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Purpose@#Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%). @*Materials and Methods@#Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA. @*Results@#The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84). @*Conclusion@#Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.
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Background/Aims@#We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. @*Methods@#In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. @*Results@#In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1–2 tubular adenomas 10 adenomas, 5–10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%–55.1%) discontinued the surveillance at the patient age of 80–84 years. @*Conclusions@#A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.
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Objective@#: Markers of neuroinflammation during ischemic stroke are well characterized, but additional markers of neural damage are lacking. The study identified associations of behavioral disorders after stroke with histologic neural damage and molecular biological change. @*Methods@#: Eight-week-old, 25 g male mice of the C57BL/6J strain were subjected to middle cerebral artery occlusion (MCAO) to induce ischemic stroke. The control group was a healthy wild type (WT), and the experimental group were designed as a low severity MCAO1 and a high severity MCAO2 based on post-stroke neurological scoring. All groups underwent behavioral tests, realtime polymerase chain reaction, triphenyltetrazolium chloride (TTC) staining and Hematoxylin and Eosin staining. One-way analysis of variance was used to analyze statistical significance between groups. @*Results@#: In TTC staining, MCAO1 showed 29.02% and MCAO2 showed 38.94% infarct volume (p<0.0001). The pro-inflammatory cytokine interleukin (IL)-1β was most highly expressed in MCAO2 (WT 0.44 vs. MCAO1 2.69 vs. MCAO2 5.02, p<0.0001). From the distance to target in the Barnes maze test, WT had a distance of 178 cm, MCAO1 had a distance of 276 cm, and MCAO2 had a distance of 1051 (p=0.0015). The latency to target was 13.3 seconds for WT, 27.9 seconds for MCAO1, and 87.9 seconds for MCAO2 (p=0.0007). Prospero homeobox 1 (Prox1) was most highly expressed in MCAO2 (p=0.0004). Doublecortin (Dcx) was most highly expressed in MCAO2 (p<0.0001). @*Conclusion@#: The study demonstrated that histological damage to neural cells and changes in brain mRNA expression were associated with behavioral impairment after ischemic stroke. Prox1 and Dcx may be biomarkers of neural damage associated with long-term cognitive decline, and increased expression at the mRNA level was consistent with neural damage and long-term cognitive dysfunction.
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Chikungunya fever, a viral illness transmitted to humans through the bites of infected mosquitoes, presents with symptoms such as high fever, severe myalgia, headache, arthralgia, rash, and vomiting. This disease predominantly manifests in Southeast Asia, Africa, and Central and South America, with a limited occurrence in Northeast Asia. To date, no such a documented case has been reported in South Korea. Herein, we present the first adolescent case of chikungunya fever in South Korea following a travel to Bali, Indonesia.
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Tumor necrosis factor receptor-associated periodic syndrome (TRAPS, OMIM: #142680) is a rare autoinflammatory disease (AID) with recurrent febrile episodes. To our knowledge, we report herein the first case of a patient with TRAPS in South Korea whose symptoms included fever, arthralgia, abdominal pain, rash, myalgia, cough, and lymphadenopathy. A pathogenic de novo mutation, c.175T>C (p.Cys59Arg), in the tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) gene, was confirmed by gene sequencing. The patient has been with tocilizumab (an interleukin-6 inhibitor); tocilizumab administration every other week has completely alleviated the patient’s symptoms. Our report further expands the clinical spectrum of patients with TRAPS and reaffirms the use of tocilizumab as a viable alternative treatment option for those patients who are unsatisfactorily responsive to other commonly used biologics, such as canakinumab, anakinra, infliximab, and etanercept. Furthermore, our report may aid in increasing awareness about the existence of mutation-confirmed TRAPS in South Korea in addition to emphasizing the importance of actively pursuing genetic testing to correctly diagnose rare AID.
