation zirconia (HTML: Katana Zr, HTML Plus, 3Y-TZP; UTML: Katana Zr, UTML, 5Y-TZP) and five strength-gradient multilayer zirconia (AIDI: optimill 3D PRO Zir; PRIT: Priti multidisc ZrO₂ multicolor; UPCE: Explore Esthetic; ZCPC: IPS e.max ZirCAD Prime; ZYML: Katana YML) materials. Cubes (10 × 10 × 10 mm³) were milled in varying positions within the disks. Geometrical measurements were applied before and after dense sintering using a micrometer screw gauge, light microscopy, as well as surface scans and shrinkages were calculated. Data were analyzed using Kolmogorov–Smirnov, five-way ANOVA followed by the Scheffé post hoc test, and partial eta squared, as well as the Kruskal–Wallis test, including Bonferroni correction (p < 0.05). The highest influence on the shrinkage was exerted by the zirconia material (^η_P² = 0.893, p < 0.001), followed by the test method (^η_P² = 0.175, p < 0.001), while the vertical and horizontal position and measurement point showed no impact on the shrinkage results (p = 0.195–0.763) in the global analysis. Depending on the test method, the pooled shrinkage values of all tested zirconia materials varied between 17.7 and 20.2% for micrometer screw gauge, 17.7 and 20.1% for light microscopy, and 17.8 and 21.1% for surface scan measurements. The shrinkage values measured in the upper, middle, and lower multilayered vertical direction did not differ significantly in the global analysis for the multilayer materials. Therefore, a uniform shrinkage of these strength-gradient multilayer zirconia materials within clinically relevant restorations can be assumed. Full article

Background: Percutaneous vertebral augmentation techniques, including vertebroplasty, kyphoplasty, and bone tumor radiofrequency ablation (BT-RFA), are commonly used to treat painful vertebral compression fractures (VCFs). While generally safe and effective, they carry risks, including cement extravasation, which can lead to pulmonary embolism or spinal cord compression. This study aims to compare the rate of cement extravasation across different vertebral augmentation techniques and identify potential risk factors. Methods: A retrospective cohort study was conducted at a comprehensive cancer center on 1002 procedure encounters in 888 patients who underwent vertebral augmentation for painful VCFs. Data were collected on patient demographics, fracture pathology, procedure type, imaging guidance, and pain scores. Intraoperative and postoperative imaging were manually reviewed to assess cement extravasation. Statistical analyses were performed using pairwise comparisons with Tukey’s Honest Significant Difference adjustment to compare cement extravasation rates across the procedure groups and generalized linear mixed models to assess the association between the cement extravasation with other variables. Results: Cement extravasation occurred in 573 (57.2%) encounters. Kyphoplasty had the lowest rate of cement extravasation (46.2%) with significantly lower odds compared to vertebroplasty (OR: 0.42, 95% CI: 0.30–0.58; p < 0.0001) and BT-RFA (OR: 0.57, 95% CI: 0.42–0.77; p = 0.0009). Pathologic fractures and multilevel augmentations were linked to a 64% (p = 0.001) and 63% (p = 0.0003) increased odds of cement extravasation, respectively. Male sex and older age were protective factors. Conclusions: Cement extravasation is a common but largely asymptomatic complication of percutaneous vertebral augmentation. It is crucial to consider patient-specific risk factors when selecting an augmentation technique to optimize outcomes. Kyphoplasty may be the optimal choice for patients at increased risk of cement extravasation. Full article

