Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease

Extramedullary multiple myeloma (EMD) is an aggressive subentity of multiple myeloma (MM) with poor progno‑ sis. As more innovative therapeutic approaches are needed for the treatment of MM with EMD, we conducted this multicenter, non-randomized phase II trial of daratumumab in combination with dexamethasone, cyclophospha‑ mide, etoposide and cisplatin (DARA-DCEP). A total of 32 patients (median age 59, range 35–73) were treated with DARA-DCEP. Based on the best response during the study, the complete remission (CR) rate was 35.5% and overall response rate (ORR) 67.7%. During the median follow-up of 11 months, the median progression-free survival (PFS) was 5 months and median overall survival (OS) 10 months. There were 7 long-term responders whose median PFS was not reached. The most common grade≥3 hematologic AE was thrombocytopenia. The most common non-hematologic AE was nausea (22.6%), followed by dyspepsia, diarrhea and stomatitis (all 12.9%). Grade≥3 daratumumab infusionrelated reaction was noted in 9.7% of the patients. Except for the planned 30% dose adjustment in cycle 1, only 2 patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we success‑ fully laid grounds for implementing immunochemotherapy in MM treatment.This work was supported by grants from the Korea Health Technolà ¢ ogy R&D Project through the Korea Health Industry Development Institute (KHIDI, HI14C1277)

The association of asthma and its subgroups with osteoporosis: a cross-sectional study using KoGES HEXA data

Background A few studies have reported the association between asthma and osteoporosis. We aimed to analyze the association of asthma and its subgroups with osteoporosis in the Korean adult population. Methods We used the health examinee (HEXA) data from the Korean Genome and Epidemiology Study (KoGES) obtained between 2004 and 2016. We included 162,579 participants (n = 3,160 with asthma; n = 159,419 controls) who reported their previous histories of asthma and osteoporosis. The participants were categorized into 3 groups based on asthma management: participants who did not need further treatment due to controlled symptoms (well controlled); participants with ongoing treatment (being treated); participants who were not treated even though they had symptoms (not being treated). Multiple logistic regression analyses were used to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for osteoporosis. Subgroup analyses for age and sex were conducted. Results The prevalence of osteoporosis was higher in patients with asthma (13.6%) than in controls (6.8%). In the full-adjusted model, the aORs for osteoporosis were 1.74 (95% CI 1.55–1.94, P < 0.001) in patients with asthma compared to controls. There were consistent findings across the age and sex subgroups. The aORs for osteoporosis were 1.43 (95% CI 1.10–1.86, P = 0.008) in the well-controlled asthma group; 1.55 (95% CI 1.28–1.89, P < 0.001) in the being treated asthma group; and 1.96 (95% CI 1.66–2.31, P < 0.001) in the not being treated asthma group compared to the control group. Conclusion Asthma was associated with osteoporosis in the Korean adult population. Patients with asthma not being treated showed the highest ORs for osteoporosis.This research was funded by National Research Foundation (NRF) of Korea, grant number (NRF-2018-R1D1A1A0-2085328 by Hyo Geun Choi, NRF-2020R1G1A1005390 by Jee Hye Wee). The funding organization did not contribute to the design or conduct of this study, preparation, review, approval, or decision to submit this manuscript for publication

Real-Life Efficacy and Tolerability of Lacosamide in Pediatric Patients Aged 4 Years or Older with Drug-Resistant Epilepsy

