Samsung Medical Center Research Articles

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Biomechanical Comparison of 1.2-mm Suture Tape, 2.0-mm Suture Tape, and 0.5-mm Suture Using Various Arthroscopic Knot Techniques.

The biomechanical properties of the 1.2-mm suture tape have outperformed conventional sutures in previous studies. To compare the loop and knot security of 2 tape-type and 1 cord-type sutures using different arthroscopic knot techniques. Controlled laboratory study. The biomechanical characteristics of the 1.2-mm tape, 2.0-mm tape, and 0.5-mm No. 2 suture were compared using 4 different knot types: 2 sliding knots (Samsung Medical Center [SMC] and Tennessee) and 2 nonsliding knots (2-throw surgeon's and 2-throw square) with 2 and 3 additional reverse half-hitches on alternating posts (RHAPs) in a closed-loop system on a materials testing device. Each configuration was tested for loop security (maximal load applied between 0 and 3 mm of displacement), knot security (ultimate failure load), and failure mode with cyclical loading (30 N load for 20 cycles at 1 cycle per sec until failure). Loop and knot security among the configurations were compared using an analysis of variance. With 2 RHAPs, the 2.0-mm tape showed significantly greater loop security than the 1.2-mm tape and suture (P = .001). With 3 RHAPs, the loop security of the suture was significantly superior compared with the 1.2-mm tape (P = .010). Regarding knot security, with 2 RHAPs, the 2.0-mm tape was significantly better than the 1.2-mm tape and suture (P < .001), while with 3 RHAPs, the suture was significantly superior to the 1.2-mm tape (P = .012). Using a square knot with 2 RHAPs, the 2.0-mm tape had significantly greater loop security (P = .001) and better knot security (P = .001) to the 1.2-mm tape and suture. Using the Tennessee knot with 2 RHAPs, the 1.2-mm tape had less loop security (P = .011) and knot security (P = .005) than the suture. Using the SMC knot with 3 RHAPs, the 2.0-mm tape and suture were significantly superior in loop security (P = .001) and knot security (P < .001) to the 1.2-mm tape. There was no significant difference in the failure mode between tapes and sutures with 2 and 3 RHAPs. With 2 RHAPs, the 2.0-mm tape demonstrated greater resistance to suture loop displacement and better knot security compared with the 1.2-mm tape and suture. However, with 3 RHAPs, the 1.2-mm tape manifested weaker loop and knot security compared with the suture.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn’s disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn’s disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn’s disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0–6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0–6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48–26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with “cannot be passed” compared to the cases without stenosis (HR 12.34; 95% CI 1.66–91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Comprehensive Clinical Characterization of Decade-Long Survivors of Metastatic Breast Cancer.

Elucidating the clinical features of metastatic breast cancer (MBC) patients with an exceptionally favorable prognosis may offer insights to improve the survival of more typical patients. We collected comprehensive real-world data on clinicopathologic characteristics, treatments, and outcomes of 110 consecutive MBC patients who survived for over ten years from the clinical data warehouse of Samsung Medical Center. The cohort included 54 hormone receptor (HR)-positive/HER2-negative (HR+/HER2-), 21 HR+/HER2+, 16 HR-/HER2+, and 14 triple-negative breast cancer (TNBC) patients. The median age at MBC diagnosis was 48.5 years. Approximately 70% of patients initially had a single-organ metastasis. The most common site of metastasis was the lung (46.4%), followed by distant lymph nodes (37.3%). During a median follow-up of 14.6 years, the median duration of systemic therapy was 11, 8.4, 7.3, and 0.8 years in the HR+/HER2-, HR+/HER2+, HR-/HER2+, and TNBC subgroups, respectively. Seven HER2+ and ten TNBC patients received systemic treatment for less than two years and remained treatment-free for most of the follow-up period, suggesting a potential chance of cure. The TNBC subtype (p < 0.001) and local treatment with curative intent within 1 year of MBC diagnosis (p = 0.002) were significantly associated with long-term treatment-free survival. The survival of HER2+ MBC and TNBC patients, but not that of HR+/HER2- patients, plateaued approximately 13 years after MBC diagnosis. A small subset of patients with HER2+ MBC and metastatic TNBC may be curable with multimodality therapy. Prospective studies integrating clinical and genomic data may identify unique clinicogenomic features of MBC patients who can achieve durable disease control without prolonged chemotherapy.

Predicting the Risk of Sleep Disorders Using a Machine Learning-Based Simple Questionnaire: Development and Validation Study.

