Optimizing angular range in digital breast tomosynthesis: A phantom study investigating lesion detection across varied breast density and thickness.

PURPOSE: To determine the optimal angular range (AR) for digital breast tomosynthesis (DBT) systems that provides highest lesion visibility across various breast densities and thicknesses. METHOD: A modular DBT phantom, consisting of tissue-equivalent adipose and glandular modules, along with a module embedded with test objects (speckles, masses, fibers), was used to create combinations simulating different breast thicknesses, densities, and lesion locations. A prototype DBT system operated at four ARs (AR±7.5°, AR±12.5°, AR±19°, and AR±25°) to acquire 11 projection images for each combination, with separate fixed doses for thin and thick combinations. Three blinded radiologists independently assessed lesion visibility in reconstructed images; assessments were averaged and compared using linear mixed models. RESULTS: Speckle visibility was highest with AR±7.5° or AR±12.5°, decreasing with wider ARs in all density and thickness combinations. The difference between AR±7.5° and AR±12.5° was not statistically significant, except for the tube-side speckles in thin-fatty combinations (5.83 [AR±7.5°] vs. 5.39 [AR±12.5°], P = 0.019). Mass visibility was not affected by AR in thick combinations, while AR±12.5° exhibited the highest mass visibility for both thin-fatty and thin-dense combinations (P = 0.032 and 0.007, respectively). Different ARs provided highest fiber visibility for different combinations; however, AR±12.5° consistently provided highest or comparable visibility. AR±12.5° showed highest overall lesion visibility for all density and thickness combinations. CONCLUSIONS: AR±12.5° exhibited the highest overall lesion visibility across various phantom thicknesses and densities using a projection number of 11.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Investigating the impact of environmental enrichment on proteome and neurotransmitter-related profiles in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Accelerated fusion dynamics by recombinant human bone morphogenetic protein-2 following transforaminal lumbar interbody fusion, particularly in osteoporotic conditions.

BACKGROUND CONTEXT: Early fusion is crucial in interbody procedures to minimize mechanical complications resulting from delayed union, especially for patients with osteoporosis. Bone morphogenetic proteins (BMPs) are used in spinal fusion procedures; however, limited evaluation exists regarding time-to-fusion for BMP use, particularly in patients with osteoporosis. PURPOSE: To evaluate the difference in time-to-fusion after single-level transforaminal lumbar interbody fusion (TLIF) surgery between recombinant human bone morphogenetic protein-2 (rhBMP-2) usage and nonusage groups according to bone density. STUDY DESIGN: Retrospective single-center cohort study. PATIENT SAMPLE: This study enrolled 132 patients (mean age, 65.25±8.66; male patients, 40.9%) who underwent single-level TLIF for degenerative disorders between February 2012 and December 2021, with pre and postoperative computed tomography (CT). OUTCOME MEASURE: The interbody fusion mass and bone graft status on postoperative CT scans was obtained annually, and time-to-fusion was recorded for each patient. METHODS: The patients were divided into 2 groups based on rhBMP-2 use during the interbody fusion procedure. Patients were further divided into osteoporosis, osteopenia, and normal groups based on preoperative L1 vertebral body attenuation values, using cutoffs of 90 and 120 Hounsfield units. It was strictly defined that fusion is considered complete when a trabecular bone bridge was formed, and therefore, the time-to-fusion was measured in years. Time-to-fusion was statistically compared between BMP group and non-BMP groups, followed by further comparison according to bone density. RESULTS: The time-to-fusion differed significantly between BMP and non-BMP groups, with half of the patients achieving fusion within 2.5 years in the BMP group compared with 4 years in the non-BMP group (p<.001). The fusion rate varied based on bone density, with the maximum difference observed in the osteoporosis group, when half of the patients achieved fusion within 3 years in the BMP group compared to 5 years in the non-BMP group (p<.001). Subgroup analysis was conducted, revealing no significant associations between time-to-fusion and factors known to influence the fusion process, including age, gender, medical history, smoking and alcohol use, and medication history, except for rh-BMP2 use and bone density. CONCLUSIONS: RhBMP-2 usage significantly reduced time-to-fusion in single-level TLIF, especially in patients with osteoporosis. LEVEL OF EVIDENCE: Level III.

