Epidural dexmedetomidine or esketamine versus fentanyl to decrease ropivacaine use for labor analgesia: A randomized non-inferiority study.

Background: Epidural nonopioid adjuvants also reduce local anesthetic use. We aimed to test the hypothesis that, compared with the present standard fentanyl, the hourly consumption of local anesthetic was at least as good when dexmedetomidine or esketamine was combined with local anesthetic for patient-controlled epidural analgesia (PCEA). Methods: A total of 120 laboring nulliparous subjects requiring labor analgesia were recruited for the final statistical analysis. Subjects were randomized to receive 0.075 % ropivacaine added with one of three equivalent adjuvants: 0.4 µg/mL fentanyl, 0.4 µg/mL dexmedetomidine, or 1.0 mg/mL esketamine. The primary outcome was hourly ropivacaine consumption. Compared with the fentanyl group, a 20 % difference in hourly local anesthetic consumption between the dexmedetomidine and esketamine groups was considered a clinical difference (non-inferiority margin). Results: The hourly ropivacaine consumption of the fentanyl group was 12.4 (95 % confidence interval CI 11.2 to 13.6) ml/h, so the prespecified non-inferiority limit was 2.5 ml/h. The hourly ropivacaine consumption of the fentanyl group was not inferior to that of the dexmedetomidine group (12.4 ml/h vs. 11.9 ml/h, risk difference, 0.5; 95 % confidence interval CI, -1.0 to 2.0, meeting criteria for non-inferiority). However, the hourly ropivacaine consumption of the esketamine group was 14.3 ml/h, and that of the fentanyl group was 12.4 ml/h (risk difference, 1.9, 95 % CI, 0.2 to 3.6), failing to confirm non-inferiority with a non-inferiority margin of 20 %. The incidence of pruritus was highest in the fentanyl group, whereas the occurrence of mild dizziness was highest in the esketamine group. Conclusions: In setting of the conditions of this study, epidural dexmedetomidine was non-inferior compared with epidural fentanyl in combination with ropivacaine for PCEA during labor. Meanwhile, we failed to establish the non-inferiority of epidural esketamine compared with epidural fentanyl in combination with ropivacaine for labor analgesia.

Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

Observational Study: Clinical characteristics and Survival Rates in Patients with Prostate Cancer with Normal Prostate-Specific Antigen Concentrations.

Objectives: This study aimed to explore the clinical characteristics of patients with prostate cancer with prostate-specific antigen (PSA) concentrations of less than 4 ng/mL (normal PSA) to provide clinical insights regarding diagnosis and treatment. Methods: We recruited 35 patients with prostate cancer with normal PSA who were admitted to Xi'an People's Hospital from January 2013 to January 2018, and further determined their clinical characteristics, serum PSA concentration, prostate volume, tumor pathology, surgical margins, seminal vesicle invasion, lymph node metastasis, Gleason score, TNM staging, risk classification, and survival, and described the patients' interventions and treatments. All patients and their families signed informed consent forms before enrollment. Results: In our study, we observed a 3-year survival rate of 77.14% for patients with prostate cancer and normal PSA concentrations. This outcome can be attributed to several clinical characteristics, including the absence of obvious clinical presentation, a high detection rate of seminal vesicle invasion, as well as high Gleason scores and risk levels. The primary outcome, 3-year survival rate, reflects the long-term prognosis of this specific patient subgroup. We also conducted correlation analyses to better understand the relationships between these clinical characteristics and patient survival.

Non-coding RNAs in enzalutamide resistance of castration-resistant prostate cancer.

Enzalutamide (Enz) is a next-generation androgen receptor (AR) antagonist used to treat castration-resistant prostate cancer (CRPC). Unfortunately, the relapsing nature of CRPC results in the development of Enz resistance in many patients. Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins, which include microRNAs (miRNA), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs with known and unknown functions. Recently, dysregulation of ncRNAs in CRPC, particularly their regulatory function in drug resistance, has attracted more and more attention. Herein, we introduce the roles of dysregulation of different ncRNAs subclasses in the development of CRPC progression and Enz resistance. Recently determined mechanisms of Enz resistance are discussed, focusing mainly on the role of AR-splice variant-7 (AR-V7), mutations, circRNAs and lncRNAs that act as miRNA sponges. Also, the contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are discussed. We summarize the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and highlight the prospect of future therapeutic strategies against Enz resistance.

Determination of the Dose-Response Relationship of Epidural Dexmedetomidine Combined with Ropivacaine for Labor Analgesia.

