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AbstractBackgroundObjectivesMaterial and methodsResultsConclusions and significanceThe Canalith Repositioning Maneuver (CRM) is often ineffective for persistent geotropic direction-changing positional nystagmus (DCPN). In these cases, determining the lesion side can be challenging, as the null plane side and the side with stronger nystagmus on the roll test are frequently opposite.This study investigates whether the low therapeutic efficacy of CRM in persistent DCPN could be attributed to incorrect determination of the lesion side.This prospective randomized trial involved two groups of patients with persistent geotropic DCPN, categorized based on the method used to determine the lesion side: the null plane side and the side with stronger nystagmus on the head roll test. We assessed the therapeutic efficacy of CRM on the null plane side (null plane group) and the side with stronger nystagmus on the head roll test (stronger nystagmus group).Both groups showed minimal or no immediate therapeutic effect of CRM, with a low short-term effect observed in both as well. No significant differences were found in the immediate and short-term therapeutic effects of CRM between the two groups.The limited therapeutic effect of CRM in persistent geotropic DCPN does not appear to result from incorrect determination of the lesion side. [ABSTRACT FROM AUTHOR]

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion: Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cells show remarkable efficacy for some hematological malignancies. However, CAR targets that are expressed at high level and selective to tumors are scarce. Several strategies have been proposed to tackle the on-target off-tumor toxicity of CAR-T cells that arise from suboptimal selectivity, but these are complicated, with many involving dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40. Our system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which we show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. Simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag may further enhance safety by enabling permanent in vivo depletion of the switchable CAR-T cells when necessary. In summary, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the range of CAR targets. The therapeutic success of CAR-T cells depends on the availability of selective and high-density targets, which limits their applicability due to on-target off-tumor toxicity. Here authors overcome this limitation in a mouse model of immune therapy in which an adaptor is an epitope-tagged single chain variable fragment targeting the tumour antigen, and the CAR-T cells are targeting the epitope, thus enabling a precise dose-switch. [ABSTRACT FROM AUTHOR]

Background: Defects in the ataxin-2 (ATXN-2) protein and CAG trinucleotide repeat expansion in its coding gene, Atxn-2, cause the neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2). While clinical studies suggest potential benefits of human-derived mesenchymal stem cells (hMSCs) for treating various ataxias, the exact mechanisms underlying their therapeutic effects and interaction with host tissue to stimulate neurotrophin expression remain unclear specifically in the context of SCA2. Methods: Human bone marrow-derived MSCs (hMSCs) were injected into the cisterna magna of 26-week-old wild-type and SCA2 mice. Mice were assessed for impaired motor coordination using the accelerating rotarod, open field test, and composite phenotype scoring. At 50 weeks, the cerebellum vermis was harvested for protein assessment and immunohistochemical analysis. Results: Significant loss of NeuN and calbindin was observed in 25-week-old SCA2 mice. However, after receiving multiple injections of hMSCs starting at 26 weeks of age, these mice exhibited a significant improvement in abnormal motor performance and a protective effect on Purkinje cells. This beneficial effect persisted until the mice reached 50 weeks of age, at which point they were sacrificed to study further mechanistic events triggered by the administration of hMSCs. Calbindin-positive cells in the Purkinje cell layer expressed bone-derived neurotrophic factor after hMSC administration, contributing to the protection of cerebellar neurons from cell death. Conclusion: In conclusion, repeated administration of hMSCs shows promise in alleviating SCA2 symptoms by preserving Purkinje cells, improving neurotrophic support, and reducing inflammation, ultimately leading to the preservation of locomotor function in SCA2 mice. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis investigated the impact of salvage surgery on 5‐year overall survival (OS) and prognostic factors in recurrent oral cavity cancer (rOCC) patients. Relevant literature before May 2022 was reviewed, including retrospective cohort studies and observational studies comparing salvage surgery to other treatments. Risk‐of‐bias assessments were conducted using the Newcastle–Ottawa scale. Statistical and subgroup analyses assessed the impact of salvage surgery on 5‐year OS and prognostic factors. 3036 documents were initially retrieved, with 14 retrospective cohort studies (2069 participants) included. Meta‐analysis of 5‐year OS in salvage surgery patients yielded a rate of 43.0%. Subgroup analysis showed higher OS in Asians (49.9% vs. 36.9%, p = 0.003) and late‐relapse (63.8% vs. 30.0%, p = 0.004) groups. Prognostic factors revealed hazards associated with nodal recurrence, extranodal extension, and perineural invasion. Salvage surgery is a viable option for rOCC patients, showing favorable 5‐year OS outcomes. Low publication bias enhances study reliability, but its single‐arm design limits conclusions on salvage surgery superiority over other treatments. [ABSTRACT FROM AUTHOR]

Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague–Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients. [ABSTRACT FROM AUTHOR]

As persistent elevation of transforming growth factor‐β (TGF‐β) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF‐β would be effective against both exacerbations. The effects of TGF‐β and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF‐β inhibitor in ameliorating the pathogenic role of TGF‐β in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF‐β causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF‐β in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro‐inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF‐β inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell‐induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF‐β inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival. [ABSTRACT FROM AUTHOR]

Background: While numerous studies have been conducted on sudden sensorineural hearing loss (SSNHL), research on how treatment outcomes and prognosis vary by age remains insufficient. This study aims to investigate the differences in recovery rates among SSNHL patients divided by age groups. Methods: A retrospective study was conducted on 177 patients diagnosed with SSNHL from 2020 to 2023. The patients were categorized into four age groups: under 20, 30–40, 50–60, and over 70. Recovery rates and associated symptoms were compared across these groups. Results: Significant recovery rates were observed in all age groups except for those over 70 (p = 0.006, p = 0.003, p = 0.009). No significant differences were found in recovery rates based on gender (p > 0.75) or symptoms such as tinnitus, ear fullness, and dizziness (p > 0.05). Conclusions: The study revealed that younger and middle-aged adults showed statistically significant improvements in recovery rates, while the elderly exhibited relatively lower recovery rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Spinal metastases can cause instability, making it difficult for clinicians to decide on the best treatment. While guidelines exist for stable and unstable spinal metastases, those with intermediate instability (a SINS of 7–12) pose a clinical challenge. This study examines risk factors that might require surgical intervention following initial radiotherapy in these patients. We analyzed data from 469 patients with spinal metastases treated between 2019 and 2021. Our findings show that patients with primary tumors in the lung, liver, or kidney, higher Bilsky grades of spinal cord compression, lytic bone lesions, and higher radiation doses are more likely to need surgery. These results suggest that the careful evaluation of these factors can help us to develop better treatment strategies for patients with intermediate spinal instability. Background: One important determinant in choosing a treatment modality is spinal instability. Clear management guidelines are suggested for stable and unstable spinal metastatic lesions, but lesions in the intermediate instability category (SINS [spinal instability neoplastic score] score of 7–12) remain a clinical dilemma. This study aims to analyze the risk factors necessitating surgical intervention after radiotherapy (RT) in patients with those lesions. Methods: A multicenter cohort of 469 patients with spinal metastases of intermediate instability who received radiotherapy (RT) as the initial treatment between 2019 and 2021 were retrospectively enrolled. All patients were neurologically intact at the time of RT. According to the performance of surgical intervention after RT, various clinical and radiographic risk factors for surgical intervention were compared between surgery and non-surgery groups using uni- and multivariate analyses. A recursive partitioning analysis (RPA) was performed using significant determinants identified in multivariate analysis. Results: The mean age at the time of RT was 59.9 years and there were 198 females. The lung was the most common primary site. During the mean follow-up duration of 18.2 months, surgical treatment was required in 79 (17.9%) of patients. The most common surgical method was decompressive laminectomy with stabilization (62.0%), followed by vertebrectomy with stabilization (22.8%) and stabilization only (15.2%). The mean SINS for the total cohort was 9.0. Multivariate regression analyses revealed that the primary tumor site of the lung, liver, and kidney, higher Bilsky grades of ESCC, lytic bone lesions, and higher EQD210 were significant risk factors for surgical intervention after RT. Among them, Bilsky grade, primary tumor type of the lung, liver, and kidney, and EQD210 were the most important determinants for expecting the probability of surgical intervention on RPA. Conclusions: Surgical intervention was performed in 17.9% of patients with intermediate instability after RT as the initial treatment. The primary tumor site of the lung, liver, and kidney, higher Bilsky grade of ESCC, and EQD210 were the most important determinants for expecting the probability of surgical intervention. Therefore, the optimal treatment strategy needs to be devised by carefully evaluating the risk of surgical intervention. [ABSTRACT FROM AUTHOR]

