Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening.

While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.

A Case of Neck Pain in a Patient with Spontaneous Cerebrospinal Fluid Leak Who Showed Characteristic Findings on Cervical Spine MRI.

We report a case of a patient with neck pain only who was diagnosed with spontaneous cerebrospinal fluid leak (SCFL) based on characteristic findings on cervical spine magnetic resonance imaging (MRI). The patient was a 47-year-old man who had been experiencing neck pain for 3 days. He experienced neck pain when he got up in the morning and could not keep standing. Cervical spine MRI showed significant dilatation of the anterolateral dural canal veins at the C2 level. Under the suspicion of SCFL, additional thoracic spine MRI was performed, which revealed epidural fluid collection in the lower thoracic spine. He underwent bed rest, but his symptoms returned. Epidural blood patch (EBP) was performed. The symptoms improved after EBP, and the venous dilatation disappeared on MRI. Venous dilatation in SCFL is considered an effect of epidural space enlargement due to dural sac shrinkage caused by cerebrospinal fluid loss. Therefore, venous dilatation in the cervical spine is an indirect finding of SCFL. It has been reported that images of epidural fluid collection and dural canal collapse on spinal MRI are useful as direct findings in the diagnosis of SCFL, and these findings are most noticeable at the thoracic level. Because SCFL with neck pain only also exists, dilated images of the epidural vein are valuable for diagnosing SCFL, and neurospine surgeons should be aware of this finding when encountering patients complaining of neck pain.

Reducing Chronic Spine Pain in an Adult Male by Decreasing Lumbar Scoliosis and Increasing Cervical Lordosis Using Chiropractic BioPhysics® Protocols: A 26-Month Follow-Up Case Report.

We present a case report of a patient suffering from chronic low back pain (CLBP) and chronic non-specific neck pain (CNSNP), both of which were caused and complicated by a physically demanding occupation, a history of mixed martial arts, and lumbar scoliosis. Improvements in patient-reported outcomes (PROs) and radiographic findings were observed following conservative spine rehabilitation. The patient, a 34-year-old male, had experienced chronic spine pain, particularly CLBP and CNSNP, for several years. He reported severe pain and increasing disability after a recent neck injury sustained while practicing jiu-jitsu. Radicular pain, along with numbness and tingling, was noted in the right upper extremity, extending to the first three digits, and there were also altered sensations and temperature changes in both feet. He described sharp, pinching mid-back pain and worsening disability due to the persistent pain, which led him to seek manual manipulative chiropractic spine therapy, though he reported little benefit from it. The patient had relied on over-the-counter pain medications for many years without achieving long-term pain and disability relief, and these medications were no longer used following treatment. Chiropractic BioPhysics® (CBP®) spinal structural rehabilitation protocols were used to improve coronal and sagittal balance, as well as paraspinal muscular strength, addressing posture, mobility, and related aspects. These protocols include postural exercises, postural Mirror Image® traction, and postural spinal manipulative therapy. All PROs improved, with a near resolution of all initial symptoms of chronic spine pain. Outcomes measured included disability indices and health-related quality of life (HRQoL) indicators. Radiographic parameter improvements were significant, demonstrating improved coronal and sagittal balance as a result of the treatment. Following 30 in-office treatments, administered three times per week for 10 weeks, initial outcomes were reassessed. The patient then received 13 in-office treatments periodically over one year, and all initial outcomes were repeated. The improvements remained stable over time. A 26-month follow-up found that the improvements were sustained over a very long period without additional treatment after the 13-month examination. Chronic spine pain, specifically CLBP and CNSNP, is a significant source of suffering and contributes substantially to the global burden of disease. Improvement in HRQoLs, PROs, and objective spine parameters are desirable clinical outcomes. Our case report documents objective improvement in lumbar scoliosis and spine pain, which is rare in conservative studies. This successful treatment of chronic pain with long-term follow-up contributes to the growing evidence supporting conservative, non-surgical treatments for CNSNP and CLBP. Successful management of chronic spine pain was observed in a patient undergoing CBP® treatment. The treatment was designed to address abnormal sagittal and coronal postural balance and radiographic abnormalities indicating spinal misalignment and reassess progress in PROs, as well as objective and subjective HRQoL measures, both following treatment and 13 months later. However, larger studies are needed to draw firm conclusions regarding the efficacy of this treatment for chronic pain.

Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing.

Background: Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients' prognoses and quality of life. Method: The present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations. Result: The obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies. Conclusions: We first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.

Healthcare providers' knowledge, attitude, and practice towards cervical cancer screening in Sub-Saharan Africa: systematic review and meta-analysis.

Introduction: Cervical cancer is a prevalent cancer among women in low and middle-income countries, but it can be largely prevented through screening programs and HPV vaccination. This study aimed to determine the level of knowledge, attitudes, and practices regarding cervical cancer screening among healthcare providers in Sub-Saharan African countries. Methods: Systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Relevant databases including PubMed, Cochrane Library, AJOL, Google Scholar, and ScienceDirect databases were used to retrieve and search articles. The study included published and unpublished research written in English between January 2013 and May 16, 2024 for studies reporting knowledge, attitude, and practice towards cervical cancer screening among healthcare providers in Sub-Saharan Africa. This review has been registered on PROSPERO. The heterogeneity of the data was evaluated using the I2 statistic. A meta-analysis was conducted using STATA 17 software, with a 95% confidence interval. The researchers also conducted publication bias and sensitivity analysis. Results: The review included 30 studies involving 7542 healthcare providers. The pooled magnitude of good knowledge status towards cervical cancer was 67.93% (95% CI: 53.36-82.50) whereas the pooled magnitude of positive attitude towards cervical cancer was 55.26% (95% CI: 34.28- 76.23). The results also showed that about 49.68% (95% CI: 33.18-66.17) of healthcare providers had good knowledge status about cervical cancer screening, 66.63%(95% CI: 50.36- 82.89) had a positive attitude towards it, and only 17.23% (95% CI; 6.08-28.37) had ever screened for cervical cancer. Conclusion: The overall magnitude of knowledge and attitude of healthcare providers in Sub-Saharan Africa towards cervical cancer and its screening was suboptimal. Furthermore, a low percentage of female healthcare providers in the region had undergone screening for cervical cancer. As a result, policymakers and program administrators should focus on improving the knowledge, attitude, and practices of healthcare providers to meet the global health goal of cervical cancer screening and effectively eliminating cervical cancer. Healthcare providers must serve as role models for other women who should also undergo screening. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023495241.

Adaptive brachytherapy for cervical cancer in combined 1.5 T MR/HDR suite: Impact of repeated imaging.

Introduction: At our department we have a dedicated 1.5 Tesla MRI/HDR brachytherapy suite, which provides the possibility of repeated MRI scanning before, during and after applicator insertion and before and/or after irradiation for patients with advanced cervical cancer. In this study we analysed the effect of this adaptive workflow. We investigated the number of interventions, their impact on organ doses (OAR) and the respective dose differences between total prescribed and total delivered doses. Materials and methods: Seventy patients with locally advanced cervical cancer FIGO2009 stages IB-IVA, treated from June 2016 till August 2020, were retrospectively analysed. The standard brachytherapy schedule consisted of two applicator insertions and delivery of three or four HDR fractions.OARs were recontoured on the repeated MRI scans. The D2cm3 dose difference between total prescribed and total delivered dose for bladder, rectum, sigmoid and bowel were calculated. Results: In total 153 interventions were performed, 3 replacements of the applicator, 23 adaptations of needle positions, bladder filling was changed 74 times and repeated rectal degassing 53 times. The impact of the rectal interventions was on average -1.2 Gy EQD23. Dose differences between total delivered and total prescribed D2cm3 for bladder, rectum, sigmoid and bowel were -0.6, 0.3, 2.2 and -0.6 Gy EQD23, respectively. Conclusions: An MRI scanner integrated into the brachytherapy suite enables multiple interventions based on the scans before treatment planning and dose delivery. This allows for customized treatment according to the changing anatomy of the individual patient and a better estimation of the delivered dose.

