Search

PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were  80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

This study aimed to systematically evaluate the impact of a low-dose (LD) protocol using tube current reduction on image quality, the confidence for intervention planning and guidance, and diagnostic yield for computed tomography (CT) myelography. We retrospectively analyzed 68 patients who underwent CT myelography, with 34 investigations performed with a standard-dose (SD) and 34 investigations performed with a LD protocol (using tube current reduction). The different scans were matched considering variables such as sex, age, presence of spinal instrumentation, and body diameter. All images were evaluated by two readers (R1 and R2) using Likert scales. Image noise was measured using attenuation values of paraspinal muscle tissue. Images were reconstructed with model-based iterative reconstruction (post-myelography diagnostic scans) or hybrid reconstruction (planning, periprocedural, and diagnostic scans). Image quality, overall artifacts, image contrast, and confidence for planning or intervention guidance were rated good to perfect for both SD and LD scans according to evaluations of both readers. Inter-reader agreement was good to very good for the images from intervention planning (κ ≥ 0.80) as well as for intervention guidance (κ ≥ 0.77), as well as for diagnostic scans (κ ≥ 0.85). Image noise was similar between SD and LD scans performed for planning of the interventional procedures (model-based iterative reconstruction: SD 45.37 ± 7.29 HU vs. LD 45.17 ± 9.12 HU; hybrid reconstruction: SD 46.05 ± 7.43 HU vs. LD 45.05 ± 8.69 HU; p > 0.05). The volume-weighted CT dose index (CTDIvol) and size-specific dose estimate (SSDE) were significantly lower for the planning scans as well as the periprocedural scans when using the LD protocol as compared to the SD protocol (p < 0.05). In conclusion, implementation of a LD protocol with tube current reduction for CT myelography is a feasible option to reduce radiation exposure, especially when combined with iterative image reconstruction. In our study, LD imaging did not have a relevant negative impact on image quality, confidence for intervention planning or guidance, or diagnostic certainty for CT myelography. [ABSTRACT FROM AUTHOR]

This article reviews the self-supervised learning methods for CT image denoising and reconstruction. Currently, deep learning has become a dominant tool in medical imaging as well as computer vision. In particular, self-supervised learning approaches have attracted great attention as a technique for learning CT images without clean/noisy references. After briefly reviewing the fundamentals of CT image denoising and reconstruction, we examine the progress of deep learning in CT image denoising and reconstruction. Finally, we focus on the theoretical and methodological evolution of self-supervised learning for image denoising and reconstruction. [ABSTRACT FROM AUTHOR]

Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on firstgeneration biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75-100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0-2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one "on-demand" dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Major efforts in computed tomography (CT) have been focused on reducing radiation dose to patients while maintaining adequate diagnostic quality. To that end, research tools have been developed to simulate reduced‐dose images via either image‐based or projection‐based methods. The former is limited to fully capturing realistic texture, streak, and non‐stationary characteristics of reduced dose, while the latter is impractical clinically.To develop and validate an image‐based noise addition method that accounts for such attributes while being practical in clinical settings.A noise addition method was developed to add realistic noise in the image domain. The method first estimates the noise power spectrum (NPS) of CT images, which are also forward‐projected to form synthetic projections. The projection data are supplemented with random white noise proportional to their attenuation values. The noise sinogram is then back‐projected onto the image, filtered by the NPS, and scaled according to the desired dose reduction level. The tool was evaluated using both phantom images and patient data. The phantom images were acquired using a multi‐sized image quality phantom (Mercury Phantom 3.0, Duke University), and a thorax anthropomorphic phantom (Lungman Phantom, Kyoto Kagaku) at different dose levels and reconstruction settings. The patient images consisted of two dose levels of various CT examinations and reconstruction settings. The simulated and real reduced‐dose images were compared in terms of the noise magnitude and texture (i.e., NPS average frequency, NPS‐fav). The utility of this methodology was also assessed for routine clinical use for CT protocol review.For the phantom images, the percent errors in the noise magnitude between the simulated images and the actual images of the Mercury Phantom and anthropomorphic phantom images were 3.34% and 3.50%, respectively. The difference in fav was 0.07 mm−1 for the Mercury Phantom and 0.06 mm−1 for the anthropomorphic phantom between the simulated and actual images. The average noise magnitude percent error between the simulated and actual patient images was 4.61% with noise texture judged to be visually comparable with some kernel dependencies. When implemented clinically, the tool proved practical to simplify the process of estimating radiation dose reduction for CT protocols, resulting in a 50% dose reduction of our multiple myeloma protocol.The method generated simulated CT images with realistic noise properties similar to images acquired at the same radiation exposure without needing access to raw projection data. [ABSTRACT FROM AUTHOR]

Introduction: Computed Tomography (CT) scans account for only 15% of total diagnostic procedures but for over half of the collective dose of radiation. The increasing awareness about the harmful effects of radiation has also created a need for developing techniques that decrease radiation exposure while at the same time providing a reasonably good image quality. The majority of the CT units today use Filtered Back Projection (FBP) as the means of image reconstruction. However, FBP leads to coupling between image noise and radiation exposure and limits the dose reduction possible while providing diagnostic quality images. Second-generation Iterative Reconstruction (IR) techniques have caught the attention of medical researchers because they provide a superior image quality than FBP at the same radiation dose showing potential for dose reduction. Aim: To compare the image quality and radiation dose in standard dose CT head reconstructed with FBP and low dose CT head reconstructed with Sinogram Affirmed Iterative Reconstruction (SAFIRE) and FBP both. Materials and Methods: A cross-sectional analytical study was conducted on 100 patients in the emergency department of Vardhman Mahavir Medical College and Safdarjung Hospital in India from November 2018 to April 2020. Patients referred for emergency Non-contrast Computed Tomography (NCCT) head for any indication excluding post-op cases and those with metallic artifacts were included. Fifty patients chosen using systematic random sampling underwent low-dose CT head using the Care Dose 4D Automatic Exposure Control (AEC) system with reconstruction using SAFIRE (Group-A) and FBP (Group-B). Another 50 patients who were within five years of the corresponding Group-A and B patients underwent standard dose head CT reconstruction using FBP (Group-C). CTDI vol, DLP, and effective dose were recorded in all patients. Image quality was assessed objectively using the unpaired t-test for Group-A and C and paired t-test for Group-A and B. Subjective image analysis between the groups was done using a 4-point Likert scale. Results: Image quality parameters were found to be better in Group-A compared to Group-C (p<0.05). The mean values in low dose SAFIRE group, low dose FBP group, and standard dose FBP group were as follows: Grey Matter (GM) Signal-to-Noise Ratio (SNR) (14±3.29, 8.96±2 and 9.24±1.96), White Matter (WM) SNR (14.6 ±3.73, 6.9±3.79 and 7.11±1.68), Cerebrospinal Fluid (CSF) SNR (1.65±1.12, 0.86±0.80 and 1.08±0.61) and Contrastto-Noise Ratio (CNR) (3.06±0.94, 1.81±0.69 and 1.74±0.69), respectively. Group-A had significantly improved image quality parameters than Group-B and Group-C. Radiation dose reduction of 42%, 39.34%, and 42.5% was achieved in CTDIvol, DLP, and effective dose respectively in low dose group. Conclusion: Low dose CT head reconstructed with SAFIRE were significantly better in image quality compared to standarddose CT head images reconstructed using FBP, while allowing for up to 42% reduction in dose. [ABSTRACT FROM AUTHOR]

