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Mitotane is an adrenolytic drug that exhibits therapeutic effects within a narrow target range (14–20 μg/dL). Various complications develop if the upper limit is exceeded. We present the case of a 5-year-old girl with breast development, acne, and pubic hair who was diagnosed with an adrenal mass that was subsequently excised. The pathological finding was adrenocortical carcinoma with a high risk of malignancy, and adjuvant therapy (combined mitotane and radiation therapy) was recommended. Mitotane was initiated at a low dose to allow monitoring of the therapeutic drug level, and high-dose hydrocortisone was also administered. However, the patient exhibited elevated adrenocorticotropic hormone levels and vague symptoms such as general weakness and difficulty concentrating. It was important to determine if these symptoms were signs of the neurological complications that develop when mitotane level is elevated. Encephalopathy progression and pubertal signs appeared 6 months after diagnosis, induced by high mitotane level. The mitotane decreased to subtherapeutic level several months after its discontinuation, at which time endocrinopathy (central hypothyroidism, hypercholesterolemia, and secondary central precocious puberty) developed. The case shows that low-dose mitotane can trigger neurological and endocrinological complications in a pediatric patient, indicating that the drug dose should be individualized with frequent monitoring of the therapeutic level.

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Palisading encapsulated neuroma is a rare, benign, cutaneous nerve sheath tumor. It usually occurs as an asymptomatic solitary skin-colored papule and commonly affects the nose and cheeks. Sometimes, it involves other sites, including the shoulder, upper arm, and trunk, but rarely involves the oral mucosa, including that of the lip. In our case, a 63-year-old female patient complained of a pinkish rubbery nodule on her lower lip. Histopathologic examination demonstrated a well-circumscribed nodule encapsulated by connective tissue stroma in the dermis. The nodule consisted of palisading spindle-shaped tumor cells with wavy and basophilic nuclei. The cells were arranged in streaming fascicles with multiple clefts and were strongly positive for S-100 proteins. To our knowledge, only three cases of palisading encapsulated neuroma on the lower lip have been reported in the Korean literature. Herein, we report a rare case of an oral palisaded encapsulated neuroma.

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg(-1) IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg(-1) IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...

Background To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. Materials and methods We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. Results The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P, Highlights • Multicenter retrospective study of salvage WBRT for recurrent brain metastasis. • Subsequent use of systemic treatment after salvage WBRT showing better OS. • Limitations of previous graded prognostic assessments for recurrent brain metastasis. • Novel RPA classification consisting of four simple clinical factors predicts OS.

The smoking status of kidney transplant recipients and living donors has not been explored concurrently in a prospective study, and the synergistic adverse impact on outcomes remains uncertain. The self-reported smoking status and frequency were obtained from recipients and donors at the time of kidney transplantation in a prospective multicenter longitudinal cohort study (NCT02042963). Smoking status was categorized as "ever smoker" (current and former smokers collectively) or "never smoker." Among 858 eligible kidney transplant recipients and the 858 living donors, 389 (45.3%) and 241 (28.1%) recipients were considered ever smokers at the time of transplant. During the median follow-up period of 6 years, the rate of death-censored graft failure was significantly higher in ever-smoker recipients than in never-smoker recipients (adjusted HR, 2.82; 95% CI 1.01-7.87; P = 0.048). A smoking history of >20 pack-years was associated with a significantly higher rate of death-censored graft failure than a history of ≤20 pack-years (adjusted HR, 2.83; 95% CI 1.19-6.78; P = 0.019). No donor smoking effect was found in terms of graft survival. The smoking status of the recipients and donors or both did not affect the rate of biopsy-proven acute rejection, major adverse cardiac events, all-cause mortality, or post-transplant diabetes mellitus. Taken together, the recipient's smoking status before kidney transplantation is dose-dependently associated with impaired survival.

Upon injury, inflammation and repair processes are orchestrated to maintain tissue homeostasis. The Wnt ligands play essential roles in cell differentiation and proliferation for tissue repair and regeneration. It is increasingly clear that Wnt ligands play crucial immune-modulatory roles in inflammatory diseases. It is predicted that comprehensive research regarding the cross-talk between nonimmune and immune cells in tissue injury and repair will flourish. The Wnt system and immune system interaction will be critical to understanding tissue injury, inflammation, and repair. In this study, we will first introduce the Wnt system and review the role of the Wnt system in tissue regeneration and repair. We will review the previous literature regarding how the Wnt ligands regulate the immune system. Next, we will discuss the current and future perspectives of Wnt ligands to target cancer and other immunological diseases. Finally, we will discuss the quintessential Wnt antagonist Dickkopf1 as an immunomodulatory ligand.

We evaluated the temporal trend of preemptive kidney transplantation (KT) and the effect of pretransplant dialysis duration on post-transplant outcomes. This was a nationwide cohort study of the first-time 3392 living donor KT (LDKT) recipients (2014-2019). The annual changes in proportion of preemptive KT, factors associated with preemptive KT, and post-transplant outcomes were analyzed. Preemptive KT was performed in 816 (24.1%) patients. Annual trend analysis revealed gradual decrease in preemptive KT over time (P = 0.042). Among the underlying causes of preemptive KT, the proportion of diabetes increased and that of glomerulonephritis decreased during the study period. Glomerulonephritis as the primary renal disease was a predictor of preemptive KT. Patients with pretransplant dialysis >6 months showed increased graft failure risk than preemptive KT in the subdistribution of hazard model for competing risk (adjusted hazard ratio [aHR], 2.53; 95% confidence interval [CI], 1.09-5.87; P = 0.031) and in propensity score-matched analysis (aHR, 2.45; 95% CI, 1.02-5.92; P = 0.034); however, pretransplant dialysis ≤6 months showed comparable graft survival with preemptive KT in both analyses. Preemptive KT declined over successive years, associated with an increase in diabetes and a decrease in glomerulonephritis as underlying causes of KT. Short period of dialysis less than 6 months does not affect graft survival compared with preemptive KT; however, longer dialysis decreases graft survival.

