Atlantic salmon (Salmo salar) waste as a unique source of biofunctional protein hydrolysates: Emerging productions, promising applications, and challenges mitigation.

The Atlantic salmon is an extremely popular fish for its nutritional value and unique taste among several fish species. Researchers are focusing on the utilization of Atlantic salmon waste for generating protein hydrolysates rich in peptides and amino acids and investigating their health benefits. Several technological approaches, including enzymatic, chemical, and the recently developed subcritical water hydrolysis, are currently used for the production of Atlantic salmon waste protein hydrolysates. Hydrolyzing various wastes, e.g., heads, bones, skin, viscera, and trimmings, possessing antioxidant, blood pressure regulatory, antidiabetic, and anti-inflammatory properties, resulting in applications in human foods and nutraceuticals, animal farming, pharmaceuticals, cell culture, and cosmetics industries. Furthermore, future applications, constraints several challenges associated with industrial hydrolysate production, including sensory, safety, and economic constraints, which could be overcome by suggested techno processing measures. Further studies are recommended for developing large-scale, commercially viable production methods, focusing on eradicating sensory constraints and facilitating large-scale application.

Cloning, characterization of ß-glucosidase from Furfurilactobacillus rossiae in bioconversion and its efficacy.

Minor ginsenosides produced by ß-glucosidase are interesting biologically and pharmacologically. In this study, new ginsenoside-hydrolyzing glycosidase from Furfurilactobacillus rossiae DCYL3 was cloned and expressed in Escherichia coli strain BL21. The enzyme converted Rb1 and Gyp XVII into Rd and compound K following the pathways: Rb1→Rd and Gyp XVII→F2→CK, respectively at optimal condition: 40 °C, 15 min, and pH 6.0. Furthermore, we examined the cytotoxicity, NO production, ROS generation, and gene expression of Gynostemma extract (GE) and bioconverted Gynostemma extract (BGE) in vitro against A549 cell lines for human lung cancer and macrophage RAW 264.7 cells for antiinflammation, respectively. As a result, BGE demonstrated significantly greater toxicity than GE against lung cancer at a dose of 500 µg/mL but in normal cells showed lower toxicity. Then, we indicated an enhanced generation of ROS, which may be boosting cancer cell toxicity. By blocking the intrinsic way, BGE increased p53, Bax, Caspase 3, 9, and while Bcl2 is decreased. At 500 µg/mL, the BGE sample was less toxic in normal cells and decreased the LPS-treated NO and ROS level to reduce inflammation. In addition, BGE inhibited the expression of pro-inflammatory genes COX-2, iNOS, IL-6, and IL-8 in RAW 264.7 cells than the sample of GE. In conclusion, FrBGL3 has considerable downstream applications for high-yield, low-cost, effective manufacture of minor ginsenosides. Moreover, the study's findings imply that BGE would be potential materials for anti-cancer and anti-inflammatory agent after consideration of future studies.

•The first time ß-glucosidase (FrBGL3) from Furfurilactobacillus rossiae was identified and characterized.•FrBGL3 activity in ginsenoside and gypenoside bioconversion were found and confirmed.•Application in Gynostemma extract bioconversion by FrBGL3 boosts anti-inflammatory and anti-cancer activities.

The Clinical Outcomes of Cervical Spine Chordoma: A Nationwide Multicenter Retrospective Study.

OBJECTIVE: Chordoma, a rare malignant tumor originating from embryonal notochord remnants, exhibits high resistance to conventional treatments, making surgical resection imperative. However, the factors influencing prognosis specifically for cervical spine chordoma have not been clearly identified. We investigate the prognosis of cervical spine chordoma with factors influential in a nationwide multicenter retrospective study. METHODS: This study included all patients diagnosed with cervical spine chordoma at 7 tertiary referral centers from January 1998 to March 2023, excluding those with clivus and thoracic spine chordomas extending into the cervical spine. Local recurrence (LR) was identified through follow-up magnetic resonance imaging, either as reappearance in completely resected tumors or regrowth in residual tumors. The study assessed LR and overall survival, analyzing factors influencing LR and death. RESULTS: Forty-five patients with cervical spine chordoma had a mean age of 46.4 years. Over a median follow-up of 52 months, LR and distant metastasis were observed in 21 (46.7%) and 4 patients (8.9%), respectively, and 16 patients (36%) were confirmed dead. The 5-year and 10-year cumulative LR rates were 51.3% and 60%, respectively, while the 5-year and 10-year survival rates were 82% and 53%. Age was the only significant factor affecting mortality (hazard ratio, 1.04; 95% confidence interval, 1.04-1.07; p=0.015). Notably, the degree of resection and adjuvant therapy did not statistically significantly impact local tumor control and mortality. CONCLUSION: This study, the largest multicenter retrospective analysis of cervical spine chordoma in Korea, identified age as the only factor significantly affecting patient survival.