Sleep disorders, such as obstructive sleep apnea (OSA), comorbid insomnia and sleep apnea (COMISA), and insomnia are common and can have serious health consequences. However, accurately diagnosing these conditions can be challenging as a result of the underrecognition of these diseases, the time-intensive nature of sleep monitoring necessary for a proper diagnosis, and patients' hesitancy to undergo demanding and costly overnight polysomnography tests. We aim to develop a machine learning algorithm that can accurately predict the risk of OSA, COMISA, and insomnia with a simple set of questions, without the need for a polysomnography test. We applied extreme gradient boosting to the data from 2 medical centers (n=4257 from Samsung Medical Center and n=365 from Ewha Womans University Medical Center Seoul Hospital). Features were selected based on feature importance calculated by the Shapley additive explanations (SHAP) method. We applied extreme gradient boosting using selected features to develop a simple questionnaire predicting sleep disorders (SLEEPS). The accuracy of the algorithm was evaluated using the area under the receiver operating characteristics curve. In total, 9 features were selected to construct SLEEPS. SLEEPS showed high accuracy, with an area under the receiver operating characteristics curve of greater than 0.897 for all 3 sleep disorders, and consistent performance across both sets of data. We found that the distinction between COMISA and OSA was critical for accurate prediction. A publicly accessible website was created based on the algorithm that provides predictions for the risk of the 3 sleep disorders and shows how the risk changes with changes in weight or age. SLEEPS has the potential to improve the diagnosis and treatment of sleep disorders by providing more accessibility and convenience. The creation of a publicly accessible website based on the algorithm provides a user-friendly tool for assessing the risk of OSA, COMISA, and insomnia.

Etiology and prognosis of nephrocalcinosis according to gestational age in Korean children

BackgroundNephrocalcinosis (NC) is defined as deposition of calcium in renal tubules and interstitium and is highly related with prematurity and monogenic diseases. Recent studies have reported that NC might be a specific finding of underlying hereditary renal diseases. This study evaluated the risk factors, underlying monogenic causes, and clinical outcomes of NC in Korean children according to gestational age (GA).MethodsA total of 464 patients younger than 18 years who were diagnosed with NC by ultrasonography from January 2013 to December 2022 in Samsung Medical Center were enrolled. Medical record data of sex, GA, birth weight, underlying disease, medication history, ultrasonography and genetic analysis were reviewed retrospectively.ResultsThe male to female ratio was 1:0.98, and the mean age at first diagnosis of NC was 385 days. Approximately 62% of patients experienced confirmed resolution of NC after about one year. In comparison of the preterm (mean GA 28 weeks and 2 days) and full-term (mean GA 38 weeks and 2 days) groups, bronchopulmonary dysplasia, patent ductus arteriosus, and use of furosemide and vitamin D were more frequent in the preterm group. In the full-term group, a larger proportion of cases showed persistent NC without resolution and chronic kidney disease (CKD). Genetic analyses were performed in 56 patients, and the monogenic mutation rate was significantly higher in full-term children (OR 10.02, 95% CI [2.464–40.786], p = 0.001).ConclusionWhile the overall outcomes of pediatric NC are favorable, underlying monogenic causes should be studied, especially in full-term patients without known clinical risk factors.

Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study.

We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Impact of programmed death-ligand 1 (PD-L1) positivity on clinical and molecular features of patients with metastatic gastric cancer.

Programmed death-ligand 1 (PD-L1) is an important screening biomarker to select patients with gastric cancer (GC) for optimized treatment, including immune checkpoint inhibitors (ICI). In this single-institution retrospective cohort study, patients with metastatic GC with available PD-L1 results between October 2019 and September 2021 were identified by reviewing their electronic medical records. Genomic data were obtained from the Samsung Medical Center Clinical Sequencing Platform. Among the 399 patients, 276 (69%) had a PD-L1 combined positive score (CPS) ≥1, 155 (39%) had a CPS between 1 and 5, and 121 (30%) had a CPS ≥5. Of the 121 patients with CPS ≥5, 28 (23%) had a known etiology for "inflamed tumor," with Epstein-Barr virus (EBV) positivity (N = 11) or high tumor mutational burden (TMB) (N = 17), which included microsatellite instability (MSI) (N = 9). PD-L1 CPS ≥5 was observed in 11/11 (100%) patients with EBV positivity, 9/12 (75%) patients with MSI, and 17/33 (52%) patients with high TMB. For the 108 patients who received ICI therapy, CPS ≥5 was the only predictor significantly associated with survival in multivariable analyses, including TMB, MSI, or EBV. Objective response rate (ORR) was 49% in patients with CPS ≥5, 30% in patients with 1 ≤ CPS <5, and 19% in patients with CPS <1. Among the 31 responders to ICI therapy, 27 (87%) had a CPS of ≥1. Mutations in TET2, IRS2, DOT1L, PTPRT, and LRP1B were associated with a higher ORR (63%-100%), whereas MDC1 mutations were associated with a low ORR (22%). PD-L1 expression is an independent and sensitive biomarker for ICI therapy. Considering its significant association with several gene alterations, including PIK3CA mutations and MET amplification, combining ICI therapy with other targeted agents may be a promising therapeutic strategy for GC.