Oncogenic KRASG12D induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN), and drives pancreatic ductal adenocarcinoma (PDAC). Angiopoietin-like 4 (ANGPTL4) is known to be involved in the regulation of cancer growth and metastasis. However, whether ANGPTL4 affects KRASG12D-mediated ADM and early PDAC intervention remains unknown. In the current study, we investigated the role of ANGPTL4 in KRASG12D-induced ADM, PanIN formation, and PDAC maintenance. We found that ANGPTL4 was highly expressed in human and mouse ADM lesions and contributed to the promotion of KRASG12D-driven ADM in mice. Consistently, ANGPTL4 rapidly induced ADM in three-dimensional culture of acinar cells with KRAS mutation and formed ductal cysts that silenced acinar genes and activated ductal genes, which are characteristic of in vivo ADM/PanIN lesions. We also found that periostin works as a downstream regulator of ANGPTL4-mediated ADM/PDAC. Genetic ablation of periostin diminished the ADM/PanIN phenotype induced by ANGPTL4. A high correlation between ANGPTL4 and periostin was confirmed in human samples. These results demonstrate that ANGPTL4 is critical for ADM/PanIN initiation and PDAC progression through the regulation of periostin. Thus, the ANGPTL4/periostin axis is considered a potential target for ADM-derived PDAC.

BACKGROUND Autonomic dysreflexia (AD) can be a life-threatening condition in patients with spinal cord injury. It is important to prevent bladder overdistension in these patients as it may trigger AD. Sensation-dependent bladder emptying (SDBE), as a method of bladder management, improves the quality of life and allows physiologic voiding. In this study, we report disruption of the SDBE habit after bladder overdistension leading to AD with chest pain. CASE SUMMARY A 47-year-old male with a diagnosis of C4 American Spinal Cord Injury Association impairment scale A had been emptying his bladder using the clean intermittent catheterization method with an itchy sensation in the nose as a sensory indication for a full bladder for 23 years, and the usual urine volume was about 300-400 mL. At the time of this study, the patient had delayed catheterization for approximately five hours. He developed severe abdominal pain and headache and had to visit the emergency room for bladder overdistension (800 mL) and a high systolic blood pressure (205 mmHg). After control of AD, a hypersensitive bladder was observed despite using anticholinergic agents. The sensation indicating bladder fullness changed from nose itching to pain in the abdomen and precordial area. Moreover, the volume of the painful bladder filling sensation became highly variable and was noted when the bladder urine volume exceeded only 100 mL. The patient refused intermittent clean catheterization. Finally, a cystostomy was performed, which relieved the symptoms. CONCLUSION Patients using physiologic feedback, such as SDBE, for bladder management are recommended to avoid bladder overdistension.

Objective To analyze the relationship between body composition, metabolic parameters, and bone mineral density (BMD) according to sex and the degree of obesity in children and adolescents. Methods A total of 236 subjects with obesity, aged 10 to 15 years (36.9% girls), were enrolled. Obesity was classified into simple (SmOb) and extreme (ExOb) forms. The BMD of the total body, less head, was measured by dual energy x-ray absorptiometry, and the BMD z-score was used to evaluate the relationship of body composition with metabolic parameters. Results BMD z-scores were higher in subjects with ExOb than in those with SmOb. Lean mass index (LMI), body mass index z-score, and vitamin D intake showed positive relationships, whereas percentage of body fat and serum leptin level showed negative relationships with BMD z-scores in boys. In girls, LMI and body mass index z-score showed positive relationships with BMD z-scores. In multivariable linear regressions, serum leptin level showed negative relationships with BMD z-score, only in boys. In addition, positive relationships of LMI and negative relationships of percentage of body fat with BMD z-scores were observed in subjects with SmOb. However, positive relationships of LMI with BMD z-scores were attenuated in subjects with ExOb. Conclusion High BMD appears to be positively associated with lean mass in children and adolescents with obesity, which might be a natural protective mechanism to withstand the excess weight. However, excessive body fat appears to be negatively associated with BMD, which might attenuate the positive relationship between lean mass and BMD in subjects with ExOb.

Aim The aim of this study was to examine the effects of a mobile web‐based self‐management program on menopausal symptoms, self‐efficacy and quality of life in breast cancer patients with chemotherapy‐induced amenorrhoea. Design A quasi‐experimental pretest–posttest design with repeated measures. Methods The study was carried out at a university medical centre between October 2017 and September 2018. The intervention group received a 12‐week mobile web‐based self‐management program including education and coaching/support. Multiple instruments were used to measure menopausal symptoms, self‐efficacy, and quality of life at pre‐test, after the intervention (post‐test), and 3 months post‐intervention (follow‐up test). Repeated measure ANOVA was used to analyse the data. Results In the intervention group, menopausal symptoms were significantly improved compared to the control group at the follow‐up test. In the follow‐up test, the intervention group's self‐efficacy and quality of life were significantly improved, whereas that of the control group was decreased.