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Purpose@#Encephalitis is a heterogeneous syndrome that occurs in childhood and is not rare. However, epidemiological studies of encephalitis based on the International Encephalitis Consortium (ICS) and expert recommendations are lacking. We investigated the aetiology and prognosis of encephalitis in Korean children. @*Materials and Methods@#This retrospective study included children aged <19 years hospitalised for encephalitis at Severance Children’s Hospital between 2005 and 2020. The 2013 ICS criteria were used to diagnose encephalitis, and causality was classified according to the site from which the specimen was obtained. Neurological sequelae were categorised using the modified Rankin Scale (mRS) score. @*Results@#In total, 551 children were included, with 7% classified as possible, 77% as probable, and 15% as proven cases. A cause was identified in 42% of the cases (n=222), with viruses being the most common (42%), followed by bacteria (38%) and autoimmune encephalitis (12%). In cases of proven/probable encephalitis (n=65), bacteria accounted for 52%, followed by viruses (25%) and autoimmune encephalitis (22%). In cases with a single pathogen, the anti-N-methyl-D-aspartate receptor autoantibody (n=14) was the most common, followed by Group B streptococcus (n=13), herpes simplex virus (n=11), enterovirus (n=4), and others. Approximately 37% of patients had severe sequelae (mRS score ≥3) at discharge, which decreased to 31% 6 months after discharge. @*Conclusion@#This large-scale study showed that autoimmune and infectious causes accounted for a significant proportion of encephalitis in Korean children. Further studies are needed to determine whether early targeted treatment following early diagnosis leads to a favourable prognosis in these populations.
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A 6-month-old female Border Collie presented with a history of collapse after strenuous exercise. The dog was normal between episodes but experienced loss of focus and ataxia after exercise. This is particularly noticeable under hot weather conditions. No remarkable findings were observed in the diagnostic tests. Based on these results, the patient was tentatively diagnosed with Border Collie collapse (BCC). After exercise restriction, the dog had no episode of collapse and remained clinically well with no signs until the follow-up period of 8 months was complete. To our knowledge, this is the first case report of BCC in South Korea.
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Background@#Cyclosporine A (CsA)-induced kidney injury is characterized by renal impairment with inflammatory cell infiltrations, apoptosis, fibrosis, and hypoxic injury. It is not clear whether omega-3 fatty acids (O-3 FAs), which have anti-inflammatory and antioxidant roles, affect nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The aim of this study was to investigate whether O-3 FAs affect Nrf2 expression and exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in CsA-induced nephropathy. @*Methods@#Male Sprague-Dawley rats were divided into control, CsA-treated, and CsA-treated with O-3 FA groups. Nrf2 expression was measured by Western blots and immunohistochemical staining. @*Results@#Kidney function was impaired in the CsA-treated rats compared to the controls. Caspase-3 and caspase-7 were activated in the CsA-treated group, and the Bax/Bcl2 ratio was higher. O-3 FAs attenuated these apoptosis-related changes. ED-1 and inhibition of kappa B (IĸB) protein expression were significantly upregulated in the CsA-treated group. Compared to the control group, O-3 FA supplementation attenuated the increased expression of ED-1 and IĸB related to inflammation. Smad2/3, Smad4, and transforming growth factor-β1 were activated in the CsA group, and O-3 FA treatment prevented these changes related to renal fibrosis. The expression of Nrf2 was reduced in CsA-treated rats, but Nrf-2 was increased by O-3 FA treatment. @*Conclusions@#We suggest that Nrf2 is a potential mediator induced by O-3 FA supplementation and that it attenuates pro-inflammatory pathways, fibrotic processes, and apoptosis. Further studies are needed to elucidate the crosstalk between Nrf2 expression and signals related to O-3 FA treatment.
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@#The coronavirus disease (COVID-19) pandemic has transformed clinical practice and health systems. This paper provides an overview of COVID-19 clinical management and health-care pathway challenges that the World Health Organization and its Member States in the Western Pacific Region have faced. The experiences and lessons identified can help countries to better prepare for future pandemics.
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Purpose@#Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. @*Materials and Methods@#Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. @*Results@#From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. @*Conclusion@#We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.
