Influence of allergic status and nasal polyposis on long-term Benralizumab response in eosinophilic severe asthma.

Objective: It is unclear whether Benralizumab effectiveness in severe eosinophilic asthma can be influenced by nasal polyposis (NP) or allergic status associations. We evaluated whether Benralizumab long-term efficacy in asthma outcomes could be different in subjects with atopy (SAEA) compared to the effectiveness in those without allergies (SNAEA) and in individuals with NP compared to those without NP. Methods: This observational retrospective study considered 95 consecutive patients divided into allergic (SAEA; n:65[68.4%]; skin prick tests positive [SPT] and/or IgE values ≥100 UI/mL), and non-allergic (SNAEA; n:30[31.6%], SPT negative and normal IgE levels<100 UI/mL). Overall population was also divided into two groups according to NP presence (NP+:39[41%] and NP-:56[59%]). Benralizumab treatment mean was19.7±7.2 months (range 12-35). Results: No differences in Benralizumab effectiveness were found in asthma outcomes in patients with/without NP. SNOT-22 improvement was higher in NP+ (-22±24) compared to NP- groups (6.33±15.5;p=0.055). FEV1 (16.33±19.22%), ACT(7.45±3.95) increases and frequency of SABA use (3.37±4.99) reduction were higher in SAEA compared to what obtained in non-allergic subjects (FEV1:8.15±15.6%,p=0.043; ACT:4.89±3.57,p=0.005; SABA use:-1.16±1.84;p=0.015). 93.8% of SAEA patients whereas only 72.2% of SNAEA individuals reduced OC doses at least half after Benralizumab (p=0.035). These results were partially confirmed by linear regression models showing associations between allergic status and FEV1, ACT and SABA use changes (ß=8.37;p=0.048, ß=2.056;p=0.033 and ß=-2.184;p=0.042 respectively). Conclusion: Benralizumab effectiveness in asthma appears to be independent of NP presence. The allergic eosinophilic disease, compared to just eosinophilic asthma, may be a more severe phenotype. Benralizumab may have greater efficacy in SAEA on some outcomes.

Severe asthma and long-term Benralizumab effectiveness in real-life.

OBJECTIVE: Long-term efficacy of Benralizumab in real life is not clearly known. We assessed the long-term effectiveness persistence to anti-IL-5R treatment in a group of severe eosinophilic asthmatics. PATIENTS AND METHODS: We retrospectively analyzed 95 individuals affected by severe asthma (36 males  ̶ 37.9%; mean age 58.1 ± 12.2) treated with Benralizumab (mean time 19.7 ± 7.2 months, range 12-35). Outcomes were evaluated at the beginning and at the end of patients' treatment periods. RESULTS: Mean baseline blood eosinophils were 897.5 ± 720.1 cells/µL (11 ± 5.6%) decreasing to 7.4 ± 20.6 cells/µL (0.97 ± 0.26%; p < 0.0001) after Benralizumab. FENO likewise decreased from 63.9 ± 68.4 to 28.4 ± 23.6 ppb, while FEV1% significantly improved (p < 0.0001). Mean FEF25-75 also increased from 45.8 ± 24.6% to 60.7 ± 24.6%, whereas RAW dropped from 202.15 ± 109.6% to 135.2 ± 54.75% (p < 0.0001). Also, lung volumes greatly decreased. ACT/ACQ significantly improved, while exacerbations number fell from 4.1 ± 2.4, before anti-IL-5R, to 0.33 ± 0.77, after treatment (p < 0.0001). Rhinitis severity levels and SNOT-22 also changed favorably. Patients that took long-term OCs were 71.6% before treatment, decreasing to 23.2% after Benralizumab (p < 0.0001), with an OCs dose reduction from 14.8 ± 8.9 to 1.45 ± 2.8 mg/day (p < 0.0001). 51.6% of subjects used SABA as needed before Benralizumab, falling to 4.2% after treatment. Several patients showed a reduction of ICS doses, SABA use and maintenance therapy step-down. Clinical/biological response with anti-IL-5R remained constant or even improved in terms of exacerbations or maintenance therapy reductions over time. On the contrary, FEF25-75% improvement slowed down in the long-term. No relationship was found between baseline blood eosinophil number and therapeutic response. CONCLUSIONS: Long-term Benralizumab effectiveness persistence in all outcomes in real life was confirmed.