Background: Breathing signal‐guided 4D CT sequence scanning such as the intelligent 4D CT (i4DCT) approach reduces imaging artifacts compared to conventional 4D CT. By design, i4DCT captures entire breathing cycles during beam‐on periods, leading to redundant projection data and increased radiation exposure to patients exhibiting prolonged exhalation phases. A recently proposed breathing‐guided dose modulation (DM) algorithm promises to lower the imaging dose by temporarily reducing the CT tube current, but the impact on image reconstruction and the resulting images have not been investigated. Purpose: We evaluate the impact of breathing signal‐guided DM on 4D CT image reconstruction and corresponding images. Methods: This study is designed as a comparative and retrospective analysis based on 104 4D CT datasets. Each dataset underwent retrospective reconstruction twice: (a) utilizing the acquired clinical projection data for reconstruction, which yields reference image data, and (b) excluding projections acquired during potential DM phases from image reconstruction, resulting in DM‐affected image data. Resulting images underwent automatic organ segmentation (lung/liver). (Dis)Similarity of reference and DM‐affected images were quantified by the Dice coefficient of the entire organ masks and the organ overlaps within the DM‐affected slices. Further, for lung cases, (a) and (b) were deformably registered and median magnitudes of the obtained displacement field were computed. Eventually, for 17 lung cases, gross tumor volumes (GTV) were recontoured on both (a) and (b). Target volume similarity was quantified by the Hausdorff distance. Results: DM resulted in a median imaging dose reduction of 15.4% (interquartile range [IQR]: 11.3%–19.9%) for the present patient cohort. Dice coefficients for lung (n=73$n=73$) and liver (n=31$n=31$) patients were consistently high for both the entire organs and the DM‐affected slices (IQR lung: 0.985/0.982$0.985/0.982$ [entire lung/DM‐affected slices only] to 0.992/0.989$0.992/0.989$; IQR liver: 0.977/0.972$0.977/0.972$ to 0.986/0.986$0.986/0.986$), demonstrating that DM did not cause organ distortions or alterations. Median displacements for DM‐affected to reference image registration varied; however, only two out of 73 cases exhibited a median displacement larger than one isotropic 1 mm3${\rm mm}^3$ voxel size. The impact on GTV definition for the end‐exhalation phase was also minor (median Hausdorff distance: 0.38 mm, IQR: 0.15–0.46 mm). Conclusion: This study demonstrates that breathing signal‐guided DM has a minimal impact on image reconstruction and image appearance while improving patient safety by reducing dose exposure. [ABSTRACT FROM AUTHOR]

Low contrast resolution in abdominal computed tomography (CT) may be negatively affected by attempts to lower patient doses. Iterative reconstruction (IR) algorithms play a key role in mitigating this problem. The reconstructed slice thickness also influences image quality. The aim was to assess the interaction and influence of patient dose, slice thickness, and IR strength on image quality in abdominal CT. With a simultaneous acquisition, images at 42 and 98 mAs were obtained in 25 patients. Multiplanar images with slice thicknesses of 1, 2, and 3 mm and advanced modeled iterative reconstruction (ADMIRE) strengths of 3 (AD3) and 5 (AD5) were reconstructed. Four radiologists evaluated the images in a pairwise manner based on five image criteria. Ordinal logistic regression with mixed effects was used to evaluate the effect of tube load, ADMIRE strength, and slice thickness using the visual grading regression technique. For all assessed image criteria, the regression analysis showed significantly (p < 0.001) higher image quality for AD5, but lower for tube load 42 mAs, and slice thicknesses of 1 mm and 2 mm, compared to the reference categories of AD3, 98 mAs, and 3 mm, respectively. AD5 at 2 mm was superior to AD3 at 3 mm for all image criteria studied. AD5 1 mm produced inferior image quality for liver parenchyma and overall image quality compared to AD3 3 mm. Interobserver agreement (ICC) ranged from 0.874 to 0.920. ADMIRE 5 at 2 mm slice thickness may allow for further dose reductions due to its superiority when compared to ADMIRE 3 at 3 mm slice thickness. Combination of thinner slices and higher ADMIRE strength facilitates imaging at low dose. [ABSTRACT FROM AUTHOR]

AbstractThis study used real-world data from three separate United States (US) databases to evaluate dosing patterns and time to next treatment (TTNT) following the first-incident adverse event (AE) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with first-line ibrutinib with and without dose reduction (DR). Median TTNT or death in patients with and without a DR following an AE in each database was as follows: Optum Clinformatics Data Mart (CDM): 59.5 and 30.6 months; ConcertAI: 27.1 and 18.0 months; and Medicare Fee-for-Service (FFS): 49.8 and 22.0 months, respectively. Median TTNT or death in patients with cardiac AEs, with and without a DR, was: Optum CDM: 44.4 and 22.9 months; ConcertAI: 29.9 and 18.3 months; and Medicare FFS: 49.6 and 14.0 months, respectively. Ibrutinib DR was associated with fewer outpatient visits and lower CLL/SLL-related medical costs. These findings suggest that utilizing ibrutinib DR may effectively manage tolerability without compromising clinical efficacy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to propose a methodological approach for reducing the radiation dose in pediatric conebeam computed tomography (CBCT), focusing exclusively on balancing image quality with dose optimization. Materials and Methods: The dose-area product (DAP) for exposure was reduced using copper-plate attenuation of an X-ray source. The thickness of copper (Cu) was increased from 0 to 2.2 mm, and 10 different DAP levels were used. The QUART DVT_AP phantom and pediatric radiologic dentiform were scanned under the respective DAP levels. The contrast-to-noise ratio (CNR), image homogeneity, and modulation transfer function (MTF) were analyzed using the QUART DVT_AP phantom. An expert evaluation (overall image grade, appropriateness of field of view, artifacts, noise, and resolution) was conducted using pediatric dentiform images. The critical DAP level was determined based on phantom and dentiform analysis results. Results: CNR and image homogeneity decreased as the DAP was reduced; however, there was an inflection point of image homogeneity at Cu 1.6 mm (DAP=138.00 mGy·cm2), where the value started increasing. The MTF showed constant values as the DAP decreased. The expert evaluation of overall image grades showed "no diagnostic value" for dentiform images with Cu 1.9-2.2 mm (DAP=78.00-103.33 mGy·cm2). The images with Cu 0-1.6 mm (DAP=138.00-1697.67 mGy·cm2) had a "good," "moderate," or "poor but interpretable" grade. Conclusion: Reducing DAP beyond a 1.6-mm Cu thickness degraded CBCT image quality. Image homogeneity and clinical image grades indicated crucial decision points for DAP reduction in pediatric CBCT scans. [ABSTRACT FROM AUTHOR]

