Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. Materials and Methods: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. Results: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). Conclusion Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. Methods: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. Results: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusions: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. Methods: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. Results: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusions: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. Methods: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. Results: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusions: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. Methods: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. Results: Recommendations for nine PICO (population, intervention, comparator, and outcome) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. Conclusions: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague–Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

BACKGROUND: Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. METHODS: The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery. RESULTS: Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization. CONCLUSION Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.