Purpose The aim of this study was to evaluate the efficacy and safety of adjunctive lacosamide therapy in pediatric patients aged ≥4 years with drug-resistant epilepsy (DRE). Methods Medical records of children aged 4 to 19 years treated with lacosamide as adjunctive therapy for DRE were retrospectively reviewed. The patients were divided into two groups according to their age at the start of lacosamide treatment: group A (aged 4–15 years) and group B (aged 16–19 years). Changes in seizure frequency from baseline, adverse events, and the retention rate were evaluated at each follow-up visit. Results Sixty-two patients (33 males and 29 females) with a mean age of 11.4 years (range, 4 to 19) were included. The mean duration of follow-up was 20.1±12.9 months. The mean maintenance dose of lacosamide was 6.7±4.8 mg/kg/day. Forty-two patients (67.7%) were responders (≥50% reduction in seizures) with 19.4% (12/62) achieving freedom from seizures. The response rate did not differ significantly between groups A and B (67.6% vs. 68.0%, P=0.795) and was not affected by the concomitant use of sodium channel blockers. Significant independent factors associated with a good response to lacosamide treatment were a shorter duration of epilepsy (P=0.035) and fewer concomitant anti-seizure medications (P=0.002). Mild transient adverse events were observed in 20 patients (32.3%). Conclusion Lacosamide adjunctive therapy was efficacious and tolerated in children aged ≥4 years with DRE. Early use of lacosamide may be helpful for a good response to drug-resistant seizures

A Case of Acute Myocardial Infarction with the Anomalous Origin of the Right Coronary Artery from the Ascending Aorta above the Left Sinus of Valsalva and Left Coronary Artery from the Posterior Sinus of Valsalva

Coronary anomalies are rare angiographic findings. Moreover, there are few reports of cases of an anomalous origin of the right coronary artery from the left sinus of Valsalva and of the left coronary artery from the posterior sinus of Valsalva. Here, we report a case with an anomalous origin of the right coronary artery from the ascending aorta above the left sinus of Valsalva and the left coronary artery from the posterior sinus of Valsalva. This was observed in a patient who was treated for a myocardial infarction of the inferior wall caused by a thrombus in the proximal right coronary artery. The patient was treated successfully with the implantation of a stent in the anomalous origin of the right coronary artery using a 6Fr Amplatz left 1 catheter

Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19

Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.Peer reviewe

Occult bacteremia in children with simple febrile seizure in the post-pneumococcal conjugate vaccine era

Purpose The authors aimed to investigate the utility of blood culture (BC) for children with simple febrile seizure (SFS) in the emergency department (ED) in the post-10/13-valent pneumococcal conjugate vaccine (PCV) era. Methods This study was performed at the ED of a tertiary care university-affiliated women and children’s hospital, and involved 3,237 previously healthy children aged 6-60 months who visited the ED with SFS from January 2013 through December 2017. The SFS was defined according to the International Classification of Diseases, 11th Revision codes related to seizure. The children were divided into 2 groups according to the vaccination rates of the period of their visit: the 70-PCV (70%, 2013-2014) and 97-PCV (97%, 2015-2017) groups. The primary outcome was the yield, defined as a true positivity of BC. In addition, we collected information on baseline characteristics, ED length of stay, inflammatory biomarkers, and ED outcomes. Results Of the 1,578 children with SFS who underwent BC, 1,357 belonged to the 97-PCV group. The median age of the study population was 22 months (interquartile range, 16.0-30.0), and 935 children (59.3%) were boys. Of the 41 children (2.6%) with positive BC results, 3 had the yield (0.2%): Staphylococcus aureus in 2 children and Streptococcus pneumoniae in the other. All 3 children belonged to the 97-PCV group. There were 38 contaminated BCs (2.4%; 95% confidence interval, 1.6%-3.2%). The 97-PCV group showed a shorter median ED length of stay (166.0 minutes [108.0-279.5] vs. 143.0 [109.5-209.5]; P = 0.010) and a lower rate of hospitalization (39.4% vs. 12.8%; P < 0.001). No differences between the 2 groups were found in the baseline characteristics and biomarkers. Conclusion This study suggests a low utility of BC in previously healthy children with SFS in emergency settings in the post-10/13-valent PCV era

Subarachnoid Hemorrhage Mimicking Leakage of Contrast Media After Coronary Angiography

