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Purpose@#This study aimed to evaluate the role of Doppler ultrasound (US) and elastography to identify residual breast cancer for patients showing near complete response following chemotherapy on magnetic resonance imaging (MRI). @*Methods@#Between September 2016 and January 2018, 40 breast cancer patients who showed near complete response (either tumor size ≤0.5 cm or lesion-to-background parenchymal signal enhancement ratio ≤1.6) on MRI following neoadjuvant chemotherapy were prospectively enrolled. After excluding seven women who did not undergo Doppler US and elastography, 33 women (median age, 49 years; range, 32 to 67 years) were analyzed. On the day of surgery, women underwent Doppler US and elastography for tumor bed prior to US-guided core needle biopsy. Histopathologic results of biopsy and surgery were evaluated. Negative predictive value (NPV) and false negative rate (FNR) of biopsy and the combined Doppler US and elastography were analyzed, respectively. @*Results@#After surgery, nine women had residual cancers and 24 women had pathologic complete response. The NPV and FNR of biopsy were 92% (24 of 26) and 22% (2 of 9), respectively. The NPV and FNR of combined Doppler US and elastography were 100% (14 of 14) and 0% (0 of 9), respectively. All of nine women with residual cancers had positive vascularity or elasticity. Two women with false-negative biopsy results, having 0.3 cm or 2.5 cm ductal carcinoma in situ at surgery, showed positive vascularity or elasticity. @*Conclusion@#Tumor bed showing positive vascularity or elasticity indicates residual breast cancer for patients showing near complete response on MRI following chemotherapy.
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Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
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Purpose@#Pediatric drug poisoning is a frequent reason for emergency department (ED) visits. Considering the increasing number of mental illnesses in adolescents, it has become a serious public health problem. We aimed to investigate the drug poisoning in the ED. @*Methods@#We retrospectively analyzed children aged 1-17 years with diagnostic codes related to drug poisoning who visited the ED from January 1, 2010 through October 7, 2022. Exclusion criteria were non-pharmaceutical poisoning, insufficient data, and poisoning via respiratory, dermal or ocular route. Baseline characteristics, clinical manifestations, and outcomes of drug poisoning were analyzed in the study population, according to intention of poisoning and drug category. @*Results@#A total of 197 cases of 161 children were analyzed. Compared with non-intentional poisoning, intentional poisoning was associated a higher age, a longer time from ingestion to visit, and higher proportions of girls, antipyretics/analgesics or psychotropic drugs, symptoms related to the gastrointestinal, neurologic or cardiopulmonary systems (P = 0.034), psychiatric comorbidity, multiple drug ingestion, suicide attempt, decontamination (P = 0.017), the use of antidote, history of drug poisoning, and hospitalization (P = 0.004; all other Ps < 0.001). Acetaminophen, a representative of antipyretics/analgesics, was associated with a longer time from ingestion to visit and higher proportions of girls (P = 0.004), the presence of initial gastrointestinal symptoms, suicide attempt (P = 0.001), the use of antidote, and hospitalization (all other Ps < 0.001). Psychotropic drug was associated with higher proportions of psychiatric comorbidity (P < 0.001) and multiple drug ingestion (P = 0.012). @*Conclusion@#This study will enable pediatricians or emergency physicians to obtain an overview of the management of drug poisoning in EDs.
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Objective@#To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts. @*Materials and Methods@#A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared. @*Results@#A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40–78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8–19.7] vs. 9.8 [17 of 1726;95% CI: 5.7–15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%–34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%–24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%–28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%–18.9%; P < 0.001). @*Conclusion@#DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts.
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Background/Aims@#The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD. @*Methods@#Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline. @*Results@#The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD. @*Conclusions@#The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.
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This study aimed to investigate the concentrations of nonpersistent endocrine-disrupting chemicals (EDCs) and per- and polyfluoroalkyl substances (PFAS) in human milk through a literature review and to affirm the association between EDCs and lifestyle factors based on the reviewed literature. We analyzed studies reporting EDC concentrations in breast milk from literature published on Google Scholar and PubMed between 2000 and 2022. In Korea, most EDC concentrations in breast milk were comparable to or lower than those in other countries. However, the concentrations of PFAS in breast milk, especially perfluorooctanoic acid, have shown an increasing trend compared to the past in Korea. Considering the potential risks of EDCs, breastfeeding mothers should take measures to minimize their exposure to these chemicals.
