Treatment of Pelvic and Spinal Bone Metastases: Radiotherapy and Hyperthermia Alone vs. in Combination.

Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions.

Age-Related Differences in Neutralizing Antibody Responses against SARS-CoV-2 Delta and Omicron Variants in 151 SARS-CoV-2-Naïve Metropolitan Residents Boosted with BNT162b2.

BACKGROUND: Although age negatively correlates with vaccine-induced immune responses, whether the vaccine-induced neutralizing effect against variants of concern (VOCs) substantially differs across age remains relatively poorly explored. In addition, the utility of commercial binding assays developed with the wild-type SARS-CoV-2 for predicting the neutralizing effect against VOCs should be revalidated. METHODS: We analyzed 151 triple-vaccinated SARS-CoV-2-naïve individuals boosted with BNT162b2 (Pfizer-BioNTech). The study population was divided into young adults (age < 30), middle-aged adults (30 ≤ age < 60), and older adults (age ≥ 60). The plaque reduction neutralization test (PRNT) titers against Delta (B.1.617.2) and Omicron (B.1.1.529) variants were compared across age. Antibody titers measured with commercial binding assays were compared with PRNT titers. RESULTS: Age-related decline in neutralizing titers was observed for both Delta and Omicron variants. Neutralizing titers for Omicron were lower than those against Delta in all ages. The multiple linear regression model demonstrated that duration from third dose to sample collection and vaccine types were also significant factors affecting vaccine-induced immunity along with age. The correlation between commercial binding assays and PRNT was acceptable for all age groups with the Delta variant, but relatively poor for middle-aged and older adults with the Omicron variant due to low titers. CONCLUSIONS: This study provides insights into the age-related dynamics of vaccine-induced immunity against SARS-CoV-2 VOCs, corroborating the need for age-specific vaccination strategies in the endemic era where new variants continue to evolve. Moreover, commercial binding assays should be used cautiously when estimating neutralizing titers against VOCs, particularly Omicron.

Realistic Estimation of COVID-19 Infection by Seroprevalence Surveillance of SARS-CoV-2 Antibodies: An Experience From Korea Metropolitan Area From January to May 2022.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, leading to the coronavirus disease 2019 (COVID-19) pandemic. Because a significant proportion of the COVID-19 confirmed cases were concentrated in the capital metropolitan area of South Korea, and a large proportion of the population in the area had been adequately vaccinated against COVID-19, we conducted a seroprevalence surveillance study focusing on the residents of the capital metropolitan area in South Korea. METHODS: We used a quota-sampling method to obtain blood samples from 1,000 individuals per round, equally stratified across seven age categories and sexes and regions, from five medical institutions located within the capital metropolitan area of South Korea. During five consecutive months (rounds) between January 2022 and May 2022, a total of 5,000 samples were analyzed for anti-spike (S) and anti-nucleocapsid (N) antibodies. RESULTS: High anti-S seropositivity was observed in all age groups, which corresponded to the vaccine coverage during the study period. Both the cumulative incidence based on polymerase chain reaction (PCR) and the estimated seroprevalence based on anti-N seropositivity increased in the fourth and fifth rounds, which corresponded to April 2022 and May 2022. Seroprevalence coincided with the cumulative incidence during the first three rounds, but exceeded from the fourth survey onwards when infection with omicron variants was increased rapidly in Korea. CONCLUSION: Seroprevalence confirmed the number of infection cases outside of PCR testing-based surveillance. Seroepidemiological surveillance can help us understand vaccine responses and detect hidden infections, thereby providing appropriate public health guidance for achieving population-level immunity.

3D hepatic organoid production from human pluripotent stem cells.

Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.

