SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model / 한국실험동물학회지

Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease

Objective@#To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. @*Materials and Methods@#This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1–7 according to acquisition conditions. CT images in groups 2–7 were converted into the target CT sty le (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. @*Results@#Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2–7 improved after CT conversion (original vs. converted: 0.63vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists’ scores were significantly higher (P < 0.001) and less variable on converted CT. @*Conclusion@#CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

Acute Pancreatitis Associated with Eosinophilic Gastroduodenitis: A Case Report / 대한췌담도학회지

Acute pancreatitis caused by eosinophilic gastroenteritis is a rare disease, and little has been reported so far. Diagnosing eosinophilic gastroenteritis is difficult because the symptoms and laboratory findings are not specific. We report a rare case of eosinophilic gastroenteritis related to acute pancreatitis as a possible cause of idiopathic acute pancreatitis. A 61-year-old man visited the hospital complaining of epigastric pain. Although no pancreatic abnormalities were confirmed on imaging studies, the patient showed hyperamylasemia and hyperlipasemia. Serum eosinophil fractions were initially normal. However, they were elevated on follow-up examinations, and a large number of eosinophils were observed in the biopsies of the stomach and duodenum, which led to the diagnosis of eosinophilic gastroduodenitis related to acute pancreatitis.

Clinical Characteristics of Gynecologic Problems During Childhood in the Korean Population

Background@#This study analyzed common gynecologic problems among Korean patients younger than ten years. @*Methods@#We performed a retrospective analysis of medical records of patients younger than ten years who visited the Pediatric and Adolescent Gynecology Clinic at Samsung Medical Center between 1995 and 2020. @*Results@#Among the 6,605 patients who visited the Pediatric and Adolescent Gynecology Clinic, data from 642 patients younger than ten years were analyzed in this study. The most common chief complaint was genital anomalies, followed by increased vaginal discharge and abnormal findings on clinical examinations. The most common disease entity was agglutination of the labia minora, which was commonly discovered incidentally during routine screenings. Vulvovaginitis, the second most common disease, was identified by symptoms of vaginal discharge, pruritus, and vaginal spotting. Neoplasm, issues with vaginal bleeding, and “other causes” were additional categories of gynecologic problems.245 patients (38.2%) were referred from primary care sources, 175 patients (27.4%) sought care directly at the clinic, 169 patients (26.3%) were referrals from the institution’s pediatric department, and the remainder were referrals from other departments. @*Conclusion@#This study provides information about the gynecologic problems most frequently encountered in pediatric patients. The study provides helpful insight for primary care physicians into the proper management and timing of referrals for these gynecologic problems of pediatric patients.

Real-World Treatment Intensity and Patterns in Patients With Myopic Choroidal Neovascularization:Common Data Model in Ophthalmology

Background@#A paucity of data addressing real-world treatment of myopic choroidal neovascularization (mCNV) in the era of anti-vascular endothelial growth factor (VEGF) drugs led us to investigate real-world treatment intensity and treatment patterns in patients with mCNV. @*Methods@#This is a retrospective, observational study using the Observational Medical Outcomes Partnership-Common Data Model database of treatment-naïve patients with mCNV over the 18-year study period (2003–2020). Outcomes were treatment intensity (time trends of total/average number of prescriptions, mean number of prescriptions in the first year and the second year after initiating treatment, proportion of patients with no treatment in the second year) and treatment patterns (subsequent patterns of treatment according to the initial treatment). @*Results@#Our final cohort included 94 patients with at-least 1-year observation period. Overall, 96.8% of patients received anti-VEGF drugs as first-line treatment, with most of injections from bevacizumab. The number of anti-VEGF injections in each calendar year showed an increasing trend over time; however, there was a drop in the mean number of injections in the second year compared to the first year from 2.09 to 0.47. About 77% of patients did not receive any treatment in their second year of treatment regardless of drugs. Most of patients (86.2%) followed non-switching monotherapy only and bevacizumab was the most popular choice either in the first-line (68.1%) or in the second-line (53.8%) of treatment. Aflibercept was increasingly used as the first-line treatment for patients with mCNV. @*Conclusion@#Anti-VEGF drugs have become the treatment of choice and second-line treatment for mCNV over the past decade. Anti-VEGF drugs are effective for the treatment of mCNV as the non-switching monotherapy is the main treatment regimen in most cases and the number of treatments decreases significantly in the second year of treatment.