Objectives To examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. Methods We conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. Results A total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90–1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02–1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49–0.87) compared to TNFi. Conclusion In this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.

Summary: Purpose: Cardio-cerebrovascular diseases constitute the most common and fatal disease among menopausal women. However, the risk of cardio-cerebrovascular diseases in menopausal women compared to men has been underestimated, with insufficient related studies. Therefore, we examined the incidence and risk factors of cardio-cerebrovascular diseases among Korean menopausal women. Methods: A retrospective observational study design with secondary analysis was conducted using data from the Korean Genome and Epidemiology Study survey. We used the study’s data of 1,197 menopausal women, aged 40–64 years, who did not have cardio-cerebrovascular diseases at baseline and their related data from the biennial follow-ups over 14 years. Cardio-cerebrovascular diseases were defined as hypertension, coronary artery disease, or stroke. The incidence of cardio-cerebrovascular diseases was calculated per person-years, and multivariate Cox proportional hazards models were used to determine the predictors of cardio-cerebrovascular diseases during the follow-up period. Results: Of the 1,197 cases, 264 were early or surgical menopausal women. The overall incidence of cardio-cerebrovascular diseases was 18.75 per 1,000 person-years. Early or surgical menopause (HR = 4.32, p

Breast cancer (BC) among Asians accounts for ~ 40% of the global BC burden. Differences in BC risk, presentation, tumor biology, and response to treatment exist between Asian and non-Asian patients; however, Asian patients are often under-represented in clinical trials. This narrative review summarizes the efficacy and safety of pharmacological therapies for BC in Asian populations, with a focus on outcomes in Asian versus non-Asian patients treated with chemotherapy, hormone therapy, anti-human epidermal growth factor receptor-2 targeted therapies, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, mammalian target of rapamycin inhibitors, bone-targeted therapies, poly-ADP ribose polymerase, phosphoinositide 3-kinase, and checkpoint inhibitors. While most therapies have demonstrated comparable efficacy and safety in Asian and non-Asian patients with BC, differences that are largely attributed to pharmacogenetic variations between populations exist. Pharmacogenetic differences may contribute to a reduced clinical benefit of tamoxifen, whereas improved clinical outcomes have been reported with tyrosine kinase inhibitors and CDK4/6 inhibitors in Asian versus non-Asian patients with BC. In particular, Asian patients have an increased incidence of hematological toxicities, including neutropenia, although adverse events can be effectively managed using dose adjustments. Recent trials with CDK4/6 inhibitors have increased efforts to include Asians within study subsets. Future clinical trials enrolling higher numbers of Asian patients, and an increased understanding of differences in patient and tumor genetics between Asians and non-Asians, have the potential to incrementally improve the management of BC in Asian patients.

Prcis Bruch membrane opening-minimum rim width (BMO-MRW) is overall a useful parameter for diagnosing early glaucoma in myopic eyes. Purpose The aim of this study was to determine the diagnostic value of BMO-MRW compared with peripapillary retinal nerve fiber layer (pRNFL) thickness for detecting early glaucoma in patients with moderate to severe myopia. Methods One eye was randomly selected from each of the 253 subjects (127 normal controls, 82 with glaucoma suspect, and 44 with early glaucoma). All patients underwent visual acuity testing, refractive error assessment, slit-lamp inspection, intraocular pressure measurement, fundus photography, perimetry. BMO-MRW and pRNFL thickness data were obtained using spectral-domain optical coherence tomography. Area under the receiver operating characteristic curves (AUC) for global and sectoral thickness parameters were calculated. Results Global analyses for the discrimination of early glaucoma in all myopic subjects showed comparable AUCs between BMO-MRW and pRNFL thickness [AUC 0.952 (95% confidence interval, 0.918-0.975) and 0.934 (95% confidence interval, 0.896-0.961), respectively, P=0.345]. However, in sectoral analysis, BMO-MRW showed significantly better diagnostic performance than pRNFL thickness except for the superotemporal sector. The AUC for discriminating early glaucoma from glaucoma suspect, BMO-MRW showed statistically better diagnostic performance in the inferotemporal, inferonasal, superonasal, and nasal sectors. When dividing the subject based on a threshold Bruch membrane opening (BMO) area of 2.5 mm2, the diagnostic power of BMO-MRW was generally lower except for the inferonasal sector in the subgroup with a large BMO area. Conclusions BMO-MRW was overall a useful parameter for diagnosing early glaucoma in myopic eyes. However, its diagnostic performance was decreased in myopic eyes with large BMO and there were no significant differences from pRNFL thickness.

BACKGROUND Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. METHODS A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. RESULTS A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59-7.31; p < 0.001). CONCLUSION Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Background: Evidence for using high-flow nasal cannula (HFNC) in hypercapnia is still limited. Most of the clinical studies had been conducted retrospectively, and there had been conflicting reports for the effects of HFNC on hypercapnia correction in prospective studies. Therefore, more evidence is needed to understand the effect of the HFNC in hypercapnia.Methods: We conducted a multicenter prospective observational study after applying HFNC to 45 hospitalized subjects who had moderate hypercapnia (arterial partial pressure of carbon dioxide [PaCO2], 43–70 mm Hg) without severe respiratory acidosis (pH

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients’ blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.

