Management and outcome of metastatic pheochromocytomas/paragangliomas: an overview

xlomafota.13 shared this article with you from Inoreader Management and outcome of metastatic pheochromocytomas/paragangliomas: an overview Via Latest Results for Journal of Endocrinological Investigation Abstract Background Metastatic pheochromocytomas and paragangliomas (PPGLs) occur in about 5–26% of cases and are characterized by a heterogeneous prognosis. Metastases can be synchronous at the initial diagnosis, but they can occur also many years after surgery for the primary tumor. To date, the treatment of patients affected by metastatic PPGLs represents a clinical challenge because of the lack of guidelines. Aim The aim of this article is to review the available management options and their impact on the outcomes of patients with metastatic PPGLs. Results Generally, treatments are not curative. Surgery, when possible, can be used to reduce hormonal symptoms and cardiovascular morbidity. Chemotherapy plays a role in patients with high burden tumor and rapid disease progression. Tyrosine kinases inhibitors (TKIs) might be considered for their ability to block the angiogenesis and cell growth. Radiation therapy and interventional radiology techniques can help in the management of local metastases to control symptoms and avoid tumor progression. On the other hand, peptide receptor radionuclide therapy (PRRT), using 90Y or 177Lu-DOTATATE, could be a promising therapy. In addition, high specific 131I-MIBG was approved by the Food and Drug Administration (FDA) in the US for the treatment of patients affected by metastatic and unresectable 131I-MIBG positive PPGLs. Considering the different pathways involved in the pathogenesis of PPGLs, several target therapies have been pr oposed and are under evaluation in clinical trials. Conclusions The choice of the appropriate treatment should be based on multidisciplinary and personalized approach taking into account the rarity and the variability of these tumors. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Biological insight into the extracellular vesicles in women with and without gestational diabetes

xlomafota.13 shared this article with you from Inoreader Biological insight into the extracellular vesicles in women with and without gestational diabetes Via Latest Results for Journal of Endocrinological Investigation Abstract Purpose Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles (EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy. Methods We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry. Results The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (p = 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (p = 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs. Conclusions These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Assessment of non-traumatic vertebral fractures in Cushing’s syndrome patients

xlomafota.13 shared this article with you from Inoreader Assessment of non-traumatic vertebral fractures in Cushing's syndrome patients Via Latest Results for Journal of Endocrinological Investigation Abstract Purpose Hypercortisolism has detrimental effects on bone metabolism with the consequences of bone loss and bone fractures. We aimed to evaluate the frequency of vertebral fragility fractures and to determine the factors associated with Cushing's syndrome (CS). Methods A total of 135 patients diagnosed with Cushing's syndrome [108 patients with Cushing's disease and 27 patients with adrenocortical adenoma] and 107 healthy controls were included in this cross-sectional study. The available clinical, laboratory, and radiologic data of patients with CS were recorded, retrospectively. Lateral vertebral radiograms were evaluated for vertebral fragility fractures according to Genant's semi-quantitative method. Bone mineral density (BMD) was determined using a Dual-energy X-ray absorptiometry (DEXA). Results Vertebral fragility fractures (VFs) were observed in 75.3% (n = 61) of the patients. The median number of VFs was six (min–max: 2–12). All patients with vertebral fractures had thoracic VF, and 50.7% of the patients had lumbar fragility fractures. Thirty-three (40.7%) patients with vertebral fractures had normal bone densitometry values. Osteoporosis and osteopenia were observed in 16.2% and 40.7% of the patients, respectively. The duration of active disease, the presence of ACTH-secreting pituitary adenoma, and 24-h urinary cortisol did not influence the presence of vertebral fractures. Vertebral fractures were independently associated with age, FSH, LH levels, and lumbar BMD (R2 = 68.18%, p = 0.028). The femoral neck BMD (but not lumbar BMD) was independently associated with age, BMI, and PTH levels (R2 = 48.48%, p < 0.001). Conclusion Vertebral fracture frequency was higher in CS patients. Most of the patients with vertebral fractures had multiple fractures. Although low lumbar BMD was associated with VF, patients with CS with normal bone densitometry could experience VF. Vertebral radiograph evaluations as a part of routine evaluation for silent vertebral fractures may help to prevent further fractures in patients with CS. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lipocalin-2: a role in hepatic gluconeogenesis via AMP-activated protein kinase (AMPK)