Neutrophil Extracellular Traps as a Biomarker in Refractory Non-Type 2 CRSwNP.

PURPOSE: Chronic rhinosinusitis (CRS) is classified into type 2 (T2) and non-T2 inflammation. T2 CRS presents as a severe form, CRS with nasal polyps (CRSwNP), which often occurs with asthma as a comorbidity worldwide. Some cases of non-T2 CRS show nasal polyposis and refractoriness, mainly in Asian countries. However, its mechanism remains elusive. To investigate a biomarker for the refractoriness of non-T2 CRSwNP via RNA sequencing. METHODS: RNA sequencing by using nasal polyps (NPs) and ethmoidal mucosa (EM) from CRS subjects and uncinate tissues from controls was performed, and differentially expressed genes (DEGs) were analyzed (cutoffs: expression change > 2-fold, P < 0.01). Immunofluorescence staining and enzyme-linked immunosorbent assay were performed. RESULTS: We identified DEGs among T2-NP, non-T2-NP, T2-EM, non-T2-EM, and controls (NP vs. controls: 1,877 genes, EM vs. controls: 1,124 genes, T2-NP vs. controls: 1,790 genes, non-T2-NP vs. controls: 2,012 genes, T2-EM vs. controls: 740 genes, non-T2-EM vs. controls: 1,553 genes). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that neutrophil extracellular trap (NET) formation, systemic lupus erythematosus, and the phagosome were enriched in non-T2-NP vs. controls and non-T2-EM vs. controls. Immunofluorescence staining confirmed that NETs were elevated in non-T2-NP. Cytokine analysis demonstrated that NETs were significantly related to the refractoriness in non-T2-NPs. CONCLUSIONS: This study demonstrated DEGs between T2 and non-T2 inflammation. These results suggest that NETs may contribute to the refractoriness in non-T2-NPs and have a promise as a therapeutic strategy for patients with refractory non-T2-NP.

Exploring the concept of disease control in chronic cough.

Background: Disease control in chronic diseases is an overarching concept that reflects the degree to which the goals of therapy are met. However, to date, there is no consensus on the definition of disease control in chronic cough. This study aimed to provide a conceptual exploration of patient-reported cough control in chronic cough. Methods: This research is comprised of two subanalyses. First, patients with chronic cough receiving care at referral clinics were evaluated. Correlation analyses were performed between patient-reported cough control (a 5-point Likert scale), cough-specific patient-reported outcomes (PROs) and generic health PRO scores. Second, a survey was conducted among patients with refractory chronic cough and physicians to identify factors pertinent to cough control. Results: The analysis of 341 patients (mean age: 55.5±15.1 years; female: 66.6%) revealed that cough control rating was moderately correlated with cough severity visual analogue scale and Leicester Cough Questionnaire scores, while demonstrating weaker correlations with cough-associated throat symptoms, cough-related complications or general health-related quality of life (QoL). In the survey of patients and physicians, both groups considered certain factors, such as cough frequency, severity and impact on QoL, to be relevant to the concept of cough control. However, patients rated "need for cough rescue drug" notably higher than physicians. Conclusion: Patient-reported cough control was associated with cough severity or impact on QoL; however, cough control may not be fully captured by conventional cough PRO measurement tools. Further studies are warranted to define the consensus and tools to measure disease control in chronic cough.

Dexmedetomidine alleviates CoCl2-induced hypoxic cellular damage in INS-1 cells by regulating autophagy.