Clinical characteristics and survival analysis of cutaneous metastases in a single tertiary centre in Korea.

Cutaneous metastasis (CM) refers to the spread of malignancy to the skin. CM is perceived as an advanced stage. It might be the first sign of a primary cancer or an indicator of recurrence. To identify primary cancers associated with CMs and perform a survival analysis according to advanced stage of cutaneous metastasis at a single tertiary centre in Korea. A total of 219 patients from Samsung Medical Center from January 2009 to April 2020 were retrospectively analysed to identify cases with biopsy-proven CMs. According to advanced stage of metastasis, patients were divided into three stages, CM only (CMO), CM with lymph node metastasis (CM/LM) and CM with distant metastasis (CM/DM), to analyse clinical characteristics and survival rate. The most common CM from primary cancer was breast cancer, followed by lung cancer, stomach cancer, colorectal cancer and others. When all primary cancers were included, the median survival period was 4.82 years for the CMO stage, 2.15 years for the CM/LM stage and 0.80 years for the CM/DM stage, with a tendency to deteriorate with advancing stage. At 1- and 3-year after occurrence of CM, the CM/DM stage showed a significantly poorer survival rate than the other two stages. This study showed a median survival period of 22 months for CM patients overall. Breast cancer has greater accessibility to the skin than other cancers. Therefore, breast cancer can metastasize to the skin without involving lymph nodes or other sites.

Prediction Model for Postoperative Quality of Life Among Breast Cancer Survivors Along the Survivorship Trajectory From Pretreatment to 5 Years: Machine Learning-Based Analysis.

Breast cancer is the most common cancer and the most common cause of cancer death in women. Although survival rates have improved, unmet psychosocial needs remain challenging because the quality of life (QoL) and QoL-related factors change over time. In addition, traditional statistical models have limitations in identifying factors associated with QoL over time, particularly concerning the physical, psychological, economic, spiritual, and social dimensions. This study aimed to identify patient-centered factors associated with QoL among patients with breast cancer using a machine learning (ML) algorithm to analyze data collected along different survivorship trajectories. The study used 2 data sets. The first data set was the cross-sectional survey data from the Breast Cancer Information Grand Round for Survivorship (BIG-S) study, which recruited consecutive breast cancer survivors who visited the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, between 2018 and 2019. The second data set was the longitudinal cohort data from the Beauty Education for Distressed Breast Cancer (BEST) cohort study, which was conducted at 2 university-based cancer hospitals in Seoul, Korea, between 2011 and 2016. QoL was measured using European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 questionnaire. Feature importance was interpreted using Shapley Additive Explanations (SHAP). The final model was selected based on the highest mean area under the receiver operating characteristic curve (AUC). The analyses were performed using the Python 3.7 programming environment (Python Software Foundation). The study included 6265 breast cancer survivors in the training data set and 432 patients in the validation set. The mean age was 50.6 (SD 8.66) years and 46.8% (n=2004) had stage 1 cancer. In the training data set, 48.3% (n=3026) of survivors had poor QoL. The study developed ML models for QoL prediction based on 6 algorithms. Performance was good for all survival trajectories: overall (AUC 0.823), baseline (AUC 0.835), within 1 year (AUC 0.860), between 2 and 3 years (AUC 0.808), between 3 and 4 years (AUC 0.820), and between 4 and 5 years (AUC 0.826). Emotional and physical functions were the most important features before surgery and within 1 year after surgery, respectively. Fatigue was the most important feature between 1 and 4 years. Despite the survival period, hopefulness was the most influential feature on QoL. External validation of the models showed good performance with AUCs between 0.770 and 0.862. The study identified important factors associated with QoL among breast cancer survivors across different survival trajectories. Understanding the changing trends of these factors could help to intervene more precisely and timely, and potentially prevent or alleviate QoL-related issues for patients. The good performance of our ML models in both training and external validation sets suggests the potential use of this approach in identifying patient-centered factors and improving survivorship care.