Introduction: Computed Tomography (CT) scans account for only 15% of total diagnostic procedures but for over half of the collective dose of radiation. The increasing awareness about the harmful effects of radiation has also created a need for developing techniques that decrease radiation exposure while at the same time providing a reasonably good image quality. The majority of the CT units today use Filtered Back Projection (FBP) as the means of image reconstruction. However, FBP leads to coupling between image noise and radiation exposure and limits the dose reduction possible while providing diagnostic quality images. Second-generation Iterative Reconstruction (IR) techniques have caught the attention of medical researchers because they provide a superior image quality than FBP at the same radiation dose showing potential for dose reduction. Aim: To compare the image quality and radiation dose in standard dose CT head reconstructed with FBP and low dose CT head reconstructed with Sinogram Affirmed Iterative Reconstruction (SAFIRE) and FBP both. Materials and Methods: A cross-sectional analytical study was conducted on 100 patients in the emergency department of Vardhman Mahavir Medical College and Safdarjung Hospital in India from November 2018 to April 2020. Patients referred for emergency Non-contrast Computed Tomography (NCCT) head for any indication excluding post-op cases and those with metallic artifacts were included. Fifty patients chosen using systematic random sampling underwent low-dose CT head using the Care Dose 4D Automatic Exposure Control (AEC) system with reconstruction using SAFIRE (Group-A) and FBP (Group-B). Another 50 patients who were within five years of the corresponding Group-A and B patients underwent standard dose head CT reconstruction using FBP (Group-C). CTDI vol, DLP, and effective dose were recorded in all patients. Image quality was assessed objectively using the unpaired t-test for Group-A and C and paired t-test for Group-A and B. Subjective image analysis between the groups was done using a 4-point Likert scale. Results: Image quality parameters were found to be better in Group-A compared to Group-C (p

Background. Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications. Aim. To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy. Materials and methods. The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up. Results. Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0–10) from 6.3±1.4 to 4.3±2.4 (p0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%. Conclusion. Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.

Objective. Deep learning reconstruction (DLR) algorithms exhibit object-dependent resolution and noise performance. Thus, traditional geometric CT phantoms cannot fully capture the clinical imaging performance of DLR. This study uses a patient-derived 3D-printed PixelPrint lung phantom to evaluate a commercial DLR algorithm across a wide range of radiation dose levels. Method. The lung phantom used in this study is based on a patient chest CT scan containing ground glass opacities and was fabricated using PixelPrint 3D-printing technology. The phantom was placed inside two different size extension rings to mimic a small- and medium-sized patient and was scanned on a conventional CT scanner at exposures between 0.5 and 20 mGy. Each scan was reconstructed using filtered back projection (FBP), iterative reconstruction, and DLR at five levels of denoising. Image noise, contrast to noise ratio (CNR), root mean squared error, structural similarity index (SSIM), and multi-scale SSIM (MS SSIM) were calculated for each image. Results. DLR demonstrated superior performance compared to FBP and iterative reconstruction for all measured metrics in both phantom sizes, with better performance for more aggressive denoising levels. DLR was estimated to reduce dose by 25%–83% in the small phantom and by 50%–83% in the medium phantom without decreasing image quality for any of the metrics measured in this study. These dose reduction estimates are more conservative compared to the estimates obtained when only considering noise and CNR. Conclusion. DLR has the capability of producing diagnostic image quality at up to 83% lower radiation dose, which can improve the clinical utility and viability of lower dose CT scans. Furthermore, the PixelPrint phantom used in this study offers an improved testing environment with more realistic tissue structures compared to traditional CT phantoms, allowing for structure-based image quality evaluation beyond noise and contrast-based assessments. [ABSTRACT FROM AUTHOR]

Objective: The recommended dose of a rituximab course for the treatment of Rheumatoid Arthritis (RA) consists of two infusions of 1000 mg with a 2‐week interval. Evidence is growing that a lower dose could be as effective. We aimed to investigate patients' and rheumatologists' perceptions on dose reduction of rituximab. Methods: Patients with RA treated with rituximab, and rheumatologists were invited for a qualitative study via individual semi‐structured interviews. Participants were recruited based on purposive sampling to ensure diversity. Interviews were analysed according to the principles of grounded theory and the constant comparative method. Results: Sixteen patients and 13 rheumatologists were interviewed. Patients and rheumatologists perceived the benefits of rituximab dose reduction for reasons of safety and societal costs. Furthermore, available evidence for the effectiveness of lower doses was mentioned as an argument in favour, in addition to the possibility to tailor the dose based on the patients' clinical manifestations. However, patients and rheumatologists had concerns about the potential loss of effectiveness and quality of life. Moreover, some rheumatologists felt uncomfortable with dose reduction due to insufficient experience with rituximab in general. Patients and rheumatologists emphasised the importance of shared decision‐making, underscoring the pivotal role of physicians in this process by explaining the reasoning behind dose reduction. Conclusion: Although some concerns on effectiveness were perceived, both patients and rheumatologists saw potential benefits of dose reduction in terms of safety, societal costs, and application of a personalised approach. As a result, most rheumatologists and patients showed a willingness to consider dose reduction strategies. [ABSTRACT FROM AUTHOR]

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin's lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn's disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin's lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care. [ABSTRACT FROM AUTHOR]

Summary: Osimertinib is used as the first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early dose reduction is often required due to adverse events (AEs). This study aimed to evaluate the effect of early dose reduction of osimertinib on efficacy and safety. This was a retrospective study including patients with EGFR-mutated NSCLC who were started on osimertinib as the first-line therapy between August 2018 and December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 months of osimertinib initiation or started at 40 mg/day were defined as the dose reduction group. The primary endpoint was progression-free survival (PFS). Factors affecting PFS were explored using the Cox proportional hazards model. A total of 85 patients were included in this study. No significant differences in patient characteristics were observed between the dose reduction (n = 25) and standard dose groups (n = 60). The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC. [ABSTRACT FROM AUTHOR]