Up-regulated DSG2 promotes tumor growth and reduces immune infiltration in cervical cancer.

BACKGROUND: Desmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods. METHODS: Several online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro. RESULTS: Bioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro. CONCLUSIONS: In summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC.

A Novel Ultrasound-Based Radiomics Model for the Preoperative Prediction of Lymph Node Metastasis in Cervical Cancer.

OBJECTIVE: The purpose of this retrospective study was to establish a combined model based on ultrasound (US)-radiomics and clinical factors to predict preoperative lymph node metastasis (LNM) in cervical cancer (CC) patients non-invasively. METHODS: A total of 131 CC patients who had cervical lesions found by transvaginal sonography (TVS) from the First Affiliated Hospital of Anhui Medical University (Hefei, China) were retrospectively analyzed. The clinical independent predictors were selected using univariate and multivariate logistic regression analysis. US-radiomics features were extracted from US images; after selecting the most significant features by univariate analysis, Spearman's correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm; four machine-learning classification algorithms were used to build the US-radiomics model. Fivefold cross-validation was then used to test the performance of the model and compare the ability of the clinical, US-radiomics and combined models to predict LNM in CC patients. RESULTS: Red blood cell, platelet and squamous cell carcinoma-associated antigen were independent clinical predictors of LNM (+) in CC patients. eXtreme Gradient Boosting performed the best among the four machine-learning classification algorithms. Fivefold cross-validation confirmed that eXtreme Gradient Boosting indeed performs the best, with average area under the curve values in the training and validation sets of 0.897 and 0.898. In the three prediction models, both the US-radiomics model and the combined model showed good predictive efficacy, with average area under the curve values in the training and validation sets of 0.897, 0.898 and 0.912, 0.905, respectively. CONCLUSION: US-radiomics features combined with clinical factors can preoperatively predict LNM in CC patients non-invasively.

Cervical precancer and invasive cancer among women living with HIV in Latin America: A systematic review and meta-analysis.

BACKGROUND: Data on the occurrence of cervical precancer and cancer among women living with HIV (WLHIV) in Latin American countries (LAC) are scarce and highly heterogeneous. METHODS: We conducted a systematic review summarizing data about the incidence/prevalence of invasive cervical cancer (CC) and high-grade precancerous lesions among WLHIV in LAC. Literature in PubMed and LILACS was searched. The primary outcome was invasive cancer incidence, and prevalence of high-grade lesions as key indicators for the WHO CC elimination strategy. Individual reports on invasive cancer incidence and prevalence of precancerous lesions were obtained, and a random effects meta-analysis was conducted for the latter. RESULTS: In total, 34,343 WLHIV from four studies reporting CC incidence in seven LAC were included, and 6079 WLHIV from 17 studies reporting prevalence of precancerous lesions in three LAC were included. CC incidence ranged between 136.0 and 398.4 per 100,000 WLHIV (with or without antiretroviral therapy). The weighted prevalence of high-grade lesions was 4.1% (95%CI: 3.8%-6.0%) with a double peak at ages 20-24 and 35-39 years. Differences in prevalence of high-grade lesions were also observed by screening approach: co-testing (11.9%), colposcopy (6.0%), cytology (4.2%), and HPV tests (3.2%). CONCLUSIONS: The high incidence of invasive cancer and prevalence of high-grade lesions underline challenges to reach the WHO's elimination goal of CC incidence below four per 100,000 among WLHIV. Moreover, the high prevalence of high-grade lesions at younger ages than in the general population is a call to accelerate the implementation of the new WHO screening recommendations in WLHIV.

Non-canonical olfactory pathway activation induces cell fusion of cervical cancer cells.