Association of Untreated Pre-surgical Depression With Pain and Outcomes After Spinal Surgery.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: Untreated pre-surgical depression may prolong post-surgical pain and hinder recovery. However, research on the impact of untreated pre-surgical depression on post-spinal surgery pain is lacking. Therefore, this study aimed to assess pre-surgical depression in patients and analyze its relationship with post-surgical pain and overall post-surgical outcomes. METHODS: We recruited 100 patients scheduled for lumbar spine surgery due to spondylolisthesis, degenerative lumbar disc diseases, and herniated lumbar disc diseases. Psychiatrists evaluated them for the final selection. We assessed the Beck Depression Inventory (BDI), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and EuroQoL 5 Dimensions (EQ-5D) scores, numerical back and leg pain scales, and medication dosage data collected before and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Ninety-one patients were included in this study; 40 and 51 were allocated to the control and depression groups, respectively. The pre- and post-surgical leg pain, back pain, and functional scores were not different. However, the depression group showed higher ODI and EQ-5D and lower JOA scores than the control group 3 months post-surgery. Partial correlation analysis revealed an inverse correlation between the JOA and BDI scores and a positive correlation between the EQ-5D and BDI scores at 3 months postoperatively. CONCLUSION: Untreated depression can prolong postoperative pain and hinder recovery. Detecting and treating depression in patients before spine surgery may improve their overall quality of life and functional recovery.

Mammographic density assessment: comparison of radiologists, automated volumetric measurement, and artificial intelligence-based computer-assisted diagnosis.

BACKGROUND: Artificial intelligence-based computer-assisted diagnosis (AI-CAD) is increasingly used for mammographic exams, and its role in mammographic density assessment should be evaluated. PURPOSE: To assess the inter-modality agreement between radiologists, automated volumetric density measurement program (Volpara), and AI-CAD system in breast density categorization using the Breast Imaging-Reporting and Data System (BI-RADS) density categories. MATERIAL AND METHODS: A retrospective review was conducted on 1015 screening digital mammograms that were performed in Asian female patients (mean age = 56 years ± 10 years) in our health examination center between December 2022 and January 2023. Four radiologists with two different levels of experience (expert and general radiologists) performed density assessments. Agreement between the radiologists, Volpara, and AI-CAD (Lunit INSIGHT MMG) was evaluated using weighted kappa statistics and matched rates. RESULTS: Inter-reader agreement between expert and general radiologists was substantial (k = 0.65) with a matched rate of 72.8%. The agreement was substantial between expert or general radiologists and Volpara (k = 0.64-0.67) with a matched rate of 72.0% but moderate between expert or general radiologists and AI-CAD (k = 0.45-0.58) with matched rates of 56.7%-67.0%. The agreement between Volpara and AI-CAD was moderate (k = 0.53) with a matched rate of 60.8%. CONCLUSION: The agreement in breast density categorization between radiologists and automated volumetric density measurement program (Volpara) was higher than the agreement between radiologists and AI-CAD (Lunit INSIGHT MMG).

Removal of PFAS by hydrotalcite: Adsorption mechanisms, effect of adsorbent aging, and thermal regeneration.

Layered double hydroxides (LDH) have been shown to be effective adsorbents, but their utility for the treatment of per- and polyfluoroalkyl substances (PFAS) in water has not been fully explored. In this study, the adsorption of 9 PFAS on hydrotalcite (HT), a type of LDH, was investigated using reaction solutions with environmentally relevant PFAS concentrations. The adsorption of individual PFAS by HT depended upon a range of factors, including the temperature used to pre-treat (i.e., calcine) the HT, aging conditions, and the presence of anions in the solution. HT calcined near 400 °C most effectively adsorbed PFAS, but its ability to adsorb PFAS was sensitive to storage conditions. The adsorption of CO2 and moisture from air, which likely resulted in the re-intercalation of CO32- into the interlayer regions of HT, was observed to reduce PFAS adsorption and may explain performance loss over time. The adsorption trend among 9 PFAS and the influence on this process by Cl-, NO3-, SO42-, and CO32- indicated that adsorption occurred via a combination of ion exchange, electrostatic attraction, and hydrophobic interactions, although the relative importance of each mechanism deserves further investigation. During this study, we also demonstrated for the first time that HT can be thermally regenerated at 400 °C without affecting its ability to adsorb PFOS and PFBA. Overall, our results suggest that HT may serve as an effective alternative for PFAS treatment.

Impact of sagittal and coronal pelvic tilt on hip subluxation in non-ambulatory flaccid neuromuscular scoliosis patients following spinal correction.