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Purpose@#To evaluate the postoperative changes in macular vessel density and the multifocal electroretinogram (mfERG) in the epiretinal membrane (ERM) of a combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). And we compared these results with those of idiopathic ERM.Method: We retrospectively reviewed the records of 15 patients (15 eyes) with an epiretinal membrane of a CHRRPE, and 21 patients (21 eyes) with idiopathic ERM who were treated with pars plana vitrectomy and removal of the ERM. The best corrected visual acuity, central macula thickness, foveal and perifoveal vessel density, foveal avascular zone (FAZ), and mfERG rings 1 and 2 P1 amplitudes were analyzed before and 6 months after ERM removal. @*Results@#The average macular vessel density in the CHRRPE with ERM was reduced (p = 0.047) compared to an idiopathic epiretinal membrane, but the central foveal vessel density was significantly increased (p = 0.003). In CHRRPE, the preoperative FAZ was significantly reduced, and while it increased significantly 6 months postoperatively. After removing the ERM, the P1 amplitude increased significantly on mfERG, but there was no significant difference compared to the idiopathic ERM. @*Conclusions@#The macular mean superficial capillary plexus (SCP) vascular density was reduced in CHRRPE and the foveal SCP vascular density and FAZ were increased. Considering the increased size of the FAZ area after surgery, physical removal of the ERM affected the structural recovery of the fovea, but resulted in no significant improvement of the macular superficial microvascular system.
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Rubinstein-Taybi syndrome (RSTS) is an extremely rare genetic disorder affecting multi-organ systems. A tendency to form keloid is one of the common dermatologic manifestations.We describe a 23-year-old female presented with extensive keloids which developed spontaneously. She had typical facial features, broad thumbs, and dental defects, which were suspicious features of genetic syndrome. Direct sequencing for cyclic-AMP-regulated enhancer binding protein revealed a novel mutation. So far, 23 cases of RSTS have been reported in Korean literature. To the best of our knowledge, this is the first report in Korea to describe confirmed case of RSTS with extensive keloids as a chief manifestation.
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Purpose@#Laparoscopic surgery is a choice in several emergency settings. However, there has been no nationwide study or survey that has compared the clinical use of laparoscopic emergency surgery (LES) versus open abdominal emergency surgery (OES) in Korea.Therefore, we examined the state of LES across multiple centers in Korea and further compared this data with the global state based on published reports. @*Methods@#Data of 2,122 patients who received abdominal emergency surgery between 2014 and 2019 in three hospitals in Korea were collected and retrospectively analyzed. Several clinical factors were investigated and analyzed. @*Results@#Of the patients, 1,280 (60.3%) were in the OES group and 842 (39.7%) were in the LES group. The most commonly operated organ in OES was the small bowel (25.8%), whereas that for LES was the appendix. In appendectomy and cholecystectomy, 93.7% and 88.0% were in the LES group. In small bowel surgery, gastric surgery, and large bowel surgery, 89.4%, 92.0%, and 79.1% were in the OES group. The severity-related factors of patient status demonstrated statistically significant limiting factors of selection between LES and OES. @*Conclusion@#Although our study has several limitations, compared to the LES data from other countries, the general LES state was similar in appendectomies, cholecystectomies, and small bowel surgeries. However, in gastric and colorectal surgeries, the LES state was different from those of other countries. This study demonstrated the LES state and limiting factors of selection between LES and OES in various operated organs. Further studies are required to analyze these differences and the various limiting factors.
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Purpose@#This study aimed to evaluate the effectiveness of simulation-based education on communication and clinical judgment in nursing students and nurses. @*Methods@#A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. Seven databases were searched to obtain articles published in Korean or English. Of 12,864 articles reviewed, 36 were included in a systematic review and 23 in a meta-analysis. To estimate the size of the effects of simulation-based education, a meta-analysis was performed using the R package meta program. The risk of bias was assessed using RoB 2.0 and ROBINS-I. @*Results@#The effect sizes (ES) of simulation-based education on communication and clinical judgment were ES=0.77, 95% confidence interval (95% CI)=0.43 to 1.12 on communication-related variables and ES=1.84, 95% CI=1.03 to 2.65 on clinical judgment. @*Conclusion@#Simulation-based education for nursing students and nurses is useful for improving their communication and clinical judgment. Thus, it is necessary to develop and apply simulation-based education programs for nursing students and nurses to improve their abilities in communications and clinical judgment.