Abstract Background 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation. Case presentation We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA's linked prescription and medical claims databases (2018–2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients. Plain language summary Treatment patterns in patients with tenosynovial giant cell tumors in the USA This database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA's prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients. Summary points Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm affecting the synovial membrane lining joints, bursae and tendon sheaths. Pexidartinib is currently the only systemic treatment approved by the US FDA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Other systemic therapies have been investigated in clinical studies of TGCT patients, none of them have been approved by the FDA for the treatment of TGCT specifically. Using a real-world claims database, this study characterized TGCT patients newly treated with pexidartinib or other unapproved systemic treatments and described their treatment patterns, including treatment duration and dosing. In this study, we found that although the median duration of pexidartinib treatment was not reached, patients on pexidartinib had the highest 12-month probability of remaining on treatment. Dose reductions after the first medication claim were commonly observed in the pexidartinib cohort (34.1%) and some patients (9.8%) had evidence of dose increase. Dose levels of the non-FDA-approved systemic therapies were consistent with the recommended dosages for other indications, as per their label, none of which were TGCT. As expected, 63.6–82.9% of TGCT patients treated with non-FDA-approved systemic therapies discontinued treatment at 12 months. This study provided novel insights into how systemic therapies for TGCT are used in real-world clinical practice, where surgery has been the standard of care. Given the large unmet need for the treatment of TGCT patients, and as pexidartinib is the only regulatory-approved systemic treatment, there is opportunity for its wider use in this patient population. [ABSTRACT FROM AUTHOR]

Background/Aim: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. Materials and Methods: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm³, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. Results: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. Conclusion: The combination of lowdose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect. [ABSTRACT FROM AUTHOR]

Introduction Biologic therapy is an effective treatment for inflammatory bowel disease [IBD]. However due to cost and safety concerns, dose de-escalation strategies after achieving remission have been suggested. Aim To critically review available data on dose de-escalation of biologics [or other advanced therapies] in IBD. We will focus on studies evaluating de-escalation to standard dosing in patients initially optimised, and also on studies assessing de-escalation from standard dosing. Methods A systematic bibliographic search was performed. Results The mean frequency of de-escalation after previous dose intensification [12 studies, 1,474 patients] was 34%. The corresponding frequency of de-escalation from standard dosing [five studies, 3,842 patients] was 4.2%. The relapse rate of IBD following anti-tumour necrosis factor [TNF] de-escalation to standard dosing in patients initially dose-escalated [10 studies, 301 patients] was 30%. The corresponding relapse rate following anti-TNF de-escalation from standard dosing [nine studies, 494 patients] was 38%. The risk of relapse was lower for patients in clinical, biologic, and endoscopic/radiological remission at the time of de-escalation. A role of anti-TNF therapeutic drug monitoring in the decision to dose de-escalate has been demonstrated. In patients relapsing after de-escalation, re-escalation is generally effective. De-escalation is not consistently associated with a better safety profile. The cost-effectiveness of the de-escalation strategy remains uncertain. Finally, there is not enough evidence to recommend dose de-escalation of biologics different from anti-TNFs or small molecules. Conclusions Any consideration for de-escalation of biologic therapy in IBD must be tailored, taking into account the risks and consequences of a flare and patients' preferences. [ABSTRACT FROM AUTHOR]

Background: 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient's feeling of autonomy and psychiatric rehabilitation. Case presentation: We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions: Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications: Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery. [ABSTRACT FROM AUTHOR]

Objectives: To introduce an automated computational algorithm that estimates the global noise level across the whole imaging volume of PET datasets. Methods: [18F]FDG PET images of 38 patients were reconstructed with simulated decreasing acquisition times (15–120 s) resulting in increasing noise levels, and with block sequential regularized expectation maximization with beta values of 450 and 600 (Q.Clear 450 and 600). One reader performed manual volume-of-interest (VOI) based noise measurements in liver and lung parenchyma and two readers graded subjective image quality as sufficient or insufficient. An automated computational noise measurement algorithm was developed and deployed on the whole imaging volume of each reconstruction, delivering a single value representing the global image noise (Global Noise Index, GNI). Manual noise measurement values and subjective image quality gradings were compared with the GNI. Results: Irrespective of the absolute noise values, there was no significant difference between the GNI and manual liver measurements in terms of the distribution of noise values (p = 0.84 for Q.Clear 450, and p = 0.51 for Q.Clear 600). The GNI showed a fair to moderately strong correlation with manual noise measurements in liver parenchyma (r = 0.6 in Q.Clear 450, r = 0.54 in Q.Clear 600, all p < 0.001), and a fair correlation with manual noise measurements in lung parenchyma (r = 0.52 in Q.Clear 450, r = 0.33 in Q.Clear 600, all p < 0.001). Classification performance of the GNI for subjective image quality was AUC 0.898 for Q.Clear 450 and 0.919 for Q.Clear 600. Conclusion: An algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. Clinical relevance statement: An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking of clinical PET imaging within and across institutions. Key Points: • Noise is an important quantitative marker that strongly impacts image quality of PET images. • An automated computational noise measurement algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. • An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking as well as protocol harmonization. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of CAREdose4D on the dose and image quality in Brain Computed Tomography (CT). Materials and Methods: Noise, Signal-to-Noise Ratio (SNR), and Contrast-to-Noise Ratio (CNR) for Gray Matter (GM), White Matter (WM), Cerebrospinal Fluid (CSF), and skull bones were investigated in brain CT scans of 60 patients. In addition, a phantom study was conducted to examine the effect of CAREdose 4D on the same subject in the brain, chest, abdomen, and pelvic CT protocols. Volume CT dose index (CTDIvol) and Dose Length Product (DLP) were recorded for each scan. Data were analyzed by T-test and Mann-Whitney statistical test with a significance level of less than 0.05. Results: The following results were obtained in active and passive modes of CAREdose 4D in brain CT of patients, respectively: CTDIvol, 15.76±3.94 and 16.96±2.14 mGy (p0.05). There was no significant difference between SNRs and noise of various tissues of the brain (p>0.05) but CNR difference for gray matter, white matter, and cerebrospinal fluid (CSF) was significant (p

Background: Abdominal radiographs remain useful in newborns. Given the high radiation sensitivity of this population, it is necessary to optimize acquisition techniques to minimize radiation exposure. Objective: Evaluate the effects of three additional filtrations on radiation dose and image quality in abdominal X-rays of newborns using an anthropomorphic phantom. Material and method: Abdominal radiographs of an anthropomorphic newborn phantom were performed using acquisition parameters ranging from 55 to 70 kV and from 0.4 to 2.5 mAs, without and with three different additional filtrations: 0.1 mm copper (Cu) + 1 mm aluminum (Al), 0.2 mm copper + 1 mm aluminum, and 2 mm aluminum. For each X-ray the dose area product (DAP) was measured, the signal-to-noise ratio (SNR) was calculated, and image quality (IQ) was evaluated by two blinded radiologists using the absolute visual grading analysis (VGA) method. Results: Adding an additional filtration resulted in a significant reduction in DAP, with a decrease of 42% using 2 mm Al filtration, 65% with 0.1 mm Cu + 1 mm Al filtration, and 78% with 0.2 mm Cu + 1 mm Al filtration (p < 0.01). The addition of 2 mm aluminum filtration does not significantly decrease the SNR (p = 0.31), CNR (p = 0.52) or the IQ (p = 0.12 and 0.401 for reader 1 and 2, respectively). However, adding copper-containing filtration leads to a significant decrease in, SNR, CNR and IQ. Conclusion: Adding a 2 mm Al additional filtration for abdominal radiographs in newborns can significantly reduce the radiation dose without causing a significant decrease in image quality.