Multinucleation occurs in various types of advanced cancers and contributes to their malignant characteristics, including anticancer drug resistance. Therefore, inhibiting multinucleation can improve cancer prognosis; however, the molecular mechanisms underlying multinucleation remain elusive. Here, we introduced a genetic mutation in cervical cancer cells to induce cell fusion-mediated multinucleation. The olfactory receptor OR1N2 was heterozygously mutated in these fused cells; the same OR1N2 mutation was detected in multinucleated cells from clinical cervical cancer specimens. The mutation-induced structural change in the OR1N2 protein activated protein kinase A (PKA), which, in turn, mediated the non-canonical olfactory pathway. PKA phosphorylated and activated furin protease, resulting in the cleavage of the fusogenic protein syncytin-1. Because this cleaved form of syncytin-1, processed by furin, participates in cell fusion, furin inhibitors could suppress multinucleation and reduce surviving cell numbers after anticancer drug treatment. The improved anticancer drug efficacy indicates a promising therapeutic approach for advanced cervical cancers.

Six versus 12-Hours Balloon Catheter Placement for the Induction of Labor: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Balloon catheters have shown promising results in the induction of labor (IOL); however, evidence regarding the optimal time of balloon catheter placement is still lacking. Thus, this study aims to evaluate the efficacy and safety of six-hour placement compared to 12 hours. DATA SOURCE: We conducted a comprehensive search through a search strategy across "Embase, SCOPUS, PubMed (via MEDLINE), and Cochrane Central Register of Controlled Trials (CENTRAL)" from inception until April 20, 2024. STUDY ELIGIBILITY CRITERIA: We included the randomized controlled trials (RCTs) evaluating the efficacy and safety of six-hour balloon catheter placement compared with 12 hours for cervical ripening in IOL. Covidence was used to screen eligible articles. METHODS: All relevant outcome data were synthesized using risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42024540935 RESULTS: We included five RCTs with 960 women undergoing the IOL with balloon catheter placement. Six-hour placement was associated with significant lower insertion to overall delivery interval (MD: -4.25, 95% CI [-5.34, -3.15], P< 0.00001) and insertion to vaginal delivery interval (MD: -4.65, 95% CI [-6.08, -3.23], P< 0.00001) without significant difference in BISHOP score change (MD: -0.02, 95% CI [-0.23, 0.20], P= 0.88), catheter removal to delivery interval (MD: 0.72, 95% CI [-0.39, 1.83], P= 0.20) and total duration of oxytocin infusion (MD: -0.36, 95% CI [-0.85, 0.14], P= 0.16) compared to twelve hours. Also, significantly lower overall cesarean delivery (CD) rate (RR: 0.81, 95% CI [0.68, 0.96], P= 0.01) and CD due to malpresentation (RR: 0.39, 95% CI [0.16, 0.93], P= 0.03) were observed with six-hour placement. CONCLUSION: A planned six-hour balloon catheter placement reduced insertion to delivery intervals and CD rate and has equal efficacy in BISHOP score change and catheter removal to delivery interval compared to twelve hours.

Effect of the basilar invagination (type B) on cervical spine: a case-control study at MRI.

OBJECTIVE: To evaluate the effect of the basilar invagination (BI) type B on cervical spine. METHODS: The research protocol used head magnetic resonance imaging (MRI) exams from 41 participants with BI type B and 158 controls. The criterion for BI was the distance of the odontoid apex to Chamberlain's line (DOCL) equal to or greater than 7 mm. The clivus length (CLI), clivus canal angle (CCA), Welcker's basal angle (WBA), Boogaard's angle (BOA), upper cervical lordosis angle (UCL), and total cervical lordosis angle (CL) were evaluated. The descriptive analysis, group comparisons, and correlations between skull base and cervical spine parameters were performed at the 95% confidence interval. RESULTS: Participants with BI type B showed shorter clivus length (CLI: 25.7mm±7.3); greater angulation of the skull base (WBA: 126.5±10.4); greater inclination foramen magnum (BOA: 151.5±14.5); decrease in the value of the (CCA: 131.6±15); and greater angulations of UCL (17.9 ±13.8) and CL (29.7 ±19.9) in comparison to the control group (P < 0.05). Clivus length and CCA correlated inversely with UCL and CL, while BOA correlated directly with UCL and CL. The WBA did not correlate with CL (P < 0.05). CONCLUSION: The deformation of skull base in the BI of type B caused, on average, a hyperlordosis of almost 30 degrees in the C2-C6 segment. This change was approximately 17º in the C2-C4, with the clivus hypoplasia being a risk factor for cervical hyperlordosis.