Background: Although several small cohort studies have shown the utility of argon plasma coagulation (APC) in the treatment of gastric dysplasia, its clinical significance has not been established. This study aims to assess the efficacy of APC as a first line treatment for gastric dysplasia, and identify risk factors for residual dysplasia. Methods: A total of 179 cases of gastric dysplasia were treated with APC and have been followed-up with upper endoscopy within 1 year. The overall incidence and the characteristics of lesions with residual dysplasia in follow-up endoscopy were analyzed by logistic regression. Results: Among 179 lesions treated with APC, 171 (95.5%) lesions have achieved complete ablation in the follow-up endoscopy. Additional APC was applied for residual dysplasia, achieving complete ablation in 97.77% (175/179). The upper third location of the gastric dysplasia was significantly associated with residual dysplasia, while tumor size, horizontal location, macroscopic morphology and grade of dysplasia showed no significant associations with residual dysplasia following the initial APC. Conclusions: APC with meticulous follow-up can be recommended as a first line treatment in patients with gastric dysplasia. [ABSTRACT FROM AUTHOR]

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (<6 months) and a long-duration (LD) group (≥6 months). Mechanical complications, such as screw loosening, cage subsidence, and adjacent vertebral fractures, were investigated. Postoperative 1-year union rate was also evaluated on computed tomography. Clinical outcomes were recorded using visual analog scale (VAS) and Oswestry Disability Index (ODI). Between-group differences for these radiographic and clinical outcomes were analyzed. Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was −3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes. [ABSTRACT FROM AUTHOR]

Summary: Teriparatide and denosumab, anti-osteoporosis medications with different mechanisms, have been widely used in the patients with osteoporotic vertebral fracture (OVF) considered as advanced osteoporosis. Teriparatide has been shown to enhance bone formation and fracture healing in OVF, but there are still no sufficient evidences discussing about the role of denosumab in newly developed OVF. In this study, we found the similar radiological deformation and functional outcomes of conservative treatment with teriparatide and denosumab in thoracolumbar (TL) OVF, and teriparatide showed a more frequent incidence of fracture union with paravertebral bone bridge formation compared to denosumab. Introduction: Teriparatide and denosumab have been widely used to treat advanced osteoporosis and prevent subsequent fractures in patients with OVCF. Unlike teriparatide, which is considered to be effective in fracture healing, there is still no clear role and evidence for the effect of denosumab in acute OVCF. This study compared the radiological and functional outcomes of conservative treatment with teriparatide and denosumab in TL-OVF. Methods: This retrospective study enrolled 78 women with mean age of 74.69 ± 7.66 (60–92) years diagnosed as a TL-OVF with no neurological deficits. All patients were treated conservatively with teriparatide (34 of group T, once-daily 20 μg) or denosumab (44 of group D, once-6 months 60 mg) for 6 months. We evaluated the radiological deformation (kyphotic angle, segmental vertebral kyphotic angle, and compression ratio) and the incidence of fracture union with paravertebral bone bridge formation (FUPB) and functional outcomes using the visual analog scale (VAS) and Oswestry Disability Index (ODI) at 0, 3, and 6 months. Results: In the radiological deformation and functional outcomes, there were no significant differences at 0, 3, and 6 months between the two groups (P > 0.05). However, the incidence of FUPB at 6 months was higher in group T (20/34, 58.8%) compared to group D (11/44, 25.0%) (P = 0.004), and teriparatide was the most statistically significant factor for achieving FUPB (OR 4.486, P = 0.012) in multivariable logistic analysis. Conclusions: Teriparatide and denosumab, despite of their different pharmacological mechanisms, showed similar radiological deformation and functional outcomes in the conservative treatment of TL-OVF. However, teriparatide showed a significantly higher incidence of fracture union with paravertebral bone bridge formation. [ABSTRACT FROM AUTHOR]

Summary: With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years. Purpose: This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years. Methods: The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017–2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan–Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. Results: The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09–0.71; p = 0.009). No difference was observed between the groups regarding mortality. Conclusion: The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is the standard treatment for early malignant stomach lesions. However, this procedure is technically demanding and carries a high complication risk. The level of difficulty in performing ESD is influenced by the location of the lesion. In our study, we aimed to investigate and analyze the effectiveness of robot-assisted ESD for lesions situated in challenging locations within the stomach. Methods: We developed a gastric simulator that could be used to implement various gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator for the dissection procedures. Robot-assisted or conventional ESD was performed at challenging or easy locations by two ESD-trainee endoscopists. Results: The procedure time was remarkably shorter for robotic ESD than conventional dissection at challenging locations (6.2 vs. 10.2 min, P < 0.05), mainly due to faster dissection (220.3 vs. 101.9 mm2/min, P < 0.05). The blind dissection rate was significantly lower with robotic ESD than with the conventional method (17.6 vs. 35.2%, P < 0.05) at challenging locations. Conclusion: The procedure time was significantly shortened when robot-assisted gastric ESD procedures were performed at challenging locations. Therefore, our robotic device provides simple, effective, and safe multidirectional traction for endoscopic submucosal dissection at challenging locations, thereby reducing difficulty of the procedure. [ABSTRACT FROM AUTHOR]

