Real-world outcomes following ibrutinib dose reduction in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

This 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.

Image quality-based dose optimization in pediatric cone-beam computed tomography: A pilot methodological study.

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.

Image quality assessments in abdominal CT: Relative importance of dose, iterative reconstruction strength and slice thickness.

INTRODUCTION: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: Combination of thinner slices and higher ADMIRE strength facilitates imaging at low dose.

Imatinib dose reduction after major molecular response in chronic-phase chronic myeloid leukemia.

BACKGROUND: In people with chronic-phase chronic myeloid leukemia (CML) receiving imatinib and achieving major molecular response (MMR), dose reduction may decrease adverse events but may be associated with a loss of molecular response. Whether digital droplet polymerase chain reaction (ddPCR) can identify persons in whom dose reduction might be unsuccessful is unknown. METHODS: Data from 716 consecutive subjects who achieved MMR after initial imatinib therapy (400 mg/day) were obtained. A total of 486 subjects remained on full-dose imatinib, whereas 230 subjects had their dose reduced to 300 or 200 mg/day. The outcomes of these cohorts were compared via landmark and propensity score matching analyses. RESULTS: Imatinib dose reduction showed no significant effect on the subsequent achievement of deeper molecular responses (4- and 4.5-log reductions in BCR::ABL1 transcripts; MR4 and MR4.5), maintenance of MMR, or attainment of therapy-free remission when compared with subjects without dose reduction. In subjects achieving MR4, however, the probability of maintaining MR4 (p = .002) was lower in the reduced-dose group. In multivariable analyses, failure to achieve MR4.5 as determined by ddPCR at the time of dose reduction was significantly associated with briefer MMR failure-free survival (FFS; hazard ratio [HR], 10.3; 95% confidence interval [CI], 1.3-82.9; p = .03) and MR4 FFS (HR, 6.8; 95% CI, 2.6-18.0; p < .001). CONCLUSIONS: Imatinib dose reduction after achieving MMR does not adversely affect response deepening or MMR maintenance in chronic-phase CML but compromises MR4 maintenance. The results of ddPCR may identify people who benefit from imatinib dose reduction.

Enhancing Cone-Beam CT Image Quality in TIPSS Procedures Using AI Denoising.

Purpose: This study evaluates a deep learning-based denoising algorithm to improve the trade-off between radiation dose, image noise, and motion artifacts in TIPSS procedures, aiming for shorter acquisition times and reduced radiation with maintained diagnostic quality. Methods: In this retrospective study, TIPSS patients were divided based on CBCT acquisition times of 6 s and 3 s. Traditional weighted filtered back projection (Original) and an AI denoising algorithm (AID) were used for image reconstructions. Objective assessments of image quality included contrast, noise levels, and contrast-to-noise ratios (CNRs) through place-consistent region-of-interest (ROI) measurements across various critical areas pertinent to the TIPSS procedure. Subjective assessments were conducted by two blinded radiologists who evaluated the overall image quality, sharpness, contrast, and motion artifacts for each dataset combination. Statistical significance was determined using a mixed-effects model (p ≤ 0.05). Results: From an initial cohort of 60 TIPSS patients, 44 were selected and paired. The mean dose-area product (DAP) for the 6 s acquisitions was 5138.50 ± 1325.57 µGy·m2, significantly higher than the 2514.06 ± 691.59 µGym2 obtained for the 3 s series. CNR was highest in the 6 s-AID series (p < 0.05). Both denoised and original series showed consistent contrast for 6 s and 3 s acquisitions, with no significant noise differences between the 6 s Original and 3 s AID images (p > 0.9). Subjective assessments indicated superior quality in 6 s-AID images, with no significant overall quality difference between the 6 s-Original and 3 s-AID series (p > 0.9). Conclusions: The AI denoising algorithm enhances CBCT image quality in TIPSS procedures, allowing for shorter scans that reduce radiation exposure and minimize motion artifacts.

Deep Learning-Based Denoising Enables High-Quality, Fully Diagnostic Neuroradiological Trauma CT at 25% Radiation Dose.

RATIONALE AND OBJECTIVES: Traumatic neuroradiological emergencies necessitate rapid and accurate diagnosis, often relying on computed tomography (CT). However, the associated ionizing radiation poses long-term risks. Modern artificial intelligence reconstruction algorithms have shown promise in reducing radiation dose while maintaining image quality. Therefore, we aimed to evaluate the dose reduction capabilities of a deep learning-based denoising (DLD) algorithm in traumatic neuroradiological emergency CT scans. MATERIALS AND METHODS: This retrospective single-center study included 100 patients with neuroradiological trauma CT scans. Full-dose (100%) and low-dose (25%) simulated scans were processed using iterative reconstruction (IR2) and DLD. Subjective and objective image quality assessments were performed by four neuroradiologists alongside clinical endpoint analysis. Bayesian sensitivity and specificity were computed with 95% credible intervals. RESULTS: Subjective analysis showed superior scores for 100% DLD compared to 100% IR2 and 25% IR2 (p < 0.001). No significant differences were observed between 25% DLD and 100% IR2. Objective analysis revealed no significant CT value differences but higher noise at 25% dose for DLD and IR2 compared to 100% (p < 0.001). DLD exhibited lower noise than IR2 at both dose levels (p < 0.001). Clinical endpoint analysis indicated equivalence to 100% IR2 in fracture detection for all datasets, with sensitivity losses in hemorrhage detection at 25% IR2. DLD (25% and 100%) maintained comparable sensitivity to 100% IR2. All comparisons demonstrated robust specificity. CONCLUSIONS: The evaluated algorithm enables high-quality, fully diagnostic CT scans at 25% of the initial radiation dose and improves patient care by reducing unnecessary radiation exposure.