xlomafota.13 shared this article with you from Inoreader Lipocalin-2: a role in hepatic gluconeogenesis via AMP-activated protein kinase (AMPK) Via Latest Results for Journal of Endocrinological Investigation Abstract Purpose Evidence is accumulating that lipocalin2 (LCN2) is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase (AMPK) or forkhead transcription factor O1 (FoxO1), which influences insulin sensitivity and gluconeogenesis in liver. Methods LCN2 knockout (LCN2KO) mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic gluconeogenesis through pyruvate tolerance test (PTT), glucose tolerance test (ipGTT), insulin tolerance test (ITT), and hyperinsulinemic-euglycemic clamps, respectively. LCN2KO mice and WT mice in vivo, and in vitro HepG2 cells were co-transfected with adenoviral FoxO1-siRNA (Ad-FoxO1-siRNA) or adenovirus expressing constitutively active form of AMPK (Ad-CA-AMPK), or dominant negative adenovirus AMPK (Ad-DN-AMPK), the relative mRNA and protein levels of two key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) were measured. Results Improved insulin sensitivity and inhibited gluconeogenesis in the LCN2KO mice were confirmed by pyruvate tolerance tests and hyperinsulinemic-euglycemic clamps. Nuclear FoxO1 and its downstream genes PEECK and G6P were decreased in the livers of the LCN2KO mice, and AMPK activity was stimulated and directly phosphorylated FoxO1. In vitro, AMPK activity was inhibited in HepG2 cells overexpressing LCN2 leading to a decrease in phosphorylated FoxO1 and an increase in nuclear FoxO1. Conclusion The present study demonstrates that LCN2 regulates insulin sensitivity and glucose metabolism through inhibiting AMPK activity, and regulating FoxO1 and its downstream genes PEPCK/G6P, which regulate hepatic gluconeogenesis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Testing the sleep hygiene recommendation against nighttime exercise

xlomafota.13 shared this article with you from Inoreader Testing the sleep hygiene recommendation against nighttime exercise Via Latest Results for Sleep and Breathing Abstract Purpose Experts have recommended exercise for improved sleep, but often with the caveat that one should avoid nighttime exercise. The aim of this study was to challenge this recommendation in a sample who might be most prone to sleep impairment after nighttime exercise. The secondary aims were to assess whether or not post-treatment sleep was correlated with anxiolytic effects or downregulation of body temperature. Methods Twelve sedentary adults with insomnia completed two treatments (separated by 2–5 days) in counterbalanced order: (1) 30 min of moderate treadmill exercise (60–70% maximum heart rate) + 15 min of moderate resistance exercise and (2) a control treatment (reading). Each treatment was completed 2 h before bedtime and followed by a 10-min shower, a light snack, 8 h of polysomnographic recording, and a sleep questionnaire. State anxiety was assessed before and 30 min after each treatment and 10 min before bedtime. Body temperature was assessed from pre-exercise to wake time. Results No significant treatment differences in sleep were found, and Hedges g paired comparisons indicated small effect sizes; however, two participants had severely disturbed objective sleep following exercise. Significant correlations were found between change in state anxiety from pre-exercise to bedtime and TST (r = 0.69, p = 0.03). Stage 1 (r = 0.67, p = 0.03), WASO (r = 0.69, p = 0.03), and sleep efficiency (r = 0.66, p = 0.02). No significant correlations were found of sleep with temperature decline. Conclusions Profound sleep disturbance after exercise in some participants, and no marked sleep improvement in the others, provides some support for caution regarding late-night exercise for sedentary individuals with insomnia. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells

xlomafota.13 shared this article with you from Inoreader CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells Via Latest Results for Human Cell Abstract CBX8 is the core component of the PCG family protein PRC1 complex. It is overexpressed in many solid tumors and plays an important role in the prognosis and biological behaviors of tumors such as occurrence, development, invasion, and metastasis. However, exploration of the role and molecular mechanism of CBX8 in tumors is still in its infancy. Our study found that the down-regulation of CBX8 expression by RNA interference induced differential expression of several microRNAs in human colon cancer cells. The 5 most differentially expressed miRNA precursors (pre-miRNA) (hsa-miR-363-3p, hsa-miR-378a-3p, hsa-miR-371b-3p, hsa-miR-361-3p, and hsa-miR-576-3p) share a common motif sequence: ARAAAKUGCMC. We selected miR-378a-3p and further revealed that the negative regulation of miRNA expression by CBX8 mainly occurs in the processing of pre-miRNA to mature miRNA. CBX8 uses its own RNA-binding domain to interact with pre-miRNA, and is dependent on its own nuclear localiz ation characteristics to limit nucleoplasmic transport of pre-miRNA. Changing the characteristic sequence of pre-miRNA or mutating the RNA-binding domain and nuclear localization signal of CBX8 can effectively weaken the regulation of miR-378a-3p expression by CBX8. However, our experimental results showed that miR-378a-3p inhibited the malignant expression of human colon cancer cells by targeting PDIA4, resulting in increased activity of caspases-3 and -7. In summary, our study suggests that CBX8 acts as an independent RNA-binding protein to regulate miRNA expression. Simultaneously, this study shows the correlation between the CBX8/miR-378a-3p/PDIA4 pathway and the malignant biological properties of colorectal cancer, suggesting this proposed pathway as a possible therapeutic target for human cancers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