Purpose: Syphilis infections are becoming more prevalent in the Republic of Korea, and inadequately treated syphilis can lead to congenital syphilis (CS) in newborns. This study aimed to analyze the clinical manifestations of syphilis in mothers and newborns and to make suggestions to improve disease prognosis. Methods: This single-center study was performed between August 2009 and August 2019 and included 29 newborns with CS. We retrospectively evaluated the clinical features, rapid plasma reagin (RPR) card test, fluorescent treponemal antibody absorption test (FTA-ABS), morbidity, and treatment regimen of all the syphilis-affected mothers and their newborns. Results: At the time of delivery, mean maternal age was 29.0±6.1 years old, and newborn gestational age was 38.0 weeks. In cases when syphilis was confirmed during the second and third trimesters of pregnancy, the newborn with CS had morbidity (p=0.004). The mean RPR titer was related to morbidity (p= 0.036). Positive results of FTA-ABS IgM (p

Purpose: Obesity among children from low-income families is becoming a social problem. The aim of this study was to evaluate the effectiveness of an obesity prevention program that included physical activity, nutrition education, behavioral modification, and primary caregiver participation components among children from low-income families.Methods: The study analyzed a nonequivalent control group using a pretest-posttest design. A total of 77 children were recruited from six community childcare centers using purposive sampling. For the intervention group (n=40), the pretest was administered before the combined intervention program involving the participants' primary caregivers was conducted for 8 weeks. The posttest was conducted immediately after the program and again four weeks after the program.Results: Flexibility (F=4.64, p=.020), muscular endurance (F=11.22, pp=.010), body image satisfaction scores (F=4.74, p=.012), and self-esteem scores (F=3.81, p=.029) showed significant differences and interactions between group and time for the intervention and control groups.Conclusion: Strategies to actively engage the primary caregivers of low-income families in children's obesity programs are needed. Obesity prevention programs for children based on the program in this study should be routinely developed, and continuing attention should be given to children from low-income families.

PURPOSE To evaluate whether allergic conjunctivitis (AC) could be induced by Acanthamoeba excretory-secretory protein (ESP) and analyze the therapeutic effect of resolvin (Rv) D1 and antiallergic agents. METHODS Human conjunctival epithelial cells (HCVCs) were treated with 10 µg/well of ESP, and Th2 cytokines were measured using real-time PCR. C57BL/6 mice were treated with 10 µg/5 µL of ESP after sensitization, and conjunctivas isolated from the mice were stained with hematoxylin and eosin (H&E) for the analysis of eosinophils and periodic acid-Schiff (PAS) for the analysis of goblet cells. Cytokine levels in the eye-draining lymph nodes (dLNs) and spleens were measured using the enzyme-linked immunosorbent assay (ELISA). Then, the treatment effects of RvD1 and the antiallergic agents (olopatadine, bepotastine, and alcaftadine) on the HCVCs, mouse conjunctivas, dLNs, and spleens were assessed. RESULTS Th2 cytokines were increased in the ESP-treated conjunctival cells. Mouse conjunctivas treated with ESP showed significant infiltration of eosinophils and goblet cells, and the dLN and spleen exhibited increased IL-4, IL-5 and IL-13 levels. All findings were significantly decreased upon treatment with RvD1 and the antiallergic agents. CONCLUSIONS Acanthamoeba could be used to establish an animal model of AC, which could be effectively treated with RvD1 or topical antiallergic agents.

Introduction IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). This study evaluated the safety, pharmacokinetics, and pharmacodynamics of IMC-001 in patients with advanced solid tumors. Materials and Methods This open-labeled phase I study used a standard 3 + 3 dose-escalation design, with doses ranging from 2 to 20 mg/kg. IMC-001 was administered intravenously every 2 weeks until disease progression or unacceptable toxicity. The dose-limiting toxicity window was defined as 21 days from the first dose. Results Fifteen subjects were included in 5 dose-escalation cohorts. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common adverse events (AEs) were general weakness, decreased appetite, fever, and cough. No grade 4 or 5 treatment emergent AEs were reported during the study. One subject in the 2 mg/kg cohort showed grade 2 immune-induced thyroiditis and diabetes mellitus suspected to be related to IMC-001. Over the dose range of 2–20 mg/kg IMC-001, the AUC0–14d, AUC0—∞, and Cmax generally increased in a dose-proportional manner for each step of dose escalation. Of the 15 enrolled patients, 1 subject with rectal cancer showed a partial response, and the disease control rate was 33.3%. Conclusions IMC-001 demonstrated a favorable safety profile up to 20 mg/kg administered intravenously every 2 weeks and showed preliminary efficacy in patients with advanced solid tumors. Based on pharmacokinetic and pharmacodynamic data, 20 mg/kg was selected as the recommended phase II dose. Clinical trial identification NCT03644056 (date of registration: August 23, 2018).

