Clinical value of O-RADS combined with serum CA125 and HE4 for the diagnosis of ovarian tumours.

BACKGROUND: Ovarian tumors (OTs) are common gynecological tumors in women. It is very important to correctly distinguish benign and malignant OTs. PURPOSE: To assess the diagnostic performance of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) and evaluate the clinical value of O-RADS combined with serum carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) in differentiating benign from malignant OTs. MATERIAL AND METHODS: A retrospective analysis was performed on 431 cases including pathology and clinical data. The receiver operating characteristic (ROC) curve was drawn, and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: In premenopausal women, O-RADS and O-RADS combined with serum CA125 and HE4 showed sensitivity at 92.2% and 94.8%, specificity at 91.8% and 93.4%, and accuracy at 91.9% and 93.8%, respectively. In postmenopausal women, the sensitivity of O-RADS, O-RADS combined with serum CA125 and HE4 was 94.8% and 95.8%, specificity was 83.9% and 93.6%, and accuracy was 90.5% and 95.6%, respectively. The sensitivity, specificity, and accuracy of O-RADS combined with CA125 and HE4 in premenopausal and postmenopausal women were higher than that of O-RADS (P<0.05). CONCLUSION: O-RADS has high diagnostic performance in OTs. When O-RADS is combined with CA125 and HE4 in the diagnosis of OTs, the sensitivity and specificity are improved, which is helpful to improve the diagnostic efficiency of OTs and has high clinical application value.

Evaluating the safety and efficacy of microwave ablation in treatment of cervical metastatic lymph nodes of papillary thyroid carcinoma compared to repeat surgery.

OBJECTIVE: To evaluate the safety and efficacy of microwave ablation (MWA) versus repeat surgery for treating metastatic lymph nodes (MLNs) in papillary thyroid carcinoma (PTC). METHODS: Between July 2017 and October 2020, 67 patients were enrolled in this retrospective study. 19 and 48 patients underwent MWA and repeat surgery, respectively. The primary and secondary endpoints were recurrence-free survival and complication rates, respectively. The largest diameter, volume and volume reduction ratio (VRR) were analyzed before and after MWA. The effects of different ablation powers on the largest diameter, volume and VRR were investigated. Pre and posttreatment variables (e.g., baseline characteristics, serum thyroglobulin [Tg] levels, hospitalization time, treatment costs, recurrence-free survival and complication rates) were compared between groups. RESULTS: The largest diameter and volume postablation at each follow-up were smaller than the preablation levels (p < 0.05), except at the 1-month follow-up (p > 0.05). The largest diameter, volume, and VRR among the different ablation powers were not significantly different (p > 0.05). The mean serum Tg levels and biochemical remission rates were not significantly different between the groups (p > 0.05). Compared to reoperation, MWA had a shorter hospitalization time and lower treatment cost (p < 0.001). Total and minor complications were higher in the reoperation group (p < 0.05), but major complications were comparable (p > 0.05). The recurrence-free survival rate between groups was not significantly different (p = 0.401). The 1- and 3-year recurrence-free survival rates were comparable between the groups. CONCLUSIONS: MWA may be a safe and effective alternative to repeat surgery for treating MLNs of PTC in select patients.

Cathelicidin is a "fire alarm", generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa.

Pulmonary infections are a major global cause of morbidity, exacerbated by an increasing threat from antibiotic-resistant pathogens. In this context, therapeutic interventions aimed at protectively modulating host responses, to enhance defence against infection, take on ever greater significance. Pseudomonas aeruginosa is an important multidrug-resistant, opportunistic respiratory pathogen, the clearance of which can be enhanced in vivo by the innate immune modulatory properties of antimicrobial host defence peptides from the cathelicidin family, including human LL-37. Initially described primarily as bactericidal agents, cathelicidins are now recognised as multifunctional antimicrobial immunomodulators, modifying host responses to pathogens, but the key mechanisms involved in these protective functions are not yet defined. We demonstrate that P. aeruginosa infection of airway epithelial cells promotes extensive infected cell internalisation of LL-37, in a manner that is dependent upon epithelial cell interaction with live bacteria, but does not require bacterial Type 3 Secretion System (T3SS). Internalised LL-37 acts as a second signal to induce inflammasome activation in airway epithelial cells, which, in contrast to myeloid cells, are relatively unresponsive to P. aeruginosa. We demonstrate that this is mechanistically dependent upon cathepsin B release, and NLRP3-dependent activation of caspase 1. These result in LL-37-mediated release of IL-1ß and IL-18 in a manner that is synergistic with P. aeruginosa infection, and can induce caspase 1-dependent death of infected epithelial cells, and promote neutrophil chemotaxis. We propose that cathelicidin can therefore act as a second signal, required by P. aeruginosa infected epithelial cells to promote an inflammasome-mediated altruistic cell death of infection-compromised epithelial cells and act as a "fire alarm" to enhance rapid escalation of protective inflammatory responses to an uncontrolled infection. Understanding this novel modulatory role for cathelicidins, has the potential to inform development of novel therapeutic strategies to antibiotic-resistant pathogens, harnessing innate immunity as a complementation or alternative to current interventions.