The influence of preoperative 12-item veterans rand physical component scores on outcomes following cervical disc replacement.

PURPOSE: To evaluate the influence of preoperative VR-12 physical component scores (PCS) on outcomes following cervical disc replacement (CDR). METHODS: Patients undergoing elective CDR were retrospectively identified. Patient-reported outcomes (PROs) of interest included VR-12 PCS/VR-12 Mental Component Score (MCS)/9-Item Patient Health Questionnaire (PHQ-9)/Short Form-12 (SF-12) PCS and MCS/Patient-Reported Outcome Measurement Information System-Physical Function (PROMIS-PF)/Visual Analog Scale-Neck Pain (VAS-NP)/VAS-Arm Pain (VAS-AP)/Neck Disability Index (NDI). Baseline up to two-year postoperative scores were obtained (average follow-up: 9.2 ± 6.8months). Two cohorts were created: VR-12 PCS < 35 or VR-12 PCS ≥ 35. Improvements in scores from baseline to six weeks postoperatively and to final follow-up were calculated. Changes in scores were compared to previously reported thresholds to determine rates of minimum clinically important difference (MCID). RESULTS: Of 127 patients, 64 were in the worse VR-12 PCS group. Patients with better VR-12 PCS were more likely to have private insurance (p = 0.034). When accounting for insurance differences, the worse VR-12 PCS group reported inferior NDI/VAS-NP/PHQ-9/PROMIS-PF/VR-12 PCS/SF-12 PCS at six weeks and final follow-up (p ≤ 0.015, all). The worse VR-12 PCS group reported greater improvements in VAS-AP and VR-12 PCS by six weeks and in NDI/VR-12 MCS/VR-12 PCS/SF-12 PCS by final follow-up (p ≤ 0.026, all). Patients with worse VR-12 PCS reported greater MCID achievement for VR-12 MCS and SF-12 PCS (p ≤ 0.034, both). CONCLUSION: Following surgery, patients with worse VR-12 PCS report greater improvements in PROs, highlighting the increased relative impact of surgery for patients with worse baseline physical function. These findings can be used to optimize patient experience perioperatively and inform postoperative expectations.

Salvage hysterectomy for persistent residual cervical cancer: assessment of prognostic factors.

In this multicenter retrospective cohort study of 99 patients who underwent salvage hysterectomy for residual disease in the uterine cervix following the completion of definitive radiotherapy for cervical cancer across 25 Japan Clinical Oncology Group-affiliated centers from 2005-2014, (i) time duration from the completion of definitive radiotherapy to the diagnosis of residual disease in the uterine cervix, (ii) salvage hysterectomy surgical margin status, and (iii) extent of residual disease, were independently associated with progression-free survival (PFS). Specifically, (i) time duration to identify residual disease of >62 days was associated with decreased PFS compared to ≤62 days (4-year rates 21.8% vs. 55.0%, adjusted-hazard ratio [aHR]=2.69, 95% confidence interval [CI]=1.55-4.67); (ii) presence of tumor in the surgical margin of hysterectomy specimen was associated with 4 times increased risk of disease progression compared to tumor-free surgical margin (4-year PFS rates 0% vs. 45.3%, aHR=4.27, 95% CI=2.20-8.29); and (iii) hazards of disease progression was 4.5-fold increased when the residual disease extended beyond the uterine cervix compared to residual disease within the uterine cervix only (4-year PFS rates 11.1% vs. 50.6%, aHR=4.54, 95% CI=2.60-7.95). In the absence of these 3 prognostic factors, 4-year PFS rate reached nearly 80% (78.6%, SAL-HYS criteria). In sum, these data suggested that early detection of persistent, residual disease following definitive radiotherapy for cervical cancer may be the key to improve survival if salvage hysterectomy is considered as a tailored treatment option. Ideal surgical candidate would be uterine cervix-contained disease and assurance of adequate tumor-free surgical margin.

