Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells

Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Functional Gastrointestinal Disorders and Abdominal Visceral Fat in Children and Adolescents / 대한소아소화기영양학회지

Purpose@#Few reports have investigated the correlation between functional gastrointestinal disorders (FGIDs) and the degree of obesity in children and adolescents. Thus, this study aimed to examine the relationship between FGIDs and the degree of obesity in children and adolescents. @*Methods@#Children and adolescents (<19 years old) who had undergone abdominopelvic computed tomography and had been diagnosed with FGIDs from 2015 to 2016 were included in this retrospective case-control study in a ratio of 1:2. Abdominal visceral fat was measured using an image analysis software. @*Results@#The mean age of all 54 FGID patients was 12.9±3.4 years, and the male: female ratio was 1:1.2. We observed no difference in body mass index (BMI) between the FGID and control groups (19.5±4.6 vs. 20.6±4.3 kg/m2 , p=0.150). However, the FGID group had less abdominal visceral fat than that of the control group (26.2±20.0 vs. 34.4±26.9 cm2 , p=0.048). Boys in the FGID group had lower BMI (18.5±3.5 vs. 20.9±4.3 kg/m2 , p=0.019) and less abdominal visceral fat (22.8±15.9 vs. 35.9±31.8 cm2 , p=0.020) than those of boys in the control group. However, we found no difference in BMI (20.5±5.3 vs. 20.4±4.2 kg/m2 , p=0.960) and abdominal visceral fat (29.0±22.9 vs. 33.1±22.1 cm2 , p=0.420) between girls in both groups. @*Conclusion@#Our study revealed a difference in the relationship between FGID and the degree of obesity according to sex, which suggests that sex hormones influence the pathogenesis of FGIDs. Multicenter studies with larger cohorts are required to clarify the correlation between FGID subtypes and the degree of obesity.

The incidence and clinical characteristics of myocarditis and pericarditis following mRNA-based COVID-19 vaccination in Republic of Korea adolescents from July 2021 to September 2022

Objectives@#Age-specific information regarding myocarditis/pericarditis in adolescents following mRNA-based coronavirus disease 2019 (COVID-19) vaccination in Asia remains insufficient. This study investigated the incidence and clinical characteristics of myocarditis/pericarditis in Republic of Korea adolescents after mRNA-based COVID-19 vaccination. @*Methods@#This retrospective descriptive study utilized patient data from the Korea Immunization Management System. Incidence rates were calculated according to age and sex. Clinical characteristics (symptoms/signs, laboratory values, and imaging results) were compared between mild and severe cases. @*Results@#Between July 19, 2021 and September 30, 2022, 3,728,224 individuals aged 12 to 19 years received 6,484,165 mRNA-based COVID-19 vaccines, and 173 cases met the case definition for myocarditis/pericarditis: 151 mild (87.3%) and 22 severe (12.7%). The incidence was 3.8-fold higher in males than in females. Troponin I/troponin T was elevated in 96% of myocarditis cases, demonstrating higher sensitivity than creatine kinase-myocardial band (67.6%) or C-reactive protein (75.2%). ST-segment or Twave on electrography abnormalities were found in 60.3% (85/141). Paroxysmal/sustained atrial/ventricular arrhythmias were more common in severe than in mild cases (45.5% vs. 16.8%, p=0.008). Edema on T2-weighted magnetic imaging occurred in 21.6% (8/37) and 62.5% (5/8) of mild and severe cases, respectively (p=0.03). Abnormal pericardial fluid collection or pericardial inflammation was found in 75.4% of pericarditis cases (49/65). @*Conclusion@#Myocarditis/pericarditis occurred in rare cases following mRNA-based COVID-19 vaccination. Most cases were mild, but the incidence was higher in adolescent males and after the second dose. As bivalent severe acute respiratory syndrome coronavirus 2 mRNA vaccination started in South Korea in October 2022, the post-vaccination incidence of myocarditis/pericarditis should be closely monitored, considering clinical characteristics.