Background: Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic ß-cell damage by regulating autophagy under hypoxia. Methods: INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine. Results: Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1. Conclusions: Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.

Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics.

Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.

The Effect of Transpedicular Injection of Recombinant Human Bone Morphogenetic Protein-2/Beta-Tricalcium Phosphate Carrier on the Prevention of Proximal Junctional Kyphosis in Adult Spinal Deformity Surgery: A Pilot Study.

BACKGROUND AND OBJECTIVES: Several studies have explored strategies to prevent proximal junctional kyphosis (PJK) which is the unresolved issue in adult spinal deformity (ASD) surgery. This study aimed to investigate the preventive effects of upper instrumented vertebrae (UIV) recombinant human bone morphogenetic protein-2 (rhBMP-2) with beta-tricalcium phosphate (ß-TCP) carrier injection on PJK. METHODS: This study was conducted through a retrospective analysis of data collected both prospectively and retrospectively. In the rhBMP-2 group, consisting of 25 patients with ASD, rhBMP-2 along with ß-TCP carrier was administered to the UIV through the pedicle. To minimize time-related bias, control-1 included 66 patients who had undergone ASD surgery by the same surgeon in the year preceding the commencement of the study. Control-2 consisted of 63 patients who had undergone ASD surgery by the same surgeon during the year after the end of the study. The primary outcome is the occurrence of PJK within one year postsurgery, and the secondary outcome is the change in Hounsfield unit of the UIV one year after the surgery. RESULTS: When comparing baseline characteristics with control groups, a significant difference was observed only in body mass index, with control-1 (P = .006) and control-total (control-1 + control-2, P = .026) having a higher body mass index than the study group. In the rhBMP-2 group, there were 3 cases (PJK rate, 12.0%) of PJK, whereas control-1 and control-2 had 26 cases (PJK rate, 39.4%, P = .012) and 20 cases (PJK rate, 31.7%, P = .057), respectively. In the control-total, there were 46 cases (PJK rate, 35.7%, P = .020) of PJK. The UIV that received rhBMP-2 showed a statistically significant increase in Hounsfield unit measurements compared to preoperative values 1 year after surgery (P = .001). CONCLUSION: The transpedicular injection of rhBMP-2/ß-TCP carrier at the UIV significantly contributed to the prevention of PJK and effectively increased trabecular bone density at the UIV.

Efficacy and Safety of Biportal Endoscopic Decompressive Laminectomy in Octogenarians With Severe Lumbar Spinal Stenosis.

BACKGROUND: Lumbar spinal stenosis (LSS) is prevalent among octogenarians, causing significant pain and disability. Surgical intervention is often required because of the ineffectiveness of conservative treatments. This study investigates the efficacy and safety of biportal endoscopic decompressive laminectomy (BED) in octogenarians with severe LSS, evaluating its potential as a minimally invasive surgical option. METHODS: This retrospective study included 107 patients aged 80 years or older who underwent BED for LSS between March 2017 and December 2022. Data were collected from electronic medical records, including demographic information, clinical outcomes, and surgical details. Patients with fractures, infectious spondylitis, herniated discs, and follow-up less than 12 months were excluded. Clinical outcomes were assessed using the visual analog scale, Oswestry Disability Index, European Quality of Life-5 Dimensions, and painDETECT at baseline and at 3, 6, and 12 months after surgery. RESULTS: The mean age of the 107 patients was 84.1 years, with 59% being women. Significant improvements were observed in visual analog scale scores for lower back and lower extremities pain, Oswestry Disability Index, European Quality of Life-5 Dimensions, and painDETECT scores, indicating reduced pain, decreased disability, and enhanced quality of life. There were no significant differences in outcomes between patients aged 80 to 84 and those 85 or older. Surgery-related outcomes such as operation time, blood loss, and complications were similar in both age groups. CONCLUSIONS: BED is a safe and effective treatment for LSS in octogenarians, providing significant pain relief and functional improvement. This minimally invasive technique is also viable for patients older than 85 years, without increased risk of complications, supporting its broader indications in managing LSS in the elderly. CLINICAL RELEVANCE: This study highlights the efficacy and safety of BED for LSS in octogenarians, demonstrating its potential to improve quality of life and function with low risks, making it a feasible option for elderly patients.