Abstract Shading, the predominant condition in most of the eucalyptus cultivation cycle, causes changes in the morphological and physiological weed's characteristics, which can alter their responses to glyphosate and carfentrazone-ethyl, important herbicides for the crop. The objective was to evaluate the influence of light on the efficiency of glyphosate and carfentrazone-ethyl used alone and in a mixture in Digitaria insularis control, a priority pest in the crop. The experiment was carried out in a 3 × 6 factorial scheme. The first factor corresponded to 3 cultivation environments (full sunlight, 45 and 63% shading) and the second factor to doses of glyphosate and carfentrazone-ethyl applied isolated (1920 and 40 g ai ha−1) and mixed (1536 + 8; 1152 + 16; 768 + 24 and 384 + 32 g ai ha−1), respectively. Shading increased D. insularis sensitivity to glyphosate alone and in a mixture with carfentrazone-ethyl. In shading, the glyphosate application alone at a dose of 1920 g ha−1 and in a mixture with carfentrazone-ethyl at doses of 1536 + 8 and 1152 + 16 g ha−1 were efficient in D. insularis control. In the environment of 63% shading, the dose of 768 + 24 g ha−1 was also efficient in this species control. None of the doses were effective in controlling D. insularis in full sunlight. Isolated carfentrazone-ethyl was inefficient in controlling D. insularis, regardless of the growth environment. Shading increases the quantum yield of photosystem II and reduces the electron transport rate, photosynthetic rate, stomatal conductance, and transpiration rate of D. insularis. In shady environments, it is possible to control D. insularis with lower glyphosate doses, used alone and mixed with carfentrazone-ethyl.

Abstract Purpose Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. Methods Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). Results Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3–3) was higher compared with conventional imaging at 120 kVp (2; 2–2), 100 kVp (1; 1–2), and 80 kVp (1; 1–1) (all p

Purpose: Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. Methods: Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). Results: Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3–3) was higher compared with conventional imaging at 120 kVp (2; 2–2), 100 kVp (1; 1–2), and 80 kVp (1; 1–1) (all p < 0.001). Indicated by an intraclass correlation coefficient of 0.945 (95% confidence interval: 0.927–0.960), interrater reliability was excellent. Conclusions: In abdominal CT with maximised dose reduction, tin prefiltration at 100 kVp allows for superior image quality over Sn 150 kVp and conventional imaging without spectral shaping. [ABSTRACT FROM AUTHOR]

Shading, the predominant condition in most of the eucalyptus cultivation cycle, causes changes in the morphological and physiological weed's characteristics, which can alter their responses to glyphosate and carfentrazone-ethyl, important herbicides for the crop. The objective was to evaluate the influence of light on the efficiency of glyphosate and carfentrazone-ethyl used alone and in a mixture in Digitaria insularis control, a priority pest in the crop. The experiment was carried out in a 3 × 6 factorial scheme. The first factor corresponded to 3 cultivation environments (full sunlight, 45 and 63% shading) and the second factor to doses of glyphosate and carfentrazone-ethyl applied isolated (1920 and 40 g ai ha−1) and mixed (1536 + 8; 1152 + 16; 768 + 24 and 384 + 32 g ai ha−1), respectively. Shading increased D. insularis sensitivity to glyphosate alone and in a mixture with carfentrazone-ethyl. In shading, the glyphosate application alone at a dose of 1920 g ha−1 and in a mixture with carfentrazone-ethyl at doses of 1536 + 8 and 1152 + 16 g ha−1 were efficient in D. insularis control. In the environment of 63% shading, the dose of 768 + 24 g ha−1 was also efficient in this species control. None of the doses were effective in controlling D. insularis in full sunlight. Isolated carfentrazone-ethyl was inefficient in controlling D. insularis, regardless of the growth environment. Shading increases the quantum yield of photosystem II and reduces the electron transport rate, photosynthetic rate, stomatal conductance, and transpiration rate of D. insularis. In shady environments, it is possible to control D. insularis with lower glyphosate doses, used alone and mixed with carfentrazone-ethyl. [ABSTRACT FROM AUTHOR]

Background: Many healthcare institutions have guidelines concerning the usage of protective procedures, and various x‐ray shields have been used to reduce unwanted radiation exposure to medical staff and patients when using x‐rays. Most x‐ray shields are in the form of sheets and lack elasticity, which limits their effectiveness in shielding areas with movement, such as the thyroid. To overcome this limitation, we have developed an innovative elastic x‐ray shield. Purpose: The purpose of this study is to explain the methodology for developing and evaluating a novel elastic x‐ray shield with sufficient x‐ray shielding ability. Furthermore, valuable knowledge and evaluation indices are derived to assess our shield's performance. Methods: Our x‐ray shield was developed through a process of embedding Bi2O3 particles into porous polyurethane. Porous polyurethane with a thickness of 10 mm was dipped into a solution of water, metal particles, and chemical agents. Then, it was air‐dried to fix the metal particles in the porous polyurethane. Thirteen investigational x‐ray shields were fabricated, in which Bi2O3 particles at various mass thicknesses (ranging from 585 to 2493 g/m2) were embedded. To determine the performance of the shielding material, three criteria were evaluated: (1) Dose Reduction Factor (DRF$DRF$), measured using inverse broad beam geometry; (2) uniformity, evaluated from the standard deviation (SD$SD$) of the x‐ray image obtained using a clinical x‐ray imaging detector; and (3) elasticity, evaluated by a compression test. Results: The elastic shield with small pores, containing 1200 g/m2 of the metal element (Bi), exhibited a well‐balanced performance. The DRF$DRF$ was approximately 80% for 70 kV diagnostic x‐rays. This shield's elasticity was −0.62 N/mm, a loss of only 30% when compared to porous polyurethane without metal. Although the non‐uniformity of the x‐ray shield leads to poor shielding ability, it was found that the decrease in the shielding ability can be limited to a maximum of 6% when the shield is manufactured so that the SD$SD$ of the x‐ray image of the shield is less than 10%. Conclusions: It was verified that an elastic x‐ray shield that offers an appropriate reduction in radiation exposure can be produced by embedding Bi2O3 particles into porous polyurethane. Our findings can lead to the development of novel x‐ray shielding products that can reduce the physical and mental stress on users. [ABSTRACT FROM AUTHOR]

