Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Background: Ablative oncologic procedures for colorectal or gynecologic malignancies can result in large skin or tissue volume defects. Although direct closure may be possible, such attempts can lead to postoperative complications such as wound breakdown, organ prolapse, chronic seroma, or infection. Various procedures, from flap surgery to local wound care, can be useful additions to improve patient outcomes. Methods: This study retrospectively reviews cases of patients with multiple comorbidities who had undergone concomitant interventions after pelvic ablative surgery. Various interventions after pelvic ablative surgery, from reconstructing the defect to managing postoperative complications, are described. Results: Careful planning and selection of the reconstruction method can significantly improve patient outcomes. The authors suggest using gluteal flaps for most reconstructive demands. Conclusion This case series emphasizes the utility of using various flaps, especially the gluteal flap, in reconstructing oncologic defects in the pelvic and perineal regions. The insights gained from this study will hopefully be of assistance to future research and clinical practice, ultimately improving patient outcomes.

Background: Capsulectomy is a crucial procedure in cosmetic breast surgery, and there is demand for an efficient and convenient tool to perform it. This study analyzed the postoperative outcomes of total capsulectomy by comparing an ultrasonic system to conventional electrosurgery. Methods: This retrospective cohort study included patients who underwent total capsulectomy and implant removal from 2012 to 2020. The ultrasonic surgery group underwent this procedure using the Harmonic scalpel, while the electrosurgery group underwent the same surgery using conventional electrocautery. A statistical analysis of the two groups was performed using multivariate linear regression analysis to determine the unbiased effect of ultrasonic surgery on operative efficiency and outcomes. Results: A total of 89 patients were included in the study. The operative time was significantly shorter in the ultrasonic surgery group (60 minutes vs. 70 minutes, P=0.002). After adjusting for other independent variables that might also be related to the outcomes, shorter operative time (P=0.014) and faster drain removal (P=0.003) were associated with the use of ultrasonic surgery. Conclusions The use of an ultrasonic system (Harmonic scalpel) for total capsulectomy and explantation in cosmetic breast revision surgery was associated with shorter operative times and faster drain removal than conventional electrosurgery.

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with ZVAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

Maintaining the patency of the external auditory canal (EAC) during reconstruction is important because of its physiological role in hearing and immunological protective functions. The curved shape of the EAC presents a challenge when performing a skin graft. One of the key points for a successful skin graft is to ensure compression on the wound bed, and many novel methods, including prefabricated ear molds, have been reported for this purpose. In this study, we present a case of a skin graft performed to reconstruct a skin defect following excision of actinic keratosis in the EAC, using the cover of an ear thermometer probe as a mold for the graft to match the curvature of the EAC. This is an economical and practical method for secure compression dressing of a skin graft in the EAC.

Purpose: With the increasing incidence of recompression fractures after vertebroplasty or kyphoplasty, this study analyzed the risk factors that affect the occurrence of recompression vertebral fractures, such as cement distribution, existence of avascular necrosis (Kummell’s disease), type of procedures, bone mineral density, sex, and age. Materials and Methods: Two hundred and thirty-eight patients who underwent vertebroplasty or kyphoplasty at the author’s clinic from 2005 to 2015 were enrolled in this study. The patients were divided into four groups according to the distribution of injected cement. The patients were classified as type 1 and type 2 when injected cement was contacted only to the upper or lower endplate of the body respectively. They were classified as type 3 when both the upper and lower endplates were contacted by injected cement. When neither the upper nor the lower endplate was contacted, the patients were called type 4. This study statistically evaluated the effects of the risk factors, including the cement distribution on the incidence of recompression vertebral fracture after vertebroplasty or kyphoplasty. Results: There were 59 cases (24.8%) of recompression fracture after vertebroplasty or kyphoplasty, among the 238 cases. According to the analysis, the recompression of the vertebral body after vertebroplasty or kyphoplasty occurred more often when the compression fracture was accompanied by osteonecrosis at the body (p<0.05). The patients who had injected cement distributed at both upper and lower plate simultaneously (type 3) had a lower incidence of recompression fracture of the vertebral body after vertebroplasty or kyphoplasty (p=0.008). In addition, the kyphoplasty group had a lower incidence of recompression after the procedure than vertebroplasty group (p=0.02). Conclusion Careful attention should be given to these patients with osteonecrosis at the compression fracture level through a preoperative evaluation. In addition, if the injected cement does not contact both the upper and lower endplates, careful observation is required during the follow-up period based on the high incidence of vertebral recompression fractures proven through this study. Further technical and biomechanical research and efforts will be needed to make the cement contact both endplates.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

Background: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. Methods: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. Results: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. Conclusions The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.