We report a patient who developed subarachnoid hemorrhage (SAH) just after coronary angiography (CAG) with non-ionic contrast media (CM) and minimal dose of heparin. The 55-year-old man had a history of acute ST elevation myocardial infarction that had been treated with primary percutaneous coronary intervention and was admitted for a follow-up CAG. The CAG was performed by the transradial approach, using 1000 U of unfractionated heparin for the luminal coating and 70 mL of iodixanol. At the end of CAG, he complained of nausea and rapidly became stuporous. Brain CT showed a diffusely increased Hounsfield unit (HU) in the cisternal space, similar to leakage of CM. The maximal HU was 65 in the cisternal space. No vascular malformations were detected on cerebral angiography. The patient partially recovered his mental status and motor weakness after 2 days. Two weeks later, subacute SAH was evident on magnetic resonance imaging. The patient was discharged after 28 days

Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies

Background Very little is known for the direction or causality of the relationship between lifetime sleep experiences and in vivo Alzheimers disease (AD) pathologies. This study aimed to examine the relationship between sleep experiences during the young adulthood, midlife, and late-life periods and in vivo cerebral beta-amyloid (Aβ) deposition and AD signature regional neurodegeneration in cognitively normal (CN) old adults. Methods This study included 202 CN old adults who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimers Disease (KBASE) study. All participants underwent a comprehensive clinical assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] Fluorodeoxyglucose-PET, and magnetic resonance imaging. The quality and duration of sleep were assessed for the following age periods: 20–30s, 40–50s, and the most recent month. All analyses were adjusted for age, gender, education, apolipoprotein E ε4 status, vascular risk score, Hamilton Depression Rating Scale score, and use of sleep medication. Results Bad sleep quality and short sleep duration during midlife were significantly associated with increased Aβ deposition and AD signature regional hypometabolism, respectively. Although current bad sleep quality appeared to be associated with increased Aβ accumulation, this association disappeared after controlling for the effects of midlife sleep quality. Neither the quality nor duration of sleep during young adulthood was related to Aβ burden or neurodegeneration. Conclusions Bad sleep quality during midlife increases pathological Aβ deposition in the brain, while short sleep duration during the same period accelerates regional hypometabolism.This study was supported by a grant from the Ministry of Science, ICT, and Future Planning, Republic of Korea (Grant No: NRF-2014M3C7A1046042) and 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 No: HI18C0630). The funding source had no role in the design of the study; collection, analysis, and interpretation of the data; and writing of the manuscript

Synergistic interaction between APOE and family history of Alzheimers disease on cerebral amyloid deposition and glucose metabolism

Background Recently, the field of gene-gene or gene-environment interaction research appears to have gained growing interest, although it is seldom investigated in Alzheimers disease (AD). Hence, the current study aims to investigate interaction effects of the key genetic and environmental risks—the apolipoprotein ε4 allele (APOE4) and family history of late-onset AD (FH)—on AD-related brain changes in cognitively normal (CN) middle-aged and older adults. Methods [11C] Pittsburg compound-B (PiB) positron emission tomography (PET) imaging as well as [18F] fluoro-2-deoxyglucose (FDG) PET that were simultaneously taken with T1-weighted magnetic resonance imaging (MRI) were obtained from 268 CNs from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE). Composite standardized uptake value ratios were obtained from PiB-PET and FDG-PET images in the AD signature regions of interests (ROIs) and analyzed. Voxel-wise analyses were also performed to examine detailed regional changes not captured by the ROI analyses. Results A significant synergistic interaction effect was found between the APOE4 and FH on amyloid-beta (Aβ) deposition in the AD signature ROIs as well as other regions. Synergistic interaction effects on cerebral glucose metabolism were observed in the regions not captured by the AD signature ROIs, particularly in the medial temporal regions. Conclusions Strong synergistic effects of APOE4 and FH on Aβ deposition and cerebral glucose metabolism in CN adults indicate possible gene-to-gene or gene-to-environment interactions that are crucial for pathogenesis of AD involving Aβ. Other unspecified risk factors—genes and/or environmental—that are captured by the positive FH status might either coexpress or interact with APOE4 to alter AD-related brain changes in CN. Healthy people with both FH and APOE4 need more attention for AD prevention.This study was supported by a grant from the Ministry of Science and ICT, Republic of Korea (grant no. NRF-2014M3C7A1046042). The funding source had no role in the study design, data collection, data analysis, data interpretation, writing of the manuscript, or decision to submit it for publication