Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Association of early vertebroplasty with risk of hip replacement: A nationwide population-based cohort study in Taiwan.

Studies show that vertebral fractures could predict the risk of hip fractures. We aimed to evaluate the potential benefits of whether the timing of vertebroplasty (VP) for vertebral fracture associated with the risk of hip fracture for hip replacement.We identified 142,782 patients from the Taiwan National Health Insurance Database with thoracolumbar vertebral fracture (International Classification of Diseases, Ninth Revision, Clinical Modification:805.2-805.9) who were followed up from 2000 to 2013. These patients were divided into those who underwent VP (VP group) (International Classification of Diseases, Ninth Revision, Clinical Modification : 78.49) within 3 months and those who did not (non-VP group). After adjusting for the confounding factors, the Cox proportional hazards analysis was used to estimate the effect of early VP on reducing the risk of hip fracture. The difference in the risk of hip replacement, between the VP group and non-VP group was estimated using the Kaplan-Meier method with the log-rank test.In the 14-year follow-up, the cumulative incidence rate of hip replacement in the VP group was lower than that in the non-VP group (0.362% and 0.533%, respectively, long-rank P < .001). There was a significant difference between the 2 groups since the first-year follow-up.Our study showed that early VP performed to avoid progression of the kyphotic changes following thoracolumbar vertebral fracture may reduce the risk of hip fracture. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Preoperative grading of intracranial meningioma by magnetic resonance spectroscopy (1H-MRS).

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery.

Dose Comparison Using Thermoluminescent Dosimeters During Multislice Computed Tomography With Different Parameters for Simulated Spine Tumor Examination.

This study aims to compare the effect of Philips' Brilliance 64-slice and 256-slice (multislice) computed tomography on effective doses when changing the operating parameters for simulated examinations of patients' spine tumors, including changes in pitch, tube voltage (kV), and effective tube current-time product (mA s). This study considers the possibility of using other probable operating conditions to reduce patients' effective doses. The absorbed doses to organs and skin are measured by taking data from thermoluminescent dosimeters (GR-200 and GR-200F) in relevant positions on the anthropomorphic Rando phantom. We also used an American College of Radiology computed tomography accreditation phantom to experiment with image spatial resolution under various scan conditions in order to achieve results over 5 line pairs per cm, the analytical capability required to meet diagnostic needs. The results show that, in general, when we change the pitch, effective tube current-time product, and tube voltage, the effective doses from 256-slice computed tomography exceed those from 64-slice computed tomography.

The Efficacy of Therapeutic Plasma Exchange in Antiphospholipid Antibody-positive Patients With Spontaneous Intracerebral Hemorrhage and High D-dimer Levels.

OBJECTIVE: We investigated the efficacy of plasma exchange (PE) in antiphospholipid antibody (aPL)-positive patients with a spontaneous intracerebral hemorrhage (ICH) and high D-dimer levels. MATERIALS AND METHODS: From May 2013 to May 2016, we evaluated 32 patients who were below the age of 50 and presented with spontaneous ICH. Five patients were positive for aPL antibody and 3 had a higher level of D-dimer. These 3 patients underwent 5 sessions of PE using fresh frozen plasma as replacement fluid. We analyzed the days postadmission until PE-start, the days of intensive care unit (ICU) hospitalization, D-dimer series, Glasgow Coma Scale (GCS) scores, and modified Rankin scale (mRS) scores. D-dimer levels and GCS scores were recorded at both pre-PE and post-PE stages. The mRS scores were recorded at pre-PE stage and 3 months post-PE. RESULTS: The mean postadmission period until PE-start was 8.33 days. The mean ICU hospitalization was 17.33 days. The D-dimer level pre-PE ranged from 2.34 to 5.44 mg/L fibrinogen equivalent unit (FEU). The D-dimer level post-PE ranged from 1.05 to 3.30 mg/L FEU. The amount of decline of the D-dimer level between pre-PE and post-PE ranged from 0.65 to 2.14 mg/L FEU. The GCS score pre-PE was between 7 and 8. The highest post-PE GCS score was 14. The improved GCS scores post-PE ranged from 3 to 6. The improved mRS scores of 3 months post-PE ranged from 3 to 4. CONCLUSIONS: The concurrent presence of positive aPL and a higher D-dimer level may worsen the neurological outcome of patients with a spontaneous ICH. Aggressive PE is effective for the treatment of such patients, decreasing the extent of the ICU hospitalization.

Urethral hemangioma in a prepubertal female patient: Report of a rare case.

RATIONALE: Urethral hemangiomas commonly occur in men or elderly women. We presented a rare case of urethral hemangioma in a prepubertal female patient. PATIENTS CONCERNS: An 8-year-old girl had the complaints of bloody staining of clothing, a foul perineal odor, and urethral pain. She was brought to our genitourinary outpatient department for survey and a single, 1-cm compressible reddish nodule at the 10-2 o'clock position in the distal urethra was found. DIAGNOSES: Urethral hemangioma in a prepubertal girl was diagnosed after excision of the urethral nodule. INTERVENTIONS: Excision with 8 "stay" sutures in the protruding urethral mucosa was performed. OUTCOMES: Normal micturition without symptom recurrence was noted at the 3-month follow-up. LESSONS: Urethral hemangioma is also found in prepubertal female patient. Increased physician awareness and early recognition of a urethral hemangioma can avoid unnecessary examinations and patient anxiety. The procedure of excision with 8 "stay" sutures in the protruding urethral mucosa facilitates mobilization from the distal urethra and provides a good surgical view of abnormal proliferative blood vessels. Therefore, the lesion can be removed as clean as possible.

Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.

INTRODUCTION: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. METHODS AND RESULT: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. CONCLUSION: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model.

Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome.A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model.The overall tumor control rate was 94.1% in the 36-month (range 18-87 months) follow-up period (mean volume change of -43.3%). Volume regression (mean decrease of -50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of -3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9).Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled.

Spondylodiscitis with Epidural and Psoas Muscle Abscesses as Complications After Transrectal Ultrasound-guided Prostate Biopsy: Report of a Rare Case.

A 71-year-old man presented with spondylodiscitis with epidural and psoas muscle abscesses following transrectal ultrasound (TRUS)-guided prostate biopsy. These rare complications were detected by computed tomography of the abdomen and magnetic resonance imaging of the lumbar spine. The patient was successfully treated with antibiotics and underwent neurosurgery. Awareness of presentations such as backache and weakness of the lower limbs after prostate biopsy is important as these symptoms are usually mistaken for bone or muscle problems and often not recognized as being related to infection. LEARNING POINTS: We describe the case of a patient who experienced two major complications (spondylodiscitis with epidural abscess and psoas muscle abscess) following prostate biopsy.Awareness of these potential complications following prostate biopsy is essential to prevent life-threatening consequences.

Successful treatment of a pancreatic pseudocyst accompanied by massive hemothorax: a case report.

BACKGROUND: It is rare to encounter massive hemothorax as a complication of pancreatic pseudocyst. In addition, as no obvious hypotension and abdominal discomfort were noted, it was difficult to consider gastrointestinal lesion a possibility. CASE PRESENTATION: A 54-year-old Taiwanese man had tightness on the left side of his chest and shortness of breath for 3 days. He had a history of acute pancreatitis 3 months ago. After history taking and a series of examinations including thoracocentesis and computed tomography of his abdomen and chest, the diagnosis was finally confirmed based on the high amylase levels in his pleural fluid. CONCLUSIONS: Treatment with distal pancreatectomy and splenectomy was subsequently successfully performed. Based on our experience, we briefly discuss the currently available treatment options for pancreatic pseudocyst.

A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.

Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.