Radiologic myosteatosis predicts major complication risk following esophagectomy for cancer: a multicenter experience.

BACKGROUND: Myosteatosis is a measure of skeletal muscle quality that is readily identifiable on computed tomography (CT). The effect of preoperative myosteatosis on outcomes after radical esophagectomy remains unclear. This study aimed to correlate the presence of myosteatosis on CT scan with perioperative morbidity, mortality, and survival outcomes after esophagectomy in an Australian population across 3 esophageal cancer centers. METHODS: A retrospective analysis was performed for all patients undergoing radical esophagectomy for cancer across 3 centers. Radiologic assessment of preoperative CT images was performed to determine the presence of myosteatosis. The outcomes measured included perioperative complication rate, overall survival (OS), and disease-free survival (DFS). RESULTS: A total of 462 patients were included in the analysis (male patients, 78.4%; median age, 67 years). Moreover, 353 patients (76.4%) had myosteatosis on CT. Compared to patients with normal skeletal muscle attenuation, patients with myosteatosis had a higher rate of major (Clavien-Dindo grade ≥ IIIb) complication (14.7% vs 24.9%, respectively; P = .026) and a higher rate of 30-day mortality (0.0% vs 4.0%, respectively; P = .048). Myosteatosis was associated with a major complication on multivariate analysis (hazard ratio, 1.906; 95% CI, 1.057-3.437; P = .032). There was no difference in OS and DFS between patients with and without myosteatosis (OS: 59 vs 56 months, respectively [P = .465]; DFS: 39 vs 42 months, respectively; P = .172). CONCLUSION: The presence of myosteatosis on radiologic imaging was associated with an increased risk of major complications and 30-day mortality. Identifying myosteatosis can be an adjunct to preoperative nutritional assessment and prognostication, facilitating early recognition of patients at risk of complications.

Impact of Atrial Fibrillation with Rapid Ventricular Response on Atrial Fibrillation Recurrence: From the CODE-AF Registry.

Background/Objectives: Relatively little has been established about the association of rapid ventricular response (RVR) with further recurrence of atrial fibrillation (AF). This study investigated the impact of RVR on the recurrence of AF. Methods: Data were obtained from a multicenter, prospective registry of non-valvular AF patients. RVR was defined as AF with a ventricular rate > 110 bpm. The primary endpoint was the recurrence of AF, defined as the first AF detected on 12-lead electrocardiography during follow-up. Secondary endpoints included manifestation of AF during follow-up and major adverse cardiovascular events (MACEs), a composite of thromboembolic events, major bleeding, myocardial infarction, and death. Results: Among 5533 patients, 493 (8.9%) presented RVR. Patients with RVR were younger, had smaller left atrial diameters, and more frequently had paroxysmal AF. During the mean follow-up duration of 28.6 months, the RVR group exhibited significantly lower recurrence of AF (hazard ratio: 0.58, 95% confidence interval: 0.53-0.65, p < 0.001). There was no significant difference in the occurrence of MACEs between patients with RVR and those without RVR (0.96, 0.70-1.31, p = 0.800). AF with RVR was identified as an independent negative predictor of AF recurrence (0.61, 0.53-0.71, p < 0.001). Conclusions: In patients with AF, those with RVR had a significantly lower recurrence of AF without an increase in MACEs. RVR is a favorable marker that may benefit from early rhythm control.

Surgery on the C3-4 Level and the Presence of Ligamentum Flavum Hypertrophy Increases the Risk of 30-Day Reoperation Rate After Anterior Cervical Discectomy and Fusion.