Diagnostic performance of the gallbladder reporting and data system combined with color doppler flow imaging for gallbladder cancer in the Asian population.

Purpose: Evaluating the performance of the Gallbladder Reporting and Data System (GB-RADS) combined with Color Doppler Flow Imaging (CDFI) for the diagnosis of gallbladder wall thickening disease in an Asian population. Methods: In this study, the lesions were classified and the actual incidence rate of malignant tumors was calculated for each GB-RADS category, following the guidelines provided by GB-RADS. To evaluate the diagnostic performance of GB-RADS and GB-RADS combined with CDFI, we plotted Receiver Operator Characteristic (ROC) curves. The sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (AC) were also calculated. Inter-observer agreement (IRA) between the two observers was assessed using Kappa values. Results: The incidence of malignancy risk for GB-RADS 2, 3, 4, and 5 was 9%, 12.5%, 72.2%, and 100%. The AUC for GB-RADS was 0.855 (95% CI: 0.800-0.900), with a sensitivity of 82.5%, a specificity of 84.6%, and an accuracy of 83.8%. The AUC of GB-RADS combined with CDFI was 0.965 (95% CI: 0.930-0.985), with a sensitivity of 96.2%, a specificity of 94.6%, and an accuracy of 95.2%. The AUC, sensitivity, specificity, and accuracy of GB-RADS combined with CDFI for diagnosing gallbladder malignancy were higher than those of GB-RADS alone, and the differences were statistically significant (all P < 0.05). The IRA was excellent between the two observers (Kappa = 0.870). Conclusions: GB-RADS combined with CDFI demonstrated excellent diagnostic accuracy when it comes to distinguishing various diseases that caused gallbladder wall thickening in the Asian population, which has good clinical value and can improve the detection rate of malignant tumors in patients with gallbladder wall thickening.

Evaluating the risk of malignancy in adnexal masses: validation of O-RADS and comparison with ADNEX model, SA, and RMI.

OBJECTIVES: To evaluate the diagnostic value of Ovarian-adnexal Reporting and Data System (O-RADS), and to compare it with Assessment of Different NEoplasias in the adnexa (ADNEX) model, Subjective Assessment (SA), and Risk of Malignancy Index (RMI) in differentiating benign and malignant adnexal masses (AMs). MATERIAL AND METHODS: Ultrasound characteristics of 445 patients included in the study were retrospectively analyzed and evaluated using diagnostic models. The diagnostic performances of ultrasound diagnostic models were measured by assessing, receiver-operating characteristic curves, sensitivities, positive predictive values, positive likelihood ratios, specificities, negative predictive values, and negative likelihood ratios. Kappa values were used to evaluate inter-reviewer agreement (IRA). RESULTS: Of the 445 AMs, 265 were benign and 180 were malignant. The area under the curve (AUC) of O-RADS (0.941), ADNEX model (0.925), and SA (0.931) were higher than RMI (0.815) (all p < 0.05). The sensitivity of O-RADS (93.3%), ADNEX model (94.4%), and SA (96.1%) were higher than RMI (70.6%) (p > 0.05), and there was no statistical significance among them (p > 0.05). The specificity of O-RADS, ADNEX model, SA, and RMI was 90.2%, 90.6%, 90.2%, and 92.5%, respectively, with no statistical significance (p > 0.05). All four ultrasound diagnostic methods showed better IRA. CONCLUSIONS: O-RADS, ADNEX model and SA have better diagnostic value in differentiating benign and malignant AMs than RMI.

Cardiac metabolism in HFpEF: from fuel to signalling.

