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.

Coexistence of urinary tuberculosis and urothelial carcinoma: A case report.

BACKGROUND: Taiwan has a high prevalence of tuberculosis and urothelial carcinoma. However, the simultaneous occurrence of both disorders in one patient is uncommon. Tuberculosis and urothelial carcinoma share some common risk factors and could demonstrate overlapping clinical manifestations. CASE SUMMARY: Herein, we report the case of a patient who presented with fever, persistent hematuria, and pyuria. Chest computed tomography scans revealed a bilateral upper lobes cavitary lesion with fibrosis. Severe hydronephrosis of the right kidney and renal stones and cysts in the left kidney were observed. Initial microbiological testing was negative; however, a polymerase chain reaction assay of the urine confirmed a urinary tuberculosis infection. The patient was started on an anti-tuberculosis regimen. Ureteroscopy performed to resolve obstructive nephropathy revealed the incidental finding of a left middle-third ureteral tumor. Examination after biopsy and transurethral resection of the bladder tumor indicated urothelial carcinoma. The patient underwent laparoscopic nephroureterectomy, with bladder cuff excision for the right kidney and ureter, and holmium laser ablation of the ureteral lesion to preserve the left kidney and ureter. He has remained stable after the procedures. CONCLUSION: Although establishing a causal relationship between tuberculosis and cancer is difficult, medical personnel should consider their correlation.

Slow skeletal muscle troponin T acts as a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma.

Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.

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.

A survey for ketamine abuse and its relation to the lower urinary tract symptoms in Taiwan.

We aimed to explore the correlation between ketamine abuse and lower urinary tract symptoms (LUTS) and epidemiology of ketamine cystitis. Questionnaire records of ketamine abusers, such as sex, age, and details of using ketamine, including consumption method, amount, duration of ketamine use, and LUTS, were obtained from two private rehabilitation centers. We analyzed these factors and established a severity forecasting module. One hundred and six ketamine abusers completed the questionnaires. LUTS showed an onset time of 24.67 ± 26.36 months among ketamine abusers. Overactive bladder symptom score, international prostate symptom score-storage, interstitial cystitis symptom index, interstitial cystitis problem index, and visual analogue scale score were 5.25 ± 4.43, 5.95 ± 5.72, 10.96 ± 6.66, 9.73 ± 5.82, and 2.55 ± 3.18, respectively. All symptom scores were positively correlated with the duration of ketamine abuse. Ketamine snorting was significantly correlated with all symptom scores compared to smoking. Hydrodistention, intravesical hyaluronic acid instillation, intravesical injection with botulinum toxin, and hyperbaric-oxygen therapy showed better effect than oral treatment. Ketamine can induce severe storage symptoms, such as frequency or nocturia depending on the duration of abuse. Ketamine snorting may cause worse LUTS than smoking. Combining ketamine and other substances may exacerbate LUTS. Intravesical therapy may lead to better outcomes than oral treatment.

Kidney Transplantation from an extracorporeal membrane oxygenation-supported brain-dead donor: A case report.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) can deliver effective respiratory and circulatory maintenance to organ donors, improve organ function, and shorten warm ischemic time before harvesting. However, ECMO-supported brain-dead donors (DBDs) still have a high risk of acute kidney injury related to decreased renal oxygen delivery and inflammatory damage, which may cause early graft failure. PATIENT CONCERNS: Kidney transplantation from an ECMO-supported DBD. DIAGNOSES: We found an extremely abnormal "very dark blue" appearance of the graft kidneys from an ECMO-supported DBD during kidney procurement. INTERVENTIONS: Rather than discarding the graft kidneys, we performed an on-table biopsy. Pretransplant biopsy results revealed minimal interstitial fibrosis in the section of these graft kidneys. OUTCOMES: Two candidates received graft kidneys, and the two grafts remained functional until the 8-month follow-up. LESSONS: Currently, there is no standard method for evaluating graft kidney function of ECMO-supported DBDs. Regardless of the donors' preoperative serum creatinine (SCr) level, estimated glomerular filtration rate (eGFR), or gross appearance of the graft kidney, we believe that it is more reliable to include pretransplant biopsy as a criterion in clinical practice to safely accept kidneys from ECMO-supported DBDs.

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.

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.