Background: Currently, little is known about the relationship between the temporal radiographic latent trajectories, which are based on the extent of coronavirus disease 2019 (COVID-19) pneumonia and clinical outcomes. This study aimed to elucidate the differences in the temporal trends of critical laboratory biomarkers, utilization of critical care support, and clinical outcomes according to temporal radiographic latent trajectories. Methods: We enrolled 2,385 patients who were hospitalized with COVID-19 and underwent serial chest radiographs from December 2019 to March 2022. The extent of radiographic pneumonia was quantified as a percentage using a previously developed deep-learning algorithm. A latent class growth model was used to identify the trajectories of the longitudinal changes of COVID-19 pneumonia extents during hospitalization. We investigated the differences in the temporal trends of critical laboratory biomarkers among the temporal radiographic trajectory groups. Cox regression analyses were conducted to investigate differences in the utilization of critical care supports and clinical outcomes among the temporal radiographic trajectory groups. Results: The mean age of the enrolled patients was 58.0 ± 16.9 years old, with 1,149 (48.2%) being male. Radiographic pneumonia trajectories were classified into three groups: The steady group (n = 1,925, 80.7%) exhibited stable minimal pneumonia, the downhill group (n = 135, 5.7%) exhibited initial worsening followed by improving pneumonia, and the uphill group (n = 325, 13.6%) exhibited progressive deterioration of pneumonia. There were distinct differences in the patterns of temporal blood urea nitrogen (BUN) and C-reactive protein (CRP) levels between the uphill group and the other two groups. Cox regression analyses revealed that the hazard ratios (HRs) for the need for critical care support and the risk of intensive care unit admission were significantly higher in both the downhill and uphill groups compared to the steady group. However, regarding in-hospital mortality, only the uphill group demonstrated a significantly higher risk than the steady group (HR, 8.2; 95% confidence interval, 3.08–21.98). Conclusion Stratified pneumonia trajectories, identified through serial chest radiographs, are linked to different patterns of temporal changes in BUN and CRP levels. These changes can predict the need for critical care support and clinical outcomes in COVID-19 pneumonia.Appropriate therapeutic strategies should be tailored based on these disease trajectories.

Purpose: We aim to determine whether preoperative percutaneous needle aspiration or biopsy (PCNA/Bx) increases recurrence risk and reduces survival in stage I lung cancer patients, using a nationwide lung cancer registry. Materials and Methods: We retrospectively included 3,452 patients diagnosed with stage I lung cancer who underwent curative surgery between 2014 and 2019, as recorded in the Korean Association of Lung Cancer Registry. To balance the characteristics of patients with and without PCNA/Bx, we applied inverse probability of treatment weighting. We used cumulative incidence plots and a weighted subdistribution hazard model to analyze time to recurrence. Recurrence-free survival and overall survival were analyzed using Kaplan-Meier curves and weighted Cox proportional hazard ratio models. Results: In patients with adenocarcinoma, the use of PCNA/Bx was associated with a 1.9-fold increase (95% confidence interval [CI], 1.5 to 2.4) in the risk of recurrence and a 1.7-fold decrease (95% CI, 1.3 to 2.2) in recurrence-free survival. Subgroup analysis based on pathologic pleural invasion revealed that the risk of recurrence increased when PCNA/Bx was performed, with 2.1-fold (95% CI, 1.5 to 2.8) in patients without pleural invasion and 1.6-fold (95% CI, 1.0 to 2.4) in those with pleural invasion. No association was found between the use of PCNA/Bx and overall survival. Conclusion Preoperative PCNA/Bx was associated with increased recurrence risks in stage I adenocarcinoma, regardless of pathologic pleural invasion status. In early lung cancer cases where adenocarcinoma is strongly suspected and curative surgery is feasible, the use of transthoracic biopsy should be approached with caution.