Objective: KINDLE‐Korea is part of a real‐world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non‐small cell lung cancer (NSCLC). Materials and Methods: The KINDLE was an international real‐world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE‐Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. Results: A total of 461 patients were enrolled. The median age was 66 years (range: 24–87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)‐based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. Conclusion: This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype. Materials and Methods Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population. Results A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1-expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02). Conclusion Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC. [ABSTRACT FROM AUTHOR]

Background: The association between cannabis use and access to waitlisting, transplantation, and post‐transplant outcomes remains uncertain. Methods: Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post‐transplant outcomes was evaluated using Cox proportional hazards models. Results: Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR].82 [95% confidence interval (CI):.72,.94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR.92, [95% CI:.79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy‐proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death‐censored graft failure was similarly elevated (aHR 1.60 [95% CI:.95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI:.90, 1.96]), death with graft function (aHR 1.06 [95% CI:.59, 1.89]), or hospital readmission in the first‐year post‐transplant (aHR 1.26 [95% CI:.95, 1.68]). Conclusions: Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users. [ABSTRACT FROM AUTHOR]

Military personnel in combat face a high risk of developing posttraumatic stress disorder (PTSD). In this study, a protocol-based scoping review was conducted to identify the current status of research on the efficacy of acupuncture for treating combat-related PTSD in military personnel. A literature search was conducted across 14 databases in November 2022, and data from the included studies were collected and descriptively analyzed. A total of eight studies were included. Participants were assessed for core PTSD symptoms using the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 and the Clinician-Administered PTSD Scale, as well as related symptoms, such as sleep issues. Although the efficacy of acupuncture has been substantiated in numerous studies, certain metrics did not exhibit improvement. Auricular acupuncture was the most commonly used treatment (50%) followed by manual acupuncture (25%) and a combination of both (25%). Shenmen and Kidney points were frequently targeted at auricular acupoints. The treatment period varied between 5 days and 2 months. While adverse events were reported in two of the fifty-five patients in the intervention group and in four of the sixty-four patients in the control group in the randomized controlled trial studies, no fatal adverse events were reported. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compared the long-term surgical outcomes of single-port laparoscopy with other surgical methods (multi-port laparoscopy, robot-assisted laparoscopy, and laparotomy) in endometrial cancer (EC) surgical staging. After conducting propensity score matching, all surgical methods demonstrated comparable survival outcomes with respect to disease-free survival and overall survival. Consequently, single-port laparoscopy is deemed a viable option for surgical staging in EC. This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared to multi-port (p = 0.001) and robot-assisted (p = 0.031) laparoscopy. Single-port laparoscopy resulted in a significantly higher 3-year OS than laparotomy (p = 0.013). After propensity score matching, the four groups demonstrated similar survival outcomes (3-year DFS: p = 0.533; 3-year OS: p = 0.328) and recurrence rates (10.3%, 12.1%, 10.3%, and 15.9% in the single-port, multi-port, and robot-assisted laparoscopy and laparotomy groups, respectively, p = 0.552). Recurrence most commonly occurred in distant organs. The single-port laparoscopy group had the longest operative time (205.1 ± 76.9 min) but the least blood loss (69.5 ± 90.8 mL) and the shortest postoperative hospital stay (5.2 ± 2.3 days). In contrast, the laparotomy group had the shortest operative time (163.4 ± 51.0 min) but the highest blood loss (368.3 ± 326.4 mL) and the longest postoperative hospital stay (10.3 ± 4.6 days). The transfusion rate was 0% in the single-port laparoscopy group and 3.7% in the laparotomy group. Notably, the laparotomy group had the highest wound complication rate (p = 0.001), whereas no wound hernias were observed in the three minimally invasive approaches. In conclusion, the survival outcomes were comparable between the methods, with the benefit of lower blood loss and shorter hospital stay observed in the single-port laparoscopy group. This study suggests that single-port laparoscopy is a feasible approach for endometrial cancer surgical staging. [ABSTRACT FROM AUTHOR]

Purpose: This single center study aims to compare the treatment outcomes and procedure-related complications of coil embolization in elderly patients (60–79 years) and very elderly patients (aged 80 years or older) with cerebral aneurysms. Methods: Data was collected from 504 elderly patients aged 60 years or older who underwent coil embolization for intracranial aneurysms from 2018 to 2021. The study evaluated patient-related and anatomical factors and assessed various outcomes, comparing results between groups using statistical analysis and propensity score matching. Results: A total of 503 cerebral aneurysms were analyzed from individuals aged 60–79 years (n = 472) and those aged 80 years or older (n = 31). The majority of the aneurysms were unruptured with an average size of 3.5 mm in height and 3.4 mm in width. The patients were compared using 1:1 propensity score matching, and no significant differences were found in factors other than age and aortic elongation. Logistic analysis revealed that being over 80 years old and having a severe aortic arch elongation were identified as risk factors for procedure-related events in both total and unruptured cases. Conclusions: The study compared coil embolization treatment for cerebral aneurysms in patients aged 60–79 and over 80, finding no significant difference in treatment outcomes except for procedure-related events. Procedure-related events were associated with severe aortic arch elongation and being over 80 years old. Coil embolization can be considered safe and effective for patients over 80, but further trials are needed for accurate conclusions. [ABSTRACT FROM AUTHOR]