Clinical Characteristics and Followup Assessment in Patients Diagnosed With Alzheimer’s Dementia Through Regional Dementia Centers and Conventional Hospital System

Background@#The rapidly increasing socioeconomic strain caused by dementia represents a significant public health concern. Regional dementia centers (RDCs) have been established nationwide, and they aim to provide timely screening and diagnosis of dementia. This study investigated the clinical characteristics and progression of patients diagnosed with Alzheimer’s dementia (AD), who underwent treatment in RDCs or conventional communitybased hospital systems. @*Methods@#This retrospective single-center cohort study included patients who were diagnosed with AD between January 2019 and March 2022. This study compared two groups of patients: the hospital group, consisting of patients who presented directly to the hospital, and the RDC group, those who were referred to the hospital from the RDCs in Pohang city. The clinical courses of the patients were monitored for a year after AD diagnosis. @*Results@#A total of 1,209 participants were assigned to the hospital (n = 579) or RDC group (n = 630). The RDC group had a mean age of 80.1 years ± 6.6 years, which was significantly higher than that of the hospital group (P < 0.001). The RDC group had a higher proportion of females (38.3% vs. 31.9%; P = 0.022), higher risk for alcohol consumption (12.4% vs. 3.3%; P < 0.001), and greater number of patients who discontinued treatment 1 year after diagnosis (48.3% vs. 39.0%; P = 0.001). In the linear regression model, the RDC group was independently associated with the clinical dementia rating sum of boxes increment (β = 22.360, R 2 = 0.048, and P < 0.001). @*Conclusion@#Patients in the RDC group were older, had more advanced stages of conditions, and exhibited a more rapid rate of cognitive decline than patients diagnosed through the conventional hospital system. Our results suggested that RDC contributed to the screening of AD in a local region, and further nationwide study with the RDC database of various areas of Korea is needed.

Recent Updates on Tinnitus Management

In this comprehensive review, we discuss recent updates on tinnitus evaluation and treatment. Tinnitus evaluation commences with comprehensive medical history taking and audiological evaluation, which can provide valuable insight into the nature and extent of auditory disturbances. Additionally, tinnitus evaluation includes investigation of psychosomatic comorbidities to determine the intricate interplay between psychological factors and tinnitus perception. Various therapeutic approaches are available to minimize the burden of tinnitus. Cognitive behavioral therapy reshapes negative thought patterns and behaviors that are closely associated with tinnitus-induced distress. Acceptance and commitment therapy fosters mindfulness and value-aligned actions to address emotional effects. Tinnitus retraining therapy combines counseling and sound therapy for habituation. Tailor-made notched music therapy offers customized auditory experiences for symptom relief. Hearing aids and cochlear implants compensate for hearing loss and associated stress. Both neuromodulation and neurofeedback may be potentially useful. The role of pharmacotherapy and dietary supplements remains uncertain. Physiotherapy and head-neck manipulation relieve tinnitus associated with orofacial factors. Virtual reality, smartphone applications, and photobiomodulation may serve as novel therapeutic avenues. Although promising interventions are available, further research is warranted to confirm their effectiveness and long-term effects.

Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma

Background/Aims@#Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. @*Methods@#This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. @*Results@#Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. @*Conclusions@#Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.

Clinical outcomes and genotype-phenotype correlations in patients with complete and partial androgen insensitivity syndromes

Purpose@#Androgen insensitivity syndrome (AIS) is a rare X-linked recessive disorder caused by unresponsiveness to androgens because of mutations in the AR gene. Here, we investigated the clinical outcomes and molecular spectrum of AR variants in patients with AIS attending a single academic center. @*Methods@#This study included 19 patients with AIS who were confirmed by molecular analysis of AR. Clinical features and endocrinological findings were retrospectively collected, including presenting features, external genitalia, sex of rearing, timing of gonadectomy, pubertal outcomes, and sex hormone levels. Molecular analysis of AR was performed using Sanger, targeted gene panel, or whole-exome sequencing. @*Results@#Among all 19 patients, 14 (74%) were classified as having complete AIS (CAIS), whereas 5 (26%) had partial AIS (PAIS). All patients with CAIS, and 3 patients with PAIS were reared as female. One patient with CAIS manifested a mixed germ cell tumor at the age of 30 years. Molecular analysis of AR identified 19 sequence variants; 12 (63%) were previously reported, and the remaining 7 (37%) were novel. Missense mutations were the most common type (12 of 19, 63%), followed by small deletions, nonsense mutations, an insertion, and a splice site mutation. @*Conclusion@#Here, we describe the clinical outcomes and molecular characteristics of 19 Korean patients with AIS. Patients with PAIS manifested various degrees of masculinization of the external genitalia. Nonsense and frameshift mutations were frequent in patients with CAIS, whereas patients with PAIS harbored exclusively missense mutations.