Data of postoperative complications related to fibrinogen-to-albumin ratio in pancreatic resections.

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications.

Risk factors for diabetic foot ulcers: an Albanian retrospective study of inpatients with type 2 diabetes.

OBJECTIVE: The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D. PATIENTS AND METHODS: We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring ≥14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes-related complications at the time of hospital admission were evaluated through a retrospective chart review. RESULTS: Mean age of study participants was 54.8±10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR=0.62; p=0.007], HDL-cholesterol [OR=0.00; p<0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p<0.0001], fasting plasma glucose (FPG) [OR=1.06; p<0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age <55 years [OR=0.12; p=0.05] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p<0.0001), ulcer surface area (r=0.50; p<0.0001), ulcer grade (r=0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p<0.0001), and metformin therapy alone (r=0.72; p<0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p<0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (>100 mg/dl) and mean HbA1c values >7.5%. Moreover, in DFU group HbA1c values were markedly elevated (≥10%) particularly in patients with a grade 3 ulcer and an ulcer surface area ≥4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN. CONCLUSIONS: The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D.

The importance of subcapsular anesthesia in the anesthesiological management for thyroid radiofrequency ablation.

Radiofrequency ablation is a minimally invasive procedure alternative to surgery to treat benign thyroid nodules causing compressive symptoms. Tolerability of this procedure, aimed at treatment of benign conditions, is fundamental. In this study, we evaluated if local anesthesia should be enough to reduce both hospital costs and sedation-related risks for the patient, avoiding deep sedation and presence of the anesthesiologist. From July 2017 to August 2018, 14 consecutive patients (mean age 60.1 years) were treated and divided in two groups: Group A (7 patients) underwent systemic sedoanalgesia (intravenous remifentanil/fentanyl ± intravenous midazolam ± intravenous acetaminophen/nonsteroidal anti-inflammatory drugs) + subcutaneous anesthesia (lidocaine), with anesthesiologist. Group B (7 patients) underwent mild systemic sedoanalgesia (oral solution morphine sulfate + intravenous midazolam + intravenous acetaminophen) + both subcutaneous and subcapsular anesthesia (mepivacaine + bupivacaine), without anesthesiologist. Tolerability, sedation grade (Ramsay scale), total opioid dose, complications, and results at 12 months were analyzed and compared. Mean tolerability was 9.4 in group A and 8.9 in group B (p: 0.786). Mean sedation grade was 3.86 in group A and 2.71 in group B (p: 0.016). Mean total opioid dose was 70.9 mg in group A and 10 mg in group B (p:0.00015). No complications were observed. At 12 months, mean volume reduction was 56.1% in the group A and 60% in the group B. In thyroid radiofrequency ablation, subcapsular anesthesia can decrease both total opioid dose and level of patient's sedation without significant differences in tolerability, allowing to perform ablation without the anesthesiologist.

Localised amyloidosis of the bladder: A rare mimic of urinary tract malignancy (case report and literature review).

INTRODUCTION: Localised amyloidosis of the urinary tract is rare and often presents with haematuria. PRESENTATION OF CASE: A 59 year old male presented with recurrent episodes of frank haematuria exacerbated by anticoagulation after a minor stroke. He had a background of hypertension, hypercholesterolaemia, and Parkinson's disease. Initial investigations did not reveal a cause, but eventual cystoscopic biopsy showed bladder mucosa expanded by deposits of amorphous, pale, eosinophilic, proteinaceous material and immunohistochemical staining revealed the presence of amyloid deposition. Workup for systemic amyloidosis was negative. A diagnosis of primary localised amyloidosis of the bladder was made. Trans-urethral resection was performed and annual cystoscopic surveillance was commenced. He was followed up for 11 years without recurrence. DISCUSSION: A comprehensive literature review revealed 349 published cases of localised amyloidosis of the urinary tract, with a median age of 57 (interquartile range 49-69), and a male preponderance (1.5 to 1). Painless visible haematuria (65%) was the most frequent presenting complaint and the bladder was the most common site of involvement (71%). Transurethral resection was the most common form of management (42%) but a proportion of patients underwent more radical surgery (nephroureterectomy/nephrectomy 9%, cystectomy 1%). Median follow up was 33 months (interquartile range 12-108) and 35% of patients had recurrent disease. This patient represents a typical case of localised amyloidosis of the urinary tract. CONCLUSION: This is the most up to date review of the literature describing localised amyloidosis of the urinary tract. The disease is rare, but salient to the urologist as it invariably mimics urinary tract malignancy.

Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency.

BACKGROUND: Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of conventional glucocorticoids (GCs) vs. DR-HC and of high vs. low doses of GCs, after 48 months of observation. METHODS: We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4.2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained. RESULTS: After 48 months, patients in group A had a significant increase from baseline in BMI (P < 0.001), waist circumference (P = 0.001), systolic blood pressure (P = 0.001), LDL cholesterol (P = 0.018), HbA1c (P = 0.020) and FRS (P = 0.002). By contrast, patients in group B had a significant decrease in BMI (P = 0.002), waist circumference (P = 0.015), diastolic blood pressure (P = 0.031), total (P = 0.006) and LDL cholesterol (P = 0.005), HbA1c (P < 0.001) and FRS (P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed. CONCLUSIONS: DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.

Transmucosal oxygen tension of the clitoris: a new parameter for future investigations of the sexual, metabolic, and cardiovascular health of women.

BACKGROUND: Several studies suggested that abnormalities in tissue perfusion of external genitalia and vagina can lead to female sexual dysfunctions (FSDs) and can be associated to metabolic and cardiovascular risk factors. However, there are some technical difficulties in assessing these abnormalities. The measurement of oxygen partial pressure is a noninvasive method to measure oxygen partial pressure (pO2) at the skin surface to assess tissue perfusion. The aim of this study was to evaluate whether transmucosal oxygen tension (TmPO2) can be measured at the mucosal surface of clitoris and whether the measurements are reliable. METHODS: TmPO2 was measured in six young healthy women by using a device to measure transcutaneous pO2 on the skin and by choosing a small sensor, usually used for newborns. The identical procedure for the detection of pO2 at the skin surface was used. RESULTS: The mean value of TmPO2 was 42.3 mmHg (range: 24.1-53.4 mmHg). All the trend curves of the TmPO2 showed the same behavior: after a stabilization time, there was a stable pO2 (plateau phase) that corresponds to the TmPO2 of the clitoris. These curves had a similar trend to those recorded at the skin surface. CONCLUSIONS: TmPO2 can be easily measured at the mucosal surface of clitoris. Large epidemiological studies in healthy and unhealthy women and in women with FSD are needed to establish both the normal range of TmPO2 and the meaning that different values of TmPO2 can have on sexual and general health of the women.

Long-term functional outcomes after replacement of the esophagus with gastric, colonic, or jejunal conduits: a systematic literature review.

It is generally recognized that in patients with an intact stomach diagnosed with esophageal cancer, gastric tubulization and pull-up shall always be the preferred technique for reconstruction after an esophageal resection. However, in cases with extensive gastroesophageal junction (GEJ) cancer with aboral spread and after previous gastric surgery, alternative methods for reconstruction have to be pursued. Moreover, in benign cases as well as in those with early neoplastic lesions of the esophagus and the GEJ that are associated with long survival, it is basically unclear which conduit should be recommended. The aim of this study is to determine the long-term functional outcomes of different conduits used for esophageal replacement, based on a comprehensive literature review. Eligible were all clinical studies reporting outcomes after esophagectomy, which contained information on at least three years of follow-up after the operation in patients who were older than 18 years of age at the time of the operation. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic web-based search using MEDLINE, the Cochrane Library, and EMBASE databases was performed, reviewing medical literature published between January 2006 and December 2015. The scientific quality of the data was generally low, which allowed us to incorporate only 16 full text articles for the final analyses. After a gastric pull-up, the proportion of patients who suffered from dysphagia varied substantially but seemed to decrease over time with a mild dysphagia remaining during long-term follow-up. When reflux-related symptoms and complications were addressed, roughly two third of patients experienced mild to moderate reflux symptoms a long time after the resection. Following an isoperistaltic colonic graft, the functional long-term outcomes regarding swallowing difficulties were sparsely reported, while three studies reported reflux/regurgitation symptoms in the range of 5% to 16%, one of which reported the symptom severity as being mild. Only one report was available after the use of a long jejunal segment, which contained only six patients, who scored the severity of dysphagia and reflux as mild. Very few if any data were available on a structured assessment of dumping and disturbed bowel functions. Few high-quality data are available on the long-term functional outcomes after esophageal replacement irrespective of the use of a gastric tube, the right or left colon or a long jejunal segment. No firm conclusions regarding the advantages of one graft over the other can presently be drawn.