[Usefulness of Copper Filter Addition and Potential for Dose Reduction in Hip-joint Radiography].

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.

Identifying risk factors of dose reduction or treatment discontinuation due to fatigue or gastrointestinal symptoms in patients receiving lenvatinib treatment for hepatocellular carcinoma.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In clinical practice, patients weighing less than 55 kg who start with a full dose will likely experience weight loss or discontinuation during treatment.

Dose reduction and discontinuation due to the combination of CDK4/6 inhibitors and endocrine drugs: a systematic review and meta-analysis.

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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Ultralow dose coronary calcium scoring CT at reduced tube voltage and current by using deep learning image reconstruction.

OBJECTIVE: To explore the potential of the deep learning reconstruction (DLR) for ultralow dose calcium scoring CT (CSCT) with simultaneously reduced tube voltage and current. METHODS: In this prospective study, seventy-five patients (group A) undergoing routine dose CSCT (120kVp/30mAs) were followed by a low dose (120kVp/20mAs) scan and another 81 (group B) were followed by an ultralow dose (80kVp/20mAs) scan. The hybrid iterative reconstruction was used for the routine dose data while the DLR for data of reduced dose. The calcium score and risk categorization were compared, where the correlation was evaluated using the intraclass correlation coefficient (ICC). The noise suppression performance of DLR was characterized by the contrast-to-noise ratio (CNR) between coronary arteries and pericoronary fat. RESULTS: The effective dose was 0.32 ± 0.03 vs. 0.48 ± 0.05 mSv for the two scans in group A and 0.09 ± 0.01 vs. 0.49 ± 0.05 mSv in group B. No significant difference was found on CACSs within either group (A: p = 0.10, ICC=0.99; B: p = 0.14, ICC=0.99), nor was it different on risk categorization (A: p = 0.32, ICC=0.99; B: p = 0.16, ICC=0.99). The DLR images exhibited higher CNR in both groups (A: p < 0.001; B: p = 0.001). CONCLUSIONS: The DLR allowed reliable calcium scoring in not only low dose CSCT with reduced tube current but ultralow dose CSCT with simultaneously reduced tube voltage and current, showing feasibility to be adopted in routine applications.

Dose reduced preoperative chemotherapy in older patients with resectable gastroesophageal cancer: A real-world data study.

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.

Semaglutide for the management of diabesity: The real-world experience.

BACKGROUND: Diabesity (diabetes as a consequence of obesity) has emerged as a huge healthcare challenge across the globe due to the obesity pandemic. Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials. However, more real-world data is needed to further improve the clinical practice. AIM: To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity. METHODS: We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States. Several parameters were analyzed including demographic information, the data on improvement of glycated hemoglobin (HbA1c), body weight reduction and insulin dose adjustments at 6 and 12 months, as well as at the latest follow up period. The data was obtained from the electronic patient records between January 2019 to May 2023. RESULTS: 106 patients (56 males) with type 2 diabetes mellitus (T2DM), mean age 60.8 ± 11.2 years, mean durations of T2DM 12.4 ± 7.2 years and mean semaglutide treatment for 2.6 ± 1.1 years were included. Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4 ± 24.6 kg to 99.9 ± 24.9 kg at 12 months and 96.8 ± 22.9 kg at latest follow up and HbA1c improvement from baseline of 82 ± 21 mmol/mol to 67 ± 20 at 12 months and 71 ± 23 mmol/mol at the latest follow up. An insulin dose reduction from mean baseline of 95 ± 74 units to 76.5 ± 56.2 units was also observed at the latest follow up. Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide. CONCLUSION: Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight, HbA1c and insulin doses without major adverse effects. Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.

Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy-Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single-Centre Experience.

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11).

Impact of breathing signal-guided dose modulation on step-and-shoot 4D CT image reconstruction.

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 mm 3 ${\rm mm}^3$ 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.

Effectiveness and Safety of Varying Doses of Linezolid With Bedaquiline and Pretomanid in Treatment of Drug-Resistant Pulmonary Tuberculosis: Open-Label, Randomized Clinical Trial.

