Selective Binding of Tannic Acid-Conjugated Lipid Nanovesicles to Proline-Rich Proteins Enhances Transdermal Lipophilic-Antioxidant Delivery.

Tannic acid (TA) possesses a notable ability to adhere to proline-rich proteins that make up skin cells and the extracellular matrix (ECM) in the skin tissue. Drug carriers with this specific adhesion ability exhibit improved drug delivery efficiency on the skin. Taking advantage of this, this study presents skin-adhesive TA-conjugated lipid nanovesicles (TANVs) for enhanced transdermal antioxidant delivery. We found that TANVs exhibited selective intermolecular interactions with keratinocyte proline-rich proteins (KPRPs) and collagen that makes up skin cells by hydrogen bonding and van der Waals interactions, further enabling the strong bonding to macroscopic skin itself and ECM. We used vitamin E (α-tocopherol), which is known to effectively reduce oxidative stress but has limited skin penetration, as a drug to verify improved in vitro delivery and therapeutic efficacy. The evaluation revealed that the antioxidant-loaded TANVs exerted excellent scavenging effects against reactive oxygen species induced by ultraviolet light or peroxides in the skin, thereby enabling the development of an active drug delivery system for dermal therapy.

Scalp Cooling in Preventing Persistent Chemotherapy-Induced Alopecia: A Randomized Controlled Trial.

PURPOSE: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 µm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.

Long-term health outcomes by cancer diagnosed age among adolescent and young adult: multinational representative database.

BACKGROUND: The cancer experienced in adolescent and young adult (AYA) could disturb developmental changes and long-term life. The current AYA guidelines and research for survivorship were developed and reported according to the general age range of 15-39 years; however, expected life events vary by diagnosed age. We aimed to examine the social, psychological, and physical well-being of AYA cancer survivors by age at diagnosis using a multinational representative dataset focusing on age at diagnosis. METHODS: We conducted a cross-sectional study using the US and Korean National Health and Nutrition Examination Surveys from 2007 to 2018. Participants diagnosed with any cancer aged 15-39 years and were aged > 18 years at the survey year were defined as AYA cancer survivors. AYA were classified into three groups based on their diagnosed age: adolescent survivors (diagnosed between the ages of 15 and 19, n = 45), young adult survivors (diagnosed between the ages of 20 and 29, n = 238), and late young adult survivors (diagnosed between the ages of 30 and 39, n = 539). We also selected an age-, sex-, race-, and survey year-matched general population with 1:5 ratio among participants without cancer (N = 4110). RESULTS: The average age of the survey was 29.1, 43.7, and 48.7 years for AYA survivors diagnosed during adolescence, young adulthood, and late young adulthood, respectively. Adolescent survivors had more non-couple marital status (adjusted odds ratio (aOR), 1.34; 95% CI, 1.10-1.64) and unemployed (aOR, 1.30; 95% CI, 1.05-1.61) compared to late young adult survivors. Comparing with the matched general, adolescent survivors were more in poor general health (aOR, 4.65; 95% CI, 2.09-10.38) and unemployed (aOR, 2.17; 95% CI, 1.12-4.24) and late young adult survivors were more non-couple (aOR, 1.40; 95% CI, 1.05-1.86). CONCLUSION: This study provides evidence for future studies on long-term health, which may vary according to age at the time of diagnosis among AYA with cancer.

Current outcomes following upper and lower extremity arterial trauma from the National Trauma Data Bank.