Background: The safety and efficacy of dexmedetomidine for epidural labor analgesia have been reported in numerous literatures, but the optimal dose has not been fully determined. The objective of this study was to determine the dose-response relationship of epidural dexmedetomidine (combined with ropivacaine) for labor analgesia. Methods: A total of 120 full-term laboring parturients requesting epidural labor analgesia were enrolled in the study from July 5, 2020 to September 22, 2021. The parturients were randomly assigned to receive 0, 0.1, 0.2, 0.3, 0.4 or 0.5 µg/mL dexmedetomidine combined with 0.075% ropivacaine epidurally. An effective dose was defined as numerical rating scale (NRS) pain score ≤3 at 30-minutes of epidural drug injection. The dose-response relationship of dexmedetomidine (with ropivacaine) for epidural labor analgesia was performed using probit regression. The median effective dose (ED50) and the 95% effective dose (ED95) values for epidural dexmedetomidine combined with 0.075% ropivacaine with 95% confidence intervals (CIs) were derived by interpolation. Results: The estimated values of ED50 and ED95 with 95% CIs for epidural dexmedetomidine (combined with 0.075% ropivacaine) were 0.085 (0.015 to 0.133) µg/mL and 0.357 (0.287 to 0.493) µg/mL, respectively. No differences were found among groups for sensory block level, number of parturients with Bromage score >0, total dosage of analgesics, cesarean delivery rate, fetal birth weight, Apgar score at 1-minute, Apgar score at 5-minutes and adverse effects. Compared with other groups, group dexmedetomidine 0.5 µg/mL had a longer duration of the first stage of labor. Conclusion: The ED50 and ED95 values of dexmedetomidine for epidural labor analgesia was 0.085 and 0.357 µg/mL under the conditions of this study. Dexmedetomidine is a suitable adjuvant for epidural labor analgesia.

Mutational analysis of renal angiomyolipoma associated with tuberous sclerosis complex and the outcome of short-term everolimus therapy.

To identify clinical characteristics and mutation spectra in Chinese patients with renal angiomyolipoma (AML) associated with the tuberous sclerosis complex (TSC, TSC-AML), examined the efficacy and safety of short-term everolimus therapy (12 weeks). We analyzed the frequency distribution of each TSC-related clinical feature and investigated gene mutations by genetic testing. Some subjects received everolimus for 12 weeks at a dose of 10 mg/day, and the efficacy and safety of short-term everolimus therapy were examined. Finally, 82 TSC-AML patients were enrolled for analysis in this study. Of the 47 patients who underwent genetic testing, 22 patients (46.81%) had at least one detectable mutation in the TSC1 or TSC2 gene: 7 were TSC1 gene mutations, 13 were TSC2 gene mutations, and 2 were found in both TSC1 and TSC2. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05), and the mean reduction rate of volume for all cases was 56.47 ± 23.32% over 12 weeks. However, 7 patients (7/25; 28.00%) experienced an increase in renal AML tumor volume within 12 weeks after discontinuation of the everolimus treatment. Although most patients (27/30, 90.00%) experienced some adverse events during the treatment period, all such events were mild, and no patients discontinued or needed dose reduction because of adverse events. Overall, in this study, the mutation rate of TSC-AML patients is much lower than other reports. Short-term everolimus treatment for TSC-AML is effective and safe, but the stability is much lower than long-term therapy.

Wedge resection of the tarsal plate combined with the modified Hotz procedure for correction of involutional lower eyelid entropion.

OBJECTIVES: To investigate the outcomes for correction of involutional lower eyelid entropion by wedge resection of the tarsus combined with the modified Hotz procedure. DESIGN: Retrospective study. PARTICIPANTS: Patients with lower eyelid involutional entropion that was surgically repaired by wedge resection of the tarsal plate combined with the modified Hotz procedure. METHODS: In a consecutive series of 43 patients with involutional lower eyelid entropion, wedge resection combined with the modified Hotz procedure was performed with an average follow-up period of 29.6 months (range, 6-62 months). RESULTS: Among the patients, 93% had an excellent outcome within the follow-up period. For one patient, the outcome of both eyes was poor. For another patient, incision dehiscence of the eyelid margin in one eye occurred after the stitches were removed. The incision was sutured again, and it healed well. One patient complained of foreign body sensation in one eye after removal of the skin stitches. The complaint was resolved after wearing a corneal contact lens. No other significant complications occurred. CONCLUSIONS: In our clinic, tarsal plate wedge resection combined with the modified Hotz procedure has been highly effective for correction of involutional lower eyelid entropion. Although this approach does not directly address lateral canthal tendon laxity, it does preserve the eyelid in case there is a future need for reconstruction due to ocular surface disease or trauma. Thus, wedge resection of the tarsal plate combined with modified Hotz procedure is a safe and effective method for involutional lower eyelid entropion.

Lower eyelid tension balance reconstruction: A new procedure for the repair of congenital epiblepharon with epicanthus.