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The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother.Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.
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Despite recent advances in artificial intelligence (AI) software with improved performance in mammography screening for breast cancer, insufficient data are available on its performance in detecting cancers that were initially missed on mammography. In this study, we aimed to determine whether AI software-aided mammography could provide additional value in identifying cancers detected through supplemental screening ultrasound. We searched our database from 2017 to 2018 and included 238 asymptomatic patients (median age, 50 years; interquartile range, 45–57 years) diagnosed with breast cancer using supplemental ultrasound. Two unblinded radiologists retrospectively reviewed the mammograms using commercially available AI software and identified the reasons for missed detection.Clinicopathological characteristics of AI-detected and AI-undetected cancers were compared using univariate and multivariate logistic regression analyses. A total of 253 cancers were detected in 238 patients using ultrasound. In an unblinded review, the AI software failed to detect 187 of the 253 (73.9%) mammography cases with negative findings in retrospective observations. The AI software detected 66 cancers (26.1%), of which 42 (63.6%) exhibited indiscernible findings obscured by overlapping dense breast tissues, even with the knowledge of magnetic resonance imaging and post-wire localization mammography. The remaining 24 cases (36.4%) were considered interpretive errors by the radiologists. Invasive tumor size was associated with AI detection after multivariable analysis (odds ratio, 2.2; 95% confidence intervals, 1.5–3.3; p < 0.001). In the control group of 160 women without cancer, the AI software identified 19 false positives (11.9%, 19/160). Although most ultrasound-detected cancers were not detected on mammography with the use of AI, the software proved valuable in identifying breast cancers with indiscernible abnormalities or those that clinicians may have overlooked.
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Background@#The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. @*Methods@#Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. @*Results@#Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. @*Conclusions@#The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.
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Purpose@#To assess the diagnostic performances of diffusion-weighted imaging (DWI)-included non-contrast magnetic resonance imaging (MRI) compared to standard contrastenhanced MRI for infectious spondylitis. @*Materials and Methods@#This study involved 154 participants: a spondylitis group (n = 76) and a control group (n = 78) with Modic type 1 degeneration or recent compression fractures. Two readers independently reviewed paraspinal soft tissue signal change and abscess with 5-scale confidence scores based on two image sets: one featuring both non-contrast-enhanced MRI (NCEI) and DWI and the other consisting of NCEI and contrast-enhanced fat-suppressed T1-weighted imaging (CEFST1). The diagnostic performance of the two image sets was compared using McNemar tests for sensitivity, specificity, and area under the receiver operating characteristics (AUROC) analysis. Interobserver agreements (κ) for each images sets were also calculated. @*Results@#The sensitivity and specificity for infectious spondylitis were 90.8% and 69.2% for NCEI + DWI, 96.1% and 60.3% for NCEI + CEFST1 in reader 1, whereas it was 92.1% and 66.7% for NCEI + DWI, and 96.1% and 68.0% for NCEI + CEFST1 in reader 2. Sensitivities and specificities were not significantly different between NCEI + DWI and NCEI + CEFST1 (reader 1: p = 0.289, 0.065; reader 2: p = 0.250, > 0.999, respectively). However, the AUROC was not considerably different between the two modalities in only one reader (p = 0.306 in reader 1, p = 0.031 in reader 2). Interobserver agreement for infectious spondylitis was moderate (κ = 0.55) in NCEI + DWI and substantial (κ = 0.66) in NCEI + CEFST1. @*Conclusion@#Non-contrast enhanced MRI with additional DWI is as effective for diagnosing infectious spondylitis as a contrast-enhanced MRI.
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Purpose@#The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC). @*Materials and Methods@#Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model. @*Results@#LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model. @*Conclusion@#The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.