Short-term effects of ambient temperature on acute exacerbation of inflammatory bowel disease: A nationwide case-crossover study with external validation.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder characterized by chronic and relapsing manifestations. Several environmental factors are known as triggers for exacerbation of IBD. However, an association between exacerbation of IBD and ambient temperature is uncertain. This study aimed to estimate the risk of acute exacerbation of IBD due to ambient temperature. We performed a bidirectional case-crossover study using a nationwide claim data from South Korea. The external validation was conducted with a large prospective cohort in the United Kingdom. We confirmed significant associations between acute exacerbation of IBD and the short-term ambient temperature changes toward severe temperatures, in the cold weather (-19.4°C-4.3°C) (odd ratio [OR] = 1.13, 95% confidence interval [CI]: 1.13-1.14) and in the hot weather (21.3°C-33.5°C) (OR = 1.16, 95% CI: 1.15-1.17). However, the association was not significant in the moderate weather (4.3°C-21.3°C). The external validation suggested consistent results with additional elevation of acute exacerbation risk in the colder weather (-13.4°C to 2.6°C) (OR = 1.90, 95% CI: 1.62-2.22) and in the hotter weather (15.7°C-28.4°C) (OR = 1.41, 95% CI: 1.32-1.51). We observed and validated that the short-term ambient temperature changes were associated with acute exacerbation of IBD in the cold and hot weathers. Our findings provide evidence that temperature changes are associated with the acute exacerbation of IBD.

A Systemic Lupus Erythematosus Patient with Cutaneous Mycobacterium haemophilum Infection under Belimumab Treatment: A Case Report.

A 38-year-old female with systemic lupus erythematosus (SLE) initiated belimumab treatment. One month later, she presented with a reddish painful swelling on her right lower leg. She was treated with ceftriaxone and vancomycin. However, novel erythematous papules and indurated nodules appeared on both her lower legs. Skin biopsy revealed microabscess formation with mixed cell granuloma surrounded by inflammatory cell infiltration within the dermis with subcutaneous fat tissue. A large number of acid-fast bacilli were observed with Ziehl-Neelsen staining. DNA sequencing of both the hsp65 and the 16S rRNA sequences showed a 100% match with the corresponding region of Mycobacterium haemophilum. Mycobacterial culture revealed satellite growth enhancement on Middlebrook 7H11 agar plates around a paper strip containing hemin. She was treated with levofloxacin, rifabutin, and ethambutol. Within 13 months, her cutaneous lesions improved markedly without any side effects. The B cell-targeted biologic belimumab, a fully humanized IgG1γ monoclonal antibody that inactivates B lymphocyte stimulator, has been considered to be beneficial for active SLE. However, this therapy could increase the risk for the development of biologic therapy-associated mycobacterial infections, both tuberculosis and nontuberculous mycobacteria infections.

Giant Fibrovascular Polyp Mimicking Esophageal Malignancy on 18 F-FDG PET/CT.

ABSTRACT: A 52-year-old man presented with continuous dull pain from the throat to the epigastric region with dysphagia. Initial endoscopy misdiagnosed a subepithelial tumor causing external compression of the esophagus. A CT scan visualized a 14.0 × 4.0-cm pedunculated mass inside the esophagus. Subsequent 18 F-FDG PET/CT identified an intense FDG-avid area in the mass, which strongly suggested esophageal cancer. Total mass excision was performed, and fibrovascular polyp with chronic ulcerative inflammation was finally confirmed on histologic examination.

Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations.

Three-dimensional (3D) genomics shows immense promise for studying X chromosome inactivation (XCI) by interrogating changes to the X chromosomes' 3D states. Here, we sought to characterize the 3D state of the X chromosome in naïve and primed human pluripotent stem cells (hPSCs). Using chromatin tracing, we analyzed X chromosome folding conformations in these cells with megabase genomic resolution. X chromosomes in female naïve hPSCs exhibit folding conformations similar to the active X chromosome (Xa) and the inactive X chromosome (Xi) in somatic cells. However, naïve X chromosomes do not exhibit the chromatin compaction typically associated with these somatic X chromosome states. In H7 naïve human embryonic stem cells, XIST accumulation observed on damaged X chromosomes demonstrates the potential for naïve hPSCs to activate XCI-related mechanisms. Overall, our findings provide insight into the X chromosome status of naïve hPSCs with a single-chromosome resolution and are critical in understanding the unique epigenetic regulation in early embryonic cells.