BackgroundThe aim of this study was to develop a machine learning(ML) based model to accurately predict pathologic complete response(pCR) to neoadjuvant chemotherapy(NAC) using pretreatment clinical and pathological characteristics of electronic medical record(EMR) data in breast cancer(BC).Methods The EMR data from patients diagnosed with early and locally advanced BC and who received NAC followed by curative surgery were reviewed. A total of 16 clinical and pathological characteristics was selected to develop ML model. We practiced six ML models using default settings for multivariate analysis with extracted variables. ResultsIn total, 2,065 patients were included in this analysis. Overall, 30.6% (n=632) of patients achieved pCR. Among six ML models, the LightGBM had the highest area under the curve (AUC) for pCR prediction. After hyper-parameter tuning with Bayesian optimization, AUC was 0.810. Performance of pCR prediction models in different histology-based subtypes was compared. The AUC was highest in HR+HER2- subgroup and lowest in HR-/HER2- subgroup (HR+/HER2- 0.841, HR+/HER2+ 0.716, HR-/HER2 0.753, HR-/HER2- 0.653).ConclusionsA ML based pCR prediction model using pre-treatment clinical and pathological characteristics provided useful information to predict pCR during NAC. This prediction model would help to determine treatment strategy in patients with BC planned NAC.

BackgroundRisk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk.MethodsWe analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan–Meier analyses, log-rank testing and Cox proportional hazards models.ResultsData from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.ConclusionsModified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.

PURPOSE In the phase III SOLAR-1 trial ( NCT02437318 ), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA)–mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. We assessed health-related quality of life using patient-reported outcome measures in these patients. MATERIALS AND METHODS In the PIK3CA-mutant cohort, 341 patients were randomly assigned 1:1 to receive alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Patient-reported outcomes were evaluated with the European Organisation for Research and Treatment of Cancer QoL of Cancer Patients and Brief Pain Inventory-Short Form questionnaires. Changes from baseline and time to 10% deterioration were analyzed using repeated measurement models and Cox models, respectively. RESULTS Global Health Status/QoL and functional status were maintained from baseline (mean changes < 10 points) in the alpelisib (overall change from baseline [95% CI], −3.50 [−8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [−4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (−3.77; 95% CI, −8.35 to 0.80; P = .101). Time to 10% deterioration for Global Health Status/QoL was similar between arms (hazard ratio, 1.03; 95% CI, 0.72 to 1.48). Compared with placebo, deterioration in social functioning and in diarrhea, appetite loss, nausea or vomiting, and fatigue symptom subscales occurred with alpelisib. Numerical improvement in Worst Pain was observed with alpelisib versus placebo (42% v 32%, week 24; P = .090). CONCLUSION In SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative PIK3CA-mutated advanced breast cancer.

We aimed to evaluate the feasibility of multidomain intervention (MI) tailored to the Korean context. In an outcome assessor-blinded, randomized controlled trial, participants without dementia and with one or more modifiable dementia risk factors, aged 60-79 years, were randomly assigned to the facility-based MI (FMI; n=51), the home-based MI (HMI; n=51), or the control group receiving general health advice (n=50). The 24-week intervention comprised vascular risk management, cognitive training, social activity, physical exercise, nutrition guidance, and motivational enhancement. The FMI participants performed all intervention programs at a facility three times a week. The HMI participants performed some programs at a facility once every 1-2 weeks and performed others at home. The primary outcome was feasibility measured through retention, adherence, and at least no differences from the control group in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the FMI and HMI groups, the retention rates were 88.2% and 96.1%, and adherence to the intervention was 94.5% and 96.8%, respectively. The RBANS total scale index score improved significantly in the FMI (5.46 ± 7.50, P = 0.004) and HMI (5.50 ± 8.14, P = 0.004) groups compared to the control group (-0.74 ± 11.51). The FMI and HMI are feasible and there are indicators of efficacy.

OBJECTIVE: We aimed to determine whether the posture control training in the sitting posture using virtual reality (VR) training program affects sitting balance and trunk stability in children with spastic cerebral palsy (CP). METHODS: The experiment was conducted for 4 weeks by randomly allocating 20 children with CP. The experimental group (n = 10) performed balance training in the sitting position using a VR training program, and the control group (n = 10) performed arm reach training in the sitting position. To evaluate static and dynamic sitting balance and trunk stability, the Wii Balance Board and Balancia software, the modified functional reach test, and the Korean version of the Trunk Control Measurement Scale were used. RESULTS: There were significant differences between the two groups in the changes in speed and postural swing distance before and after training (p

Summary Background Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. Methods This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov , NCT03056755 . Findings Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. Interpretation BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. Funding Novartis Pharmaceuticals.

Purpose: Aromatase inhibitors (AIs) are widely prescribed for postmenopausal women with breast cancer and are known to cause musculoskeletal pain. This study aimed to identify factors associated with AI continuation intention among breast cancer survivors (BCS). Methods: A cross-sectional survey was conducted on 123 BCS (stages I–III), who had been taking AIs for at least 6 weeks. Participants were recruited from a cancer center in Goyang, Korea, from September to November 2019. Descriptive statistics, Welch analysis of variance, Pearson correlation coefficients, and simple linear regression were used for the analysis.Results: Belief in endocrine therapy was a significant predictor of AI continuation intention (β=.66, p

Current guidelines recommend that patients with pulmonary arterial hypertension (PAH) avoid pregnancy because of a high mortality risk for the patients and their offspring. Still, some PAH patients become pregnant. We herein report the mid-term maternal and offspring outcomes of 25 consecutive pregnancies in 16 patients with PAH. Five patients had a total of 8 abortions (5 spontaneous, 3 induced; one of these patients developed right ventricular failure and underwent urgent lung transplantation). Thirteen patients delivered a total of 18 healthy children. One of these patients developed right heart failure in the postpartum period, requiring urgent lung transplantation. All other patients did well and were alive after a follow-up period of 1-12 (median, 6) years. Their infants were also doing well, and all had normal results on a standardized infant developmental questionnaire. These data suggest that nowadays, pregnancy can be associated with good outcomes in selected patients with PAH.