Anti-fatigue effect of tormentic acid through alleviating oxidative stress and energy metabolism-modulating property in C2C12 cells and animal models

BACKGROUND/OBJECTIVES@#Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H2O2 -stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models.MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H2O2 . Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. @*RESULTS@#TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H2O2 -stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H2O2 -stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. @*CONCLUSIONS@#TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

Association Between Body Mass Index, Body Shape Perception and Depression in Korean Female Population: The Korean National Health and Nutrition Examination Survey / 생물치료정신의학

Objectives@#The purpose of this study was to investigate the association between body mass index (BMI) and body shape perception and depression. @*Methods@#This study was based on data from 2016, 2018, and 2020 Korean National Health and Nutrition Examination Survey (KNHANES). The subjects were 7,302 adult female aged 19 to 65. We performed chi-square test with the RaoScott correction and Logistic regression analyses to examine the association among BMI, body shape perception, and depression. @*Results@#All demographic variables such as age, household income, education, marital status, medical service satisfaction, body shape perception, medical conditions except drinking problem, smoking and physical activity were correlated with depression. The rate of depression decreased from underweight to normal weight and overweight, and increased from obesity to severe obesity (p<0.001). And people who perceived themselves thin or overweight had more depression than normal (p<0.001). @*Conclusions@#The results of this study suggest that appropriate body mass index and normal body shape perception have a positive effect on mental health.

Retrospective Analysis of the Efficacy and Safety of Omidenepag Isopropyl 0.002% Ophthalmic Solution in Korean Patients

Purpose@#This study aimed to analyze the clinical efficacy and safety of omidenepag isopropyl (OMDI) 0.002% in Korean patients. @*Methods@#A retrospective study was conducted involving 306 patients diagnosed with glaucoma or ocular hypertension, who were administered OMDI 0.002% from May 2021 to June 2022. The primary outcomes were the change in intraocular pressure (IOP) at months 1, 3, and 6 compared to the baseline IOP, and the reactions to the OMDI drug. @*Results@#Out of 235 patients who met the study inclusion criteria, the mean IOP was 16.5 ± 3.4 mmHg at baseline, 14.5 ± 3.0 mmHg at month 1, 14.3 ± 2.7 mmHg at month 3, and 14.7 ± 3.1 mmHg at month 6. The mean IOP reduction at month 6 was -1.6 ± 2.8 mmHg (p < 0.001). On analyzing the IOP by types of glaucoma, the mean IOP change at the 6-month point showed statistically significant results in all types, including normal tension glaucoma, primary open-angle glaucoma, and ocular hypertension (p < 0.05). The frequency of side effects in all patients was 29.8%, with the most commonly reported adverse drug reaction being hyperemia in 18.7% of the total patients. There was one case (0.4%) of uveitis after OMDI administration, but no other systemic adverse drug reactions were reported. @*Conclusions@#Omidenepag isopropyl demonstrated a statistically significant IOP-lowering effect in Korean patients with various types of glaucoma. This suggests that OMDI could potentially serve as a first-line treatment for glaucoma.

Influence of Long-term Oral Steroid Intake on Glaucoma and Ocular Hypertension

Purpose@#The aim of this study was to evaluate the risk factors associated with glaucoma or ocular hypertension (OHT) in patients taking oral corticosteroids for extended periods, and to aid in managing intraocular pressure (IOP) in patients with these risk factors. @*Methods@#A cross-sectional study was performed involving 690 patients who visited a tertiary referral hospital and had been using oral corticosteroids for more than six months. Patients' demographics, tonometry results, drug type, dosage, duration, ophthalmic history, and the use of glaucoma eye drops were analyzed to determine the risk factors associated with glaucoma or OHT. @*Results@#In a generalized linear model analysis comparing patients' eyes diagnosed with glaucoma or ocular hypertension to those without such diagnoses, no statistical difference was observed between the two groups in terms of drug type, age, and duration of oral corticosteroid use. However, the dosage was found to be statistically significant (odds ratio 1.09, p = 0.0294). @*Conclusions@#No difference in the incidence of glaucoma or OHT was found based on the type of oral steroid, age, or duration of use. However, a higher incidence of glaucoma and OHT was observed among patients taking higher doses of oral steroids. Therefore, it is suggested that using lower doses of oral steroids may be more beneficial for managing IOP.

Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease

Background@#Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. @*Methods@#We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. @*Results@#There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). @*Conclusions@#Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.

Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data

Background@#and Purpose Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer’s disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. @*Methods@#We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. @*Results@#Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18–9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. @*Conclusions@#Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

Effect of Intraoperative Mitomycin C on the Surgical Outcomes of Ahmed Glaucoma Valve Implantation with Ciliary Sulcus Tube Placement

Purpose@#To evaluate the effect of intraoperative mitomycin C (MMC) on the surgical outcomes of ciliary sulcus (CS) Ahmed glaucoma valve (AGV) tube placement. @*Methods@#A retrospective review of medical records of 54 consecutive patients who underwent AGV implantation with tube placed in CS was performed. Consecutive cases operated without the use of intraoperative MMC from 2017 to 2019 were compared with consecutive cases operated with MMC from 2019 to 2021. Surgical failure was defined as intraocular pressure (IOP) exceeding 21 mmHg in two consecutive visits after postoperative 3 months or ≤30% IOP reduction, IOP ≤5 mmHg in two consecutive visits, or loss of light perception. Kaplan-Meier survival analysis and log-rank test were performed to compare the surgical failure rates. @*Results@#A total of 54 eyes of 54 patients were investigated. Mean follow-up period after AGV implantation was 1.4 ± 0.8 years. The MMC group showed significantly lower IOP during the 1st postoperative month (20.5 ± 8.6 mmHg vs. 15.8 ± 6.4 mmHg, p = 0.027), but the difference did not persist 6 months after the surgery (p = 0.805). The mean number of postoperative antiglaucoma medications was significantly lower in the MMC group in the 1st postoperative month (p = 0.047) but no difference was found at 6 months. No statistical difference was noted in the rates of postoperative complications. Kaplan-Meier survival analysis showed comparable survival rates between MMC group and no MMC group (p = 0.356). @*Conclusions@#The intraoperative use of MMC significantly lowered IOP in the 1st postoperative month but did not increase 6 months success rates in patients receiving AGV tube placement in CS.

The Clinical Outcomes of Marginal Donor Hearts: A Single Center Experience

Background and Objectives@#Although the shortage of donor is a common problem worldwide, a significant portion of unutilized hearts are classified as marginal donor (MD) hearts. However, research on the correlation between the MD and the prognosis of heart transplantation (HTx) is lacking. This study was conducted to investigate the clinical impact of MD in HTx. @*Methods@#Consecutive 73 HTxs during 2014 and 2021 in a tertiary hospital were analyzed.MD was defined as follows; a donor age >55 years, left ventricular ejection fraction 240 minutes, or significant cardiac structural problems. Preoperative characteristics and postoperative hemodynamic data, primary graft dysfunction (PGD), and the survival rate were analyzed. Risk stratification by Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was performed to examine the outcomes according to the recipient state. Each group was sub-divided into 2 risk groups according to the IMPACT score (low <10 vs. high ≥10). @*Results@#A total of 32 (43.8%) patients received an organ from MDs. Extracorporeal membrane oxygenation was more frequent in the non-MD group (34.4% vs. 70.7, p=0.007) There was no significant difference in PGD, 30-day mortality and long-term survival between groups. In the subgroup analysis, early outcomes did not differ between low- and high-risk groups. However, the long-term survival was better in the low-risk group (p=0.01). @*Conclusions@#The outcomes of MD group were not significantly different from non-MD group. Particularly, in low-risk recipient, the MD group showed excellent early and longterm outcomes. These results suggest the usability of selected MD hearts without increasing adverse events.

