Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

BACKGROUND: Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi-omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi-omics technology-based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. METHODS: First, we provided a general review of epilepsy, BTRE, and multi-omics techniques. Next, we described the specific multi-omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. RESULTS: Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma-related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR-128 and miRNA-196b participate in BTRE development. miR-128 might be negatively associated with the possibility of tumor-related epilepsy development. The lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non-epileptic gliomas. In another proteomics study, a high expression of AQP-4 was detected in the brain of GBM patients with seizures. By using quantitative RT-PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki-67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma-related epileptogenesis. Another metabolomics study found that SV2A, P-gb, and CAD65/67 have the potential to function as biomarkers for BTRE. CONCLUSIONS: Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Case Reports: A role of postoperative radiation therapy in completely resected early stage intrathyroid thymic carcinoma: a case report and literature review of the diagnosis and treatment.

Background: Intrathyroid thymic carcinoma (ITTC) is a rare malignant tumor of the thyroid, probably arising from ectopic thymus or branchial pouch remnants. Most of the literature recommended radical resection as the fundamental treatment for ITTC, and postoperative radiation appears to be able to reduce the recurrence rate in patients with advanced ITTC. However, the issue of adjuvant radiotherapy in completely resected early-stage ITTC has been controversial. Case presentation: Here, we reported a new case of early-stage ITTC that treated with total thyroidectomy and the right central neck dissection. Postoperative external beam radiation therapy (50.0 Gy/25 fractions) was given to the thyroid bed and bilateral cervical lymph node area since the tumor involved part of the sternal thyroid muscle. At 4-year follow-up after completion of radiotherapy, she is without evidence of locally recurrent or distant disease. Conclusion: Since there are no current guidelines for early-stage ITTC, in combination with this case and previous literature, we may suggest routine adjuvant radiotherapy should be considered in patients with incompletely resected tumors and extraparenchymal extension of ITTC. Moreover, we summarized comprehensive and advanced diagnosis, treatment, prognosis of ITTC and comparison between ITTC, primary squamous cell carcinoma of thyroid gland, differentiated thyroid cancer, and anaplastic thyroid cancer.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation.

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

The Performance of Transvaginal Two-Dimensional Fundamental Sonosalpingography Combined with Saline Infusion Pelvic Sonosalpingography for Assessing Fimbrial Part's Morphology and Function of the Fallopian Tubes.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic efficacy of transvaginal two-dimensional fundamental sonosalpingography (2D-FS) combined with saline infusion pelvic sonosalpingography (SIPS) for assessing fimbrial part's morphology and function of the fallopian tubes. METHODS: One hundred and sixty-nine cases underwent 2D-FS combined with SIPS. Among them, 18 cases received laparoscopy and dye test (LDT) within 3 months after the examination and the results were regarded as reference standard. RESULTS: Excluding proximal or middle segment obstructed tubes, the remaining fimbrial parts' display rate by using 2D-FS combined with SIPS was 75.1%. According to the ultrasonic appearance, the fimbrial parts were classified into 4 types: normal, abnormal, suspected abnormal, and unclassifiable. Normal fimbrial parts accounted for 73.8% when the tubes were patent; abnormal fimbrial parts accounted for 74.1% when the tubes were partial obstructed; all became abnormal when the tubes were distal complete obstructed. The fimbrial parts which had been classified by 2D-FS combined with SIPS were compared with LDT further. This combination's accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Youden's index (YI) were 86.4, 87.5, 85.7, 77.8, 92.3, and 0.73%, respectively. The result of consistency analysis showed the combination was essentially consistent with LDT result (Kappa = 0.713). CONCLUSION: 2D-FS combined with SIPS can be a preferred method for assessment of the fimbrial part's morphology and function, with its advantages of non-invasive, intuition, and accuracy. This combination could provide an objective imaging basis for choosing clinical treatment strategies and predicting prognosis.

Application of contrast-enhanced ultrasound in the diagnosis of post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation: A case report.

INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) is a series of proliferative diseases of the lymphatic system. Among patients receiving hematopoietic stem cell transplantation (HSCT), PTLD is a prevalent complication that severely affects rates of survival. Ultrasound plays an essential role in the early diagnosis of PTLD. Contrast-enhanced ultrasonography (CEUS) and CEUS-guided biopsy are critical procedures for tumor diagnosis. PATIENT CONCERNS: Herein, we report the case of a 40-year-old male patient with acute lymphoblastic leukemia who received HSCT more than 1 year ago. Sonography revealed a small hypoechoic nodule in the liver four months after HSCT. Eight months after HSCT, larger and more nodules were observed via ultrasound; CT was used to identify the lesions. DIAGNOSES: CEUS and CEUS-guided biopsy were performed, and the pathological diagnosis was PTLD. INTERVENTIONS: The final clinical diagnosis was PTLD, and cyclophosphamide, epirubicin, and dexamethasone were administered as chemotherapy. OUTCOMES: The patient was discharged after his condition improved. CONCLUSION: Ultrasound can be used to effectively detect lesions of PTLD early after HSCT. Furthermore, CEUS and CEUS-guided biopsy were effective for early confirmatory diagnoses of PTLD after HSCT.

Feasibility of a 5G-Based Robot-Assisted Remote Ultrasound System for Cardiopulmonary Assessment of Patients With Coronavirus Disease 2019.

