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Expert Opinion on Drug Safety Sep 2023Chronic urticaria (CU) is a prevalent chronic skin condition characterized by recurrent wheals. Clinical guidelines recommend multiple drugs for CU treatment. Our study... (Review)
Review
BACKGROUND
Chronic urticaria (CU) is a prevalent chronic skin condition characterized by recurrent wheals. Clinical guidelines recommend multiple drugs for CU treatment. Our study aims to compare the effectiveness and safety of drug therapy for CU.
METHODS
We conducted a comprehensive search of randomized controlled trials (RCTs) and real-world studies (RWSs) in PubMed, EMBASE, and Cochrane. A network meta-analysis (NMA) was conducted to assess the response rate, decline in Urticaria Activity Score over 7 Days (UAS7), Dermatology Life Quality Index (DLQI), and adverse event rates of standard-dose and high-dose H1 antihistamine (H1AH), omalizumab (OMA) 75, 150, and 300 mg, cyclosporine and placebo. The risk-benefit assessment was conducted by probabilistic simulation and stochastic multicriteria acceptability analysis (SMAA).
RESULTS
A total of 39 studies were identified, including 37 RCTs and 2 RWSs. OMA 300 mg and 150 mg both had significantly higher response rate than standard-dose H1AH ( < 0.05, respectively). OMA 300 mg and 150 mg both consistently led to a huge drop in UAS7 and DLQI compared to standard-dose H1AH and high-dose H1AH ( < 0.05).
CONCLUSION
Regarding risk-benefit assessment, OMA 300 mg emerges as the optimal pharmacological intervention for CU, while OMA 150 mg stands as a secondary alternative compared to H1 antihistamines and cyclosporine.
PubMed: 37750025
DOI: 10.1080/14740338.2023.2262377 -
Journal of Pharmaceutical Sciences Oct 2023Cell therapy uses living cells as a drug to treat diseases. To develop a cell therapy drug product (DP), cryopreservation plays a central role in extending the shelf... (Review)
Review
Cell therapy uses living cells as a drug to treat diseases. To develop a cell therapy drug product (DP), cryopreservation plays a central role in extending the shelf life of these living medicines by pausing their biological activities, especially preventing degradation, at a temperature as low as liquid nitrogen. This helps overcome the temporal and geographical gaps between centralized manufacturing and clinical administration, as well as allowing sufficient time for full release testing and flexibility in scheduling patients for administration. Cryopreservation determines or influences several key manufacturing, logistical, or clinical in-use processes, including formulation, filling, controlled rate freezing, cryogenic storage and transportation, thawing, and dose preparation. This article overviews the key technical aspects of cell therapy DP development and elucidates fundamental principles of cryobiology that should be considered when we design and optimize the relevant processes. This article also discusses the challenges that motivate continued innovation for cell therapy drug product development.
Topics: Humans; Freezing; Cryopreservation; Temperature; Cell Differentiation; Cell- and Tissue-Based Therapy
PubMed: 37549846
DOI: 10.1016/j.xphs.2023.08.001 -
Transplant Immunology May 2024This study examines the effect of belatacept based salvage regimens on kidney transplant outcomes.
INTRODUCTION
This study examines the effect of belatacept based salvage regimens on kidney transplant outcomes.
METHODS
This single-center retrospective study included all adult kidney transplant recipients between 2011 and 2022 who were converted to belatacept salvage therapy during their follow up. eGFR, graft survival, incidence of infections and neoplasia, histology and DSA data were collected through systematic review of the medical record.
RESULTS
Patients were divided into 3 groups based on salvage regimen: Mycophenolate mofetil/belatacept (MMF/Bela) (n = 28), low-dose Calcineurin inhibitors/belatacept (CNI/Bela) (n = 22), and low-dose Calcineurin inhibitors/ Mycophenolate mofetil /belatacept (CNI/MMF/Bela) (n = 13). Patients with antibody-mediated rejection were more likely to receive CNIs in addition to belatacept (low-dose CNI/MMF/Bela 54%, low-dose CNI/Bela 45%, MMF/Bela 3.6%, p < 0.001). DSA decreased in all groups after transition to belatacept by 15.67% (p = 0.15). No difference in Glomerular filtration rate (eGFR) over time was observed between the groups, and eGFR remained stable over the first year after transition to belatacept. The incidence of death and allograft failure was similar between the groups (low- dose CNI/MMF/Bela n = 3, low-dose CNI/Bela n = 7, MMF/Bela n = 4; p = 0.41). Patients in the low-dose CNI/Bela cohort who were transitioned to belatacept within 6 months from transplant showed a decline in eGFR over the first year after transition, while the other treatment cohorts demonstrated stable or slight increase in eGFR.
CONCLUSIONS
The present study demonstrates comparable transplant outcomes in terms of eGFR, graft survival, incidence of infections and neoplasia, rejection rate and donor specific antibody (DSA) in three belatacept-based maintenance immunosuppression regimens supporting the safety and efficacy of these therapeutic options.
PubMed: 38810889
DOI: 10.1016/j.trim.2024.102050 -
Environmental Science and Pollution... Oct 2023Radiation is present everywhere in the earth, and human beings are continuously exposed to gamma radiation. The health consequences of environmental radiation exposure...
