Background: Pig red blood cells (RBCs) are rapidly eliminated when transfused into nonhuman primates (NHPs) because of immune reactions involving antibody binding and complement activation. We assessed the relationship between post-transfusion hemolysis and complement activation. Methods: RBCs for transfusion were prepared from wild-type (WT) and genetically modified pigs and NHPs. After the withdrawal of 25% of the blood volume, NHPs received transfusions of WT (N = 4), triple knockout (TKO, N = 8), and TKO pig RBCs expressing human CD55 and CD39 (TKO/hCD55.hCD39, N = 4). Additional groups received repeated xenotransfusions (ReXTf, N = 3), NHP RBC transfusions (N = 3), or a saline infusion (N = 4).Blood samples were collected at multiple time points to measure Hb and complement fragment (C3a, C4a, and factor Bb) levels and agglutination titers. Results: Hb levels were restored by transfusions but not by saline infusion. The degree of complement activation varied with the type of transfused RBCs, with significant increases in C3a and factor Bb levels immediately after xenotransfusions but not allotransfusions.These increases were particularly notable in ReXTf and negatively correlated with Hb levels on post-transfusion day 1 (ρ = –0.547 and –0.556; P = 0.0187 and 0.0165, respectively).In TKO/hCD55.hCD39 pig RBC transfusions, C3a and factor Bb peak levels were delayed until post-transfusion day 3, unlike in TKO pig RBC transfusions. Conclusions Post-transfusion complement activation varies depending on prior sensitization and genetic modifications in pig RBCs. Monitoring complement activation can provide insight into the survival and compatibility of transfused RBCs in NHPs.

Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Methods: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19–related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Results: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. Conclusion: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19’s impact on GN.

Background/Aims: To compare the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2018 and Korean Liver Cancer Association-National Cancer Center (KLCANCC) 2018 criteria for diagnosing hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI) with hepatobiliary agent (HBA). Methods: We searched the MEDLINE and EMBASE for studies from January 1, 2018, to October 20, 2021, that compared the diagnostic performance of two imaging criteria on HBA-MRI. A bivariate random-effects model was fitted to calculate the per-observation sensitivity and specificity, and the estimates of paired data were compared. Subgroup analysis was performed based on the observation size. Meta-regression analysis was also performed for study heterogeneity. Results: Of the six studies included, the pooled sensitivity of the definite HCC category of the KLCA-NCC criteria (82%; 95% confidence interval [CI], 74% to 90%; I 2 =84%) was higher than that of LR-5 of LI-RADS v2018 (65%; 95% CI, 52% to 77%; I 2 =96%) for diagnosing HCC (p<0.001), while the specificity was lower for KLCA-NCC criteria (87%; 95% CI, 84% to 91%; I 2 =0%) than LI-RADS v2018 (93%; 95% CI, 91% to 96%; I 2 =0%) (p=0.017). For observations sized ≥20 mm, the sensitivity was higher for KLCA-NCC 2018 than for LI-RADS v2018 (84% vs 74%, p=0.012), with no significant difference in specificity (81% vs 85%, p=0.451). The reference standard was a significant factor contributing to the heterogeneity of sensitivities. Conclusions The definite HCC category of KLCA-NCC 2018 provided a higher sensitivity and lower specificity than the LR-5 of LI-RADS v2018 for diagnosing HCC using MRI with HBA.

Purpose: This study aimed to identify the risk factors associated with the occurrence and prognosis of hypertrophic scarring following thyroidectomy. Materials and Methods: A total of 4238 patients who underwent thyroidectomy were included in this study. A multivariable logistic regression model was developed to identify the risk factors for hypertrophic scar development and its prognosis. Results: Our analysis revealed that hypertrophic scar development was associated with younger age [odds ratio (OR)=0.949, p<0.0001], male sex (OR=0.562, p<0.0001), higher body mass index (OR=1.137, p<0.0001), prominent sternocleidomastoid muscles (OR=2.522, p<0.0001), scarring located within 1 cm of the sternal notch (OR=4.345, p<0.0001), and a history of keloid development (OR=2.789, p=0.0031). Additionally, scar location within 1 cm of the sternal notch (beta=4.326, p=0.0429) and a history of keloid development (beta=23.082, p<0.0001) were found to be associated with the prognosis of hypertrophic scarring. Conclusion The findings of this study provide valuable insights into the risk factors associated with hypertrophic scarring following thyroidectomy. Clinicians can use this information to predict the occurrence of hypertrophic scarring and its prognosis, and take preventative measures accordingly.

