Development and Validation of a Mortality Risk Score for Repaired Tetralogy of Fallot.

BACKGROUND: Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. METHODS AND RESULTS: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all-cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6-35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78-0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71-0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end-systolic volume index, and lower biventricular global function index as independent predictors of death. A risk-scoring algorithm dividing patients into low-risk (score ≤4) versus high-risk (score >4) groups was validated to effectively discriminate risk of death (15-year survival of 95% versus 74%, respectively; P<0.001). CONCLUSIONS: This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.

Modulatory Effects of the Kuwanon-Rich Fraction from Mulberry Root Bark on the Renin-Angiotensin System.

In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin-angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.

Microbial Community Changes in Silkworms Suspected of Septicemia and Identification of Serratia sp.

Diseases that occur in silkworms include soft rot, hardening disease, digestive diseases, and sepsis. However, research on the causes of bacterial diseases occurring in silkworms and the resulting changes in the microbial community is lacking. Therefore, we examined the morphological characteristics of sepsis and changes in the microbial community between silkworms that exhibit a unique odor and healthy silkworms; thus, we established a relationship between disease-causing microorganisms and sepsis. After producing a 16S rRNA amplicon library for samples showing sepsis, we obtained information on the microbial community present in silkworms using next-generation sequencing. Compared to that in healthy silkworms, in silkworms with sepsis, the abundance of the Firmicutes phylum was significantly reduced, while that of Proteobacteria was increased. Serratia sp. was dominant in silkworms with sepsis. After bacterial isolation, identification, and reinfection through the oral cavity, we confirmed this organism as the disease-causing agent; its mortality rate was 1.8 times higher than that caused by Serratia marcescens. In summary, we identified a new causative bacterium of silkworm sepsis through microbial community analysis and confirmed that the microbial community balance was disrupted by the aberrant proliferation of certain bacteria.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

Ultrasonographic findings of facial muscles in patients with severe facial palsy who showed no improvement for more than 3 months on acute stage.

INTRODUCTION/AIMS: The study aimed to visualize the changes in the facial muscles of patients with severe facial palsy who showed no improvement for more than 3 months on acute stage. METHODS: The 102 patients with severe facial palsy over House-Brackmann grade IV or an 80% degenerative ratio on ENoG at the initial examination, who showed no improvement for more than 3 months on acute stage were indicated to undergo ultrasonography of the face to evaluate the facial muscles. RESULTS: Muscular degeneration was observed in 537/918 muscles (58.5%). Muscle volume shrinkage was observed in 209/918 muscles (22.8%). Fascial adhesions were observed in 209/918 muscles (22.7%). Among all the muscles assessed for degenerative changes, zygomaticus major/minor was the most affected by degenerative changes (91.2%). Degenerative changes were observed in the levator labii superioris muscle in 84.3% patients. The shrinkage was most frequently observed in the zygomaticus major muscle (61/102 patients [59.8%]), followed by the zygomaticus minor muscle (43.1%). Shrinkage of the levator labii suprioris was observed in 24.5% patients. The zygomaticus major/minor muscle had the highest proportion of fascial adhesions in 61.8% and 66.7% patients respectively. The levator labii suprioris muscle showed the lowest proportion of fascial adhesions, with only 7.8% patients being affected. DISCUSSION: This study confirmed that the zygomaticus major, zygomaticus minor, and levator labii suprioris muscles, which raise the corner of the mouth, are the first to degenerate in patients with severe facial paralysis. This study demonstrated that ultrasonography is a simple and non-invasive examination for facial paralysis.

All-Cause and Cause-Specific Mortality among Patients with Vitiligo: A Nationwide Population-Based Study in Korea.

Vitiligo is a common autoimmune skin disorder; however, there is limited information about risks of mortality among patients with vitiligo. Therefore, we aimed to investigate the mortality in patients with vitiligo. A population-based cohort study was conducted using the data linkage of the National Health Insurance Service database and the National Death Registry. Patients with incident vitiligo were matched with sociodemographic factors-matched controls without vitiligo in a 1:5 ratio. All-cause and cause-specific mortalities were compared between patients with vitiligo and controls. In total, 107,424 patients with incident vitiligo and 537,120 matched controls were included. The mortality rates were 34.8 and 45.3 per 10,000 person-years in patients and controls, respectively. Patients with vitiligo showed a significantly lower risk of mortality (adjusted hazard ratio = 0.75, 95% confidence interval = 0.72-0.78). The cause-specific mortality from infectious diseases, oncologic diseases, hematologic diseases, endocrine diseases, neurologic diseases, cardiovascular diseases, respiratory diseases, and renal/urogenital disease was significantly lower in patients with vitiligo. Patients with vitiligo were associated with a lower risk of mortality, suggesting that vitiligo-associated autoimmunity might contribute to reduced morbidity and mortality.

Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19.

Importance: Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified. Objective: To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19. Design, Setting, and Participants: This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023. Exposures: Receipt of diagnosis of COVID-19. Main Outcomes and Measures: The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses. Results: A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19. Conclusions and Relevance: In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.

Sphincter of Oddi incompetence associated with duodenal stenosis in a newborn: A case report.

Newborn incompetence of the sphincter of Oddi is rare. While there are many causes of reflux of air or ingested contrast material into the biliary tree in adults, in the newborn, it is usually due to incompetence of the sphincter of Oddi associated with partial or complete duodenal obstruction. This paper presents upper gastrointestinal series findings of incompetence of the sphincter of Oddi associated with duodenal stenosis in a 3-day-old newborn. If pneumobilia is identified in the newborn, although the possibility is low, clinicians should consider incompetence of the sphincter of Oddi with duodenal obstruction as well as portal vein gas.

[Rice Bodies Presenting as Intra-Articular Masses in Pediatric Idiopathic Arthritis: A Case Report]. / 소아기 특발성 ê´€ì ˆì—¼ 환자에서 ê´€ì ˆ 내 ì¢ ì–‘í˜•íƒœë¡œ 나타난 쌀소체: 증례 ë³´ê³ .

Rice bodies are commonly detected in adults with rheumatoid arthritis and rarely occur in children. An 11-year-old female adolescent who visited our hospital for evaluation of knee pain underwent a MRI scan, which revealed an intra-articular mass. Arthroscopic examination of the mass confirmed conglomerated rice bodies. We report a case of rice bodies that clinically presented as intra-articular masses.

[Complete Rupture of the Extensor Hallucis Longus Tendon with Accessory Slip Mimicking a Partial Rupture: A Case Report]. / 부분파열로 오인된 긴엄지발가락폄근의 주힘줄의 ì™„ì „íŒŒì—´ê³¼ 동반된 보조힘줄: 증례 ë³´ê³ .

The accessory tendon of the extensor hallucis longus is a common type of extensor hallucis longus variation. This is a case of a 38-year-old female patient who initially considered conservative treatment for a suspected partial rupture, but finally underwent surgery after being diagnosed with a complete rupture of the main tendon and accessory tendon medial to the main tendon on MRI scan.

Autoimmune, Inflammatory, Atopic, Thyroid, and Psychiatric Outcomes of Offspring Born to Mothers With Alopecia Areata.

Importance: Alopecia areata (AA) is associated with diverse autoimmune and psychiatric disorders. However, an investigation on the long-term outcomes for offspring born to mothers diagnosed with AA is lacking. Objective: To investigate the risks for autoimmune, inflammatory, atopic, thyroid, and psychiatric outcomes of offspring born to mothers with AA. Design, Setting, and Participants: This retrospective population-based birth cohort study used the linked birth registration database with the Nationwide Health Insurance Service database of Korea. The participants included all newborns born to mothers with 3 or more visits with International Classification of Diseases, Tenth Revision code of L63 and 1:10 birth year, sex, insurance, income, and location of residence-matched control offspring born to mothers without AA during the years from 2003 to 2015. The analysis was conducted from July 2022 to January 2023. Exposure: Maternal AA. Main Outcomes and Measures: The occurrence of the following diseases was measured in newborns from birth to December 31, 2020: AA, alopecia totalis/universalis (AT/AU), vitiligo, psoriasis, inflammatory bowel disease, rheumatoid arthritis, atopic dermatitis, allergic rhinitis, asthma, hyperthyroidism, hypothyroidism, Graves disease, Hashimoto thyroiditis, attention-deficit hyperactivity disorder, mood disorder, and anxiety disorder. Multivariable Cox proportional hazard analyses were performed with the following covariates: birth year, age, insurance type, income level, location of residence, maternal age, mode of delivery, maternal history of atopic disorders, and autoimmune disorders. Results: In total, 67 364 offspring born to 46 352 mothers with AA and 673 640 controls born to 454 085 unaffected mothers were analyzed. The risk of AA (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.88-2.30), AT/AU (aHR, 1.57; 95% CI, 1.18-2.08), vitiligo (aHR, 1.47; 95% CI, 1.32-1.63), atopic disorders (aHR, 1.07; 95% CI, 1.06-1.09), hypothyroidism (aHR, 1.14; 95% CI, 1.03-1.25), and psychiatric disorders (aHR, 1.15; 95% CI, 1.11-1.20) was significantly increased in offspring born to mothers with AA. Among them, 5088 born to mothers with AT/AU were at much greater risk for the development of AT/AU (aHR, 2.98; 95% CI, 1.48-6.00) and psychiatric disorders (aHR, 1.27; 95% CI, 1.12-1.44). Conclusions and Relevance: In this Korean retrospective population-based birth cohort study, maternal AA was associated with the development of autoimmune/inflammatory, atopic, thyroid, and psychiatric disorders in their offspring. Clinicians and parents need to be aware of the potential for these comorbidities to occur.