Direct indicators of social distancing effectiveness in COVID-19 outbreak stages: a correlational analysis of case contacts and population mobility in Korea.

OBJECTIVES: The effectiveness of social distancing during the coronavirus disease 2019 (COVID-19) pandemic has been evaluated using the magnitude of changes in population mobility. This study aimed to investigate a direct indicator-namely, the number of close contacts per patient with confirmed COVID-19. METHODS: From week 7, 2020 to week 43, 2021, population movement changes were calculated from the data of two Korean telecommunication companies and Google in accordance with social distancing stringency levels. Data on confirmed cases and their close contacts among residents of Gyeonggi Province, Korea were combined at each stage. Pearson correlation analysis was conducted to compare the movement data with the change in the number of contacts for each confirmed case calculated by stratification according to age group. The reference value of the population movement data was set using the value before mid-February 2020, considering each data's characteristics. RESULTS: In the age group of 18 or younger, the number of close contacts per confirmed case decreased or increased when the stringency level was strengthened or relaxed, respectively. In adults, the correlation was relatively low, with no correlation between the change in the number of close contacts per confirmed case and the change in population movement after the commencement of vaccination for adults. CONCLUSIONS: The effectiveness of governmental social distancing policies against COVID-19 can be evaluated using the number of close contacts per confirmed case as a direct indicator, especially for each age group. Such an analysis can facilitate policy changes for specific groups.

Generation of ventralized human thalamic organoids with thalamic reticular nucleus.

Human brain organoids provide unique platforms for modeling several aspects of human brain development and pathology. However, current brain organoid systems mostly lack the resolution to recapitulate the development of finer brain structures with subregional identity, including functionally distinct nuclei in the thalamus. Here, we report a method for converting human embryonic stem cells (hESCs) into ventral thalamic organoids (vThOs) with transcriptionally diverse nuclei identities. Notably, single-cell RNA sequencing revealed previously unachieved thalamic patterning with a thalamic reticular nucleus (TRN) signature, a GABAergic nucleus located in the ventral thalamus. Using vThOs, we explored the functions of TRN-specific, disease-associated genes patched domain containing 1 (PTCHD1) and receptor tyrosine-protein kinase (ERBB4) during human thalamic development. Perturbations in PTCHD1 or ERBB4 impaired neuronal functions in vThOs, albeit not affecting the overall thalamic lineage development. Together, vThOs present an experimental model for understanding nuclei-specific development and pathology in the thalamus of the human brain.

Treatment for subarachnoid hemorrhage due to ruptured posterior cerebral arterial dolichoectasia with aortic arch anomaly.

Subarachnoid hemorrhage (SAH) due to ruptured posterior cerebral artery (PCA) intracranial arterial dolichoectasia (IADE) is very rare. As these lesions are difficult to treat microsurgically, neurointervention is preferred because the dolichoectatic artery does not have a clear neck, and the surgical field of view was deep seated with the SAH. However, in some cases, neurointervention is difficult due to anatomical variation of the blood vessel to access the lesion. In this case, a 30-year-old male patient presented with a ruptured PCA IADE and an aortic arch anomaly. Aortic arch anomalies render it difficult to reach the ruptured PCA IADE via endovascular treatment. The orifice of the vertebral artery (VA) was different from the usual cases, so it was difficult to find the entrance. After only finding the VA and arriving at the lesion along the VA, trapping was performed. Herein, we report the PCA IADE with aortic arch anomaly endovascular treatment methods and results.