Recent studies on osteosarcoma regimens have mainly focused on modifying the combination of antineoplastic agents rather than enhancing the therapeutic efficacy of each component. Here, an albumin nanocluster (NC)‐assisted methotrexate (MTX), doxorubicin (DOX), and cisplatin (MAP) regimen with improved antitumor efficacy is presented. Human serum albumin (HSA) is decorated with thiamine pyrophosphate (TPP) to increase the affinity to the bone tumor microenvironment (TME). MTX or DOX (hydrophobic MAP components) is adsorbed to HSA‐TPP via hydrophobic interactions. MTX‐ or DOX‐adsorbed HSA‐TPP NCs exhibit 20.8‐ and 1.64‐fold higher binding affinity to hydroxyapatite, respectively, than corresponding HSA NCs, suggesting improved targeting ability to the bone TME via TPP decoration. A modified MAP regimen consisting of MTX‐ or DOX‐adsorbed HSA‐TPP NCs and free cisplatin displays a higher synergistic anticancer effect in HOS/MNNG human osteosarcoma cells than conventional MAP. TPP‐decorated NCs show 1.53‐fold higher tumor accumulation than unmodified NCs in an orthotopic osteosarcoma mouse model, indicating increased bone tumor distribution. As a result, the modified regimen more significantly suppresses tumor growth in vivo than solution‐based conventional MAP, suggesting that HSA‐TPP NC‐assisted MAP may be a promising strategy for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Background: Recent biomechanical studies have reported that stress on the posterior cruciate ligament (PCL) graft increases as the posterior tibial slope (PTS) decreases (flattened) in knees with single-bundle (SB) and double-bundle PCL reconstruction. Clinical studies of SB PCL reconstruction have shown that a flattened PTS is associated with a lesser reduction in posterior tibial translation. There is no long-term study on the clinical outcomes and graft survival rates of SB PCL reconstruction based on the medial and lateral PTSs measured on magnetic resonance imaging. Hypothesis: Flattened medial and lateral PTSs are associated with poor clinical outcomes and graft survival rates at a minimum 10-year follow-up after SB PCL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: In this cohort study, we retrospectively reviewed 46 patients (mean age, 28.8 ± 9.9 years) who underwent primary SB PCL reconstruction between 2000 and 2009. They were followed up for a minimum of 10 years. The medial and lateral PTSs were measured on preoperative magnetic resonance imaging. As a previous study reported that a steeper medial or lateral PTS showed a higher risk of anterior tibial translation at thresholds of 5.6° and 3.8°, respectively, the patients were divided into 2 groups based on the cutoff values of both the medial (≤5.6° vs >5.6°) and lateral (≤3.8° vs >3.8°) PTSs. Clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity score), radiological outcomes (side-to-side difference [SSD] on stress radiography and osteoarthritis progression), and graft survival rates were compared between the groups at the last follow-up. Results: All clinical scores and the progression of osteoarthritis demonstrated no significant difference between the 2 subgroups of both the medial and lateral PTS groups. The mean SSD on stress radiography after SB PCL reconstruction was significantly greater in patients with a medial PTS ≤5.6° than in patients with a medial PTS >5.6° (8.4 ± 3.9 vs 5.1 ± 2.9 mm, respectively; P =.030), while the lateral PTS subgroups after SB PCL reconstruction demonstrated no significant difference. The minimum 10-year graft survival rate was significantly lower in patients with a medial PTS ≤5.6° (68.4% vs 92.6%, respectively; P =.029) and a lateral PTS ≤3.8° (50.0% vs 91.7%, respectively; P =.001). Conclusion: A flattened medial PTS (≤5.6°) was associated with an increased SSD on stress radiography, and both flattened medial (≤5.6°) and lateral (≤3.8°) PTSs resulted in lower graft survival rates at a minimum 10-year follow-up after primary SB PCL reconstruction. [ABSTRACT FROM AUTHOR]

Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing a percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods A total of 4119 consecutive subjects who underwent a PCI with a DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient's age and mean blood pressure. Major adverse cardiovascular events (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Results During a median follow-up duration of 3.51 years (interquartile range, 1.35–6.37 years), there were 746 MACEs (18.1%). A multivariable analysis showed that a higher ePWV was associated with a higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81–3.42; p < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33–8.80; p < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; p < 0.001). Conclusion ePWV demonstrated a significant association with MACEs in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risks within this high-risk patient population. [ABSTRACT FROM AUTHOR]

Objective: Conservatrice et Hémodynamique de l'Insuffisance Veineuse en Ambulatoire, the French acronym for CHIVA, is a strategy aimed to convert a venous reflux into a physiological drainage. We compared CHIVA with radiofrequency ablation and determined its possible advantages. Methods: We retrospectively analyzed the clinical recurrence, ultrasound recurrence, quality of life scores, and complications. They were compared after propensity score matching. Results: 212 limbs of 166 patients were included: 42 limbs underwent radiofrequency ablation and 170 limbs underwent CHIVA. The hospital stay was shorter in the CHIVA group. There was no difference in clinical, ultrasound recurrence, quality of life scores and complications between the two groups. The preoperative saphenous vein diameter was larger in the recurrence cases. Conclusions: CHIVA showed comparable results to radiofrequency ablation. There was more ultrasound recurrence with larger vein diameters. The CHIVA appears to be a simple and more efficient treatment method when performed on select patients. [ABSTRACT FROM AUTHOR]

1 Paraffin bath therapy is a noninvasive treatment that widely used for pain control and functional improvement in various hand diseases. 2 However, there are few large-scale studies of paraffin bath therapy, and there is insufficient evidence of its efficacy. 3 This meta-analysis showed that paraffin bath therapy alone or combination with other treatments significantly reduced the visual analogue scale score and enhanced grip and pinch strengths. 4 Paraffin bath therapy exerts positive effects in the treatment of various hand diseases including osteoarthritis, carpal tunnel syndrome, spasticity in stroke and post-traumatic stiffness, thereby improving quality of life. Paraffin bath therapy is noninvasive and is widely used in various hand diseases. Paraffin bath therapy is easy to use, has fewer side effects, and can be applied to various diseases with different etiologies. However, there are few large-scale studies of paraffin bath therapy, and there is insufficient evidence of its efficacy. The purpose of the study was to investigate the effectiveness of paraffin bath therapy for pain relief and functional improvement in various hand diseases through a meta-analysis. Systematic review and meta-analysis of randomized controlled trials. We searched for studies using PubMed and Embase. Eligible studies were selected based on the following criteria: (1) patients with any diseases of the hand; (2) comparison between paraffin bath therapy and no paraffin bath therapy; and (3) sufficient data on changes in the visual analog scale (VAS) score, grip strength, pulp-to-pulp pinch strength, or Austrian Canadian (AUSCAN) Osteoarthritis Hand index before and after paraffin bath therapy. Forest plots were drawn to visualize the overall effect. Jadad scale score, I2 statistics, and subgroup analyses were used to assess the risk of bias. A total of five studies included 153 patients who were treated and 142 who were not treated with paraffin bath therapy. The VAS were measured in all 295 patients included in the study, while the AUSCAN index was measured in the 105 patients with osteoarthritis. Paraffin bath therapy significantly reduced the VAS scores (mean difference [MD], −1.27; 95% confidence interval [CI] −1.93 to −0.60). In osteoarthritis, paraffin bath therapy significantly improved grip and pinch strength (MD −2.53; 95% CI 0.71-4.34; MD 0.77; 95% CI 0.71-0.83) and reduced the VAS and AUSCAN scores (MD −2.61; 95% CI −3.07 to −2.14; MD −5.02; 95% CI −8.95 to −1.09). Paraffin bath therapy significantly reduced the VAS and AUSCAN scores, and improved grip and pinch strength in patients with various hand diseases. Paraffin bath therapy is effective for alleviating pain and improving function in hand diseases, thereby improving quality of life. However, owing to the small number of patients included in the study and its heterogeneity, a further large-scale, well-structured study is needed. [ABSTRACT FROM AUTHOR]

