Evaluation of demarcation line after epithelium-off iontophoresis corneal collagen cross-linking for progressive keratoconus

The aim of the study was to visualize and evaluate the characteristics and depth of the demarcation line with anterior segment optical coherence tomography (AS-OCT) after epithelium-off iontophoresis corneal collagen cross-linking (epi-off I-CXL). In this prospective, consecutive, single center study 18 eyes of 18 patients with keratoconus were involved. One month after epi-off I-CXL, all the patients underwent an AS-OCT scan to search for a demarcation line and its characteristics. The corneal stromal demarcation line was identified in all the eyes. Mean depth of the corneal stromal demarcation line was 261.8 ± 46.7 μm (range: 184 to 362 μm), at 56.7 ± 12% corneal depth. In conclusion, epi-off I-CXL determines a demarcation line that can be visualized with AS-OCT, which seems clearly distinguishable and similar to that created in standard CXL

Role of glucose-lowering medications in erectile dysfunction

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting

The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor

Reactive oxygen species (ROS) are highly reactive chemical species containing oxygen, controlled by both enzymatic and nonenzymatic antioxidant defense systems. In the heart, ROS play an important role in cell homeostasis, by modulating cell proliferation, differentiation, and excitation-contraction coupling. Oxidative stress occurs when ROS production exceeds the buffering capacity of the antioxidant defense systems, leading to cellular and molecular abnormalities, ultimately resulting in cardiac dysfunction. In this review, we will discuss the physiological sources of ROS in the heart, the mechanisms of oxidative stress-related myocardial injury, and the implications of experimental studies and clinical trials with antioxidant therapies in cardiovascular diseases

Refractive surgical correction and treatment of keratoconus

Keratoconus is an ectatic corneal disorder that causes severe vision loss. Surgical options allow us to correct, partially or totally, the induced refractive error. Intracorneal ring segments (ICRS) implantation represents a minimally invasive surgical option that improves visual acuity, with a high success rate and a low overall complication rate. Corneal allogenic ICRS consists of ring segments derived from allogenic eye bank-processed donor corneas. Selective topography-guided transepithelial photorefractive or phototherapeutic keratectomy combined with CXL is another way in selected cases to improve spectacles corrected distance visual acuity. The microphotoablative remodeling of the central corneal profile is generally planned by optimizing the optical zones and minimizing tissue consumption. Phakic intraocular lens (PIOL) implant is considered in patients with stable disease and acceptable anatomical requirements. The two types of pIOLs, depending on their implantation inside the eye, are anterior chamber-pIOLs, which fixate to the anterior surface of the iris by using a polymethomethacrolate claw at the two haptics, and posterior chamber-pIOLs. In patients with both cataracts and keratoconus, the correct IOL power is difficult to obtain due to the irregular corneal shape and K values. Toric IOL is recommended, but carefully judging the topography and the possible need of subsequent keratoplasties

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

Major vascular traumas to the neck, upper limbs, and chest: Clinical presentation, diagnostic approach, and management strategies

Major vascular traumas to the neck, upper limbs, and chest may arise from penetrating and/or blunt mechanisms, resulting in a range of clinical scenarios. Lesions to the carotid arteries may also lead to neurologic complications, such as stroke. The increasing use of invasive arterial access for diagnostic and/or interventional purposes has increased the rate of iatrogenic injuries, which usually occur in older and hospitalized patients. Bleeding control and restoration of perfusion represent the two main goals of treatment for vascular traumatic lesions. Open surgery still represents the gold standard for most lesions, although endovascular approaches have increasingly emerged as feasible and effective options, particularly for management of subclavian and aortic injuries. In addition to advanced imaging (including ultrasound, contrast-enhanced cross-sectional imaging, and arteriography) and life support measures, multidisciplinary care is required, particularly in the setting of concomitant injuries to the bones, soft tissues, or other vital organs. Modern vascular surgeons should be familiar with the whole armamentarium of open and endovascular techniques needed to manage major vascular traumas safely and promptly