PURPOSE: To evaluate the actual change in clinical hip pain and hip migration after operation for non-ambulatory flaccid neuromuscular (NM) scoliosis and investigate whether there is an association between hip migration and coronal/sagittal pelvic tilt (CO-PT/SA-PT). PATIENTS AND METHODS: This retrospective, single-center, observational study evaluated a total of 134 patients with non-ambulatory flaccid neuromuscular scoliosis who underwent surgery performed by a single surgeon between 2003 and 2020, with at least 2 years of follow-up period. Operation procedures were conducted in two stages, beginning with L5-S1 anterior release followed by posterior fixation. Radiologic parameters were measured at preoperative, immediate postoperative, and last follow-up periods with clinical hip pain and clinical hip dislocation events. RESULTS: The significant improvements occurred in various parameters after correction surgery for NM scoliosis, containing Cobb's angle of major curve and CO-PT. However, Reimer's hip migration percentage (RMP) was increased on both side of hip (High side, 0.23 ± 0.16 to 0.28 ± 0.21; Low side, 0.20 ± 0.14 to 0.23 ± 0.18). Hip pain and dislocation events were also increased (Visual analog scale score, 2.5 ± 2.3 to 3.6 ± 2.6, P value < 0.05; dislocation, 6-12). Logistic regression analysis of the interactions between ΔRMP(High) and the change of sagittal pelvic tilt (ΔSA-PT) after correction reveals a significant negative association. (95% CI 1.003-1.045, P value = 0.0226). CONCLUSIONS: In cases of non-ambulatory flaccid NM scoliosis, clinical hip pain, and subluxation continued to deteriorate even after correction of CO-PT. There was a relationship between the decrease in SA-PT, and an increase in hip migration percentage on high side, indicating the aggravation of hip subluxation.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

Cost-effectiveness analysis of the 20-valent pneumococcal conjugate vaccine for the pediatric population in South Korea.

OBJECTIVES: To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%. METHODS: We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model. RESULTS: In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13. CONCLUSIONS: In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage.

Percutaneous distal chevron osteotomy is associated with lower immediate postoperative pain and a greater range of motion than the open technique: A prospective randomized study.

PURPOSE: The results of past studies comparing percutaneous techniques with traditional open techniques for hallux valgus are controversial. Therefore, this study aimed to compare the radiologic and clinical outcomes of percutaneous and open distal chevron osteotomies. METHODS: Seventy-one patients with mild to severe hallux valgus deformity were randomized to undergo percutaneous distal chevron osteotomy (percutaneous group, n = 36) or open distal chevron osteotomy (open group, n = 35) between October 2019 and September 2020. Radiological and clinical outcomes were assessed preoperatively and postoperatively. Outcome measures included the foot and ankle outcome score, foot functional index, visual analogue scale (VAS) scores for pain, range of motion (ROM) of the first metatarsophalangeal (MTP) joint, hallux valgus angle, intermetatarsal angle, and first metatarsal shortening. Additionally, the first metatarsal declination angle was measured to evaluate sagittal malunion. RESULTS: The mean first metatarsal declination angle decreased significantly at 12 months postoperatively in both groups (p = 0.021 and p < 0.001 in the percutaneous and open groups, respectively), and the decrement was significantly greater in the open group (p = 0.033). The mean VAS score for pain on postoperative day one was 4.2 ± 1.9 and 5.3 ± 1.7 in the percutaneous and open groups, respectively (p = 0.019). The mean ROM of the first MTP joint did not change significantly after surgery, from 72.5 ± 7.5 preoperatively to 71.0 ± 9.5 at 12 months postoperatively in the percutaneous group (p = 0.215); however, it decreased significantly from 70.6 ± 7.3 preoperatively to 63.4 ± 10.4 at 12 months postoperatively in the open group (p < 0.001). There were no significant differences between the groups regarding other clinical outcomes. CONCLUSION: The percutaneous group showed a lower immediate pain level at postoperative day 1 and better ROM of the first MTP joint at 12 months postoperatively.

A predictive model using MRI and clinicopathologic features for breast cancer recurrence in young women treated with upfront surgery.