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Thyroid hormone plays a vital role in regulating human metabolism. They affect the functions of major organs, such as the brain, liver, skeletal muscle, and heart. Hypothyroidism can lead to dilated cardiomyopathy and decreased heart function. In this report, we describe a case of a teenage boy who developed dilated cardiomyopathy due to hypothyroidism and was considered to undergo heart transplantation. Levothyroxine monotherapy was initiated but produced no improvement. Thereafter, a combination therapy of liothyronine and levothyroxine was administered, and heart function was gradually restored; he recovered completely after 6 months. Cardiac myocytes respond more specifically to liothyronine than to levothyroxine. Therefore, we suggest that liothyronine and levothyroxine combination therapy should be considered rather than levothyroxine monotherapy for hypothyroidism accompanied by heart disease.
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Background: Intralesional immunotherapy has been reported to be effective for warts and to show good safety profiles, but this has not yet been systematically studied. Aims: To determine the efficacy and safety of intralesional immunotherapy for treating non-genital warts. Methods: We comprehensively searched the MEDLINE, Embase, Web of Science and Cochrane Library databases from the times of their inception to January 3, 2020. The primary outcome was the rate of complete response of all lesions. The distant complete response rate of warts located in an anatomically different body part and the recurrence rate were also analyzed. Results: A total of 54 prospective studies was ultimately included. The immunotherapeutic agents used were Mycobacterium w vaccine, measles, mumps and rubella vaccine, purified protein derivative, Candida antigen, interferon, bacillus Calmette-Guérin vaccine and others. The pooled rate of complete response among all patients with non-genital warts treated using intralesional immunotherapy was 60.6% (95% confidence interval 54.8–66.5%). The pooled recurrence rate was 2.0% (95% confidence interval, 1.1–2.9%). All reported adverse events were mild and transient. Limitations: The heterogeneity among studies Conclusion: Intralesional immunotherapy is suggested for use in patients with multiple warts, given its promising results, good safety profile and low recurrence rate.
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Background/Aims@#The effects of probiotics in children vary based on diseases and probiotic strains. We aim to investigate the effectiveness of Saccharomyces boulardii and lactulose for treating childhood functional constipation. @*Methods@#This open-label randomized controlled trial was conducted at 10 university hospitals in Korea. Children who were diagnosed with functional constipation were allocated to 3 groups (lactulose monotherapy, combination therapy, and S. boulardii monotherapy). The primary outcome was treatment success rate that was accordingly defined as ≥ 3 bowel movements without incontinence at week 12. The cumulative successful maintenance and drug maintenance rates without drug changes were calculated throughout the study period. We compared stool frequency, incontinence, consistency, and painful defecation at week 2 among the 3 groups. @*Results@#Overall, 187 children were assigned to the lactulose monotherapy (n = 69), combination therapy (n = 68), or S. boulardii monotherapy (n = 50) groups. The primary outcome was significantly higher in the lactulose monotherapy group (26.1%) or combination therapy group (41.2%) than in the S. boulardii monotherapy group (8.0%). The S. boulardii monotherapy group showed a significantly lower cumulative successful maintenance and drug maintenance rate than the other 2 groups. There were no significant intergroup differences in the frequency of defecation, incontinence, painful defecation, or stool consistency during the follow-up at week 2. @*Conclusion@#S. boulardii monotherapy was not superior to lactulose monotherapy or combination therapy and showed a higher drug change rate, supporting the current recommendation of probiotics in the treatment of childhood functional constipation.
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Preserving intact genetic material and delivering it to the next generation are the most significant tasks of living organisms. The integrity of DNA sequences is under constant threat from endogenous and exogenous factors. The accumulation of damaged or incompletely-repaired DNA can cause serious problems in cells, including cell death or cancer development. Various DNA damage detection systems and repair mechanisms have evolved at the cellular level. Although the mechanisms of these responses have been extensively studied, the global RNA expression profiles associated with genomic instability are not well-known. To detect global gene expression changes under different DNA damage and hypoxic conditions, we performed RNA-seq after treating human cervical cancer cells with ionizing radiation (IR), hydroxyurea, mitomycin C (MMC), or 1% O2 (hypoxia). Results showed that the expression of 184–1037 genes was altered by each stimulus. We found that the expression of 51 genes changed under IR, MMC, and hypoxia. These findings revealed damage-specific genes that varied differently according to each stimulus and common genes that are universally altered in genetic instability.
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Background@#The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice. @*Methods@#Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck. @*Results@#Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively. @*Conclusion@#The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.