Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion

The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. However, the ‘nanoformulation’ suffers from a lack of systematic understanding about the requirements of polymeric stabilizers. Furthermore, the polymers that can be used for the preparation of nanocrystals are so limited that finding a proper stabilizer for a given formulation is often difficult. In this study, amino acid copolymers whose properties can systematically be tailored are developed, and their morphological and compositional effects are investigated. Copolymers containing lysine (K) as their hydrophilic segments, and phenylalanine (F) or leucine (L) as their hydrophobic segments successfully produce stable nanocrystals (200–300 nm) in water, while copolymers of K and alanine (A) could not generate nanosized particles. Not the morphology but the hydrophobicity of copolymers seems to be a critical parameter in the preparation of drug nanocrystals by wet comminution. The effective stabilization performance of copolymers requires the hydrophobic moiety content to be higher than 15 mol%. Comminution for only 5 min is long enough for nanocrystal preparation, and the crystallinity of drug is found intact after the processing.     

Larynx preservation surgery in pyriform sinus cancer

As a general rule, surgery, whenever possible followed by irradiation, is considered to be a standard treatment for pyriform sinus cancer. In early primary lesions, many different approaches have been tried for larynx preservation. From 1990-1997, 7 patients with pyriform sinus carcinoma without the involvement of pyriform sinus apex were treated with partial laryngopharyngectomy at the Asan Medical Center. Three patients were T1 stage and four were T2. All patients had nodal metastases and were treated with neck dissection and postoperative radiotherapy. Follow-up period was 1-8 years. One regional recurrence and one distant metastasis occurred; however, there was no recurrence at the primary site. The voices of all the patients were saved. The most uncomfortable postoperative symptom was mild aspiration. From these results, we can conclude that partial laryngopharyngectomy with neck dissection might be the favorable treatment modality for selected cases of pyriform sinus cancer.     

H-ras gene mutations in salivary gland mucoepidermoid carcinomas

BACKGROUND: The authors' recent investigation of salivary gland tumors in ras gene alteration has suggested that K-ras activation may not play a role in their oncogenesis but H-ras may, especially in mucoepidermoid carcinomas. A study was undertaken to assess the overall incidence of mutated H-ras genes in mucoepidermoid carcinomas and to discover its potential correlation with clinicopathologic parameters. METHODS: Fifty samples from patients with salivary gland mucoepidermoid carcinoma were analyzed for point mutations at codons 12, 13, and 61 of the H-ras gene using the polymerase chain reaction followed by automated direct sequencing methodology. RESULTS: Mutated H-ras genes were detected in 9 patients, for an overall incidence of 18% (9 of 50 patients). All but 1 of the mutations occurred at codon 12: a GGC-to-GTC transversion in 8 patients and a GGC-to-GAC transition in 1 patient, resulting in the amino acid substitution of valine and aspartic acid, respectively, for glycine. One of the samples showed concurrent mutations at codons 12 (GGC-to-GTC) and 13 (GGT-to-GGA). None of the samples demonstrated mutations involving codon 61. The H-ras mutations were observed in 5% (1of 21), 17% (2 of 12), and 35% (6 of 17) of low, intermediate, and high grade lesions, respectively. CONCLUSIONS: These data suggest involvement of H-ras activation in conjunction with other yet-unknown events in the development and/or progression of mucoepidermoid carcinomas. It is noteworthy that a stepwise increase in the frequency of H-ras mutations strongly correlates with tumor grade (P = 0.017). Molecular analysis of this gene alteration may provide assistance in the determination of tumor grade and differentiation.     

Perception of human papilloma virus (HPV) vaccination during the COVID-19 pandemic

The COVID 19 pandemic is far from over, and vaccines remain important tool for fighting the disease. As the preventive effects of the COVID-19 vaccine emerges, it is likely that the perception of importance and safety of vaccines have a positive effect on the acceptance of other vaccines. However, it is still unclear how COVID-19 pandemic has affected the general vaccination perception and acceptance. Therefore, the objective of this study was to investigate the impact of the COVID-19 pandemic on the perception of HPV vaccination. This study involved an offline survey of 161 women aged between 20 and 49 years who visited the gynecologic clinic at Chung-nam National University Sejong Hospital from January 2021 to June 2021. The questionnaire consists of items related to experience and knowledge of COVID-19 and HPV viruses, as well as attitudes toward HPV vaccination. Knowledge about COVID-19 virus and HPV correlated positively with their experiences (P = .011 and P = .045, respectively). Positive attitude was increased, and negative attitude was reduced toward HPV vaccination in the COVID-19 pandemic era. Participants stated that accurate information and cost reduction about HPV vaccine was needed to increase the HPV vaccination rate. During the COVID-19 pandemic era, positive attitudes towards HPV vaccination have tended to increase. To increase the HPV vaccination rate, public efforts are needed for further information and cost reduction.     