Improved Outcomes After Pulmonary Valve Replacement in Repaired Tetralogy of Fallot.

BACKGROUND: The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. OBJECTIVES: The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. METHODS: A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. RESULTS: Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). CONCLUSIONS: Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.

Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination.

BACKGROUND: Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited. OBJECTIVE: To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination. METHODS: This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared. RESULTS: A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status. LIMITATIONS: Possible selection bias and residual confounders. CONCLUSION: These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.

[Primary Neuroendocrine Carcinoma of the Breast: A Case Report and Literature Review]. / ìœ ë°©ì—ì„œ 발생한 원발성 ì‹ ê²½ë‚´ë¶„ë¹„ì•”ì¢ : 증례 ë³´ê³ ì™€ ë¬¸í—Œê³ ì°°.

In general, neuroendocrine cancer develops in the digestive or respiratory tract, and when it is found in other organs, it is often due to metastasis. Primary neuroendocrine carcinoma of the breast occurs very rarely, and the exact clinical picture, radiological findings, treatment and prognosis are not well known. Furthermore, only a small number of literature reports have been published. Here, we report the imaging findings of primary neuroendocrine carcinoma in the breast of a 51-year-old female, along with a literature review.

[Radiologic Manifestations of Pulmonary Nuclear Protein in Testis Midline Carcinoma: A Case Report]. / 폐에 발생한 ê³ í™˜ 핵단백질 ì •ì¤‘ì„ ì•”ì˜ ì˜ìƒì˜í•™ì  소견: 증례 ë³´ê³ .

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

Epidemiology and comorbidity of hidradenitis suppurativa in Korea for 17 years: A nationwide population-based cohort study.

Hidradenitis suppurativa (HS) is associated with various metabolic and autoimmune diseases. The epidemiology has been analyzed in various studies worldwide. However, epidemiological data on HS for Asian populations are limited. This study aimed to analyze the change in the prevalence and incidence of HS over 17 years in South Korea using the Korean National Health Insurance Service (NHIS) database. This study also evaluated the comorbidities in patients with HS. Population-based data from the NHIS database of Korea were obtained between January 2003 and December 2019. Odds ratios were estimated to determine the association between comorbidities and HS during the study period. Hazard ratios for the risk of incident comorbidities in patients with HS were obtained using the multivariable Cox proportional hazard analysis. This study included 45 511 patients with HS and 910 220 controls matched for age, sex, insurance type, and income level. The incidence rate of HS per 1 000 000 person-years in Korea increased from 11.69 in 2003 to 78.78 in 2019. The annual prevalence per 1 000 000 people also increased from 34.68 in 2003 to 140.10 in 2019, showing a similar trend. Many comorbidities, including atopic, metabolic and end-organ, autoimmune/inflammatory, and psychiatric diseases were associated with HS at baseline. In many diseases, the risk of incident comorbidities in patients with HS was higher than that in controls. The incidence and prevalence of HS in Korea have increased over the past 17 years. Various comorbidities, including allergic diseases, hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, chronic hepatitis and cirrhosis, chronic kidney disease, inflammatory bowel diseases, rheumatoid arthritis, vitamin D deficiency, and psychiatric diseases, were associated with HS. Physicians need to keep in mind and closely monitor these comorbidities in patients with HS.

The optimal scaffold for silk sericin-based bone graft: collagen versus gelatin.

BACKGROUND: Silk sericin is an active ingredient in bone grafts. However, the optimal scaffold for silk sericin has yet to be identified. METHOD: A critical-sized bone defect model in rat calvaria was used to evaluate bone regeneration. Silk sericin from Yeonnokjam, Bombyx mori, was incorporated into gelatin (group G, n = 6) and collagen (group C, n = 6). Bone regeneration was evaluated using micro-computed tomography (mCT) and histology. RESULTS: Group C showed a larger bone volume than group G in the mCT analysis (P = 0.001). Histological analysis showed a larger area of bony defects in group G than in group C. The bone regeneration area in group C was significantly larger than that in group G (P = 0.003). CONCLUSION: Compared with gelatin, collagen shows better bone regeneration in silk sericin-based bone grafts.