BACKGROUND: Treatment of drug-resistant tuberculosis with bedaquiline-pretomanid-linezolid regimen has demonstrated good treatment efficacy. Given linezolid's toxicity profile, prudence suggests reconsidering its dose and duration. We determined the effectiveness and safety of structured dose reduction of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant (pre-XDR) or treatment-intolerant/nonresponsive multidrug-resistant (MDRTI/NR) pulmonary tuberculosis. METHOD: Adults with pre-XDR or MDRTI/NR pulmonary tuberculosis were enrolled in a multicenter, parallel-group, randomized clinical trial in India. Patients were randomized to 26 weeks of bedaquiline, pretomanid, and daily linezolid, at 600 mg for 26 weeks (arm 1); 600 mg for 9 weeks followed by 300 mg for 17 weeks (arm 2); or 600 mg for 13 weeks followed by 300 mg for 13 weeks (arm 3). Study end points included sustained cure, bacteriological failure, toxicity, and death. RESULTS: Of 403 patients enrolled, 255 (63%) were <30 years old, 273 (68%) had prior tuberculosis episodes, and 238 (59%) were malnourished. At the end of treatment, after excluding those with negative baseline cultures, cure was seen in 120 (93%), 117 (94%), and 115 (93%) in arms 1, 2, and 3 respectively. Myelosuppression seen in 85 patients each in arms 1 and 2 and 77 patients in arm 3, not significantly different. Peripheral neuropathy was noticed in 66 patients (30, 17, and 19 in arms 1, 2, and 3) at 10-26 weeks (P = .02). The linezolid dose was reduced because of toxicity in 13, 2, and 4 patients in arms 1, 2, and 3, respectively. CONCLUSIONS: In adults with pre-XDR or MDRTI/NR pulmonary tuberculosis, structured linezolid dose reduction to 300 mg/d is as effective as the standard 600-mg dose but with fewer cases of peripheral neuropathy when given with bedaquiline and pretomanid. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2021/03/032189).

Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience.

BACKGROUND: Pembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs. METHODS: We identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs. RESULTS: The median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs. CONCLUSIONS: Our study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.

Dose optimization in newborn abdominal radiography: Assessing the added value of additional filtration on radiation dose and image quality using an anthropomorphic phantom.

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.

Optimizing neurointerventional procedures: an algorithm for embolization coil detection and automated collimation to enable dose reduction.

Purpose: Monitoring radiation dose and time parameters during radiological interventions is crucial, especially in neurointerventional procedures, such as aneurysm treatment with embolization coils. The algorithm presented detects the presence of these embolization coils in medical images. It establishes a bounding box as a reference for automated collimation, with the primary objective being to enhance the efficiency and safety of neurointerventional procedures by actively optimizing image quality while minimizing patient dose. Methods: Two distinct methodologies are evaluated in our study. The first involves deep learning, employing the Faster R-CNN model with a ResNet-50 FPN as a backbone and a RetinaNet model. The second method utilizes a classical blob detection approach, serving as a benchmark for comparison. Results: We performed a fivefold cross-validation, and our top-performing model achieved mean mAP@75 of 0.84 across all folds on validation data and mean mAP@75 of 0.94 on independent test data. Since we use an upscaled bounding box, achieving 100% overlap between ground truth and prediction is not necessary. To highlight the real-world applications of our algorithm, we conducted a simulation featuring a coil constructed from an alloy wire, effectively showcasing the implementation of automatic collimation. This resulted in a notable reduction in the dose area product, signifying the reduction of stochastic risks for both patients and medical staff by minimizing scatter radiation. Additionally, our algorithm assists in avoiding extreme brightness or darkness in X-ray angiography images during narrow collimation, ultimately streamlining the collimation process for physicians. Conclusion: To our knowledge, this marks the initial attempt at an approach successfully detecting embolization coils, showcasing the extended applications of integrating detection results into the X-ray angiography system. The method we present has the potential for broader application, allowing its extension to detect other medical objects utilized in interventional procedures.

Key Component Analysis of the Time Toxicity Interaction of Five Antibiotics to Q67.

Antibiotics are considered as persistent emerging contaminants. The phenomenon of mixed exposure to the environment is a common occurrence causing serious harm to human health and the environment. Therefore, we employed enrofloxacin (ENR), chlortetracycline (CTC), methotrexate (TMP), chloramphenicol (CMP), and erythromycin (ETM) in this study. Nine treatments were designed using the uniform design concentration ratio (UDCR) method to systematically determine the toxicity of individual contaminants and their mixtures on Vibrio qinghaiensis sp.-Q67 through the time-dependent microplate toxicity assay. The combinatorial index (CI) method and the dose reduction index (DRI) were used to analyze the toxic interactions of the mixtures and the magnitude of the contribution of each component to the toxic interactions. The results showed that the toxicities of ENR, CTC, TMR, CMP, and ETM and their mixtures were time-dependent, with toxic effects being enhanced except when exposure time was prolonged. The types of toxic interactions in the ENR-CTC-TMR-CMP-ETM mixtures were found to be correlated with the proportion of each component's concentration, where the proportion of the components exerted the most significant influence. Through DRI extrapolation, it was determined that the primary components of the mixture exhibited a pronounced dependency on time. Specifically, at the 4 h mark, TMP emerged as the predominant component, gradually giving way to ENR as time advanced. Upon analyzing the frequency of mixture interactions under specified effects, the additive effect appeared most frequently (66.6%), while the antagonist effect appeared the least frequently (15.9%) among the nine rays.