Whole exome sequencing and clinical investigation of young onset dystonia: What can we learn?

BackgroundDystonia is a heterogeneous movement disorder involving various genetic backgrounds, and the implication of whole exome sequencing (WES) has yet to be clearly elucidated. In this study, we performed WES in Korean patients with young-onset dystonia. MethodsWe recruited patients with young-onset dystonia based on the new MDS dystonia classification at Samsung Medical Centre from 2015 to 2019. We excluded subjects diagnosed by single gene tests (GCH1, TOR1A, PANK2, PRRT2, and SGCE) or levodopa trials and subjects with focal or possible secondary dystonia. We performed WES in all enrolled subjects and confirmed the results with Sanger sequencing. ResultsOf the 43 patients, we detected 11 disease-causing variants, classified as either pathogenic or likely pathogenic, in 9 patients (20.9%). Generalized dystonia, infancy-childhood-onset dystonia, and other combined neurologic manifestations were related with PV/LPV. When we retrospectively reviewed the patients with PV/LPV, brain imaging was diagnostic in 3 subjects (HTRA1, SCL20A, and WDR45), clinical characteristics of paroxysmal presentation were observed in 2 (ADCY5 and ATP1A3), and microcephaly was noted in 1 patient (KMT2B). ConclusionClinical exome sequencing is helpful for the diagnosis of dystonia, especially for that with infancy-childhood onset, and generalized dystonia with other neurologic manifestations. Additionally, careful evaluations and examinations could provide information for selecting candidates for genetic testing.

Topographical Association Between Left Ventricular Strain and Brain Lesions in Patients With Acute Ischemic Stroke and Normal Cardiac Function.

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes. To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients. Data for pathologically diagnosed cHCC-CC patients (n = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review. Patients (n = 141) who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group. Seventy patients in two groups, respectively, were selected by 1:1 matching. Cumulative disease-free survival (DFS) and overall survival (OS) in the cHCC-CC group were significantly worse than in the HCC group both before and after matching. Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group (75.5% vs 33.3%, P < 0.001). Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group. In cHCC-CC subgroup analysis, frequency of locoregional therapies > 3, tumor size > 3 cm, and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis. Only a maximum tumor size > 3 cm was a predisposing factor for death. The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver. Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer

BackgroundCyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2− MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance.MethodsTissue was collected from 89 patients with HR+/HER2− MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival.ResultsNovel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C.ConclusionsWe identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET.Trial registrationClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Development and validation of a distress measurement for insulin injections among patients with diabetes

Insulin injections are stressful but necessary for people with diabetes. This study aimed to develop and validate the Distress of Self-Injection (DSI) scale for patients with diabetes aged ≥ 10 years. We created a questionnaire to evaluate DSI after examining each item following a literature review. The DSI scale with 20 questions in three domains (physical [4], psychosocial [7], and process [9]) was developed and tested at the Samsung Medical Center in Seoul, Korea, from April to September 2021. To verify structural validity, exploratory and confirmatory factor analyses (CFA) were conducted. Internal consistency was also calculated. To assess construct and criterion validity, the correlation between the DSI scale and Korean version of the Problem Areas in Diabetes (PAID-K) scale was obtained. Cronbach’s alpha varied from 0.69 to 0.87, and the DSI score was 0.90, demonstrating acceptable internal consistency. CFA fit indices (CFI = 0.980; RMSEA = 0.033) were favorable. DSI and pertinent PAID-K domains correlated strongly. For measuring self-injection distress, the DSI score had good accuracy. For patients with diabetes aged ≥ 10 years who self-inject insulin, the DSI was a viable and accurate method for quantifying discomfort associated with insulin injection. Health practitioners should use the DSI to communicate with patients about their suffering.

Interrater reliability of motor severity scales for hemifacial spasm

To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants’ motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee’s scale), clinical grading of spasm intensity (Chen’s scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc’s scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from “poor” to “moderate”; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee’s, Chen’s, and Tunc’s scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc’s scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc’s scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training.