Assessment of Nutritional Adequacy of Gimbap Sold in Convenience Stores Focused on Protein and Mineral Content

This study examined the nutritional information using the nutrition labels of gimbap sold at convenience stores and evaluated nutritional adequacy compared to dietary reference intakes for Korean adolescents. Thirty gimbaps (triangular gimbaps and regular gimbaps according to the main ingredients of vegetables, fish, and meat) were purchased at five convenience stores of different brands with many stores in Korea. The food and nutrition labels of the gimbaps were investigated, and nine minerals were analyzed using inductively coupled plasma–mass spectrometry (ICP-MS). The average price of gimbap was 1,906.7 won, and average energy was 292.0 kcal, and the protein content was 15.5% of the recommended intake for Korean male adolescents aged 15∼18 years. The mineral content ranged from 6.9% for zinc to 39.0% for selenium. Except for sodium and selenium, the energy, protein, and mineral content did not meet 1/3 of dietary reference intakes for adolescents. For the index of nutritional quality (INQ), calcium and zinc were the lowest in the triangular and regular gimbap, respectively. The INQ of potassium was significantly higher in triangular gimbap with vegetables. The content and INQ of selenium were in regular gimbap with fish, and the zinc INQ was in regular gimbap with meat. Overall, gimbap sold in convenience stores has a high sodium content, and the contents of energy, protein, and minerals, except selenium, are insufficient for a single meal.

Plasma Cell-Free DNA in Uterine Cervical Cancer: Therapeutic Monitoring and Prognostic Values after Radical Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT). @*Materials and Methods@#Twenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months. @*Results@#In total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA. @*Conclusion@#Our findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

A Case of Heart Transplantation for Fulminant Myocarditis After ChAdOx1nCoV-19 Vaccination

Vaccines have become the mainstay of management against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) in the absence of effective antiviral therapy. Various adverse effects of COVID-19 vaccination have been reported, including cardiovascular complications such as myocarditis or pericarditis. Herein, we describe clinical records of a 63-year woman with fulminant myocarditis following ChAdOx1 nCoV-19 vaccination that was salvaged by heart transplantation. She complained chest pain, nausea, vomiting, and fever after the second vaccination. After the heart transplantation, the patient died due to necrotizing pneumonia on the 54th day of onset. Fulminant myocarditis is very rare after ChAdOx1 nCoV-19 vaccination but can be fatal.

Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment. @*Materials and Methods@#This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT. @*Results@#With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding. @*Conclusion@#We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Influencing Factors of Depression and Stress of the Elderly in Seoul: Analysis of 2018 Community Health Survey Data

Objective@#This study analyzed the relationship between sociodemographics and health behaviors that affect depression and stress of the aged 65 or older living in Seoul in 2018. @*Methods@#The subjects were selected according to the purpose by receiving raw data from the Korea Centers for Disease Control and Prevention, and 5,753 respondents were analyzed. @*Results@#In depression, the demographic and sociological factors with differences were sex, marriage, single-person household,current basic living, economic activity and monthly income, and the health behaviors with significant differences were past smoking, diabetes and insufficient annual medical use. In the stress level, the demographic and sociological factors with differences were age, sex, current basic living, monthly income and education, and the health behaviors with significant differences were current/past smoking, diabetes and insufficient annual medical use. The factors affecting depression and stress were not completely consistent but similar, and both had low rates of expert counseling. @*Conclusion@#This study is meaningful in that it identified the factors affecting the depression and stress of the elderly especially in Seoul, the metropolitan city. If future research reveals additional factors, it will be helpful to suggest the direction of government policy and contribute to improving the quality of life of the elderly in the super-aged era.

Dosimetric evaluation of magnetic resonance imaging-guided adaptive radiation therapy in pancreatic cancer by extent of re-contouring of organs-at-risk

Purpose@#The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. @*Materials and Methods@#We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. @*Results@#Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations—large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. @*Conclusion@#More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.