Background: The effects of inspiratory muscle training (IMT) with pulmonary rehabilitation (PR) on patients with non‐small cell lung cancer (NSCLC) receiving radiotherapy (RT) have not previously been reported. This pilot study aimed to determine the effectiveness of IMT with PR on respiratory muscles and exercise capacity of NSCLC patients receiving RT. Methods: We retrospectively analyzed 20 patients who underwent RT for NSCLC. The rehabilitation included IMT, stretching, strengthening, and aerobic exercises three times a week for 4 weeks with concurrent RT. IMT training lasted 10 min, consisting of one cycle of 30 breaths using the Powerbreathe KH1 device in the hospital by a physical therapist. Patients underwent two IMT sessions at home daily at an intensity of approximately 30%–50% of the participant's maximum inspiratory muscle pressure (MIP) using the threshold IMT tool. We analyzed the results from the respiratory muscle strength test, pulmonary function test, 6‐min walk test (6MWT), cardiopulmonary function test, cycle endurance test (CET), Inbody test, grip measurement, knee extensor/flexor strength measurement, Cancer Core Quality of Life Questionnaire (EORTCQ‐C30), and NSCLC 13 (EORTC‐LC13). Results: There were no adverse events during evaluation and IMT with PR. MIP (60.1 ± 25.1 vs. 72.5 ± 31.9, p = 0.005), 6MWT (439.2 ± 97.1 vs. 60.7 ± 97.8, p = 0.002), CET (181.39 ± 193.12 vs. 123.6 ± 87.6, p = 0.001), knee extensor (14.4 ± 5.3 vs. 17.4 ± 5, p = 0.012), and knee flexor (14.0 ± 5.2 vs. 16.9 ± 5.5, p = 0.004) significantly improved after IMT with PR. Conclusion: IMT with PR appears effective on respiratory muscles and exercise capacity without adverse events in NSCLC patients who underwent RT. [ABSTRACT FROM AUTHOR]

Background: Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL. Methods: A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity. Results: Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408–1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823). Conclusions: Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL. [ABSTRACT FROM AUTHOR]

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non‐gender CHA2DS2‐VASc scores 0–1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non‐gender CHA2DS2‐VASc scores 0–1. Methods: This multi‐center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non‐VKA oral anticoagulant (NOAC) in non‐gender CHA2DS2‐VASc score 0–1 and further stratified by biomarker‐based ABCD score (Age [≥60 years], B‐type natriuretic peptide [BNP] or N‐terminal pro‐BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed‐up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37–4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56–5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non‐gender CHA2DS2‐VASc scores 0–1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1. [ABSTRACT FROM AUTHOR]

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances. [ABSTRACT FROM AUTHOR]

Background: The combined anterior–posterior approach has shown good clinical outcomes for multilevel cervical diseases. This work describes the biomechanical advantage of cervical-pedicle-screw fixation over lateral-mass-screw fixation in combined anterior–posterior cases. Method: Seventy-six patients who received combined cervical surgery from June 2013 to December 2020 were included. The patients were divided into two groups: the lateral-mass-screw group (LMS) and the pedicle-screw group (PPS). Radiological outcomes were assessed with lateral cervical spine X-rays for evaluating sagittal alignment, subsidence, and bone remodeling. Results: At 1 year postoperatively, the numbers of patients whose C2–C7 cervical lordosis was less than 20 degrees decreased by more in the PPS group (p-value = 0.001). The amount of vertical-length change from immediately to 1 year postsurgery was less in the PPS group than in the LMS group (p-value = 0.030). The mean vertebral-body-width change was larger in the PPS group than in the LMS group during 3 months to 1 year postsurgery (p-value = 0.000). Conclusions: In combined anterior–posterior cervical surgery cases, maintenance of cervical lordosis and protection of the vertebral body from subsidence were better with the pedicle-screw fixation. More bone remodeling occurred when using the pedicle-screw fixation method. [ABSTRACT FROM AUTHOR]

A significant mismatch between proximal and distal reference lumen diameters of the target lesion may pose challenges during percutaneous coronary intervention (PCI) and therefore influence the outcomes. We investigated total 1706 lesions underwent IVUS guided percutaneous coronary intervention, that were divided into 2 groups, including 411 lesions in Mismatch group and 1295 lesions in Non-Mismatch group. After propensity score matching, 397 lesions in each group were selected for final data set. The analysis showed that Mismatch group PCI required more frequently use of post-stenting optimization (79.6% vs 53.9%, P <.001) using higher max pressure (19.5 ± 3.9 vs 16.7 ± 3.7 atm, P <.001). Besides, Mismatch group also encountered more PCI major complications (7.8% vs 4.0%, P =.024) and lower procedure success rate (91.4% vs 95.5%, P =.022). On final angiogram, Mismatch group had smaller minimum lumen diameter (2.62 ±.45 vs 2.90 ±.57 mm, P <.001) and lower angiographic success rate (93.2% vs 96.7%, P =.023). On final IVUS, Mismatch group had higher rate of incomplete stent apposition and stent edge dissection (6.3% vs 3.0%, P =.029 and 2.5% vs.5%, P =.021, respectively). In conclusion, reference mismatch posed significant challenging during PCI that led to unfavorable procedural outcomes. These impacts may translate into long-term clinical implications that need to be addressed in future studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies of patient positioning during spinal surgery evaluated intraoperative or immediate postoperative outcomes after short-instrumented lumbar fusion. However, patient positioning during long-instrumented fusion for an adult spinal deformity (ASD) might be associated with differences in intraoperative parameters such as blood loss and longer-term outcomes such as spine alignment, and comparing types of surgical tables in the context of these larger procedures and evaluating longer-term outcome scores seem important.Questions/purposes: (1) Do blood loss and the number of transfusions differ between patients who underwent multi-level spinal fusion with a Wilson frame and those with a four-poster frame? (2) Does restoration of lumbar lordosis and the sagittal vertical axis differ between patients who underwent surgery with the use of one frame or the other? (3) Do clinical outcomes as determined by Numeric Rating Scale and Oswestry Disability Index scores differ between the two groups of patients? (4) Are there differences in postoperative complications between the two groups?Methods: Among 651 patients undergoing thoracolumbar instrumented fusion between 2015 and 2018, 129 patients treated with more than four levels of initial fusion for an ASD were identified. A total of 48% (62 of 129) were eligible; 44% (57 of 129) were excluded because of a history of fusion, three-column osteotomy, or surgical indications other than degenerative deformity, and another 8% (10 of 129) were lost before the minimum 2-year follow-up period. Before January 2017, one surgeon in this study used only a Wilson frame; starting in January 2017, the same surgeon consistently used a four-poster frame. Forty patients had spinal fusion using the Wilson frame; 85% (34 of 40) of these had follow-up at least 2 years postoperatively (mean 44 ± 13 months). Thirty-two patients underwent surgery using the four-poster frame; 88% (28 of 32) of these were available for follow-up at least 2 years later (mean 34 ± 6 months). The groups did not differ in terms of age, gender, BMI, type of deformity, or number of fused levels. Surgical parameters such as blood loss and the total amount of blood transfused were compared between the two groups. Estimated blood loss was measured by the amount of suction drainage and the amount of blood that soaked gauze. The decision to transfuse blood was based on intraoperative hemoglobin values, a protocol that was applied equally to both groups. Radiologic outcomes including sagittal parameters and clinical outcomes such as the Numerical Rating Scale score for back pain (range 0-10; minimal clinically important difference [MCID] 2.9) and leg pain (range 0-10; MCID 2.9) as well as the Oswestry Disability Index score (range 0-100; MCID 15.4) were also assessed through a longitudinally maintained database by two spine surgeons who participated in this study. Repeated-measures analysis of variance was used to compare selected radiologic outcomes between the two groups over time.Results: Blood loss and the total amount of transfused blood were greater in the Wilson frame group than in the four-poster frame group (2019 ± 1213 mL versus 1171 ± 875 mL; mean difference 848 [95% CI 297 to 1399]; p = 0.003 for blood loss; 1706 ± 1003 mL versus 911 ± 651 mL; mean difference 795 [95% CI 353 to 1237]; p = 0.001 for transfusion). Lumbar lordosis and the sagittal vertical axis were less restored in the Wilson frame group than in the four-poster frame group (7° ± 10° versus 18° ± 14°; mean difference -11° [95% -17° to -5°]; p < 0.001 for lumbar lordosis; -22 ± 31 mm versus -43 ± 27 mm; mean difference 21 [95% CI 5 to 36]; p = 0.009 for the sagittal vertical axis). Such differences persisted at 2 years of follow-up. The proportion of patients with the desired correction was also greater in the four-poster frame group than in the Wilson frame group immediately postoperatively and at 2 years of follow-up (50% versus 21%, respectively; odds ratio 3.9 [95% CI 1.3 to 11.7]; p = 0.02; 43% versus 12%, respectively; odds ratio 5.6 [95% CI 1.6 to 20.3]; p = 0.005). We found no clinically important differences in postoperative patient-reported outcomes including Numeric Rating Scale and Oswestry Disability Index scores, and there were no differences in postoperative complications at 2 years of follow-up.Conclusion: The ideal patient position during surgery for an ASD should decrease intra-abdominal pressure and induce lordosis as the abdomen hangs freely and hip flexion is decreased. The four-poster frame appears advantageous for long-segment fusions for spinal deformities. Future studies are needed to extend our analyses to different types of spinal deformities and validate radiologic and clinical outcomes with follow-up for more than 2 years.Level Of Evidence Level: III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic obstructive pulmonary disease (COPD) is increasingly common and may have an adverse impact on outcomes in patients undergoing total joint arthroplasty (TJA) of lower extremity. The purpose of this meta-analysis is to compare the postoperative complications between COPD and non-COPD patients undergoing primary TJA including total hip and knee arthroplasty. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies published before December 2021. Postoperative outcomes were compared between patients with COPD versus those without COPD as controls. The outcomes were mortality, re-admission, pulmonary, cardiac, renal, thromboembolic complications, surgical site infection (SSI), periprosthetic joint infection (PJI), and sepsis. Results: A total of 1,002,779 patients from nine studies were finally included in this meta-analysis. Patients with COPD had an increased risk of mortality (OR [odds ratio] = 1.69, 95% confidence interval [CI] 1.42–2.02), re-admission (OR = 1.54, 95% CI 1.38–1.71), pulmonary complications (OR = 2.73, 95% CI 2.26–3.30), cardiac complications (OR = 1.40, 95% CI 1.15–1.69), thromboembolic complications (OR = 1.21, 95% CI 1.15–1.28), renal complications (OR = 1.50, 95% CI 1.14–1.26), SSI (OR = 1.23, 95% CI 1.18–1.30), PJI (OR = 1.26, 95% CI 1.15–1.38), and sepsis (OR = 1.36, 95% CI 1.22–1.52). Conclusion: Patients with comorbid COPD showed an increased risk of mortality and postoperative complications following TJA compared with patients without COPD. Therefore, orthopedic surgeons can use the study to adequately educate these potential complications when obtaining informed consent. Furthermore, preoperative evaluation and medical optimization are crucial to minimizing postoperative complications from arising in this difficult-to-treat population. Level of evidence: Level III. Registration: None. [ABSTRACT FROM AUTHOR]