OBJECTIVE: The modern treatments of trauma have changed in recent years. We aim to evaluate the factors associated with limb salvage and mortality after extremity arterial trauma, especially with respect to the type of conduit used in revascularization. METHODS: The National Trauma Data Bank was queried to identify patients with upper and lower extremity (UE and LE) arterial injuries between 2016 and 2020. The patients were stratified by the types of arterial repair. The primary outcome was in-hospital mortality. RESULTS: 8780 patients were found with 5054 (58%) UE and 3726 (42%) LE injuries. Eighty-three percent were men, and the mean age was 34 ± 15 years. Penetrating mechanism was the predominant mode of injury in both UEs and LEs (73% and 67%, respectively) with a mean injury severity score of 14 ± 8. For UEs, the majority underwent primary repair (67%, P < .001), whereas the remainder received either a bypass (20%) or interposition graft (12%). However, LEs were more likely to receive a bypass (52%, P < .00001) than primary repair or interposition graft (34% and 14%, respectively). Compared with the extremely low rates of amputation and mortality among UE patients (2% for both), LE injuries were more likely to result in both amputation (10%, P < .001) and death (6%, P < .001). Notably, compared with primary repair, the use of a prosthetic conduit was associated with a 6.7-fold increase in the risk of amputation in UE and a 2.4-fold increase in LE (P < .0001 for both). Synthetic bypasses were associated with a nearly 3-fold increase in return to the operating room (OR) in UE bypasses (P < .05) and a 2.4-fold increase in return to the OR in LE bypasses (P < .0001). CONCLUSIONS: In recent years, most extremity vascular trauma was due to penetrating injury with a substantial burden of morbidity and mortality. However, both limb salvage rates and survival rates have remained high. Overall, LE injuries more often led to amputation and mortality than UE injuries. The most frequently used bypass conduit was vein, which was associated with less risk of unplanned return to the OR and limb loss, corroborating current practice guidelines for extremity arterial trauma.

Development and Validation of the Facial Line Distress Scale for Lateral Canthal Lines: FINE-LCL.

Background: Currently available patient-reported outcome measures (PROM) have limited ability to assess unique issues related to lateral canthal lines (LCL). This study aimed to develop a PROM to assess the severity and psychosocial impact of LCL in afflicted patients. Methods: We conducted a cross-sectional survey at a tertiary hospital and two local clinics in Korea. Exploratory factor analysis was conducted to identify the underlying factor structure of the Facial Line Distress Scale for LCL (FINE-LCL), and the internal consistency and test-retest reliability were also examined. Results: We developed a questionnaire comprising 20 items in four domains. Coefficient alphas ranged from 0.94 to 0.97 for subdomains and 0.97 for the total questionnaire. The test-retest intraclass correlation coefficient ranged from 0.77 to 0.90. The FINE-LCL was moderately correlated with the appearance appraisal score and body image. Analysis of the accuracy of the FINE-LCL score in predicting severe LCL was characterized by an area under the curve of 0.79. Conclusions: FINE-LCL is a reliable, valid, and comprehensive PROM for the assessment of the severity of LCL and their associated distress.

Mammographic density changes after neoadjuvant chemotherapy in triple-negative breast cancer: Association with treatment and survival outcome.

PURPOSE: To investigate the association of mammographic breast density with treatment and survival outcomes in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC). METHODS: This retrospective study evaluated 306 women with TNBC who underwent NAC followed by surgery between 2010 and 2019. The baseline density and the density changes after NAC were evaluated. Qualitative breast density (a-d) was evaluated using the Breast Imaging Reporting and Data System. Quantitative breast density (%) was evaluated using fully automated software (the Laboratory for Individualized Breast Radiodensity Assessment) in the contralateral breast. Multivariable logistic regression analysis was used to evaluate the association between breast density and pathologic complete response (pCR), stratified by menopausal status. Cox proportional hazard regression analysis was used to evaluate the association among breast density, the development of contralateral breast cancer, and the development of locoregional recurrence and/or distant metastasis. RESULTS: Contralateral density reduction ≥10 % was independently associated with pCR in premenopausal women (odds ratio [OR], 2.5; p = 0.022) but not in postmenopausal women (OR, 0.9; p = 0.823). During a mean follow-up of 65 months, 10 (3 %) women developed contralateral breast cancer, and 68 (22 %) women developed locoregional recurrences and/or distant metastases. Contralateral density reduction ≥10 % showed no association with the occurrence of contralateral breast cancer (hazard ratio [HR], 3.1; p = 0.308) or with locoregional recurrence and/or distant metastasis (HR, 1.1; p = 0.794). CONCLUSION: In premenopausal women, a contralateral breast density reduction of ≥10 % after NAC was independently associated with pCR, although it did not translate into improved outcomes.

