Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism. Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences. Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred. Conclusions and Relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.

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

Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism. Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences. Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred. Conclusions and Relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.

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

Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism. Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences. Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred. Conclusions and Relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.

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

Objective: We aimed to elucidate the metabolic function and phenotype of AK5, a gene with an unknown function in metabolism. Methods: We generated AK5 knockout (KO) mice and administered high-fat and fasting diets to the mice to confirm their physiological phenotype and metabolic differences. Results: In the high-fat diet (HFD) test, no differences in body weight, epididymal white adipose tissue (eWAT), or fat mass of AK5 KO mice were observed. In indirect calorimetry, the respiratory exchange ratio and activity counts increased in normal chow diet mice, but there was no difference between the HFD groups. At the mRNA level, there were no significant differences in the expression of lipid metabolism markers between wild-type and AK5 KO mice. Still, the glucose signal of adipocytes increased in AK5 KO mice. In the fasting test, the eWAT of AK5 KO mice was significantly reduced, as was the expression of lipid metabolism and inflammation-related immune markers. Thus, the apoptosis of adipocytes increased, and an imbalance in energy metabolism occurred. Conclusions and Relevance: When AK5 KO mice are energy deficient, it becomes difficult to use eWAT for energy storage, imbalance occurs, and apoptosis of adipocytes in eWAT increases.

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC β-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates.Two high-risk clones, ST235 (N = 41) and ST111 (N = 20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metalloβ-lactamase (MBL) genes, blaIMP-6 (N = 38), blaVIM-2 (N = 3), and blaNDM-1 (N = 2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene–negative isolates. Conclusions Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC β-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates.Two high-risk clones, ST235 (N = 41) and ST111 (N = 20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metalloβ-lactamase (MBL) genes, blaIMP-6 (N = 38), blaVIM-2 (N = 3), and blaNDM-1 (N = 2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene–negative isolates. Conclusions Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC β-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates.Two high-risk clones, ST235 (N = 41) and ST111 (N = 20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metalloβ-lactamase (MBL) genes, blaIMP-6 (N = 38), blaVIM-2 (N = 3), and blaNDM-1 (N = 2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene–negative isolates. Conclusions Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.