Comparison of the protein acetylome of endothelial cells upon shear flow and resveratrol treatment

Background: Posttranslational acetylation/deacetylation known as the acetylome is important in regulating protein activity. Shear flow (SF) and resveratrol (RSV) are two stimuli that represent physical and chemical signal separately. The acetylome co-regulated by these two stimuli remain unclear. Methods: Human umbilical cord vein endothelial cells (HUVECs) were subjected to either SF of 12 dynes/cm2 or 10 μM RSV. The purified acetylated peptides were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The signaling cascades of the identified acetylome were predicted by ingenuity pathway analysis (IPA). Co-immunoprecipitation was applied to confirm the acetylation status of proteins. Results: Five groups of proteins showed an increased acetylation upon SF and RSV treatment. After algorithm, 628 proteins with increased acetylation and 22 proteins with decreased acetylation were identified in the SF acetylome. For the acetylome regulated by RSV, 145 proteins with increased acetylation and 23 proteins with decreased acetylation were identified. Compared these two acetylomes, 129 proteins with increased acetylation and 2 proteins with decreased acetylation were co-regulated by both SF and RSV treatments. IPA analysis showed that this co-regulated acetylome was involved in heat shock response, and the signals of eNOS, STAT3, JAK/STAT and ERK/MAPK. Co-immunoprecipitation analysis further confirmed the acetylated status of mitochondrial HSP60 and mitochondrial citrate synthase. Conclusions: This study indicated that physical signal is more complicated than chemical signal in the case of acetylome. The co-regulated proteins are worthy for further study in discussing synergetic effect between physical and chemical signal in cardioprotection

Adrenal computed tomography and NP-59 usefulness for diagnosing aldosterone-producing adenomas and idiopathic hyperaldosteronism in primary hyperaldosteronism

AbstractObjectivesTwo major causes of primary aldosteronism are aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA). In this study, we attempted to determine the role of NP-59 in identifying APA prior to adrenalectomy, especially when diagnostic computer tomography (CT) is equivocal.MethodsWe performed a retrospective analysis in patients with a clinical diagnosis of primary aldosteronism. The medical records of 36 patients were reviewed, which included 25 patients who had received adrenalectomy. All patients underwent adrenal CT alone or a combination of adrenal CT and NP-59 prior to surgery for the subtyping of primary aldosteronism, based on the protocols established in our institution. The accuracy of the adrenal CT and NP-59 findings was determined by a comparison with the pathologic findings and postoperative outcomes.ResultsTwenty-three patients received unilateral adrenalectomy under the diagnosis of APA. The diagnoses were based on CT findings in 11 patients and on CT and NP-59 findings in 12 patients. The results of pathology were adrenal cortical adenoma in these 23 patients and the positive predictive value was 100%. Blood pressure and potassium levels significantly improved after surgery in these patients (p < 0.01). Serum biochemistry and adrenal size of the limbs and bodies of patients with IHA were not significantly different from those of patients with APA.ConclusionFor the subtyping of primary aldosteronism, the imaging modality of adrenal CT alone or the combination of adrenal CT and NP-59 adrenal scan has a high positive predictive value for APAs. We suggest that all patients undergo an adrenal CT as their initial study, after confirming the diagnosis of primary aldosteronism, and to use NP-59 when adrenal CT findings are atypical or inconclusive. Lateralization by this modality prior to adrenalectomy can reduce unnecessarily invasive examinations such as adrenal venous sampling and also provide excellent treatment outcomes

Preoperative treatment with 5α-reductase inhibitors and the risk of hemorrhagic events in patients undergoing transurethral resection of the prostate – A population-based cohort study

OBJECTIVES: To assess the associations between preoperative treatment with 5-alpha reductase inhibitors and the risks of blood transfusion during transurethral resection of the prostate and blood clot evacuation or emergency department visits for hematuria within 1 month after surgery. METHODS: We used data from the Taiwan National Health Insurance Research Database in this population-based cohort study. A total of 3,126 patients who underwent first-time transurethral resection of the prostate from 2004 to 2013 were identified. Adjusted odds ratios estimated by multiple logistic regression models were used to assess the independent effects of the preoperative use of 5-alpha reductase inhibitors on the risks of perioperative hemorrhagic events after adjustment for potential confounders. RESULTS: Two hundred and ninety-seven (9.4%) patients were treated with 5-alpha reductase inhibitors fo

