Case report: Adjuvant therapy with toceranib for an incompletely resected renal cell carcinoma with suspected pulmonary metastasis in a dog

Primary renal neoplasia is rare in humans and dogs, with renal cell carcinoma (RCC) being the most common form of this cancer. As RCC is often diagnosed at an advanced stage, pulmonary metastasis is frequently observed. Tyrosine kinase inhibitors (TKIs) are the standard adjuvant treatments for metastatic RCC in humans. Similarly, in veterinary medicine, recent trials have employed TKIs for early-stage RCC patients who underwent complete surgical resection and showed no distant metastasis. However, the use of TKIs has not yet been reported commonly in cases of advanced RCC with metastasis. This case study presents the first clinical outcomes of TKI therapy in a dog with incompletely resected RCC and metastasis. A 5-year-old spayed female Chihuahua was referred to our hospital with a right renal mass and multiple pulmonary nodules suspected to be metastases. A portion of the renal mass was surgically removed, and histopathological examination revealed RCC with a high mitotic index. Adjuvant chemotherapy was administered, owing to incomplete resection with suspected pulmonary metastasis. An anticancer drug response prediction test was conducted using patient tissues. Since toceranib showed the most favorable responsiveness, it was selected as a therapeutic agent. Toceranib was orally administered at a dosage of 2.27 mg/kg every 48 h. Regular medical records for potential adverse effects were obtained, including systemic blood pressure, complete blood count, serum biochemical examination, and urinalysis. After 2 weeks of toceranib therapy, partial remission of pulmonary nodules continued for 2 months. The patient did not experience any adverse effects of the anticancer drug during the 4-month follow-up period. However, the patient died from an unidentified cause 6 months after the initial detection of the renal mass. This report describes the use of toceranib in dogs with RCC. In the present case, the patient showed an initial response to chemotherapy, and despite the presence of several poor prognostic factors, the dog survived beyond the expected 3-month lifespan to 6 months. Notably, no adverse events were observed during treatment

A case of generalized tonic seizures related to acute myocarditis

It is challenging to clinically distinguish between convulsive syncope and true seizure. We describe a 7-year-old girl presenting with generalized tonic seizure caused by acquired complete atrioventricular block related to acute myocarditis. After hospitalization following 6 episodes of new-onset fever with seizure, she had a short episode of abrupt complete atrioventricular block followed by another generalized tonic seizure. The concentrations of cardiac enzymes were elevated, and her echocardiogram showed a decreased left ventricular function. This case underlines the necessity of cardiac investigations in children with convulsive syncope

Clinical Characteristics of Febrile UTI First Developed Over 5 Years of Age

Purpose Febrile urinary tract infection (UTI) is one of the commonest bacterial infections in children. The purpose of this study is to investigate the clinical characteristics of the first episode of febrile UTI occurring in children over 5 years compared to those in infants younger than a year. Methods We retrospectively reviewed the medical records of 10 patients over 5 years, having febrile UTI, and 25 controls under 1 year. Clinical characteristics including symptoms at admission, the time interval between symptom onset and hospital visit and/or diagnosis, duration of fever, urinalysis, and other laboratory and imaging test results were compared between the two groups. Results Most patients in the control group showed only high fever at the time of presentation to the hospital. However, 60% of the case group had fever along with gastrointestinal (GI) symptoms such as abdominal and flank pain, vomiting, as well as relatively mild pyuria. The case group showed a longer duration between symptom onset and hospital visit and/or diagnosis. Conclusions Delay in diagnosis and initiation of treatment of UTI increases the risk of permanent renal scarring and associated complications. Therefore, early diagnosis and treatment of febrile UTI is vital for very young infants, as well as children considering that febrile UTI could be an important cause of febrile illness in children over 5 years

The combined clinical impact of red blood cell distribution width and vascular calcification on cardiovascular events and mortality in patients with end-stage kidney disease

Background Little is known about how the interaction between red blood cell distribution width (RDW) and vascular calcification (VC) affects cardiovascular (CV) events and mortality in end-stage kidney disease (ESKD) patients. This study investigated the combined prognostic effect of RDW and VC in ESKD patients starting dialysis. Methods A retrospective single-center study of 582 ESKD patients was conducted. VC was assessed by calculating the aortic calcification index (ACI) using computed tomography. Patients were divided into low ACI-low RDW, low ACI-high RDW, high ACI-low RDW, and high ACI-high RDW groups based on median ACI (17.12) and RDW (14.3) values. The association between RDW and VC and the composite endpoint of CV events and death was analyzed. Results During a median follow-up of 3.1 years (range, 1.5–5.5 years), 165 CV events (28.4%) and 124 deaths (21.4%) occurred. Cox regression showed that the low ACI-high RDW (adjusted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.04–2.66; p = 0.03) and high ACI-low RDW (adjusted HR, 1.95; 95% CI, 1.21–3.14; p = 0.006) groups had a greater risk of CV events and death than the low ACI-low RDW group. The high ACI-high RDW group had the greatest risk (adjusted HR, 2.23; 95% CI, 1.42–3.52; p = 0.001). The effect of the interaction between ACI and RDW on CV events and mortality was statistically significant (p = 0.005). Conclusion High RDW and VC interact to increase the risk of CV events and death in ESKD patients