Background: The use of computed tomography (CT) for attenuation correction (AC) in whole‐body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose. Purpose: The purpose of this study was to investigate the ultra‐low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC‐CT and how it affects PET image quality. Methods: The study evaluated a range of ultra‐low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDIVol reported by the scanner. Several voxel‐based and volumes of interest (VOI)‐based comparisons were performed to compare the ultra‐low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra‐low dose CT settings. Results: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU‐60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel‐based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%. Conclusions: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI. [ABSTRACT FROM AUTHOR]

Background: Radiation dose reduction has been the focus of many research activities in x‐ray CT. Various approaches were taken to minimize the dose to patients, ranging from the optimization of clinical protocols, refinement of the scanner hardware design, and development of advanced reconstruction algorithms. Although significant progress has been made, more advancements in this area are needed to minimize the radiation risks to patients. Purpose: Reconstruction algorithm‐based dose reduction approaches focus mainly on the suppression of noise in the reconstructed images while preserving detailed anatomical structures. Such an approach effectively produces synthesized high‐dose images (SHD) from the data acquired with low‐dose scans. A representative example is the model‐based iterative reconstruction (MBIR). Despite its widespread deployment, its full adoption in a clinical environment is often limited by an undesirable image texture. Recent studies have shown that deep learning image reconstruction (DLIR) can overcome this shortcoming. However, the limited availability of high‐quality clinical images for training and validation is often the bottleneck for its development. In this paper, we propose a novel approach to generate SHD with existing low‐dose clinical datasets that overcomes both the noise texture issue and the data availability issue. Methods: Our approach is based on the observation that noise in the image can be effectively reduced by performing image processing orthogonal to the imaging plane. This process essentially creates an equivalent thick‐slice image (TSI), and the characteristics of TSI depend on the nature of the image processing. An advantage of this approach is its potential to reduce impact on the noise texture. The resulting image, however, is likely corrupted by the anatomical structural degradation due to partial volume effects. Careful examination has shown that the differential signal between the original and the processed image contains sufficient information to identify regions where anatomical structures are modified. The differential signal, unfortunately, contains significant noise and has to be removed. The noise removal can be accomplished by performing iterative noise reduction to preserve structural information. The processed differential signal is subsequently subtracted from TSI to arrive at SHD. Results: The algorithm was evaluated extensively with phantom and clinical datasets. For better visual inspection, difference images between the original and SHD were generated and carefully examined. Negligible residual structure could be observed. In addition to the qualitative inspection, quantitative analyses were performed on clinical images in terms of the CT number consistency and the noise reduction characteristics. Results indicate that no CT number bias is introduced by the proposed algorithm. In addition, noise reduction capability is consistent across different patient anatomical regions. Further, simulated water phantom scans were utilized in the generation of the noise power spectrum (NPS) to demonstrate the preservation of the noise‐texture. Conclusions: We present a method to generate SHD datasets from regularly acquired low‐dose CT scans. Images produced with the proposed approach exhibit excellent noise‐reduction with the desired noise‐texture. Extensive clinical and phantom studies have demonstrated the efficacy and robustness of our approach. Potential limitations of the current implementation are discussed and further research topics are outlined. [ABSTRACT FROM AUTHOR]

Background: Follow-up scoliosis radiographs are performed to assess the degree of spinal curvature and skeletal maturity, which can be done at lower radiation exposures than those in standard-dose radiography. Objective: Describe and evaluate a protocol that reduced the radiation in follow-up frontal-view scoliosis radiographs. Materials and methods: We implemented a postero-anterior lower dose modified-technique for scoliosis radiography with task-based definition of adequate image quality and use of technique charts based on target exposure index and patient's height and weight. We subsequently retrospectively evaluated 40 consecutive patients who underwent a follow-up radiograph using the modified-technique after an initial standard-technique radiograph. We evaluated comparisons of proportions for subjective assessment with chi-squared tests, and agreements of reader's scores with intraclass correlation coefficients and Bland–Altman plots. We determined incident air kerma, exposure index, deviation index/standard deviation, dose-area product (DAP), and effective dose for each radiograph. We set statistical significance at P<0.05. Results: Forty patients (65% female), aged 4–17 years. Median effective dose was reduced from 39 to 10 µSv (P<0.001), incident air kerma from 139 to 29 µSv (P<0.001), and DAP from 266 to 55 mGy*cm2 (P<0.001). All modified-technique parameters were rated with a mean score of acceptable or above. All modified-technique measurements obtained inter- and intra-observer correlation coefficient agreements of 0.86 ("Good") or greater. Conclusion: Substantial dose reduction on follow-up scoliosis imaging with existing radiography units is achievable through task-based definition of adequate image quality and tailoring of radiation to each patient's height and weight, while still allowing for reliable assessment and reproducible measurements. [ABSTRACT FROM AUTHOR]

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03–0.22]), as well as early-career clinicians (0.53 [0.30–0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9–16.3]), (2.9 [1.5–6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial. [ABSTRACT FROM AUTHOR]

Imaging of the cervical spine in general radiography is most frequently performed using an anti-scatter grid. The purpose of this study was to investigate the effects of a gridless setting on image quality and radiation dose during digital radiography of the anteroposterior (AP) and lateral (LAT) cervical spine. A phantom study was performed with a variety of tube voltages (63–75 kV) with and without an anti-scatter grid. The tube current time product (mAs) and dose area product (DAP) were recorded and used to calculate effective dose (ED) and individual organ dose using PCXMC 2.0 software, as well as entrance surface dose (ESD) and objective image quality: signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective visual image quality grading characteristics (VGC) was performed by five qualified radiographers. In a gridless setting, the AP and LAT positions showed significantly lower DAP (1.6 μGym2; 61.3 % and 1.6 μGym2; 51.2%), ESD (27.6 μGy; 57.3% and 77.2 μGy; 47.2%) and ED (4.2 μSv; 61.3% and 2.3 μSv; 48.9%). In a gridless setting in the AP position, there is a slight significant deterioration in image quality. In the lateral projection, on the other hand, the image quality without the use of grid was only significantly reduced in three of six criteria and there was no difference in the objective image quality between the two settings examined. The results of this study show that gridless setting significantly decreases radiation dose and image quality, but the quality in the lateral projection is still acceptable for diagnostic purpose. The protocol without the use of the anti-scatter grid in cervical spine radiography leads to a reduction in the radiation dose in both projections, but the image quality in the AP is significantly reduced for all criteria examined, with a slight deterioration in image quality in the lateral projection. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to use electronic opioid dispensing data to develop an individual segmented trajectory approach for identifying opioid use patterns. The resulting opioid use patterns can be used for examining the association between opioid use and drug overdose. Methods: We retrospectively assembled a cohort of members on long‐term opioid therapy (LTOT) between January 1, 2006 and June 30, 2019 who were 18 years and older and enrolled in one of three health care systems in the US. We have developed an individual segmented trajectory analysis for identifying various opioid use patterns by scanning over the follow‐up and finding distinct opioid use patterns based on variability measured with coefficient of variation and trends of milligram morphine equivalents levels. Results: Among 31, 865 members who were on LTOT between January 1, 2006 and June 30, 2019, 58.3% were female, and the average age was 55.4 years (STD = 15.4). The study population had 152 557 person‐years of follow‐up, with an average follow‐up of 4.4 years per enrollment per person (STD = 3.4). This novel approach identified up to 13 distinct patterns including 88 756 episodes of "stable" pattern (42.1%) with an average follow‐up of 11.2 months, 29 140 episodes of "increasing" pattern (13.8%) with an average follow‐up of 6.0 months, 13 201 episodes of ≤10% dose reduction (6.3%) with an average follow‐up of 10.4 months, 7286 episodes of 11%–20% dose reduction (3.5%) with an average follow‐up of 5.3 months, 4457 episodes of 21%–30% dose reduction (2.1%) with an average follow‐up of 4.0 months, and 9903 episodes of >30% dose reduction (4.7%) with an average follow‐up of 2.6 months. Conclusions: A novel approach was developed to identify 13 distinct opioid use patterns using each individual's longitudinal dispensing data and these patterns can be used in examining overdose risk during the time that these patterns are ongoing. [ABSTRACT FROM AUTHOR]