Ischemia-reperfusion injury after spinal cord decompressive surgery-An in vivo rat model.

BACKGROUND: Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy (DCM), some individuals experience no improvement or even a decline in neurological function after surgery, with spinal cord ischemia-reperfusion injury (SCII) identified as the primary cause. Spinal cord compression results in local ischemia and blood perfusion following decompression is fundamental to SCII. However, owing to inadequate perioperative blood flow monitoring, direct evidence regarding the occurrence of SCII after decompression is lacking. The objective of this study was to establish a suitable animal model for investigating the underlying mechanism of spinal cord ischemia-reperfusion injury following decompression surgery for degenerative cervical myelopathy (DCM) and to elucidate alterations in neurological function and local blood flow within the spinal cord before and after decompression. METHODS: Twenty-four Sprague-Dawley rats were allocated to three groups: the DCM group (cervical compression group, with implanted compression material in the spinal canal, n = 8), the DCM-D group (cervical decompression group, with removal of compression material from the spinal canal 4 weeks after implantation, n = 8), and the SHAM group (sham operation, n = 8). Von Frey test, forepaw grip strength, and gait were assessed within 4 weeks post-implantation. Spinal cord compression was evaluated using magnetic resonance imaging. Local blood flow in the spinal cord was monitored during the perioperative decompression. The rats were sacrificed 1 week after decompression to observe morphological changes in the compressed or decompressed segments of the spinal cord. Additionally, NeuN expression and the oxidative damage marker 8-oxoG DNA were analyzed. RESULTS: Following spinal cord compression, abnormal mechanical pain worsened, and a decrease in forepaw grip strength was observed within 1-4 weeks. Upon decompression, the abnormal mechanical pain subsided, and forepaw grip strength was restored; however, neither reached the level of the sham operation group. Decompression leads to an increase in the local blood flow, indicating improved perfusion of the spinal cord. The number of NeuN-positive cells in the spinal cord of rats in the DCM-D group exceeded that in the DCM group but remained lower than that in the SHAM group. Notably, a higher level of 8-oxoG DNA expression was observed, suggesting oxidative stress following spinal cord decompression. CONCLUSION: This model is deemed suitable for analyzing the underlying mechanism of SCII following decompressive cervical laminectomy, as we posit that the obtained results are comparable to the clinical progression of degenerative cervical myelopathy (DCM) post-decompression and exhibit analogous neurological alterations. Notably, this model revealed ischemic reperfusion in the spinal cord after decompression, concomitant with oxidative damage, which plausibly underlies the neurological deterioration observed after decompression.

Robot-assisted cervical esophagectomy with simultaneous transhiatal abdominal procedure for thoracic esophageal carcinoma.

BACKGROUND: Minimally invasive robot-assisted cervical esophagectomy has been sporadically reported as a novel thoracic esophagectomy technique for patients with thoracic esophageal carcinoma. Most reports indicate that the abdominal component of robot-assisted cervical esophagectomy is performed sequentially after the cervical phase. However, if the cervical and abdominal phases are performed simultaneously using a nerve integrity monitoring system with no administration of muscle relaxants, there are two major advantages: a reduced risk of recurrent nerve palsy and a shorter operative time. We herein report our experience performing novel robot-assisted transcervical esophagectomy with a simultaneous transhiatal abdominal approach using a nerve integrity monitoring system. METHODS: Thirty cases of robot-assisted cervical esophagectomy performed from 2023 to April 2024 were reviewed. The operative and short-term surgical outcomes of this procedure were compared with those of robot-assisted cervical esophagectomy using a sequential abdominal approach, and the feasibility and efficacy of the simultaneous procedure were analyzed. RESULTS: All patients successfully underwent robot-assisted cervical esophagectomy with no intraoperative adverse events. There were no differences in the patients' demographic or operative data between the two groups. There was no difference in the mean operation time for the cervical procedure (p = 0.23). However, there was a significant difference in the total time for the whole procedure (sequential group: 453.8 ± 26.8 min, simultaneous group: 291.2 ± 36.1 min; p < 0.01). There were no differences in postoperative surgical complications between the groups. There was also no difference in the total number of surgically harvested mediastinal lymph nodes (p = 0.33). CONCLUSIONS: Robot-assisted transcervical esophagectomy, a new technique for thoracic esophageal cancer, was safe and feasible under intraoperative management using nerve integrity monitoring without muscle relaxants. This procedure facilitates intraoperative monitoring of recurrent laryngeal nerve activity, significantly shortening the total operative time.