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The diagnosis of gastrointestinal stromal tumor (GIST) has become relatively common in recent years, but little is known about its association with other malignancies. We present a rare case of successfully treated metachronous GIST and colon cancer with concurrent FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and imatinib. A 63-year-old man presented with abdominal pain that had started 2 weeks ago, and endoscopic ultrasonography showed masses that were compatible with GIST on the duodenum. He underwent Whipple surgery. One year after the GIST diagnosis, two liver masses were found on abdominal computed tomography images taken for surveillance. A liver biopsy showed metastatic adenocarcinoma, not GIST. Colonoscopy was then performed to identify the primary site of the metastatic adenocarcinoma in the liver, and sigmoid colon cancer was found. He received 12 cycles of adjuvant FOLFOX concurrently with adjuvant imatinib. There were no serious adverse events of grade 3 or higher from either imatinib or chemotherapy. He has completed adjuvant imatinib and FOLFOX chemotherapy and there is no evidence of disease recurrence. When a synchronous or metachronous tumor is found in a GIST patient, the clinician should keep in mind the possibility of another primary tumor of different histopathology, as well as GIST recurrence.
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Purpose@#We aimed to determine whether patients with esophageal cancer with a low baseline body mass index (BMI) have a poor prognosis following radiotherapy (RT). @*Materials and Methods@#We retrospectively analyzed data from 50 patients with esophageal cancer to determine whether a low starting BMI (before RT) was associated with a poor outcome. All study participants were diagnosed with non-metastatic esophageal squamous cell carcinoma (SCC). @*Results@#The number of patients at each T stage were as follows: 7 (14%) patients at T1, 18 (36%) at T2, 19 (38%) at T3, and 6 (12%) at T4. Based on BMI, 7 (14%) patients were defined as underweight. A low BMI was common in patients with T3/T4 stage esophageal cancer (7/43, p = 0.01). Overall, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 26.3% and 69.2%, respectively. In univariate analysis, clinical factors associated with poor PFS included being underweight (BMI <18.5 kg/m2; p = 0.011) and a positive N status (p = 0.017). Univariate analysis also revealed that being underweight was associated with a decrease in OS (p = 0.003). However, being underweight was not an independent prognostic factor for PFS and OS. @*Conclusion@#Patients with esophageal SCC with a low starting BMI (BMI <18.5 kg/m2) are more prone to have a negative survival outcome following RT than patients who are considered to be normal weight or overweight. For this reason, it is important that clinicians pay more attention to BMI when treating patients with esophageal SCC.
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Background@#Food allergy (FA) can have a profound effect on quality of life (QoL), stress, and anxiety in the family. We aimed to validate the Korean version of the Food Allergy Quality of Life-Parental Burden (FAQL-PB) and identify factors related to the parental psychosocial burden of caring for children with FAs. @*Methods@#Parents of children aged between 6 months and 17 years with immunoglobulin E (IgE)-mediated FAs from the Pediatric Allergy Department of five university hospitals in Korea were enrolled in the study. Parents were asked to complete the FAQL-PB, Food Allergy Independent Measure-Parent Form (FAIM-PF), Child Health Questionnaire-Parents Form 28 (CHQ-PF28), Beck’s Anxiety Inventory, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 for depression. Statistical analyses included internal consistency, test-retest reliability, concurrent validity, discriminative validity, and logistic regression analyses. @*Results@#A total of 190 parents were enrolled. Social activity limitation was the item with the highest FAQL-PB scores. The Cronbach’s α for each item was higher than 0.8. The test-retest reliability was good (intra-class correlation coefficient, 0.716; 95% confidence interval [CI], 0.100–0.935). An increase in the FAQL-PB was significantly associated with an increase in the FAIM-PF (β = 0.765, P < 0.001) (concurrent validity). There was a positive correlation between parental burden, anxiety, and depression, while resilience was inversely correlated with parental burden (all P < 0.001). The total FAQL-PB score in parents of children who had experienced anaphylaxis was significantly higher than that in parents of children who did not experience it (P = 0.008). When adjusting for age, sex, and underlying diseases, anaphylaxis β = 9.32; 95% CI, 2.97 to 15.68), cow’s milk (CM) allergy (β = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (β = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (β = 1.05; 95% CI, 0.07 to 1.41), higher depression (β = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (β = −0.42; 95% CI, −0.61 to −0.2) were significantly associated with greater parental burden in children with IgE-mediated FAs. @*Conclusion@#FAQL-PB is a reliable and valid tool for use in Korea. Anaphylaxis, CM or soybean allergies, more anxiety and depression symptoms, and lower resilience are associated with poorer QoL in parents of children with FAs.