Association between low C-peptide and fragility fractures in postmenopausal women without diabetes.

PURPOSE: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. METHODS: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. RESULTS: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively). CONCLUSIONS: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Cost-effectiveness analysis of late prophylaxis vs. on-demand treatment for severe haemophilia A in Italy.

INTRODUCTION: Long-term regular administrations of factor VIII (FVIII) concentrate (prophylaxis) initiated at an early age prevents bleeding in patients with severe haemophilia A (HA). The 5-year prospective Italian POTTER study provided evidence of benefits in adolescents and adults of late prophylaxis (LP) vs. on-demand therapy (OD) in reducing bleeding episodes and joint morbidity and improving quality of life; however, costs were increased. AIM: The aim of this study was to determine the cost-effectiveness of LP vs. OD with sucrose-formulated recombinant FVIII in adolescents and adults with severe HA in Italy. METHODS: A Markov model evaluated lifetime cost-effectiveness of LP vs. OD in patients with severe HA in Italy, from both the healthcare and societal perspectives. Clinical input parameters were taken from the POTTER study and published literature. Health utility values were assigned to each health state as measured by the joint disease severity Pettersson score. Costs were expressed in Euro (€) 2014, including drug and other medical costs. Sensitivity analyses were performed considering societal perspective (including productivity lost) and varying relative risk of bleeding episodes between regimens. Clinical outcomes and costs were discounted at 6% according to previous studies. RESULTS: Lifetime incremental discounted quality-adjusted life-years (QALYs) were +4.26, whereas incremental discounted costs were +€229,694 from a healthcare perspective, with estimated incremental cost-effectiveness ratios (ICERs) equal to €53,978/QALY. Sensitivity analyses confirmed the base-case results showing lower ICERs with the societal perspective. CONCLUSION: Late prophylaxis vs. on-demand therapy results in a cost-effective approach with ICERs falling below the threshold considered acceptable in Italy.

Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy.

Intraoperative neurophysiological monitoring for the resection of brain tumors in pediatric patients.

Intraoperative neurophysiology (ION) is the gold standard to map and monitor brain functions during supratentorial surgery in critical areas. This is of great value for the surgery of brain gliomas in adults, but the same ION techniques can be used in the pediatric population with respect to both epilepsy and brain tumor surgery. While the principles of most ION techniques are the same for adults and children, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation of afferent and efferent pathways within the brain and the spinal cord. Accordingly, some adjustments, particularly with regards to stimulation parameters, are needed in younger children. This paper will review current ION techniques to assist during the resection of brain tumors in children, focusing on the aspects peculiar to mapping and monitoring of sensori-motor functions in the pediatric population. On the other hand, awake surgery, of common use in adult patients when aiming to identify cortical and subcortical cognitive functions, is of very limited use in children and will not be discussed here.

SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-α.

