Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: This study explores effective fixation methods for Pauwel type III femoral neck fractures by evaluating the biomechanical benefits of adding a screw to the Femoral Neck System (FNS). Methods: Computed tomography (CT) scans of an 82-year-old female patient with an intertrochanteric fracture were used to establish a finite element femur model with heterogeneous material properties. Finite element models of Pauwel type III fractures were created with and without an additional screw. The central and inferior trajectories of the FNS bolt were examined separately and combined with an additional screw for virtual fixation. Walking and stair-climbing loads were applied. Results: With the addition of a screw, both peak maximum and minimum principal strains consistently stayed comparable or decreased in models with both central and inferior bolt trajectories, while the volume of elements with principal strain exceeding 1% decreased by more than half. The peak von Mises stress observed in the implants ranged from 215.7 to 359.3 MPa, remaining below the titanium alloy's yield strength of 800 MPa. For normal walking, the addition of a screw to the central bolt trajectory model decreased the fracture gap by 50.6% and reduced sliding distance by 8.6%. For the inferior bolt trajectory, the gap was reduced by 57.9% and sliding distance by 25.0%.Under stair-climbing conditions, these improvements were also evident; the central trajectory model saw a halved fracture gap and a 7.9% decrease in sliding distance, while the inferior trajectory model experienced a 55.7% gap reduction and a 27.2% decrease in sliding distance. The additional screw increased the area ratio of the fracture site experiencing interfragmentary compression 34%–39%, while the additional screw alleviated peak interfragmentary compression by 12%–18% under both normal walking and stair-climbing conditions. Conclusions The addition of a screw reduced the fracture gap, sliding distance, and peak interfragmentary compression, while increasing the area ratio of interfragmentary compression under both walking and stair-climbing loads, regardless of the FNS bolt trajectory, suggesting a better mechanical environment for fracture healing.

Background: The removal of a well-fixed acetabular cup is a challenging, labor-intensive, and time-consuming step during revision hip arthroplasty. Although the advent of the manual osteotome, Explant, has simplified the procedure, it is still a stressful process as it dissipates the surgeon’s strength and time and risks an iatrogenic pelvic fracture. Recently, EZX, a powered tool for extraction of well-fixed acetabular cups with semicircular blade was invented. This study aimed to compare Explant and EZX in an experimental condition for their efficacy and safety. Methods: Cementless acetabular cups were press-fitted to 20 hemipelvic polyurethane models using foam adhesives. Ten cups were removed with each tool for comparison of the elapsed time, loads on the entire hemipelvis, periacetabular strain and temperature, volume of periacetabular bone removed, and diameter of the remaining acetabular rim. Strains and loads were quantitatively assessed using strain gauges and load cells for precise and reliable measurements. Results: The mean duration required to remove a well-fixed cup with EZX was 38.5 seconds (range, 25–55), whereas that with Explant was 543.7 seconds (range, 214–1,051) (p < 0.001). The load on the entire hemipelvis with EZX (mean, 9.1 kgf; range, 6.4–11.3) was 33% lower than that with Explant (mean, 13.6 kgf; range, 9.2–17.1) (p < 0.001). The periacetabular peak strains at the 3 positions with EZX were significantly lower than those with Explant (p < 0.001). The temperature during the removal did not differ significantly between the 2 tools. Although the mean volume of bone loss with Explant was 2.4 mL more than that with EZX (p < 0.001), the mean diameters of the remaining acetabular rim were not significantly different, measuring 54.1 mm with both tools. Conclusions The present experiment revealed that a well-fixed cup could be removed using a powered tool with less strength and time and less load on the entire pelvis. Although the powered tool removed a larger volume of bone, the diameters of the remaining acetabular rims were equivalent. This tool may help surgeons remove well-fixed cups in a short time and reduce the deforming load on the bone around the cup without increasing the size of the subsequent reconstruction cup.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: This study aimed to evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiotherapy (RT). Materials and Methods: A total of 229 patients who received RT in 10 tertiary hospitals between 2010 and 2019 were included in this multicenter analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS), and overall survival (OS) were evaluated. Results: After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 patients (99.6%) achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a poor prognostic factor for LRFS (hazard ratio, 3.72; confidence interval, 1.38 to 10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 patients (30.1%). Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 patients (4.8%) after RT. Conclusion Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for RT to the stomach is not high.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p < 0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p < 0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.