BACKGROUND: Congenital epiblepharon with epicanthus (CEE) is a common eyelid malposition in Asian children, which generally involves the lower eyelid. The induced cilial entropion may cause constant ocular irritation that requires surgical repair. The purpose of this study is to report the outcomes and surgical details of a novel procedure, lower eyelid tension balance reconstruction (LETBR), for the correction of CEE. METHODS: Patients diagnosed with CEE underwent LETBR, which consists of modified half Z epicanthoplasty, and fixation between marginal orbicularis oculi muscle and lower eyelid retractor was reviewed retrospectively. The outcomes were classified as 'good' with no cilia-ocular surface contact, 'fair' with 5 or fewer asymptomatic cilia-ocular surface points of contact and 'poor' with most of the eyelashes remaining in contact with the eyeball. The surgical outcomes (good, fair or poor), recurrence and complications were evaluated. RESULTS: One hundred and forty-nine eyelids of 78 patients (43 females and 35 males; mean age 6.6 ±â€¯2.4 years, range 4-17 years) were evaluated in this study. The mean follow-up time was 14 months (range 9-24 months). At the last follow-up time, 144 of 149 eyelids were judged as 'good' (96.6%), the other 5 eyelids were judged as 'fair' (3.4%) and no eyelid was assessed with a 'poor' outcome. There were no significant complications or complaints about scarring on eyelids from patients or their parents. CONCLUSION: LETBR is effective, safe and stable for patients with CEE.

Immunoproapoptotic molecule scFv-Fdt-tBid modified mesenchymal stem cells for prostate cancer dual-targeted therapy.

Highly efficient target therapy is urgently needed for prostate cancer with overexpression of γ-seminoprotein (γ-SM). Recent studies indicated that mesenchymal stem cells (MSCs) are attractive candidate for cell-based, targeted therapy due to their tumor tropism. Here we designed a dual-target therapeutic system in which MSCs were engineered to produce and deliver scFv-Fdt-tBid, a novel γ-SM-targeted immunoproapoptotic molecule. Such engineered MSCs (MSC.scFv-Fdt-tBid) would home to tumor sites and release the fusion protein to induce the apoptosis of prostate cancer cells. Our data demonstrated that scFv-Fdt-tBid showed a selective, potent and dose-dependent inhibition for γ-SM-positive cells (LNCaP, C4-2, 22Rv1) rather than γ-SM-negative cells and MSCs. Importantly, MSC.scFv-Fdt-tBid caused cell death through an apoptosis-dependent manner. Further, the tropism of MSC.scFv-Fdt-tBid to prostate cancer was verified both in vitro and in vivo. Finally, the in vivo experiments demonstrated that MSC.scFv-Fdt-tBid significantly inhibited γ-SM-positive tumor growth without toxic side effects. Collectively, this study represented a novel immunoproapoptotic molecule scFv-Fdt-tBid for γ-SM-positive tumors and demonstrated the therapeutic efficiency and safety of scFv-Fdt-tBid-modified MSCs against prostate cancers.

Modified Hotz Procedure Combined With Modified Z-Epicanthoplasty Versus Modified Hotz Procedure Alone for Epiblepharon Repair.

PURPOSE: To compare the outcomes of the modified Hotz procedure alone and combined with modified Z-epicanthoplasty for correction of epiblepharon. METHODS: Seventy-one Chinese patients who underwent epiblepharon repair were divided into 2 groups. In group 1, 33 patients (59 eyes) were operated on with the modified Hotz procedure. In group 2, 38 patients (71 eyes) were operated on with the modified Hotz procedure combined with modified Z-epicanthoplasty. Treatment outcomes were classified as "excellent" with no cilium-ocular surface touching, "fair" with 5 or fewer cilia-ocular surface touchings, and "poor" with more than 5 cilia-ocular surface touchings. Incision scars were evaluated by the Vancouver scar scale (VSS). RESULTS: There were no significant differences in the age or sex distribution between the two groups. For group 1, the outcome was excellent for 46 eyes (78%) and fair or poor for 13 eyes (22%). For group 2, the outcome was excellent for 70 eyes (98.6%) and fair for only 1 eye (1.4%). Thus, group 2 had significantly more excellent outcomes compared with group 1 (p < 0.001). The Vancouver scar scale of the lower eyelids in group 1 was 1.10 ± 0.30 and 1.04 ± 0.20 in group 2 after correcting for the follow-up period (p = 0.292). The medial canthus Vancouver scar scale in group 2 was 1.13 ± 0.37, which was not different from the lower eyelid Vancouver scar scale (p = 0.471). CONCLUSIONS: The modified Hotz procedure combined with modified Z-epicanthoplasty is more effective in correcting lower eyelid epiblepharon than the modified Hotz procedure alone. The combined procedure does not produce obvious lower eyelid or medial canthus scars.