BACKGROUND AND OBJECTIVES: Cervical myelopathy caused by C3-4 level degeneration often exhibits different characteristics after anterior cervical discectomy and fusion (ACDF) than other cervical levels. This study compared the outcomes of C3-4 ACDF with surgeries at other levels and identified risk factors of 30-day reoperation after ACDF. METHODS: We retrospectively analyzed patients who underwent ACDF for degenerative cervical disease from 2018 to 2023. The patients were divided into 2 groups based on the level of surgery: C3-4 and non-C3-4 groups. Radiological outcomes, including cervical alignment and range of motion (ROM), were analyzed. Clinical outcomes were assessed with patient-reported outcomes and the rates of 30-day reoperation and complications after ACDF. Patient-reported outcomes included visual analog scale for neck pain, visual analog scale for arm pain, and modified Japanese Orthopedic Association scores. Risk factors of 30-day reoperation were assessed. RESULTS: Of 259 patients, 74 (28.6%) and 185 (71.4%) were in the C3-4 and non-C3-4 groups, respectively. The C3-4 group exhibited lower C2-7 ROM (P = .019), higher C3-4 ROM (P = .015), and greater C3-4 %ROM (P = .014). The C3-4 group demonstrated lower preoperative and 1-month postoperative modified Japanese Orthopedic Association scores (P < .001; P < .001, respectively). The rate of 30-day reoperation was significantly higher in the C3-4 group (9.5%) compared with the non-C3-4 group (2.2%) (P = .014). In addition, C3-4 surgical level (odds ratio = 4.99, P = .034) and ligament flavum hypertrophy (odds ratio = 5.84, P = .018) were identified as independent risk factors of 30-day reoperation after ACDF. CONCLUSION: Surgery on C3-4 level showed a higher risk of 30-day reoperation than other levels. It is likely due to C3-4 surgical level, and ligament flavum hypertrophy contributes to cord compression, particularly in the unstable early postoperative period.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

Deoxybouvardin targets EGFR, MET, and AKT signaling to suppress non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) remains a significant challenge, as it is one of the leading causes of cancer-related deaths, and the development of resistance to anticancer therapy makes it difficult to treat. In this study, we investigated the anticancer mechanism of deoxybouvardin (DB), a cyclic hexapeptide, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. DB inhibited the viability and growth of HCC827 cells in a concentration- and time-dependent manner. In vitro kinase assay showed DB inhibited epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition (MET), and AKT, and their phosphorylation was suppressed in HCC827 cells treated with DB. A molecular docking model suggested that DB interacts with these kinases in the ATP-binding pockets. DB induces ROS generation and cell cycle arrest. DB treatment of HCC827 cells leads to mitochondrial membrane depolarization. The induction of apoptosis through caspase activation was confirmed by Z-VAD-FMK treatment. Taken together, DB inhibited the growth of both GEF-sensitive and GEF-resistant NSCLC cells by targeting EGFR, MET, and AKT and inducing ROS generation and caspase activation. Further studies on DB can improve the treatment of chemotherapy-resistant NSCLC through the development of effective DB-based anticancer agents.

Incidence and Risk Factors of Proximal Junctional Complications and Rod Fractures After Long-Segment Fusion Surgery With Anterior Column Realignment for Adult Spinal Deformity: A Minimum 2-Year Follow-Up.

BACKGROUND AND OBJECTIVES: To investigate the incidence and risk factors of proximal junctional kyphosis (PJK), proximal junctional failure (PJF), and rod fractures in patients undergoing long-segment (≥4 levels) fusion surgery with anterior column realignment (ACR) for adult spinal deformity. METHODS: Patients aged ≥60 years with at least a 2-year follow-up were grouped based on PJK, PJF, and rod fracture occurrence. Patient, surgical, and radiographic factors were compared to identify risk factors for these complications. Independent risk factors were identified using univariate and multivariate logistic regression. RESULTS: Among 106 patients, the incidence rates of PJK, PJF, and rod fractures were 15.1%, 28.3%, and 17.9%, respectively. PJK was significantly associated with fewer fusion levels (odds ratio [95% CI], 0.30 [0.13-0.69]), a cranially directed uppermost instrumented vertebra (UIV) screw angle (1.40 [1.13-1.72]), postoperative overcorrection of age-adjusted pelvic incidence-lumbar lordosis (LL) (7.22 [1.13-45.93]), and a large increase in thoracic kyphosis (1.09 [1.01-1.17]). PJF risks were associated with a cranial UIV screw orientation (1.23 [1.09-1.39]), overcorrection of age-adjusted pelvic incidence-LL (10.80 [2.55-45.73]), and a smaller change in sacral slope (0.87 [0.80-0.94]). For rod fractures, prominent factors included a greater number of fusion levels (1.70 [1.17-2.46]), a larger postoperative LL (1.07 [1.01-1.15]), a smaller postoperative thoracic kyphosis (0.92 [0.86-0.98]), and smaller changes in sacral slope (0.73 [0.58-0.92]) and pelvic tilt (0.72 [0.56-0.91]). CONCLUSION: The incidence and risk factors of PJK, PJF, and rod fractures were similar to those observed in previous studies on long-segment fusion surgery without ACR. The number of ACR levels was not a significant risk factor for PJK, PJF, or rod fractures. When performing deformity correction using ACR, surgeons should carefully consider the direction of the UIV screw and ensure that overcorrection is avoided.

