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Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and...
To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (=1.541 for local adverse reactions in the control group, =0.718 for the observation group; =0.483 for systemic adverse reactions in the control group, =0.179 for the observation group, value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (=4.147, <0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all -values <0.001, and -values of the observation group were 15.480, 27.087, 28.938, all -values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all -values <0.001, and -values of 9.436, 13.184, and 22.377 in the observation group, respectively; all -values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (-values 0.621, 0.473, 1.825, and 0.342, respectively, and -values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (-values of 1.663, 0.095, 0.305, 0.951, -values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (-values of the conventional group were 3.453, 5.469, 6.273, -values <0.05, and the -values of the observation group were 2.900, 4.575, 5.988, -values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (-value in the conventional group was -5.328, -4.254, -0.690, -value was 0.000, 0.000, 0.492, respectively, and -value in the observation group was -6.087, -5.087, -0.324, -value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (-values of 0.723, 1.553, 0.766, and 0.234, respectively; -values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (-values of 0.170, -0.166, -0.449, 0.839, -values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (-values 1.507, 1.467, -0.337, 0.804, -values 0.134, 0.145, 0.737, 0.422, respectively). Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.
Topics: Humans; Child; Desensitization, Immunologic; Retrospective Studies; Child, Preschool; Adolescent; Animals; Immunoglobulin E; Asthma; Allergens; Male; Rhinitis, Allergic; Female; Mites; Treatment Outcome
PubMed: 38955723
DOI: 10.3760/cma.j.cn112150-20230915-00194 -
Radiography (London, England : 1995) Jul 2024Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important...
INTRODUCTION
Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important role in the management and care of RT trial patients. The COVID-19 pandemic caused major disruption to RT trial delivery. Measures to mitigate COVID-19 risk continue to have an effect on patient contact and communication within cancer centres in the United Kingdom (UK). This study aimed to explore patient perspectives regarding their recent RT trial experience in Northern Ireland (NI), UK.
METHODS
A single centre service evaluation was conducted in NI. Patients who were recruited into a RT clinical trial from January 2020 to January 2023 were invited to participate. Surveys were posted to 50 participants in April 2023. Quantitative and qualitative data was captured and analysed using descriptive statistics and Braun and Clarke's six-step thematic analysis framework respectively. Ethical approval was obtained through Ulster University and the NHS Trust.
RESULTS
Forty-three of the 50 invited participants responded (86%). Forty-two respondents (79%) had a prostate cancer diagnosis. Forty-one (98%) participants indicated that CRRs were always approachable, polite and courteous and would recommend taking part in a RT trial to friends and family. Identified areas for improvement included aspects regarding consent and participant decision-making.
CONCLUSION
This study suggests that despite the implemented measures to suspend research and mitigate COVID-19 risk, patients remained highly satisfied with the quality of care that they received through their participation in RT trials.
IMPLICATIONS FOR PRACTICE
The results of this service evaluation will facilitate maintenance and improvement of patient focused delivery of cancer trials within the host centre. This study builds on evidence highlighting the importance of the CRR role and role development for radiographers.
PubMed: 38955645
DOI: 10.1016/j.radi.2024.06.014 -
Biofabrication Jul 2024Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g., in various malignant and non-malignant...
Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g., in various malignant and non-malignant diseases such as multiple myeloma (MM), primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived from in vivo studies in mice, as in vitro studies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survival in vitro for up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCs in vitro. Our innovative model system is suitable for in-depth in vitro studies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.
PubMed: 38955197
DOI: 10.1088/1758-5090/ad5dfe -
Biomedicine & Pharmacotherapy =... Jul 2024Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth,...
Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death.
Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133 and CD44 cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5 MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.
PubMed: 38955086
DOI: 10.1016/j.biopha.2024.117059 -
Sleep Jul 2024The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating...
The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating novel therapeutics for excessive daytime sleepiness. In the latter, sleep onset latency (SOL) is typically the sole MWT endpoint. Here, we explored microsleeps, sleep probability measures derived from automated sleep scoring, and quantitative electroencephalography (qEEG) features as additional MWT biomarkers of daytime sleepiness, using data from a phase 1B trial of the selective orexin receptor 2 agonist danavorexton (TAK-925) in people with narcolepsy type 1 (NT1) or type 2 (NT2). Danavorexton treatment reduced the rate and duration of microsleeps during the MWT in NT1 (days 1 and 7; p ≤ 0.005) and microsleep rate in NT2 (days 1 and 7; p < 0.0001). Use of an EEG-sleep-staging-derived measure to determine the probability of wakefulness for each minute revealed a novel metric to track changes in daytime sleepiness, which were consistent with the θ/α ratio, a known biomarker of drowsiness. The slopes of line-fits to both the log-transformed sleepiness score or log-transformed θ/α ratio correlated well to (inverse) MWT SOL for NT1 (R = 0.93 and R = 0.83, respectively) and NT2 (R = 0.97 and R = 0.84, respectively), suggesting that individuals with narcolepsy have increased sleepiness immediately after lights-off. These analyses demonstrate that novel EEG-based biomarkers can augment SOL as predictors of sleepiness and its response to treatment and provide a novel framework for the analysis of wake EEG in hypersomnia disorders.
PubMed: 38954525
DOI: 10.1093/sleep/zsae148 -
Supportive Care in Cancer : Official... Jul 2024Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly...
PURPOSE
Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients.
METHODS
We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis.
RESULTS
Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions.
CONCLUSION
This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.
Topics: Humans; Multiple Myeloma; Lenalidomide; Male; Female; Middle Aged; Aged; Qualitative Research; London; Maintenance Chemotherapy; Interviews as Topic; Quality of Life; Transplantation, Autologous; Antineoplastic Agents
PubMed: 38954025
DOI: 10.1007/s00520-024-08663-4 -
Inflammatory Bowel Diseases Jul 2024There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to...