OBJECTIVES: To identify preoperative breast MR imaging and clinicopathological variables related to recurrence and develop a risk prediction model for recurrence in young women with breast cancer treated with upfront surgery. METHODS: This retrospective study analyzed 438 consecutive women with breast cancer aged 35 years or younger between January 2007 and December 2016. Breast MR images before surgery were independently reviewed by breast radiologists blinded to patient outcomes. The clinicopathological data including patient demographics, clinical features, and tumor characteristics were reviewed. Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with recurrence. The risk prediction model for recurrence was developed, and the discrimination and calibration abilities were assessed. RESULTS: Of 438 patients, 95 (21.7%) developed recurrence after a median follow-up of 65 months. Tumor size at MR imaging (HR = 1.158, p = 0.006), multifocal or multicentric disease (HR = 1.676, p = 0.017), and peritumoral edema on T2WI (HR = 2.166, p = 0.001) were identified as independent predictors of recurrence, while adjuvant endocrine therapy (HR = 0.624, p = 0.035) was inversely associated with recurrence. The prediction model showed good discrimination ability in predicting 5-year recurrence (C index, 0.707 in the development cohort; 0.686 in the validation cohort) and overall recurrence (C index, 0.699 in the development cohort; 0.678 in the validation cohort). The calibration plot demonstrated an excellent correlation (concordance correlation coefficient, 0.903). CONCLUSION: A prediction model based on breast MR imaging and clinicopathological features showed good discrimination to predict recurrence in young women with breast cancer treated with upfront surgery, which could contribute to individualized risk stratification. CLINICAL RELEVANCE STATEMENT: Our prediction model, incorporating preoperative breast MR imaging and clinicopathological features, predicts recurrence in young women with breast cancer undergoing upfront surgery, facilitating personalized risk stratification and informing tailored management strategies. KEY POINTS: Younger women with breast cancer have worse outcomes than those diagnosed at more typical ages. The described prediction model showed good discrimination performance in predicting 5-year and overall recurrence. Incorporating better risk stratification tools in this population may help improve outcomes.

Effect of saline irrigation temperature difference on postoperative acute pain and hypothermia during biportal endoscopic spine surgery.

BACKGROUND: Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions. MATERIALS AND METHODS: Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36oC), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups. RESULTS: Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30 min after the operation was started. CONCLUSIONS: Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates.

Analytical Method Development and Dermal Absorption of 4-Amino-3-Nitrophenol (4A3NP), a Hair Dye Ingredient under the Oxidative or Non-Oxidative Condition.

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962-0.9993), accuracy (93.5-111.73%), and precision (1.7-14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 µL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 µg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 µg/cm2), respectively.

Long-Term Incidence of Adjacent Segmental Pathology After Minimally Invasive vs. Open Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the incidence of adjacent segmental pathology (ASP) following minimally invasive (MI) vs open transforaminal lumbar interbody fusion (TLIF) and to identify factors linked to ASP requiring reoperation. METHODS: This retrospective study reviewed the outcomes of patients who underwent MI-TLIF or open TLIF. Radiographic ASP (RASP) was evaluated using X-ray imaging to distinguish between degenerative changes, spondylolisthesis, and instability in the adjacent spinal segment. Clinical ASP (CASP) was assessed with the visual analog scale score for leg and back pain and the Oswestry disability index. Patient data were collected 1, 2, 5, and 10 years postoperatively. The timing and frequency of ASP reoperation were analyzed. RESULTS: Five years postoperatively, the RASP rate was 35.23% and 45.95% in the MI-TLIF and open TLIF groups. The frequency of CASP differed significantly between the MI-TLIF and open TLIF groups at 1 year postoperatively. The rates of RASP, CASP, and ASP necessitating reoperation were not significantly different 10 years postoperatively. Cranial facet violation significantly affected ASP in both groups. In the open TLIF group, preoperative adjacent segment disc degeneration significantly influenced ASP. CONCLUSION: The RASP rate at 5 years postoperatively and the CASP rate at 1 year postoperatively differed significantly between groups. There was no difference in the rate of ASP requiring reoperation. Cranial facet violation is a crucial driving factor for ASP after both surgical procedures.

Exploration of neuroanatomical characteristics to differentiate prodromal Alzheimer's disease from cognitively unimpaired amyloid-positive individuals.

Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer's disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at < 0.1, there were no differences in global and regional SUVR between CU A+ and prodromal AD groups. Regional volume differences between the two groups were observed in the amygdala, hippocampus, entorhinal cortex, insula, parahippocampal gyrus, and inferior temporal and parietal cortices. LASSO logistic regression model showed significant associations between prodromal AD and atrophy in the entorhinal cortex, inferior parietal cortex, both amygdalae, and left hippocampus. The mean SUVR in the right superior parietal cortex (beta coefficient = 0.0172) and its interaction with the regional volume (0.0672) were also selected in the LASSO model. The mean SUVR in the right superior parietal cortex was associated with an increased likelihood of prodromal AD (Odds ratio [OR] 1.602, p = 0.014), particularly in participants with lower regional volume (OR 3.389, p < 0.001). Only regional volume differences, not amyloid deposition, were observed between CU A+ and prodromal AD. The reduced volume in the superior parietal cortex may play a significant role in the progression to prodromal AD through its interaction with amyloid deposition in that region.