Background/Objectives: Hemoperfusion (HP) is employed to modulate cytokine storms in severe coronavirus disease 2019 (COVID-19) patients, requiring careful attention for success and safety. Therefore, we investigated whether our care bundles could enhance HP performance. Methods: We conducted a retrospective cohort study on adult patients (≥20 years old) with severe COVID-19 pneumonia. In the first wave (Phase I), we identified HP-related issues and addressed them with care bundles in the second wave (Phase II). The care bundles included early temperature control, precise hemodynamic monitoring, and clot prevention measures for the HP membrane. The HP success rate and associated adverse events (AEs) were assessed between the two phases. Results: The study included 60 HP (HA330) sessions from 27 cases (Phase I: 21 sessions from 9 cases; Phase II: 39 sessions from 18 cases). Patient characteristics and treatments for COVID-19 were similar, except for baseline body temperature (BT) and heart rate (HR). Phase II showed a higher success rate (67% vs. 89%, p = 0.19), although it did not reach statistical significance. Phase I recorded a significantly higher frequency of AEs (3 [IQR 1, 4] events/case vs. 1 [IQR 0, 2] events/case, p = 0.014). After implementing the care bundles, hypothermia significantly decreased (78% vs. 33%, p = 0.037), with an adjusted odds ratio of 0.15; 95% CI 0.02–0.95, p = 0.044 for baseline BT. Conclusions: Further exploration with a larger sample size is required to establish the advantages of care bundles. However, the bundles’ implementation has significantly improved hypothermia prevention. Full article

Studies have evaluated vitamin D₃’s therapeutic potential in estrogen-responsive cancers, with conflicting findings. We have shown that the proliferation of breast cancer cells is regulated by 24R,25-dihydroxyvitamin D₃ (24R,25(OH)₂D₃) depending on estrogen receptor alpha 66 (ERα66) expression, suggesting that this could also be the case for estrogen-sensitive laryngeal cancer cells. Accordingly, we examined levels of ERα isoforms in ERα66-positive UM-SCC-12 and ERα66-negative UM-SCC-11A cells and their response to 24R,25(OH)₂D₃. 24R,25(OH)₂D₃ stimulated proliferation, increased the expression of metastatic markers, and inhibited apoptosis in UM-SCC-12 cells while having the opposite effect in UM-SCC-11A cells. To evaluate if vitamin metabolites could act via autocrine/paracrine mechanisms, we assessed the expression, protein levels, and activity of vitamin D₃ hydroxylases CYP24A1 and CYP27B1. Both cell types expressed both mRNAs; but the levels of the enzymes and their activities were differentially regulated by estrogen. ERα66-negative UM-SCC-11A cells produced more 24,25(OH)₂D₃ than UM-SCC-12 cells, but comparable levels of 1,25(OH)₂D₃ when treated with 25(OH)D₃ These results suggest that the regulation of vitamin D₃ metabolism in laryngeal cancer cells is modulated by ERα66 expression, and support a role for 24R,25(OH)₂D₃ as an autocrine/paracrine regulator of laryngeal cancer. The local metabolism of 25(OH)D₃ should be considered when determining the potential of vitamin D₃ in laryngeal cancer. Full article

Background: Vaccines that prevent SARS-CoV-2 infection are considered the most promising approach to modulating the pandemic. There is scarce evidence on the efficacy and safety of different vaccine prime-boost combinations in MHD patients since most clinical trials have used homologous mRNA vaccine regimens. Methods: This prospective observational study assessed the immunogenicity and safety of homologous CoronaVac^® (SV-SV), ChAdOx1 nCoV-19 (AZD1222) (AZ-AZ), and the heterologous prime-boost of SV-AZ, among MHD patients. Results: A total of 130 MHD participants were recruited. On day 28, after the second dose, seroconversion results of the surrogate virus neutralization test were not different between vaccine regimens. The magnitude of the receptor-binding domain-specific IgG was highest among the SV-AZ. Different vaccine regimens had a distinct impact on seroconversion, for which the heterologous vaccine regimen demonstrated a higher probability of seroconversion (OR 10.12; p = 0.020, and OR 1.81; p = 0.437 for SV-AZ vs. SV-SV, and SV-AZ vs. AZ-AZ, respectively). There were no serious adverse events reported in any of the vaccine groups. Conclusions: Immunization with SV-SV, AZ-AZ, and SV-AZ could generate humoral immunity without any serious adverse events among MHD patients. Using the heterologous vaccine prime-boost seemed to be more efficacious in terms of inducing immunogenicity. Full article

Legumes are an economical source of protein, starch, dietary fibre, fatty acids, vitamins and minerals. However, they are not as fully utilised, due to volatile compounds contributing to their undesirable odour. The purpose of this work was to understand the processing time’s effect on the legumes’ volatile profile. Hence, this study investigated the effects of hydrothermal processing times on the volatile and fatty acids profiles of cowpeas, chickpeas and kidney beans. All legumes were pre-soaked (16 h) and then hydrothermally processed at 95 °C for 15 to 120 min, using an open system to approximate standard household cooking practices and a closed system to represent industrial processing. Alcohol, aldehyde, acid and ester volatile compounds showed decreasing trends during processing, which can be associated with enzyme inactivation and process-induced degradation. This work showed that processing at 95 °C for 30 min significantly reduced the number of compounds commonly associated with undesirable odour, but showed no significant change in the fatty acid profile. Other volatiles, such as furanic compounds, pyrans and sulphur compounds, showed an increasing trend during processing, which can be related to the Maillard reactions. This observation contributes to the growing knowledge of legume processing and its impact on volatile flavour. It can advise consumers and the industry on selecting processing intensity to maximise legume utilisation. Full article

This study aimed to develop perilla fruit oil (PFO)-fortified soybean milk (PFO-SM), identify its sensory acceptability, and evaluate its health outcomes. Our PFO-SM product was pasteurized, analyzed for its nutritional value, and had its acceptability assessed by an experienced and trained descriptive panel (n = 100) based on a relevant set of sensory attributes. A randomized clinical trial was conducted involving healthy subjects who were assigned to consume deionized water (DI), SM, PFO-SM, or black sesame-soybean milk (BS-SM) (n = 48 each, 180 mL/serving) daily for 30 d. Accordingly, health indices and analyzed blood biomarkers were recorded. Consequently, 1% PFO-SM (1.26 mg ALA rich) was generally associated with very high scores for overall acceptance, color, flavor, odor, taste, texture, and sweetness. We observed that PFO-SM lowered levels of serum triglycerides and erythrocyte reactive oxygen species, but increased phagocytosis and serum antioxidant activity (p < 0.05) when compared to SM and BS-SM. These findings indicate that PFO supplementation in soybean milk could enhance radical-scavenging and phagocytotic abilities in the blood of healthy persons. In this regard, it was determined to be more efficient than black sesame supplementation. We are now better positioned to recommend the consumption of PFO-SM drink for the reduction of many chronic diseases. Randomized clinical trial registration (Reference number 41389) by IRSCTN Registry. Full article

The specific irradiation of tumors with selective radiolabeled antibodies constitutes an attractive therapeutic approach. Consequent preclinical research has been conducted by both biologists to identify pertinent targets and to select corresponding antibodies (mAb) and by radiochemists to radiolabel mAbs. These numerous preclinical investigations have ascertained the therapeutic interest of radioimmunotherapy (RIT) protocols in mice models. Here, we summarize the clinical studies that have been performed the last decade, including clinical trials (phases I, II, and III), prospective and retrospective studies, and cases series. We thereby reported 92 clinical studies. Among them, 62 concern the treatment of hematological malignancies, and 30 concern solid tumors. For hematologic diseases, the analysis was complex due to the high discrepancy of therapeutic strategies (first-line therapy, consolidation, stem cell transplantation conditioning) as well as the high variety of malignancies that were treated. The clinical studies from the last decade failed to expand anti-CD20 RIT indications but confirmed that RIT using radiolabeled anti-CD20 remains a pertinent choice for patients with relapse follicular lymphomas. For solid tumors, the positive benefit of RIT is more mitigated, apart for few malignancies that can be treated locally. Clinical trials also demonstrated the potential of some antibody formats, such as F(ab′)₂, which has already been approved by the China State FDA under the trend name Licartin®. Despite disparate results, mAb fragments are an interesting prospect for the improvement of RIT efficiency as well as for pretargeted strategies that delay the injection of radioactive treatments from the mAb ones. Full article

