Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Orthopedic surgeons treating fractures need to consider comorbidities, including chronic kidney disease (CKD), which affects millions worldwide. CKD patients are at elevated risk of fractures due to osteoporosis, especially in advanced stages. In addition, fractures in CKD patients pose challenges due to impaired bone healing and increased post-fracture complications including surgical site infection and nonunion. In this article, we will discuss factors that must be considered when treating fractures in CKD patients.Perioperative management includes careful adjustment of hemodialysis schedules, selection of anesthetic methods, and addressing bleeding tendencies. Tourniquet usage for fractures in limbs with arteriovenous fistulae should be cautious. Pain medication should be administered carefully, with opioids like hydromorphone preferred over nonsteroidal anti-inflammatory drugs. Medical management after fractures should address underlying factors and include physical rehabilitation to reduce the risk of subsequent fractures. A comprehensive approach to fracture management in CKD patients can improve outcomes.