Radiation is present everywhere in the earth, and human beings are continuously exposed to gamma radiation. The health consequences of environmental radiation exposure are a serious societal issue. The purpose of this study was to analyse outdoor radiation in four districts of Gujarat, India: Anand, Bharuch, Narmada, and Vadodara during summer and winter seasons. This study illustrated the influence of lithology of areas on gamma radiation dose values. Summer and winter seasons are the primary factors that alter the causes directly or indirectly; therefore, the influence of season fluctuation on radiation dose rate was investigated. The annual dose rate and mean gamma radiation dose rate values from four districts were found to be greater than the global population weight average value. The mean value of gamma radiation dose rate from 439 locations in the summer and winter seasons was 136.23 nSv/h and 141.58 nSv/h, respectively. According to a paired differences sample study, the significance value between outdoor gamma dose rate in summer and winter seasons was 0.05 indicating that seasons have a significant impact on gamma radiation dose rate. The impact of various types of lithology on gamma radiation dose was studied in all 439 places, and the statistical analysis revealed that there was no significant association between lithology and gamma radiation dose rate in the summer season, but a relationship between lithology and gamma dose rate was observed in the winter season.
Topics: Humans; Gamma Rays; Environmental Exposure; Environmental Pollution; India; Radiation Exposure; Seasons
PubMed: 36807856
DOI: 10.1007/s11356-023-25711-4 -
Journal of Contemporary Brachytherapy Feb 2024Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our...
PURPOSE
Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our institute's patients after replacing low-dose-rate (LDR) with pulse-dose-rate (PDR) brachytherapy.
MATERIAL AND METHODS
We retrospectively collected data from all patients treated between 2009 and 2020 for squamous cell carcinoma (floor of the mouth, tongue, and oropharynx) using adjuvant interstitial BT with or without external RT. Primary outcome was local control. Secondary outcomes were regional control rate and toxicity. Statistical analysis of local and regional recurrences were described using Kaplan-Meier method. Prognostic value of each factor for recurrence or toxicity was evaluated with bivariate Fine-Gray model.
RESULTS
Data from 66 patients were analyzed. Local and regional recurrences were reported in 11% and 20% of the patients, respectively. No significant factors were identified in the present study. Grade 2 and 3 acute mucositis were reported in 21% of patients, and were more frequent in the BT only group. Almost half (47%) of the patients described acute pain following BT, and 26% required stage 2 or 3 analgesics. Trophic disorders were observed in 16 patients. Five patients presented with soft tissue necrosis (STN) and required medical treatment, of whom one subsequently required hyperbaric oxygen therapy. No predictive factors were identified for STN risk. Two patients developed osteoradionecrosis.
CONCLUSIONS
Oral and oropharyngeal PDR-BT as adjuvant treatment is safe and effective for well-defined indications.
PubMed: 38584888
DOI: 10.5114/jcb.2024.135626 -
Radiotherapy and Oncology : Journal of... Jan 2024The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s....
BACKGROUND AND PURPOSE
The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study.
MATERIALS AND METHODS
The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models.
RESULTS
The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate.
CONCLUSION
Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.
Topics: Humans; Animals; Mice; Protons; Electrons; Radiotherapy Dosage; Radiometry; Proton Therapy; Neoplasms; Biological Products
PubMed: 37839557
DOI: 10.1016/j.radonc.2023.109953 -
Medical Physics Sep 2023Ultra-high dose rate (UHDR) FLASH beams typically deliver dose at rates of >40 Gy/sec. Characterization of these beams with respect to dose, mean dose rate, and dose...
BACKGROUND
Ultra-high dose rate (UHDR) FLASH beams typically deliver dose at rates of >40 Gy/sec. Characterization of these beams with respect to dose, mean dose rate, and dose per pulse requires dosimeters which exhibit high temporal resolution and fast readout capabilities.
PURPOSE
A diode EDGE Detector with a newly designed electrometer has been characterized for use in an UHDR electron beam and demonstrated appropriateness for UHDR FLASH radiotherapy dosimetry.
METHODS
Dose linearity, mean dose rate, and dose per pulse dependencies of the EDGE Detector were quantified and compared with dosimeters including a W1 scintillator detector, radiochromic film, and ionization chamber that were irradiated with a 10 MeV UHDR beam. The dose, dose rate, and dose per pulse were controlled via an in-house developed scintillation-based feedback mechanism, repetition rate of the linear accelerator, and source-to-surface distance, respectively. Depth-dose profiles and temporal profiles at individual pulse resolution were compared to the film and scintillation measurements, respectively. The radiation-induced change in response sensitivity was quantified via irradiation of ∼5kGy.