Emulating trial to evaluate the effectiveness of routine supportive care on mortality among cancer patients experiencing distress at the time of diagnosis.

INTRODUCTION: Few studies have evaluated the effectiveness of interventions for distress during cancer diagnosis on clinical outcomes in a real-world setting. We aimed to evaluate whether routine information and psychosocial support to patients experiencing distress at the time of diagnosis could decrease the risk of mortality within 1 and 3 years after diagnosis. MATERIAL AND METHODS: We conducted a retrospective cohort study of 4880 newly diagnosed cancer patients who reported distress scores of ≥4 using the tablet or kiosk-based screening between July 2014 and December 2017 at a university-affiliated cancer center in Seoul, South Korea. We performed an emulated target trial with two groups: those that received information and psychosocial support and those that did not. Cox proportional hazards models were used to identify the associations between information and psychosocial support and all-cause mortality. RESULTS: Of all the patients, 16.6 % had routine information and psychosocial support. The hazard ratio (HR) for one-year mortality comparing participants with information and psychosocial support to those without it were 0.73 (95 % confidence interval (CI) = 0.54, 0.99). Age < 50 and 50 - <60 group had a stronger effect of information and psychosocial support on reducing mortality within one-year than these in age ≥ 60 (p for interaction = 0.03). In terms of three-year mortality, the HR comparing participants with information and psychosocial support to those without it was 0.93 (95 % CI = 0.76, 1.14). CONCLUSION: This large-scale real-world study suggests that timely psychosocial care benefits newly diagnosed cancer patients who had distress during pre-treatment period.

Psychometric validation of the Functional Assessment of Cancer Therapy-Endometrial among endometrial cancer patients.

OBJECTIVE: To evaluate a psychometric validation of the endometrial cancer subscales (EnCS) in the Functional Assessment of Cancer Therapy-Endometrial (FACT-EN) among patients with endometrial cancer. METHODS: This cross-sectional study was conducted at a tertiary university-based hospital in South Korea between April and October 2022. Participants completed a survey questionnaire that included the FACT-EN. Exploratory and confirmatory factor analyses (EFA, CFA) and the reliability were measured using the intraclass correlation coefficient (ICC) under a two-way mixed model. Pearson's correlations were used to evaluate the validity. We also tested known-group validity. RESULTS: In total, 240 patients with endometrial cancer participated in the survey. In EFA, we found EnCS included four domains. In CFA, four-factor solution model was good: CFI = 0.659; SRMR = 0.066, and RMSEA = 0.073. The mean (SD) of total score of FACT-EN was 122.84 (23.58). The floor and ceiling effects were 0.4% and 0.4%, respectively. Cronbach's α coefficients for the five scales of the EnCS ranged from 0.78 to 0.91. The ICC of EnCS was 0.76. The convergent and discriminant validity of EnCS was acceptable. In the group analysis, older age and lower ECOG performance scores were associated with higher EnCS scores. The stomach and vaginal domains in EnCS were higher in patients who had completed treatment for more than 1 year compared to those who were still undergoing treatment. CONCLUSIONS: FACT-EN has demonstrated its validity as an assessment tool with significant implications for capturing various symptoms in patients with endometrial cancer.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists.

OBJECTIVE: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). RESULTS: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training (P = 0.002). CONCLUSION: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Assessment of potential ecological risk for polycyclic aromatic hydrocarbons in urban soils with high level of atmospheric particulate matter concentration.