Objective: This study investigated potential relationships between the kinetics of nucleolar precursor bodies (NPBs) in the pronucleus and developmental morphokinetics and euploidy in human preimplantation genetic testing for aneuploidy (PGT-A) cycles. Methods: The morphokinetic analysis of 200 blastocysts obtained from 53 PGT-A cycles was performed retrospectively in a time-lapse incubator. At the time of pronuclear breakdown (PNBD), we categorized the blastocysts into two groups based on the kinetic degree of clustering NPBs at the interface of the two pronuclei: clustered NPBs (CL) and non-clustered NPBs (NCL). We then compared morphokinetic parameters, abnormal behavioral events, and the rate of aneuploidy between the two groups. Results: Pronuclear fading and the first cleavage occurred earlier in the NCL group than in the CL group. However, the initiation of blastocyst formation and blastocyst expansion was delayed in the NCL group relative to the CL group. No differences were found in the rate of abnormal cleavage events, such as multinucleation at the 2-cell stage, direct cleavage from one to three cells, and from two to five cells between the CL and NCL groups. However, the fragmentation rate at the 8-cell stage was higher in the NCL group than in the CL group (10.3% vs. 1.9%, p<0.05). Additionally, the euploid rate in the CL group was significantly higher than in the NCL group (37.9% vs. 12.4%, p<0.05). Conclusion These results demonstrate the effectiveness of combining NPB clustering at PNBD with morphokinetics as a parameter for selecting embryos with higher developmental potential in in vitro fertilization.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Background: Currently, little is known about the relationship between the temporal radiographic latent trajectories, which are based on the extent of coronavirus disease 2019 (COVID-19) pneumonia and clinical outcomes. This study aimed to elucidate the differences in the temporal trends of critical laboratory biomarkers, utilization of critical care support, and clinical outcomes according to temporal radiographic latent trajectories. Methods: We enrolled 2,385 patients who were hospitalized with COVID-19 and underwent serial chest radiographs from December 2019 to March 2022. The extent of radiographic pneumonia was quantified as a percentage using a previously developed deep-learning algorithm. A latent class growth model was used to identify the trajectories of the longitudinal changes of COVID-19 pneumonia extents during hospitalization. We investigated the differences in the temporal trends of critical laboratory biomarkers among the temporal radiographic trajectory groups. Cox regression analyses were conducted to investigate differences in the utilization of critical care supports and clinical outcomes among the temporal radiographic trajectory groups. Results: The mean age of the enrolled patients was 58.0 ± 16.9 years old, with 1,149 (48.2%) being male. Radiographic pneumonia trajectories were classified into three groups: The steady group (n = 1,925, 80.7%) exhibited stable minimal pneumonia, the downhill group (n = 135, 5.7%) exhibited initial worsening followed by improving pneumonia, and the uphill group (n = 325, 13.6%) exhibited progressive deterioration of pneumonia. There were distinct differences in the patterns of temporal blood urea nitrogen (BUN) and C-reactive protein (CRP) levels between the uphill group and the other two groups. Cox regression analyses revealed that the hazard ratios (HRs) for the need for critical care support and the risk of intensive care unit admission were significantly higher in both the downhill and uphill groups compared to the steady group. However, regarding in-hospital mortality, only the uphill group demonstrated a significantly higher risk than the steady group (HR, 8.2; 95% confidence interval, 3.08–21.98). Conclusion Stratified pneumonia trajectories, identified through serial chest radiographs, are linked to different patterns of temporal changes in BUN and CRP levels. These changes can predict the need for critical care support and clinical outcomes in COVID-19 pneumonia.Appropriate therapeutic strategies should be tailored based on these disease trajectories.

Purpose: We aim to determine whether preoperative percutaneous needle aspiration or biopsy (PCNA/Bx) increases recurrence risk and reduces survival in stage I lung cancer patients, using a nationwide lung cancer registry. Materials and Methods: We retrospectively included 3,452 patients diagnosed with stage I lung cancer who underwent curative surgery between 2014 and 2019, as recorded in the Korean Association of Lung Cancer Registry. To balance the characteristics of patients with and without PCNA/Bx, we applied inverse probability of treatment weighting. We used cumulative incidence plots and a weighted subdistribution hazard model to analyze time to recurrence. Recurrence-free survival and overall survival were analyzed using Kaplan-Meier curves and weighted Cox proportional hazard ratio models. Results: In patients with adenocarcinoma, the use of PCNA/Bx was associated with a 1.9-fold increase (95% confidence interval [CI], 1.5 to 2.4) in the risk of recurrence and a 1.7-fold decrease (95% CI, 1.3 to 2.2) in recurrence-free survival. Subgroup analysis based on pathologic pleural invasion revealed that the risk of recurrence increased when PCNA/Bx was performed, with 2.1-fold (95% CI, 1.5 to 2.8) in patients without pleural invasion and 1.6-fold (95% CI, 1.0 to 2.4) in those with pleural invasion. No association was found between the use of PCNA/Bx and overall survival. Conclusion Preoperative PCNA/Bx was associated with increased recurrence risks in stage I adenocarcinoma, regardless of pathologic pleural invasion status. In early lung cancer cases where adenocarcinoma is strongly suspected and curative surgery is feasible, the use of transthoracic biopsy should be approached with caution.

Objective: This study investigated potential relationships between the kinetics of nucleolar precursor bodies (NPBs) in the pronucleus and developmental morphokinetics and euploidy in human preimplantation genetic testing for aneuploidy (PGT-A) cycles. Methods: The morphokinetic analysis of 200 blastocysts obtained from 53 PGT-A cycles was performed retrospectively in a time-lapse incubator. At the time of pronuclear breakdown (PNBD), we categorized the blastocysts into two groups based on the kinetic degree of clustering NPBs at the interface of the two pronuclei: clustered NPBs (CL) and non-clustered NPBs (NCL). We then compared morphokinetic parameters, abnormal behavioral events, and the rate of aneuploidy between the two groups. Results: Pronuclear fading and the first cleavage occurred earlier in the NCL group than in the CL group. However, the initiation of blastocyst formation and blastocyst expansion was delayed in the NCL group relative to the CL group. No differences were found in the rate of abnormal cleavage events, such as multinucleation at the 2-cell stage, direct cleavage from one to three cells, and from two to five cells between the CL and NCL groups. However, the fragmentation rate at the 8-cell stage was higher in the NCL group than in the CL group (10.3% vs. 1.9%, p<0.05). Additionally, the euploid rate in the CL group was significantly higher than in the NCL group (37.9% vs. 12.4%, p<0.05). Conclusion These results demonstrate the effectiveness of combining NPB clustering at PNBD with morphokinetics as a parameter for selecting embryos with higher developmental potential in in vitro fertilization.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.