Impact of Neoadjuvant Chemotherapy and Preoperative Irradiation on Early Complications in Direct-to-Implant Breast Reconstruction.

Background Impact of previous radiation therapy and neoadjuvant chemotherapy (NACT) on early complications in direct-to-implant (DTI) breast reconstruction has not been elucidated. This study investigated whether DTI reconstruction is viable in patients with NACT or a history of preoperative chest wall irradiation. Methods Medical records of breast cancer patients who underwent nipple-sparing or skin-sparing mastectomy with DTI breast reconstruction from March 2018 to February 2021, with at least 1 year of follow-up in a single tertiary center, were reviewed. Demographic data, intraoperative details, and postoperative complications, including full-thickness necrosis, infection, and removal, were reviewed. Risk factors suggested by previous literature, including NACT and preoperative chest wall irradiation histories, were reviewed by multivariate analysis. Results A total of 206 breast cancer patients were included, of which, 9 were bilateral, 8 patients (3.9%) had a history of prior chest wall irradiation, and 17 (8.6%) received NACT. From 215 cases, 11 cases (5.1%) required surgical intervention for full-thickness necrosis, while intravenous antibiotics or hospitalization was needed in 11 cases (5.1%), with 14 cases of failure (6.5%) reported. Using multivariable analysis, preoperative irradiation was found to significantly increase the risk of full-thickness skin necrosis (OR = 12.14, p = 0.034), and reconstruction failure (OR = 13.14, p = 0.005). NACT was not a significant risk factor in any of the above complications. Conclusion DTI breast reconstruction is a viable option for patients who have received NACT, although reconstructive options should be carefully explored for patients with a history of breast irradiation.

PD-L1 as a Biomarker for the Efficacy of Durvalumab in Stage III EGFR Mutant NSCLC.

BACKGROUND/AIM: Durvalumab consolidation is less effective in patients with epidermal growth factor receptor mutant (EGFR M+) NSCLC. Studies of durvalumab on EGFR M+ NSCLC as an expression of programmed death-ligand 1 (PD-L1) expression are limited. The purpose of this study was to determine the effect of durvalumab on PD-L1 expression in EGFR M+ patients. PATIENTS AND METHODS: This study included 249 unresectable stage III NSCLC patients treated with durvalumab. The primary outcome was progression-free survival (PFS). Cox multivariate analysis was performed based on EGFR and PD-L1 statuses: EGFR M-, PD-L1 ≥50% (cohort A); EGFR M-, PD-L1 <50% (cohort B); EGFR M+, PD-L1 ≥50% (cohort C); and EGFR M+, PD-L1 <50% (cohort D). RESULTS: Overall, 31 of 249 (12.4%) and 218 of the 249 (87.6%) patients had EGFR M+ and EGFR M- NSCLC, respectively. Median PFSs and OSs did not differ (PFS: 16.6 vs. 18.7 months, p=0.591; OS: 37.4 vs. 35.7 months, p=0.271). Median PFS of cohort A did not significantly differ from the median PFSs of cohorts B and C, but it was significantly longer than the median PFS of cohort D (23.7 vs. 15.2 months, p=0.045). Cox multivariate analysis revealed that cohort D exhibited a worse PFS (adjusted hazard ratio=2.27, 95% confidence interval=1.11-4.66, p=0.025) compared with cohort A. Median OSs were not different between the four cohorts. CONCLUSION: Durvalumab consolidation provided similar benefit in EGFR M+ patients with PD-L1 ≥50% compared with EGFR M- patients. A therapeutic role of durvalumab in patients with EGFR M+, high PD-L1 unresectable stage III NSCLC should be considered.