Tenderization of Beef Semitendinosus Muscle by Pulsed Electric Field Treatment with a Direct Contact Chamber and Its Impact on Proteolysis and Physicochemical Properties.

In this study, the effects of pulse electric field (PEF) treatment on the tenderization of beef semitendinosus muscle were investigated. An adjustable PEF chamber was designed to make direct contact with the surface of the beef sample without water as the PEF-transmitting medium. PEF treatment was conducted with electric field strengths between 0.5 and 2.0 kV/cm. The pulse width and pulse number were fixed as 30 µs and 100 pulses, respectively. The impedance spectrum of PEF-treated beef indicated that PEF treatments induced structural changes in beef muscle, and the degree of the structural changes was dependent on the strength of the electric field. Cutting force, hardness, and chewiness were significantly decreased at 2.0 kV/cm (35, 37, and 34%, respectively) (p < 0.05). Troponin-T was more degraded by PEF treatment at 2.0 kV/cm intensity (being degraded by 90%). The fresh quality factors such as color and lipid oxidation were retained under a certain level of PEF intensity (1.0 kV/cm). These findings suggest that PEF treatment could tenderize beef texture while retaining its fresh quality.

Superfine Marigold Powder Improves the Quality of Sponge Cake: Lutein Fortification, Texture, and Sensory Properties.

This study aimed to investigate and optimize the quality and sensory properties of baked products with lutein-enriched marigold flower powder (MP). Lutein-enriched marigold flowers produced via hydroponic methods using LED lights were used as a functional material in sponge cakes to increase lutein content. MP particles were divided into coarse (Dv50 = 315 µm), fine (Dv50 = 119 µm), and superfine MP (Dv50 = 10 µm) fractions and added to the sponge cake after being designated to control (sponge cake prepared without MP), coarse MPS (sponge cake prepared with coarse MP), fine MPS (sponge cake prepared with fine MP), and superfine MPS (sponge cake prepared with superfine MP) groups. The sizes and surface properties of superfine MP particles were more homogeneous and smoother than the other samples. As the particle size decreased, the specific volume increased, whereas baking loss, hardness, and chewiness of the sponge cake decreased. Superfine MP and superfine MPS had the highest lutein content. The flavor of marigold and the overall acceptability of sponge cake with superfine MP were 7.90 ± 0.97 and 7.55 ± 0.76, which represents the highest values among the samples. The results of this study have shown that jet milling can contribute to improvements in texture, lutein content, and sensory qualities for baked products with MP.

Viral shedding patterns of symptomatic SARS-CoV-2 infections by periods of variant predominance and vaccination status in Gyeonggi Province, Korea.

OBJECTIVES: We compared the viral cycle threshold (Ct) values of infected patients to better understand viral kinetics by vaccination status during different periods of variant predominance in Gyeonggi Province, Korea. METHODS: We obtained case-specific data from the coronavirus disease 2019 (COVID-19) surveillance system, Gyeonggi in-depth epidemiological report system, and Health Insurance Review & Assessment Service from January 2020 to January 2022. We defined periods of variant predominance and explored Ct values by analyzing viral sequencing test results. Using a generalized additive model, we performed a nonlinear regression analysis to determine viral kinetics over time. RESULTS: Cases in the Delta variant's period of predominance had higher viral shedding patterns than cases in other periods. The temporal change of viral shedding did not vary by vaccination status in the Omicron-predominant period, but viral shedding decreased in patients who had completed their third vaccination in the Delta-predominant period. During the Delta-predominant and Omicron-predominant periods, the time from symptom onset to peak viral shedding based on the E gene was approximately 2.4 days (95% confidence interval [CI], 2.2 to 2.5) and 2.1 days (95% CI, 2.0 to 2.1), respectively. CONCLUSIONS: In one-time tests conducted to diagnose COVID-19 in a large population, although no adjustment for individual characteristics was conducted, it was confirmed that viral shedding differed by the predominant strain and vaccination history. These results show the value of utilizing hundreds of thousands of test data produced at COVID-19 screening test centers.