Ceramide regulates several different cellular responses including mechanisms leading to apoptosis. Serum- and glucocorticoid-inducible protein kinase (SGK)-1 is a serine threonine kinase, which activates survival pathways in response to stress stimuli. Recently, we demonstrated an anti-apoptotic role of SGK-1 in human umbilical endothelial cells treated with high glucose. In the present study, since ceramide induces apoptosis by multiple mechanisms in diabetes and its complication such as nephropathy, we aimed to investigate whether SGK-1 may protect even against apoptosis induced by ceramide in kidney cells. Human embryonic kidney (HEK)-293 cells stable transfected with SGK-1 wild type (SGK-1wt) and its dominant negative gene (SGK-1dn) have been used in this study. Apoptotic stimuli were induced by C2-ceramide and TNF-α to increase endogenous synthesis of ceramide. Upon activation with these stimuli, SGK-1wt transfected cells have a statistically significant reduction of apoptosis compared with SGK-1dn cells (P<0.001). This protection was dependent on activation of caspase-3 and Poly-ADP-ribose-polymerase-1 (PARP-1) cleavage. SGK-1 and AKT-1 two highly homologous kinases differently reacted to ceramide treatment, since SGK-1 increases in response to apoptotic stimulus while AKT-1 decreases. This enhancement of SGK-1 was dependent on p38-mitogen-activated-protein kinases (p38MAPK), cyclic-adenosine-monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide-3-kinase (PI3K) pathways. Especially, by using selective LY294002 inhibitor, we demonstrated that the most involved pathway in the SGK-1 mediated process of protection was PI3K. Treatment with inhibitor of SGK-1 (GSK650394) significantly enhanced TNF-α-dependent apoptosis in HEK-293 cells overexpressing SGK-1wt. Caspase-3, -8 and -9 selective inhibitors confirmed that SGK-1 reduced the activation of caspase-dependent apoptosis, probably by both intrinsic and extrinsic pathways. In conclusion, we demonstrated that in kidney cells, overexpression of SGK-1 is protective against ceramide-induced apoptosis and the role of SGK-1 can be potentially explored as a therapeutic target in conditions like diabetes, where ceramide levels are increased.

Retos en pos de la Educación Superior de estudiantes de comunidades marginadas en Paraguay. Relevancia del apoyo psicológico, emocional y financiero / Challenges in pursuit of higher educaton of students from marginalized communites in Paraguay. Relevance of psychological, emotonal and financial support

Introducción: Una transición saludable hacia la adultez implica la posibilidad de terminar de estudiar y encontrar un empleo adecuado para responsabilizarse de un hogar y una familia. Objetivo: Este artículo considera los retos que experimentan los jóvenes del Bañado Sur para acceder a la educación superior. Material y Métodos: Estudio cualitativo que se llevó a cabo con la primera generación de universitarios bañadenses en culminar la educación superior, así como docentes de la Universidad Nacional de Asunción, donde la mayoría de los estudiantes estuvieron matriculados. Resultados: Se nota que la meta principal para estos estudiantes es conseguir un empleo estable y digno al terminar sus estudios. Demuestra que la pobreza tiene influencia en su educación superior de maneras múltiples: la necesidad de trabajar mientras estudia, su inclinación de escoger carreras "baratas"aunque no sean de mucho interés, y la precisión de vivir lejos y depender del transporte público para llegar al trabajo, a sus clases, y a su hogar. Los participantes afirmaron la importancia del apoyo psicológico y emocional de sus familias, pares, y profesores, así como financiero, aunque sea simbólico. Las recomendaciones se centran en buscar oportunidades para acercar la vivienda y el trabajo al aula, y aumentar las posibilidades de encontrar empleos relacionados a las carreras que estudian. Igualmente se recomienda establecer programas colaborativos entre la universidad y la secundaria, para orientar a los estudiantes y prepararles para los desafíos del estudio universitario. Finalmente se propone elaborar un año "puente"entre la secundaria y la universidad para capacitar a los jóvenes en habilidades concretas que les puedan acercar a trabajos más lucrativos mientras estudian. Palabras claves: Educación superior; retos académicos; apoyo psicológico, emocional y fnanciero.

