Safety and Efficacy of Reduced Prolonged-release Tacrolimus Exposure in De Novo Kidney Transplantation: A Randomized, Open-label, Pilot Study in Asia—OPTIMIZE Study

Background. A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Methods. Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Results. Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Conclusions. Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR)

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA

Personalized Deep Learning Model for Clinical Target Volume on Daily Cone Beam Computed Tomography in Breast Cancer Patients

Purpose: Herein, we developed a deep learning algorithm to improve the segmentation of the clinical target volume (CTV) on daily cone beam computed tomography (CBCT) scans in breast cancer radiation therapy. By leveraging the Intentional Deep Overfit Learning (IDOL) framework, we aimed to enhance personalized image-guided radiation therapy based on patient-specific learning. Methods and Materials: We used 240 CBCT scans from 100 breast cancer patients and employed a 2-stage training approach. The first stage involved training a novel general deep learning model (Swin UNETR, UNET, and SegResNET) on 90 patients. The second stage used intentional overfitting on the remaining 10 patients for patient-specific CBCT outputs. Quantitative evaluation was conducted using the Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), mean surface distance (MSD), and independent samples t test with expert contours on CBCT scans from the first to 15th fractions. Results: IDOL integration significantly improved CTV segmentation, particularly with the Swin UNETR model (P values < .05). Using patient-specific data, IDOL enhanced the DSC, HD, and MSD metrics. The average DSC for the 15th fraction improved from 0.9611 to 0.9819, the average HD decreased from 4.0118 mm to 1.3935 mm, and the average MSD decreased from 0.8723 to 0.4603. Incorporating CBCT scans from the initial treatments and first to third fractions further improved results, with an average DSC of 0.9850, an average HD of 1.2707 mm, and an average MSD of 0.4076 for the 15th fraction, closely aligning with physician-drawn contours. Conclusion: Compared with a general model, our patient-specific deep learning-based training algorithm significantly improved CTV segmentation accuracy of CBCT scans in patients with breast cancer. This approach, coupled with continuous deep learning training using daily CBCT scans, demonstrated enhanced CTV delineation accuracy and efficiency. Future studies should explore the adaptability of the IDOL framework to diverse deep learning models, data sets, and cancer sites

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Original Article Purpose The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. Materials and Methods A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next followup; arm swelling that persisted over two consecutive examinations was considered PLE. Results At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p &lt; 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). Conclusion One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication. Key words Breast neoplasms, Transient lymphedema, Persistent lymphedema, Risk factors Introduction Lymphedema (LE) is a common and debilitating condition in breast cancer survivors characterized by regional swelling, typically in one or both arms Despite the frequency of this condition, there are no uniform criteria for defining LE. Symptom duration is generally not stated as part of the definition of LE, with a diagnosis of LE made primarily on the presence of swelling alon