MRI-Based Stepwise Approach to Anterior Mediastinal Cystic Lesions for Diagnosis and Further Management

As the majority of incidentally detected lesions in the anterior mediastinum is small nodules with soft tissue appearance, the differential diagnosis has typically included thymic neoplasm and prevascular lymph node, with benign cyst. Overestimation or misinterpretation of these lesions can lead to unnecessary surgery for ultimately benign conditions. Diagnosing mediastinal cysts using MRI serves as a problem-solving modality in distinguishing between surgical and nonsurgical anterior mediastinal lesions. The pitfalls of MRI evaluation for anterior mediastinal cystic lesions are as follows: first, we acknowledge the limitation of T2-weighted images for evaluating benign cystic lesions. Due to variable contents within benign cystic lesions, such as hemorrhage, T2 signal intensity may be variable. Second, owing to extensive necrosis and cystic changes, the T2 shine-through effect may be seen on diffusion-weighted images (DWI), and small solid portions might be missed on enhanced images.Therefore, both enhancement and DWI with apparent diffusion coefficient values should be considered. An algorithm will be suggested for the diagnostic evaluation of anterior mediastinal cystic lesions, and finally, a management strategy based on MRI features will be suggested.

Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center

Background@#Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. @*Methods@#This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. @*Results@#In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). @*Conclusions@#There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer. @*Materials and Methods@#After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method. @*Results@#Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy. @*Conclusion@#TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

Effects of Socioeconomic Status and Residence Areas on Long-Term Survival in Patients With Early-Onset Dementia: The Korean National Health Insurance Service Database Study

Background@#Early-onset dementia (EOD) is still insufficiently considered for healthcare policies. We investigated the effect of socio-environmental factors on the long-term survival of patients with EOD. @*Methods@#This retrospective cohort study utilized the Korean National Health Insurance Database from 2007 to 2018. We enrolled 3,825 patients aged 40 to 65 years old with all types of dementia newly diagnosed in 2009 as EOD cases. We defined socioeconomic status using the national health insurance premium (NHIP) levels. Residential areas were classified into capital, metropolitan, city, and county levels. All-cause mortality was the primary outcome. Kaplan-Meier curves and log-rank tests were employed. Further, Cox-proportional hazards models were established. @*Results@#The mean survival of the fourth NHIP level group was 96.31 ± 1.20 months, whereas that of the medical-aid group was 85.53 ± 1.30 months (P < 0.001). The patients living in the capital had a mean survival of 95.73 ± 1.34 months, whereas those living in the county had 89.66 ± 1.75 months (P = 0.035). In the Cox-proportional hazards model, the medical-aid (adjusted hazard ratio [aHR], 1.67; P < 0.001), first NHIP level (aHR, 1.26; P = 0.012), and second NHIP level (aHR, 1.26; P = 0.008) groups were significantly associated with a higher long-term mortality risk. The capital residents exhibited a significantly lower long-term mortality risk than did the county residents (aHR, 0.82; P = 0.041). @*Conclusion@#Socioeconomic status and residential area are associated with long-term survival in patients with EOD. This study provides a rational basis for establishing a healthcare policy for patients with EOD.

Prognostic value of complete metabolic response on 18F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer / 부인종양

Objective@#We investigated the prognostic value of complete metabolic response (CMR) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC). @*Methods@#PET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis. @*Results@#Between 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048). @*Conclusion@#CMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.

PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies / 부인종양

The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial / 부인종양

Objective@#Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. @*Methods@#This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). @*Results@#Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. @*Conclusion@#This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

Indocyanine green fluorescent image-guided inguinal sentinel lymph node biopsy in vulvar cancer

Objective@#To demonstrate near-infrared fluorescence image-guided inguinal sentinel lymph node (SLN) biopsy in patients with vulvar cancer. @*Methods@#A 40-year-old woman with a 3-cm-sized palpable left vulvar mass was diagnosed with vulvar cancer on biopsy with protrusion into the vaginal cavity. Pelvic contrast-enhanced magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography-computed tomography showed a small ulcerative enhancing lesion confined to the left vulva without distant metastasis. The patient was scheduled for radical vulvectomy with a left inguinal SLN biopsy. Indocyanine green was injected directly into the vulvar mass to map lymphatic drainage. A 4-cm-sized linear incision was made on the left inguinal crease, and the lymphatic channels of the left inguinal area were dissected under fluorescent image guidance using a 1588 Advanced Imaging Modalities Platform laparoscopic camera (Stryker, Kalamazoo, MI, USA). @*Results@#Fluorescence image-guided left inguinal SLN biopsy and radical vulvectomy were performed. The pathologic diagnosis confirmed vulvar adenoid cystic carcinoma with metastasis to the left inguinal lymph node (International Federation of Gynecology and Obstetrics stage IIIA). The patient was discharged without complications and received adjuvant radiotherapy. @*Conclusion@#This video demonstrates a successful ICG fluorescence image-guided left inguinal SLN biopsy in a vulvar cancer patient using a laparoscopic camera. Mapping of inguinal SLNs in patients with vulvar cancer may help in retaining surgical radicality while minimizing operative complications.

The Clinical Impact of β-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention

Background and Objectives@#The outcome benefits of β-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of β-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). @*Methods@#A total of 3,075 patients with chronic CAD were included from the Grand DrugEluting Stent registry. We analyzed β-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (β-blockers vs. no β-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of β-blockers. @*Results@#During a median (interquartile range) follow-up of 3.1 (3.0–3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, β-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63–1.24), all-cause death (HR, 0.87; 95% CI, 0.60–1.25), and MI (HR, 1.25; 95% CI, 0.49–3.15). In subgroup analysis, β-blockers were associated with a lower risk of all-cause death in patients with previous MI and/ or revascularization (HR, 0.38; 95% CI, 0.14–0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of β-blockers. @*Conclusions@#Overall, β-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of β-blockers may exist for patients with previous MI and/or revascularization.

Long-term Outcome of Fontan-Associated Protein-Losing Enteropathy: Treatment Modality and Predictive Factor of Mortality

Background and Objectives@#Protein-losing enteropathy (PLE) is a devastating complication after the Fontan operation. This study aimed to investigate the clinical characteristics, treatment response, and outcomes of Fontan-associated PLE. @*Methods@#We reviewed the medical records of 38 patients with Fontan-associated PLE from 1992 to 2018 in 2 institutions in Korea. @*Results@#PLE occurred in 4.6% of the total 832 patients after the Fontan operation. After a mean period of 7.7 years after Fontan operation, PLE was diagnosed at a mean age of 11.6years. The mean follow-up period was 8.9 years. The survival rates were 81.6% at 5 years and 76.5% at 10 years. In the multivariate analysis, New York Heart Association Functional classification III or IV (p=0.002), low aortic oxygen saturation (<90%) (p=0.003), and ventricular dysfunction (p=0.032) at the time of PLE diagnosis were found as predictors of mortality. PLE was resolved in 10 of the 38 patients after treatment. Among medical managements, an initial heparin response was associated with survival (p=0.043). Heparin treatment resulted in resolution in 4 patients. We found no evidence on pulmonary vasodilator therapy alone. PLE was also resolved after surgical Fontan fenestration (2/6), aortopulmonary collateral ligation (1/1), and transplantation (1/1). @*Conclusions@#The survival rate of patients with Fontan-associated PLE has improved with the advancement of conservative care. Although there is no definitive method, some treatments led to the resolution of PLE in one-fourth of the patients. Further investigations are needed to develop the best prevention and therapeutic strategies for PLE.

Etiology and Secular Trends in Primary Amenorrhea in 856 Patients: A 17-Year Retrospective Multicenter Study in Korea

Background@#This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea. @*Methods@#This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis. @*Results@#The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance. @*Conclusion@#The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.