Introduction: The KRAS G12C inhibitor sotorasib was approved for treating advanced NSCLC in the second line or later on the basis of the CodeBreaK100 trial. Nevertheless, data on the real-world efficacy and safety of sotorasib, and to its optimal dose, remain limited. Methods: Patients treated with sotorasib for NSCLC through the Veterans Health Administration were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review. Results: Among the 128 patients treated with sotorasib through the Veterans Health Administration, objective response rate was 34%, progression-free survival (PFS) six months, and overall survival 12 months. Similar PFS was observed among the 16 patients who received frontline sotorasib without any prior systemic therapy for NSCLC. Toxicity leading to sotorasib interruption or dose reduction occurred in 37% of patients, whereas sotorasib discontinuation for toxicity occurred in 25%. Notably, sotorasib dose reduction was associated with substantially improved PFS and OS. Conclusions: In this real-world study, the observed efficacy of sotorasib was similar to the results of CodeBreaK100. Patients who received frontline sotorasib had similar PFS to our overall cohort, suggesting that first-line sotorasib monotherapy may benefit patients who are not eligible for chemotherapy. Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy.

Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75–100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0–2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one “on-demand” dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice.

Rationale and objectives: Aim of this study was to assess the impact of contrast media dose (CMD) reduction on diagnostic quality of photon-counting detector CT (PCD-CT) and energy-integrating detector CT (EID-CT). Methods: CT scans of the abdominal region with differing CMD acquired in portal venous phase on a PCD-CT were included and compared to EID-CT scans. Diagnostic quality and contrast intensity were rated. Additionally, readers had to assign the scans to reduced or regular CMD. Regions-of-interest (ROIs) were placed in defined segments of portal vein, inferior vena cava, liver, spleen, kidneys, abdominal aorta and muscular tissue. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Results: Overall 158 CT scans performed on a PCD-CT and 68 examinations on an EID-CT were analyzed. Overall diagnostic quality showed no significant differences for PCD-CT with standard CMD which scored a median 5 (IQR:5-5) and PCD-CT with 70% CMD scoring 5 (4–5). (For PCD-CT, 71.69% of the examinations with reduced CMD were assigned to regular CMD by the readers, for EID-CT 9.09%. Averaged for all measurements SNR for 50% CMD was reduced by 19% in PCD-CT (EID-CT 34%) and CNR by 48% (EID-CT 56%). Virtual monoenergetic images (VMI)50keV for PCD-CT images acquired with 50% CMD showed an increase in SNR by 72% and CNR by 153%. Conclusions: Diagnostic interpretability of PCD-CT examinations with reduction of up to 50% CMD is maintained. PCD-CT deducted scans especially with 70% CMD were often not recognized as CMD reduced scans. Compared to EID-CT less decline in SNR and CNR is observed for CMD reduced PCD-CT images. Employing VMI50keV for CMD-reduced PCD-CT images compensated for the effects.

This article discusses the importance of centering the patient in decisions about opioid tapering. The author reflects on the historical context of opioid prescribing, highlighting how drug manufacturers influenced medical education and the subsequent rise of the opioid overdose epidemic. The article emphasizes the need for clinicians to consider the competing risks of opioid continuation versus tapering and to involve patients in decision-making. It also addresses the challenges of patient-provider relationships and provides guidance on how to approach conversations about tapering. The article concludes by emphasizing the individualized nature of these decisions and the importance of aligning them with the patient's values and preferences. [Extracted from the article]

The article "Corrigendum: Dose reduction of biologics in patients with plaque psoriasis: a review" published in Frontiers in Pharmacology on October 14, 2024, addresses an error in the original publication regarding the symbol used in the phrase related to biologic use duration. The correction clarifies that the correct symbol should be '≥' instead of '≤'. The authors emphasize that this correction does not impact the scientific conclusions of the article. The document provides information on the correction made to the discussion section of the original article and highlights the eligibility criteria for dose reduction strategies in patients with plaque psoriasis. [Extracted from the article]