Polycyclic aromatic hydrocarbons (PAHs) are known to be representative carcinogenic environmental pollutants with high toxicity. However, information on the potential ecological and environmental risks of PAH contamination in soil remains scarce. Thus, this study was evaluated the potential ecological risks of PAHs in soils of five Korean areas (Gunsan (GS), Gwangju, Yeongnam, Busan, and Gangwon) using organic carbon (OC)-normalized analysis, mean effect range-median quotient (M-ERM-Q), toxic equivalent quantity (TEQ) analysis, and risk quotient (RQ) derived by the species sensitivity distribution model. In this study, atmospheric particulate matter has a significant effect on soil pollution in GS through the presence of hopanes and the similar pattern of PAHs in soil and atmospheric PAHs. From analysis of source identification, combustion sources in soils of GS were important PAH sources. For PAHs in soils of GS, the OC-normalized analysis, M-ERM-Q, and TEQ analysis have 26.78 × 105 ng/g-OC, 0.218, and 49.72, respectively. Therefore, the potential ecological risk assessment results showed that GS had moderate-high ecological risk and moderate-high carcinogenic risk, whereas the other regions had low ecological risk and low-moderate carcinogenic risk. The risk level (M-ERM-Q) of PAH contamination in GS was similar to that in Changchun and Xiangxi Bay in China. The Port Harcourt City in Nigeria for PAH has the highest risk (M-ERM-Q = 4.02 and TEQ = 7923). Especially, compared to China (RQPhe =0.025 and 0.05), and Nigeria (0.059), phenanthrene showed the highest ecological risk in Korea (0.001-0.18). Korea should focus on controlling the release of PAHs originating from the PM in GS.

Development and Validation of Facial Line Distress Scale for Forehead Lines: FINE-FL.

BACKGROUND: Forehead lines (FL) are one of the main signs of aging. Traditional tools to measure FL have limited ability to evaluate the multidimensional impact of these lines on appearance, confidence, and psychological and social relationships. OBJECTIVES: We developed and validated the Facial Line Distress Scale-Forehead Lines (FINE-FL) to evaluate the severity and psychosocial distress associated with FL. METHODS: We conducted a cross-sectional survey for FINE-FL psychometric validation at a tertiary hospital and 2 local clinics in Korea. First, a preliminary item pool for the FINE-FL was developed through a qualitative interview based on literature reviews and expert consultations. Second, cognitive interviews and a pilot test were conducted to evaluate comprehension, ease of response, acceptability of terminology, phrasing, and response options. FINE-FL consisted of 26 items. In this study, exploratory factor analysis was conducted to identify the underlying factor structure of the FINE-FL, and internal consistency and test-retest reliability were also examined. RESULTS: We found 21 items in 4 domains. The model fit was good. Coefficient αs ranged from 0.89 to 0.95 for subdomains and 0.96 for the total. The FINE-FL was moderately correlated with the appearance appraisal score. On the test-retest, the range of the intraclass correlation coefficient was 0.65 to 0.79. CONCLUSIONS: FINE-FL is a reliable, valid, and comprehensive patient-reported outcome measure for assessing FL severity and distress. This will be helpful in determining a patient's eligibility for inclusion in a study and measuring primary or secondary effectiveness endpoints for forehead line treatment.

Problem Solving MRI to Reduce False-Positive Biopsy Related to Breast US: Conductivity vs. DWI vs. Abbreviated Contrast-Enhanced MRI.