RESULTS
The EDGE Detector agreed with film measurements in the measured range with varying dose (up to 70 Gy), dose rate (nearly 200 Gy/s), and dose per pulse (up to 0.63 Gy/pulse) on average to within 2%, 5%, and 1%, respectively. The detector also agreed with W1 scintillation detector on average to within 2% for dose per pulse (up to 0.78 Gy/pulse). The EDGE Detector signal was proportional to ion chamber (IC) measured dose, and mean dose rate in the bremsstrahlung tail to within 0.4% and 0.2% respectively. The EDGE Detector measured percent depth dose (PDD) agreed with film to within 3% and per pulse output agreed with W1 scintillator to within -6% to +5%. The radiation-induced response decrease was 0.4% per kGy.
CONCLUSIONS
The EDGE Detector demonstrated dose linearity, mean dose rate independence, and dose per pulse independence for UHDR electron beams. It can quantify the beam spatially, and temporally at sub millisecond resolution. It's robustness and individual pulse detectability of treatment deliveries can potentially lead to its implementation for in vivo FLASH dosimetry, and dose monitoring.
Topics: Radiation Dosimeters; Radiometry; Particle Accelerators; In Vivo Dosimetry
PubMed: 37249058
DOI: 10.1002/mp.16474 -
Physics in Medicine and Biology Feb 2024The aim of this work is to investigate the dose rate dependence of thermoluminescence and optically stimulated luminescence detectors (TLDs and OSLDs) in a wide uniform...
The aim of this work is to investigate the dose rate dependence of thermoluminescence and optically stimulated luminescence detectors (TLDs and OSLDs) in a wide uniform ultra-high dose rate electron beam and demonstrate the potential use of TLDs and OSLDs to correct the ion recombination in air-filled ionization chambers. This study avoids previously reported complications related to the field size and homogeneity.Two types of OSLDs (BeO and AlO:C) and three types of TLDs (LiF:Mg,Ti, LiF:Mg,Cu,P, CaF:Tm) were irradiated simultaneously in a uniform 16 MeV electron beam generated by a clinically decommissioned C-Arm LINAC, modified to deliver doses per pulse between 8.3 × 10Gy and 1.255 Gy, corresponding to instantaneous dose rates between 2 × 10Gy sand 3 × 10Gy s. A prototype ultra-thin parallel plate ionization chamber was employed as reference detector.Reproducible results were achieved both at conventional (standard deviation of the data <2%) and at the highest dose per pulse (standard deviation of the data <4%). No trend in the dose rate response of the TLDs and OSLDs was observed in the investigated dose per pulse range. The AlO:C OSLD was found to be the most precise detector, with a standard deviation of the data <2% at all investigated dose rates and dose levels.The dose rate independence of the investigated TLDs and OSLDs make them good candidates for dosimetry at ultra-high dose rates, at least up to 3 × 10Gy s. A dose rate independent method to measure the dose per pulse is proposed, which can be applied to characterize ultra-high dose rate electron beams and correct for ion recombination in ionization chambers.
Topics: Optically Stimulated Luminescence Dosimetry; Electrons; Radiometry; Luminescence
PubMed: 38198704
DOI: 10.1088/1361-6560/ad1cf5 -
Cancer Radiotherapie : Journal de La... Apr 2024Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to...
PURPOSE
Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to retrospectively compare oncologic and toxicity outcomes between the two techniques.
PATIENTS AND METHODS
From 2007 to 2018, patients at the Institut de cancérologie de Lorraine (France) who received exclusive or adjuvant interstitial brachytherapy for lip squamous carcinomas were studied. Two groups were defined: the LDR/PDR group, including patients treated with iridium-192 wires, or pulsed-dose rate technique, and the high-dose-rate group, with patients treated by high-dose-rate technique. The dose ranged between 50Gy and 65Gy (depending on previous surgery) for low-dose-/pulsed-dose rate treatments, and 39Gy for high-dose-rate (twice a day). Early, late toxicity events and oncologic control were reported.
RESULTS
Among the 61 patients whose data were analyzed retrospectively, 36 received the low-dose-/pulsed-dose rate treatment (59%) and 25 the high-dose-rate brachytherapy (41%). The median follow-up time was 44 months. At 36 months, the local control rates were 96.3% for LDR/PDR group and 100% for HDR (P=0.180). The regional control rates were 85.9% and 92% without any difference according to the two groups (P=0.179). The specific overall survival rate was 95.5% with no difference between groups. There were more grade 2 or higher mucositis in the HDR group than in LDR/PDR group (40% versus 16.7%, P=0.042). One case of grade 3 mucositis was recorded in each group. No grade 3 late complications were recorded. High-dose-rate brachytherapy reduced the length of hospitalization by 2 days (P<0.001).
CONCLUSION
High-dose- or low-dose-/pulsed-dose rate brachytherapy seemed to be as effective and well tolerated in our experience of 61 patients.
Topics: Humans; Radiotherapy Dosage; Iridium Radioisotopes; Retrospective Studies; Brachytherapy; Lip; Mucositis; Carcinoma, Squamous Cell; Head and Neck Neoplasms
PubMed: 38072744
DOI: 10.1016/j.canrad.2023.06.031 -
Journal of Radiation Research Jul 2023The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study...
Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice.
The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range.
Topics: Animals; Mice; Alcohols; Antioxidants; Gamma Rays; Glutathione; Liver; Oxidative Stress
PubMed: 37205845
DOI: 10.1093/jrr/rrad030