Introduction: The effects of switching DPP-4 inhibitors in type 2 diabetes mellitus (T2DM) patients are being widely studied. However, information of which factors affect the therapeutic response is limited. We evaluated the difference in HbA1c lowering effect by comorbidity and other variables after switching to anagliptin in patients with T2DM inadequately controlled by other DPP-4 inhibitors. Methods: In a multicenter, open-label, single-arm, prospective observational study, patients with T2DM, HbA1c ≥ 7.0% who have taken DPP-4 inhibitors other than anagliptin, either alone or in combination (DPP-4 inhibitors + metformin/sulfonylurea (SU)/thiazolidinedione (TZD)/insulin), for at least 8 weeks were enrolled. After the switch to anagliptin, HbA1c and available clinical characteristics were determined. Results: The change in HbA1c levels from baseline to week 12 and 24 was − 0.40% and − 0.42% in all patients. However, comparing the subgroups without and with comorbidities, the change in HbA1c levels at weeks 12 and 24 was − 0.68% and − 0.89% vs. − 0.27% and 0.22%, respectively. In addition, the proportion of patients achieving HbA1c < 7% from baseline to week 12 and 24 was increased to 70% and 70% vs. 20% and 24%, respectively. Duration of T2DM and different subtype classes of DPP-4 inhibitor did not significantly contribute to the change in HbA1c. Conclusion: In patients with T2DM poorly controlled by other DPP-4 inhibitors, HbA1c levels were significantly decreased after switching to anagliptin. Given that the change in HbA1c was greater in patients without comorbidities than in patients with comorbidities, switching to anagliptin before adding other oral hypoglycemic agents (OHAs) may be an option in patients without comorbidities. [ABSTRACT FROM AUTHOR]

Background: Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer. Methods: Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression‐free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune‐related adverse events (irAEs). Results: Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second‐line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all‐grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382). Conclusions: Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Length of stay and functional outcomes after total knee arthroplasty (TKA) are related to the timing and intensity of post-operative rehabilitation. OBJECTIVE: To determine the effectiveness of early and high-intensity rehabilitation after simultaneous bilateral TKA. METHODS: Prospective cohort data of 156 patients (11 men and 145 women; average age 72.0 ± 5.6 years) who underwent simultaneous bilateral primary TKA were analyzed. The intervention group (n = 82) underwent a high-intensity rehabilitation (phase II) after early postoperative standard rehabilitation (phase I) between June 2019 and May 2021. The control group (n = 74) underwent a lower-intensity rehabilitation (phase II) after phase I rehabilitation between July 2017 and May 2019. The timed up-and-go (TUG) test, timed stair climbing test (SCT), 6-minute walk test, isometric knee extensor and flexor strength of both knees, knee flexion and extension range of motion, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) for pain, stiffness, and functional levels, and the EuroQol five-dimension questionnaire were assessed preoperatively and 6 weeks after TKA. RESULTS: The average length of hospital stay was shortened by 5.7 days (p < 0.001). Phase II rehabilitation started earlier in the intervention group than in the control group (7.7 ± 1.3 vs 13.5 ± 2.0, p < 0.001). Compared with the control group, the intervention group showed significant improvements in the measures of mobility (WOMAC-function and SCT) and strength (isometric strength of both knee extensors and flexors) 6 weeks after TKA by statistically controlling for age and preoperative functional status. CONCLUSION: This study demonstrated that early and high-intensity rehabilitation could achieve functional improvement and shorten the length of hospital stay. [ABSTRACT FROM AUTHOR]