Purpose: This study evaluated thyroid cancer risk in a lung cancer screening population according to the presence of an incidental thyroid nodule (ITN) detected on low-dose chest computed tomography (LDCT). Methods: Of 47,837 subjects who underwent LDCT, a lung cancer screening population according to the National Lung Screening Trial results was retrospectively enrolled. The prevalence of ITN on LDCT was calculated, and the ultrasonography (US)/fine-needle aspiration (FNA)–based risk of thyroid cancer according to the presence of ITN on LDCT was compared using the Fisher exact or Student t-test as appropriate. Results: Of the 2,329 subjects (female:male=44:2,285; mean age, 60.9±4.9 years), the prevalence of ITN on LDCT was 4.8% (111/2,329). The incidence of thyroid cancer was 0.8% (18/2,329, papillary thyroid microcarcinomas [PTMCs]) and was higher in the ITN-positive group than in the ITN-negative group (3.6% [4/111] vs. 0.6% [14/2,218], P=0.009). Among the 2,011 subjects who underwent both LDCT and thyroid US, all risks were higher (P<0.001) in the ITNpositive group than in the ITN-negative group: presence of thyroid nodule on US, 94.1% (95/101) vs. 48.6% (928/1,910); recommendation of FNA according to the American Thyroid Association guideline and Korean Thyroid Imaging Reporting and Data System guideline, 41.2% (42/101) vs. 2.4% (46/1,910) and 39.6% (40/101) vs. 1.9% (37/1,910), respectively. Conclusion Despite a higher risk of thyroid cancer in the LDCT ITN-positive group than in the ITN-negative group in a lung cancer screening population, all cancers were PTMCs. A heavy smoking history may not necessitate thorough screening US for thyroid incidentalomas.

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Striatal changes in the pathogenesis of Alzheimer’s disease (AD) is not fully understood yet. We compared structural and functional image differences in the striatum between patients with early onset AD (EOAD) and late onset AD (LOAD) to investigate whether EOAD harbors autosomal dominant AD like imaging findings. The clinical, neuropsychological and neuroimaging biomarkers of 77 probable AD patients and 107 elderly subjects with normal cognition (NC) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)-2 dataset were analyzed. Enrolled each subject completed a 3-Tesla MRI, baseline 18F-FDG-PET, and baseline 18F-AV-45 (Florbetapir) amyloid PET studies. AD patients were divided into two groups based on the onset age of clinical symptoms (EOAD <65 yrs; LOAD ≥65 yrs). A standardized uptake value ratio of the striatum and subcortical structures was obtained from both amyloid and FDG-PET scans. Structural MR imaging analysis was conducted using a parametric boundary description protocol, SPHARM-PDM. Of the 77 AD patients, 18 were EOAD and 59 were LOAD. Except for age of symptom onset, there were no statistically significant differences between the groups in demographics and detailed neuropsychological test results. 18F-AV-45 amyloid PET showed marked β-amyloid accumulation in the bilateral caudate nucleus and left pallidum in the EOAD group. Intriguingly, the caudate nucleus and putamen showed maintained glucose metabolism in the EOAD group compared to the LOAD group. Our image findings in the striatum of EOAD patients suggest that sporadic EOAD may share some pathophysiological changes noted in autosomal dominant AD.

Purpose: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m2 ), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0–1. Materials and Methods: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0–1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. Results: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P–Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, p=0.003). Conclusion The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0–1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0–1.

Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.