Comparison of metastasectomy and stereotactic body radiation therapy for pulmonary oligometastasis from hepatocellular carcinoma: a propensity score-weighted analysis.

PURPOSE: While there is a growing role for local therapy in patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis, it remains unclear whether metastatectomy or stereotactic body radiation therapy (SBRT) is the more effective treatment for these patients. We aimed to compare the oncologic outcomes of metastasectomy and SBRT for HCC with pulmonary oligometastasis. METHODS: We retrospectively analyzed 209 HCC patients with 322 metastatic lung lesions who underwent either metastasectomy (150 patients with 241 lesions) or SBRT (59 patients with 81 lesions) between January 2008 and December 2018. Propensity score-based inverse probability of treatment weighting (IPTW) was used to minimize potential bias between the two groups. RESULTS: The median follow-up duration was 39.8 months (range, 2.3-166.9). The 2-year rate of freedom from local progression (FFLP) was 98.2% in the metastasectomy group and 97.0% in the SBRT group (p = 0.197). The 2-year rates of overt systemic progression-free survival (ovPFS, 51.0% vs. 46.1%; p = 0.274), progression-free survival (PFS, 26.3% vs. 9.1%; p = 0.074), and overall survival (OS, 74.0% vs. 57.6%; p = 0.006) were higher in the metastasectomy group. After IPTW adjustment, the 2-year rates of ovPFS (50.8% vs. 52.7%; p = 0.396), PFS (23.0% vs. 24.7%; p = 0.478), and OS (72.6% vs. 83.0%, p = 0.428) were not significantly different between the two groups. In multivariate analysis, viable intrahepatic lesions and the number of prior liver-directed therapies were found to be significant prognostic factors for OS and PFS. The time interval between HCC diagnosis and the development of pulmonary metastases was also significantly associated with OS. CONCLUSIONS: Both metastasectomy and SBRT demonstrated excellent local control and comparable oncologic outcomes in patients with pulmonary oligometastasis from HCC. The treatment modality for these patients could be determined based on the individual patient's condition and intrahepatic disease status.

Effectiveness of a protein-supplemented very-low-calorie diet program for weight loss: a randomized controlled trial in South Korea.

Introduction: Weight-loss strategies through meal replacements are effective and sustainable options. However, few studies have assessed their effects on weight loss including body composition through protein-supplemented meal replacements targeting the Asian population, including Koreans. This study aimed to assess the effectiveness and safety of a protein-supplemented very-low-calorie diet (PSVLCD) for weight reduction and changes in body composition in individuals with obesity over a 12-month long-term period. Methods: In total, 106 participants with obesity were randomly assigned to a PSVLCD or control group (food-based calorie-restricted diet). Body weight, waist circumference, body composition, and blood marker levels were measured throughout the study. Statistical analyses were performed to compare outcomes between the groups. Results: Among the 106 participants, 84 completed the 12-month follow-up. Intention-to-treat analysis showed that the mean weight loss from baseline to 12 months was -6.86 kg (8.21% of baseline weight) in the PSVLCD group and - 4.66 kg (5.47% of initial body weight) in the control group; the difference was -2.20 kg with a marginally significant interval (95% confidence interval [CI], -4.90; 0.50). Waist circumference (-8.35 cm vs. -4.85 cm; mean difference, -3.49 cm; 95% CI, -6.48 to -0.50) and visceral fat area (-28.28 cm2 vs. -13.26 cm2; mean difference, -15.03cm2; 95% CI, -29.01 to -1.04) also significantly decreased in the PSVLCD group at 12 months. Discussion: The PSVLCD group demonstrated a substantial initial reduction in waist circumference that was sustained over the study period, alongside a marginally significant decrease in weight. These findings suggest that a protein-supplemented very-low-calorie diet may be an effective strategy for long-term weight management and body composition improvement in individuals with obesity. Clinical trial registration: ClinicalTrials.gov, identififer NCT04597788.