Legumes are a vital candidate in the fight for food security as a sustainable and nutritious food source. The current study systematically investigated the effects of hydrothermal processing of varying durations (15–120 min) on the texture, starch and protein digestibility of cowpeas (Vigna unguiculata), chickpeas (Cicer arietinum) and kidney beans (Phaseolus vulgaris). Texture analysis and in vitro oral-gastro-intestinal digestion of each legume was combined with kinetic modelling to explore the rate and extent of their changes observed during hydrothermal processing. All three legumes showed rapid initial texture decay in the first 30 min of processing. Chickpeas showed the fastest rate of texture degradation with processing duration, whereas texture degradation of kidney bean was slower but reached the lowest hardness value among all beans when processed up to 120 min. The rate of starch and protein digestion increased with prolonged processing duration, whilst showing an inverse relationship with texture values. The extent of starch digestion continually increased with processing duration for all three legumes, whereas the extent of protein digestion decreased after 60 min in cowpeas. This study systematically demonstrated how choosing different processing times can modulate the rate of texture degradation, starch and protein digestion in legumes. The findings of this study can aid consumers and manufacturers on optimal processing to achieve the desired texture or modulate starch and protein digestibility. Full article

Legumes are rich in unsaturated fatty acids, which make them susceptible to (non) enzymatic oxidations leading to undesirable odour formation. This study aimed to characterise the volatile and fatty acid profiles of eleven types of legumes using headspace solid-phase microextraction gas chromatography–mass spectrometry (HS-SPME-GC-MS) and GC coupled with a flame ionisation detector (GC-FID), respectively. Volatile aldehydes, alcohols, ketones, esters, terpenes and hydrocarbons were the chemical groups identified across all the legumes. The lipids comprised palmitic, stearic, oleic, linoleic and α-linolenic acids, with unsaturated fatty acids comprising at least 66.1% to 85.3% of the total lipids for the legumes studied. Multivariate data analysis was used to compare volatile and fatty acid profiles between legumes, which allow discriminant compounds pertinent to specific legumes to be identified. Results showed that soybean, chickpea and lentil had distinct volatile and fatty acid profiles, with discriminating volatiles including lactone, ester and ketone, respectively. While all three Phaseolus cultivars shared similar volatile profiles, 3-methyl-1-butanol was found to be the only volatile differentiating them against the other eight legumes. Overall, this is the first time a multivariate data analysis has been used to characterise the volatile and fatty acid profiles across different legume seeds, while also identifying discriminating compounds specific for certain legume species. Such information can contribute to the creation of legume-based ingredients with specific volatile characteristics while reducing undesirable odours, or potentially inform relevant breeding programs. Full article

Targeted therapies, such as radioimmunotherapy (RIT), present a promising treatment option for the eradication of tumor lesions. RIT has shown promising results especially for hematologic malignancies, but the therapeutic efficacy is limited by unfavorable tumor-to-background ratios resulting in high radiotoxicity. Pretargeting strategies can play an important role in addressing the high toxicity profile of RIT. Key to pretargeting is the concept of decoupling the targeting vehicle from the cytotoxic agent and administrating them separately. Studies have shown that this approach has the ability to enhance the therapeutic index as it can reduce side effects caused by off-target irradiation and thereby increase curative effects due to higher tolerated doses. Pretargeted RIT (PRIT) has been explored for imaging and treatment of different cancer types over the years. This review will give an overview of the various targeted therapies in which pretargeting has been applied, discussing PRIT with alpha- and beta-emitters and as part of combination therapy, plus its use in drug delivery systems. Full article