BACKGROUND
There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to evaluate the efficacy of proactive TDM in IBD patients treated with intravenous (iv) vedolizumab (VDZ).
METHODS
This single-center retrospective cohort study included consecutive IBD patients treated with maintenance iv VDZ therapy undergoing TDM from November 2016 to March 2023. Patients were followed through June 2023 and were divided in to 2 groups: those who had at least 1 proactive TDM vs those who underwent only reactive TDM. A survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event, or an IBD-related surgery.
RESULTS
The study population consisted of 94 patients (proactive TDM, n = 72) with IBD (ulcerative colitis, n = 53). Patients undergoing at least 1 proactive TDM compared with patients having only reactive TDM demonstrated a higher cumulative probability of drug persistence (Log-rank P < .001). In multivariable Cox proportional hazard regression analysis, at least 1 proactive TDM was the only factor associated with drug persistence (hazard ratio, 14.3; 95% confidence interval [CI], 3.8-50; P < .001). A ROC analysis identified a VDZ concentration of 12.5 µg/mL as the optimal drug concentration threshold associated with drug persistence (area under the ROC curve: 0.691; 95% CI, 0.517-0.865; P = .049).
CONCLUSION
In this single-center retrospective study reflecting real-life clinical practice, proactive TDM was associated with increased drug persistence in patients with IBD treated with iv VDZ.
PubMed: 38953651
DOI: 10.1093/ibd/izae140 -
Nigerian Medical Journal : Journal of... 2023Ovarian cancer is the second most prevalent but most lethal gynaecologic malignancy in our institution. This study aimed at determining the rate of non-diagnosis in...
BACKGROUND
Ovarian cancer is the second most prevalent but most lethal gynaecologic malignancy in our institution. This study aimed at determining the rate of non-diagnosis in suspected lesions and reviewing the management challenges of ovarian tumours highly suspicious for malignancy in our hospital.
METHODOLOGY
A three-year retrospective review of patients' records from the ward, clinic, theatre, and histopathology laboratory was carried out. Cases with high indices of suspicion for ovarian cancer (ovarian tumour with malignant radiologic features with any of ascites, pleural effusion, as well as cachexia, anaemia, or evidence of metastasis) were included. In-depth interviews were carried out with a consultant from each specialty of Radiology, Radio-oncology, Pathology, and Gynaecologic oncology at the gynaecologic oncology multidisciplinary team meeting.
RESULTS
One hundred and twenty-two cases of highly suspicious ovarian malignancies were seen with a mean age of 40.6 years. Of these, 28 (23%) had surgery and 77% did not have any form of histological diagnosis. Of those that had surgery, 13 (46.4%) had upfront surgery and 15 (53.6%) neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Only two cases had documented complete (R) debulking. Among those that had upfront surgery, one case (7.7%) was an ovarian fibroid and one (7.7%) was a fibrosarcoma while two cases (15.4%) were borderline ovarian tumours. Chemotherapy was commenced based on malignant cells on ascitic or pleural fluid cytology in three cases. Of all the malignant cases, epithelial carcinomas were commonest accounting for 48%. Aside from the general late presentation of cases, insufficient funds for treatment, poor coverage of health insurance for cancer care, unavailability of routine immunohistochemistry, lack of germline and somatic testing, non-availability or prohibitive cost of some chemotherapeutic agents, unavailability of maintenance therapies, inadequate capacity to manage toxicities, inadequate skill across all specialties, unavailability / erratic function of computerized tomography scans and unavailable positron emission tomography, lack of interventional radiology facility amongst others were all identified as challenges to management.
CONCLUSION
Most patients with tumours highly suspicious for ovarian cancers did not get a histologic diagnosis and probably died undiagnosed. Management of ovarian cancer remains a challenge despite advances in surgical and chemotherapeutic options. Health insurance for all, infrastructure development, and training of all disciplines involved is recommended.
PubMed: 38952886
DOI: 10.60787/NMJ-64-4-217 -
Frontiers in Oncology 2024Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients...
BACKGROUND
Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.
METHODS
Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis.
RESULTS
1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.
CONCLUSION
1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.
PubMed: 38952544
DOI: 10.3389/fonc.2024.1390820 -
Biological Psychiatry Global Open... Jul 2024Psychological treatments for persecutory delusions, particularly cognitive behavioral therapy for psychosis, are efficacious; however, mechanistic theories explaining... (Review)
Review
Psychological treatments for persecutory delusions, particularly cognitive behavioral therapy for psychosis, are efficacious; however, mechanistic theories explaining why they work rarely bridge to the level of cognitive neuroscience. Predictive coding, a general brain processing theory rooted in cognitive and computational neuroscience, has increasing experimental support for explaining symptoms of psychosis, including the formation and maintenance of delusions. Here, we describe recent advances in cognitive behavioral therapy for psychosis-based psychotherapy for persecutory delusions, which targets specific psychological processes at the computational level of information processing. We outline how Bayesian learning models employed in predictive coding are superior to simple associative learning models for understanding the impact of cognitive behavioral interventions at the algorithmic level. We review hierarchical predictive coding as an account of belief updating rooted in prediction error signaling. We examine how this process is abnormal in psychotic disorders, garnering noisy sensory data that is made sense of through the development of overly strong delusional priors. We argue that effective cognitive behavioral therapy for psychosis systematically targets the way sensory data are selected, experienced, and interpreted, thus allowing for the strengthening of alternative beliefs. Finally, future directions based on these arguments are discussed.
PubMed: 38952435
DOI: 10.1016/j.bpsgos.2024.100333