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Scientific Reports Jul 2024Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a... (Observational Study)
Observational Study
Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1-4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy.
Topics: Humans; Psoriasis; Interleukin-17; Microscopy, Confocal; Female; Male; Antibodies, Monoclonal, Humanized; Middle Aged; Adult; Pilot Projects; Follow-Up Studies; Aged; Skin; Treatment Outcome; Severity of Illness Index; Antibodies, Monoclonal
PubMed: 38956402
DOI: 10.1038/s41598-024-65902-8 -
CEN Case Reports Jul 2024A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody...
A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333 IU/mL), proteinuria (1.21 g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1 year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.
PubMed: 38955948
DOI: 10.1007/s13730-024-00910-1 -
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 -
Scientific Reports Jul 2024The objective of this cross-sectional study was to examine the extent of sleep quality among individuals undergoing maintenance hemodialysis (MHD) and to scrutinize...
The objective of this cross-sectional study was to examine the extent of sleep quality among individuals undergoing maintenance hemodialysis (MHD) and to scrutinize whether hope and family function serve as mediators in the association between anxiety and sleep quality in this cohort. A convenience sampling method was used to recruit 227 patients receiving maintenance hemodialysis from two tertiary hospitals in Wuhan. Participants completed several self-report questionnaires, including the Sociodemographic questionnaire, Hospital Anxiety and Depression Scale, Athens Insomnia Scale, Herth Hope Index, and Family APGAR Index. As per the findings of the chain mediation analysis, it was observed that the sleep quality scores were directly predicted by anxiety. Moreover, anxiety positively predicted sleep quality scores through hope and family function as mediators. The observed types of mediation were partial mediation. The total indirect effect value was 0.354, indicating the mediating effect of hope and family function, while the total effect value was 0.481, representing the overall effect of anxiety on sleep quality. The total effect size was 73.60% (0.354/0.481), indicating that the mediation accounted for a significant portion of the relationship. This study established the chain mediating effect of hope and family function between anxiety and sleep quality in patients receiving maintenance hemodialysis. The findings highlight the importance of addressing anxiety and promoting hope and family function to improve sleep quality in this population. The findings suggest that healthcare professionals should be attentive to the anxiety levels of these patients and implement targeted interventions to help alleviate anxiety, enhance hope, and improve family functioning, with the ultimate goal of improving sleep quality in this population.
Topics: Humans; Renal Dialysis; Male; Female; Middle Aged; Anxiety; Hope; Sleep Quality; Cross-Sectional Studies; Adult; Aged; Surveys and Questionnaires; Family; Self Report
PubMed: 38956144
DOI: 10.1038/s41598-024-65901-9 -
East Asian Archives of Psychiatry :... Dec 2023We present a young woman with clozapine-resistant schizoaffective disorder who was treated with maintenance electroconvulsive therapy and multiple antipsychotics but...
We present a young woman with clozapine-resistant schizoaffective disorder who was treated with maintenance electroconvulsive therapy and multiple antipsychotics but continued to have auditory hallucinations. She had a haemorrhagic stroke secondary to a ruptured arteriovenous malformation at the right superior temporal gyrus, which was excised during emergency craniotomy. Despite having neurological deficits after the stroke, she reported cessation of auditory hallucinations. Magnetic resonance imaging of the brain showed Wallerian degeneration over the right temporal region. Personalised neuromodulation intervention may be a more effective treatment option for clozapine-resistant schizophrenia.
Topics: Humans; Female; Hallucinations; Clozapine; Psychotic Disorders; Adult; Antipsychotic Agents; Hemorrhagic Stroke; Temporal Lobe; Magnetic Resonance Imaging; Schizophrenia, Treatment-Resistant
PubMed: 38955785
DOI: 10.12809/eaap2340 -
Clinical and Translational Science Jul 2024Ovaries play a crucial role in the regulation of numerous essential processes that occur within the intricate framework of female physiology. They are entrusted with the... (Review)
Review
Ovaries play a crucial role in the regulation of numerous essential processes that occur within the intricate framework of female physiology. They are entrusted with the responsibility of both generating a new life and orchestrating a delicate hormonal symphony. Understanding their functioning is crucial for gaining insight into the complexities of reproduction, health, and fertility. In addition, ovaries secrete hormones that are crucial for both secondary sexual characteristics and the maintenance of overall health. A three-dimensional (3D) prosthetic ovary has the potential to restore ovarian function and preserve fertility in younger females who have undergone ovariectomies or are afflicted with ovarian malfunction. Clinical studies have not yet commenced, and the production of 3D ovarian tissue for human implantation is still in the research phase. The main challenges faced while creating a 3D ovary for in vivo implantation include sustenance of ovarian follicles, achieving vascular infiltration into the host tissue, and restoring hormone circulation. The complex ovarian microenvironment that is compartmentalized and rigid makes the biomimicking of the 3D ovary challenging in terms of biomaterial selection and bioink composition. The successful restoration of these properties in animal models has led to expectations for the development of human ovaries for implantation. This review article summarizes and evaluates the optimal 3D models of ovarian structures and their safety and efficacy concerns to provide concrete suggestions for future research.
Topics: Female; Humans; Ovary; Printing, Three-Dimensional; Animals; Tissue Engineering; Fertility; Fertility Preservation; Tissue Scaffolds
PubMed: 38955776
DOI: 10.1111/cts.13863 -
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