INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution’s experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

OBJECTIVE: To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture. METHODS: Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared. RESULTS: When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS. CONCLUSION For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.
Humans ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Bone Plates ; Biomechanical Phenomena ; Finite Element Analysis

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.