Hepatobiliary disease resection in patients with advanced epithelial ovarian cancer: prognostic role and optimal cytoreduction

Objective: The purpose of this study was to evaluate the feasibility and safety in terms of prognostic significance and perioperative morbidity and mortality of cytoreduction in patients affected by advance ovarian cancer and hepato-biliary metastasis. Methods: Patients with a least one hepatobiliary metastasis who have undergone surgical treatment with curative intent of were considered for the study. Perioperative complications were evaluated and graded with Accordion severity Classification. Five-year PFS and OS were estimated using the Kaplan–Meier curve. Results: Sixty-seven (20.9%) patients had at least one metastasis to the liver, biliary tract, or porta hepatis. Forty-four (65.7%) and 23 (34.3%) patients underwent respectively high and intermediate complexity surgery according. Complete cytoreduction was achieved in 48 (71.6%) patients with hepato-biliary disease. In two patients (2.9%) severe complications related to hepatobiliary surgery were reported. The median PFS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) was 19 months [95% confidence interval (CI) 16.2–21.8] and 8 months (95% CI 6.1–9.9). The median OS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) 45 months (95% CI 21.2–68.8 months) and 23 months (95% CI 13.9–32.03). Conclusions: Hepatobiliary involvement is often associated with high tumor load and could require high complex multivisceral surgery. In selected patients complete cytoreduction could offer survival benefits. Morbidity related to hepatobiliary procedures is acceptable. Careful evaluation of patients and multidisciplinary approach in referral centers is mandatory

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

Penumbra indigo percutaneous aspiration thrombectomy system in the treatment of aortic endograft iliac limb occlusion: results from an Italian Multicentre Registry

Objective: This study aimed to evaluate the safety and effectiveness of the Penumbra Indigo percutaneous aspiration thrombectomy (PAT) system in the clinical presentation of iliac limb occlusion (ILO) after endovascular aortic repair (EVAR).Methods: A retrospective, observational, multicentre study conducted in eight Italian vascular centres. Consecutive patients presenting with ILO after EVAR were eligible. To assess vessel revascularisation, Thrombo-aspiration In Peripheral Ischaemia (TIPI) classification (score 0-3) was used at presentation (t1), after PAT (t2), and after adjunctive procedures (t3). Successful revascularisation was considered TIPI 2-3 (near complete or complete). Primary intra-operative outcomes were technical success (TS) of Indigo PAT and combined TS of PAT associated with adjunctive procedures when needed. Primary follow up outcomes were safety and effectiveness at one, six, and 12 months.Results: From September 2019 to December 2021, there were 48 ILO and 17 patients (35%) [median age 75 years, IQR 71, 83 years; male, 14 (82%); urgent, 8 (47%)] were treated and enrolled. The median time after primary EVAR was 24 months (IQR 0, 42 months). The median clot age from ILO diagnosis to PAT was three days (IQR 1, 12 days). Ten patients (59%) presented with limb threatening ischaemia. At t1, TIPI 0 and 1 was present in 13 (76%) and four (24%) cases, respectively. At t2, primary TS (TIPI 2-3) was achieved in 14 cases (82%) after Indigo PAT (p < .001). Fifteen patients (88%) required adjunctive procedures (14 re-linings, one surgical patch angioplasty). At t3, combined TS was achieved in 16 cases (94%). Intra-operative complication included one (6%) distal embolisation, treated successfully. The 30 day mortality was one case (6%) due to pneumonia. At one, six, and 12 months, clinical success was 100% without ILO recurrence. The median follow up was 23 months (IQR 11, 41 months): at 18 months, survival and freedom from re-intervention were 91 + 8% and 90 + 9%, respectively.Conclusion: This study reports for the first time the efficacy and safety of Penumbra Indigo PAT for ILO after EVAR, with promising technical and clinical success up to one year

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy