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.

The HeartWare Ventricular Assist Device (HVAD) was widely used for mechanical circulatory support in patients with end-stage heart failure. However, there have been reports of a critical issue with HVAD pumps failing to restart, or experiencing delays in restarting, after being stopped. This case report describes 2 instances of HVAD failure-to-restart during heart transplantation surgery and routine outpatient care. Despite multiple attempts to restart the pump using various controllers and extensions, the HVAD failed to restart, triggering a hazard alarm for pump stoppage. In one case, the patient survived after receiving a heart transplantation, while in the other, the patient died immediately following the controller exchange. These cases highlight the rare but life-threatening complication of HVAD failure-to-restart, underscoring the importance of awareness among clinicians, patients, and caregivers, and adherence to the manufacturer’s guidelines and recommendations for HVAD management.

Purpose: This study aimed to evaluate the quality of artificial intelligence (AI)/machine learning (ML) studies on hemorrhagic stroke using the Minimum Information for Medical AI Reporting (MINIMAR) and Minimum Information About Clinical Artificial Intelligence Modeling (MI-CLAIM) frameworks to promote clinical application. Materials and Methods: PubMed, MEDLINE, and Embase were searched for AI/ML studies on hemorrhagic stroke. Out of the 531 articles found, 29 relevant original research articles were included. MINIMAR and MI-CLAIM scores were assigned by two experienced radiologists to assess the quality of the studies. Results: We analyzed 29 investigations that utilized AI/ML in the field of hemorrhagic stroke, involving a median of 224.5 patients. The majority of studies focused on diagnostic outcomes using computed tomography scans (89.7%) and were published in computer science journals (48.3%). The overall adherence rates to reporting guidelines, as assessed through the MINIMAR and MI-CLAIM frameworks, were 47.6% and 46.0%, respectively. In MINIMAR, none of the studies reported the socioeconomic status of the patients or how missing values had been addressed. In MI-CLAIM, only two studies applied model-examination techniques to improve model interpretability. Transparency and reproducibility were limited, as only 10.3% of the studies had publicly shared their code. Cohen’s kappa between the two radiologists was 0.811 and 0.779 for MINIMAR and MI-CLAIM, respectively. Conclusion The overall reporting quality of published AI/ML studies on hemorrhagic stroke is suboptimal. It is necessary to incorporate model examination techniques for interpretability and promote code openness to enhance transparency and increase the clinical applicability of AI/ML studies.

Colorectal strictures are uncommon in patients with ulcerative colitis (UC). An extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is rarely involved in the colon but may be associated with inflammatory bowel diseases. A 41-year-old female with a six-year history of UC presented with a severe stricture of the sigmoid colon that prevented the passage of a colonoscope. A histological examination revealed non-specific inflammation and fibrosis without dysplasia or cancer.Despite conventional treatment, including mesalazine and azathioprine for one year after that visit, the stricture persisted. In addition, diffuse, edematous exudative inflammation and multiple shallow ulcers were observed in the distal rectum, revealing a MALT lymphoma testing positive for CD20, CD43, CD5, and Bcl-2, but negative for CD3, CD10, CD23, and cyclin-D1. Four weekly doses of rituximab were administered. Follow-up colonoscopy performed one month after treatment revealed slight improvement in the rectal lesion without remnant histological evidence of a MALT lymphoma. In addition, the stricture showed marked improvement, and the colonoscope could pass easily through the stricture site. This is the first case report on an improvement of a severe sigmoid colon stricture in a patient with UC after rituximab treatment for a concomitant rectal MALT lymphoma.

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Background and Objectives: Several cases involving severe right ventricular (RV) failure in advanced cancer patients have been found to be pulmonary tumor thrombotic microangiopathies (PTTMs). This study aimed to discover the nature of rapid RV failure syndrome with a suspected diagnosis of PTTM for better diagnosis, treatment, and prognosis prediction in clinical practice. Methods: From 2011 to 2021, all patients with clinically suspected PTTM were derived from the one tertiary cancer hospital with more than 2000 in-hospital bed. Results: A total of 28 cases of clinically suspected PTTM with one biopsy confirmed case were included. The most common cancer types were breast (9/28, 32%) and the most common tissue type was adenocarcinoma (22/26, 85%). The time interval from dyspnea New York Heart Association (NYHA) Grade 2, 3, 4 to death, thrombocytopenia to death, desaturation to death, admission to death, RV failure to death, cardiogenic shock to death were 33.5 days, 14.5 days, 7.4 days, 6.4 days, 6.1 days, 6.0 days, 3.8 days and 1.2 days, respectively. The NYHA Grade 4 to death time was 7 days longer in those who received chemotherapy (7.1 days vs.13.8 days, p value=0.030). However, anticoagulation, vasopressors or intensive care could not change clinical course. Conclusions Rapid RV failure syndrome with a suspected diagnosis of PTTM showed a rapid progressive course from symptom onset to death. Although chemotherapy was effective, increased life survival was negligible, and treatments other than chemotherapy did not help to improve the patient’s prognosis.

Purpose: The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. Materials and Methods: Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. Results: After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. Conclusion The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.