Introduction: Healthy transitions to adulthood imply the possibility of completing schooling and obtaining employment capable of sustaining a household and family. Objetives: This article considers the challenges that youth from the Bañado Sur face when pursuing higher education. Methodology: This qualitative study was conducted with first-generation university students from the Bañado, and instructors from the National University of Asunción, where most of these students matriculate. Results: Notably, the primary goal for students is to be able to obtain stable, respectable employment upon completing their studies. It shows that poverty influences their experience of higher education in multiple ways: the need to work while studying, the tendency to choose "cheap" majors even if they are not of particular interest, and the constraint of living far away and relying on public transportation to get to work, classes and home. Participants highlighted the importance of psychological and emotional support on the part of families, peers, and teachers, in addition to financial support, even if only symbolic. Recommendations focus on bringing opportunities for housing and employment closer to the classroom, and improving the possibility of fnding work related to their feld of study. It may also be benefcial to establish collaborative programs between the university and secondary schools, in order to better orient students and prepare them for the challenges of university education. Finally, establishing a "bridge" year between secondary school and university may provide youth with training in concrete skills that would facilitate higher paid work during school. Keywords: Higher education; academic challenges; psychological, emotional and fnancial support

Pharmacological treatment and prevention of chronic venous ulcers: a review.

Chronic venous insufficiency and chronic venous ulcers represent an important medical problem, because of the high incidence and prevalence in the general population, and need to be considered as a lifelong degenerative condition, with socioeconomic consequences. Ulceration is a severe complication of the post-thrombotic syndrome, often precipitated by minor trauma. The rate of post-thrombotic syndrome varies between 20% and 100% of patients with deep vein thrombosis, mostly occurring within two years of an initial thrombotic event. This syndrome is difficult to treat, causes significant disability and reduces the quality of life. To date, there are no effective therapies of chronic venous ulcers and no definite strategies for identifying patients at risk for the development of ulceration. The role of adequate compression with elastic stockings is well recognized. Several systemic drugs have been tested for a possible effect on chronic venous ulcer healing, but none has been widely accepted as standard therapy in this setting. It has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. Waiting for the results in this field, an adequate management of anticoagulation in terms of anticoagulant intensity and duration should be recommended for the prevention of recurrent deep vein thrombosis, post-thrombotic syndrome and chronic venous ulcers.

[A case of stable microvascular angina with normal coronary arteries: certainties and doubts]. / Un caso di angina microvascolare stabile a coronarie indenni: certezze e dubbi.

Myocardial ischemia is caused in most cases by the obstruction of epicardial coronary vessels. Several studies, however, have shown that abnormalities in the coronary microcirculation can also contribute to myocardial ischemia. Microvascular dysfuntion is defined as primary microvascular angina (MVA) to distinguish it from other forms of secondary microvascular angina due to such diseases as arterial hypertension, left ventricular hypertrophy, myocardial disease, metabolic syndrome and collagen diseases. We present the case report of a 48-year-old male patient who coronarographically showed coronary slow flow with delayed distal vessel opacification in the absence of coronary stenosis. Whilst this phenomenon is still not completely understood, strong evidence suggests that the primary alteration is caused by a dysfunction of small coronary vessels.

Factors influencing illness representations and perceived adherence in haemophilic patients: a pilot study.

Illness representations of chronic patients are important to explain adherence and preventive behaviours. However, it is unclear if the patient's objective health status may influence illness representations and perceived adherence. This study explored if health status and socio-demographic characteristics influence illness representations and perceived adherence in haemophilic patients. Fifty patients (25 on-demand and 25 on prophylaxis) ageing from 13-73, completed the Illness Perceptions Questionnaire-Revised and the Morisky Medication Adherence Scale. Patients' cognitive illness representations were influenced by type of treatment, haemophilia severity, presence of inhibitor and co-morbidity. Perceived chronicity was influenced by patient's age (P = 0.021). Perceived adherence was not influenced by the health status, but was affected by the relationship status (P = 0.048). Perceived adherence was predicted by perceived chronicity (ß = 0.412; P = 0.003) and by emotions (ß = -0.308; P = 0.023). Patient's health status seems to affect cognitive illness representations but not perceived adherence. Perceived chronicity and negative emotions, which affected perceived adherence, were not influenced by the health status. Physician-patient communication addressing perceived chronicity and emotions rather than patients' health status may influence patient's adherence. Psycho-educational groups could be offered to promote patient's well-being and adjustment to haemophilia, and improve adherence.

Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes.

UNLABELLED: In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. INTRODUCTION: It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density. METHODS: Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay. RESULTS: rteen percent of the population had osteoporosis and 38% had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). CONCLUSIONS: These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.