Level of professional ethics awareness and medical ethics competency of dental hygienists and dental hygiene students: the need to add ethics items to the Korean Dental Hygienist Licensing Examination

Purpose This study aimed to evaluate the level of professional ethics awareness and medical ethics competency in order to assess the potential need for ethics items to be included on the Korean Dental Hygienist Licensing Examination. Methods In total, 358 clinical dental hygienists and dental hygiene students completed a structured questionnaire to evaluate their level of ethical awareness and medical ethics competency. The sub-factors of medical ethics were classified into relationships with patients, medical and social relations, and individual specialized fields. Results Only 32.1% of participants indicated that they had taken a course on professional ethics in the university curriculum, but 95.2% of respondents considered professional ethics to be important. The overall score for medical ethics competency was average (3.37 out of 5). The score for relationships with patients was 3.75 points, followed by medical and social relations (3.19 points) and individual specialized fields (3.16 points). The level of professional ethics awareness was higher among participants who had taken a course on professional ethics than among those who had not done so or who did not remember whether they had done so. Conclusion Dental hygienists were aware of the importance of professional ethics, but their medical ethics competency was moderate. Therefore, medical ethics should be treated as a required subject in the university curriculum, and medical ethics competency evaluations should be strengthened by adding ethics items to the Korean Dental Hygienist Licensing Examination

Differences in Circulating Dendritic Cell Subtypes in Pregnant Women, Cord Blood and Healthy Adult Women

Different subtypes of dendritic cells (DC) influence the differentiation of naíve T lymphocytes into T helper type 1 (Th1) and Th2 effector cells. We evaluated the percentages of DC subtypes in peripheral blood from pregnant women (maternal blood) and their cord blood compared to the peripheral blood of healthy non pregnant women (control). Circulating DC were identified by flow cytometry as lineage (CD3, CD14, CD16, CD19, CD20, and CD56)-negative and HLA-DR-positive cells. Subtypes of DC were further characterized as myeloid DC (CD11c+/CD123±), lymphoid DC (CD11c-/CD123+++) and less differentiated DC (CD11c-/CD123±). The frequency of DC out of all nucleated cells was significantly lower in maternal blood than in control (P<0.001). The ratio of myeloid DC/lymphoid DC was significantly higher in maternal blood than in control (P<0.01). HLA-DR expressions of myeloid DC as mean fluorescence intensity (MFI) were significantly less in maternal blood and in cord blood than in control (P<0.001, respectively). The DC differentiation factors, TNF-α and GM-CSF, released from mononuclear cells after lipopolysaccharide stimulation were significantly lower in maternal blood than in control (P<0.01). The distribution of DC subtypes was different in maternal and cord blood from those of non-pregnant women. Their role during pregnancy remains to be determined

Psychometric properties and factor structure of the Korean version of the screen for child anxiety related emotional disorders (SCARED)

The aim of this study was to examine the psychometric properties of the Korean version of Screen for Child Anxiety Related Emotional Disorders (SCARED) on a sample of Korean youths and to examine the cross-cultural differences in adolescents anxiety. Our study included 147 adolescents (ages 12–17, 92 girls), 93 with major depressive disorder and 54 as controls. Participants were evaluated using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), SCARED, Child Behavior Checklist (CBCL), Disruptive Behavioral Disorder Scale (DBD) and Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Pearsons r and Cronbachs α values of the SCARED were calculated, and exploratory factor analysis was conducted. The Korean SCARED scores were correlated with the total anxiety scores of K-SADS-PL (r = 0.74) and the CBCL anxious/depressed subscale scores (r = 0.35). Results showed a five-factor structure with good internal consistency, in which some items were loaded on different factors compared to previous studies. The Korean SCARED demonstrated promising psychometric properties, and could be a valid scale for screening anxiety symptoms in primary care. The fact that different items comprised the factors may reflect the cultural difference between United States and Korea in experiencing anxiety.This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2015R1A2A2A01004501) and was supported by Promising-Pioneering Research Program through Seoul National University (SNU) in 2015. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.This study was supported by the Chung Yang, Cha Young Sun, & Jang Hi Joo Memorial Fund. This study was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea (Korea Mouse Phenotyping Project, NRF-2013M3A9D5072550, NRF-2020M3A9D5A01082439, NRF2019R1A2C2087198, and NRF- 2019M3A9H1103792)

A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) tests sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.This study was supported by grants from the National Research Foundation (NRF) funded by the Ministry of Science & ICT (No. 2017M3A9A7050614, No. 2020R1C1C1012749, and NRF-2017R1D1A1B06029547) and the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (No. HI22C0147