Comparative effectiveness of multiple androgen receptor signaling inhibitor medicines with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a study in the real world.

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR.

INTRODUCTION: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. METHODS: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. This data, combined with initial hemoglobin levels, is processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by utilizing fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor's precision. RESULTS: The estimated blood loss percentage error of the monitor was 5.2% for free blood, -5.7% for small sponge, -6.3% for medium sponge, and -6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. CONCLUSION: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions.

Ultrasound-assisted modified paramedian technique for spinal anesthesia in elderly.

BACKGROUND: At present, there are two techniques which are widely applied clinically; the midline and the paramedian. Both methods are difficult for clinicians when treating the elderly. The aim of this work is to explore the feasibility of an ultrasound-assisted modified paramedian technique for spinal anesthesia in the elderly. This would provide clinicians with a new and easy-to-operate technique. METHODS: A total of 150 elderly patients who were scheduled for urology surgery under spinal anesthesia in our hospital were randomly divided into three groups (n = 50): (i) midline technique group (group M), (ii) paramedian technique group (group P), and (iii) modified paramedian technique group (group PM). All spinal anesthesia were performed by the same second-year resident. RESULTS: Compared with groups M and P, group PM had significantly higher first-attempt success rate (P < 0.05, especially in patients aged 65-74 years), fewer attempts (P < 0.05), and higher patient satisfaction score (P < 0.05). Compared with group M, the time taken to perform spinal anesthesia and the number of needle redirections were significantly reduced in group PM (P < 0.05). There was no statistically significant difference between groups PM and P. There were also no statistically significant differences in the cases of inconsistency between ultrasound-assisted and landmark-guided location of intervertebral space, the time taken to ultrasound-assisted location, the onset time to pain block at T10, the incidence of hypotension, anesthesia effect and the incidence of headache, lower back pain, or nausea and vomiting, within 24 h after surgery. CONCLUSIONS: The modified paramedian technique in spinal anesthesia for elderly patients can significantly improve the first-attempt success rate, reduce both the number of attempts and procedure time, and minimize tissue damage during the operation. Compared with the traditional techniques, the modified paramedian technique combines the advantages of both the midline and the paramedian methods, and is easy to learn. It is worthy of further research and application. TRIAL REGISTRATION: Prospectively registered at the China Clinical Trial Registry, registration number ChiCTR2100047635 , date of registration: 21/06/2021.

[Involvement of cAMP-PKA pathway in group â ¡ metabotropic glutamate receptors-mediated regulation of respiratory rhythm from neonatal rat brainstem slice].

The study aims to identify the role of cAMP-PKA pathway in the group Ⅱ metabotropic glutamate receptors (mGluRs)-mediated regulation of respiratory rhythm from the brainstem slice. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The brainstem slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2) bubbling, and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve rootlets was recorded by suction electrode. Eighteen brainstem slice preparations were divided into 3 groups. In group 1, group Ⅱ mGluRs specific antagonist (2S)-α-ethylglutamic acid (EGLU) was added into the perfusion solution for 10 min. In group 2, after application of Forskolin for 10 min, washout with MKS, the slice was perfused with Rp-cyclic 3', 5'-hydrogen phosphorothioate adenosine triethylammonium salt (Rp-cAMPS) alone for another 10 min. In group 3, after application of Rp-cAMPS for 10 min, additional EGLU was added into the perfusion for another 10 min. The results showed EGLU shortened respiratory cycle (RC), but the changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Forskolin induced significant decreases in RC, and increased TI, IA. Rp-cAMPS could make the opposite effect compared with the changes of RRDA with Forskolin. The effect of EGLU on the RRDA was inhibited after blocking the cAMP-PKA pathway. Taken together, cAMP-PKA pathway may play an important role in the group Ⅱ mGluRs-mediated regulation of RRDA in the brainstem slice of neonatal rats.