Introduction: A one-way valve lesion plays an important role in the formation of Baker's cysts and serves as an important landmark for accessing these cysts during arthroscopic surgery. This study aimed to investigate the incidence of one-way valve lesions and their effect on clinical outcomes in patients who underwent arthroscopic cystectomy for Baker's cysts. Materials and methods: Patients who underwent arthroscopic cystectomy for Baker's cysts between June 2005 and November 2017 were retrospectively reviewed. Patient demographic characteristics, radiologic/arthroscopic findings (presence of one-way valve lesions, concurrent chondral and meniscal lesions, and cyst wall thickness), and clinical outcomes (clinical recurrence rate, Lysholm score, and complications) at the 2-year follow-up were evaluated. Subgroup analysis was performed to compare clinical outcomes between patients with and without one-way valve lesions. Results: Thirty patients (mean age, 57.4 ± 9.4 years) were included in this study. One-way valve lesions were surgically documented in 11 patients (36.7%). Ten patients (33.3%) had chondral lesions with an International Cartilage Repair Society grade ≥ 3, and 23 patients (76.7%) had concurrent chondral and meniscal lesions. At the 2-year follow-up, none of the patients had experienced clinical recurrence; the mean Lysholm score was 76.3 ± 17.5 (48–100). Three patients reported persistent pain, while two reported numbness or paresthesia. Subgroup analysis showed no significant differences in clinical recurrence rates, Lysholm scores, and complication rates between the groups. Conclusions: The incidence of one-way valve lesions during arthroscopic cystectomy for Baker's cysts was lower than that previously reported. Arthroscopic cystectomy showed good clinical results in patients with and without these lesions. [ABSTRACT FROM AUTHOR]

Objectives: Obliteration with cauterization of the internal opening of pyriform sinus fistulas, with or without marsupialization, has been a mainstay for preventing recurrence. However, this procedure predisposes patients to recurrence caused by the reopening of the cauterized orifice. We applied suture ligation to secure the closure of the internal orifice following cauterization and evaluated treatment Methods: A total of 42 patients were diagnosed with third or fourth branchial cleft anomaly with internal pyriform sinus fistula and treated either with cauterization or with cauterization and suture ligation, between January 2008 and December 2020. The medical records were reviewed to assess demographic characteristics, clinical presentations, diagnoses, surgical treatment, and outcomes. Treatment flow characteristics for intractable patients were analyzed. Results: The median age of onset was 9 years (range, 0-57 years). Neck swelling (n = 32, 76.2%) was commonly encountered symptom, and a history of neck infection was found in 27 patients (64.3%). After initial treatment, 11 cases (56.2%) recurred. Younger age (≤9 years) and thyroid involvement were associated with recurrence (P =.034 and P =.046, respectively). Cauterization with suture ligation presented lower recurrence rate (19.2%) than cauterization only (37.5%, P =.037). Cauterization with suture ligation for recurrent cases (n = 11) showed 81.8% (9/11) of cure rate. Intractable fistulas (n = 2) from both groups were also salvaged by suture ligation. Conclusions: Suture ligation with cauterization for an internal orifice of branchial anomaly showed lower recurrence rate than cauterization only. This method was beneficial for refractory cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced therapies have provided substantial clinical benefits in oncology, but low response rates in lung cancer patients remain challenging. Using preclinical models of human lung cancer, we investigated the anti-tumor potency of nanomedicine-based gene delivery for the tumor suppressor RB94 and explored the mechanisms underlying its activity. This nanomedicine (scL-RB94) elicited significant anti-tumor responses reflecting enhanced tumor immunogenicity and reduced immunosuppression. The potential of scL-RB94 to improve outcomes in lung cancer patients is discussed. Because lung cancer remains the most common and lethal of cancers, novel therapeutic approaches are urgently needed. RB94 is a truncated form of retinoblastoma tumor suppressor protein with elevated anti-tumor efficacy. Our investigational nanomedicine (termed scL-RB94) is a tumor-targeted liposomal formulation of a plasmid containing the gene encoding RB94. In this research, we studied anti-tumor and immune modulation activities of scL-RB94 nanocomplex in preclinical models of human non-small cell lung cancer (NSCLC). Systemic treatment with scL-RB94 of mice bearing human NSCLC tumors significantly inhibited tumor growth by lowering proliferation and increasing apoptosis of tumor cells in vivo. scL-RB94 treatment also boosted anti-tumor immune responses by upregulating immune recognition molecules and recruiting innate immune cells such as natural killer (NK) cells. Antibody-mediated depletion of NK cells blunted the anti-tumor activity of scL-RB94, suggesting that NK cells were crucial for the observed anti-tumor activity in these xenograft models. Treatment with scL-RB94 also altered the polarization of tumor-associated macrophages by reducing immune-suppressive M2 macrophages to lower immune suppression in the tumor microenvironment. Collectively, our data suggest that the efficacy of scL-RB94 against NSCLC is due to an induction of tumor cell death as well as enhancement of innate anti-tumor immunity. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies in transgenic models of Alzheimer's disease (AD) suggest that DHP1401 has neuroprotective and memory-enhancing effects.Objective: To evaluate the efficacy and safety of DHP1401 in AD patients treated with donepezilMethods:Methods: In a double-blind study, patients with mild-to-moderate AD were randomized (1:1:1) to receive a twice daily total dose of 500 mg or 1000 mg DHP1401 or placebo for 24 weeks. Tolerability and safety were monitored at baseline and weeks 12 and 24.Results: total of 180 patients were randomized to Active 1 (500 mg: n = 62), Active 2 (1000 mg: n = 53), and control groups (n = 65) in 16 sites in Korea. There was no significant difference in the Alzheimer's Disease Assessment Scale (ADAS-cog) score, the primary efficacy endpoint, from baseline. However, in the subgroup with mild AD patients (MMSE, 20-26) who received the high dose of DHP1401 and the group that received donepezil 5 mg, the ADAS-cog scores improved. MMSE and K-TMT-e type B were significant in both active groups at week 24. The most frequently observed symptom was dizziness (2.78%), and the most commonly observed reactions were related to metabolism and nutrition disorders (5.00%). No remarkable adverse events were observed for 24 weeks.Conclusion: Although the effectiveness of DHP1401 was not proved to be superior as the primary efficacy endpoint, the secondary endpoints, MMSE and K-TMT-e type B, showed significant beneficial effects. Also, the subgroups showed that ADAS-cog scores significantly were improved. DHP1401 could be proven beneficial for the AD treatment by further clinical trials. [ABSTRACT FROM AUTHOR]

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD. [ABSTRACT FROM AUTHOR]

To investigate the biological significance of I Selenomonas i in asthma, we adopted a murine asthma model. Airway microbiota in severe asthma and relationship to asthma severity and phenotypes. The purpose of this study is to understand the characteristics of the asthmatic airway by analyzing the airway bacteriome, to identify the microbial genera associated with asthma clinical indices, and to investigate the polymicrobial interactions based on the asthma severity grouping. [Extracted from the article]

Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast and gastric cancers and this causes poor clinical outcomes. Although both T‐DM1 and Enhertu are approved as an HER2‐targeting antibody‐drug conjugate (ADC), the effects of these drugs are still not satisfactory to eradicate diverse tumors expressing HER2. To address this shortfall in HER2‐targeted therapeutics, an elaborate cleavable linker is created and a novel HER2‐targeting ADC composed with trastuzumab and monomethyl auristatin F, which is being investigated in a phase 1 clinical trial and is referred to as LegoChem Bisciences‐ADC (LCB‐ADC). LCB‐ADC displays a higher cytotoxic potency than T‐DM1 and it also has a higher G2/M arrest ratio. In animal studies, LCB‐ADC produces noticeable tumor growth inhibition compared with trastuzumab or T‐DM1 in an HER2 high‐expressing N87 xenograft tumor. Especially, LCB‐ADC shows good efficacy in terms of suppressing tumor growth in a patient‐derived xenograft (PDX) model of HER2‐positive gastric cancer as well as in T‐DM1‐resistant models such as HER2 low‐expressing HER2 low expressing JIMT‐1 xenograft tumor and PDX. Collectively, the results demonstrate that LCB‐ADC with the elaborate linker has a higher efficacy and greater biostability than its ADC counterparts and may successfully treat cancers that are nonresponsive to previous therapeutics. [ABSTRACT FROM AUTHOR]

Aims: Postoperative tendon adhesions contribute to functional disability and reconstructive failure. In this study, we present the long-term outcomes of a prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesion after tendon injury. Methods: The study was conducted between March 2014 and February 2017. Patients, aged 19–65 years, with an acute single flexor tendon injury in zones 1 or 2, distal to the palmar digital crease were candidates for the study. Patients were allocated to either an ADM treatment group or a control group without ADM treatment. Results: A total of 37 patients were enrolled in the study: 21 patients in the ADM group and 16 patients in the control group. At six months after surgery, the range of motion in the proximal interphalangeal joint was 81.0±5.1 degrees in the ADM group and 75.8±6.9 degrees in the control group. The range of motion in the distal interphalangeal joint was 79.9±7.1 in the ADM group and 71.2±5.7 degrees in the control group, with significant difference (p=0.03 and p<0.05, respectively). In addition, the total active motion was higher in the ADM group than in the control group. The patients' scores on the Patient Satisfaction Questionnaire were also significantly different, with higher satisfaction scores in the ADM group (p=0.02). The minimal follow-up period was six months. Conclusion: The use of ADM after tendon repair has the potential to significantly improve the outcome of tendon surgery in terms of range of motion. Declaration of interest: None of the authors has any financial interest in the products, devices, or drugs mentioned in this article. [ABSTRACT FROM AUTHOR]

Background/Aims: Although the epidemiology of pyogenic liver abscess (PLA) continues to change, only a few population‐based studies have been conducted in Korea. This study investigated the epidemiology and clinical outcomes of PLA patients during a period of 10 years. Methods: We analysed the Health Insurance Review and Assessment Service data between 2007 and 2017. The data included annual incidence rates, demographic data, underlying diseases, complications and mortality of PLA patients. Results: The annual incidence of PLA for all age groups was 10.9 per 100 000 population. The incidence was gradually increased from 5.7 per 100 000 in 2007 to 14.4 per 100 000 in 2017. In patients with liver abscess, the prevalence of diabetes and malignancy were 37.24% and 26.5% respectively. Metastatic infection was reported in 1.74% of the patients, and endophthalmitis was most common. The mean in‐hospital mortality was 9.6%, and there was no significant difference in mortality by year during the observation period. Mortality increased with age and was greatly affected by the underlying diseases, especially cancer. Based on the multivariate analysis results, the mortality of PLA patients was associated with older age, female sex, diabetes, malignancy and chronic kidney disease. Conclusion: The PLA incidence is rapidly increasing in Korea, especially in people with comorbidities. In addition, the causes and risk factors of PLA infections are changing and thus further research on epidemiology, different diagnosis and management approaches is required. [ABSTRACT FROM AUTHOR]

Background: Although the inter-arm blood pressure (BP) difference has been advocated to be associated with cardiovascular events, the implication of inter-leg BP difference has not been well established. This study was conducted to investigate whether inter-arm and -leg BP differences have prognostic value in patients undergoing percutaneous coronary intervention (PCI). Methods: In this prospective study, we consecutively enrolled 667 patients who underwent PCI. Both arm and leg BPs were measured at the day after PCI. The primary outcome was a major adverse cardiovascular event (MACE) including cardiac death, acute coronary syndrome, coronary revascularization, stroke, and hospitalization for heart failure during the follow-up period. Results: Mean age was 64.0±11.1 years old, and males were predominant (70.5%). During a mean follow-up period of 3.0 years, MACE occurred in 209 (31.3%) patients. The inter-leg systolic BP difference (ILSBPD) was significantly higher in patients with MACE than those without (9.9±12.3 vs. 7.2±7.5 mmHg, P = 0.004). The inter-arm systolic BP difference was not significantly different between patients with and without MACE (P = 0.403). In multivariable Cox regression analysis, increased ILSBPD was independently associated with the development of MACE (per 5 mmHg; hazard ratio, 1.07; 95% confidence interval, 1.01–1.14). The inter-arm systolic BP difference was not associated with MACE in the multivariable analysis. Conclusion: Increased ILSBPD was independently associated with worse cardiovascular outcomes after PCI. As ILSBPD is easy to measure, it may be helpful in the risk stratification of patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse. Methods: Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 106 cells/200 µL) were subcutaneously injected into the flank of each mouse. One week after the injection of AGS cells, ZPE was administered to the skin tissue [10 or 50 mg/(kg·d)] in the low- and high-dose groups, respectively for 20 days. Control animals were injected with vehicle only. After 3 weeks, the tumor was extracted and carried out for immunohistochemistry, the tendency of apoptosis and p53 in the body was checked using TdT-mediated dUTP nick-end labeling (TUNEL) assay. For 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V dead cell staining, cell cycle arrest and Western blotting, AGS gastric carcinoma cells were incubated with various concentrations of ZPE for 24 h. Cell survival rates were analyzed by MTT assays. Apoptosis was analyzed using annexin V dead cell staining and cell cycle arrest and measured using Muse cell analyzer. Results: High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10–85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G1 phase in ZPE (10–70 µ g/mL) groups. ZPE decreased the expression of anti-apoptotic proteins (p-Akt, p-MDM2, Bcl-2), while increased pro-apoptotic proteins (cleaved PARP, p53, pro-Caspase 3, Bax). TUNEL assays revealed an increase in cell apoptosis. Immunohistochemistry staining confirmed the involvement of p53. Conclusion: ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm.Methods: A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated.Results: Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group.Conclusions: Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10 years. [ABSTRACT FROM AUTHOR]