Background Trastuzumab deruxtecan (T-DXd, DS-8201) is an antibody-drug conjugate with a HER2 antibody, tetrapeptide-based cleavable linker, and a novel topoisomerase I inhibitor payload. DESTINY-Breast01 (NCT03248492) is an open-label, international, multicenter, phase 2 study of T-DXd in patients with HER2 positive metastatic breast cancer (MBC) and supported regulatory approval in the US and Japan. Updated longer-term safety and efficacy results are presented here. Methods All patients were required to have MBC that progressed on or after T-DM1. 253 patients were enrolled and 184 received T-DXd 5.4 mg/kg, representing the primary analysis set. The primary endpoint was ORR. Additional endpoints included duration of response, PFS, and OS. Results Patients had received a median of 6 previous lines of treatment for MBC. In this updated data cutoff (8 June 2020) compared to the prior data cutoff (1 Aug 2019), median duration of follow-up has increased from 11.1 to 20.5 mo; 37 patients (20.1%) remain on treatment. Confirmed ORR was 61.4% (12 CRs) with a median duration of response of 20.8 mo; the disease control rate was 97.3% (95% CI, 93.8-99.1). The updated mPFS was 19.4 mo (95% CI, 14.1 mo-NE). Estimated OS was 85% (95% CI, 79%-90%) at 12 months and 74% (95% CI, 67%-80%) at 18 months. The preliminary mOS is 24.6 mo (estimated at 35% maturity with only 17 patients at risk at 24 months). The safety profile of T-DXd was similar as that previously reported; with an additional 9 mo follow-up, only 3 new cases of T-DXd-related interstitial lung disease (ILD) were reported. Results are summarized in the table below. Conclusion Consistent with prior results, T-DXd demonstrated high rates of durable responses in a heavily pretreated population of patients with MBC. From this single-arm, phase 2 study, the PFS and immature OS results are encouraging; these endpoints will be further evaluated in the ongoing randomized controlled studies of T-DXd. For patients who remained on treatment for this longer duration (double that of the previous report), the rate of discontinuation or ILD did not notably increase. Continued attention to pulmonary symptoms and careful monitoring is warranted. Updated Results for DESTINY-Breast011 Aug 2019 datacut8 Jun 2020 datacutPatients remaining on treatment, n/N (%)79/184 (42.9%)37/184 (20.1%)Median duration of follow-up11.1 months20.5 monthsORR60.9%61.4%CR6.0%6.5%PR54.9%54.9%SD36.4%35.9%Duration of response, median (95% CI)14.8 months (13.8-16.9)20.8 months (15.0-NE)PFS, median (95% CI)16.4 months (12.7-NE)19.4 months (14.1-NE)OSMedian (95% CI)NE (NE-NE)24.6 months (23.1-NE)Point estimate at 12 mo (95% CI)86.2% (79.8-90.7)85% (79-90)Point estimate at 18 mo (95% CI)–74% (67-80)SafetyPatients with a TEAE, n (%)183 (99.5%)183 (99.5%)Grade ≥3105 (57.1%)113 (61.4%)Associated with discontinuation28 (15.2%)34 (18.5%)Associated with death10 (5.4%)10 (5.4%)Drug-related ILD per ILD adjudication committeea25 (13.6%)28 (15.2%)Grade 5 drug-related ILD per ILD adjudication committee4 (2.2%)5 (2.7%)a1 grade 1 and 1 grade 3 event are pending adjudication and are not included. Citation Format: Shanu Modi, Cristina Saura, Toshinari Yamashita, Yeon Hee Park, Sung-Bae Kim, Kenji Tamura, Fabrice Andre, Hiroji Iwata, Yoshinori Ito, Junji Tsurutani, Joohyuk Sohn, Neelima Denduluri, Christophe Perrin, Kenjiro Aogi, Eriko Tokunaga, Seock-Ah Im, Keun Seok Lee, Sara A Hurvitz, Javier Cortes, Caleb Lee, Yali Liu, Lin Zhang, Javad Shahidi, Antoine Yver, Jose Baselga, Ian E Krop. Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd ) in HER2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-06.

