Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Dementia is a neuropsychiatric disorder that primarily affects the elderly, leading to a widespread decline in cognitive function and significant impairment of occupational, social, and personal functioning. In addition to cognitive deficits, dementia is frequently comorbid with behavioral and psychological symptoms of dementia (BPSD), such as agitation.When present, these secondary symptoms can exacerbate the clinical course of the disease, reduced treatment responsiveness, increased rates of admission to long-term care facilities, extended hospitalization, higher risk of personal injury and a substantial socioeconomic burden. Given these consequences, early management of BPSD—particularly agitation—is critical to mitigating these risks. Although antipsychotics are commonly prescribed to manage agitation, risperidone remains the only agent approved by regulatory authorities for this indication. Recently, however, brexpiprazole, a medication with a pharmacological profile distinct from that of risperidone, received U.S. FDA approval (on May 11, 2023) for the treatment of agitation associated with Alzheimer’s disease. Agitation is among the most prevalent BPSD manifestations, with symptoms ranging from verbal to physical aggression. Given its recent approval and unique pharmacodynamic properties, brexpiprazole may have strong potential as a therapeutic option for this population. This paper aims to review the pharmacological mechanisms, clinical evidence, and future perspectives of brexpiprazole as a novel therapeutic option for managing agitation in patients with Alzheimer’s disease.

Background: Enchondroma is a common benign bone tumor in the hand, often leading to delayed diagnosis due to its asymptomatic nature. The surgical treatment strategy for enchondroma, particularly in pathologic fractures, remains unclear. This study aimed to evaluate the outcomes of treatment for non- or minimally displaced pathologic fractures in enchondroma using autogenous bone grafts alone, without metal fixation. Methods: A retrospective analysis was conducted on 34 patients who underwent surgery for enchondroma and pathologic fractures. Clinical and radiographic outcomes were assessed, including pain scores, range of motion (ROM), Disabilities of the Arm, Shoulder, and Hand (DASH) score, grip strength, fracture union time, and complications. Results: All patients reported pain at the fracture site preoperatively. The preoperative pain visual analog scale (VAS) score was 4.5.Postoperatively, the pain VAS score improved significantly to 2.3. The postoperative average total ROM was 253.8°. The average DASH score was 5.1, and grip strength was 97.8% compared to the unaffected side. Bony union was achieved in all cases with an average union time of 10.9 weeks. No complications were observed except for 1 suspected recurrence. Conclusions Early single-stage surgical treatment with curettage and autogenous bone grafts without fixation yielded satisfactory results for non- or minimally displaced pathologic fractures in enchondroma. This non-fixative technique offers a viable option with reduced treatment duration and implant-related complications.

Background: The management of distal radius fractures (DRFs) has evolved with the introduction of volar locking plate (VLP) fixation.Nevertheless, despite the low occurrence rates, reduction loss following VLP fixation has been reported in several studies. Our objective was to determine the incidence and features of reduction loss in patients despite the appropriate application of VLP fixation for DRF. Methods: This retrospective study was conducted between March 2017 and August 2023, during which a single hand surgeon performed VLP procedures for DRFs. This study included 379 patients (382 wrists) including 3 patients who underwent bilateral surgery. We identified patients who experienced reduction loss after VLP fixation (group 1) and patients without stability problems (group 2) and compared the 2 groups. Results: The mean age of the patients was 63.5 years, with a standard deviation of 13.8. There were 90 male patients (23.6%) and 289 female patients (75.7%). We identified 14 cases of DRFs, in which reduction loss occurred even after VLP fixation during the follow-up period (group 1, 3.7%). The remaining DRFs were assigned to group 2 (n=368, 96.3%). Among the 14 patients, 7 cases of screw breakage were identified as causing the loss of fracture reduction. As the joint surface collapsed and sank down to the distal row locking screw, 4 cases presented with distal locking screws penetrating into the radiocarpal joint. There were no significant differences between the 2 groups in terms of sex, weight, fracture arm direction, and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification. However, patients in group 1 were statistically significantly older than those in group 2 (average age, 77.5 years vs. 62 years). Among 4 patients experiencing distal screw violation of the radiocarpal joints, 3 underwent partial or complete screw removal immediately after fracture consolidation or union. Conclusions While rare, reduction loss remains a potential complication following VLP fixation, especially in elderly patients with intra-articular DRFs. However, with diligent monitoring and timely intervention, such as implant removal if necessary, acceptable outcomes can still be attained.

Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background: Enchondroma is a common benign bone tumor in the hand, often leading to delayed diagnosis due to its asymptomatic nature. The surgical treatment strategy for enchondroma, particularly in pathologic fractures, remains unclear. This study aimed to evaluate the outcomes of treatment for non- or minimally displaced pathologic fractures in enchondroma using autogenous bone grafts alone, without metal fixation. Methods: A retrospective analysis was conducted on 34 patients who underwent surgery for enchondroma and pathologic fractures. Clinical and radiographic outcomes were assessed, including pain scores, range of motion (ROM), Disabilities of the Arm, Shoulder, and Hand (DASH) score, grip strength, fracture union time, and complications. Results: All patients reported pain at the fracture site preoperatively. The preoperative pain visual analog scale (VAS) score was 4.5.Postoperatively, the pain VAS score improved significantly to 2.3. The postoperative average total ROM was 253.8°. The average DASH score was 5.1, and grip strength was 97.8% compared to the unaffected side. Bony union was achieved in all cases with an average union time of 10.9 weeks. No complications were observed except for 1 suspected recurrence. Conclusions Early single-stage surgical treatment with curettage and autogenous bone grafts without fixation yielded satisfactory results for non- or minimally displaced pathologic fractures in enchondroma. This non-fixative technique offers a viable option with reduced treatment duration and implant-related complications.