Heart failure (HF) is marked by distinctive changes in myocardial uptake and utilization of energy substrates. Among the different types of HF, HF with preserved ejection fraction (HFpEF) is a highly prevalent, complex, and heterogeneous condition for which metabolic derangements seem to dictate disease progression. Changes in intermediate metabolism in cardiometabolic HFpEF-among the most prevalent forms of HFpEF-have a large impact both on energy provision and on a number of signalling pathways in the heart. This dual, metabolic vs. signalling, role is played in particular by long-chain fatty acids (LCFAs) and short-chain carbon sources [namely, short-chain fatty acids (SCFAs) and ketone bodies (KBs)]. LCFAs are key fuels for the heart, but their excess can be harmful, as in the case of toxic accumulation of lipid by-products (i.e. lipotoxicity). SCFAs and KBs have been proposed as a potential major, alternative source of energy in HFpEF. At the same time, both LCFAs and short-chain carbon sources are substrate for protein post-translational modifications and other forms of direct and indirect signalling of pivotal importance in HFpEF pathogenesis. An in-depth molecular understanding of the biological functions of energy substrates and their signalling role will be instrumental in the development of novel therapeutic approaches to HFpEF. Here, we summarize the current evidence on changes in energy metabolism in HFpEF, discuss the signalling role of intermediate metabolites through, at least in part, their fate as substrates for post-translational modifications, and highlight clinical and translational challenges around metabolic therapy in HFpEF.

Safety and efficacy of thermal ablation for cervical metastatic lymph nodes in papillary thyroid carcinoma: A systematic review and meta-analysis.

Background: To evaluate the safety and efficacy of radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) for the treatment of cervical metastatic lymph nodes (CMLNs) of papillary thyroid carcinoma (PTC). Methods: The Pubmed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies on the safety and efficacy of thermal ablations (RFA, MWA, and LA) for the treatment of CMLNs of PTC until March 30, 2022. A review of 334 potential papers identified 17 eligible papers including 312 patients. Fixed-effects model or random-effects model was used to evaluate the pooled proportions of volume reduction rate (VRR), complete disappearance, and recurrence, and pooled estimates of changes in the largest diameter, volume, and serum Tg after ablation. The pooled proportions of overall and major complications were calculated. Subgroup analysis based on treatment modalities. The heterogeneity among studies was analyzed by using Q statistics and inconsistency index I2 . MINORS scale was used to evaluate the quality of the studies. Results: 17 eligible studies were finally identified, including 312 patients and 559 CMLNs. The pooled proportions of VRR, complete disappearance and recurrence of CMLNs were 91.28% [95% confidence interval (CI): 86.60-95.97%], 67.9% [95% CI: 53.1-81.1%] and 7.8% [95%CI: 3.0-14.1%], respectively. The pooled estimates of changes in the largest diameter, volume and serum Tg were 8.12 mm [95%CI: 6.78-9.46 mm], 338.75 mm3 [95%CI: 206.85 -470.65 mm3] and 5.96 ng/ml [95%CI: 3.68-8.24 ng/ml], respectively. The pooled proportions of overall and major complications were 2.9% [95%CI: 0.3-7.1%] and 0.3% [95%CI: 0-1.9%], respectively. Significant between-study heterogeneity was observed for complete disappearance (P<0.01, I2 =88.6%), VRR (P<0.001, I2 =99.9%), recurrence (P=0.02, I2 =47.76%), overall complications (P<0.02, I2 =44.8%), and changes in the largest diameter (P < 0.001, I2 =82.6%), volume (P<0.001, I2 =97.0%), and serum Tg (P < 0.001, I2 =93.7%). Subgroup analysis showed heterogeneity of the VRR among the treatment modality (I2 range: 84.4-100%). The VRR of MWA was the highest (97.97%), followed by RFA (95.57%) and LA (84.46%) (P < 0.001). Conclusion: All thermal ablations were safe and effective for the treatment of CMLNs of PTC. However, each treatment had significant heterogeneity in VRR. Compared with RFA and MWA, LA was less effective in reducing the volume of CMLNs of PTC.

Ablation of Enpp6 Results in Transient Bone Hypomineralization.

Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6 -/- ). Micro-computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6 -/- tibias (p < 0.05) that normalized by 12 weeks of age. Whole-bone cortical analysis also revealed significantly hypomineralized proximal bone in 4- but not 12-week-old Enpp6 -/- mice (p < 0.05) compared with WT animals. Back-scattered SEM revealed a failure in 4-week-old trabecular bone of mineralization foci to propagate. Static histomorphometry revealed increased osteoid volume (p > 0.01) and osteoid surface (p < 0.05), which recovered by 12 weeks but was not accompanied by changes in osteoblast or osteoclast number. This study is the first to characterize the skeletal phenotype of Enpp6 -/- mice, revealing transient hypomineralization in young animals compared with WT controls. These data suggest that ENPP6 is important for bone mineralization and may function upstream of PHOSPHO1 as a novel means of generating its substrates inside matrix vesicles. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.