BACKGROUND: While breast ultrasound (US) is a useful tool for diagnosing breast masses, it can entail false-positive biopsy results because of some overlapping features between benign and malignant breast masses and subjective interpretation. PURPOSE: To evaluate the performance of conductivity imaging for reducing false-positive biopsy results related to breast US, as compared to diffusion-weighted imaging (DWI) and abbreviated MRI consisting of one pre- and one post-contrast T1-weighted imaging. STUDY TYPE: Prospective. SUBJECTS: Seventy-nine women (median age, 44 years) with 86 Breast Imaging Reporting and Data System (BI-RADS) category 4 masses as detected by breast US. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted turbo spin echo sequence, DWI, and abbreviated contrast-enhanced MRI (T1-weighted gradient echo sequence). ASSESSMENT: US-guided biopsy (reference standard) was obtained on the same day as MRI. The maximum and mean conductivity parameters from whole and single regions of interest (ROIs) were measured. Apparent diffusion coefficient (ADC) values were obtained from an area with the lowest signal within a lesion on the ADC map. The performance of conductivity, ADC, and abbreviated MRI for reducing false-positive biopsies was evaluated using the following criteria: lowest conductivity and highest ADC values among malignant breast lesions and BI-RADS categories 2 or 3 on abbreviated MRI. STATISTICAL TESTS: One conductivity parameter with the maximum area under the curve (AUC) from receiver operating characteristics was selected. A P-value <0.05 was considered statistically significant. RESULTS: US-guided biopsy revealed 65 benign lesions and 21 malignant lesions. The mean conductivity parameter of the single ROI method was selected (AUC = 0.74). Considering conductivity (≤0.10 S/m), ADC (≥1.60 × 10-3 mm2 /sec), and BI-RADS categories 2 or 3 reduced false-positive biopsies by 23% (15 of 65), 38% (25 of 65), and 43% (28 of 65), respectively, without missing malignant lesions. DATA CONCLUSION: Conductivity imaging may show lower performance than DWI and abbreviated MRI in reducing unnecessary biopsies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/ß-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/ß-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3ß (GSK3ß), and ß-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

Medial arterial calcification score is associated with increased risk of major limb amputation.

OBJECTIVE: The pedal medial arterial calcification (MAC) score has been associated with risk of major limb amputation in patients with chronic limb-threatening ischemia. This study aimed to validate the pedal MAC scoring system in a multi-institutional analysis to validate its usefulness in limb amputation risk prediction. METHODS: A multi-institution, retrospective study of patients who underwent endovascular or open surgical infrainguinal revascularization for chronic limb-threatening ischemia was performed. MAC scores of 0 to 5 were assigned based on visible calcified arteries on foot X ray then trichotomized (0-1, 2-4, 5) for analysis. The primary outcome was major limb amputation at 6 months. Adjusted Kaplan-Meier models were used to analyze time-to-major amputation across groups. RESULTS: There were 176 patients with 184 affected limbs (mean age, 66 years; 61% male; 60% White), of whom 97% presented with a wound. The MAC score was 0 in 41%, 1 in 9%, 2 in 13%, 3 in 11%, 4 in 13%, and 5 in 13% of the limbs. There were 26 major amputations (14%) and 16 deaths (8.7%) within 6 months. Patients with MAC 5 had a significantly higher risk of major limb amputation than both the 0 to 1 and 2 to 4 groups (P = .001 and P = .044, respectively), and lower overall amputation-free survival (log-rank P = .008). CONCLUSIONS: Pedal MAC score is a reproducible and generalizable measure of inframalleolar arterial disease that can be used with Wound, Ischemia, and foot Infection staging to predict major limb amputation in patients with chronic limb-threatening ischemia.

Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors.

BACKGROUND: The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. METHODS: We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. RESULTS: Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00-1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07-1.40), and lower household income (aOR 1.16, 95% CI 1.01-1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15-1.60) and have hypertension (aOR 1.18, 95% CI 1.03-1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05-1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. CONCLUSIONS: This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.

Discovery, verification, and validation of walnut protein marker peptides using LC-MS approaches.

A key requirement of liquid chromatography-mass spectrometry (LC-MS)-based allergenic food protein analysis methods is to use protein marker peptides with good analytical performances in LC-MS analysis of commercial processed foods. In this study, we developed a multi-stage walnut protein marker peptide selection strategy involving marker peptide discovery and verification and LC-MS validation of chemically equivalent stable isotope-labeled peptides. This strategy proposed three walnut protein marker peptides, including two new marker peptides. Our LC-MS-based walnut protein analysis method using the three stable isotope-labeled peptides showed acceptable linearity (R2 >0.99), matrix effects (coefficient of variation <±15%), sensitivity (limit of detection >0.3 pg/µL, limit of quantification >0.8 pg/µL), recovery (85.1-103.4%), accuracy, and precision (coefficient of variation <10%). In conclusion, our multi-stage marker peptide selection strategy effectively selects specific protein marker peptides for sensitive detection and absolute quantification of walnut proteins in LC-MS analysis of commercial processed foods.