StarD13 differentially regulates migration and invasion in prostate cancer cells

xlomafota.13 shared this article with you from Inoreader StarD13 differentially regulates migration and invasion in prostate cancer cells Via Latest Results for Human Cell Abstract Prostate cancer is the second most commonly diagnosed cancer in men and one of the main leading causes of cancer deaths among men worldwide. Rapid uncontrolled growth and the ability to metastasize to other sites are key hallmarks in cancer development and progression. The Rho family of GTPases and its activators the GTPase-activating proteins (GAPs) are required for regulating cancer cell proliferation and migration. StarD13 is a GAP for Rho GTPases, specifically for RhoA and Cdc42. We have previously shown that StarD13 acts as a tumor suppressor in astrocytoma as well as breast and colorectal cancer. In this study, we performed a functional comparative analysis of StarD13 targets/and or interacting molecules to understand the general role that StarD13 plays in cancers. Our data highlight the importance of StarD13 in modulating several hallmarks of cancer. Findings from database mining and immunohistochemistry revealed that StarD13 is underexpressed in prostate cancers, in addition knocking down Stard13 increased cancer cell proliferation, consistent with its role as a tumor suppressor. Stard13 depletion, however, led to an increase in cell adhesion, which inhibited 2D cell migration. Most interestingly, StarD13 depletion increases invasion and matrix degradation, at least in part, through its regulation of Cdc42. Altogether, the data presented suggest that StarD13 acts as a tumor suppressor inhibiting prostate cancer cell invasion. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of prolonged clamping of the portal vein during liver transplantation in infants with biliary atresia: renewed interest in a long-standing issue

xlomafota.13 shared this article with you from Inoreader Impact of prolonged clamping of the portal vein during liver transplantation in infants with biliary atresia: renewed interest in a long-standing issue Via Latest Results for Surgery Today Abstract Purpose Various approaches to portal vein (PV) reconstruction have been described; however, there is still scope to improve the safety and efficiency of how PV anastomosis is performed in infants. Methods We analyzed, retrospectively, the predictive factors for PV reanastomosis during living donor liver transplantation (LDLT) in 117 infants (< 1 year old) with biliary atresia (BA). Results Twenty-six infants required PV reanastomosis because of intraoperative PV thrombosis in 21 and insufficient PV flow in 5. Univariate analysis identified multiple previous laparotomies and a prolonged anhepatic phase (AHP) as significant risk factors for repeated PV anastomosis. The AHP cutoff value for identifying patients requiring PV reanastomosis was 134 min. Multivariate analysis revealed prolonged AHP > 134 min (odds ratio, 15.98; 95% confidence interval, 5.05–50.6; P < 0.001) as an independent risk factor for repeated PV anastomosis. The plasma D-dimer and fibrinogen degradation product concentration just after reperfusion were significantly higher in patients requiring PV reanastomosis (P < 0.001). Patients requiring reanastomosis of the PV had a higher incidence of PV complications after LDLT than those who did not need PV reanastomosis (P = 0.01). Conclusion Attempting to minimize the AHP is indispensable for successful LDLT in infants with BA. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

What is the recommended procedure for recurrent rectal prolapse?