Use of a commercial artificial intelligence-based mammography analysis software for improving breast ultrasound interpretations.

OBJECTIVES: To evaluate the use of a commercial artificial intelligence (AI)-based mammography analysis software for improving the interpretations of breast ultrasound (US)-detected lesions. METHODS: A retrospective analysis was performed on 1109 breasts that underwent both mammography and US-guided breast biopsy. The AI software processed mammograms and provided an AI score ranging from 0 to 100 for each breast, indicating the likelihood of malignancy. The performance of the AI score in differentiating mammograms with benign outcomes from those revealing cancers following US-guided breast biopsy was evaluated. In addition, prediction models for benign outcomes were constructed based on clinical and imaging characteristics with and without AI scores, using logistic regression analysis. RESULTS: The AI software had an area under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI, 0.79-0.82) in differentiating between benign and cancer cases. The prediction models that did not include AI scores (non-AI model), only used AI scores (AI-only model), and included AI scores (integrated model) had AUROCs of 0.79 (95% CI, 0.75-0.83), 0.78 (95% CI, 0.74-0.82), and 0.85 (95% CI, 0.81-0.88) in the development cohort, and 0.75 (95% CI, 0.68-0.81), 0.82 (95% CI, 0.76-0.88), and 0.84 (95% CI, 0.79-0.90) in the validation cohort, respectively. The integrated model outperformed the non-AI model in the development and validation cohorts (p < 0.001 for both). CONCLUSION: The commercial AI-based mammography analysis software could be a valuable adjunct to clinical decision-making for managing US-detected breast lesions. CLINICAL RELEVANCE STATEMENT: The commercial AI-based mammography analysis software could potentially reduce unnecessary biopsies and improve patient outcomes. KEY POINTS: • Breast US has high rates of false-positive interpretations. • A commercial AI-based mammography analysis software could distinguish mammograms having benign outcomes from those revealing cancers after US-guided breast biopsy. • A commercial AI-based mammography analysis software may improve interpretations for breast US-detected lesions.

Safety and Efficacy of HL301 In Radiation Pneumonitis in Patients With Unresectable Non-Small Cell Lung Cancer Receiving Curative Concurrent Chemoradiotherapy: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 2a Clinical Trial.

PURPOSE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. METHODS AND MATERIALS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535). CONCLUSIONS: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.

Risk Factors and Characteristics of In-Hospital Falls After Spine Surgery: A Retrospective, Single-Center Cohort Study in the Republic of Korea.

Background: Falls after orthopaedic surgery can cause serious injuries, which lengthen hospital stays and increase medical expenses. This has prompted hospitals to implement various fall-prevention protocols. The aims of this study were to determine the incidence of in-hospital falls after spine surgery, to analyze the overall risk factors, to discern factors that have a major influence on falls, and to evaluate the effectiveness of the fall-prevention protocol that we implemented. Methods: This was a retrospective, single-center study including patients who underwent spine surgery from January 2011 to November 2021 at the National Health Insurance Service Ilsan Hospital (NHISIH) in Goyang, Republic of Korea. Reported falls among these patients were examined. Patient demographics; surgery type, date, and diagnosis; and fall date and time were evaluated. Results: Overall, 5,317 spine surgeries were performed, and 128 in-hospital falls were reported (overall incidence: 2.31%). From the multivariable analyses, older age and American Society of Anesthesiologists (ASA) score were identified as independent risk factors for in-hospital patient falls (multivariable adjusted hazard ratio [aHR] for age 70 to 79 years, 1.021 [95% confidence interval (CI), 1.01 to 1.031]; for age ≥80 years, 1.035 [1.01 to 1.06]; and for ASA score of 3, 1.02 [1.01 to 1.031]). Similar results were seen in the subgroup who underwent primary surgery. Within 2 weeks following surgery, the highest frequency of falls occurred at 3 to 7 days postoperatively. The lowest fall rate was observed in the evening (6 to 10 p.m.). Morbidities, including rib, spine, and extremity fractures, were recorded for 14 patients, but none of these patients underwent operative treatment related to the fall. The NHISIH implemented a comprehensive nursing care service in May 2015 and a fall protocol in May 2017, but the annual incidence rate did not improve. The fall rate was higher after thoracolumbar surgeries (2.47%) than after cervical surgeries (1.20%). Moreover, a higher fall rate was observed in thoracolumbar cases with a greater number of fusion levels and revision spine surgeries. Conclusions: Patients with advanced age, more comorbidities, a greater number of fusion levels, and revision surgeries and who are female are more vulnerable to in-hospital falls after spine surgery. Novel strategies that target these risk factors are warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.