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival

Spontaneous regression of adrenal metastasis from renal cell carcinoma after sunitinib withdrawal: case report and literature review

Abstract Background The spontaneous regression of metastatic renal cell carcinoma is a rare phenomenon, with an estimated incidence of < 1%. We report a case of post-nephrectomy renal cell carcinoma adrenal metastasis, followed by the spontaneous regression of the metastasis after withdrawal of sunitinib. Case presentation The patient was a 55-year-old male with clear cell type renal cell carcinoma who previously underwent a left laparoscopic radical nephrectomy. After 51 months of follow up, a recurrence in the left renal fossa was observed and subsequently excised. Four months after excision, an abdominal Computerized tomography (CT) identified an adrenal metastasis of 1.6 cm. The patient was treated with sunitinib. However, the treatment was discontinued because of gastrointestinal side effects and fatigue. Eleven months after the discontinuation of sunitinib treatment, a progression in the adrenal metastasis growth (5.7 cm) was observed, whereas 16 months after the discontinuation, a regression of the adrenal metastasis growth (3.4 cm) was observed. During subsequent follow-ups, a gradual reduction in the size of the adrenal metastasis (1.8 cm) was observed. After 44 months from the discontinuation of sunitinib treatment, the patient was still alive and followed up in the outpatient department. Conclusions Sunitinib is a multi-targeted inhibitor of vascular endothelial growth factor (VEGF) receptors. This compound reduces tumor angiogenesis and has been approved worldwide for the treatment of advanced renal cell carcinoma. To our knowledge, this is the fourth case of the spontaneous regression of metastatic renal cell carcinoma after the discontinuation of sunitinib treatment

Functional outcome prediction after partial nephrectomy using R.E.N.A.L. nephrometry, PADUA classification, and Centrality index score

Objective: Several scoring systems have been proposed to quantify surgical complexity, and provide an insight into expected peri- and postoperative surgical outcomes following partial nephrectomy. However, it is still unclear which of the scoring systems has a better outcome in predicting functional outcomes after partial nephrectomy. In the present study, we assess the use of R.E.N.A.L. (Radius, Exophytic/endophytic properties of the tumor, Nearness of tumor deepest portion to the collecting system or sinus, Anterior/posterior descriptor and Location relative to the polar line.), PADUA (preoperative aspects and dimensions used for an anatomical score), and centrality index scores to predict the renal function for patients who underwent partial nephrectomy. Materials and methods: We retrospectively reviewed 26 cases with renal tumors managed with open partial nephrectomy at our institution from January 2008 to October 2013. R.E.N.A.L., PADUA, and centrality index scores were assigned according to the described protocols for those systems. We evaluated the association between scoring systems and both early and late postoperative functional outcomes. Results: The mean age of the study population was 56 years. Of the patients, 18 (69%) were men. The mean tumor size was 4.04 cm. Each scoring system performed significant correlation with both early and late functional outcomes (p < 0.05), whereas R.E.N.A.L nephrometry and PADUA classification showed high correlation (−0.715 and −0.721) and centrality index showed moderate correlation (0.451). Diameter of tumors, as a single anatomical parameter, does not correlate with functional outcome significantly (p = 0.974 1 day after surgery and p = 0.865 1 year after surgery). Conclusion: R.E.N.A.L., PADUA, and centrality index scores were inversely associated with renal function preservation after partial nephrectomy. In this regard it is possible to use these scoring systems preoperatively to gauge the magnitude of functional decrease

Adrenal cystic lymphangioma: A case report and review of the literature

A 37-year-old female was being evaluated for fever when a huge cystic lesion of about 9 × 10.5 cm2 in size in the right adrenal fossa with internal septal structures containing spots of calcification was found incidentally on computed tomography. A right adrenal cyst was suspected, and right adrenalectomy and surgical resection of the lesion were then performed. The pathology showed multilocular spaces lined by flat cells, compatible with adrenal cystic lymphangioma. Immunohistochemically, the tumor was strongly positive for D2-40 and CD31. She received regular imaging follow-up, and no metastatic disease has been found until now. The radiological and pathological features of adrenal cysts and the treatment strategy for adrenal lymphangiomas are discussed