Angioleiomyoma of the knee: An uncommon cause of leg pain. A systematic review of the literature

Abstract Objective Angioleiomyoma is a rare benign painful soft tissue tumor, whose knee location is rare. Due its rarity, and not characteristic aspect on MRI the preoperative diagnosis is difficult. Methods We performed a systematic review of the literature, including a case of venous type angioleiomyoma that we have recently managed. Results A total of 24 published papers with 30 cases (including our illustrative case) were identified and included in our review. The mean patient age was 42.3 years (range18-63). The average size of the lesion was 17.8 mm. The presenting symptom was leg pain in 90% of cases. On magnetic resonance imaging (MRI), the lesion appeared isointense in T1 in 80% of cases and hyperintense on T2 in 90% of cases. Avid homogeneous enhancement after gadolinium administration was detected in 94% of cases. All patients underwent surgery and total resection was achieved in 100% of cases. No recurrence was observed after a mean follow-up of 19.5 months. Conclusion Angioleiomyoma occurs rarely in the knee and generally is associated with localized or radiating pain. The preoperative diagnosis is difficult also after completion of MRI study and requires high index of suspicion. Angioleiomyoma widens the spectrum of soft tissue lesions of the extremities and should be included in the differential diagnosis of lesions in this area

Bladder tissue passive response to monotonic and cyclic loading

The fundamental passive mechanical properties of the bladder need to be known in order to design the most appropriate long-term surgical repair procedures and develop materials for bladder reconstruction. This study has focused on the bladder tissue viscoelastic behavior, providing a comprehensive analysis of the effects of fibers orientation, strain rate and loading history. Whole bladders harvested from one year old fat pigs (160 kg approximate weight) were dissected along the apex-to-base direction and samples were isolated from the lateral region of the wall, as well as along apex-to-base and transverse directions. Uniaxial monotonic (stress relaxation) and cyclic tests at different frequencies have been performed with the Bose Electroforce® 3200. Normalized stress relaxation functions have been interpolated using a second-order exponential series and loading and unloading stress-strain curves have been interpolated with a non-linear elastic model. The passive mechanical behavior of bladder tissue was shown to be heavily influenced by frequency and loading history, both in monotonic and cyclic tests. The anisotropy of the tissue was evident in monotonic and in cyclic tests as well, especially in tests performed on an exercised tissue and at high frequencies. In contrast, transverse and apex-to-base samples demonstrated an analogous relaxation behavior

Decipher the glioblastoma microenvironment: The first milestone for new groundbreaking therapeutic strategies

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies

Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies

Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clini-cians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs

Irisin and incretin hormones: Similarities, differences, and implications in type 2 diabetes and obesity

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Irisin, a myokine released in response to a high-fat diet and exercise, enhances GSIS. Similar to GLP-1, irisin augments insulin biosynthesis and promotes accrual of β-cell functional mass. In addition, irisin and GLP-1 share comparable pleiotropic effects and activate similar intracellular pathways. The insulinotropic and extra-pancreatic effects of GLP-1 are reduced in type 2 diabetes (T2D) patients but preserved at pharmacological doses. GLP-1 receptor agonists (GLP-1RAs) are therefore among the most widely used antidiabetes drugs, also considered for their cardiovascular benefits and ability to promote weight loss. Irisin levels are lower in T2D patients, and in diabetic and/or obese animal models irisin administration improves glycemic control and promotes weight loss. Interestingly, recent evidence suggests that both GLP-1 and irisin are also synthesized within the pancreatic islets, in α-and β-cells, respectively. This review aims to describe the similarities between GLP-1 and irisin and to propose a new potential axis–involving the gut, muscle, and endocrine pancreas that controls energy homeostasis

Impaired leptin signalling in obesity: Is leptin a new thermolipokine?

Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies

Effects of extra virgin olive oil polyphenols on beta-cell function and survival

Extra virgin olive oil (EVOO) is a major component of the Mediterranean diet and is appreciated worldwide because of its nutritional benefits in metabolic diseases, including type 2 diabetes (T2D). EVOO contains significant amounts of secondary metabolites, such as phenolic compounds (PCs), that may positively influence the metabolic status. In this study, we investigated for the first time the effects of several PCs on beta-cell function and survival. To this aim, INS-1E cells were exposed to 10 μM of the main EVOO PCs for up to 24 h. Under these conditions, survival, insulin biosynthesis, glucose-stimulated insulin secretion (GSIS), and intracellular signaling activation (protein kinase B (AKT) and cAMP response element-binding protein (CREB)) were evaluated. Hydroxytyrosol, tyrosol, and apigenin augmented beta-cell proliferation and insulin biosynthesis, and apigenin and luteolin enhanced the GSIS. Conversely, vanillic acid and vanillin were pro-apoptotic for beta-cells, even if they increased the GSIS. In addition, oleuropein, p-coumaric, ferulic and sinapic acids significantly worsened the GSIS. Finally, a mixture of hydroxytyrosol, tyrosol, and apigenin promoted the GSIS in human pancreatic islets. Apigenin was the most effective compound and was also able to activate beneficial intracellular signaling. In conclusion, this study shows that hydroxytyrosol, tyrosol, and apigenin foster beta-cells’ health, suggesting that EVOO or supplements enriched with these compounds may improve insulin secretion and promote glycemic control in T2D patients

Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

Accumulating evidence supports the early use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose transporter-2 inhibitors (SGLT-2is) for the treatment of type 2 diabetes. Indeed, these compounds exert numerous pleiotropic actions that favorably affect metabolism and diabetes comorbidities, showing an additional effect beyond glucose control. Although a substantial amount of knowledge has been generated regarding the mechanism of action of both drug classes, much remains to be understood. Growth hormone (GH) is an important driver for multiple endocrine responses involving changes in glucose and lipid metabolism, and affects several tissues and organs (e.g., bone, heart). It acts directly on several target tissues, including skeletal muscle and bone, but several effects are mediated indirectly by circulating (liver-derived) or locally produced IGF-1. In consideration of the multiple metabolic and cardiovascular effects seen in subjects treated with GLP-1RAs and SGLT-2is (e.g., reduction of hyperglycemia, weight loss, free/fat mass and bone remodeling, anti-atherosclerosis, natriuresis), it is reasonable to speculate that GH and IGF-1 may play a about a relevant role in this context. This narrative mini-review aims to describe the involvement of the GH/IGF-1/IGF-1R axis in either mediating or responding to the effects of each of the two drug classes

Prevalence and predictors of atypical histology in endometrial polyps removed by hysteroscopy: a secondary analysis from the SICMIG hysteroscopy trial

The aim of this study is to assess the prevalence of atypical hyperplasia (AH) and endometrial cancer (EC) within endometrial polyps (EPs) removed by hysteroscopy

Comparison of prasugrel and clopidogrel used as antiplatelet medication for endovascular treatment of unruptured intracranial aneurysms: A meta-analysis

BACKGROUND: Clopidogrel is routinely used to decrease ischemic complications during neurointerventional procedures. However, the efficacy may be limited by antiplatelet resistance. PURPOSE: Our aim was to analyze the efficacy of prasugrel compared with clopidogrel in the cerebrovascular field. DATA SOURCES: A systematic search of 2 large databases was performed for studies published from 2000 to 2018. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting treatment-related outcomes of patients undergoing neurointerventional procedures under prasugrel, and studies comparing prasugrel and clopidogrel. DATA ANALYSIS: Random-effects meta-analysis was used to pool the overall rate of complications, ischemic and hemorrhagic events, and influence of the dose of prasugrel. DATA SYNTHESIS: In the 7 included studies, 682 and 672 unruptured intracranial aneurysms were treated under prasugrel (cases) and clopidogrel (controls), respectively. Low-dose (20 mg/5 mg; loading and maintenance doses) prasugrel compared with the standard dose of clopidogrel (300 mg/75 mg) showed a significant reduction in the complication rate (OR 0.36; 95% CI, 0.17–74, P .006; I2 0%). Overall, the ischemic complication rate was significantly higher in the clopidogrel group (40/672 6%; 95% CI, 3%–13%; I2 83% versus 16/682 2%; 95% CI, 1%–5%; I2 73%; P .03). Low and high loading doses of prasugrel were associated with 0.6% (5/535; 95% CI, 0.1%–1.6%; I2 0%) and 9.3% (13/147; 95% CI, 0.2%–18%; I2 60%) intraperiprocedural hemorrhages, respectively (P .001), whereas low and high maintenance doses of prasugrel were associated with 0% (0/433) and 0.9% (2/249; 95% CI, 0.3%–2%; I2 0%) delayed hemorrhagic events, respectively (P .001). LIMITATIONS: Retrospective series and heterogeneous endovascular treatments were limitations. CONCLUSIONS: In our study, low-dose prasugrel compared with clopidogrel premedication was associated with an effective reduction of the ischemic events with an acceptable rate of hemorrhagic complications