Epidemiology and Transmission Dynamics of Infectious Diseases and Control Measures

The epidemiology and transmission dynamics of infectious diseases must be understood at the individual and community levels to improve public health decision-making for real-time and integrated community-based control strategies. Herein, we explore the epidemiological characteristics for assessing the impact of public health interventions in the community setting and their applications. Computational statistical methods could advance research on infectious disease epidemiology and accumulate scientific evidence of the potential impacts of pharmaceutical/nonpharmaceutical measures to mitigate or control infectious diseases in the community. Novel public health threats from emerging zoonotic infectious diseases are urgent issues. Given these direct and indirect mitigating impacts at various levels to different infectious diseases and their burdens, we must consider an integrated assessment approach, ‘One Health’, to understand the dynamics and control of infectious diseases.     

The Korea Cohort Consortium: The Future of Pooling Cohort Studies

ObjectivesWe introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies.MethodsWe mainly focused on the characteristics of individual cohort studies from the KCC. We developed “PROFAN”, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated.ResultsThe KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917–72 102.ConclusionsWe propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.     

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era

BackgroundStudies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).MethodsThis multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.ResultsA total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn’s disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn’s disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020).ConclusionRegardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.     

Congenital Heart Surgery Skill Training Using Simulation Models: Not an Option but a Necessity

Congenital heart surgery (CHS) is technically demanding, and its training is extremely complex and challenging. Training of the surgeon’s technical skills has relied on a preceptorship format in which the trainees are gradually exposed to patients in the operating room under the close tutelage of senior staff surgeons. Training in the operating room is an inefficient process and the concept of a learning curve is no longer acceptable in terms of patient outcomes. The benefits of surgical simulation in training of congenital heart surgeons are well known and appreciated. However, adequate surgical simulation models and equipment for training have been scarce until the recent development of three-dimensionally (3D) printed models. Using comprehensive 3D printing and silicone-molding techniques, realistic simulation training models for most congenital heart surgical procedures have been produced. Newly developed silicone-molded models allow efficient CHS training in a stress-free environment with instantaneous feedback from the proctors and avoids risk to patients. The time has arrived when all congenital heart surgeons should consider surgical simulation training before progressing to real-life operating in a similar fashion to the aviation industry where all pilots are required to complete simulation training before flying a real aircraft. It is argued here that simulation training is not an option anymore but should be a mandatory component of CHS training.     

Agreement and Reliability between Clinically Available Software Programs in Measuring Volumes and Normative Percentiles of Segmented Brain Regions

ObjectiveTo investigate the agreement and reliability of estimating the volumes and normative percentiles (N%) of segmented brain regions among NeuroQuant (NQ), DeepBrain (DB), and FreeSurfer (FS) software programs, focusing on the comparison between NQ and DB.Materials and MethodsThree-dimensional T1-weighted images of 145 participants (48 healthy participants, 50 patients with mild cognitive impairment, and 47 patients with Alzheimer’s disease) from a single medical center (SMC) dataset and 130 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset were included in this retrospective study. All images were analyzed with DB, NQ, and FS software to obtain volume estimates and N% of various segmented brain regions. We used Bland–Altman analysis, repeated measures ANOVA, reproducibility coefficient, effect size, and intraclass correlation coefficient (ICC) to evaluate inter-method agreement and reliability.ResultsAmong the three software programs, the Bland–Altman plot showed a substantial bias, the ICC showed a broad range of reliability (0.004–0.97), and repeated-measures ANOVA revealed significant mean volume differences in all brain regions. Similarly, the volume differences of the three software programs had large effect sizes in most regions (0.73–5.51). The effect size was largest in the pallidum in both datasets and smallest in the thalamus and cerebral white matter in the SMC and ADNI datasets, respectively. N% of NQ and DB showed an unacceptably broad Bland–Altman limit of agreement in all brain regions and a very wide range of ICC values (-0.142–0.844) in most brain regions.ConclusionNQ and DB showed significant differences in the measured volume and N%, with limited agreement and reliability for most brain regions. Therefore, users should be aware of the lack of interchangeability between these software programs when they are applied in clinical practice.