Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

Background: To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. Methods: A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. Results: The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. Conclusions: ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

A nomogram based on LI-RADS features, clinical indicators and quantitative contrast-enhanced MRI parameters for predicting glypican-3 expression in hepatocellular carcinoma.

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy.

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

Diagnostic Accuracy and Interobserver Agreement of PI-RADS Version 2 and Version 2.1 for the Detection of Transition Zone Prostate Cancers.

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naïve patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.

Biparametric prostate MRI and clinical indicators predict clinically significant prostate cancer in men with "gray zone" PSA levels.

PURPOSE: To predict clinically significant prostate cancer (cs-PCa) by combining the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators in men with prostate-specific antigen (PSA) levels in the gray zone of 4-10 ng/mL. METHOD: We retrospectively analyzed 364 patients with elevated PSA levels in the gray zone who had pathologically confirmed disease and had undergone MRI examinations from January 2015 to October 2019; a training group (n = 255) and validation group (n = 109) were randomly established. Multivariate logistic regression analysis of the training group was performed to identify the independent predictors for cs-PCa, thereby establishing a predictive model that was evaluated in the training and validation groups by analyzing the receiver operating characteristic (ROC) curve. RESULTS: In the training group, the PI-RADS v2 score and prostate volume (PV) were independent predictors of cs-PCa (P < 0.05). The prediction model comprising the PI-RADS v2 score and PV had a larger AUC than the other predictors alone in the training group. The diagnostic sensitivity and specificity of the prediction model were 84.1 % and 83.4 %, respectively. The prediction model was indicated to have better predictive performance in the validation group. CONCLUSIONS: The prediction model exhibits a satisfactory predictive value for cs-PCa in men with PSA levels in the gray zone. PI-RADS v2 is the strongest univariate predictor for the detection of cs-PCa in men with PSA in the gray zone, but combining this with the PV can provide superior predictive ability.

[Establishment and rudimentary application of the method of recording auditory brainstem responses electrically stimulated via round-window niche in cochlear implants].

OBJECTIVE: To establish the method of recording auditory brainstem responses electrically stimulated via round-window niche in cochlear implants. METHODS: Self-made platinum iridium alloy as a spherical electrode stimulation electrode, modified cochlear implants connected to in vitro speech processor as a electro-stimulator and evoke potential instrument for Bio-logic Navigator Pro, 17 cochlear implant patients with various ages and of different causes, including auditory neuropathy (2 cases), ossified cochlea (1 case), inner ear malformation (5 cases), leukodystrophy (1 case), unknown and reason (8 cases) were investigated during cochlear implant surgery. Before cochlear implantation, stimulation electrode was placed in the round-window niche while charge balanced biphasic constant current was used as electrical stimulation via round window niche, and then electrically evoked auditory brainstem response was recorded. RESULTS: Electrically evoked auditory brainstem response waveforms were clearly recorded in all 17 cases. The latencies of III and V waves were (2.12 +/- 0.18) ms and (4.18 +/- 0.19) ms respectively, with threshold as (220.0 +/- 16.04) CL. The waveforms of the 2 patients with auditory neuropathy, 5 patients with inner ear malformation, 1 patient with ossified cochlea and 1 patient with leukodystrophy were well differentiated. CONCLUSIONS: Monitoring electrically evoked auditory brainstem response was an objective nerve electrophysiological testing method that accurately reflects function completeness of auditory pathway. It had important value for helping making the judgment whether patients could acquire auditory response after cochlear implantation. This method was safe and gave high emission of auditory response, therefore should be spread widely.

[Local response caused by implant after cochlear implantation].

OBJECTIVE: To approach the incidence rate, symptoms, etiologies, correlating reasons, consequences and treatments of local responses caused by implant after cochlear implantation and to provide reference for the future works. METHODS: From 1995 to 2007 there were 997 cases adopted cochlear implantation in Peding Union Medical College Hospital. Ten cases experienced local responses were analyzed retrospectively. RESULTS: The incidence of local response was 1.003%. There were 6 males and 4 females. The ages were between 13 months to 8 years old. The average age was 34 months. The devices mainly were made by Cochlear and Med-EL companies. The mainly symptoms and signs were local swellings, complaint of pruritus after ear, decrease of sound legibility and so on. Onset frequencies of this disease was 1 to 8 times. The bacterium cultured of displacing liquids was negative. But the IgE was detected in 2 cases. Results showed the patients were midrange status of hypersensitivity. Positive conservative treatments must be done including antibiotics, antihistamines, necessarily using immunotherapy. CONCLUSIONS: Besides local infection of bacteria, the allergy caused by silicone of implant coupled be a reason. Although the diagnose of this disease was difficult, but the screening of source of hypersensitivity was necessary before operation. It was recurrent attacks and maybe liable by kindred patients. Onset age was more below 4 years old. The patch test should be done again when the symptoms were occurrence after operation. If severe secondary infection was occurred and the states could not be well controlled the devices in the body must be explanted immediately. When the conditions were stable reimplantation could be experienced by non-sensibilisinogen devices.

[Cochlear implantation in patients with otitis media-related diseases].