Clinical severity according to the primary infection variant in patients with suspected SARS-CoV-2 reinfection in Korea.

OBJECTIVES: We aimed to evaluate the severity of suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection according to variants of concern in Gyeongsangbuk-do and Daegu, Korea. METHODS: The database of coronavirus disease 2019 (COVID-19) cases reported from epidemiological investigations through the integrated system operated by the Korea Disease Control and Prevention Agency, from January 20, 2020 to May 7, 2022 was combined with data from the Health Insurance Review and Assessment Service system. The severity odds ratio (SOR) in secondary infection episodes compared with primary infection was estimated using a generalized linear model with a binomial distribution. RESULTS: In all patients, the SOR of SARS-CoV-2 reinfection was 0.89 (95% confidence interval [CI], 0.82 to 0.95), and the severity was lower than in the first infection. Patients who had been vaccinated within 91 days showed a more attenuated SOR (0.85; 95% CI, 0.74 to 0.98). However, despite vaccination, in patients with both primary and secondary infections caused by the Omicron variant, the severity was reduced to a lesser extent than in patients primarily infected with other variants. CONCLUSIONS: We could make efforts to relieve the severity of COVID-19 in vulnerable populations, in which death is more likely, by recommending booster vaccinations in case of a resurgence.

Decreased birth weight after prenatal exposure to wildfires on the eastern coast of Korea in 2000.

OBJECTIVES: In April 2000, a series of wildfires occurred simultaneously in five adjacent small cities located on the eastern coast of Korea. These wildfires burned approximately 23,794 hectares of forestland over several days. We investigated the effects of prenatal exposure to the by-products generated by wildfire disasters on birth weight. METHODS: Birth weight data were obtained for 1999-2001 from the birth registration database of the Korean National Statistical Office and matched with the zip code and exposed/unexposed pregnancy week for days of the wildfires. Generalized linear models were then used to assess the associations between birth weight and exposure to wildfires after adjusting for fetal sex, gestational age, parity, maternal age, maternal education, paternal education, and average exposed atmospheric temperature. RESULTS: Compared with unexposed pregnancies before and after the wildfires, mean birth weight decreased by 41.4 g (95% confidence interval [CI], -72.4 to -10.4) after wildfire exposure during the first trimester, 23.2 g (95% CI, -59.3 to 13.0) for exposure during the second trimester, and 27.0 g (95% CI, -63.8 to 9.8) during the third trimester. In the adjusted model for infants exposed in utero during any trimester, the mean birth weight decreased by 32.5 g (95% CI, -53.2 to -11.7). CONCLUSIONS: We observed a 1% reduction in birth weight after wildfire exposure. Thus, exposure to by-products generated during a wildfire disaster during pregnancy may slow fetal growth and cause developmental delays.

Associations of cold exposure with hospital admission and mortality due to acute kidney injury: A nationwide time-series study in Korea.

BACKGROUND: Emerging evidence supports an association between heat exposure and acute kidney injury (AKI). However, there is a paucity of studies on the association between cold exposure and AKI. OBJECTIVE: We aimed to investigate the associations of cold exposure with hospital admission and mortality due to AKI and to explore whether these associations were influenced by age and sex. METHODS: Information on daily counts of hospital admission and mortality due to AKI in 16 regions of Korea during the cold seasons (2010-2019) was obtained from the National Health Insurance Service (a single national insurer providing universal health coverage) and Statistics Korea. Daily mean temperature and relative humidity were calculated from hourly data obtained from 94 monitoring systems operated by the Korean Meteorological Administration. Associations of low temperatures (<10th percentile of daily mean temperature) and cold spells (≥2 consecutive days with <5th percentile of daily mean temperature) up to 21 days with AKI were estimated using quasi-Poisson regression models adjusted for potential confounders (e.g., relative humidity and air pollutants) with distributed lag models and univariate meta-regression models. RESULTS: Low temperatures were associated with hospital admission due to AKI [relative risk (RR) = 1.12, 95 % confidence interval (CI): 1.09, 1.16]. Cold spells were associated with hospital admission (RR = 1.87, 95 % CI: 1.46, 2.39) and mortality due to AKI (RR = 4.84, 95 % CI: 1.30, 17.98). These associations were stronger among individuals aged ≥65 years than among those aged <65 years. CONCLUSION: Our results underscore the need for the general population, particularly the elderly, physicians, and other healthcare providers to be more vigilant to cold exposure, given the risk of AKI. Government agencies need to develop specific strategies for the prevention and early detection of cold exposure-related AKI.

