Purpose: 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. Materials and Methods: 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. Results: 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. Conclusion 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.

Background: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using realworld data. Methods: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. Results: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88–1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62–0.97; P = 0.024). Conclusion As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71–0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73–0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Objective: To assess the influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida. Methods: A retrospective study was conducted using the Korean National Health Insurance Service database spanning from January 2005 to December 2019. All live-born offspring of nulligravida (n=3,685,817) were included. The maternal age was subdivided into the following subgroups: <25 years (n=153,818), 25-29 years (n=845,355), 30-34 years (n=1,738,299), 35-39 years (n=787,530), 40-44 years (n=151,519), and >44 years (n=9,296). Outcomes were assessed based on International Classification of Diseases-10 codes. Adjusted odds ratios (aOR) were calculated with the group of 25-29 years as a reference.Result Most congenital malformations showed an age dependent increase, but cleft lip and abdominal wall defect exhibited a U-shape curve, indicating an increase even in those <25 years old. Similarly, various disorders included in the neonatal composite outcomes from short-term outcomes showed aged dependent escalation. However, the preterm birth from the short-term outcome and most of the long-term developmental outcomes, except for motor developmental delay and Tics, showed a U-shaped pattern. The aOR of autism and cerebral palsy, showing the most obvious U-shaped curved in the long-term outcomes, was 1.50 (95% confidence interval [CI], 1.24-1.82) and 1.54 (95% CI, 1.17-2.03), respectively in the group >44 years old and 1.18 (95% CI, 1.11-1.25) and 1.19 (95% CI, 1.09-1.30) in <25 years old group. Conclusion Overall, an advanced maternal age has an age-dependent correlation with most congenital malformations and shortand long-term outcomes of neonates.

Purpose: Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. Materials and Methods: Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. Results: From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. Conclusion We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Background/Aims: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. Methods: Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebogroup (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. Results: Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological wellbeing (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. Conclusions The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.

Purpose: Cancer antigen 15-3 (CA15-3) is a serum tumor marker for breast cancer (BC) extensively used in clinical practice. CA15-3 is non-invasive, easily available, and a costeffective tumor marker for immediate diagnosis, monitoring and prediction of BC recurrence. We hypothesized that an elevation of CA15-3 may have prognostic impact in patients with early BC with normal serum CA15-3 level. Methods: This was a retrospective cohort study, which included patients with BC who received curative surgery at a comprehensive single institution between 2000 and 2016.CA15-3 levels from 0 to 30 U/mL were considered normal, and patients who had CA15-3 > 30 U/mL, were excluded from the study. Results: The mean age of study participants (n = 11,452) was 49.3 years. The proportion of participants with elevated CA15-3 ≥ 1 standard deviation (SD) compared with the previous examination during follow-up was 23.3% (n = 2,666). During the follow-up (median followup 5.8 years), 790 patients experienced recurrence. The fully-adjusted hazard ratio (HR) for recurrence comparing participants with stable CA15-3 level to subjects with elevated CA15-3 level was 1.76 (95% confidence interval [CI], 1.52–2.03). In addition, if the CA15-3was elevated ≥ 1 SD, the risk was much higher (HR, 6.87; 95% CI, 5.81–8.11) than in patients without elevated CA15-3 ≥ 1 SD. In sensitivity analysis, the recurrence risk was consistently higher in participants with elevated CA15-3 levels than in participants without elevated CA15-3 levels. The association between elevated CA15-3 levels and incidence of recurrence was observed in all subtypes and the association was stronger in patients with N+ than in patients with N0 stage (p-value for interaction < 0.01). Conclusion The results of the present study demonstrated that elevation of CA15-3 in patients with early BC and initial normal serum CA15-3 levels has a prognostic impact.

A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 μIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule.Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulininduced hypoglycemia in dogs.

Background: s: Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. Methods: Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. Results: Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0–3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46–1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30–1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49–3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27–1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18–1.96). Conclusion In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.

Purpose: In this study, we examined the impact of reconstruction using tissue expander insertion (TEI) on the risk of radiation dermatitis in patients undergoing postmastectomy radiotherapy (PMRT). Methods: Between August 2015 and March 2019, patients with breast cancer who had received systemic chemotherapy and PMRT were prospectively included. Skin parameters, including melanin, erythema, hydration, sebum, and elasticity, were measured using a multiprobe instrument at 6 time points: before the initiation of radiotherapy (pre-RT), at weeks 1, 3, and 5 during radiotherapy (weeks 1–5), and 1 and 3-month after radiotherapy (post-RT-1m and post-RT-3m). Patient-reported outcomes (PROs) were assessed at each time point.Changes in biophysical parameters and PRO were compared between patients with and without TEI (TEI+ vs. TEI−). Results: Thirty-eight patients, including 18 with TEI+ and 20 with TEI-, were analyzed. The pattern of time-course changes in biophysical parameters and PRO did not differ between TEI+ and TEI− patients. The melanin index was highest at post-RT-1m, while the erythema index was highest at week 5. At post-RT-3m, TEI+ patients presented higher melanin values than TEI- patients, with no statistical significance (coefficient, 47.9 vs. 14.2%; p = 0.07). In all patients, water content decreased throughout the measurement period. At post-RT-3m, TEI+ patients demonstrated a further decrease in water content, while the TEI- group nearly recovered the water content to pre-RT status (coefficient, −17.1, −2.5; p = 0.11). The sebum and elasticity levels were not altered by TEI. Conclusion In patients undergoing PMRT, TEI did not significantly affect the changing patterns of skin biophysical parameters and PRO during radiotherapy.