OBJECTIVE: To evaluate the indications, surgical techniques and complications of cochlear implantation in patients with otitis media-related diseases. METHODS: Retrospective study of the data collected from patients receiving cochlear implantation. Totally 866 cases of cochlear implantation were performed in Peking Union Medical College Hospital from May 1995 to February 2006. Among which, 41 patients with otitis media-related diseases were grouped into 5 types: chronic secretory otitis media (13 cases), silent (subclinical) otitis media (18 cases), dry eardrum perforation (1 case), bilateral cholesteatoma of middle ear (2 cases) and middle ear granuloma (7 cases). Seven cases were accompanied with deformities of middle ear and (or) inner ear. Pedicled aponeurosis of occipitofrontalis muscle was transplanted to cover and protect the inserted electrodes and facial nerve in a patient with bilateral cholesteatoma after radical mastoidectomy. RESULTS: All the 41 patients with otitis media-related diseases were successfully implanted in one stage or staged operations and followed up uneventfully for 5 months to 6 years and 11 months. All implant devices had worked normally and all patients had performed well. CONCLUSIONS: Patients with chronic secretory otitis media, silent (subclinical) otitis media, middle ear granuloma or dry ear-drum perforation could be operated in one stage or staged procedures safely and effectively. Patients with bilateral cholesteatoma could be implanted after radical removal of related lesions. Pedicled aponeurosis of occipitofrontalis muscle could be transplanted in cases of mastoid bowl to cover and protect the inserted electrodes and the exposed facial nerve and with easy access to observe the mastoid cavity. Active suppurative otitis media was contraindicated for cochlear implantation. Long-term following-up was essential for better evaluation of the outcomes of cochlear implantation in patients with otitis media-related diseases.

[Voice analysis in pre-lingual cochlear implant adults].

OBJECTIVE: To observe voice characteristic of pre-lingual cochlear implant adults for cochlear implantation and phoniatrics. METHODS: 3s-sustained voice of vowel [ a: ] of 28 pre-lingual cochlear implant adults, 18 pre-lingual deafness adults and 10 adults with normal hearing were analyzed. Specifically, the Voice analyses include fundamental frequency, first formant, second formant, frequency perturbation quotient (FPQ), amplitude perturbation quotient (APQ) and harmonic noise ratio (HNR). The outcomes of 3 groups were compared. RESULTS: The fundamental frequency was lower in cochlear implant group [(175.42+/-25. 31) Hz] than that in deafness group [(210.84+/-54.300) Hz] (P = 0.02). The position of formant of cochlear implant group [F2 = (1264. 64 +/- 152.19) Hz] was more access to normal than that of normal hearing group[ F2 = (1422.44 +/- 232. 37) Hz, P = 0. 02]. FPQ of cochlear implant group (2.09 +/- 1.15) was more access to normal than that of deafness group (5.32+/-4.29, P=0.006). The voice of cochlear implanted and deafness adults were much more different individually. CONCLUSIONS: In the aspect of acoustic characteristic of voice, pre-lingual cochlear implant adults could benefit cochlear implantation finitely. As speech perception of pre-lingual cochlear implant adults was far worse than that of children and post-lingual cochlear implant adults, the general outcome of pre-lingual cochlear implant adults was very limited. Cochlear implant of those candidate should be cautious.

[Clinical review of cochlear implant in 533 cases].

OBJECTIVE: To summarize and analyze the etiology, surgical indications, operation methods and outcomes of cochlear implantation. METHODS: 533 cases (534 ears) with severe and profound hearing loss received cochlear implant, 489 were pre-lingual deafness and 38 cases were post-lingual deafness. Their ages at implant, 1 to approximately 3 were 167, approximately 5 were 77, approximately 7 were 73, approximately 14 were 136, approximately 17 were 28, >17 were 52. 76 cases (14. 3%) were found the middle and inner ear malformations. That included Mondini 26 in cases, Common cavity in 10 cases and Large vestibule aqueduct syndrome in 20 cases. The average pure tone threshold were 105.5 dB HL, ABR threshold were >95 dB nHL and 40 Hz threshold in 500 Hz were 101.7 dB. The devices they used were Nucleus 22M in 27 ears, 24M in 308 ears, 24R Contour in 131 ears and 24R ST in 21 ears; Med El C40+ in 44 ears; Clarion CI in 3 ears. Facial recess approach was performed in normal cases, and in Common cavity cases horizontal semicircular canal approach was used. Preoperative hearing and speech evaluations were done in most cases. RESULTS: In 26 Mondini case, gusher were happened in 20 cases. The insertion depth in normal cases: Nucleus were 30 bands, Med El were 31 mm. In Mondini cases, Nucleus were 28 bands. In Common cavity cases, Nucleus were 26 bands. Of 533 cases, The average of open set sentences discrimination of post-lingual deafness was 70%, the satisfaction rate of questionnaire for pre-lingual deafness under 17 years old was 94.7%. CONCLUSIONS: Cochlear implant is a useful method to restore the hearing of the patients with severe and profound hearing loss. It is important for the outcomes with proper preoperative assessment, surgery and postoperative speech and hearing evaluations.