Effects of Arborvitae (Thuja plicata) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.

AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.

Molecular Activities and Mechanisms of Action of Substances and Molecules from Medicinal Plants from Sub-Saharan Africa on Prostate and Cervical Cancer Cells.

BACKGROUND: Despite years of medical research, cancer remains a major public health problem worldwide, particularly in Africa. The cost, duration, and toxicity of currently available treatments are all drawbacks. Plant secondary metabolites are significant anticancer compounds. Already used in traditional health systems, plants are currently the subject of numerous studies to discover new anti-cancer drugs. OBJECTIVE: This review assesses the literature on the cytotoxic effect of plant substances (extracts) and molecules on prostate and cervical cancer cell lines. METHOD: PubMed, Science Direct, and Google Scholar were used to find in vitro studies carried out between 2006 and 2023 related to the cytotoxicity of extracts, substances and/or molecules from plants harvested in sub-Saharan Africa against prostate and/or cervical cancer cell lines. RESULTS: A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases. All the plants listed had a cytotoxic effect on prostate and/or cervical cancer cells. Some plant extracts or molecules showed significant activity with an IC50< 20 µg/ml. Burkina Faso and South Africa had the most plant extracts tested for prostate and cervical cancer, respectively. CONCLUSION: A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases.

Atherosclerosis in patients with cervical artery dissection.

INTRODUCTION: Cervical artery dissection (CeAD) is considered a non-atherosclerotic arteriopathy, but atherosclerosis of the cervical arteries may co-exist. We explored the frequency and clinical importance of co-existent atherosclerosis in patients with CeAD. PATIENTS AND METHODS: Single-center exploratory study from the Stroke Center Basel, Switzerland. We re-reviewed duplex ultrasound images at (i) baseline and (ii) last follow-up visit for the presence versus absence of the following atherosclerotic manifestations in the carotid arteries: (i) abnormal carotid intima-media thickness, (ii) plaques, and (iii) atherosclerotic stenosis. We investigated whether CeAD patients with versus without co-existing atherosclerosis differ regarding (a) recurrence of CeAD and (b) occurrence of vascular events (myocardial infarction, peripheral artery disease, or ischemic stroke) using logistic regression with adjustment for age and follow-up time. RESULTS: Among 294 CeAD patients (median age 46 [IQR 37-53], 41.8% women), 35 (12%) had any atherosclerotic signs at baseline. Among 196 patients with available follow-up, another 21/196 (11%) patients developed atherosclerosis during a median follow-up of 55.7 months. Patients with atherosclerosis had decreased odds of recurrent CeADs when compared to patients without atherosclerosis (OR 0.03, 95% CI = 0.00-0.30). During follow-up, 6 (15%) vascular events occurred among 40 CeAD patients with atherosclerosis and 13 (8.5%) among 153 patients without atherosclerosis (OR 1.38, 95% CI = 0.39-4.55, data for 3 patients were missing). DISCUSSION AND CONCLUSION: Signs of atherosclerosis in the carotid artery were detectable in 12% of CeAD patient at baseline. Additionally, 11% of CeAD patients developed new signs of atherosclerosis within the following 5 years. The presence of atherosclerosis may suggest a lower risk for recurrent CeAD. Whether it might indicate an increased risk for late clinical vascular events deserves further studies.