INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively. Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes. Conclusions TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Background: Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations. Methods: This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID. Results: Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001). Conclusion Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Background/Aims: The aim of this study was to investigate the effect of a surgical treatment algorithm recently proposed by the American Association for the Study of Liver Diseases (AASLD) on survival outcomes in patients with early-stage hepatocellular carcinoma (HCC) and identify effective alternative treatment modalities when liver transplantation (LT) is not available. Methods: We studied the clinical data of 1,442 patients who were diagnosed with early-stage HCC (a single lesion measuring 2–5 cm in size or 2 to 3 lesions measuring ≤3 cm in size) be-tween 2013 and 2018 and classified as Child-Turcotte-Pugh (CTP) A or B. Analyses were separately performed for individuals recommended for resection (single lesion, CTP A and no clinically significant portal hypertension) and those recommended for LT (single lesion with impaired liver function such as CTP B or clinically significant portal hypertension or multiple lesions). Results: Of 791 patients recommended for surgical resection, 85.8% underwent resection. The 5-year survival rate was higher for patients who underwent surgical resection than for those who received other treatments (89.4% vs 72.3%). Among 651 patients recommended for LT, only 3.4% underwent the procedure. The most common alternative treatment modalities were transarterial therapy (39.3%) followed by resection (28.9%) and ablation (27.8%). The overall survival rate associated with transarterial therapy was lower than that for resection and ablation, whereas that of the latter two treatments were comparable. Conclusions The survival outcomes of treatment strategies that most closely aligned with the algorithm proposed by the AASLD were superior to those of alternative treatment approaches.However, LT in patients with early-stage HCC can be challenging. When LT is not feasible, resection and ablation can be considered first-line alternative options.

The Korean Enhanced Recovery After Surgery (ERAS) Committee within the Korean Society of Surgical Metabolism and Nutrition was established to develop ERAS guidelines tailored to the Korean context. This guideline focuses on creating the most current evidence-based practice guidelines for ERAS purposes, based on systematic reviews. All key questions targeted randomized controlled trials exclusively, and if fewer than 2 were available, studies employing propensity score matching were also included. Recommendations for each key question were marked with strength of recommendation and level of evidence following internal and external review processes by the committee.

The Korean Enhanced Recovery After Surgery (ERAS) Committee within the Korean Society of Surgical Metabolism and Nutrition was established to develop ERAS guidelines tailored to the Korean context. This guideline focuses on creating the most current evidence-based practice guidelines for ERAS purposes, based on systematic reviews. All key questions targeted randomized controlled trials exclusively, and if fewer than 2 were available, studies employing propensity score matching were also included. Recommendations for each key question were marked with strength of recommendation and level of evidence following internal and external review processes by the committee.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Naturally occurring compounds have widely been applied to treat diverse pharmacological effects, including asthma, allergic diseases, antioxidants, inflammation, antibiotics, and cancer. Recent research has revealed the essential role of the thymic stromal lymphopoietin (TSLP) in regulating inflammatory responses at mucosal barriers and maintaining immune homeostasis. Asthma, inflammation, and chronic obstructive pulmonary disease are allergic disorders in which TSLP plays a significant role. Although TSLP’s role in type 2 immune responses has undergone comprehensive investigation, its involvement in inflammatory diseases and cancer has also been found to be expanding. However, investigating how to block the TSLP pathway using natural products has been limited. This paper summarizes the roles of various medicinal plants and their chemical components that effectively inhibit the TSLP pathway. In addition, we also highlight the contributions of several plant-derived compounds to treat allergic diseases via targeting TSLP. This review intends to offer innovative concepts to scientists investigating the use of naturally produced compounds and extracts for the treatment of allergic illnesses.

Background: This study analyzed the epidemiology and treatment outcomes of germ cell tumorpatients at a single institution. Methods: A retrospective analysis was conducted on intracranial germ cell tumor (iGCT) pa-tients treated at a single tertiary hospital from 2004 to 2019. Patients were categorized based on treatment modality: Korean Society for Pediatric Neuro-Oncology (KSPNO) protocol or bleomycin, etoposide, and cisplatin with radiation therapy. Results: Forty-nine iGCT patients treated with combined chemotherapy and radiotherapywere analyzed. The median age was 19 years (range: 6–40), with a median follow-up duration of 148.0 months (range: 10.5–265.5). Tumors were most common in the pineal gland (51.0%). Although no significant differences in outcomes were observed between treatment modalities, outcomes varied significantly by pathological type. The 10-year progression-free survival rates for germinoma and non-germinomatous germ cell tumors (NGGCTs) were 88.1% and 32.7%, respectively (p=0.003), while the 10-year overall survival rates were 92.9% and 67.5%, respectively (p<0.001). Fourteen patients experienced CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 adverse events, with one eventrelated death. Conclusion Pure germinoma demonstrated higher survival and lower recurrence rates comparedto NGGCT. The KSPNO protocol appears to be an acceptable and safe treatment option for iGCT patients. Further multi-institutional studies with larger cohorts are warranted.