Identification of potential biomarkers related to mesenchymal stem cell response in patients with Alzheimer’s disease

BackgroundPreclinical studies showed that mesenchymal stem cells (MSCs) ameliorate tau phosphorylation, amyloid-beta accumulation, and inflammation in Alzheimer’s disease (AD) mouse models via secretion of neurotrophic factors and cytokines. We aimed to identify CSF biomarkers that can be used to predict or monitor the response to MSCs in patients with AD.MethodsAD patients were injected with human umbilical cord blood-MSCs (n = 22) or placebo (n = 12). The cerebrospinal fluid (CSF) samples were collected at baseline, one day after the first injection, and one day after the third injection. The patients injected with MSCs were classified into good responder (GR) or poor responder (PR) groups based on the rate of changes in the ratio of total-tau and phosphorylated-tau in the CSF. We selected three typical participants in each group, and their CSF protein levels were analyzed using liquid chromatography/tandem mass spectrometry (LC–MS/MS).ResultsIn the LC–MS/MS analysis, 1,667 proteins were identified. Eleven proteins showed significant differences between the typical GR and PR at baseline. Based on their significance level and known functions, two proteins, reticulocalbin-3 (RCN3) and follistatin-related protein 3 (FSTL3), were selected as potential biomarkers to predict MSC response. A total of 173 proteins showed significant change one day after the third injection compared to the baseline in typical GR. We excluded 45 proteins that showed significant change after the third injection compared to the baseline in the typical PR. Based on their significance level and known function, four proteins, scrapie-responsive protein 1 (SCRG1), neural proliferation differentiation and control protein (NPDC1), apolipoprotein E (ApoE), and cystatin C (CysC), were selected as potential biomarker to monitor MSC response. Additionally, functional analysis revealed that the increased CSF proteins after the third injection compared to the baseline in the typical GR were associated with synaptogenesis.ConclusionsThis study identified two proteins (RCN3 and FSTL3) that may be potential biomarkers for predicting MSC response and four proteins (SCRG1, NPDC1, ApoE, CysC) that may be potential biomarkers for monitoring MSC response in patients with AD. Further studies are needed to validate our results.Trial registration Clinical Trials.gov, NCT02054208. Registered on 4 February 2014. Samsung Medical Center IRB File No.2017-04-025. Registered on 20 June 2017.

Clinical relevance of deep learning models in predicting the onset timing of cancer pain exacerbation

Cancer pain is a challenging clinical problem that is encountered in the management of cancer pain. We aimed to investigate the clinical relevance of deep learning models that predict the onset of cancer pain exacerbation in hospitalized patients. We defined cancer pain exacerbation (CPE) as the pain with a numerical rating scale (NRS) score of ≥ 4. We investigated the performance of the deep learning models using the Matthews correlation coefficient (MCC) with different input lengths and time binning. All the pain records were obtained from the electronic medical records of the hematology-oncology wards in a Samsung Medical Center between July 2016 and February 2020. The model was externally validated using the holdout method with 20% of the datasets. The most common type of cancer was lung cancer (n = 745, 21.7%), and the median CPE per day was 1.01. The NRS pain records showed circadian patterns that correlated with NRS pain patterns of the previous days. The correlation of the NRS scores showed a positive association with the closeness of the NRS pattern of the day with forecast date and size of time binning. The long short-term memory-based model exhibited a good performance by demonstrating 9 times the best performance and 8 times the second-best performance among 21 different settings. The best performance was achieved with 120 h input and 12 h bin lengths (MCC: 0.4927). Our study demonstrated the possibility of predicting CPE using deep learning models, thereby suggesting that preemptive cancer pain management using deep learning could potentially improve patients’ daily life.

Deep learning model for distinguishing Mayo endoscopic subscore 0 and 1 in patients with ulcerative colitis

The aim of this study was to address the issue of differentiating between Mayo endoscopic subscore (MES) 0 and MES 1 using a deep learning model. A dataset of 492 ulcerative colitis (UC) patients who demonstrated MES improvement between January 2018 and December 2019 at Samsung Medical Center was utilized. Specifically, two representative images of the colon and rectum were selected from each patient, resulting in a total of 984 images for analysis. The deep learning model utilized in this study consisted of a convolutional neural network (CNN)-based encoder, with two auxiliary classifiers for the colon and rectum, as well as a final MES classifier that combined image features from both inputs. In the internal test, the model achieved an F1-score of 0.92, surpassing the performance of seven novice classifiers by an average margin of 0.11, and outperforming their consensus by 0.02. The area under the receiver operating characteristic curve (AUROC) was calculated to be 0.97 when considering MES 1 as positive, with an area under the precision-recall curve (AUPRC) of 0.98. In the external test using the Hyperkvasir dataset, the model achieved an F1-score of 0.89, AUROC of 0.86, and AUPRC of 0.97. The results demonstrate that the proposed CNN-based model, which integrates image features from both the colon and rectum, exhibits superior performance in accurately discriminating between MES 0 and MES 1 in patients with UC.