Lenvatinib (LEN) is the standard treatment for hepatocellular carcinoma (HCC). In clinical practice, gastrointestinal (GI) symptoms such as fatigue and loss of appetite often lead to dose reduction or treatment discontinuation. This study aimed to identify the predictors of patients who will experience dose reduction or treatment discontinuation owing to fatigue or GI symptoms during LEN treatment for HCC.We retrospectively identified 99 patients who received LEN at the Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and December 2023. To investigate the risk factors for treatment discontinuation or dose reduction due to fatigue or GI symptoms during LEN administration, patients were divided into two groups based on whether treatment discontinuation or dose reduction occurred due to fatigue or GI symptoms during LEN administration (37 patients) or not (62 patients). We compared baseline characteristics between the two groups.Multivariate analysis revealed that body weight (odds ratio 4.310, 95% confidence interval 1.380–13.500; P = 0.002) was an independent risk factor that significantly contributed to treatment discontinuation or dose reduction owing to fatigue or GI symptoms during LEN administration. The cut-off value calculated using the body weight curve was 55.0 kg. Using this cutoff value, the sensitivity and specificity of body weight to detect treatment discontinuation or dose reduction due to fatigue or GI symptoms during LEN administration were 83.9% and 56.8%, respectively.In clinical practice, patients weighing less than 55 kg who start with a full dose will likely experience weight loss or discontinuation during treatment. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of CDK4/6 inhibitors, the number of discontinuations and reductions due to adverse events is increasing. Therefore, we examined the risk of dose reduction, discontinuation, and occurrence of serious adverse events and death due to adverse events when CDK4/6 inhibitors are combined with endocrine drugs.We searched English-language articles published up to February 10, 2024, using RR values (risk ratio) to indicate the risk of discontinuation, dose reduction, death, and the risk of serious adverse events.When CDK4/6 inhibitors were used in combination with endocrine drugs, abemaciclib resulted in the highest risk of discontinuation, dose reduction, and serious adverse events. Ribociclib caused the highest risk of death.When using CDK4/6 inhibitors in the clinical setting, a comprehensive evaluation should be performed to avoid dosage reductions and discontinuations and to choose the most appropriate treatment regimen.Methods: With the widespread use of CDK4/6 inhibitors, the number of discontinuations and reductions due to adverse events is increasing. Therefore, we examined the risk of dose reduction, discontinuation, and occurrence of serious adverse events and death due to adverse events when CDK4/6 inhibitors are combined with endocrine drugs.We searched English-language articles published up to February 10, 2024, using RR values (risk ratio) to indicate the risk of discontinuation, dose reduction, death, and the risk of serious adverse events.When CDK4/6 inhibitors were used in combination with endocrine drugs, abemaciclib resulted in the highest risk of discontinuation, dose reduction, and serious adverse events. Ribociclib caused the highest risk of death.When using CDK4/6 inhibitors in the clinical setting, a comprehensive evaluation should be performed to avoid dosage reductions and discontinuations and to choose the most appropriate treatment regimen.Results: With the widespread use of CDK4/6 inhibitors, the number of discontinuations and reductions due to adverse events is increasing. Therefore, we examined the risk of dose reduction, discontinuation, and occurrence of serious adverse events and death due to adverse events when CDK4/6 inhibitors are combined with endocrine drugs.We searched English-language articles published up to February 10, 2024, using RR values (risk ratio) to indicate the risk of discontinuation, dose reduction, death, and the risk of serious adverse events.When CDK4/6 inhibitors were used in combination with endocrine drugs, abemaciclib resulted in the highest risk of discontinuation, dose reduction, and serious adverse events. Ribociclib caused the highest risk of death.When using CDK4/6 inhibitors in the clinical setting, a comprehensive evaluation should be performed to avoid dosage reductions and discontinuations and to choose the most appropriate treatment regimen.Conclusion: With the widespread use of CDK4/6 inhibitors, the number of discontinuations and reductions due to adverse events is increasing. Therefore, we examined the risk of dose reduction, discontinuation, and occurrence of serious adverse events and death due to adverse events when CDK4/6 inhibitors are combined with endocrine drugs.We searched English-language articles published up to February 10, 2024, using RR values (risk ratio) to indicate the risk of discontinuation, dose reduction, death, and the risk of serious adverse events.When CDK4/6 inhibitors were used in combination with endocrine drugs, abemaciclib resulted in the highest risk of discontinuation, dose reduction, and serious adverse events. Ribociclib caused the highest risk of death.When using CDK4/6 inhibitors in the clinical setting, a comprehensive evaluation should be performed to avoid dosage reductions and discontinuations and to choose the most appropriate treatment regimen. [ABSTRACT FROM AUTHOR]

Introduction: Older patients with gastroesophageal (GE) cancer are at increased risk of low treatment tolerability and poor outcome. Dose reduced chemotherapy has been shown to improve tolerability without compromising efficacy in advanced GE cancer. However, the impact of reduced dose preoperative chemotherapy in the curative setting of older patients is unknown. The primary aim of this study was to investigate if dose reduction during preoperative chemotherapy impacts survival in older patients aged≥70 years with resectable GE cancer., Materials and Methods: This cohort study included consecutive patients referred to perioperative chemotherapy treated from November 2016 until October 2021. The primary endpoint was overall survival (OS) estimated by Kaplan-Meier analysis. The log-rank test was used to compare survival rates. A multivariate analysis was made to control for potentially interacting covariates., Results: A total of 548 patients (age ≥ 70, 179; age < 70, 369) were included. Fewer older compared to younger patients had Eastern Cooperative Oncology Group Performance Status 0 at baseline (50 % vs 63 %, p = 0.007). Preoperative chemotherapy was more often initiated at reduced dose in older patients compared to younger (37 % vs 14 %, p < 0.001). Older patients who did not receive a reduce dose in the second or subsequent cycles of preoperative chemotherapy were less likely to complete preoperative chemotherapy when compared to the younger patients (75 % vs 85 %, p = 0.03). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with significantly better OS for the older patient population (HR = 0.54, 95 % CI: 1.2-2.9, p = 0.006) but not for the younger (HR = 0.97, 95 % CI: 0.75-1.4, p = 0.83). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with lower mortality risk in the multivariate analysis for the older patients (HR = 0.56, 95 % CI: 0.33-0.97, p = 0.04)., Discussion: Dose reduction in the second or subsequent preoperative chemotherapy cycles seems safe and feasible in older patients without compromising survival and may result in a benefit in OS. This finding should be validated in an independent cohort or a randomized trial., Competing Interests: Declaration of Competing Interest Josephine Skjoldbirk Andersen: None. Kristian Egebjerg: None. Michael Patrick Achiam: None. Camilla Qvortrup: Grants from Servier, personal fees from Pierre Fabre. Lene Bæksgaard: None. Cecilia M. Lund: None. Morten Mau-Sørensen: Morten Mau-Sørensen has served on advisory boards for Astellas, MSD/Merck, AstraZeneca, and BMS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT -adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well.To evaluate the pharmacogenetic significance of NUDT15 in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia.We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC&#95;000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for NUDT15*3 , were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.

Purpose: In this study, we evaluated image quality and radiation dose reduction when a Copper (Cu) filter was added to hip joint X-ray imaging., Methods: We measured effective energy without (0 mm) and with (0.1/0.2 mm) Cu-added filter at 70 kV, and we calculated soft tissue-bone contrast and signal-difference-to-noise-ratio (SDNR) under constant entrance surface dose. After that, we estimated the dose reduction rate., Results: The effective energy was 32.07 keV for 0 mm Cu, 37.59 keV for 0.1 mm Cu, and 40.91 keV for 0.2 mm Cu. As the thickness of the Cu-added filter was increased, contrast decreased, but SDNR increased. The dose reduction rate in bone calculated measuring SDNR was 34% for 0.1 mm Cu and 47% for 0.2 mm Cu in max., Conclusion: It was suggested that adding Cu filter to hip-joint X-ray imaging could reduce entrance surface dose while maintaining the image quality based on SDNR.