Introduction Adding pertuzumab(P) on trastuzumab(H) with cytotoxic chemotherapy increased pathologic complete response (pCR) of early or locally advanced HER2 positive breast cancer (EBC) with neoadjuvant chemotherapy. Since 63.6% of pCR rate has been reported from TRYPHAENA trial, TCHP regimen has been used as a standard of neoadjuvant treatment regimen for patients with HER2 positive EBC. However, this regimen has profound toxicities in terms of myelosuppression, neurotoxicity, and etc. Furthermore we still need more information on clinical outcomes and toxicities with this regimen. Therefore, we report real world experience of EBC patients treated with neoadjuvant TCHP followed by curative surgery. Methods We retrospectively reviewed electronic medical record of EBC patients who received neoadjuvant TCHP. Information which we gathered included patients’ and tumor characteristics at the time of diagnosis, details of neoadjuvant chemotherapy, pathologic assessment of tumor response to neoadjuvant TCHP and recurrence free survival after curative surgery. pCR was defined as absence of residual invasive cancer on pathologic evaluation of the resected breast specimen and all sampled regional lymph nodes (ypT0/isN0). Results Between February 2016 and August 2019, 447 patients were treated with neoadjuvant TCHP followed by curative surgery. Median age at BC diagnosis was 56. In clinical stage, stage II was 54.6% and 45.4% of stage III and hormone receptor (HR) positive BC was 48.3%. Most commonly reported adverse event(AE) was mucositis (84%) followed by diarrhea (77%). In terms of Grade 3 AE, anorexia(6%), diarrhea(2%) were frequently observed and 9(2%) of febrile neutropenia occurred despite of prophylactic use of peg-filgrastim. Forty percent of patients experienced dose reduction due to AEs. Of 447 patients, 29% of patients underwent total mastectomy and 71% of breast conserving surgery. In terms of clinical outcome, pCR rate was 64%; 77% of HR negative BCs and 50% of HR positive BCs. Among baseline characteristics, high nuclear grade, high histologic grade, HR stats affected to pCR status (Ps Key words: neoadjuvant chemotherapy, HER2+ breast cancer, pertuzumab, pathologic complete response Citation Format: Ji-Yeon Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park. Real Would Evidence (RWE) of neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in patients with HER2 positive early or locally advanced breast cancer treated Single institutional experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-38.

Background: Young-PEARL study showed median progression-free survival (PFS) of 20·1 months in the palbociclib plus endocrine therapy group versus 14·4 months in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], log-rank p=0·0235). We conducted exploratory biomarker analysis to predict the efficacy of the trial. Methods: This was a phase II trial that randomized 184 patients with HR+ MBC in premenopausal women to palbociclib plus exemestane with GNRH agonist (Arm A, n=79) versus capecitabine (Arm B, n=62). We performed targeted sequencing (CancerSCANTM) containing 375 cancer-related genes (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response in terms of PFS. Result: By research-based PAM50 subtyping, 73% of patients classified as Luminal (Luminal A and Luminal B), and showed better prognosis in all patients and Arm A (p Conclusions: The alteration of a few genes including Rb1 loss may be associated with resistance of palbociclib in HR-positive premenopausal population with MBC. Luminal type showed better prognosis, and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. ESR1 mutation was found in low population frequency because all patients didn’t received AI therapy. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy. Clinical trial information: NCT02592746. Citation Format: Kyunghee Park, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Woong-Yang Park, Seock-Ah Im, Yeon Hee Park. Exploratory biomarker analysis of Young-PEARL [palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with HR (hormone receptor)-positive, HER2-negative metastatic breast cancer (MBC)] study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-19.

Background: In the PAKT study, addition of the oral AKT inhibitor capivasertib to 1st-line paclitaxel therapy for metastatic TNBC resulted in significantly longer progression-free survival (PFS; primary endpoint; Schmid, J Clin Oncol 2020). The stratified PFS hazard ratio was 0.74 (95% CI, 0.50-1.08; one-sided P=0.06; predefined significance level of 0.10, one-sided; median PFS 5.9 vs 4.2 months with capivasertib vs placebo). Overall survival (OS) results were immature at the primary analysis with 53% of events but suggested long OS with capivasertib (HR, 0.61; 95% CI, 0.37-0.99; two-sided P=0.04). Here we report final results. Methods: This double-blind, placebo-controlled, randomised phase II trial, recruited women with untreated, metastatic TNBC. Total of 140 patients were randomly assigned (1:1) to paclitaxel 90mg/m2 (days 1, 8, 15) with either capivasertib (400mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints included OS in the ITT population and in patients with and without PIK3CA/AKT1/PTEN-alterations. Results: With a median F/U of 40.0 months, median OS was longer in the capivasertib arm (19.1 vs 13.5 months, stratified HR 0.70, 95% CI 0.47-1.05, p=0.085). In contrast to the earlier analysis, no meaningful differences were seen in terms of benefit with capivasertib between patients with or without alterations of PIK3CA/AKT1/PTEN. Median OS numerically favoured capivasertib vs placebo both in the PIK3CA/AKT1/PTEN-altered (stratified HR 0.58, 95% CI 0.21-1.58, p=0.290) and PIK3CA/AKT1/PTEN non-altered subgroup (stratified HR 0.74, 95% CI 0.47-1.18, p=0.207). The safety profile of capivasertib plus paclitaxel was unchanged. Conclusions: Final OS results show a numerical trend favouring capivasertib; effects were observed regardless of PIK3CA/AKT1/PTEN alterations. Consistent with the previously observed PFS benefit, these findings support further evaluation of first-line Capivasertib plus paclitaxel for metastatic TNBC in the ongoing Capitello290 randomised phase III trial in patients with and without PIK3CA/AKT1/PTEN alterations. Citation Format: Peter Schmid, Jacinta Abraham, Stephen Chan, Adrian Murray Brunt, Gia Nemsadze, Richard D Baird, Yeon Hee Park, Peter Hall, Timothy Perren, Robert C Stein, László Mangel, Jean-Marc Ferrero, Melissa Phillips, John Conibear, Javier Cortes, Andrew Foxley, Elza de Bruin, Robert McEwen, Myria Nikolaou, Daniel Stetson, Brian Dougherty, Aaron Prendergast, Max McLaughlin-Callan, Matthew Burgess, Cheryl Lawrence, Hayley Cartwright, Kelly Mousa, Nicholas Turner, Duncan Wheatley. Mature survival update of the double-blind placebo-controlled randomised phase II PAKT trial of first-line capivasertib plus paclitaxel for metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-11.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of dual antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the resistance mechanisms. This randomized phase 2 pilot study evaluated safety and efficacy of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than two HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was Aug 4, 2020. Results: As a pilot study, 15 patients were enrolled and followed for a median of 2.3 months. At data cutoff, 11 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: H1047R, H1047L, E542Q, E542K, E453K, N345K, and PIK3CA amplification. Five patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). All patients who have reached PR remain on investigational treatment at the data cutoff point, and the longest one is on treatment for 7.8 months. One of the SD patients ended treatment due to disease progression, and the other two have been undergoing treatment. Overall, response rate was 45.5% and disease control rate was 72.7%. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 pilot study, Trastuzumab biosimilar plus Gedatolisib presented 45.5% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA aberration. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong Won Lee, Keon Uk Park, Eun Mi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Mi So Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, In Hae Park, Kyong Hwa Park. Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis] [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-39.