Clinical features related to alcohol co-ingestion of deliberate self-poisoning patients visiting the emergency department

Purpose@#Alcohol is one of the most commonly co-ingested agents in deliberate self-poisoning (DSP) cases presenting at the emergency department (ED). The increased impulsivity, aggressiveness, and disinhibition caused by alcohol ingestion may have different clinical features and outcomes in cases of DSP. This study investigates whether alcohol co-ingestion affects the clinical features and outcomes of DSP patients in the ED. @*Methods@#This was a single-center retrospective study. We investigated DSP cases who visited our ED from January 2010 to December 2016. Patients were classified into two groups: with (ALC+) or without (ALC–) alcohol co-ingestion. The clinical features of DSP were compared by considering the co-ingestion of alcohol, and the factors related to discharge against medical advice (AMA) of DSP were analyzed. @*Results@#A total of 689 patients were included in the study, with 272 (39.5%) in the ALC+ group. Majority of the ALC+ group patients were middle-aged males (45-54 years old) and arrived at the ED at night. The rate of discharge AMA from ED was significantly higher in the ALC+ group (130; 47.8%) compared to the ALC– group (p=0.001). No significant differences were obtained in the poisoning severity scores between the two groups (p=0.223). Multivariate analysis revealed that alcohol co-ingestion (odds ratio [OR]=1.42; 95% confidence interval [CI], 1.01-1.98), alert mental status (OR=1.65; 95% CI, 1.17-2.32), past psychiatric history (OR=0.04; 95% CI, 0.01-0.28), age >65 years (OR=0.42; 95% CI, 0.23-0.78), and time from event to ED arrival >6 hrs (OR=0.57; 95% CI, 0.37-0.88) were independent predictive factors of discharge AMA (p=0.043, p=0.004, p=0.001, p=0.006, and p=0.010, respectively). @*Conclusion@#Our results determined a high association between alcohol co-ingestion and the outcome of discharge AMA in DSP patients. Emergency physicians should, therefore, be aware that DSP patients who have co-ingested alcohol may be uncooperative and at high risk of discharge AMA.

Erythema Nodosum after Vaccination against Coronavirus Disease 2019 / 대한피부과학회지

Erythema nodosum (EN) is the most common form of panniculitis and may be triggered by a variety of stimuli, including infections, drugs, pregnancy, sarcoidosis, inflammatory bowel disease, and malignancies. Rare cases of vaccination-related EN have been reported, but none due to the coronavirus disease 2019 (COVID-19) vaccine of Pfizer have been documented. We report a case of EN associated with the Pfizer vaccine. A 43-year-old woman presented with acute-onset painful nodular lesions that appeared bilaterally on the extensor surface of the lower legs. These lesions appeared 5 days after the first dose of Pfizer vaccination. The patient reported no recent infectious history other than fever for 3 days after vaccination. Skin biopsy revealed inflammation extending into the subcutaneous fat with a septal distribution. It is important for physicians to be aware of the side effects of the COVID-19 vaccine because more people are bound to be vaccinated.

History of fertility preservation

Fertility preservation refers to a procedure performed to maintain the ability to become pregnant before receiving treatment with a risk of fertility loss, such as chemo- or radiation therapy. Examples of fertility-preserving procedures include freezing, sperm freezing, embryo freezing through in vitro fertilization, and ovarian tissue freezing.Current Concepts: Until the late 1990s, awareness of fertility preservation among clinicians and patients was relatively low, and the only way to preserve and restore fertility in women with cancer was the cryopreservation of embryos. However, as the survival rate of cancer patients increased and the treatment results of various diseases improved, interest in quality of life such as pregnancy and childbirth after treatment gradually increased, and became a driving force for the development of fertility preservation. In the 2000s, several centers began cryopreserving ovarian tissue, including primordial follicles from young patients before chemotherapy. Currently, ovarian tissue cryopreservation can be used in combination with in vitro maturation and egg vitrification techniques. Novel methods to improve follicle survival after transplantation are currently being investigated. Methods to improve follicle survival after transplantation and new ovarian protective agents to protect the ovaries from cytotoxic agents are currently being studied.Discussion and Conclusion: Advances in fertility-preserving technologies in the future will contribute to the delivery of healthy children by providing tailored treatments and more individualized fertility-preserving strategies to patients whose fertility is at risk.