BACKGROUND: Traditional methods for cardiopulmonary assessment of patients with coronavirus disease 2019 (COVID-19) pose risks to both patients and examiners. This necessitates a remote examination of such patients without sacrificing information quality. RESEARCH QUESTION: The goal of this study was to assess the feasibility of a 5G-based robot-assisted remote ultrasound system in examining patients with COVID-19 and to establish an examination protocol for telerobotic ultrasound scanning. STUDY DESIGN AND METHODS: Twenty-three patients with COVID-19 were included and divided into two groups. Twelve were nonsevere cases, and 11 were severe cases. All patients underwent a 5G-based robot-assisted remote ultrasound system examination of the lungs and heart following an established protocol. Distribution characteristics and morphology of the lung and surrounding tissue lesions, left ventricular ejection fraction, ventricular area ratio, pericardial effusion, and examination-related complications were recorded. Bilateral lung lesions were evaluated by using a lung ultrasound score. RESULTS: The remote ultrasound system successfully and safely performed cardiopulmonary examinations of all patients. Peripheral lung lesions were clearly evaluated. Severe cases of COVID-19 had significantly more diseased regions (median [interquartile range], 6.0 [2.0-11.0] vs 1.0 [0.0-2.8]) and higher lung ultrasound scores (12.0 [4.0-24.0] vs 2.0 [0.0-4.0]) than nonsevere cases of COVID-19 (both, P < .05). One nonsevere case (8.3%; 95% CI, 1.5-35.4) and three severe cases (27.3%; 95% CI, 9.7-56.6) were complicated by pleural effusions. Four severe cases (36.4%; 95% CI, 15.2-64.6) were complicated by pericardial effusions (vs 0% of nonsevere cases, P < .05). No patients had significant examination-related complications. INTERPRETATION: Use of the 5G-based robot-assisted remote ultrasound system is feasible and effectively obtains ultrasound characteristics for cardiopulmonary assessment of patients with COVID-19. By following established protocols and considering medical history, clinical manifestations, and laboratory markers, this system might help to evaluate the severity of COVID-19 remotely.

Pilot Study of Robot-Assisted Teleultrasound Based on 5G Network: A New Feasible Strategy for Early Imaging Assessment During COVID-19 Pandemic.

Early diagnosis is critical for the prevention and control of the coronavirus disease 2019 (COVID-19). We attempted to apply a protocol using teleultrasound, which is supported by the 5G network, to explore the feasibility of solving the problem of early imaging assessment of COVID-19. Four male patients with confirmed or suspected COVID-19 were hospitalized in isolation wards in two different cities. Ultrasound specialists, located in two other different cities, carried out the robot-assisted teleultrasound and remote consultation in order to settle the problem of early cardiopulmonary evaluation. Lung ultrasound, brief echocardiography, and blood volume assessment were performed. Whenever difficulties of remote manipulation and diagnosis occurred, the alternative examination was repeated by a specialist from another city, and in sequence, remote consultation was conducted immediately to meet the consensus. The ultrasound specialists successfully completed the telerobotic ultrasound. Lung ultrasound indicated signs of pneumonia with varying degrees in all cases and mild pleural effusion in one case. No abnormalities of cardiac structure and function and blood volume were detected. Remote consultation on the issue of manipulation practice, and the diagnosis in one case was conducted. The cardiopulmonary information was delivered to the frontline clinicians immediately for further treatment. The practice of teleultrasound protocol makes early diagnosis and repeated assessment available in the isolation ward. Ultrasound specialists can be protected from infection, and personal protective equipment can be spared. Quality control can be ensured by remote consultations among doctors. This protocol is worth consideration as a feasible strategy for early imaging assessment in the COVID-19 pandemic.

The role of shear wave elastography on evaluation of the rigidity changes of corpus cavernosum penis in venogenic erectile dysfunction.

OBJECTIVE: The goal of this study was to evaluate the effect of shear wave elastography (SWE) on the measurement of rigidity changes of penile erection in venogenic erectile dysfunction (ED) and in rigidity alterations of corpus cavernosum penis with age in normal population. METHODS: The study was a prospective analysis of 81 patients referred to the department of urology with complaints of ED as well as 35 healthy volunteers. SWE was performed on the corpus cavernosum penis (CCP) in the flaccid state of healthy group. The patients were divided into venogenic ED (31 patients) and non-vascular ED (neither arterial insufficiency nor venogenic dysfunction) (36 patients) by performing color doppler ultrasonography in association with intracavernous injection (ICI). SWE measurements were performed in CCP in the flaccid state, after 15-20 min and 25-30 min of ICI in both patients groups. Differences between groups were compared. RESULTS: Age was significantly negatively associated with SWE values of CCP among three groups (healthy group: r = -0.584, p < 0.05; venogenic ED group: r = -0.468, p < 0.05; non-vascular ED group: r = -0.539, p < 0.05). There was no significant difference between the SWE values of three groups in the flaccid state (p > 0.05). The mean SWE values of CCP were significantly lower in the erectile state (15-20 min after ICI) compared with the flaccid state in two patients groups (p < 0.05). The mean SWE values of CCP after ICI increased with time (from 15-20 min to 25-30 min) in patients with venogenic ED (p < 0.05), while the SWE values of CCP after ICI did not statistically significantly differ with time in patients with non-vascular ED (p > 0.05). CONCLUSION: SWE is expected to be a promising approach in terms of the etiological diagnosis of ED and the quantitative evaluation of alternations of penile structures with age.