xlomafota.13 shared this article with you from Inoreader What is the recommended procedure for recurrent rectal prolapse? A retrospective cohort study in a single Japanese institution Via Latest Results for Surgery Today Abstract Purpose The choice of surgical procedure for rectal prolapse (RP) is challenging because of the high recurrence and morbidity rates. We aimed to clarify whether laparoscopic suture rectopexy (lap-rectopexy) is suitable for Japanese patients with recurrent RP. Methods We retrospectively evaluated 77 recurrent RP patients who had been treated on average 1.5 times between June 2008 and April 2016. Forty-one patients underwent lap-rectopexy and 36 underwent perineal procedures. We compared surgical outcomes and recurrence rate following surgery between the two groups. The multivariable logistic regression analysis was performed to determine risk factors of recurrent RP. Results In patients' characteristics, significant differences were observed in the type of anesthesia (p < 0.01) and length of recurrent RP (p = 0.030). The mean operative time was significantly longer in the lap-rectopexy group (p < 0.001). Blood loss, length of hospitalization, and postoperative complications were similar. The recurrence rate was significantly lower in the lap-rectopexy group (17.1% vs. 38.9%, p = 0.032). Multivariate analysis showed that only the laparoscopic approach was significantly associated with a low recurrence following surgery (odds ratio 0.273, 95% CI − 2.568 to − 0.032). Conclusion Lap-rectopexy is recommended for recurrent RP because its low recurrence rate and safety profile are similar to those of perineal procedures. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Is open abdominal management useful in nontrauma emergency surgery for older adults? A single-center retrospective study

xlomafota.13 shared this article with you from Inoreader Is open abdominal management useful in nontrauma emergency surgery for older adults? A single-center retrospective study Via Latest Results for Surgery Today Abstract Purpose Open abdominal management (OAM) is being adopted increasingly frequently in nontrauma patients. This study assessed the effectiveness of OAM in nontrauma older adults. Methods We retrospectively reviewed all adults who underwent nontrauma emergency laparotomy requiring postoperative intensive care unit (ICU) management between September 2012 and August 2017 at our hospital. Patients ≥ 80 years old, who underwent OAM, were compared with those < 80 years old. The primary outcome was the 90-day mortality. Secondary outcomes were the 30-day mortality, unplanned relaparotomy, and the ICU length of stay (LOS). Results The OAM group comprised 58 patients, including 27 who were ≥ 80 years old. The patients ≥ 80 years old in the OAM group had a significantly higher 90-day mortality rate (33% vs. 10%; p = 0.027) than those < 80 years old. There were no significant differences in the 30-day mortality rate, patients' unplanned relaparotomy rate, or ICU LOS between the patients ≥ 80 years old and those < 80 in the OAM group. Conclusions Older adults who underwent OAM had a significantly higher mortality rate than younger patients. However, the OAM strategy for older nontrauma patients may still be useful and reasonable considering the severe condition of these patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Incidence of anastomotic stricture after hepaticojejunostomy with continuous sutures in patients who underwent laparoscopic pancreaticoduodenectomy

xlomafota.13 shared this article with you from Inoreader Incidence of anastomotic stricture after hepaticojejunostomy with continuous sutures in patients who underwent laparoscopic pancreaticoduodenectomy Via Latest Results for Surgery Today Abstract Purpose Laparoscopic hepatojejunostomy (HJ) with continuous sutures is commonly performed in laparoscopic pancreaticoduodenectomy (LPD). This study aimed to investigate the long-term surgical outcomes of HJ in LPD. Methods We retrospectively evaluated 103 consecutive patients who underwent pancreaticoduodenectomy via laparoscopic HJ with continuous suturing using multifilament (n = 48) or monofilament-absorbable sutures (n = 47). Results During follow-up, anastomotic stricture of HJ was identified in 8 (7.8%) patients via balloon enteroscopy-assisted cholangiography. The median time from surgery to confirmation of stricture formation was 7.6 months (range 3.6–19.4). The incidence of HJ stricture was significantly higher in patients with a thin bile duct (diameter < 6.0 mm) than in those with a thick bile duct (diameter ≥ 6.0 mm) [7/27 (25.9%) vs. 1/76 (1.3%), respectively, p < 0.01]. Similarly, it was significantly higher in the monofilament group than in the multifilament group [7/54 (13.0%) vs. 1/49 (2.0%), respectively, p = 0.04]. In the monofilament suture group, 37.5% of patients with thin bile ducts developed stricture after HJ. A multivariate analysis revealed that a thin bile duct was an independent risk factor for HJ stricture (hazard ratio: 25.3, p < 0.01). Conclusions Stricture after laparoscopic HJ using continuous sutures frequently occurs in patients with thin bile ducts, particularly when monofilament-absorbable suture is used. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.