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Objective@#To investigate the effects of customized biomechanical foot orthosis (BFO) on kinematic data during gait in patients with hallux valgus (HV) deformities and compare the results with those of a normal control group. @*Methods@#Ten patients with HV deformities and 10 healthy volunteers were enrolled in this study. HV deformity was diagnosed using biomechanical and radiological assessments by a rehabilitation physician. Patients received the customized BFO manufactured at a commercial orthosis laboratory (Biomechanics, Goyang, South Korea) according to the strictly defined procedure by a single experienced technician. The spatiotemporal and kinematic data acquired by the Vicon 3D motion capture system (Oxford Metrics, Oxford, UK) were compared between the intervention groups (control vs. HV without orthosis) and between the HV groups (with vs. without orthosis). @*Results@#The temporal-spatial and kinematic parameters of the HV group were significantly different from those of the control group. After applying BFO to the HV group, significantly increased ranges of plantar flexion motion and hindfoot inversion were observed. Furthermore, the HV group with BFO showed improved gait cadence, walking speed, and stride length, although the results were not statistically significant. @*Conclusion@#Our results suggest that it is imperative to understand the pathophysiology of HV, and the application of customized BFO can be useful for improving kinematics in HV deformities.
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Background@#We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. @*Methods@#This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016–2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. @*Results@#A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2–100.1, P< 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7–187.3/ILI patient. @*Conclusion@#Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.
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Background@#Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. @*Methods@#AD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed.The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites,treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschoolonset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. @*Results@#A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancyonset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. @*Conclusion@#This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.
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Persistent trigeminal artery (PTA) represent an unusual remnant of the fetal carotid-basilar anastomosis. Persistent trigeminal artery variant (PTAV) is a rare anastomosis between the internal carotid artery and cerebellar artery, without an interposing basilar artery segment. We report the case of 49-year-old female with an incidentally discovered, rare variation of PTA that directly terminated in the ipsilateral superior cerebellar artery. The variation was observed on CT angiography, digital subtraction angiography, and MR angiography. Additionally, we reviewed the embryogenesis of PTA and PTAV and discussed the clinical implications of this variation.
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Coronavirus disease 2019 (COVID-19) is associated with a systemic inflammatory response that activates coagulation in symptomatic patients. In addition, a rare form of thrombosis has been reported in people who received the COVID-19 vaccine, most of whom were women younger than 50 years of age. Considering that hormonal contraceptive methods widely used by women of childbearing age increase the risk of thrombosis, the development of guidelines for the use of hormonal contraceptives in the era of the COVID-19 pandemic is necessary. In this context, the Korean Society of Contraception and Reproductive Health provides guidelines for issues regarding contraception and reproductive health during the pandemic.
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Purpose@#To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception. @*Materials and Methods@#Patients (< 18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019. @*Results@#A total of 859 enema reductions were performed during the past decade, more in males and in the age < 1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (n = 27) had a lower mean age (18.1 months vs. 22.8 months), higher failure rate of enema reduction (7.4% vs. 2.4%), and higher recurrence rate of intussusception (14.8% vs 7.3%) compared with those that occurred between 2011 and 2019 (n = 832). However, these results did not show statistical significance (p = 0.07, p = 0.15, p = 0.14, respectively). @*Conclusion@#With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.
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Hibernoma is a rare benign tumor of brown adipose tissue. Herein, we report a case of axillary hibernoma in a 53-year-old female and discuss the various radiologic findings. The US revealed a 4.5-cm well-defined oval heterogenous hyperechoic mass in the right axilla with anterior displacement of the axillary vessels. Non-enhanced chest CT showed a 5.0-cm well defined, oval, and low-attenuated mass. MRI demonstrated a 5.5-cm mass with heterogeneous intermediate-to-high signal intensity on T1-and T2-weighted images and irregular enhancement at the peripheral portion. The patient underwent an US-guided core needle biopsy and the final diagnosis was hibernoma.