Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

A predictive model for residual lesions after LEEP surgery in CIN III patients.

Background and aims: The residual lesions after Loop Electrosurgical Excision Procedure (LEEP) contributes to poor prognosis in patients with Cervical Intraepithelial Neoplasia Grade 3 (CIN3). The aim of this study is to establish an effective clinical predictive model for residual lesions in CIN3 patients after LEEP. Methods: A retrospective analysis was performed on 436 CIN3 patients who underwent total hysterectomy within 3 months after LEEP. Based on the post-hysterectomy pathologic, the patients were divided into the no residual group and residual group. Clinical parameters were compared between the two groups, and univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for residual lesions in CIN3 patients after LEEP. Using R software, a nomogram model was established and its effectiveness was evaluated using calibration plots. Results: There were 178 cases in the residual group and 258 cases in the no residual group. The two groups had no significant difference in general characteristics (p > 0.05). It was found that Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and the Gland involvement were independent risk factors for residual lesions in CIN3 patients after LEEP (all p < 0.05). The consistency index (C-index) of the nomogram model for predicting residual lesions was 0.975 (0.962-0.988). Conclusion: The Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and Gland involvement are independent risk factors related to residual tissue after LEEP surgery in CIN3 patients. The constructed nomogram can effectively predict the presence of residual tissue after LEEP surgery in CIN3 patients and has good practical value.

Single-view cone-beam x-ray luminescence optical tomography based on Group_YALL1 method.

Single-view cone beam x-ray luminescence optical tomography (CB-XLOT) has the merit of short data acquisition time, which is important for resolving fast biological processes in vivo. However, challenges remain in the reconstruction of single-view CB-XLOT. In our previous work, by using the sparsity-based reconstruction method, we have demonstrated the feasibility of single-view CB-XLOT. But, when the imaging conditions become complicated (e.g. multiple adjacent nanophosphors (NPs) contained in imaged object), it is difficult to resolve each NP by the previous method. To solve the problem, we hereby present a sparsity reconstruction method based on group information, termed Group_YALL1. The imaging performance of single-view CB-XLOT can be further improved by utilizing the group sparsity characteristic of NPs as a priori knowledge of reconstruction constraint. To assess the capability of the method, we used a customized CB-XLOT/XCT system to perform the numerical simulation and physical phantom experiments. The experimental results demonstrate that compared with the former sparse reconstruction method (e.g. YALL1), the proposed Group_YALL1 method can accurately resolve the NPs embedded in the object, even if they are close to each other. The acquired location error is less than 1 mm. Hence, this method has the potential to greatly reduce the data acquisition time while preserving a high imaging quality.

Dexmedetomidine for craniotomy under general anesthesia: A systematic review and meta-analysis of randomized clinical trials.

STUDY OBJECTIVE: To assess the efficacy and safety of dexmedetomidine as an adjunct to general anesthesia for craniotomy. DESIGN: A meta-analysis after systematically searching PubMed, Medline, EMBASE, and Cochrane library for randomized trials (RCTs). Relative risk (RR) and weighted mean difference (WMD) were calculated using random-effects meta-analysis. SETTING: Perioperative setting. PATIENTS: Twenty-two RCTs (1348 patients) with craniotomy under general anesthesia were included. INTERVENTIONS: Dexmedetomidine as an adjunct to general anesthesia versus placebo or other anesthetics. MEASUREMENTS: Primary outcomes included procedure success and postoperative pain; Secondary outcomes included cardiac adverse events, postoperative nausea and vomiting (PONV) and other clinically important outcomes. MAIN RESULTS: Dexmedetomidine vs. Placebo: High to moderate quality evidence suggested that dexmedetomidine reduced postoperative pain (WMD -0.25 cm, 95%CI -0.43 to -0.07 cm on a 10 cm visual analogue scale), postoperative nausea and vomiting (PONV, RR 0.57, 95%CI 0.39 to 0.84), hypertension (RR 0.37, 95%CI 0.22 to 0.61) and tachycardia (RR 0.32, 95%CI 0.12 to 0.85) with no significant increase of hypotension and bradycardia. Moderate quality evidence suggested no significant difference in procedural success. Dexmedetomidine vs. Active Comparators (including remifentanil, fentanyl, or propofol): Moderate quality evidence showed no difference in procedural success and postoperative pain. CONCLUSIONS: Dexmedetomidine as an adjunct to general anesthesia shows small benefits in reduction of pain, PONV, and maintains more stable hemodynamics with comparable effects on procedural success versus placebo. Very limited evidence explored comparative effects between dexmedetomidine and active controls. Further evidence is required to evaluate patient-important outcomes and optimal dosing strategies, particularly versus active comparators.

Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill patients. Guidelines recommend a semi-recumbent position (30º to 45º) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi-recumbent position for preventing VAP. OBJECTIVES: To assess the effectiveness and safety of semi-recumbent positioning versus supine positioning to prevent ventilator-associated pneumonia (VAP) in adults requiring mechanical ventilation. SEARCH METHODS: We searched CENTRAL (2015, Issue 10), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and the Chinese Biomedical Literature Database (CBM) (1978 to October 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing semi-recumbent versus supine positioning (0º to 10º), or RCTs comparing alternative degrees of positioning in mechanically ventilated patients. Our outcomes included clinically suspected VAP, microbiologically confirmed VAP, intensive care unit (ICU) mortality, hospital mortality, length of ICU stay, length of hospital stay, duration of ventilation, antibiotic use and any adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently and in duplicate screened titles, abstracts and full texts, assessed risk of bias and extracted data using standardised forms. We calculated the mean difference (MD) and 95% confidence interval (95% CI) for continuous data and the risk ratio (RR) and 95% CI for binary data. We performed meta-analysis using the random-effects model. We used the grading of recommendations, assessment, development and evaluation (GRADE) approach to grade the quality of evidence. MAIN RESULTS: We included 10 trials involving 878 participants, among which 28 participants in two trials did not provide complete data due to loss to follow-up. We judged all trials to be at high risk of bias. Semi-recumbent position (30º to 60º) versus supine position (0° to 10°) A semi-recumbent position (30º to 60º) significantly reduced the risk of clinically suspected VAP compared to a 0º to 10º supine position (eight trials, 759 participants, 14.3% versus 40.2%, RR 0.36; 95% CI 0.25 to 0.50; risk difference (RD) 25.7%; 95% CI 20.1% to 30.1%; GRADE: moderate quality evidence).There was no significant difference between the two positions in the following outcomes: microbiologically confirmed VAP (three trials, 419 participants, 12.6% versus 31.6%, RR 0.44; 95% CI 0.11 to 1.77; GRADE: very low quality evidence), ICU mortality (two trials, 307 participants, 29.8% versus 34.3%, RR 0.87; 95% CI 0.59 to 1.27; GRADE: low quality evidence), hospital mortality (three trials, 346 participants, 23.8% versus 27.6%, RR 0.84; 95% CI 0.59 to 1.20; GRADE: low quality evidence), length of ICU stay (three trials, 346 participants, MD -1.64 days; 95% CI -4.41 to 1.14 days; GRADE moderate quality evidence), length of hospital stay (two trials, 260 participants, MD -9.47 days; 95% CI -34.21 to 15.27 days; GRADE: very low quality evidence), duration of ventilation (four trials, 458 participants, MD -3.35 days; 95% CI -7.80 to 1.09 days), antibiotic use (three trials, 284 participants, 84.8% versus 84.2%, RR 1.00; 95% CI 0.97 to 1.03) and pressure ulcers (one trial, 221 participants, 28% versus 30%, RR 0.91; 95% CI 0.60 to 1.38; GRADE: low quality evidence). No other adverse events were reported. Semi-recumbent position (45°) versus 25° to 30° We found no statistically significant differences in the following prespecified outcomes: clinically suspected VAP (two trials, 91 participants, RR 0.74; 95% CI 0.35 to 1.56; GRADE: very low quality evidence), microbiologically confirmed VAP (one trial, 30 participants, RR 0.61; 95% CI 0.20 to 1.84: GRADE: very low quality evidence), ICU mortality (one trial, 30 participants, RR 0.57; 95% CI 0.15 to 2.13; GRADE: very low quality evidence), hospital mortality (two trials, 91 participants, RR 1.00; 95% CI 0.38 to 2.65; GRADE: very low quality evidence), length of ICU stay (one trial, 30 participants, MD 1.6 days; 95% CI -0.88 to 4.08 days; GRADE: very low quality evidence) and antibiotic use (two trials, 91 participants, RR 1.11; 95% CI 0.84 to 1.47). No adverse events were reported. AUTHORS' CONCLUSIONS: A semi-recumbent position (≧ 30º) may reduce clinically suspected VAP compared to a 0° to 10° supine position. However, the evidence is seriously limited with a high risk of bias. No adequate evidence is available to draw any definitive conclusion on other outcomes and the comparison of alternative semi-recumbent positions. Adverse events, particularly venous thromboembolism, were under-reported.

Efficacy and safety of focused ultrasound versus microwave therapy for cervical ectopy: a meta-analysis.

OBJECTIVES: To assess the efficacy and safety of focused ultrasound therapy (FU) and microwave therapy (MW) for cervical ectopy (CE). METHODS: We searched PubMed, EMbase, the Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journals Database (VIP), China Academic Journals Full-text Database (CNKI), and WanFang Data for randomized controlled trials (RCTs) comparing FU with MW for women with symptomatic CE from inception to 30 August 2014. Two review authors (Tang XL and Gao Z) independently screened for eligible studies according to the inclusion and exclusion criteria, extracted data and assessed risk of bias of included RCTs. Then, meta-analysis was performed using the RevMan 5.2 software. Funnel plots were used to evaluate publication bias. RESULTS: A total of 33 RCTs with 11,759 participants were included. All studies had high risk of bias. The results of meta-analysis indicated that compared to MW, FU significantly reduced the risk of vaginal bleeding (RR = 0.09, 95%CI 0.05 to 0.17, P < 0.00001) and vaginal discharge (RR = 0.10, 95%CI 0.04 to 0.24, P < 0.00001), increased the cure rate (RR = 1.10, 95%CI 1.05 to 1.15, P < 0.0001) and the total effectiveness rate (RR = 1.04, 95%CI 1.02 to 1.06, P = 0.0005), and decreased the recurrence rate (RR = 0.13, 95%CI 0.02 to 1.00, P = 0.05); however, this last difference was not statistically significant. CONCLUSION: Current available evidence suggests that FU is safer and more effective than MW for treating CE. However, some limitations will reduce the reliability of our results. Further well-designed clinical trials are needed to provide further clarification.