Local Treatment of Hepatocellular Carcinoma with Oligometastases: A Systematic Review and Meta-Analysis.

Although recent studies have shown favorable results after local treatment for oligometastases, the clinical decision of applying local treatment for oligometastatic hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aimed to investigate the benefits of local treatment for HCC oligometastases. Pubmed, Embase, Medline, and the Cochrane library were searched for studies until 1 May 2022. Clinical studies involving at least five cases of HCC oligometsatases treated with local modalities were included. The primary endpoint was overall survival (OS). The benefit of local treatment was assessed as the pooled odds ratio (OR) among comparative series, and the pooled OS percentile was calculated from all studies including patients treated with local treatment. Complications of grade ≥ 3 were assessed subjectively. A total of 10 studies involving 527 patients were included. Radiotherapy and radiofrequency ablation (RFA) were mainly performed (six and five studies) as local modalities treating oligometastases. Pooled OR of comparative series favored the use of local treatment (4.664, 95% confidence interval [CI]: 2.595-8.380, p < 0.001, I2: ~0.0%). Including all cohorts with patients who underwent local treatment, pooled rates of 1-year OS were 71.8% (95% CI: 59.0-81.9; I2 = 81.5%), and pooled 2-year OS were 43.3% (95% CI: 29.1-59.6; I2 = 85.4%). Except for temporal or pre-existing toxicities, grade ≤ 3 complications were reported less than 10% in most studies, although common toxicities include pneumothorax and hematologic deficiency after RFA and radiotherapy, respectively. Grade 5 toxicity has not yet been reported. This systematic review supports the application of local treatment for treating HCC oligometastases.

Prediction of Tumor Progression During Neoadjuvant Chemotherapy and Survival Outcome in Patients With Triple-Negative Breast Cancer.

OBJECTIVE: To investigate the association of clinical, pathologic, and magnetic resonance imaging (MRI) variables with progressive disease (PD) during neoadjuvant chemotherapy (NAC) and distant metastasis-free survival (DMFS) in patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: This single-center retrospective study included 252 women with TNBC who underwent NAC between 2010 and 2019. Clinical, pathologic, and treatment data were collected. Two radiologists analyzed the pre-NAC MRI. After random allocation to the development and validation sets in a 2:1 ratio, we developed models to predict PD and DMFS using logistic regression and Cox proportional hazard regression, respectively, and validated them. RESULTS: Among the 252 patients (age, 48.3 ± 10.7 years; 168 in the development set; 84 in the validation set), PD was occurred in 17 patients and 9 patients in the development and validation sets, respectively. In the clinical-pathologic-MRI model, the metaplastic histology (odds ratio [OR], 8.0; P = 0.032), Ki-67 index (OR, 1.02; P = 0.044), and subcutaneous edema (OR, 30.6; P = 0.004) were independently associated with PD in the development set. The clinical-pathologic-MRI model showed a higher area under the receiver-operating characteristic curve (AUC) than the clinical-pathologic model (AUC: 0.69 vs. 0.54; P = 0.017) for predicting PD in the validation set. Distant metastases occurred in 49 patients and 18 patients in the development and validation sets, respectively. Residual disease in both the breast and lymph nodes (hazard ratio [HR], 6.0; P = 0.005) and the presence of lymphovascular invasion (HR, 3.3; P < 0.001) were independently associated with DMFS. The model consisting of these pathologic variables showed a Harrell's C-index of 0.86 in the validation set. CONCLUSION: The clinical-pathologic-MRI model, which considered subcutaneous edema observed using MRI, performed better than the clinical-pathologic model for predicting PD. However, MRI did not independently contribute to the prediction of DMFS.

Correlation between standardized uptake value of 18F-FDG PET/CT and conductivity with pathologic prognostic factors in breast cancer.

We investigated the correlation between standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors' heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman's correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status.