Background/Aims: Infliximab treatment failure in patients with inflammatory bowel disease may result from sub-optimal infliximab trough level. An understanding of pharmacokinetics (PKs) is important to maintain an optimal trough level. PK studies of the switch to subcutaneous (SC) infliximab from intravenous (IV) infliximab using real-world data are lacking. We aimed to develop a population PK model of IV and SC infliximab to predict individual infliximab exposure during maintenance therapy. Methods: We used data from prospectively collected data on IV and SC infliximab concentrations in patients with inflammatory bowel disease receiving maintenance treatment from February 2020 to December 2022 at Samsung Medical Center. Population PK analysis was conducted by using a two-compartment model with first-order absorption and first-order elimination. Goodness-of-fit plots and visual predictive check were used to evaluate the PK model. Results: A total of 2,132 samples from 181 patients (149 Crohn’s disease and 32 ulcerative colitis) were analyzed. We developed an infliximab population PK model using body mass index, albumin, C-reactive protein level, and the anti-drug antibody level and validated its predictive performance. Conclusions It may be possible to predict the infliximab trough level of both IV and SC infliximab in patients with inflammatory bowel disease during maintenance treatment by using our model in real-world practice.

Background/Aims: Infliximab treatment failure in patients with inflammatory bowel disease may result from sub-optimal infliximab trough level. An understanding of pharmacokinetics (PKs) is important to maintain an optimal trough level. PK studies of the switch to subcutaneous (SC) infliximab from intravenous (IV) infliximab using real-world data are lacking. We aimed to develop a population PK model of IV and SC infliximab to predict individual infliximab exposure during maintenance therapy. Methods: We used data from prospectively collected data on IV and SC infliximab concentrations in patients with inflammatory bowel disease receiving maintenance treatment from February 2020 to December 2022 at Samsung Medical Center. Population PK analysis was conducted by using a two-compartment model with first-order absorption and first-order elimination. Goodness-of-fit plots and visual predictive check were used to evaluate the PK model. Results: A total of 2,132 samples from 181 patients (149 Crohn’s disease and 32 ulcerative colitis) were analyzed. We developed an infliximab population PK model using body mass index, albumin, C-reactive protein level, and the anti-drug antibody level and validated its predictive performance. Conclusions It may be possible to predict the infliximab trough level of both IV and SC infliximab in patients with inflammatory bowel disease during maintenance treatment by using our model in real-world practice.

Background/Aims: Infliximab treatment failure in patients with inflammatory bowel disease may result from sub-optimal infliximab trough level. An understanding of pharmacokinetics (PKs) is important to maintain an optimal trough level. PK studies of the switch to subcutaneous (SC) infliximab from intravenous (IV) infliximab using real-world data are lacking. We aimed to develop a population PK model of IV and SC infliximab to predict individual infliximab exposure during maintenance therapy. Methods: We used data from prospectively collected data on IV and SC infliximab concentrations in patients with inflammatory bowel disease receiving maintenance treatment from February 2020 to December 2022 at Samsung Medical Center. Population PK analysis was conducted by using a two-compartment model with first-order absorption and first-order elimination. Goodness-of-fit plots and visual predictive check were used to evaluate the PK model. Results: A total of 2,132 samples from 181 patients (149 Crohn’s disease and 32 ulcerative colitis) were analyzed. We developed an infliximab population PK model using body mass index, albumin, C-reactive protein level, and the anti-drug antibody level and validated its predictive performance. Conclusions It may be possible to predict the infliximab trough level of both IV and SC infliximab in patients with inflammatory bowel disease during maintenance treatment by using our model in real-world practice.

Background/Aims: Infliximab treatment failure in patients with inflammatory bowel disease may result from sub-optimal infliximab trough level. An understanding of pharmacokinetics (PKs) is important to maintain an optimal trough level. PK studies of the switch to subcutaneous (SC) infliximab from intravenous (IV) infliximab using real-world data are lacking. We aimed to develop a population PK model of IV and SC infliximab to predict individual infliximab exposure during maintenance therapy. Methods: We used data from prospectively collected data on IV and SC infliximab concentrations in patients with inflammatory bowel disease receiving maintenance treatment from February 2020 to December 2022 at Samsung Medical Center. Population PK analysis was conducted by using a two-compartment model with first-order absorption and first-order elimination. Goodness-of-fit plots and visual predictive check were used to evaluate the PK model. Results: A total of 2,132 samples from 181 patients (149 Crohn’s disease and 32 ulcerative colitis) were analyzed. We developed an infliximab population PK model using body mass index, albumin, C-reactive protein level, and the anti-drug antibody level and validated its predictive performance. Conclusions It may be possible to predict the infliximab trough level of both IV and SC infliximab in patients with inflammatory bowel disease during maintenance treatment by using our model in real-world practice.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Purpose: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. Methods: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. Results: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). Conclusion Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.