Purpose: Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool. Experimental Design: Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases. Results: Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy. Conclusions: Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.

BackgroundEpidemiological data on the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity are limited.AimsTo evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19.MethodWe performed a cohort study using the Korean COVID-19 patient database based on national health insurance data. Each person with a mental or behavioural disorder (diagnosed during the 6 months prior to their first SARS-CoV-2 test) was matched by age, gender and Charlson Comorbidity Index with up to four people without mental disorders. SARS-CoV-2-positivity risk and the risk of death or severe events (intensive care unit admission, use of mechanical ventilation and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis.ResultsAmong 230 565 people tested for SARS-CoV-2, 33 653 (14.6%) had mental disorders; 928/33 653 (2.76%) tested SARS-CoV-2 positive and 56/928 (6.03%) died. In multivariable analysis using the matched cohort, there was no association between mental disorders and SARS-CoV-2-positivity risk (odds ratio OR = 0.95; 95% CI 0.87–1.04); however, a higher risk was associated with schizophrenia-related disorders (OR = 1.50; 95% CI 1.14–1.99). Among confirmed COVID-19 patients, the mortality risk was significantly higher in patients with than in those without mental disorders (OR = 1.99, 95% CI 1.15–3.43).ConclusionsMental disorders are likely contributing factors to mortality following COVID-19. Although the infection risk was not higher for people with mental disorders overall, those with schizophrenia-related disorders were more vulnerable to infection.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2−, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p 4) (p

Introduction: We hypothesize that remote patient monitoring (RPM) for automated peritoneal dialysis (APD) and feedback could enhance patient self-management and improve outcomes. The aim of this study was to evaluate the efficacy of RPM-APD compared to traditional APD (T-APD) without RPM. Methods: In this multicenter, randomized controlled trial, patients on APD were randomized to T-APD (n = 29) or RPM-APD (n = 28) at 12 weeks and followed until 25 weeks. Health-related quality of life (HRQOL), patient and medical staff satisfaction with RPM-APD, and dialysis-related outcomes were compared between the 2 groups. Results: We found no significant differences in HRQOL scores at the time of enrollment and randomization between RPM-APD and T-APD. At the end of the study, the RPM-APD group showed better HRQOL for the sleep domain (p = 0.049) than the T-APD group and the T-APD group showed better HRQOL for the sexual function domain (p = 0.030) than the RPM-APD group. However, we found no significant interactions between the time and groups in terms of HRQOL. Different HRQOL domains significantly improved over time in patients undergoing RPM-APD (effects of kidney disease, p = 0.025) and T-APD (burden of kidney disease, p = 0.029; physical component summary, p = 0.048). Though medical staff satisfaction with RPM-APD was neutral, most patients were quite satisfied with RPM-APD (median score 82; possible total score 105 on 21 5-item scales) and the rating scores were maintained during the study period. We found no significant differences in dialysis adherence, accuracy, adequacy, overhydration status, blood pressure, or the number of unplanned visits between the 2 groups. Discussion/Conclusion: Although HRQOL and dialysis-related outcomes were comparable between RPM-APD and T-APD, RPM-APD was positive in terms of patient satisfaction. Further long-term and large-scale studies will be required to determine the efficacy of RPM-APD. Trial Registration: CRIS identifier: KCT0003390, registered on December 14, 2018 – retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=12348.

Background: In patients with breast cancer after Neoadjuvant Chemotherapy (NAC), pathological Complete Response (pCR) was associated with better long-term outcomes. We here attempted to predict pCR using machine learning. Patients and Methods: From 2008 to 2017, 1308 breast cancer patients underwent NAC before surgery, of whom 377 patients underwent Cancer SCANTM for gene data. Of 377, 238 were analyzed here, with 139 excluded due to incomplete medical data. Results: The pCR (-) vs. (+) group had 200 vs. 38 patients. In our predictive model with gene data, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was 0.909 and accuracy was 0.875. In another model without gene data, the AUC of ROC curve was 0.743 and accuracy was 0.800. We also conducted internal validation with 72 patients undergoing NAC and Cancer SCANTM during July 2017 and April 2018. When we applied a 0.4 threshold value, accuracy was 0.806 and 0.778 in the predictive model with vs. without gene profiles, respectively. Conclusion: The present predictive model may be a useful and easy-to-access tool for pCR-prediction in breast cancer patients treated with NAC.