Effect of socioeconomic disparities on the risk of COVID-19 in 8 metropolitan cities in the Korea: a community-based study.

OBJECTIVES: Socioeconomic disparities have been reported as major risk factors contributing to the spread of coronavirus disease 2019 (COVID-19) at the community level. We conducted an epidemiological study on COVID-19 incidence risk using area-based deprivation indices (DIs) reflecting the characteristics of the susceptible population. METHODS: A database of the confirmed COVID-19 cases in 8 metropolitan cities in Korea from January 20, 2020 to December 31, 2021 was combined with area-based DI scores and standardized prevalence rates of diabetes and hypertension from the Korean Community Health Survey. Relative risk (RR) levels were estimated using a generalized linear model with a Poisson distribution by age group. RESULTS: The risk of COVID-19 incidence generally increased with increasing age, especially in patients aged ≥75 years. The RR of COVID-19 incidence per interquartile range increment of the composite deprivation index (composite DI) was 1.54 (95% confidence interval [CI], 1.34 to 1.70). Notably, in the first wave, the risk of COVID-19 incidence was approximately 3 times higher in the region with the lowest socioeconomic status than in the region with the highest status (RR, 3.08; 95% CI, 2.42 to 3.78 based on the the composite DI and RR, 3.13; 95% CI, 2.53 to 3.83 based on the social deprivation index). CONCLUSIONS: This study provides scientific evidence that socioeconomic deprivation is an important risk factor for the spread of COVID-19. This finding suggests that a mid-term to long-term strategy is needed to protect susceptible populations and reduce the burden of COVID-19 in the community.

Respiratory Syncytial Virus Outbreak Without Influenza in the Second Year of the Coronavirus Disease 2019 Pandemic: A National Sentinel Surveillance in Korea, 2021-2022 Season.

BACKGROUND: This study aimed to investigate whether respiratory syncytial virus (RSV) and influenza virus (IFV) infections would occur in 2021-2022 as domestic nonpharmaceutical interventions (NPIs) are easing. METHODS: Data were collected from the Korean Influenza and Respiratory Virus Monitoring System database. The weekly positivity rates of respiratory viruses and number of hospitalizations for acute respiratory infections were evaluated (January 2016-2022). The period from February 2020 to January 2022 was considered the NPI period. The autoregressive integrated moving average model and Poisson analysis were used for data analysis. Data from 14 countries/regions that reported positivity rates of RSV and IFV were also investigated. RESULTS: Compared with the pre-NPI period, the positivity and hospitalization rates for IFV infection during 2021-2022 significantly decreased to 0.0% and 1.0%, respectively, at 0.0% and 1.2% of the predicted values, respectively. The RSV infection positivity rate in 2021-2022 was 1.8-fold higher than that in the pre-NPI period at 1.5-fold the predicted value. The hospitalization rate for RSV was 20.0% of that in the pre-NPI period at 17.6% of the predicted value. The re-emergence of RSV and IFV infections during 2020-2021 was observed in 13 and 4 countries, respectively. CONCLUSION: During 2021-2022, endemic transmission of the RSV, but not IFV, was observed in Korea.